Pancytopenia

Revision as of 07:11, 17 March 2017 by Shyam Patel (talk | contribs)
Jump to navigation Jump to search

Pancytopenia is not equivalent with bone marrow suppression. Pancytopenia is a lab finding that may related to either bone marrow suppression or peripheral sequestration/destruction. For details about bone marrow suppression click here.

WikiDoc Resources for Pancytopenia

Articles

Most recent articles on Pancytopenia

Most cited articles on Pancytopenia

Review articles on Pancytopenia

Articles on Pancytopenia in N Eng J Med, Lancet, BMJ

Media

Powerpoint slides on Pancytopenia

Images of Pancytopenia

Photos of Pancytopenia

Podcasts & MP3s on Pancytopenia

Videos on Pancytopenia

Evidence Based Medicine

Cochrane Collaboration on Pancytopenia

Bandolier on Pancytopenia

TRIP on Pancytopenia

Clinical Trials

Ongoing Trials on Pancytopenia at Clinical Trials.gov

Trial results on Pancytopenia

Clinical Trials on Pancytopenia at Google

Guidelines / Policies / Govt

US National Guidelines Clearinghouse on Pancytopenia

NICE Guidance on Pancytopenia

NHS PRODIGY Guidance

FDA on Pancytopenia

CDC on Pancytopenia

Books

Books on Pancytopenia

News

Pancytopenia in the news

Be alerted to news on Pancytopenia

News trends on Pancytopenia

Commentary

Blogs on Pancytopenia

Definitions

Definitions of Pancytopenia

Patient Resources / Community

Patient resources on Pancytopenia

Discussion groups on Pancytopenia

Patient Handouts on Pancytopenia

Directions to Hospitals Treating Pancytopenia

Risk calculators and risk factors for Pancytopenia

Healthcare Provider Resources

Symptoms of Pancytopenia

Causes & Risk Factors for Pancytopenia

Diagnostic studies for Pancytopenia

Treatment of Pancytopenia

Continuing Medical Education (CME)

CME Programs on Pancytopenia

International

Pancytopenia en Espanol

Pancytopenia en Francais

Business

Pancytopenia in the Marketplace

Patents on Pancytopenia

Experimental / Informatics

List of terms related to Pancytopenia

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Cafer Zorkun, M.D., Ph.D. [2] Ogheneochuko Ajari, MB.BS, MS [3] Shyam Patel [4]

Overview

Pancytopenia is the reduction in numbers of all three bone marrow cell types (RBCs, WBCs, and platelets). It is not a disease, but rather a lab finding that may related to bone marrow suppression caused by either insufficient production (aplastic anemia), inability of cells or mature (myelodysplasia), replacement of normal bone marrow with fibrosis (myelofibrosis) or peripheral sequestration that is not related to the bone marrow (e.g. splenomegaly or hypersplenism). or destruction (such as hemolytic anemia. HIV (human immunodeficiency virus) is itself a cause of pancytopenia. Chemotherapy is associated with pancytopenia due to drug-mediated bone marrow suppression. Pancytopenia usually requires a bone marrow biopsy in order to distinguish among different causes.

Historical Perspective

The history of pancytopenia relates to the history of each of its individual entities, namely anemia, thrombocytopenia, and leukopenia. Pancytopenia was not recognized as a distinct clinical entity until after each of its other subcomponents were characterized.

  • History of aplastic anemia: The seminal discoveries for aplastic anemia were made by Bruno Speck and Georges Mathe, who noted that immunosuppression could be used to treat aplastic anemia.[1] In the 1970s, matched sibling donor transplant was used for severe aplastic anemia.[2]

Classification

There is no classification system for pancytopenia. However, some underlying disease entities that cause pancytopenia have classification. For example, aplastic anemia is classified as moderate, severe, or very severe.

