Thrombocytopenia

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Thrombocytopenia Classification and external resources
Marked thrombocytopenia and fragmented red blood cells. Image courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology
ICD-10	D69.6, P61.0
ICD-9	287.3, 287.4, 287.5
OMIM	188000 313900
DiseasesDB	27522
MedlinePlus	000586
MeSH	D013921

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Powerpoint slides on Thrombocytopenia Images of Thrombocytopenia Photos of Thrombocytopenia Podcasts & MP3s on Thrombocytopenia Videos on Thrombocytopenia
Evidence Based Medicine
Cochrane Collaboration on Thrombocytopenia Bandolier on Thrombocytopenia TRIP on Thrombocytopenia
Clinical Trials
Ongoing Trials on Thrombocytopenia at Clinical Trials.gov Trial results on Thrombocytopenia Clinical Trials on Thrombocytopenia at Google
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US National Guidelines Clearinghouse on Thrombocytopenia NICE Guidance on Thrombocytopenia NHS PRODIGY Guidance FDA on Thrombocytopenia CDC on Thrombocytopenia
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Blogs on Thrombocytopenia
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Definitions of Thrombocytopenia
Patient Resources / Community
Patient resources on Thrombocytopenia Discussion groups on Thrombocytopenia Patient Handouts on Thrombocytopenia Directions to Hospitals Treating Thrombocytopenia Risk calculators and risk factors for Thrombocytopenia
Healthcare Provider Resources
Symptoms of Thrombocytopenia Causes & Risk Factors for Thrombocytopenia Diagnostic studies for Thrombocytopenia Treatment of Thrombocytopenia
Continuing Medical Education (CME)
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International
Thrombocytopenia en Espanol Thrombocytopenia en Francais
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List of terms related to Thrombocytopenia

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Thrombocytopenia (or -paenia, or thrombopenia in short) is the presence of relatively few platelets in blood.

Generally speaking a normal platelet count ranges from 150,000 and 450,000 per mm³. These limits, however, are determined by the 2.5th lower and upper percentile, and a deviation does not necessarily imply any form of disease. The number of platelets in a blood sample also decreases rather quickly with time and a low platelet count may be caused by a delay between sampling and analysis.

Signs and symptoms

Often, low platelet levels do not lead to clinical problems; rather, they are picked up on a routine full blood count (or CBC, complete blood count ). Occasionally, there may be bruising, particularly purpura in the forearms, nosebleeds and/or bleeding gums.

It is vital that a full medical history is elicited, to ensure the low platelet count is not due to a secondary process. It is also important to ensure that the other blood cell types red blood cells, and white blood cells, are not also suppressed.

Diagnosis

Laboratory tests might include: full blood count, liver enzymes, renal function, vitamin B12 levels, folic acid levels, erythrocyte sedimentation rate, and peripheral blood smear.

If the cause for the low platelet count remains unclear, bone marrow biopsy is often undertaken, to differentiate whether the low platelet count is due to decreased production or peripheral destruction.

Causes

There are two broad mechanisms of thrombocytopenia: reduced platelet production and increased platelet destruction. Thormbocytopenia is seen in a variety of infectious and genetic disorders as well as a side effect of a large list of phramacotherapies.

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Decreased production

Vitamin deficiencies

• Vitamin B12 deficiency
• Folic acid deficiency
• Iron deficiency

Hematologic disorders

• Pancytopenia
• Aplastic anemia
• Acute lymphoblastic leukemia
• Acute myeloid leukemia
• Chronic lymphocytic leukaemia
• Chronic myeloid leukaemia
• Hairy cell leukaemia
• Myeloma
• Non-Hodgkin lymphoma
• Myelodysplastic syndrome
• Myelofibrosis

Reduced thrombopoiesis due to reduced thrombopoietin production

• Decreased production of thrombopoietin by the liver in liver failure.

