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Latest revision as of 16:55, 14 December 2018

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Chandrakala Yannam, MD [2]; Syed Hassan A. Kazmi BSc, MD [3]; Cafer Zorkun, M.D., Ph.D. [4]

Synonyms and keywords: Aldrich syndrome

Overview

Wiskott-Aldrich syndrome (WAS) is a rare X-linked recessive disease characterized by eczema, thrombocytopenia (low platelet counts), immune deficiency, and bloody diarrhea (due to the low platelet counts). It is also sometimes called the eczema-thrombocytopenia-immunodeficiency syndrome in keeping with Aldrich's original description in 1954.^[1] The WAS-related disorders of X-linked thrombocytopenia (XLT) and X-linked congenital neutropenia (XLN) may present similar but less severe symptoms and are caused by mutations of the same gene.

Historical Perspective

The syndrome is named after Dr Robert Anderson Aldrich, an American pediatrician who described the disease in a family of Dutch-Americans in 1954, and Dr Alfred Wiskott, a German pediatrician who first noticed the syndrome in 1937.^[2] Wiskott described three brothers with a similar disease, whose sisters were unaffected. In 2006 a German research group analysed family members of Wiskott's three cases, and surmised that they probably shared a novel frameshift mutation of the first exon of the WAS gene.^[3]

Classification

Jin et al (2004) employ a numerical grading of severity:^[4]

Grade 0.5: intermittent thrombopenia
Grade 1.0: thrombopenia and small platelets
Grade 2.0: thrombopenia and normally responsive eczema or occasional upper respiratory tract infections.
Grade 2.5: thrombopenia and therapy-responsive but severe eczema or airway infections requiring antibiotics
Grade 3.0: both eczema and airway infections requiring antibiotics
Grade 4.0: eczema continuously requiring therapy and/or severe or life threatening infections
Grade 5.0: autoimmune disease or malignancy in an XLT/WAS patient.

Pathophysiology

In the Wiskott–Aldrich syndrome, the platelets are small and do not function properly. They are removed by the spleen, which leads to low platelet counts.

Wiskott–Aldrich syndrome was linked in 1994 to mutations in a gene on the short arm of the X chromosome, which was termed Wiskott-Aldrich syndrome protein (WASp). It was later discovered that the disease X-linked thrombocytopenia (XLT) was also due to WASp mutations, but different ones from those that cause full-blown Wiskott–Aldrich syndrome. Furthermore, the rare disorder X-linked neutropenia has been linked to particular mutations of the WASp gene.

The WASp gene codes for the protein by the same name, which is 502 amino acids long and is mainly expressed in hematopoietic cells (the cells in the bone marrow that develop into blood cells). The main function of WASp is to activate actin polymerization by binding to the Arp2/3 complex. In T-cell, WASp is important because it is known to be activated via T-cell receptor (TCR) signaling pathways to induce cortical actin cytoskeleton rearrangements that are responsible for forming the immunological synapse.

The immune deficiency is caused by decreased antibody production, and an inability for T cells to become polarized ^[5] (making it a combined immunodeficiency). This leads to increased susceptibility to infections, particularly of the ears and sinuses. T cells are unable to reorganize their actin cytoskeleton. The type of mutation to the WASp gene correlates significantly with the degree of severity: those that led to the production of a truncated protein caused significantly more symptoms than those with a missense mutation but a normal-length WASp. Although autoimmune disease and malignancy occur in both types of mutation, those patients with truncated WASp carry a higher risk.

A defect in CD43 molecule has been found to be associated in patients with Wiskott–Aldrich syndrome.^[6]

Causes

In Wiskott–Aldrich syndrome, the platelets are small and do not function properly. They are removed by the spleen, which leads to low platelet counts.

Wiskott–Aldrich syndrome was linked in 1994 to mutations in a gene on the short arm of the X chromosome, which was termed Wiskott-Aldrich syndrome protein (WASp). It was later discovered that the disease X-linked thrombocytopenia (XLT) was also due to WASp mutations, but different ones from those that cause full-blown Wiskott–Aldrich syndrome. Furthermore, the rare disorder X-linked neutropenia has been linked to particular mutations of the WASp gene.

The WASp gene codes for the protein by the same name, which is 502 amino acids long and is mainly expressed in hematopoietic cells (the cells in the bone marrow that develop into blood cells). The main function of WASp is to activate actin polymerization by binding to the Arp2/3 complex. In T-cell, WASp is important because it is known to be activated via T-cell receptor (TCR) signaling pathways to induce cortical actin cytoskeleton rearrangements that are responsible for forming the immunological synapse.

The immune deficiency is caused by decreased antibody production, and an inability for T cells to become polarized ^[5] (making it a combined immunodeficiency). This leads to increased susceptibility to infections, particularly of the ears and sinuses. T-cells are unable to reorganize their actin cytoskeleton. The type of mutation to the WASp gene correlates significantly with the degree of severity: those that led to the production of a truncated protein caused significantly more symptoms than those with a missense mutation but a normal-length WASp. Although autoimmune disease and malignancy occur in both types of mutation, those patients with truncated WASp carry a higher risk.

A defect in CD43 molecule has been found to be associated in patients with Wiskott–Aldrich syndrome.^[6]

Differentiating Wiskott-Aldrich Syndrome From Other Disorders of Humoral Imuunodeficiency

Wiskott-Aldrich Syndrome should be differentiated from other disorders leading to hypogammaglobulinemia and defects of humoral immunity. The following conditions may be considered as differentials:^[7]^[8]^[9]^[10]^[11]^[12]^[13]^[14]^[15]^[16]^[17]^[18]^[19]^[20]^[21]^[22]^[23]^[24]^[25]^[26]^[27]^[28]^[29]^[30]^[31]^[32]^[33]^[34]^[30]^[35]^[36]^[37]^[38]^[39]^[40]^[41]^[42]^[43]^[44]^[45]^[46]^[47]^[48]^[49]^[50]^[51]^[52]^[53]^[54]^[55]^[56]

Disorder	Mechanism	Characteristic Features	Clinical Presentation	Laboratory Findings
Wiskott-Aldrich Syndrome	Mutation in WAS gene T cells unable to reorganize actin microfilaments (microfilament defect)	X-linked recessive pattern of inheritance Increased risk of autoimmune disease and malignancy	Thrombocytopenic purpura Eczema Recurrent infections	Decreased to normal IgG and IgM Increased IgE and IgA Fewer and smaller platelets
X-Linked (Bruton) Agammaglobulinemia	Defect in tyrosine kinase gene (BTK) B cells fail to mature	X-linked recessive pattern of inheritance Increased prevalence in males	Recurrent bacterial and enteroviral infections after 6 months of age Pre-disposition to development of infections by encapsulated organisms Pre-disposition to development of Giardia infections Absent lymph nodes and tonsils	Normal CD19+ B cell count Decreased pro-B cells Increased pre-B cells Decreased immunoglobulins of all classes
Selective IgA Deficiency	Stem cell defect (Transferrable with marrow transplant) Lack of IL-4, IL-6, IL-7, IL-10, TGF-β, and IL-21 Mutations in transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI, TNFRSF13B)	Most common primary immune deficiency	Majority of the cases are asymptomatic Respiratory and gastrointestinal infections (mucosal infections) Associated with autoimmune diseases Atopy Anaphylaxis to IgA containing products	Serum IgA < 7 mg/dl Normal IgG and IgM levels
Common Variable Immunodeficiency	Defective B cell differentiation	May be acquired in 20-30 years of age	May present with other autoimmune diseases Associated with bronchiectasis Associated with lymphoma Associated with sinopulmonary infections (Bacterial, enteroviral and parasitic such as Giardia)	Decreased plasma cells Decreased immunoglobulins
Autosomal dominant hype IgE syndrome (Job's Syndrome)	Defieciency of Th17 cells due to STAT3 mutation Impaired neutrophils to sites of infection	Distinctive coarse facies Cold (non-inflammatory) Staphylococcal abscesses Retained primary teeth Eczema		Increased levels of IgE Decreased levels of interferon gamma (IFN-gamma)
Severe combined immunodeficiency (SCID)	Defective interleukin-2 receptor gamma chain Adenosine deaminase deficiency Reg 1 and Reg 2 nonsense mutations	IL-2R disease is X-linked ADA deficiency and reg mutations are typically autosomal recessive	Failure to thrive Chronic diarrhea Thrush Recurrent bacterial, viral and protozoal infections Treatment is bone marrow transplant	Decreased T cell receptor excision circles (TRECs) Abscence of thymic shadow on chest X-Ray Absent germinal centers of lymph node biopsy Absent T cells on flow cytometry
Ataxia Telangiectasia	Defect in ATM gene DNA double stranded breaks leading to cell cycle arrest	Hypersensitivity to X-Rays	Triad of: Ataxia Spider angiomas (Nests of distended capillaries) IgA deficiency	Increased alpha fetoprotein (AFP) Decreased IgA, IgG and IgE Lymphopenia Cerebellar atrophy
Hyper IgM Syndrome	Defective CD40L (CD40 ligand) on Th cells leading to class switching defect	X-linked recessive pattern of inheritance	Severe pyogenic infections in early life Opportunistic infection with: Pneumocystis jiroveci Cryptosporidium Cytomegalovirus (CMV)	Increased IgM Decreased IgG, IgA and IgE No germinal centers

Malignancy: can cause the reduction in the immunoglobulin production.

Viral infections: such as Epstein-Barr virus, HIV, cytomegalovirus are other causes of hypogammaglobulinemia..
Side effect of certain medications: Some drugs include systemic glucocorticoids, phenytoin, and carbamazepine, have been associated with IgG deficiency.
Other causes of primary humoral immunodeficiencies.
Smoking: may cause IgG2 subclass deficiency.
Protein-losing conditions: enteropathies, nephrotic syndrome, burns, and other traumas may cause abnormal loss of immunoglobulins.

Differentiating Wiskott-Aldrich Syndrome From Other Bleeding Diseases

Wiskott-Aldrich syndrome must be differentiated from other bleeding disorders. Different causes of bleeding disorders can be differentiated based on their clinical manifestation and laboratory findings. These features have discussed in the below table:

Category	Subcategory	Disease		History	Clinical manifestation						Laboratory testing					Comments
Category	Subcategory	Disease		History	Mucosal bleeding	Petechia	Ecchymoses	Menorrhagia	Hematoma	Hemarthrosis	Plt	BT	PT	PTT	TT	Comments
Platelet disorders	Qualitative Disorders of Platelet Function	Inherited Disorders of Platelet Function	Wiskott-Aldrich syndrome	Positive family history	+	+	+	+	−	−	Nl or ↓	↑	Nl	Nl	Nl	Anti-WASP antibody can be used to detect presence or absence of WAS protein In Wiskott–Aldrich syndrome, the platelets are small and do not function properly. They are removed by the spleen, which leads to low platelet counts.
			Glanzmann’s thrombasthenia	Positive family history	+	+	+	+	−	Rare	Nl or ↓	↑	Nl	Nl	Nl	AR inheritance Absence of the platelet Gp IIb/IIIa receptor Diminished for GP 2B-3A on flow cytometry
			Bernard-Soulier syndrome	Positive family history	+	+	+	+	−	−	Nl or ↓	↑	Nl	Nl	Nl	AR inheritance Absence of the platelet Gp Ib-IX-V receptor On PBS: giant platelets Ristocetin - no aggregation
			Platelet storage pool disorder: Hermansky-Pudlak syndrome Chediak-Higashi syndrome Gray platelet syndrome	Positive family history Hairy cell leukemia Cardiovascular bypass	+	+	+	+	−	−	Nl or ↓	↑	Nl	Nl	Nl	AD inheritance AbNlities of platelet granule formation
		Acquired Disorders of Platelet Function		Uremia Cardiopulmonary bypass Hematologic disorders such as: myeloproliferative and myelodysplastic syndromes	+	+	+	+	±	±	Nl or ↓	↑	Nl	Nl	Nl	−
		Von Willebrand Disease		Easy bruising Epistaxis Oral cavity bleeding Bleeding after dental extraction/surgery Menorrhagia Postpartum hemorrhage	+	+	+	+	±	±	↑	Nl	↑	↑	Nl	See the table below for the details about different types.
	Subcategory	Disease		History	Mucosal bleeding	Petechia	Ecchymoses	Menorrhagia	Hematoma	Hemarthrosis	Plt	BT	PT	PTT	TT	Comments
	Thrombocytopenia	Infection-Induced thrombocytopenia		History of prior infection	+	+	+	+	+	+	↓	↑	Nl	Nl	Nl	−
		Medication-Induced Thrombocytopenia		History of medications such as: Furosemide Nonsteroidal anti-inflammatory drugs (NSAIDs) Penicillin Quinidine Quinine Ranitidine Sulfonamides Linezolid	+	+	+	+	+	+	↓	↑	Nl	Nl	Nl	Most important part of treatment is discontinuing of the medication.
		Heparin-Induced thrombocytopenia		Thrombosis Unexplained thrombocytopenia up to 3 weeks after the end of heparin therapy	+	+	+	+	+	+	↓	↑	Nl	Nl	↑	For more information click here: Heparin-induced thrombocytopenia.
		Immune Thrombocytopenic Purpura		History of prior infection or no history	+	+	+	+	+	+	↓	↑	Nl	Nl	Nl	−
		Inherited Thrombocytopenia		Positive family history	+	+	+	+	+	+	↓	↑	Nl	Nl	Nl	−
		Thrombotic Thrombocytopenic Purpura		History of: Cancer Bone marrow transplantation Pregnancy Medication Platelet aggregation inhibitors (ticlopidine and clopidogrel) Immunosuppressants (cyclosporine, mitomycin, tacrolimus/FK506, interferon-α) HIV-1 infection	+	+	+	+	+	+	↓	↑	Nl	Nl	Nl	−
		Hemolytic Uremic Syndrome		History of: Infections Malignancy, chemotherapy, and ionizing radiation Calcineurin inhibitors and transplantation Pregnancy, HELLP syndrome, and oral contraceptive pill Systemic lupus erythematosis Antiphospholipid antibody syndrome Glomerulopathy	+	+	+	+	+	+	↓	↑	Nl	Nl	Nl	−
	Subcategory	Disease		History	Mucosal bleeding	Petechia	Ecchymoses	Menorrhagia	Hematoma	Hemarthrosis	Plt	BT	PT	PTT	TT	Comments
Vessel wall disorders	Metabolic and Inflammatory Disorders	Acute febrile illnesses Mixed cryoglobulinemia Monoclonal gammopathies Rocky Mountain spotted fever Vitamin C deficiency Cushing’s syndrome Chronic glucocorticoid therapy Vasculitis such as Henoch-Schönlein Purpura		History of the underlying disease	−	+	+	±	−	−	Nl	Nl or ↑	Nl	Nl	Nl	−
Vessel wall disorders	Inherited Disorders of the Vessel Wall	Marfan’s syndrome Ehlers-Danlos syndrome Pseudoxanthoma elasticum Hereditary hemorrhagic telangiectasia (HHT, or Osler-Weber-Rendu disease)		Positive family history	−	+	+	±	−	−	Nl	Nl or ↑	Nl	Nl	Nl	−
Coagulation factor disorders ^[57]	Fibrinogen deficiency	Different types of the fibrinogen disorders: Congenital afibrinogenemia Congenital hypofibrinogenemia Fibrinogen storage disease Congenital dysfibrinogenemia Hereditary fibrinogen Aα-Chain amyloidosis Acquired dysfibrinogenemia		Epistaxis Easy bruising Menorrhagia Muscle bleeds Hemarthrosis Bleeding from the umbilical cord stump after birth Bleeding after dental surgery or tooth extraction AbNl bleeding during or after injury, surgery, or childbirth Gastrointestinal hemorrhage Cerebral hemorrhage Thrombosis	−	−	+	+	±	+	Nl	↑	↑	↑	↑	Impaired fibrin cross-linking or clot dissolution Mild or severe bleeding idepend on levels of functional fibrinogen Variable age of onset
	Subcategory	Disease		History	Mucosal bleeding	Petechia	Ecchymoses	Menorrhagia	Hematoma	Hemarthrosis	Plt	BT	PT	PTT	TT	Comments
	Prothrombin deficiency			Epistaxis Soft-tissue hemorrhage Excessive postoperative bleeding Menorrhagia Muscle hematomas Hemarthrosis Intracranial bleeding	−	+	+	+	+	+	Nl	Nl	↑	↑	↑	−
	Factor V deficiency			Excessive bruising with minor injuries Epistaxis Hemarthrosis Menorrhagia Intracerebral hemorrhages Pulmonary hemorrhage	−	−	+	+	+	+	Nl	↑	↑	↑	Nl	The severity of bleeding related to the degree of factor V deficiency
	Factor VII deficiency			Easy bruising Mucosal bleeding Postoperative bleeding Menorrhagia Soft tissue hematomas Thrombosis				+	+	+	Nl		↑	Nl	Nl	Thrombosis in inherited factor VII deficiency Treatment with the administration of factor VII replacement therapy
	Factor X deficiency			Prolonged bleeding following circumcision Easy bruising Hematuria Menorrhagia Abortion Postpartum hemorrhage Epistaxis Pseudotumors Intracranial bleeding Hemarthroses		+	+	+	+	+	Nl	Nl	↑	↑	Nl	−
	Factor XII deficiency			Asymptomatic Recurrent miscarriages Painful leg ulcers		−	−	−	−	−	Nl	Nl	Nl	↑	Nl
	Subcategory	Disease		History	Mucosal bleeding	Petechia	Ecchymoses	Menorrhagia	Hematoma	Hemarthrosis	Plt	BT	PT	PTT	TT	Comments
	High molecular weight kininogen (HMWK) deficiency			Positive family history of bleeding		−	−	−	−	−	Nl	Nl	Nl	↑	Nl
	Prekallikrein deficiency			Positive family history of bleeding		−	−	−	−	−	Nl	Nl	Nl	↑	Nl
	Factor XIII deficiency	Sub unit A mutation disease (more common) Sub unit B mutation disease		Positive family history of bleeding	±	±	±	±	±	±	Nl	Nl	Nl or ↑	Nl	Nl	Impaired fibrin cross-linking or clot dissolution The severity of factor XIII deficiency bleeds can be different in different patients
	Hemophilia	Type A deficiency		Eeasy bruising Inadequate clotting in trauma or mild injury Spontaneous hemorrhage Hemarthrosis Epistaxis Gingival bleeding	−	−	−	+	+	+	Nl	Nl	Nl	↑	Nl	−
		Type B deficiency		Neonatal bleeding Trauma-related soft tissue hemorrhage Hemarthrosis Hematomas	−	−	−	+	+	+	Nl	Nl	Nl	↑	Nl	−
		Type C deficiency		Positive family history Bleeding after surgery or injury	−	−	−	+	Rare	Rare	Nl	Nl	Nl	↑	Nl	−
	Subcategory	Disease		History	Mucosal bleeding	Petechia	Ecchymoses	Menorrhagia	Hematoma	Hemarthrosis	Plt	BT	PT	PTT	TT	Comments
Rare diseases	Disseminated Intravascular Coagulation			Trauma Burn Crush injury Sepsis Malignancy Obstetric complication: abruption, amniotic fluid embolism Hemolytic anemia	+	+	+	+	+	+	↓	↑	↑	↑	Nl	−
Rare diseases	Vitamin K Deficiency			Bleeding after trauma Epistaxis Hematoma Gastrointestinal bleeding Menorrhagia Hematuria Gum bleeding Oozing from venipuncture sites Easy bruisability	+	−	+	+	+	+	Nl	↑	↑	Nl or mildly prolonged	Nl	−