Pathophysiology

The pathophysiology of pancytopenia relates to the underlying etiology. In most cases, pancytopenia is due to a disruption in trilineage hematopoiesis. This means that the bone marrow is not appropriately producing erythrocytes, leukocytes, and thrombocytocytes. The cause of the disruption in trilineage hematopoiesis is in turn due to the underlying cause of pancytopenia. For example, viral-mediated pancytopenia is caused by viral particles infecting hematopoietic cells and preventing normal cell division. Leukemia-mediated pancytopenia is typically due to marrow replacement of normal hematopoietic precursors, a process known as myelopthisis. Leukemic infiltration of the bone marrow creates a "crowding-out" phenomenon.

Causes

Life Threatening Causes

Life-threatening causes include conditions which may result in death or permanent disability within 24 hours if left untreated.

Common Causes

  • Aplastic anemia [3]: This is a condition characterized by immune-mediated reduction in all three hematopoietic cell lines with absence of hematopoietic precursors.[1] It is a rare condition with a prevalence of only 1-2 cases per million annually. It is most commonly diagnosed in childhood. Epidemiologic studies have shown a greater prevalence in Southeast Asia and other countries with limited access to healthcare, as viral infection can trigger aplastic crisis.[1] There are three categories: moderate, severe, and very severe. These categories are based upon the number and degree of cytopenias as well as bone marrow cellularity. The preferred treatment of aplastic anemia is bone marrow transplantation from an HLA-matched sibling. If there is no HLA-matched sibling available, the next best option is medical management with the immunosuppressive agents anti-thymocyte globulin (ATG) and cyclosporine A.[1] The reason for the efficacy of immunosuppressive medications is that the pancytopenia from aplastic anemia is due to abnormal immune activation and thus destruction of hematopoietic cells. ATG from horse has been shown to be superior compared to ATG from rabbit.[1] ATG is administered over 5 days, and cyclosporine A is administered orally for 6 months, after which response can be assessed. The combination of ATG and cyclosporine A carries a response rate of 60-70%. [2]
  • Folate deficiency: Folate is required for pyrimidine nucleotide synthesis, and thus folate deficiency can lead to decreased production of hematopoietic cells.[4] Folate deficiency occurs in persons who consume large amounts of alcohol. Folate deficiency is accompanied by macrocytosis, or large-sized cells.
  • Leishmaniasis
  • Leukemia: This can be myeloid or lymphoid, and each of these can be acute or chronic.
  • Megaloblastic anemia [3]
  • Myelodysplastic syndrome: This is a disease characterized by ineffective erythropoiesis and peripheral cytopenias. It is a clonal disorder of the hematopoietic stem cell.[5] The subtype of myelodysplastic syndrome that causes pancytopenia is termed refractory anemia with multilineage dysplasia. The pancytopenia of myelodysplastic syndrome is due to failure of maturation of hematopoietic precursors, leading to peripheral cytopenias.[5] Diagnosis of myelodysplastic syndrome is made by demonstration of at least 1 cell line with 10% of greater dysplastic cells on bone marrow biopsy. Bone marrow biopsy should also show myeloblasts less then 20% of total leukocytes. Clinical features of myelodysplastic syndrome include manifestations of specific cytopenias, such as fatigue if there is anemia, bleeding if there is thrombocytopenia, and infections if there is leukopenia.[6] The prognostication of myelodysplastic syndrome is determined by the International Prognosis Scoring System-Revised (IPSS-R), which is determined by blast count, the karyotype, and cytopenia. This clinical tool is used to estimate the time to progression to acute myeloid leukemia. The treatment of myelodysplastic syndrome is based on the subtype. Lenalidomide is highly effective for persons with deletion of chromosome 5q.[6] DNA hypomethylating agents like azacitadine and decitabine are commonly used for those with symptomatic cytopenias and without chromosome 5q deletion. In some cases, allogeneic stem cell transplantation can be done with the goal of curing myelodysplastic syndrome and preventing progression to acute myeloid leukemia.[6] Adjunctive therapies include transfusion support (such as red blood cell transfusions or platelet transfusions), growth factor support (such as filgrastim), and immunosuppressive therapy, which is particularly effective in persons with PNH clones, HLA-DR15 positivity, or STAT3-mutant cytotoxic T cells.
  • Paroxysmal nocturnal hemoglobinuria
  • Viral infections e.g. (HIV most common)
  • Vitamin B12 deficiency
  • Copper deficiency
  • Zinc deficiency