Infectious etiologies

• Sepsis, systemic viral or bacterial infection
• Dengue fever can cause thrombocytopenia by direct infection of bone marrow megakaryocytes as well as immunological shortened platelet survival
• Protozoa and protozoal conditions
• Visceral leishmaniasis
• Human granulocytic ehrlichiosis
• Human monocytotropic ehrlichiosis
• Mycoplasma pneumonia
• Staphylococcal toxic shock syndrome
• Epstein-Barr virus
• Hantavirus
• HIV-1 disease
• Infectious mononucleosis
• Lassa fever
• Measles
• Mumps
• Oklahoma tick fever
• Rubella
• Severe acute respiratory distress syndrome
• Tick born encephalitis

Intrauterine acquired conditions

• Neonatal alloimmune thrombocytopenia
• Rubella, congenital
• Syphilis, congenital

Hereditary syndromes

• Congenital Amegakaryocytic Thrombocytopenia (CAMT)
• Bernard-Soulier syndrome, associated with large platelets
• May-Hegglin anomaly, the combination of thrombocytopenia, pale-blue leuckocyte inclusions, and giant platelets
• Grey platelet syndrome
• Alport syndrome

Chromosomal abnormalities

• Jacobsen syndrome

Mendelian inherited conditions

• Autoimmune lymphoproliferative syndrome type 1
• Autoimmune lymphoproliferative syndrome type 2
• Radial aplasia-thrombocytopenia syndrome or Thrombocytopenia absent radius syndrome
• von Willebrand disease, platelet type

Autosomal dominant conditions

• Arias oculootoradial syndrome
• Complement factor H deficiency
• Fechtner syndrome
• May-Hegglin anomaly
• Platelet glycoprotein 4 deficiency
• Sebastian platelet syndrome

Autosomal recessive conditions

• Chediak-Higashi disease
• Dibasic aminoaciduria type 2
• Familial histiocytic reticulosis
• Fanconi anaemia
• Folate malabsorption hereditary
• Gaucher disease
• Griscelli syndrome type 1
• Histiocytosis X
• Holocarboxylase synthase deficiency
• Iminodipeptiduria
• Isovaleric acidaemia
• Methylmalonic aciduria type 2
• Neuroectodermal melanolysosomal disease
• Niemann-Pick disease type B
• Omenn syndrome
• Platelet glycoprotein Ib deficiency
• Propionyl-CoA carboxylase deficiency PCCA type
• Sea blue histiocytosis
• Shwachman-Diamond syndrome

X-linked inherited conditions

• GATA1-related cytopenia
• Immunodysregulation polyendocrinopathy and enteropathy, X-linked
• Wiskott-Aldrich syndrome
• X-linked hyperimmunoglobulin M syndrome
• Mitochondrial genome inherited conditions
• MELAS

Chemical exposure

Strontium-89

Zinc

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Increased destruction

Hematologic Disorders

• Idiopathic thrombocytopenic purpura (ITP)
• Thrombotic thrombocytopenic purpura (TTP)
• Hemolytic-uremic syndrome (HUS)
• Disseminated intravascular coagulation (DIC)
• Paroxysmal nocturnal hemoglobinuria (PNH)
• Neonatal alloimmune thrombocytopenia (NAITP)
• Following transfusion or post transfusion alloimmune thrombocytopenia
• Evans syndrome
• Macrophage activation syndrome

Cardiovascular causes

• Cholesterol embolism
• Intraaortic balloon pump placement
• Endocarditis

Obstetric disorders

• Eclampsia
• HELLP syndrome
• Pre-eclampsia

Autoimmunde Disorders

• Antiphospholipid syndrome
• Systemic lupus erythematosus (SLE)
• post transfusion purpura

Infectious Disorders

• Dengue fever has been shown to cause shortened platelet survival and immunological platelet destruction
• HIV [3]

Other disorders

• Splenic sequestration of platelets due to hypersplenism

Medication-induced

Thrombocytopenia associated with medications can be due to either a reduction in production of platelets or increased destruction.