Risk Factors

Positive family history of Wiskott-Aldrich syndrome, can be considered as a risk factor.

Screening

Flow cytometry:
- Anti-WASp antibody can be used to detect presence or absence of WAS protein. However, flow cytometry may not detect expression of mutated, reduced or poor WASp.^[58]
Identification of carriers: Known female carriers can be identified by using DNA mutation analysis of WAS gene.
Prenatal diagnosis: DNA analysis from chorionic villus sampling can be performed.^[59]

Natural History, Complications, and Prognosis

If left untreated, patients with Wiscott-Aldrich syndrome may progress to develop manifestations associated with thrombocytopenia, and abnormal platelet function, defective innate and adaptive immunity which include, severe bleeding (eg, epistaxis, purpura, life threatening gastrointestinal and intracranial hemorrhages), recurrent and severe bronchopulmonary infections. Malignancy and autoimmunity risk has also increased. These conditions may increase the risk of death.^[60]
Common complications of Wiscott-Aldrich syndrome include:
- Recurrent infections with bacterial, viral, fungal and opportunistic organisms. Most common clinical manifestations include otitis media, sinusitis, pneumonia, meningitis, skin infections, and sepsis.^[61]^[62]^[63]
- Bleeding diathesis (eg, epistaxis, ecchymoses, petechiae, hematemesis, intracranial and gastrointestinal hemorrhages)^[60]^[64]
- Autoimmune manifestations may occur in the form of autoimmune hemolytic anemia, immune thrombocytopenic purpura and neutropenia, vasculitis involving small and large vessels, inflammatory bowel disease, and immune-mediated damage to the kidneys and joints.^[65]^[66]^[67]
- Increased risk of malignancy such as lymphoma, leukaemia is a frequent occurence in Wiskott-Aldrich syndrome.^[68]^[69]
Prognosis is generally poor. 5-year survival rates in patients with Wiscott-Aldrich syndrome who had received stem cell transplantation is approximately 73.7% to 80%.^[70]

Diagnosis

Diagnostic Study of Choice

The first laboratory test to be performed in the diagnosis of Wiskott-Aldrich syndrome is complete blood count with differential and peripheral blood smears.
The diagnosis of Wiskott-Aldrich syndrome is suspected if a male patient who presents with bruises, petechiae, eczema, recurrent infections and the presence of congenital thrombocytopenia(< 70 000/mm3) with small platelet volume <5·0fl (micro thrombocytopenia) on the peripheral blood smear.
Identification of WAS gene mutations using DNA sequence analysis of WAS gene and detection of WASp expression by flow cytometry are necessary to confirm the diagnosis.^[71]^[63]

History and Symptoms

Patients with Wiskott-Aldrich syndrome have

Common symptoms of Wiskott-Aldrich syndrome include:
- Easy bruising
- Petechiae
- Purpura
- Eczema
- Prolonged and excessive bleeding after circumcision or from umbilical stump
- Recurrent infections
- Epistaxis (Nose bleeds)
- Hematemesis
- Hematuria
- Melena

Physical Examination

The following findings may be found in the physical examination of the patients with Wiscott-Aldrich syndrome. These include:^[72]^[73]
- Failure to thrive
- Skin examination shows bruises, petechiae, purpura, and eczema due to low platelet count. suppurative skin lesions may also be seen.
- Lymphadenopathy
- Rales and wheezing on auscultation if there is an underlying lung infection.
- Hepatosplenomegaly
- ENT examination: Carefully examine sinuses to rule out sinusitis, ears for any tympanic membrane abnormalities to rule out otitis media and throat for pharyngitis and other opportunistic infections such as oral thrush.
- CNS examination may be performed for symptoms associated with intracranial hemorrhage and infections.

Laboratory Findings

Laboratory findings consistent with the diagnosis of Wiscott-Aldrich syndrome include:
- Complete blood count (CBC) and peripheral smear may show anemia, thrombocytopenia, decreased platelet size and volume.^[74]
- Immunologic studies may show following findings:^[75]^[76]^[77]
  - Decreased levels of serum IgG and IgM and elevated levels of serum IgA and IgE antibodies.
  - Reduction in T lymphocyte count and their function.
  - Variable antibody response to vaccines, protein and polysaccharide antigens.
  - Decreased or absent concentrations of isohemagglutinins.
  - Abnormal T and B lymphocyte proliferative response to mitogens.
  - Abnormal phagocytic response
  - Natural Killer cell defects may also be found.

Electrocardiogram

There are no specific electrocardiogram findings associated with Wiskott-Aldrich syndrome.

X-ray

There are no specific x-ray findings associated with Wiskott-Aldrich syndrome. However, a chest x-ray may be helpful in the diagnosis of complications, which include pneumonia.

Echocardiography or Ultrasound

There are no specific echocardiography/ ultrasound findings associated with Wiscott-Aldrich syndrome.

CT scan

There are no CT scan findings associated with Wiscott-Aldrich syndrome. However, a CT scan may be helpful in the diagnosis of complications of this syndrome, which include pneumonia, internal hemorrhage, to diagnose malignancy and to assess splenic enlargement.^[78]

MRI

There are no specific MRI findings associated with Wiskott-Aldrich syndrome.

Treatment

Medical Therapy

Mainstay therapy for Wiskott-Aldrich syndrome is conservative therapy and supportive care, which includes:
- Prophylactic antimicrobial agents should be given to treat bacterial, viral, fungal and opportunistic infections.^[79]^[80]
  - Trimethoprim/sulfamethoxazole: 5mg/kg/day can be given to treat most bacterial and pneumocystis jirovecii pneumonia.
  - Acyclovir: 200mg/twice daily may be given to treat viral infections (eg, HSV-1)^[81]
  - Fluconazole: 3mg/kg/day may be given to treat fungal infections.
- Platelet transfusions:^[82]
  - Platelet transfusions can be given to treat bleeding episodes such as life-threatening gastrointestinal and intracranial hemorrhages. Platelet transfusions can also be given to patients who are undergoing any surgical procedure.
  - If a patient can be chosen for transfusion, platelets and blood products should be irradiated and must be obtained from a CMV free donor.
- Intravenous immunoglobulins:^[83]
  - Preferred regimen: 400 to 600 mg/kg can be given every three weeks
- Immunosuppressive agents:^[84] Rituximab can be given to treat autoimmune cytopenias such as hemolytic anemia, neutropenia, associated with Wiskott- Aldrich syndrome.
- Thrombopoietic agents: Eltrombopag may be helpful in increasing platelet count in patients with Wiskott-Aldrich syndrome but it may not improve platelet surface activation.^[85]
- Gene therapy: Gene therapy is an alternative curative treatment for Wiskott-Aldrich syndrome, which is still going under trials.^[86]

Surgery

Hematopoietic stem cell transplantation (HSCT):^[87]^[88]^[89]
- HSCT is the only standard curative treatment for Wiskott-Aldrich syndrome.
Splenectomy: Splenectomy may be considered for some patients with Wiskott-Aldrich syndrome . Splenectomy may be found to improve platelet count as well as size of the platelets . However, sepsis is a life-threatening complication after splenectomy. Prophylactic antibiotics should always be used to prevent infections.^[90]^[91]

Primary Prevention

There are no established measures for the primary prevention of the Wiskott-Aldrich syndrome. However genetic mutation analysis and prenatal molecular diagnosis can be helpful in decreaing the occurance .^[92]^[59]

Secondary Prevention

There are no established measures for the secondary prevention of the Wiskott-Aldrich syndrome.

References

↑ Aldrich RA, Steinberg AG, Campbell DC (1954). "Pedigree demonstrating a sex-linked recessive condition characterized by draining ears, eczematoid dermatitis and bloody diarrhea". Pediatrics. 13 (2): 133–9. PMID 13133561.
↑ Wiskott, A (1937). "Familiärer, angeborener Morbus Werlhofii? ("Familial congenital Werlhof's disease?")". Montsschr Kinderheilkd. 68: 212–16.
↑ Binder V, Albert MH, Kabus M, Bertone M, Meindl A, Belohradsky BH (2006). "The genotype of the original Wiskott phenotype". N. Engl. J. Med. 355 (17): 1790–3. doi:10.1056/NEJMoa062520. PMID 17065640.
↑ Jin Y, Mazza C, Christie JR; et al. (2004). "Mutations of the Wiskott-Aldrich Syndrome Protein (WASP): hotspots, effect on transcription, and translation and phenotype/genotype correlation". Blood. 104 (13): 4010–9. doi:10.1182/blood-2003-05-1592. PMID 15284122.
↑ ^5.0 ^5.1 "Wiskott-Aldrich Syndrome: Immunodeficiency Disorders: Merck Manual Professional". Retrieved 2008-03-01.
↑ ^6.0 ^6.1 PMID 1683685 (PMID 1683685)
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↑ Agarwal S, Cunningham-Rundles C (September 2007). "Assessment and clinical interpretation of reduced IgG values". Ann. Allergy Asthma Immunol. 99 (3): 281–3. doi:10.1016/S1081-1206(10)60665-5. PMC 3099256. PMID 17910333.
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↑
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[pmid17710656-89] Muñoz A, Olivé T, Martinez A, Bureo E, Maldonado MS, Diaz de Heredia C, Sastre A, Gonzalez-Vicent M (September 2007). "Allogeneic hemopoietic stem cell transplantation (HSCT) for Wiskott-Aldrich syndrome: a report of the Spanish Working Party for Blood and Marrow Transplantation in Children (GETMON)". Pediatr Hematol Oncol. 24 (6): 393–402. doi:10.1080/08880010701454404. PMID 17710656.

[pmid6767187-90] Lum LG, Tubergen DG, Corash L, Blaese RM (April 1980). "Splenectomy in the management of the thrombocytopenia of the Wiskott-Aldrich syndrome". N. Engl. J. Med. 302 (16): 892–6. doi:10.1056/NEJM198004173021604. PMID 6767187.

[pmid21906397-91] Syrigos KN, Makrilia N, Neidhart J, Moutsos M, Tsimpoukis S, Kiagia M, Saif MW (September 2011). "Prolonged survival after splenectomy in Wiskott-Aldrich syndrome: a case report". Ital J Pediatr. 37: 42. doi:10.1186/1824-7288-37-42. PMC 3179709. PMID 21906397.