Causes by Organ System

Cardiovascular No underlying causes
Chemical/Poisoning Arsenic poisoning, arsenicals, benzene solvents, genotoxic therapy, glue vapors, gold, mutagen exposure, mutagen-detoxification (GSTq1-null), radium chloride, toxins, valproic acid poisoning
Dental No underlying causes
Dermatologic Chediak-Higashi disease, dyskeratosis congenita, eosinophilic fasciitis, melanoma, reticular dysgenesis, reticulosis, systemic lupus erythematosus, xeroderma pigmentosum
Drug Side Effect Acetaminophen and Oxycodone, aclarubicin, albendazole, alemtuzumab, alkylating antineoplastic agent, auranofin, azathioprine, aztreonam, boceprevir, busulfan, carbamazepine, carboplatin, cefadroxil, ceftazidime, certolizumab pegol, chemotherapy, chloramphenicol, chlorpromazine, chlorpropamide, cromolyn, cidofovir, clomipramine, cyclophosphamide, cytotoxic drugs, dactinomycin, docetaxel, doxorubicin, ethosuximide, febuxostat, flucytosine, gemcitabine, gemifloxacin mesylate, genotoxic therapy, idarubicin, Imipenem-Cilastatin,indomethacin , infliximab, interferon beta-1a, lincomycin hydrochloride, minocycline hydrochloride, non steroidal anti-inflammatory drugs, ofatumumab, omacetaxine, oxaprozin, oxcarbazepine, penicillamine, phenacemide , phenylbutazone, piperacillin, pralatrexate, propylthiouracil, pyrimethamine, rabeprazole, sulfonamides , tamoxifen, temozolomide, thiothixene, tolazamide, tolbutamide, topoisomerase II interactive agents, trifluoperazine, trimethadione, trimethoprim-sulfamethoxazole, valganciclovir hydrochloride
Ear Nose Throat Dubowitz syndrome, Jacobsen syndrome
Endocrine Osteoporosis, panhypopituitarism, thyroid carcinoma
Environmental No underlying causes
Gastroenterologic Banti's syndrome, cirrhosis, Gaucher's disease, hepatosplenic T-cell lymphoma, hypersplenism, intrinsic factor deficiency, malabsorption syndrome, Plummer-Vinson syndrome, portal hypertension, sarcoidosis, Schwachman-Diamond syndrome, splenomegaly
Genetic Albers-Schonberg disease, ataxia telangiectasia, Banti's syndrome, Bloom syndrome , cartilage-hair hypoplasia, Chediak-Higashi disease, Diamond-Blackfan anemia, DNA repair-deficiency disorder, Down syndrome, Dubowitz syndrome, dyskeratosis congenita, familial histiocytic reticulosis, familial monosomy 7, Fanconi anemia, Gaucher's disease, hemophagocytic lymphohistiocytosis, Hoyeraal-Hreidarsson syndrome, Jacobsen syndrome, intrinsic factor deficiency, neurofibromatosis 1, Niemann-Pick disease, osteopetrosis lethal, osteopetrosis, autosomal recessive 2, Pearson syndrome, Schwachman-Diamond syndrome, severe combined immunodeficiency, TAR syndrome, trisomy 8 mosaicism, Wiskott-Aldrich syndrome, xeroderma pigmentosum
Hematologic Acute lymphoblastic leukemia, acute myeloid leukemia, aggressive NK-cell leukemia, amegakaryocytic thrombocytopenia, aplastic anemia, autoimmune lymphoproliferative syndrome type 1, autoimmune lymphoproliferative syndrome type 2, bleeding (Excessive), bone marrow tumor, Castleman's disease, chronic lymphocytic leukaemia, chronic myeloid leukaemia, cyclical neutropenia, Diamond-Blackfan anemia, familial histiocytic reticulosis, familial myelofibrosis, Fanconi anemia, Gaucher's disease, hairy cell leukemia, hematopoietic stem cell transplantation, hemoglobin E disease, hemoglobin H disease, hemoglobin SC