Mechanisms

Direct myelosuppression

• Valproic acid
• Methotrexate
• Carboplatin
• Interferon
• Other chemotherapy drugs

Immunological platelet destruction

• Drug binds Fab portion of an antibody. The classic example of this mechanism is the quinidine group of drugs. The Fc portion of the antibody molecule is not involved in the binding process.
• Drug binds to Fc, and drug-antibody complex binds and activates platelets. Heparin induced thrombocytopenia (HIT) is the classic example of this phenomenon. In HIT, the heparin-antibody-platelet factor 4 (PF4) complex binds to Fc receptors on the surface of the platelet. Since Fc portion of the antibody is bound to the platelets, they are not available to the Fc receptors of the reticulo-endothelial cells, so therefore this system cannot destroy platelets as usual. This may explain why severe thrombocytopenia is not a common feature of HIT.

Heparin-induced thrombocytopenia

(HIT or white clot syndrome): this is a rare but serious condition that may occur in a hospitalized population. The most common clinical setting for HIT is in postoperative coronary artery bypass graft recipients, who may receive large quantities of heparin during surgery. HIT typically occurs about a week after exposure to heparin. The heparin-PF4 antibody complex will activate the platelets, and this can often lead to thrombosis. The term HITT, where the last T stands for thrombosis, denotes the concept that heparin-induced thrombocytopenia often is associated with thrombosis.

List of potential etiologies:

Low molecular weight heparins Sulphonamides Drugs, hormones and mediators 5-Azacytidine Abciximab Aclarubicin Actinomycin D Aggrastat Albendazole Alemtuzumab Altretamine Amiodarone Amrinone Anagrelide Anazolene Antithymocyte globulin Ardeparin Arsenic trioxide Azathioprine Bendamustine Benoxaprofen Bortezomib Captopril Caspofungin Chloramphenicol Cilazapril Cimetidine Cladribine Clofarabine Dasatinib Decitabine Desferrioxamine Doxorubicin Efalizumab

Eflornithine Epirubicin Eptifibatide Ethanol Flucytosine Fondaparinux Ganciclovir Gemcitabine Gemtuzumab ozogamicin Gold salts Guanidinium Haem arginate Heparin Ibritumomab tiuxetan Idarubicin Imatinib mesylate Indomethacin Integrilin Interferon alpha Interleukin 10 Interleukin 2 Irinotecan Ixabepilone Lenalidomide Lomustine Melphalan Mercaptopurine Methyldopa Methyldopate Mithramycin Nelarabine Nilotinib

Nitisinone Oxaliplatin Para-amino salicylic acid Pemetrexed Penicillamine Pentamidine Phenylbutazone Pyrimethamine Quinidine Quinine Ranitidine ReoPro Rifampicin Sirolimus Sorafenib Stiripentol Sulphasalazine Sunitinib malate Temozolomide Ticlopidine Tirofiban Topotecan Trabectedin Trimetrexate Valganciclovir Valproic acid Vancomycin Vinorelbine Vorinostat

Epiphenomenon

Kasabach-Merritt syndrome Paraneoplastic syndrome

Treatment

Treatment is guided by etiology and disease severity. The main concept in treating thrombocytopenia is to eliminate the underlying problem, whether that means discontinuing suspected drugs that cause thrombocytopenia, or treating underlying sepsis. Diagnosis and treatment of serious thrombocytopenia is usually directed by a hematologist.

Specific treatment plans often depend on the underlying etiology of the thrombocytopenia.

Thrombotic thrombocytopenic purpura (TTP)

Treatment of thrombotic thrombocytopenic purpura is a medical emergency, since the hemolytic anemia and platelet activation can lead to renal failure and changes in the level of consciousness. Treatment of TTP was revolutionized in the 1980s with the application of plasmapheresis. According to the Furlan-Tsai hypothesis ^{[1] [2]} , this treatment theoretically works by removing antibodies directed against the von Willebrand factor cleaving protease, ADAMTS-13. The plasmapheresis procedure also adds active ADAMTS-13 protease proteins to the patient, restoring a more physiological state of von Willebrand factor multimers. Patients with persistent antibodies against ADAMTS-13 do not always manifest TTP, and these antibodies alone are not sufficient to explain the how plasmapheresis treats TTP.