[pmid8069912-92] Derry JM, Ochs HD, Francke U (August 1994). "Isolation of a novel gene mutated in Wiskott-Aldrich syndrome". Cell. 78 (4): 635–44. PMID 8069912.

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@@ Line 2: / Line 2: @@
 {{SI}}
-{{Infobox_Disease |
+{{CMG}}; {{AE}} {{CK}}; {{HK}}; {{CZ}}
-  Name           = {{PAGENAME}} |
-  Image          = |
-  Caption        = |
-  DiseasesDB     = 14176 |
-  ICD10          = {{ICD10|D|82|0|d|80}} |
-  ICD9           = {{ICD9|279.12}} |
-  ICDO           = |
-  OMIM           = 301000 |
-  MedlinePlus    = |
-  MeshID         = D014923 |
-}}
-{{CMG}}; {{AE}} {{CK}}
-'''Associate Editor-In-Chief:''' {{CZ}}
 {{SK}} Aldrich syndrome
-==Patient Informtion==
 ==Overview==
@@ Line 31: / Line 14: @@
 ==Classification==
 Jin et al (2004) employ a numerical grading of severity:<ref name="Jin">{{cite journal |author=Jin Y, Mazza C, Christie JR, ''et al'' |title=Mutations of the Wiskott-Aldrich Syndrome Protein (WASP): hotspots, effect on transcription, and translation and phenotype/genotype correlation |journal=Blood |volume=104 |issue=13 |pages=4010-9 |year=2004 |pmid=15284122 |doi=10.1182/blood-2003-05-1592}}</ref>
-* 0.5: intermittent thrombopenia
+* Grade 0.5: intermittent [[Thrombocytopenia|thrombopenia]]
-* 1.0: thrombopenia and small platelets
+* Grade 1.0: [[Thrombocytopenia|thrombopenia]] and small platelets
-* 2.0: thrombopenia and normally responsive eczema or occasional upper respiratory tract infections.
+* Grade 2.0: [[Thrombocytopenia|thrombopenia]] and normally responsive [[eczema]] or occasional upper [[Respiratory tract infection|respiratory tract infections]].
-* 2.5: thrombopenia and therapy-responsive but severe eczema or airway infections requiring antibiotics
+* Grade 2.5: [[Thrombocytopenia|thrombopenia]] and therapy-responsive but severe [[eczema]] or airway infections requiring antibiotics
-* 3.0: both eczema ''and'' airway infections requiring antibiotics
+* Grade 3.0: both [[eczema]] ''and'' airway infections requiring antibiotics
-* 4.0: eczema continuously requiring therapy and/or severe or life threatening infections
+* Grade 4.0: [[eczema]] continuously requiring therapy and/or severe or life threatening infections
-* 5.0: autoimmune disease or malignancy in an XLT/WAS patient.
+* Grade 5.0: [[Autoimmunity|autoimmune]] disease or [[malignancy]] in an XLT/WAS patient.
 ==Pathophysiology==
-In Wiskott–Aldrich syndrome, the platelets are small and do not function properly.  They are removed by the [[spleen]], which leads to low platelet counts.
+In the Wiskott–Aldrich syndrome, the [[Platelet|platelets]] are small and do not function properly. They are removed by the [[spleen]], which leads to low [[platelet]] counts.
-Wiskott–Aldrich syndrome was linked in 1994 to mutations in a [[gene]] on the short arm of the [[X chromosome]], which was termed ''[[Wiskott-Aldrich syndrome protein]]'' (''WASp''). It was later discovered that the disease [[X-linked thrombocytopenia]] (XLT) was also due to ''WASp'' mutations, but different ones from those that cause full-blown Wiskott–Aldrich syndrome. Furthermore, the rare disorder [[X-linked neutropenia]] has been linked to particular mutations of the ''WASp'' gene.
+Wiskott–Aldrich syndrome was linked in 1994 to mutations in a [[gene]] on the short arm of the [[X chromosome]], which was termed ''[[Wiskott-Aldrich syndrome protein]]'' (''WASp''). It was later discovered that the disease X-linked [[thrombocytopenia]] (XLT) was also due to ''WASp'' [[Mutation|mutations]], but different ones from those that cause full-blown Wiskott–Aldrich syndrome. Furthermore, the rare disorder X-linked [[neutropenia]] has been linked to particular mutations of the ''WASp'' gene.
 The ''WASp'' gene codes for the protein by the same name, which is 502 [[amino acid]]s long and is mainly expressed in [[haematopoeisis|hematopoietic]] cells (the cells in the bone marrow that develop into blood cells). The main function of WASp is to activate actin polymerization by binding to the [[Arp2/3 complex]].  In T-cell, WASp is important because it is known to be activated via [[T-cell receptor]] (TCR) signaling pathways to induce cortical actin [[cytoskeleton]] rearrangements that are responsible for forming the [[immunological synapse]].
-The immune deficiency is caused by decreased [[antibody]] production, and an inability for [[T cell]]s to become polarized <ref name="titleWiskott-Aldrich Syndrome: Immunodeficiency Disorders: Merck Manual Professional">{{cite web |url=http://www.merck.com/mmpe/sec13/ch164/ch164n.html |title=Wiskott-Aldrich Syndrome: Immunodeficiency Disorders: Merck Manual Professional |accessdate=2008-03-01 |work=}}</ref> (making it a [[combined immunodeficiency]]). This leads to increased susceptibility to infections, particularly of the ears and sinuses. T cells are unable to reorganize their actin cytoskeleton.
+The immune deficiency is caused by decreased [[antibody]] production, and an inability for [[T cell]]s to become polarized <ref name="titleWiskott-Aldrich Syndrome: Immunodeficiency Disorders: Merck Manual Professional">{{cite web |url=http://www.merck.com/mmpe/sec13/ch164/ch164n.html |title=Wiskott-Aldrich Syndrome: Immunodeficiency Disorders: Merck Manual Professional |accessdate=2008-03-01 |work=}}</ref> (making it a [[combined immunodeficiency]]). This leads to increased susceptibility to [[Infection|infections]], particularly of the [[Ear|ears]] and [[sinuses]]. T cells are unable to reorganize their actin [[cytoskeleton]]. The type of [[mutation]] to the ''WASp'' gene correlates significantly with the degree of severity: those that led to the production of a truncated protein caused significantly more symptoms than those with a [[missense mutation]] but a normal-length WASp. Although autoimmune disease and [[malignancy]] occur in both types of [[mutation]], those patients with truncated WASp carry a higher risk.
-The type of [[mutation]] to the ''WASp'' gene correlates significantly with the degree of severity: those that led to the production of a truncated protein caused significantly more symptoms than those with a [[missense mutation]] but a normal-length WASp. Although autoimmune disease and malignancy occur in both types of mutation, those patients with truncated WASp carry a higher risk.
 A defect in [[CD43]] molecule has been found to be associated in patients with Wiskott–Aldrich syndrome.<ref name="CD43 a defective molecule in Wiskott-Aldrich syndrome">{{cite pmid|1683685}}</ref>
 ==Causes==
-In Wiskott–Aldrich syndrome, the platelets are small and do not function properly.  They are removed by the [[spleen]], which leads to low platelet counts.
+In Wiskott–Aldrich syndrome, the [[Platelet|platelets]] are small and do not function properly. They are removed by the [[spleen]], which leads to low [[platelet]] counts.
-Wiskott–Aldrich syndrome was linked in 1994 to mutations in a [[gene]] on the short arm of the [[X chromosome]], which was termed ''[[Wiskott-Aldrich syndrome protein]]'' (''WASp''). It was later discovered that the disease [[X-linked thrombocytopenia]] (XLT) was also due to ''WASp'' mutations, but different ones from those that cause full-blown Wiskott–Aldrich syndrome. Furthermore, the rare disorder [[X-linked neutropenia]] has been linked to particular mutations of the ''WASp'' gene.
+Wiskott–Aldrich syndrome was linked in 1994 to [[Mutation|mutations]] in a [[gene]] on the short arm of the [[X chromosome]], which was termed ''[[Wiskott-Aldrich syndrome protein]]'' (''WASp''). It was later discovered that the disease X-linked [[thrombocytopenia]] (XLT) was also due to ''WASp'' mutations, but different ones from those that cause full-blown Wiskott–Aldrich syndrome. Furthermore, the rare disorder X-linked [[neutropenia]] has been linked to particular mutations of the ''WASp'' gene.
 The ''WASp'' gene codes for the protein by the same name, which is 502 [[amino acid]]s long and is mainly expressed in [[haematopoeisis|hematopoietic]] cells (the cells in the bone marrow that develop into blood cells). The main function of WASp is to activate actin polymerization by binding to the [[Arp2/3 complex]].  In T-cell, WASp is important because it is known to be activated via [[T-cell receptor]] (TCR) signaling pathways to induce cortical actin [[cytoskeleton]] rearrangements that are responsible for forming the [[immunological synapse]].
-The immune deficiency is caused by decreased [[antibody]] production, and an inability for [[T cell]]s to become polarized <ref name="titleWiskott-Aldrich Syndrome: Immunodeficiency Disorders: Merck Manual Professional">{{cite web |url=http://www.merck.com/mmpe/sec13/ch164/ch164n.html |title=Wiskott-Aldrich Syndrome: Immunodeficiency Disorders: Merck Manual Professional |accessdate=2008-03-01 |work=}}</ref> (making it a [[combined immunodeficiency]]). This leads to increased susceptibility to infections, particularly of the ears and sinuses. T cells are unable to reorganize their actin cytoskeleton.
+The immune deficiency is caused by decreased [[antibody]] production, and an inability for [[T cell]]s to become polarized <ref name="titleWiskott-Aldrich Syndrome: Immunodeficiency Disorders: Merck Manual Professional">{{cite web |url=http://www.merck.com/mmpe/sec13/ch164/ch164n.html |title=Wiskott-Aldrich Syndrome: Immunodeficiency Disorders: Merck Manual Professional |accessdate=2008-03-01 |work=}}</ref> (making it a [[combined immunodeficiency]]). This leads to increased susceptibility to infections, particularly of the [[Ear|ears]] and [[sinuses]]. [[T cell|T-cells]] are unable to reorganize their actin [[cytoskeleton]]. The type of [[mutation]] to the ''WASp'' gene correlates significantly with the degree of severity: those that led to the production of a truncated protein caused significantly more symptoms than those with a [[missense mutation]] but a normal-length WASp. Although [[Autoimmunity|autoimmune]] disease and [[malignancy]] occur in both types of [[mutation]], those patients with truncated WASp carry a higher risk.
-The type of [[mutation]] to the ''WASp'' gene correlates significantly with the degree of severity: those that led to the production of a truncated protein caused significantly more symptoms than those with a [[missense mutation]] but a normal-length WASp. Although autoimmune disease and malignancy occur in both types of mutation, those patients with truncated WASp carry a higher risk.
 A defect in [[CD43]] molecule has been found to be associated in patients with Wiskott–Aldrich syndrome.<ref name="CD43 a defective molecule in Wiskott-Aldrich syndrome">{{cite pmid|1683685}}</ref>
-==Differentiating ((Page name)) from Other Diseases==
+==Differentiating Wiskott-Aldrich Syndrome From Other Disorders of Humoral Imuunodeficiency==
+Wiskott-Aldrich Syndrome should be differentiated from other disorders leading to [[hypogammaglobulinemia]] and defects of [[humoral immunity]]. The following conditions may be considered as differentials:<ref name="pmid17910333">{{cite journal |vauthors=Agarwal S, Cunningham-Rundles C |title=Assessment and clinical interpretation of reduced IgG values |journal=Ann. Allergy Asthma Immunol. |volume=99 |issue=3 |pages=281–3 |date=September 2007 |pmid=17910333 |pmc=3099256 |doi=10.1016/S1081-1206(10)60665-5 |url=}}</ref><ref name="pmid7679206">{{cite journal |vauthors=Korthäuer U, Graf D, Mages HW, Brière F, Padayachee M, Malcolm S, Ugazio AG, Notarangelo LD, Levinsky RJ, Kroczek RA |title=Defective expression of T-cell CD40 ligand causes X-linked immunodeficiency with hyper-IgM |journal=Nature |volume=361 |issue=6412 |pages=539–41 |date=February 1993 |pmid=7679206 |doi=10.1038/361539a0 |url=}}</ref><ref name="pmid9255191">{{cite journal |vauthors=Levy J, Espanol-Boren T, Thomas C, Fischer A, Tovo P, Bordigoni P, Resnick I, Fasth A, Baer M, Gomez L, Sanders EA, Tabone MD, Plantaz D, Etzioni A, Monafo V, Abinun M, Hammarstrom L, Abrahamsen T, Jones A, Finn A, Klemola T, DeVries E, Sanal O, Peitsch MC, Notarangelo LD |title=Clinical spectrum of X-linked hyper-IgM syndrome |journal=J. Pediatr. |volume=131 |issue=1 Pt 1 |pages=47–54 |date=July 1997 |pmid=9255191 |doi= |url=}}</ref><ref name="pmid14663287">{{cite journal |vauthors=Winkelstein JA, Marino MC, Ochs H, Fuleihan R, Scholl PR, Geha R, Stiehm ER, Conley ME |title=The X-linked hyper-IgM syndrome: clinical and immunologic features of 79 patients |journal=Medicine (Baltimore) |volume=82 |issue=6 |pages=373–84 |date=November 2003 |pmid=14663287 |doi=10.1097/01.md.0000100046.06009.b0 |url=}}</ref><ref name="pmid10352287">{{cite journal |vauthors=Subauste CS, Wessendarp M, Sorensen RU, Leiva LE |title=CD40-CD40 ligand interaction is central to cell-mediated immunity against Toxoplasma gondii: patients with hyper IgM syndrome have a defective type 1 immune response that can be restored by soluble CD40 ligand trimer |journal=J. Immunol. |volume=162 |issue=11 |pages=6690–700 |date=June 1999 |pmid=10352287 |doi= |url=}}</ref><ref name="pmid8993019">{{cite journal |vauthors=Hayward AR, Levy J, Facchetti F, Notarangelo L, Ochs HD, Etzioni A, Bonnefoy JY, Cosyns M, Weinberg A |title=Cholangiopathy and tumors of the pancreas, liver, and biliary tree in boys with X-linked immunodeficiency with hyper-IgM |journal=J. Immunol. |volume=158 |issue=2 |pages=977–83 |date=January 1997 |pmid=8993019 |doi= |url=}}</ref><ref name="pmid20180797">{{cite journal |vauthors=Davies EG, Thrasher AJ |title=Update on the hyper immunoglobulin M syndromes |journal=Br. J. Haematol. |volume=149 |issue=2 |pages=167–80 |date=April 2010 |pmid=20180797 |pmc=2855828 |doi=10.1111/j.1365-2141.2010.08077.x |url=}}</ref><ref name="pmid20101521">{{cite journal |vauthors=Yel L |title=Selective IgA deficiency |journal=J. Clin. Immunol. |volume=30 |issue=1 |pages=10–6 |date=January 2010 |pmid=20101521 |pmc=2821513 |doi=10.1007/s10875-009-9357-x |url=}}</ref><ref name="pmid19153537">{{cite journal |vauthors=Suzuki H, Kaneko H, Fukao T, Jin R, Kawamoto N, Asano T, Matsui E, Kasahara K, Kondo N |title=Various expression patterns of alpha1 and alpha2 genes in IgA deficiency |journal=Allergol Int |volume=58 |issue=1 |pages=111–7 |date=March 2009 |pmid=19153537 |doi=10.2332/allergolint.O-08-549 |url=}}</ref><ref name="pmid11720003">{{cite journal |vauthors=Cunningham-Rundles C |title=Physiology of IgA and IgA deficiency |journal=J. Clin. Immunol. |volume=21 |issue=5 |pages=303–9 |date=September 2001 |pmid=11720003 |doi= |url=}}</ref><ref name="pmid15093556">{{cite journal |vauthors=Edwards E, Razvi S, Cunningham-Rundles C |title=IgA deficiency: clinical correlates and responses to pneumococcal vaccine |journal=Clin. Immunol. |volume=111 |issue=1 |pages=93–7 |date=April 2004 |pmid=15093556 |doi=10.1016/j.clim.2003.12.005 |url=}}</ref><ref name="pmid305332">{{cite journal |vauthors=Chipps BE, Talamo RC, Winkelstein JA |title=IgA deficiency, recurrent pneumonias, and bronchiectasis |journal=Chest |volume=73 |issue=4 |pages=519–26 |date=April 1978 |pmid=305332 |doi= |url=}}</ref><ref name="pmid5056860">{{cite journal |vauthors=Zinneman HH, Kaplan AP |title=The association of giardiasis with reduced intestinal secretory immunoglobulin A |journal=Am J Dig Dis |volume=17 |issue=9 |pages=793–7 |date=September 1972 |pmid=5056860 |doi= |url=}}</ref><ref name="pmid18683032">{{cite journal |vauthors=Aghamohammadi A, Cheraghi T, Gharagozlou M, Movahedi M, Rezaei N, Yeganeh M, Parvaneh N, Abolhassani H, Pourpak Z, Moin M |title=IgA deficiency: correlation between clinical and immunological phenotypes |journal=J. Clin. 