disease, hemophagocytic lymphohistiocytosis , hepatosplenic T-cell lymphoma, histiocytosis X, Hodgkin's lymphoma, hypersplenism, hypoplastic myelodysplastic syndromes, ineffective erythropoiesis, intestinal lymphangiectasia, intrinsic factor deficiency, iron deficiency, langerhans cell histiocytosis, leucoerythroblastic anemia, leukemia, lymphoma, malignant histiocytosis, megaloblastic anemia, myelodysplastic syndrome, myelofibrosis, myeloma, myelopathic anemia, non-Hodgkin lymphoma, paroxysmal nocturnal hemoglobinuria, Pearson syndrome, pernicious anemia, Plummer-Vinson syndrome, precursor B acute lymphoblastic leukemia, reticulosis, Schwachman-Diamond syndrome, sickle cell disease, TAR syndrome, t-cell large granular lymphocytic leukemia, Wiskott-Aldrich syndrome
Iatrogenic Radiation therapy, radioactive p32
Infectious Disease Babesiosis, brucellosis, dengue, Epstein-Barr virus , hepatitis, human immunodeficiency virus , infectious mononucleosis, kala-azar, Kikuchi disease, lassa fever, legionella pneumophila, mycobacterium tuberculosis, parvovirus B19 infection, Q fever, tuberculosis, viral infections, Whipple's disease
Musculoskeletal/Orthopedic Albers-Schonberg disease, ankylosing spondylitis, cartilage-hair hypoplasia, Ewing's sarcoma, osteoclastoma, osteopetrosis lethal, osteopetrosis, autosomal recessive 2, osteoporosis, osteosarcoma, TAR syndrome
Neurologic Ataxia telangiectasia, Down syndrome , neuroblastoma, neurofibromatosis 1, Niemann-Pick disease
Nutritional/Metabolic Anorexia nervosa, copper deficiency, folate deficiency, Gaucher's disease, glutathione synthase deficiency, iron deficiency, kwashiorkor, marasmus, obesity, vitamin B12 deficiency, vitamin C deficiency
Obstetric/Gynecologic Pregnancy
Oncologic Acute lymphoblastic leukemia, acute myeloid leukemia, aggressive NK-cell leukemia, bone marrow tumor, cancer, chondrosarcoma, chronic lymphocytic leukaemia, chronic myeloid leukaemia, epiphyseal tumors, Ewing's sarcoma, familial myelofibrosis, germ cell tumors , granuloma, hairy cell leukemia, hepatosplenic T-cell lymphoma, histiocytosis X, Hodgkin's lymphoma, hypoplastic myelodysplastic syndromes, langerhans cell histiocytosis, leukemia, lymphoma, melanoma, metastatic neoplasm, myelodysplastic syndrome, myelofibrosis, myeloma, neuroblastoma, non-Hodgkin lymphoma, osteoclastoma, osteosarcoma, precursor B acute lymphoblastic leukemia, prostate cancer, t-cell large granular lymphocytic leukemia, thymoma, thyroid carcinoma
Ophthalmologic No underlying causes
Overdose/Toxicity Colchicine toxicity
Psychiatric Anorexia nervosa
Pulmonary Sarcoidosis
Renal/Electrolyte Renal failure, chronic, systemic lupus erythematosus
Rheumatology/Immunology/Allergy Ankylosing spondylitis, auto-immune disorders, autoimmune lymphoproliferative syndrome type 1, autoimmune lymphoproliferative syndrome type 2, Castleman's disease, common variable hypogammaglobulinemia, common variable immune deficiency, eosinophilic fasciitis , Felty's syndrome, graft versus host disease, histiocytosis X, langerhans cell histiocytosis, rheumatoid disease, sarcoidosis, severe combined immunodeficiency, systemic lupus erythematosus, Wiskott-Aldrich syndrome
Sexual No underlying causes
Trauma No underlying causes
Urologic Prostate cancer
Miscellaneous Idiopathic, radioactive p32, tobacco use