ITP

In many cases, ITP is self-limited, and does not require treatment. Platelet counts less than ten thousand per mm3 usually require treatment(less than fifty thousand requires treatment, less than ten thousand is a potentially dangerous situation) and patients with significant bleeding and thrombocytopenia due to ITP are also usually treated. The threshold for treating ITP has decreased since the 1990s, and hematologists recognize that patients rarely bleed with platelet counts greater than ten thousand, though there are documented exceptions to this observation. Treatments for ITP include:

• Prednisone and other corticosteroids
• Intravenous gamma globulin
• Splenectomy
• Danazol
• Rituximab

Thrombopoetin analogues have been tested extensively for the treatment of ITP. These agents had previously shown promise but had been found to stimulate antibodies against endogenous thrombopoeitin or lead to thrombosis.

A medication known as AMG 531 was found to be safe and effective for the treatment of ITP in refractory patients. ^[3] AMG 531 is a peptide that bears no sequence homology with endogenous human thrombopoeitin, so it is not as likely to lead to neutralizing antibodies as previous peptide thrombopoeitin analogues. ^[4]

Heparin-induced thrombocytopenia and thrombosis (HITT)

Discontinuation of heparin is critical in a case of HITT. Beyond that, however, care must be taken to avoid a thrombosis, and patients started directly on warfarin after a diagnosis of HITT are at excess risk of venous limb gangrene. For this reason, patients are usually treated with a type of blood thinner called a direct thrombin inhibitor such as the FDA-approved lepirudin or argatroban. Other blood thinners sometimes used in this setting that are not FDA-approved for treatment of HITT include bivalirudin and fondaparinux. Platelet transfusions are not a routine component of the treatment of HITT, since thrombosis, not bleeding, is the usual associated problem in this illness.

Congenital amegakaryocytic thrombocytopenia (CAMT)

Bone Marrow/Stem Cell Transplant is the only thing that ultimately cures this genetic disease. Frequent platelet transfusions are required to keep the patient from bleeding to death until transplant is done.

References

External links

• 11-133b. at Merck Manual of Diagnosis and Therapy Professional Edition

• Low platelets.com a resource for patients with thrombocytopenia.

v • d • e Pathology: hematology, myeloid hematologic disease (primarily D50-D77, 280-289)
RBCs/ hemoglobinopathy	+ Polycythemia - Macrocytosis - Anemia Nutritional Iron deficiency anemia (Plummer-Vinson syndrome), Megaloblastic anemia (Pernicious anemia) Hemolytic Hereditary enzyme: G6PD Deficiency - Pyruvate kinase deficiency - Triosephosphate isomerase deficiency hemoglobin: Thalassemia - Sickle-cell disease/trait membrane: Hereditary spherocytosis - Hereditary elliptocytosis - Hereditary stomatocytosis Acquired Autoimmune (Warm, Cold), HUS, MAHA, PNH, PCH, Myelophthisic Aplastic Acquired PRCA, Diamond-Blackfan anemia, Fanconi anemia, Sideroblastic anemia Blood tests Normocytic - Microcytic - Macrocytic - Normochromic - Hypochromic Other Methemoglobinemia
Coagulation/platelets/ coagulopathy/ bleeding diathesis	+ Hypercoagulability primary: Antithrombin III deficiency - Protein C deficiency/Activated protein C resistance/Protein S deficiency/Factor V Leiden - Hyperprothrombinemia acquired: DIC (Congenital afibrinogenemia, Purpura fulminans) - autoimmune (Antiphospholipid) Other Essential thrombocytosis - clotting factor: Hemophilia (A/VIII, B/IX, C/XI) • Von Willebrand disease • Hypoprothrombinemia/II - XIII platelet function: Bernard-Soulier syndrome - Glanzmann's thrombasthenia - Gray platelet syndrome - May Hegglin anomaly - Pelger-Huet anomaly Purpura: Henoch-Schönlein, ITP (Evans syndrome), TTP Thrombocytopenia (Heparin-induced thrombocytopenia)
Monocytes/ macrophages	+ Histiocytosis WHO-I (Langerhans cell histiocytosis) WHO-II/non-Langerhans-cell (Juvenile xanthogranuloma, Hemophagocytic lymphohistiocytosis) WHO-III/malignant (Acute monocytic leukemia, Malignant histiocytosis, Erdheim-Chester disease) Other Chronic granulomatous disease -cytosis: Monocytosis - -penia: Monocytopenia
Granulocytes	+ -cytosis: granulocytosis (Neutrophilia, Eosinophilia, Basophilia) - -penia: Granulocytopenia/agranulocytosis (Neutropenia/Kostmann syndrome, Eosinopenia, Basopenia)
See also hematological malignancy and immune disorders