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+{|
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |Disorder
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |Mechanism
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |Characteristic Features
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |Clinical Presentation
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |Laboratory Findings
+|-
+! align="center" style="background:#DCDCDC;" + |[[Wiskott-Aldrich syndrome|Wiskott-Aldrich Syndrome]]
+| align="left" style="background:#F5F5F5;" + |
+* [[Mutation]] in [[WAS]] [[gene]]
+* [[T cells]] unable to reorganize [[actin]] [[microfilaments]] ([[microfilament]] defect)
+| align="left" style="background:#F5F5F5;" + |
+* [[X-linked recessive]] pattern of inheritance
+* Increased risk of [[autoimmune disease]] and [[malignancy]]
+| align="left" style="background:#F5F5F5;" + |
+* [[Thrombocytopenic purpura]]
+* [[Eczema]]
+* Recurrent [[infections]]
+| align="left" style="background:#F5F5F5;" + |
+* Decreased to normal [[Immunoglobulin G|IgG]] and [[Immunoglobulin M|IgM]]
+* Increased [[Immunoglobulin E|IgE]] and [[IgA]]
+* Fewer and smaller [[platelets]]
+|-
+! align="center" style="background:#DCDCDC;" + |[[X-linked agammaglobulinemia|X-Linked (Bruton) Agammaglobulinemia]]
+| align="left" style="background:#F5F5F5;" + |
+* Defect in [[tyrosine kinase]] [[gene]] ([[Bruton's tyrosine kinase|BTK]])
+* [[B cells]] fail to mature
+| align="left" style="background:#F5F5F5;" + |
+* [[X-linked recessive]] pattern of inheritance
+* Increased [[prevalence]] in [[males]]
+| align="left" style="background:#F5F5F5;" + |
+* Recurrent [[bacterial]] and [[enteroviral]] [[infections]] after 6 months of age
+* Pre-disposition to development of [[infections]] by [[encapsulated organisms]]
+* Pre-disposition to development of Giardia infections
+* Absent lymph nodes and tonsils
+| align="left" style="background:#F5F5F5;" + |
+* Normal [[CD19|CD19+ B cell]] count
+* Decreased pro-[[B cells]]
+* Increased pre-[[B cells]]
+* Decreased [[immunoglobulins]] of all classes
+|-
+! align="center" style="background:#DCDCDC;" + |[[IgA deficiency|Selective IgA Deficiency]]
+| align="left" style="background:#F5F5F5;" + |
+* [[Stem cell]] defect (Transferrable with [[Bone marrow transplant|marrow transplant]])
+* Lack of [[Interleukin 4|IL-4]], [[Interleukin 6|IL-6]], [[Interleukin 7|IL-7]], [[Interleukin 10|IL-10]], [[TGF beta|TGF-β]], and [[Interleukin 21|IL-21]]
+* [[Mutations]] in [[transmembrane]] activator and calcium-modulator and [[cyclophilin]] ligand interactor ([[TACI]], [[TNFRSF13B]])
+| align="left" style="background:#F5F5F5;" + |
+* Most common primary [[immune deficiency]]
+| align="left" style="background:#F5F5F5;" + |
+* Majority of the cases are [[asymptomatic]]
+* Respiratory and [[gastrointestinal]] infections ([[mucosal]] infections)
+* Associated with [[autoimmune diseases]]
+* [[Atopy]]
+* [[Anaphylaxis]] to [[IgA]] containing products
+| align="left" style="background:#F5F5F5;" + |
+* Serum [[IgA]] < 7 mg/dl
+* Normal [[IgG]] and [[IgM]] levels
+|-
+! align="center" style="background:#DCDCDC;" + |[[Common variable immunodeficiency|Common Variable Immunodeficiency]]
+| align="left" style="background:#F5F5F5;" + |
+* Defective [[B cell]] differentiation
+| align="left" style="background:#F5F5F5;" + |
+* May be acquired in 20-30 years of age
+| align="left" style="background:#F5F5F5;" + |
+* May present with other [[autoimmune diseases]]
+* Associated with [[bronchiectasis]]
+* Associated with [[lymphoma]]
+* Associated with sinopulmonary infections ([[Bacterial]], [[enteroviral]] and [[parasitic]] such as [[Giardia]])
+| align="left" style="background:#F5F5F5;" + |
+* Decreased [[plasma cells]]
+* Decreased [[immunoglobulins]]
+|-
+! align="center" style="background:#DCDCDC;" + |[[Job's syndrome|Autosomal dominant hype IgE syndrome (Job's Syndrome)]]
+| align="left" style="background:#F5F5F5;" + |
+* Defieciency of [[T helper 17 cell|Th17 cells]] due to [[STAT3]] [[mutation]]
+* Impaired [[neutrophils]] to sites of [[infection]]
+| align="left" style="background:#F5F5F5;" + |
+* Distinctive coarse facies
+* Cold (non-inflammatory) Staphylococcal abscesses
+* Retained primary teeth
+* Eczema
+| align="left" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
+* Increased levels of [[IgE]]
+* Decreased levels of [[interferon gamma]] (IFN-gamma)
+|-
+! align="center" style="background:#DCDCDC;" + |[[Severe combined immunodeficiency|Severe combined immunodeficiency (SCID)]]
+| align="left" style="background:#F5F5F5;" + |
+* Defective [[Interleukin-2 receptor|interleukin-2 receptor gamma chain]]
+* [[Adenosine deaminase]] deficiency
+* Reg 1 and Reg 2 [[nonsense mutations]]
+| align="left" style="background:#F5F5F5;" + |
+* [[Interleukin 20 receptor, alpha subunit|IL-2R]] disease is [[X-linked]]
+* [[Adenosine deaminase|ADA]] deficiency and reg mutations are typically [[autosomal recessive]]
+| align="left" style="background:#F5F5F5;" + |
+* [[Failure to thrive]]
+* [[Chronic diarrhea]]
+* [[Thrush]]
+* Recurrent [[bacterial]], [[viral]] and [[protozoal]] infections
+* Treatment is [[bone marrow]] [[transplant]]
+| align="left" style="background:#F5F5F5;" + |
+* Decreased [[T cell]] receptor excision circles (TRECs)
+* Abscence of [[thymic]] shadow on [[Chest X-ray|chest X-Ray]]
+* Absent [[germinal centers]] of [[lymph node biopsy]]
+* Absent [[T cells]] on [[flow cytometry]]
+|-
+! align="center" style="background:#DCDCDC;" + |[[Ataxia telangiectasia|Ataxia Telangiectasia]]
+| align="left" style="background:#F5F5F5;" + |
+* Defect in [[ATM|ATM gene]]
+* [[DNA]] double stranded breaks leading to [[cell cycle]] arrest
+| align="left" style="background:#F5F5F5;" + |
+* Hypersensitivity to [[X-Ray|X-Rays]]
+| align="left" style="background:#F5F5F5;" + |
+* Triad of:
+** [[Ataxia]]
+** Spider [[Angioma|angiomas]] (Nests of distended [[capillaries]])
+** [[IgA deficiency]]
+| align="left" style="background:#F5F5F5;" + |
+* Increased [[alpha fetoprotein]] ([[Alpha-fetoprotein|AFP]])
+* Decreased [[IgA]], [[IgG]] and [[IgE]]
+* [[Lymphopenia]]
+* [[Cerebellar]] atrophy
+|-
+! align="center" style="background:#DCDCDC;" + |[[Hyper IgM Syndrome Type 1|Hyper IgM Syndrome]]
+| align="left" style="background:#F5F5F5;" + |
+* Defective [[CD40L]] ([[CD40L|CD40 ligand]]) on [[T helper cell|Th cells]] leading to [[class switching]] defect
+| align="left" style="background:#F5F5F5;" + |
+* [[X-linked recessive]] pattern of inheritance
+| align="left" style="background:#F5F5F5;" + |
+* Severe pyogenic infections in early life
+* Opportunistic infection with:
+** [[Pneumocystis jiroveci]]
+** [[Cryptosporidium]]
+** [[Cytomegalovirus]] ([[Cytomegalovirus infection|CMV]])
+| align="left" style="background:#F5F5F5;" + |
+* Increased [[Immunoglobulin M|IgM]]
+* Decreased [[Immunoglobulin G|IgG]], [[IgA]] and [[Immunoglobulin E|IgE]]
+* No [[germinal centers]]
+|}
+:*Malignancy: can cause the reduction in the immunoglobulin production.
+*Viral infections: such as Epstein-Barr virus, HIV, cytomegalovirus are other causes of hypogammaglobulinemia..
+*Side effect of certain medications: Some drugs include systemic glucocorticoids, phenytoin, and carbamazepine, have been associated with IgG deficiency.
+*Other causes of primary humoral immunodeficiencies.
+*Smoking: may cause IgG2 subclass deficiency.
+*Protein-losing conditions: enteropathies, nephrotic syndrome, burns, and other traumas may cause abnormal loss of immunoglobulins.
-==Epidemiology and Demographics==
+==Differentiating Wiskott-Aldrich Syndrome From Other Bleeding Diseases==
-The combined incidence of WAS and XLT is about 4-10 in 1 million live births. There is no geographical factor.
+* Wiskott-Aldrich syndrome must be differentiated from other bleeding disorders. Different causes of bleeding disorders can be differentiated based on their clinical manifestation and laboratory findings. These features have discussed in the below table:
+{|
+! rowspan="2" align="center" style="background:#4479BA; color: #FFFFFF;" + |Category
+! rowspan="2" align="center" style="background:#4479BA; color: #FFFFFF;" + |Subcategory
+! colspan="2" rowspan="2" align="center" style="background:#4479BA; color: #FFFFFF;" + |Disease
+! rowspan="2" align="center" style="background:#4479BA; color: #FFFFFF;" + |History
+! colspan="6" align="center" style="background:#4479BA; color: #FFFFFF;" + |Clinical manifestation
+! colspan="5" align="center" style="background:#4479BA; color: #FFFFFF;" + |Laboratory testing
+! rowspan="2" align="center" style="background:#4479BA; color: #FFFFFF;" + |Comments
+|-
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |Mucosal bleeding
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |Petechia
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |Ecchymoses
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |Menorrhagia
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |Hematoma
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |Hemarthrosis
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |Plt
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |BT
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |PT
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |PTT
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |TT
+|-
+! rowspan="15" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Platelet disorders
+! rowspan="6" align="center" style="padding: 5px 5px; background: #DCDCDC;" |Qualitative Disorders of [[Platelet]] Function
+! rowspan="4" align="center" style="padding: 5px 5px; background: #DCDCDC;" |Inherited Disorders of [[Platelet]] Function
+! align="center" style="padding: 5px 5px; background: #DCDCDC;" |[[Wiskott-Aldrich syndrome]]
+| align="left" style="background:#F5F5F5;" |
+* Positive family history
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | <nowiki>+</nowiki>
+| align="center" style="background:#F5F5F5;" | <nowiki>+</nowiki>
+| align="center" style="background:#F5F5F5;" | <nowiki>+</nowiki>
+| align="center" style="background:#F5F5F5;" | −
+| align="center" style="background:#F5F5F5;" | −
+| align="center" style="background:#F5F5F5;" | Nl or ↓
+| align="center" style="background:#F5F5F5;" | ↑
+| align="center" style="background:#F5F5F5;" | Nl
+| align="center" style="background:#F5F5F5;" | Nl
+| align="center" style="background:#F5F5F5;" | Nl
+| align="left" style="background:#F5F5F5;" |
+* Anti-WASP antibody can be used to detect presence or absence of WAS protein
+* In Wiskott–Aldrich syndrome, the [[Platelet|platelets]] are small and do not function properly. They are removed by the [[spleen]], which leads to low [[platelet]] counts.
+|-
+! align="center" style="padding: 5px 5px; background: #DCDCDC;" |[[Glanzmann's thrombasthenia|Glanzmann’s thrombasthenia]]
+| align="left" style="background:#F5F5F5;" |
+* Positive family history
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | −
+| align="center" style="background:#F5F5F5;" | Rare
+| align="center" style="background:#F5F5F5;" | Nl or ↓
+| align="center" style="background:#F5F5F5;" | ↑
+| align="center" style="background:#F5F5F5;" | Nl
+| align="center" style="background:#F5F5F5;" | Nl
+| align="center" style="background:#F5F5F5;" | Nl
+| align="left" style="background:#F5F5F5;" |
+* AR inheritance
+* Absence of the platelet Gp IIb/IIIa receptor
+* Diminished for GP 2B-3A on [[Flow cytometry|flow cytometry]]
+|-
+! align="center" style="padding: 5px 5px; background: #DCDCDC;" |[[Bernard-Soulier syndrome]]