Causes in Alphabetical Order

The unnamed parameter 2= is no longer supported. Please see the documentation for {{columns-list}}.
3

Causes by Pathophysiology

Bone Marrow Failure

Peripheral Sequestration/Destruction

Causes by Mode of Inheritance

Congenital

  • Cartilage hair hypoplasia: This is a bone marrow failure condition caused by ribosomal protein mutations.[42]
  • Diamond-Blackfan syndrome: This is a rare condition affecting 5-7 persons per million and is characterized by a macrocytic anemia and less than 5% erythroid precursors including reticulocytes.[43] It is the most common inherited erythrocyte failure syndrome, and it is inherited in an autosomal dominant pattern.[42] This condition is caused by mutations in ribosomal protein genes such as RPS19. Though neutropenia and thrombocytopenia do not usually occur, moderate white blood cell and platelet count reductions have been described in some cases.[43] Fetal hemoglobin is typically increased in an effect to enhance delivery of oxygen to tissues in the setting of low hemoglobin.[43] Clinical manifestations usually include short statute, ocular abnormalities, skeletal abnormalities.It is the most common inherited erythrocyte failure syndrome.[42] The only curative therapy is bone marrow transplantation.
  • Dubowitz syndrome
  • Dyskeratosis congenita: This is a rare condition caused by short telomeres, which normally function to maintain the length and integrity of DNA.[44] It is characterized by skin abnormalities, nail abnormalities, and leukoplakia. The genes implicated include DKC1 (dyskerin), TERT, and TERC. Other genes implicated in this condition encode ribonucleoprotein enzymes. By age 30, approximately 80% of patients with this condition will develop bone marrow failure.[44]
  • Familial aplastic anemia
  • Fanconi's anemia: This is a condition characterized by erythrocyte hypoproduction due to genomic instability and increased susceptibility to DNA damaging agents.[42] [45] Diagnosis is made by demonstration of DNA crosslinking upon exposure to diepoxybutane (DEB) and mitomycin C (MCC). Patients with Fanconi anemia have a higher risk for development of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), both of which can contribute to pancytopenia.[46]
  • Pearson syndrome
  • Schwachman-Diamond syndrome: This is a condition that affects approximately 1 in 50000 persons and is characterized by bone marrow failure, pancreatic exocrine insufficiency, and skeletal abnormalities.[47] It is caused by a biallelic (two alleles) mutation in a ribosomal protein encoded by the Schwachman-Bodian-Diamond gene SBDS, located on chromosome 7.[47] Clinical manifestations in children usually include diarrhea and steatorrhea (due to pancreatic exocrine insufficiency).[48] However, there have been cases of pancytopenia from Schwachman-Diamond syndrome in the absence of diarrhea, so this condition should still be in the differential diagnosis of children with pancytopenia and bone marrow failure.
  • TAR syndrome

Acquired

Differentiating [Disease] from Other Diseases

Pancytopenia must be differentiated from a pseudo-syndromes like pseudo-thrombocytopenia, which is a laboratory artifact from platelet clumping.

Epidemiology and Demographics

Pancytopenia affects males and females equally. However, the underlying etiologies of pancytopenia can have a gender predilection.

Risk Factors

The risk factors of pancytopenia are related to the underlying cause. For example, leukemia-mediated pancytopenia can be related to risk factors such as chemical exposure, radiation, or family history.

Screening

There are no suggested screening tests for pancytopenia. The United States Preventive Services Task Force (USPSTF) does not have any recommendations for screening for pancytopenia.

Natural History, Complications, and Prognosis

Natural History

The natural history of pancytopenia is dictated by the pathophysiology of the under etiology. For example, viral-mediated pancytopenia is typically short-lived, pending clearance of the virus. Drug-induced pancytopenia typically resolves after discontinuing of the culprit drug and the drug has been metabolized by the body. Leukemia-mediated pancytopenia is usually a more long-term process, as marrow replacement by leukemia cells is difficult to overcome unless the leukemia is treated and the patient is in remission.

Complications

Complications of pancytopenia relate to deficits of the cell types that are affected. Decrease in erythrocytes causes fatigue and pallor due to decrease in oxygen delivery to tissue beds. Decrease in leukocytes and leukocyte subsets causes infections, which can be viral, bacteria, fungal, or parasitic. Decrease in thrombocytes causes bleeding, which is typically mucosal, given loss of the ability of platelets to create a hemostatic plug.