v • d • e WikiDoc Research Resources for Thrombocytopenia
Articles on Thrombocytopenia	Most recent articles on Thrombocytopenia • Most cited articles on Thrombocytopenia • Review articles on Thrombocytopenia • Articles on Thrombocytopenia in N Eng J Med, Lancet, BMJ
Media (Slides, Video, Images, MP3) on Thrombocytopenia	Powerpoint slides on Thrombocytopenia • Images of Thrombocytopenia • Photos of Thrombocytopenia • Podcasts & MP3s on Thrombocytopenia • Videos on Thrombocytopenia
Evidence Based Medicine Regarding Thrombocytopenia	Cochrane Collaboration on Thrombocytopenia • Bandolier on Thrombocytopenia • TRIP on Thrombocytopenia
Cost Effectiveness of Thrombocytopenia	Cost Effectiveness of Thrombocytopenia
Clinical Trials Involving Thrombocytopenia	Ongoing Trials on Thrombocytopenia at Clinical Trials.gov • Trial results on Thrombocytopenia • Clinical Trials on Thrombocytopenia at Google
Guidelines / Policies / Government Resources (FDA/CDC) Regarding Thrombocytopenia	US National Guidelines Clearinghouse on Thrombocytopenia • NICE Guidance on Thrombocytopenia • NHS PRODIGY Guidance • FDA on Thrombocytopenia • CDC on Thrombocytopenia
Textbook Information on Thrombocytopenia	Books and Textbook Information on Thrombocytopenia
Pharmacology Resources on Thrombocytopenia	Dosing of Thrombocytopenia • Drug interactions with Thrombocytopenia • Side effects of Thrombocytopenia • Allergic reactions to Thrombocytopenia • Overdose information on Thrombocytopenia • Carcinogenicity information on Thrombocytopenia • Thrombocytopenia in pregnancy • Pharmacokinetics of Thrombocytopenia •
Genetics, Pharmacogenomics, and Proteinomics of Thrombocytopenia	Genetics of Thrombocytopenia • Pharmacogenomics of Thrombocytopenia • Proteomics of Thrombocytopenia
Newstories on Thrombocytopenia	Thrombocytopenia in the news • Be alerted to news on Thrombocytopenia • News trends on Thrombocytopenia
Commentary on Thrombocytopenia	Blogs on Thrombocytopenia
Patient Resources on Thrombocytopenia	Patient resources on Thrombocytopenia • Discussion groups on Thrombocytopenia • Patient Handouts on Thrombocytopenia • Directions to Hospitals Treating Thrombocytopenia • Risk calculators and risk factors for Thrombocytopenia
Healthcare Provider Resources on Thrombocytopenia	Symptoms of Thrombocytopenia • Causes & Risk Factors for Thrombocytopenia • Diagnostic studies for Thrombocytopenia • Treatment of Thrombocytopenia
Continuing Medical Education (CME) Programs on Thrombocytopenia	CME Programs on Thrombocytopenia
International Resources on Thrombocytopenia	Thrombocytopenia en Espanol • Thrombocytopenia en Francais
Business Resources on Thrombocytopenia	Thrombocytopenia in the Marketplace • Patents on Thrombocytopenia
Informatics Resources on Thrombocytopenia	List of terms related to Thrombocytopenia

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