+| align="left" style="background:#F5F5F5;" |
+* Positive family history
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | −
+| align="center" style="background:#F5F5F5;" | −
+| align="center" style="background:#F5F5F5;" | Nl or ↓
+| align="center" style="background:#F5F5F5;" | ↑
+| align="center" style="background:#F5F5F5;" | Nl
+| align="center" style="background:#F5F5F5;" | Nl
+| align="center" style="background:#F5F5F5;" | Nl
+| align="left" style="background:#F5F5F5;" |
+* AR inheritance
+* Absence of the platelet Gp Ib-IX-V receptor
+* On PBS: giant platelets
+* Ristocetin - no aggregation
+|-
+! align="left" style="padding: 5px 5px; background: #DCDCDC;" |Platelet storage pool disorder:
+*[[Hermansky-Pudlak syndrome]]
+*[[Chediak-Higashi syndrome]]
+*[[Gray platelet syndrome]]
+| align="left" style="background:#F5F5F5;" |
+* Positive family history
+* [[Hairy cell leukemia]]
+* [[Cardiovascular bypass]]
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | <nowiki>+</nowiki>
+| align="center" style="background:#F5F5F5;" | <nowiki>+</nowiki>
+| align="center" style="background:#F5F5F5;" | <nowiki>+</nowiki>
+| align="center" style="background:#F5F5F5;" | −
+| align="center" style="background:#F5F5F5;" | −
+| align="center" style="background:#F5F5F5;" | Nl or ↓
+| align="center" style="background:#F5F5F5;" | ↑
+| align="center" style="background:#F5F5F5;" | Nl
+| align="center" style="background:#F5F5F5;" | Nl
+| align="center" style="background:#F5F5F5;" | Nl
+| align="left" style="background:#F5F5F5;" |
+* AD inheritance
+* AbNlities of platelet granule formation
+|-
+! colspan="2" align="center" style="padding: 5px 5px; background: #DCDCDC;" |Acquired Disorders of [[Platelet]] Function
+| align="left" style="background:#F5F5F5 " |
+* [[Chronic renal failure pathophysiology|Uremia]]
+* [[Cardiopulmonary bypass]]
+* Hematologic disorders such as: [[Myeloproliferative disease|myeloproliferative]] and [[Myelodysplastic syndrome|myelodysplastic syndromes]]
+| align="center" style="background:#F5F5F5;" | <nowiki>+</nowiki>
+| align="center" style="background:#F5F5F5;" | <nowiki>+</nowiki>
+| align="center" style="background:#F5F5F5;" | <nowiki>+</nowiki>
+| align="center" style="background:#F5F5F5;" | <nowiki>+</nowiki>
+| align="center" style="background:#F5F5F5;" |±
+| align="center" style="background:#F5F5F5;" |±
+| align="center" style="background:#F5F5F5;" | Nl or ↓
+| align="center" style="background:#F5F5F5;" | ↑
+| align="center" style="background:#F5F5F5;" | Nl
+| align="center" style="background:#F5F5F5;" | Nl
+| align="center" style="background:#F5F5F5;" | Nl
+| align="center" style="background:#F5F5F5;" | −
+|-
+! colspan="2" align="center" style="padding: 5px 5px; background: #DCDCDC;" |[[Von Willebrand disease|Von Willebrand Disease]]
+| align="left" style="background:#F5F5F5;" |
+* Easy bruising
+* [[Epistaxis]]
+* Oral cavity bleeding
+* Bleeding after dental extraction/surgery
+* [[Menorrhagia]]
+* [[Postpartum hemorrhage]]
+| align="center" style="background:#F5F5F5;" | <nowiki>+</nowiki>
+| align="center" style="background:#F5F5F5;" | <nowiki>+</nowiki>
+| align="center" style="background:#F5F5F5;" | <nowiki>+</nowiki>
+| align="center" style="background:#F5F5F5;" | <nowiki>+</nowiki>
+| align="center" style="background:#F5F5F5;" |±
+| align="center" style="background:#F5F5F5;" |±
+| align="center" style="background:#F5F5F5;" | ↑
+| align="center" style="background:#F5F5F5;" | Nl
+| align="center" style="background:#F5F5F5;" | ↑
+| align="center" style="background:#F5F5F5;" | ↑
+| align="center" style="background:#F5F5F5;" | Nl
+| align="center" style="background:#F5F5F5;" | See the table below for the details about different types.
+|-
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |Subcategory
+! colspan="2" align="center" style="background:#4479BA; color: #FFFFFF;" + |Disease
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |History
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |Mucosal bleeding
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |Petechia
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |Ecchymoses
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |Menorrhagia
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |Hematoma
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |Hemarthrosis
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |Plt
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |BT
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |PT
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |PTT
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |TT
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |Comments
+|-
+! rowspan="7" align="center" style="padding: 5px 5px; background: #DCDCDC;" |[[Thrombocytopenia]]
+! colspan="2" align="center" style="padding: 5px 5px; background: #DCDCDC;" |[[Infection]]-Induced [[thrombocytopenia]]
+| align="left" style="background:#F5F5F5;" |
+* History of prior infection
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | ↓
+| align="center" style="background:#F5F5F5;" | ↑
+| align="center" style="background:#F5F5F5;" | Nl
+| align="center" style="background:#F5F5F5;" | Nl
+| align="center" style="background:#F5F5F5;" | Nl
+| align="center" style="background:#F5F5F5;" | −
+|-
+! colspan="2" align="center" style="padding: 5px 5px; background: #DCDCDC;" |[[Medication]]-Induced [[Thrombocytopenia|Thrombocytopenia]]
+| align="left" style="background:#F5F5F5;" |
+*History of [[Medication|medications]] such as:
+** [[Furosemide]]
+** [[Non-steroidal anti-inflammatory drug|Nonsteroidal anti-inflammatory drugs]] ([[Non-steroidal anti-inflammatory drug|NSAIDs]])
+** [[Penicillin]]
+** [[Quinidine]]
+** [[Quinine]]
+** [[Ranitidine]]
+** [[Sulfonamide (medicine)|Sulfonamides]]
+** [[Linezolid]]
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | ↓
+| align="center" style="background:#F5F5F5;" | ↑
+| align="center" style="background:#F5F5F5;" | Nl
+| align="center" style="background:#F5F5F5;" | Nl
+| align="center" style="background:#F5F5F5;" | Nl
+| align="center" style="background:#F5F5F5;" | Most important part of treatment is discontinuing of the medication.
+|-
+! colspan="2" align="center" style="padding: 5px 5px; background: #DCDCDC;" |[[Heparin-Induced Thrombocytopenia|Heparin-Induced thrombocytopenia]]
+| align="left" style="background:#F5F5F5;" |
+* [[Thrombosis]]
+* Unexplained [[thrombocytopenia]] up to 3 weeks after the end of [[heparin]] therapy
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | ↓
+| align="center" style="background:#F5F5F5;" | ↑
+| align="center" style="background:#F5F5F5;" | Nl
+| align="center" style="background:#F5F5F5;" | Nl
+| align="center" style="background:#F5F5F5;" | ↑
+| align="center" style="background:#F5F5F5;" | For more information click here: [[Heparin-induced thrombocytopenia]].
+|-
+! colspan="2" align="center" style="padding: 5px 5px; background: #DCDCDC;" |[[Idiopathic thrombocytopenic purpura|Immune Thrombocytopenic Purpura]]
+| align="left" style="background:#F5F5F5;" |
+* History of prior [[infection]] or no history
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | ↓
+| align="center" style="background:#F5F5F5;" | ↑
+| align="center" style="background:#F5F5F5;" | Nl
+| align="center" style="background:#F5F5F5;" | Nl
+| align="center" style="background:#F5F5F5;" | Nl
+| align="center" style="background:#F5F5F5;" | −
+|-
+! colspan="2" align="center" style="padding: 5px 5px; background: #DCDCDC;" |Inherited [[Thrombocytopenia]]
+| align="left" style="background:#F5F5F5;" |
+* Positive family history
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | ↓
+| align="center" style="background:#F5F5F5;" | ↑
+| align="center" style="background:#F5F5F5;" | Nl
+| align="center" style="background:#F5F5F5;" | Nl
+| align="center" style="background:#F5F5F5;" | Nl
+| align="center" style="background:#F5F5F5;" | −
+|-
+! colspan="2" align="center" style="padding: 5px 5px; background: #DCDCDC;" |[[Thrombotic thrombocytopenic purpura|Thrombotic Thrombocytopenic Purpura]]
+| align="left" style="background:#F5F5F5;" | History of:
+*[[Cancer]]
+*[[Bone marrow transplantation]]
+*[[Pregnancy]]
+*[[Medication]]
+**[[Platelet]] aggregation inhibitors ([[ticlopidine]] and [[clopidogrel]])
+**Immunosuppressants ([[cyclosporine]], [[mitomycin]], [[tacrolimus]]/FK506, [[interferon|interferon-α]])
+*[[HIV-1]] infection
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | ↓
+| align="center" style="background:#F5F5F5;" | ↑
+| align="center" style="background:#F5F5F5;" | Nl
+| align="center" style="background:#F5F5F5;" | Nl
+| align="center" style="background:#F5F5F5;" | Nl
+| align="center" style="background:#F5F5F5;" | −
+|-
+! colspan="2" align="center" style="padding: 5px 5px; background: #DCDCDC;" |[[Hemolytic-uremic syndrome|Hemolytic Uremic Syndrome]]
+| align="left" style="background:#F5F5F5;" |History of:
+* [[Infections]]
+* [[Malignancy]], [[chemotherapy]], and [[ionizing radiation]]
+* [[Calcineurin inhibitor]]s and [[transplantation]]
+* [[Pregnancy]], [[HELLP syndrome]], and [[oral contraceptive pill]]
+* [[Systemic lupus erythematosis]]
+* [[Antiphospholipid syndrome|Antiphospholipid antibody syndrome]]
+* [[Glomerulopathy]]
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | ↓
+| align="center" style="background:#F5F5F5;" | ↑
+| align="center" style="background:#F5F5F5;" | Nl
+| align="center" style="background:#F5F5F5;" | Nl
+| align="center" style="background:#F5F5F5;" | Nl
+| align="center" style="background:#F5F5F5;" | −
+|-
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |Subcategory
+! colspan="2" align="center" style="background:#4479BA; color: #FFFFFF;" + |Disease
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |History
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |Mucosal bleeding
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |Petechia
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |Ecchymoses
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |Menorrhagia
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |Hematoma
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |Hemarthrosis
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |Plt
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |BT
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |PT
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |PTT
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |TT
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |Comments
+|-
+! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Vessel wall disorders
+! align="center" style="padding: 5px 5px; background: #DCDCDC;" |[[Metabolism|Metabolic]] and [[Inflammation|Inflammatory]] Disorders
+! colspan="2" align="left" style="padding: 5px 5px; background: #DCDCDC;" |
+* Acute febrile illnesses
+* [[Cryoglobulinemia|Mixed cryoglobulinemia]]
+* [[Monoclonal gammopathy|Monoclonal gammopathies]]
+* [[Rocky Mountain spotted fever]]
+* [[Vitamin C deficiency]]
+* [[Cushing's syndrome|Cushing’s syndrome]]
+* Chronic [[glucocorticoid]] therapy
+* [[Vasculitis]] such as Henoch-Schönlein Purpura
+| align="left" style="background:#F5F5F5;" |
+* History of the underlying disease
+| align="center" style="background:#F5F5F5;" |−
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" |±
+| align="center" style="background:#F5F5F5;" |−
+| align="center" style="background:#F5F5F5;" |−
+| align="center" style="background:#F5F5F5;" |Nl
+| align="center" style="background:#F5F5F5;" |Nl or ↑
+| align="center" style="background:#F5F5F5;" |Nl
+| align="center" style="background:#F5F5F5;" |Nl
+| align="center" style="background:#F5F5F5;" |Nl
+| align="center" style="background:#F5F5F5;" |−
+|-
+! align="center" style="padding: 5px 5px; background: #DCDCDC;" |Inherited Disorders of the [[Vessel wall|Vessel Wall]]
+! colspan="2" align="left" style="background:#DCDCDC;" |
+* [[Marfan's syndrome|Marfan’s syndrome]]
+* [[Ehlers-Danlos syndrome]]
+* [[Pseudoxanthoma elasticum]]
+* [[Hereditary hemorrhagic telangiectasia]] ([[Hereditary hemorrhagic telangiectasia|HHT]], or [[Osler-Weber-Rendu|Osler-Weber-Rendu disease]])
+| align="left" style="background:#F5F5F5;" |
+* Positive family history
+| align="center" style="background:#F5F5F5;" |−
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" |±
+| align="center" style="background:#F5F5F5;" |−
+| align="center" style="background:#F5F5F5;" |−
+| align="center" style="background:#F5F5F5;" |Nl
+| align="center" style="background:#F5F5F5;" |Nl or ↑
+| align="center" style="background:#F5F5F5;" |Nl
+| align="center" style="background:#F5F5F5;" |Nl
+| align="center" style="background:#F5F5F5;" |Nl
+| align="center" style="background:#F5F5F5;" |−
+|-
+! rowspan="15" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Coagulation factor disorders
+<ref name="pmid28966616" />
+! align="center" style="padding: 5px 5px; background: #DCDCDC;" |[[Fibrinogen]] deficiency
+! colspan="2" align="left" style="padding: 5px 5px; background: #DCDCDC;" |
+Different types of the [[fibrinogen]] disorders:
+* [[Fibrinogen#Congenital afibrinogenemia|Congenital afibrinogenemia]]
+* [[Fibrinogen#Congenital hypofibrinogenemia|Congenital hypofibrinogenemia]]
+* [[Fibrinogen#Fibrinogen storage disease|Fibrinogen storage disease]]
+* [[Fibrinogen#Congenital dysfibrinogenemia|Congenital dysfibrinogenemia]]
+* [[Fibrinogen#Hereditary fibrinogen A.CE.B1-Chain amyloidosis|Hereditary fibrinogen Aα-Chain amyloidosis]]
+* [[Fibrinogen#Acquired dysfibrinogenemia|Acquired dysfibrinogenemia]]