Prognosis

The prognosis of pancytopenia is related to the underlying etiology. For example, patients with unfavorable-risk leukemia will likely have a poor prognosis from a pancytopenia perspective. Patients with viral-mediated pancytopenia have a prognosis that is determined by the natural history of the virus. Epstein-Barr virus (EBV)-related pancytopenia can have a good prognosis if EBV resolves. Drug-induced pancytopenia has a favorable prognosis, as discontinuation of the offending agent can typically reverse the pancytopenia.

Diagnosis

Diagnostic Criteria

The diagnosis of pancytopenia is made when all of the following criteria are fulfilled:

  • Anemia as defined by hemoglobin level < 12 grams per deciliter (g/dl)
  • Leukopenia as defined by leukocyte count < 4000 per microliter
  • Thrombocytopenia as defined by platelet count < 150000 per microliter

History and Symptoms

Symptoms are pancytopenia are related to decrease in erythrocytes, leukocytes, and platelets. Decrease in erythrocytes causes fatigue, shortness of breath, decreased exercise tolerance, and pallor. Decrease in leukocytes causes infection, which can affect a multitude of organ systems including the central nervous system, lungs, abdomen, urinary tract, kidneys, and skin. Decrease in platelets causes mucocutaneous bleeding, typically of the nose, mouth, gastrointestinal tract, or genitourinary tract.

Physical Examination

Key components of the physical exam include assessment of the conjunctiva, oral and nasal mucosa, lymph nodes (cervical, axillary, supraclavicular, inguinal), spleen size, liver size, and skin.

The anemia component of pancytopenia can cause conjunctival pallor, mucosal pallor, and skin pallor. The leukopenia component of pancytopenia can cause variable findings depending on whether infection is present. Exam findings can include lymphadenopathy, egophony, coarse breath sounds, malodorous urine, suprapubic tenderness, costovertebral tenderness, abdominal tenderness, skin erythema, and/or skin purulence.

Laboratory Findings

Laboratory findings in pancytopenia are, by definition: Hemoglobin level < 12 grams per deciliter (g/dl) Leukocyte count < 4000 per microliter Platelet count < 150000 per microliter

Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

The treatment of pancytopenia depends on the underlying cause. If pancytopenia is due to medication adverse effect, the offending agent should be discontinued.

Surgery

The is no role for surgery for pancytopenia. However, for immune thrombocytopenia purpura (ITP) and autoimmune hemolytic anemia (AIHA), splenectomy can be considered.