+| align="left" style="background:#F5F5F5;" |
+* [[Epistaxis]]
+* Easy [[Bruise|bruising]]
+* [[Menorrhagia]]
+* [[Muscle]] bleeds
+* [[Hemarthrosis]]
+* [[Bleeding]] from the [[umbilical cord]] stump after birth
+* Bleeding after [[dental surgery]] or tooth extraction
+* AbNl bleeding during or after injury, surgery, or childbirth
+* [[Gastrointestinal tract|Gastrointestinal]] [[hemorrhage]]
+* [[Cerebral hemorrhage]]
+* [[Thrombosis]]
+| align="center" style="background:#F5F5F5;" |−
+| align="center" style="background:#F5F5F5;" |−
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" |±
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" |Nl
+| align="center" style="background:#F5F5F5;" |↑
+| align="center" style="background:#F5F5F5;" |↑
+| align="center" style="background:#F5F5F5;" |↑
+| align="center" style="background:#F5F5F5;" |↑
+| align="left" style="background:#F5F5F5;" |
+* Impaired fibrin cross-linking or clot dissolution
+* Mild or severe bleeding idepend on levels of functional fibrinogen
+* Variable age of onset
+|-
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |Subcategory
+! colspan="2" align="center" style="background:#4479BA; color: #FFFFFF;" + |Disease
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |History
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |Mucosal bleeding
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |Petechia
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |Ecchymoses
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |Menorrhagia
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |Hematoma
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |Hemarthrosis
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |Plt
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |BT
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |PT
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |PTT
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |TT
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |Comments
+|-
+! colspan="3" align="center" style="padding: 5px 5px; background: #DCDCDC;" |[[Prothrombin deficiency]]
+| align="left" style="background:#F5F5F5;" |
+* [[Epistaxis]]
+* Soft-tissue hemorrhage
+* Excessive postoperative bleeding
+* [[Menorrhagia]]
+* Muscle [[Hematoma|hematomas]]
+* [[Hemarthrosis]]
+* [[Intracranial hemorrhage|Intracranial]] bleeding
+| align="center" style="background:#F5F5F5;" | −
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | Nl
+| align="center" style="background:#F5F5F5;" | Nl
+| align="center" style="background:#F5F5F5;" | ↑
+| align="center" style="background:#F5F5F5;" | ↑
+| align="center" style="background:#F5F5F5;" | ↑
+| align="center" style="background:#F5F5F5;" | −
+|-
+! colspan="3" rowspan="1" align="center" style="padding: 5px 5px; background: #DCDCDC;" |[[Factor V deficiency]]
+| align="left" style="background:#F5F5F5;" |
+* Excessive bruising with minor injuries
+* [[Epistaxis]]
+* [[Hemarthrosis]]
+* [[Menorrhagia]]
+* [[Intracerebral hemorrhage|Intracerebral hemorrhages]]
+* [[Pulmonary hemorrhage]]
+| align="center" style="background:#F5F5F5;" | −
+| align="center" style="background:#F5F5F5;" | −
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" |Nl
+| align="center" style="background:#F5F5F5;" |↑
+| align="center" style="background:#F5F5F5;" |↑
+| align="center" style="background:#F5F5F5;" |↑
+| align="center" style="background:#F5F5F5;" |Nl
+| align="center" style="background:#F5F5F5;" |
+* The severity of bleeding related to the degree of factor V deficiency
+|-
+! colspan="3" rowspan="1" align="center" style="padding: 5px 5px; background: #DCDCDC;" |[[Factor VII deficiency]]
+| align="left" style="background:#F5F5F5;" |
+* Easy [[Bruise|bruising]]
+* Mucosal bleeding
+* Postoperative bleeding
+* [[Menorrhagia]]
+* Soft tissue hematomas
+* [[Thrombosis]]
+| align="center" style="background:#F5F5F5;" |
+| align="center" style="background:#F5F5F5;" |
+| align="center" style="background:#F5F5F5;" |
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" |Nl
+| align="center" style="background:#F5F5F5;" |
+| align="center" style="background:#F5F5F5;" |↑
+| align="center" style="background:#F5F5F5;" |Nl
+| align="center" style="background:#F5F5F5;" |Nl
+| align="left" style="background:#F5F5F5;" |
+* Thrombosis in inherited factor VII deficiency
+* Treatment with the administration of factor VII replacement therapy
+|-
+! colspan="3" rowspan="1" align="center" style="padding: 5px 5px; background: #DCDCDC;" |[[Factor X deficiency]]
+| align="left" style="background:#F5F5F5;" |
+* Prolonged bleeding following circumcision
+* Easy [[Bruise|bruising]]
+* [[Hematuria]]
+* [[Menorrhagia]]
+* Abortion
+* Postpartum hemorrhage
+* Epistaxis
+* Pseudotumors
+* Intracranial bleeding
+* Hemarthroses
+| align="center" style="background:#F5F5F5;" |
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" |Nl
+| align="center" style="background:#F5F5F5;" |Nl
+| align="center" style="background:#F5F5F5;" |↑
+| align="center" style="background:#F5F5F5;" |↑
+| align="center" style="background:#F5F5F5;" |Nl
+| align="center" style="background:#F5F5F5;" |−
+|-
+! colspan="3" rowspan="1" align="center" style="padding: 5px 5px; background: #DCDCDC;" |[[Factor XII|Factor XII deficiency]]
+| align="left" style="background:#F5F5F5;" |
+* Asymptomatic
+* Recurrent miscarriages
+* Painful leg ulcers
+| align="center" style="background:#F5F5F5;" |
+| align="center" style="background:#F5F5F5;" |−
+| align="center" style="background:#F5F5F5;" |−
+| align="center" style="background:#F5F5F5;" |−
+| align="center" style="background:#F5F5F5;" |−
+| align="center" style="background:#F5F5F5;" |−
+| align="center" style="background:#F5F5F5;" |Nl
+| align="center" style="background:#F5F5F5;" |Nl
+| align="center" style="background:#F5F5F5;" |Nl
+| align="center" style="background:#F5F5F5;" |↑
+| align="center" style="background:#F5F5F5;" |Nl
+| align="center" style="background:#F5F5F5;" |
+|-
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |Subcategory
+! colspan="2" align="center" style="background:#4479BA; color: #FFFFFF;" + |Disease
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |History
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |Mucosal bleeding
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |Petechia
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |Ecchymoses
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |Menorrhagia
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |Hematoma
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |Hemarthrosis
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |Plt
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |BT
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |PT
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |PTT
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |TT
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |Comments
+|-
+! colspan="3" align="center" style="padding: 5px 5px; background: #DCDCDC;" |[[High-molecular-weight kininogen|High molecular weight kininogen (HMWK)]] deficiency
+| align="left" style="background:#F5F5F5;" |
+* Positive family history of bleeding
+| align="center" style="background:#F5F5F5;" |
+| align="center" style="background:#F5F5F5;" |−
+| align="center" style="background:#F5F5F5;" |−
+| align="center" style="background:#F5F5F5;" |−
+| align="center" style="background:#F5F5F5;" |−
+| align="center" style="background:#F5F5F5;" |−
+| align="center" style="background:#F5F5F5;" |Nl
+| align="center" style="background:#F5F5F5;" |Nl
+| align="center" style="background:#F5F5F5;" |Nl
+| align="center" style="background:#F5F5F5;" |↑
+| align="center" style="background:#F5F5F5;" |Nl
+| align="center" style="background:#F5F5F5;" |
+|-
+! colspan="3" rowspan="1" align="center" style="padding: 5px 5px; background: #DCDCDC;" |[[Prekallikrein]] deficiency
+| align="left" style="background:#F5F5F5;" |
+* Positive family history of bleeding
+| align="center" style="background:#F5F5F5;" |
+| align="center" style="background:#F5F5F5;" |−
+| align="center" style="background:#F5F5F5;" |−
+| align="center" style="background:#F5F5F5;" |−
+| align="center" style="background:#F5F5F5;" |−
+| align="center" style="background:#F5F5F5;" |−
+| align="center" style="background:#F5F5F5;" |Nl
+| align="center" style="background:#F5F5F5;" |Nl
+| align="center" style="background:#F5F5F5;" |Nl
+| align="center" style="background:#F5F5F5;" |↑
+| align="center" style="background:#F5F5F5;" |Nl
+| align="center" style="background:#F5F5F5;" |
+|-
+! rowspan="1" align="center" style="padding: 5px 5px; background: #DCDCDC;" |[[Factor XIII deficiency]]
+! colspan="2" align="center" style="padding: 5px 5px; background: #DCDCDC;" |
+* Sub unit A mutation disease (more common)
+* Sub unit B mutation disease
+| align="left" style="background:#F5F5F5;" |
+* Positive family history of bleeding
+| align="center" style="background:#F5F5F5;" |±
+| align="center" style="background:#F5F5F5;" |±
+| align="center" style="background:#F5F5F5;" |±
+| align="center" style="background:#F5F5F5;" |±
+| align="center" style="background:#F5F5F5;" |±
+| align="center" style="background:#F5F5F5;" |±
+| align="center" style="background:#F5F5F5;" |Nl
+| align="center" style="background:#F5F5F5;" |Nl
+| align="center" style="background:#F5F5F5;" |Nl or ↑
+| align="center" style="background:#F5F5F5;" |Nl
+| align="center" style="background:#F5F5F5;" |Nl
+| align="left" style="background:#F5F5F5;" |
+* Impaired fibrin cross-linking or clot dissolution
+* The severity of factor XIII deficiency bleeds can be different in different patients
+|-
+! rowspan="3" align="center" style="padding: 5px 5px; background: #DCDCDC;" |[[Hemophilia]]
+! colspan="2" align="center" style="padding: 5px 5px; background: #DCDCDC;" |Type A deficiency
+| align="left" style="background:#F5F5F5;" |
+* Eeasy [[Bruise|bruising]]
+* Inadequate clotting in [[trauma]] or mild injury
+* Spontaneous hemorrhage
+* [[Hemarthrosis]]
+* [[Epistaxis]]
+* [[Gingival bleeding]]
+| align="center" style="background:#F5F5F5;" |−
+| align="center" style="background:#F5F5F5;" |−
+| align="center" style="background:#F5F5F5;" |−
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" |Nl
+| align="center" style="background:#F5F5F5;" |Nl
+| align="center" style="background:#F5F5F5;" |Nl
+| align="center" style="background:#F5F5F5;" |↑
+| align="center" style="background:#F5F5F5;" |Nl
+| align="center" style="background:#F5F5F5;" |−
+|-
+! colspan="2" align="center" style="padding: 5px 5px; background: #DCDCDC;" |Type B deficiency
+| align="left" style="background:#F5F5F5;" |
+* Neonatal bleeding
+* Trauma-related soft tissue hemorrhage
+* [[Hemarthrosis]]
+* [[Hematoma|Hematomas]]
+| align="center" style="background:#F5F5F5;" |−
+| align="center" style="background:#F5F5F5;" |−
+| align="center" style="background:#F5F5F5;" |−
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" |Nl
+| align="center" style="background:#F5F5F5;" |Nl
+| align="center" style="background:#F5F5F5;" |Nl
+| align="center" style="background:#F5F5F5;" |↑
+| align="center" style="background:#F5F5F5;" |Nl
+| align="center" style="background:#F5F5F5;" |−
+|-
+! colspan="2" align="center" style="padding: 5px 5px; background: #DCDCDC;" |Type C deficiency
+| align="left" style="background:#F5F5F5;" |
+* Positive family history
+* Bleeding after surgery or injury
+| align="center" style="background:#F5F5F5;" |−
+| align="center" style="background:#F5F5F5;" |−
+| align="center" style="background:#F5F5F5;" |−
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" |Rare
+| align="center" style="background:#F5F5F5;" |Rare
+| align="center" style="background:#F5F5F5;" |Nl
+| align="center" style="background:#F5F5F5;" |Nl
+| align="center" style="background:#F5F5F5;" |Nl
+| align="center" style="background:#F5F5F5;" |↑
+| align="center" style="background:#F5F5F5;" |Nl
+| align="center" style="background:#F5F5F5;" |−
+|-
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |Subcategory
+! colspan="2" align="center" style="background:#4479BA; color: #FFFFFF;" + |Disease
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |History
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |Mucosal bleeding
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |Petechia
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |Ecchymoses
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |Menorrhagia
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |Hematoma
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |Hemarthrosis
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |Plt
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |BT
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |PT
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |PTT
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |TT
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |Comments
+|-
+! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Rare diseases
+! colspan="3" align="center" style="padding: 5px 5px; background: #DCDCDC;" |[[Disseminated intravascular coagulation|Disseminated Intravascular Coagulation]]
+| align="left" style="background:#F5F5F5;" |
+* [[Trauma]]
+* [[Burn]]
+* [[Crush injury]]
+* [[Sepsis]]
+* [[Malignancy]]
+* Obstetric complication: abruption, amniotic fluid embolism
+* [[Hemolytic anemia]]
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" |↓
+| align="center" style="background:#F5F5F5;" |↑
+| align="center" style="background:#F5F5F5;" |↑