Prevention

References

  1. 1.0 1.1 1.2 1.3 1.4 Passweg JR, Tichelli A (2009). "Immunosuppressive treatment for aplastic anemia: are we hitting the ceiling?". Haematologica. 94 (3): 310–2. doi:10.3324/haematol.2008.002329. PMC 2649354. PMID 19252172.
  2. 2.0 2.1 Scheinberg P, Young NS (2012). "How I treat acquired aplastic anemia". Blood. 120 (6): 1185–96. doi:10.1182/blood-2011-12-274019. PMC 3418715. PMID 22517900.
  3. 3.0 3.1 3.2 Das Makheja K, Kumar Maheshwari B, Arain S, Kumar S, Kumari S (2013). "The common causes leading to pancytopenia in patients presenting to tertiary care hospital". Pak J Med Sci. 29 (5): 1108–11. PMC 3858928. PMID 24353701.
  4. Weston CF, Hall MJ (1987). "Pancytopenia and folate deficiency in alcoholics". Postgrad Med J. 63 (736): 117–20. PMC 2428237. PMID 3671238.
  5. 5.0 5.1 Walter MJ, Shen D, Ding L, Shao J, Koboldt DC, Chen K; et al. (2012). "Clonal architecture of secondary acute myeloid leukemia". N Engl J Med. 366 (12): 1090–8. doi:10.1056/NEJMoa1106968. PMC 3320218. PMID 22417201.
  6. 6.0 6.1 6.2 Zeidan AM, Linhares Y, Gore SD (2013). "Current therapy of myelodysplastic syndromes". Blood Rev. 27 (5): 243–59. doi:10.1016/j.blre.2013.07.003. PMC 4124605. PMID 23954262.
  7. Shah NR, Landi DB, Kreissman SG, Kulbachi E, Moran C (2011). "Presentation and outcomes for children with bone marrow necrosis and acute lymphoblastic leukemia: a literature review". J Pediatr Hematol Oncol. 33 (7): e316–9. doi:10.1097/MPH.0b013e318223fe9b. PMID 21941136.
  8. Guerrero A M, Lira V P, Bertin C P, Galleguillos V M, Ocqueteau T M (2005). "[Natural killer cell leukemia. Case report]". Rev Med Chil. 133 (4): 457–60. doi:/S0034-98872005000400010 Check |doi= value (help). PMID 15953954.
  9. Vande Zande VL, Mazza JJ, Yale SH (2004). "Hematologic and metabolic abnormalities in a patient with anorexia nervosa". WMJ. 103 (2): 38–40. PMID 15139557.
  10. Bacon BR, Treuhaft WH, Goodman AM (1981). "Azathioprine-induced pancytopenia. Occurrence in two patients with connective-tissue diseases". Arch Intern Med. 141 (2): 223–6. PMID 7458518.
  11. Poisnel E, Ebbo M, Berda-Haddad Y, Faucher B, Bernit E, Carcy B; et al. (2013). "Babesia microti: an unusual travel-related disease". BMC Infect Dis. 13: 99. doi:10.1186/1471-2334-13-99. PMC 3598249. PMID 23432953.
  12. Braier L (1983). "An hypothesis for the induction of leukemia by benzene". Arch Toxicol Suppl. 6: 42–6. PMID 6578748.
  13. Guler S, Kokoglu OF, Ucmak H, Gul M, Ozden S, Ozkan F (2014). "Human brucellosis in Turkey: different clinical presentations". J Infect Dev Ctries. 8 (5): 581–8. doi:10.3855/jidc.3510. PMID 24820461.
  14. Bajaj P, Clement J, Bayerl MG, Kalra N, Craig TJ, Ishmael FT (2014). "High-grade fever and pancytopenia in an adult patient with common variable immune deficiency". Allergy Asthma Proc. 35 (1): 78–82. doi:10.2500/aap.2014.35.3704. PMID 24433602.
  15. Abdel-Karim A, Frezzini C, Viggor S, Davidson LE, Thornhill MH, Yeoman CM (2009). "Dyskeratosis congenita: a case report". Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 108 (2): e20–4. doi:10.1016/j.tripleo.2009.03.042. PMID 19615640.
  16. Zhang X, Wang Z, Wang L, Yao H (2013). "An adult case of systemic Epstein-Barr virus-positive T/natural killer-cell lymphoproliferative disorder with good outcome". Int J Clin Exp Pathol. 6 (11): 2620–4. PMC 3816837. PMID 24228130.
  17. Roche C, Roche NC, Thefenne H, Saidi R, De Pina JJ, Molinier S; et al. (2011). "[Pancytopenia and folate deficiency: a case report]". Ann Biol Clin (Paris). 69 (3): 331–5. doi:10.1684/abc.2011.0584. PMID 21659050.