+| align="center" style="background:#F5F5F5;" |↑
+| align="center" style="background:#F5F5F5;" |Nl
+| align="center" style="background:#F5F5F5;" |−
+|-
+! colspan="3" align="center" style="padding: 5px 5px; background: #DCDCDC;" |[[Vitamin K Deficiency]]
+| align="left" style="background:#F5F5F5;" |
+* Bleeding after trauma
+* [[Epistaxis]]
+* [[Hematoma]]
+* Gastrointestinal bleeding
+* [[Menorrhagia]]
+* [[Hematuria]]
+* Gum bleeding
+* Oozing from venipuncture sites
+* Easy [[Bruise|bruisability]]
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" |−
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" | +
+| align="center" style="background:#F5F5F5;" |Nl
+| align="center" style="background:#F5F5F5;" |↑
+| align="center" style="background:#F5F5F5;" |↑
+| align="center" style="background:#F5F5F5;" |Nl or mildly prolonged
+| align="center" style="background:#F5F5F5;" |Nl
+| align="center" style="background:#F5F5F5;" |−
+|}
 ==Risk Factors==
+* Positive family history of Wiskott-Aldrich syndrome, can be considered as a risk factor.
 ==Screening==
-*Flow cytometry:
+*[[Flow cytometry]]:
-** Anti-WASp antibody can be used to detect presence or absence of WAS protein. However, flow cytometry may not detect expression of mutated,  reduced or poor WASP expression.<ref name="pmid29729304">{{cite journal |vauthors=Chiang SCC, Vergamini SM, Husami A, Neumeier L, Quinn K, Ellerhorst T, Sheppard L, Gifford C, Buchbinder D, Joshi A, Ifversen M, Kleiner GI, Bussel JB, Chandrakasan S, Pesek RD, Pozos TC, Rose MJ, Scurlock AM, Zhang K, Bryceson YT, Bleesing J, Marsh RA |title=Screening for Wiskott-Aldrich syndrome by flow cytometry |journal=J. Allergy Clin. Immunol. |volume=142 |issue=1 |pages=333–335.e8 |date=July 2018 |pmid=29729304 |doi=10.1016/j.jaci.2018.04.017 |url=}}</ref>
+** Anti-WASp antibody can be used to detect presence or absence of WAS protein. However, [[flow cytometry]] may not detect expression of mutated, reduced or poor WASp.<ref name="pmid29729304">{{cite journal |vauthors=Chiang SCC, Vergamini SM, Husami A, Neumeier L, Quinn K, Ellerhorst T, Sheppard L, Gifford C, Buchbinder D, Joshi A, Ifversen M, Kleiner GI, Bussel JB, Chandrakasan S, Pesek RD, Pozos TC, Rose MJ, Scurlock AM, Zhang K, Bryceson YT, Bleesing J, Marsh RA |title=Screening for Wiskott-Aldrich syndrome by flow cytometry |journal=J. Allergy Clin. Immunol. |volume=142 |issue=1 |pages=333–335.e8 |date=July 2018 |pmid=29729304 |doi=10.1016/j.jaci.2018.04.017 |url=}}</ref>
-* Identification of carriers: Known female carriers can be identified by using DNA mutation analysis involving [[WAS gene]].
+* Identification of carriers: Known [[female]] carriers can be identified by using [[DNA]] mutation analysis of WAS gene.
-* Prenatal diagnosis: DNA analysis from chorionic villus sampling can be performed.<ref name="pmid10073904">{{cite journal |vauthors=Giliani S, Fiorini M, Mella P, Candotti F, Schumacher RF, Wengler GS, Lalatta F, Fasth A, Badolato R, Ugazio AG, Albertini A, Notarangelo LD |title=Prenatal molecular diagnosis of Wiskott-Aldrich syndrome by direct mutation analysis |journal=Prenat. Diagn. |volume=19 |issue=1 |pages=36–40 |date=January 1999 |pmid=10073904 |doi= |url=}}</ref>
+* Prenatal diagnosis: [[DNA]] analysis from [[chorionic villus sampling]] can be performed.<ref name="pmid10073904">{{cite journal |vauthors=Giliani S, Fiorini M, Mella P, Candotti F, Schumacher RF, Wengler GS, Lalatta F, Fasth A, Badolato R, Ugazio AG, Albertini A, Notarangelo LD |title=Prenatal molecular diagnosis of Wiskott-Aldrich syndrome by direct mutation analysis |journal=Prenat. Diagn. |volume=19 |issue=1 |pages=36–40 |date=January 1999 |pmid=10073904 |doi= |url=}}</ref>
 ==Natural History, Complications, and Prognosis==
-*If left untreated, [[Patient|patients]] with Wiscott-Aldrich syndrome may progress to develop manifestations associated with [[thrombocytopenia]], defective [[Innate immune system|innate]] and [[Adaptive immune system|adaptive immunity]] which include, severe [[bleeding]] (eg, [[epistaxis]], [[purpura]], life threatening [[Gastrointestinal tract|gastrointestinal]] and [[Intracranial hemorrhage|intracranial hemorrhages]]), recurrent and severe bronchopulmonary infections. Malignancy and [[autoimmunity]] risk has also increased. These conditions may increase the risk of death.<ref name="pmid7996359">{{cite journal |vauthors=Sullivan KE, Mullen CA, Blaese RM, Winkelstein JA |title=A multiinstitutional survey of the Wiskott-Aldrich syndrome |journal=J. Pediatr. |volume=125 |issue=6 Pt 1 |pages=876–85 |date=December 1994 |pmid=7996359 |doi= |url=}}</ref>
+*If left untreated, [[Patient|patients]] with Wiscott-Aldrich syndrome may progress to develop manifestations associated with [[thrombocytopenia]], and abnormal platelet function, defective [[Innate immune system|innate]] and [[Adaptive immune system|adaptive immunity]] which include, severe [[bleeding]] (eg, [[epistaxis]], [[purpura]], life threatening [[Gastrointestinal tract|gastrointestinal]] and [[Intracranial hemorrhage|intracranial hemorrhages]]), recurrent and severe bronchopulmonary infections. Malignancy and [[autoimmunity]] risk has also increased. These conditions may increase the risk of death.<ref name="pmid7996359">{{cite journal |vauthors=Sullivan KE, Mullen CA, Blaese RM, Winkelstein JA |title=A multiinstitutional survey of the Wiskott-Aldrich syndrome |journal=J. Pediatr. |volume=125 |issue=6 Pt 1 |pages=876–85 |date=December 1994 |pmid=7996359 |doi= |url=}}</ref>
 *Common complications of Wiscott-Aldrich syndrome include:
 ** Recurrent infections with [[Bacteria|bacterial]], [[Virus|viral]], [[Fungus|fungal]] and [[Opportunistic infection|opportunistic organisms]]. Most common clinical manifestations include [[otitis media]], [[Rhinosinusitis|sinusitis]], [[pneumonia]], [[meningitis]], [[Skin and soft-tissue infections|skin infections]], and [[sepsis]].<ref name="pmid14159941">{{cite journal |vauthors=WEINTRAUB HD, WILSON WJ |title=PNEUMOCYSTIS CARINII PNEUMONIA IN WISKOTT-ALDRICH SYNDROME |journal=Am. J. Dis. Child. |volume=108 |issue= |pages=198–200 |date=August 1964 |pmid=14159941 |doi= |url=}}</ref><ref name="pmid24007832">{{cite journal |vauthors=Blancas-Galicia L, Escamilla-Quiroz C, Yamazaki-Nakashimada MA |title=[Wiskott-Aldrich Syndrome: An updated review] |language=Spanish; Castilian |journal=Rev Alerg Mex |volume=58 |issue=4 |pages=213–8 |date=2011 |pmid=24007832 |doi= |url=}}</ref><ref name="pmid12969986">{{cite journal |vauthors=Imai K, Morio T, Zhu Y, Jin Y, Itoh S, Kajiwara M, Yata J, Mizutani S, Ochs HD, Nonoyama S |title=Clinical course of patients with WASP gene mutations |journal=Blood |volume=103 |issue=2 |pages=456–64 |date=January 2004 |pmid=12969986 |doi=10.1182/blood-2003-05-1480 |url=}}</ref>
-** [[Bleeding diathesis]] (eg, [[epistaxis]], [[Bruise|ecchymoses]], [[Petechia|petechiae]], [[Intracranial hemorrhage|intracranial]] and [[Gastrointestinal bleeding|gastrointestinal hemorrhages]])<ref name="pmid7996359">{{cite journal |vauthors=Sullivan KE, Mullen CA, Blaese RM, Winkelstein JA |title=A multiinstitutional survey of the Wiskott-Aldrich syndrome |journal=J. Pediatr. |volume=125 |issue=6 Pt 1 |pages=876–85 |date=December 1994 |pmid=7996359 |doi= |url=}}</ref><ref name="pmid23449611">{{cite journal |vauthors=Notarangelo LD |title=In Wiskott-Aldrich syndrome, platelet count matters |journal=Blood |volume=121 |issue=9 |pages=1484–5 |date=February 2013 |pmid=23449611 |doi=10.1182/blood-2013-01-475913 |url=}}</ref>
+** [[Bleeding diathesis]] (eg, [[epistaxis]], [[Bruise|ecchymoses]], [[Petechia|petechiae]], [[hematemesis]], [[Intracranial hemorrhage|intracranial]] and [[Gastrointestinal bleeding|gastrointestinal hemorrhages]])<ref name="pmid7996359">{{cite journal |vauthors=Sullivan KE, Mullen CA, Blaese RM, Winkelstein JA |title=A multiinstitutional survey of the Wiskott-Aldrich syndrome |journal=J. Pediatr. |volume=125 |issue=6 Pt 1 |pages=876–85 |date=December 1994 |pmid=7996359 |doi= |url=}}</ref><ref name="pmid23449611">{{cite journal |vauthors=Notarangelo LD |title=In Wiskott-Aldrich syndrome, platelet count matters |journal=Blood |volume=121 |issue=9 |pages=1484–5 |date=February 2013 |pmid=23449611 |doi=10.1182/blood-2013-01-475913 |url=}}</ref>
 ** Autoimmune manifestations may occur in the form of [[autoimmune hemolytic anemia]], [[immune thrombocytopenic purpura]] and [[neutropenia]], [[vasculitis]] involving small and large vessels, [[inflammatory bowel disease]], and  immune-mediated damage to the [[Kidney|kidneys]] and [[Joint|joints]].<ref name="pmid12728121">{{cite journal |vauthors=Dupuis-Girod S, Medioni J, Haddad E, Quartier P, Cavazzana-Calvo M, Le Deist F, de Saint Basile G, Delaunay J, Schwarz K, Casanova JL, Blanche S, Fischer A |title=Autoimmunity in Wiskott-Aldrich syndrome: risk factors, clinical features, and outcome in a single-center cohort of 55 patients |journal=Pediatrics |volume=111 |issue=5 Pt 1 |pages=e622–7 |date=May 2003 |pmid=12728121 |doi= |url=}}</ref><ref name="pmid25877044">{{cite journal |vauthors=Chen N, Zhang ZY, Liu DW, Liu W, Tang XM, Zhao XD |title=The clinical features of autoimmunity in 53 patients with Wiskott-Aldrich syndrome in China: a single-center study |journal=Eur. J. Pediatr. |volume=174 |issue=10 |pages=1311–8 |date=October 2015 |pmid=25877044 |doi=10.1007/s00431-015-2527-3 |url=}}</ref><ref name="pmid29358862">{{cite journal |vauthors=Ohya T, Yanagimachi M, Iwasawa K, Umetsu S, Sogo T, Inui A, Fujisawa T, Ito S |title=Childhood-onset inflammatory bowel diseases associated with mutation of Wiskott-Aldrich syndrome protein gene |journal=World J. Gastroenterol. |volume=23 |issue=48 |pages=8544–8552 |date=December 2017 |pmid=29358862 |pmc=5752714 |doi=10.3748/wjg.v23.i48.8544 |url=}}</ref>
 ** Increased risk of malignancy such as [[lymphoma]], [[Leukemia|leukaemia]] is a frequent occurence in Wiskott-Aldrich syndrome.<ref name="pmid3910193">{{cite journal |vauthors=Cotelingam JD, Witebsky FG, Hsu SM, Blaese RM, Jaffe ES |title=Malignant lymphoma in patients with the Wiskott-Aldrich syndrome |journal=Cancer Invest. |volume=3 |issue=6 |pages=515–22 |date=1985 |pmid=3910193 |doi= |url=}}</ref><ref name="pmid23023736">{{cite journal |vauthors=Yoshimi A, Kamachi Y, Imai K, Watanabe N, Nakadate H, Kanazawa T, Ozono S, Kobayashi R, Yoshida M, Kobayashi C, Hama A, Muramatsu H, Sasahara Y, Jakob M, Morio T, Ehl S, Manabe A, Niemeyer C, Kojima S |title=Wiskott-Aldrich syndrome presenting with a clinical picture mimicking juvenile myelomonocytic leukaemia |journal=Pediatr Blood Cancer |volume=60 |issue=5 |pages=836–41 |date=May 2013 |pmid=23023736 |doi=10.1002/pbc.24359 |url=}}</ref>
@@ Line 87: / Line 926: @@
 ==Diagnosis==
 ===Diagnostic Study of Choice===
-*The first laboratory test to be performed in the diagnosis of Wiskott-Aldrich syndrome is complete blood count with differential and peripheral blood smears.
+*The first laboratory test to be performed in the diagnosis of Wiskott-Aldrich syndrome is [[Complete blood count|complete blood count with differential]] and [[Blood film|peripheral blood smears]].
-*The diagnosis of Wiskott-Aldrich syndrome is based on the presence of thrombocytopenia with small platelet volume.
+*The diagnosis of Wiskott-Aldrich syndrome is suspected if a [[male]] patient who presents with [[Bruise|bruises]], [[Petechia|petechiae]], [[eczema]], recurrent [[Infection|infections]] and the presence of congenital [[thrombocytopenia]](< 70 000/mm3) with small [[platelet]] volume <5·0fl  (micro thrombocytopenia) on the [[Blood film|peripheral blood smear]].
+*Identification of  WAS gene mutations using [[DNA]] sequence analysis of WAS gene and detection of WASp expression by [[flow cytometry]] are necessary to confirm the diagnosis.<ref name="pmid15284122">{{cite journal |vauthors=Jin Y, Mazza C, Christie JR, Giliani S, Fiorini M, Mella P, Gandellini F, Stewart DM, Zhu Q, Nelson DL, Notarangelo LD, Ochs HD |title=Mutations of the Wiskott-Aldrich Syndrome Protein (WASP): hotspots, effect on transcription, and translation and phenotype/genotype correlation |journal=Blood |volume=104 |issue=13 |pages=4010–9 |date=December 2004 |pmid=15284122 |doi=10.1182/blood-2003-05-1592 |url=}}</ref><ref name="pmid12969986">{{cite journal |vauthors=Imai K, Morio T, Zhu Y, Jin Y, Itoh S, Kajiwara M, Yata J, Mizutani S, Ochs HD, Nonoyama S |title=Clinical course of patients with WASP gene mutations |journal=Blood |volume=103 |issue=2 |pages=456–64 |date=January 2004 |pmid=12969986 |doi=10.1182/blood-2003-05-1480 |url=}}</ref>
 ===History and Symptoms===
-The majority of patients with [disease name] are asymptomatic.
+* Patients with Wiskott-Aldrich syndrome have
-OR
-The hallmark of [disease name] is [finding]. A positive history of [finding 1] and [finding 2] is suggestive of [disease name]. The most common symptoms of [disease name] include [symptom 1], [symptom 2], and [symptom 3]. Common symptoms of [disease] include [symptom 1], [symptom 2], and [symptom 3]. Less common symptoms of [disease name] include [symptom 1], [symptom 2], and [symptom 3].
+* Common symptoms of Wiskott-Aldrich syndrome include:
+** [[Easy bruising]]
+** [[Petechia|Petechiae]]
+** [[Purpura]]
+** [[Eczema]]
+** Prolonged and excessive [[bleeding]] after circumcision or from umbilical stump
+** Recurrent [[Infection|infections]]
+** [[Epistaxis]] (Nose bleeds)
+** [[Hematemesis]]
+** [[Hematuria]]
+** [[Melena]]
 ===Physical Examination===
@@ Line 104: / Line 952: @@
 **[[Rales]] and [[Wheeze|wheezing]] on auscultation if there is an underlying [[Respiratory tract infection|lung infection]].
 **[[Hepatosplenomegaly]]
-**ENT examination: Carefully examine sinuses to rule out [[Rhinosinusitis|sinusitis]], [[Ear|ears]] for any [[Eardrum|tympanic membrane]] abnormalities to rule out [[otitis media]] and throat for [[pharyngitis]] and other opportunistic infections such as [[Oral candidiasis|oral thrush]].
+**ENT examination: Carefully examine sinuses to rule out [[Rhinosinusitis|sinusitis]], [[Ear|ears]] for any [[Eardrum|tympanic membrane]] abnormalities to rule out [[otitis media]] and throat for [[pharyngitis]] and other opportunistic infections such as oral thrush.
-** CNS examination may be performed for symptoms associated with [[intracranial hemorrhage]] and [[Infection|infections]].
+**CNS examination may be performed for symptoms associated with [[intracranial hemorrhage]] and [[Infection|infections]].
 ===Laboratory Findings===
@@ Line 133: / Line 981: @@
 ===MRI===
 *There are no specific [[Magnetic resonance imaging|MRI]] findings associated with Wiskott-Aldrich syndrome.
-===Other Imaging Findings===
-* There are no other imaging findings associated with Wiscott-Aldrich syndrome.
-===Other Diagnostic Studies===
-* There are no other diagnostic tests associated with Wiskott-Aldrich syndrome.
 ==Treatment==
 ===Medical Therapy===
-Treatment of Wiskott-Aldrich syndrome is based on correcting symptoms. [[Aspirin]] and other [[non-steroidal anti-inflammatory drug]]s should be avoided, since these may interfere with platelet function. A protective helmet can protect children from [[intra-axial hematoma|bleeding into the brain]] which could result from head injuries.  For severely low platelet counts, patients may require platelet transfusions or a [[splenectomy]]. For patients with frequent infections, intravenous immunoglobulins (IVIG) can be given to boost the immune system.  [[Anemia]] from bleeding may require iron supplementation or [[blood transfusion]].
+* Mainstay therapy for Wiskott-Aldrich syndrome is conservative therapy and supportive care, which includes:
+** Prophylactic antimicrobial agents should be given to treat [[Bacteria|bacterial]], [[Virus|viral]], [[Fungus|fungal]] and [[Opportunistic infection|opportunistic infections]].<ref name="pmid8957959">{{cite journal |vauthors=Litzman J, Jones A, Hann I, Chapel H, Strobel S, Morgan G |title=Intravenous immunoglobulin, splenectomy, and antibiotic prophylaxis in Wiskott-Aldrich syndrome |journal=Arch. Dis. Child. |volume=75 |issue=5 |pages=436–9 |date=November 1996 |pmid=8957959 |pmc=1511781 |doi= |url=}}</ref><ref name="pmid27462353">{{cite journal |vauthors=Kim KR, Kim JM, Kang JM, Kim YJ |title=Pneumocystis jirovecii pneumonia in pediatric patients: an analysis of 15 confirmed consecutive cases during 14 years |journal=Korean J Pediatr |volume=59 |issue=6 |pages=252–5 |date=June 2016 |pmid=27462353 |pmc=4958702 |doi=10.3345/kjp.2016.59.6.252 |url=}}</ref>
+***[[Sulfamethoxazole-Trimethoprim|Trimethoprim/sulfamethoxazole]]: 5mg/kg/day can be given to treat most [[Bacteria|bacterial]] and [[pneumocystis jirovecii pneumonia]].
+***[[Acyclovir]]:  200mg/twice daily may be given to treat viral infections (eg, [[Herpes simplex|HSV-1]])<ref name="pmid8547009">{{cite journal |vauthors=Modiano P, Salloum E, Gillet-Terver MN, Barbaud A, Georges JC, Thouvenot D, Schmutz JL, Weber M |title=Acyclovir-resistant chronic cutaneous herpes simplex in Wiskott-Aldrich syndrome |journal=Br. J. Dermatol. |volume=133 |issue=3 |pages=475–8 |date=September 1995 |pmid=8547009 |doi= |url=}}</ref>
+***[[Fluconazole]]:  3mg/kg/day may be given to treat [[Fungal infection|fungal infections]].
+** [[Platelet]] transfusions:<ref name="pmid17654055">{{cite journal |vauthors=Ferrara M, Capozzi L, Coppola A, Save G, Coppola L |title=Prophylactic platelet transfusion in children with thrombocytopenic disorders: a retrospective review |journal=Hematology |volume=12 |issue=4 |pages=297–9 |date=August 2007 |pmid=17654055 |doi=10.1080/10245330701255213 |url=}}</ref>
+*** [[Platelet]] transfusions can be given to treat [[bleeding]] episodes such as life-threatening gastrointestinal and intracranial [[Bleeding|hemorrhages]]. [[Platelet]] transfusions can also be given to patients who are undergoing any surgical procedure.
+*** If a patient can be chosen for transfusion, [[Platelet|platelets]] and [[blood]] products should be irradiated and must be obtained from a [[Cytomegalovirus infection|CMV]] free donor.
+** [[Intravenous immunoglobulin|Intravenous immunoglobulins]]:<ref name="pmid5096517">{{cite journal |vauthors=Blaese RM, Strober W, Levy AL, Waldmann TA |title=Hypercatabolism of IgG, IgA, IgM, and albumin in the Wiskott-Aldrich syndrome. A unique disorder of serum protein metabolism |journal=J. Clin. Invest. |volume=50 |issue=11 |pages=2331–8 |date=November 1971 |pmid=5096517 |pmc=292175 |doi=10.1172/JCI106731 |url=}}</ref>
+*** Preferred regimen:  400 to 600 mg/kg can be given every three weeks
+** [[Immunosuppressive agents]]:<ref name="pmid17498197">{{cite journal |vauthors=Kim JJ, Thrasher AJ, Jones AM, Davies EG, Cale CM |title=Rituximab for the treatment of autoimmune cytopenias in children with immune deficiency |journal=Br. J. Haematol. |volume=138 |issue=1 |pages=94–6 |date=July 2007 |pmid=17498197 |doi=10.1111/j.1365-2141.2007.06616.x |url=}}</ref> [[Rituximab]] can be given to treat autoimmune cytopenias such as [[hemolytic anemia]], [[neutropenia]], associated with Wiskott- Aldrich syndrome.
+** [[Thrombopoietic agent|Thrombopoietic agents]]: [[Eltrombopag]] may be helpful in increasing [[platelet]] count in patients with Wiskott-Aldrich syndrome but it may not improve [[platelet]] surface activation.<ref name="pmid26224646">{{cite journal |vauthors=Gerrits AJ, Leven EA, Frelinger AL, Brigstocke SL, Berny-Lang MA, Mitchell WB, Revel-Vilk S, Tamary H, Carmichael SL, Barnard MR, Michelson AD, Bussel JB |title=Effects of eltrombopag on platelet count and platelet activation in Wiskott-Aldrich syndrome/X-linked thrombocytopenia |journal=Blood |volume=126 |issue=11 |pages=1367–78 |date=September 2015 |pmid=26224646 |pmc=4729539 |doi=10.1182/blood-2014-09-602573 |url=}}</ref>
+** [[Gene therapy]]: [[Gene therapy]] is an alternative curative treatment for Wiskott-Aldrich syndrome, which is still going under trials.<ref name="pmid21067383">{{cite journal |vauthors=Boztug K, Schmidt M, Schwarzer A, Banerjee PP, Díez IA, Dewey RA, Böhm M, Nowrouzi A, Ball CR, Glimm H, Naundorf S, Kühlcke K, Blasczyk R, Kondratenko I, Maródi L, Orange JS, von Kalle C, Klein C |title=Stem-cell gene therapy for the Wiskott-Aldrich syndrome |journal=N. Engl. J. Med. |volume=363 |issue=20 |pages=1918–27 |date=November 2010 |pmid=21067383 |pmc=3064520 |doi=10.1056/NEJMoa1003548 |url=}}</ref>
 ===Surgery===
-* Splenectomy: Splenectomy may be considered for some patients with Wiskott-Aldrich syndrome . Splenectomy may be found to improve platelet count as well as size of the platelets . However, sepsis is a life-threatening complication after splenectomy. Prophylactic antibiotics should always be used to prevent infections.<ref name="pmid6767187">{{cite journal |vauthors=Lum LG, Tubergen DG, Corash L, Blaese RM |title=Splenectomy in the management of the thrombocytopenia of the Wiskott-Aldrich syndrome |journal=N. Engl. J. Med. |volume=302 |issue=16 |pages=892–6 |date=April 1980 |pmid=6767187 |doi=10.1056/NEJM198004173021604 |url=}}</ref><ref name="pmid21906397">{{cite journal |vauthors=Syrigos KN, Makrilia N, Neidhart J, Moutsos M, Tsimpoukis S, Kiagia M, Saif MW |title=Prolonged survival after splenectomy in Wiskott-Aldrich syndrome: a case report |journal=Ital J Pediatr |volume=37 |issue= |pages=42 |date=September 2011 |pmid=21906397 |pmc=3179709 |doi=10.1186/1824-7288-37-42 |url=}}</ref>
+* [[Hematopoietic stem cell transplantation]] ([[Hematopoietic stem cell transplantation|HSCT]]):<ref name="pmid4177931">{{cite journal |vauthors=Bach FH, Albertini RJ, Joo P, Anderson JL, Bortin MM |title=Bone-marrow transplantation in a patient with the Wiskott-Aldrich syndrome |journal=Lancet |volume=2 |issue=7583 |pages=1364–6 |date=December 1968 |pmid=4177931 |doi= |url=}}</ref><ref name="pmid12598139">{{cite journal |vauthors=Antoine C, Müller S, Cant A, Cavazzana-Calvo M, Veys P, Vossen J, Fasth A, Heilmann C, Wulffraat N, Seger R, Blanche S, Friedrich W, Abinun M, Davies G, Bredius R, Schulz A, Landais P, Fischer A |title=Long-term survival and transplantation of haemopoietic stem cells for immunodeficiencies: report of the European experience 1968-99 |journal=Lancet |volume=361 |issue=9357 |pages=553–60 |date=February 2003 |pmid=12598139 |doi= |url=}}</ref><ref name="pmid17710656">{{cite journal |vauthors=Muñoz A, Olivé T, Martinez A, Bureo E, Maldonado MS, Diaz de Heredia C, Sastre A, Gonzalez-Vicent M |title=Allogeneic hemopoietic stem cell transplantation (HSCT) for Wiskott-Aldrich syndrome: a report of the Spanish Working Party for Blood and Marrow Transplantation in Children (GETMON) |journal=Pediatr Hematol Oncol |volume=24 |issue=6 |pages=393–402 |date=September 2007 |pmid=17710656 |doi=10.1080/08880010701454404 |url=}}</ref>
-* Hematopoietic stem cell transplantation (HSCT):<ref name="pmid4177931">{{cite journal |vauthors=Bach FH, Albertini RJ, Joo P, Anderson JL, Bortin MM |title=Bone-marrow transplantation in a patient with the Wiskott-Aldrich syndrome |journal=Lancet |volume=2 |issue=7583 |pages=1364–6 |date=December 1968 |pmid=4177931 |doi= |url=}}</ref><ref name="pmid12598139">{{cite journal |vauthors=Antoine C, Müller S, Cant A, Cavazzana-Calvo M, Veys P, Vossen J, Fasth A, Heilmann C, Wulffraat N, Seger R, Blanche S, Friedrich W, Abinun M, Davies G, Bredius R, Schulz A, Landais P, Fischer A |title=Long-term survival and transplantation of haemopoietic stem cells for immunodeficiencies: report of the European experience 1968-99 |journal=Lancet |volume=361 |issue=9357 |pages=553–60 |date=February 2003 |pmid=12598139 |doi= |url=}}</ref><ref name="pmid17710656">{{cite journal |vauthors=Muñoz A, Olivé T, Martinez A, Bureo E, Maldonado MS, Diaz de Heredia C, Sastre A, Gonzalez-Vicent M |title=Allogeneic hemopoietic stem cell transplantation (HSCT) for Wiskott-Aldrich syndrome: a report of the Spanish Working Party for Blood and Marrow Transplantation in Children (GETMON) |journal=Pediatr Hematol Oncol |volume=24 |issue=6 |pages=393–402 |date=September 2007 |pmid=17710656 |doi=10.1080/08880010701454404 |url=}}</ref>
+** [[Hematopoietic stem cell transplantation|HSCT]] is the only standard curative treatment for Wiskott-Aldrich syndrome.
-* HSCT is the only standard curative treatment for Wiskott-Aldrich syndrome.
+* [[Splenectomy]]: Splenectomy may be considered for some patients with Wiskott-Aldrich syndrome . [[Splenectomy]] may be found to improve [[platelet]] count as well as size of the [[Platelet|platelets]] . However, [[sepsis]] is a life-threatening complication after [[splenectomy]]. Prophylactic [[Antibiotic|antibiotics]] should always be used to prevent [[Infection|infections]].<ref name="pmid6767187">{{cite journal |vauthors=Lum LG, Tubergen DG, Corash L, Blaese RM |title=Splenectomy in the management of the thrombocytopenia of the Wiskott-Aldrich syndrome |journal=N. Engl. J. Med. |volume=302 |issue=16 |pages=892–6 |date=April 1980 |pmid=6767187 |doi=10.1056/NEJM198004173021604 |url=}}</ref><ref name="pmid21906397">{{cite journal |vauthors=Syrigos KN, Makrilia N, Neidhart J, Moutsos M, Tsimpoukis S, Kiagia M, Saif MW |title=Prolonged survival after splenectomy in Wiskott-Aldrich syndrome: a case report |journal=Ital J Pediatr |volume=37 |issue= |pages=42 |date=September 2011 |pmid=21906397 |pmc=3179709 |doi=10.1186/1824-7288-37-42 |url=}}</ref>
-===Primary Prevention===
+'''Primary Prevention'''
-*There are no established measures for the [[primary prevention]] of the Wiskott-Aldrich syndrome. However [[Genetic testing|genetic mutation analysis]] and [[Prenatal diagnosis|prenatal molecular diagnosis]] can be helpful.<ref name="pmid8069912">{{cite journal |vauthors=Derry JM, Ochs HD, Francke U |title=Isolation of a novel gene mutated in Wiskott-Aldrich syndrome |journal=Cell |volume=78 |issue=4 |pages=635–44 |date=August 1994 |pmid=8069912 |doi= |url=}}</ref><ref name="pmid10073904">{{cite journal |vauthors=Giliani S, Fiorini M, Mella P, Candotti F, Schumacher RF, Wengler GS, Lalatta F, Fasth A, Badolato R, Ugazio AG, Albertini A, Notarangelo LD |title=Prenatal molecular diagnosis of Wiskott-Aldrich syndrome by direct mutation analysis |journal=Prenat. Diagn. |volume=19 |issue=1 |pages=36–40 |date=January 1999 |pmid=10073904 |doi= |url=}}</ref>
+*There are no established measures for the [[primary prevention]] of the Wiskott-Aldrich syndrome. However [[Genetic testing|genetic mutation analysis]] and [[Prenatal diagnosis|prenatal molecular diagnosis]] can be helpful in decreaing the occurance .<ref name="pmid8069912">{{cite journal |vauthors=Derry JM, Ochs HD, Francke U |title=Isolation of a novel gene mutated in Wiskott-Aldrich syndrome |journal=Cell |volume=78 |issue=4 |pages=635–44 |date=August 1994 |pmid=8069912 |doi= |url=}}</ref><ref name="pmid10073904">{{cite journal |vauthors=Giliani S, Fiorini M, Mella P, Candotti F, Schumacher RF, Wengler GS, Lalatta F, Fasth A, Badolato R, Ugazio AG, Albertini A, Notarangelo LD |title=Prenatal molecular diagnosis of Wiskott-Aldrich syndrome by direct mutation analysis |journal=Prenat. Diagn. |volume=19 |issue=1 |pages=36–40 |date=January 1999 |pmid=10073904 |doi= |url=}}</ref>
 ===Secondary Prevention===