  18. Suyama T, Obara N, Kawai K, Yamada K, Kusakabe M, Kurita N; et al. (2013). "[Acute myeloid leukemia possibly originating from the same clone of testicular germ cell tumor]". Rinsho Ketsueki. 54 (8): 764–8. PMID 24005437.
  19. Agbaht K, Altintas ND, Topeli A, Gokoz O, Ozcebe O (2007). "Transfusion-associated graft-versus-host disease in immunocompetent patients: case series and review of the literature". Transfusion. 47 (8): 1405–11. doi:10.1111/j.1537-2995.2007.01282.x. PMID 17655584.
  20. Fino P, Fioramonti P, Onesti MG, Passaretti D, Scuderi N (2012). "Skin metastasis in patient with hairy cell leukemia: case report and review of literature". In Vivo. 26 (2): 311–4. PMID 22351675.
  21. Giri PP, Pal P, Ghosh A, Sinha R (2013). "Infection-associated haemophagocytic lymphohistiocytosis: a case series using steroids only protocol for management". Rheumatol Int. 33 (5): 1363–6. doi:10.1007/s00296-011-2291-2. PMID 22193223.
  22. Jain A, Naniwadekar M (2013). "An etiological reappraisal of pancytopenia - largest series reported to date from a single tertiary care teaching hospital". BMC Hematol. 13 (1): 10. doi:10.1186/2052-1839-13-10. PMC 4177001. PMID 24238033.
  23. Konoplev S, Medeiros LJ, Lennon PA, Prajapati S, Kanungo A, Lin P (2007). "Therapy may unmask hypoplastic myelodysplastic syndrome that mimics aplastic anemia". Cancer. 110 (7): 1520–6. doi:10.1002/cncr.22935. PMID 17701956.
  24. Mattina T, Perrotta CS, Grossfeld P (2009). "Jacobsen syndrome". Orphanet J Rare Dis. 4: 9. doi:10.1186/1750-1172-4-9. PMC 2670819. PMID 19267933.
  25. Trejo-Pérez JA, Miranda-Novales MG, Solórzano-Santos F, Cabrera-Muñoz L, Díaz-Ponce H (1993). "[Kala-azar in Mexico: report of 2 cases]". Bol Med Hosp Infant Mex. 50 (9): 662–5. PMID 8373548.
  26. Khattak MB, Ismail M, Marwat ZI, Khan F (2012). "Frequency and characterisation of pancytopenia in megaloblastic anaemia". J Ayub Med Coll Abbottabad. 24 (3–4): 53–5. PMID 24669609.
  27. Germing U, Kobbe G, Haas R, Gattermann N (2013). "Myelodysplastic syndromes: diagnosis, prognosis, and treatment". Dtsch Arztebl Int. 110 (46): 783–90. doi:10.3238/arztebl.2013.0783. PMC 3855821. PMID 24300826.
  28. Zhang ZN, Liu EK (1991). "[Clinical features of paroxysmal nocturnal hemoglobinuria (PNH) in China as compared with those in United Kingdom]". Zhonghua Nei Ke Za Zhi. 30 (5): 276–9, 317. PMID 1879240.
  29. Rajput R, Sehgal A, Jain D, Sen R, Gupta A (2012). "Acute parvovirus b19 infection leading to severe aplastic anemia in a previously healthy adult female". Indian J Hematol Blood Transfus. 28 (2): 123–6. doi:10.1007/s12288-011-0112-0. PMC 3332267. PMID 23730023.
  30. Franck JL, Bouteiller G, Gayrard M, Arlet J (1979). "[D-penicillamine in rheumatoid arthritis : hematological incidents and accidents (author's transl)]". Sem Hop. 55 (27–30): 1325–7. PMID 228408.
  31. Song IC, Lee HJ, Kim HJ, Bae SB, Lee KT, Yang YJ; et al. (2013). "A multicenter retrospective analysis of the clinical features of pernicious anemia in a Korean population". J Korean Med Sci. 28 (2): 200–4. doi:10.3346/jkms.2013.28.2.200. PMC 3565130. PMID 23400269.
  32. Birkeland AC, Auerbach AD, Sanborn E, Parashar B, Kuhel WI, Chandrasekharappa SC; et al. (2011). "Postoperative clinical radiosensitivity in patients with fanconi anemia and head and neck squamous cell carcinoma". Arch Otolaryngol Head Neck Surg. 137 (9): 930–4. doi:10.1001/archoto.2011.154. PMC 3343719. PMID 21930984.
  33. Bauer H (2001). "[Fatal outcome of a multisystemic sarcoidosis in a 54-year-old patient]". Pneumologie. 55 (7): 343–6. doi:10.1055/s-2001-15617. PMID 11481582.
  34. Palmer K, Green TD, Roberts JL, Sajaroff E, Cooney M, Parrott R; et al. (2007). "Unusual clinical and immunologic manifestations of transplacentally acquired maternal T cells in severe combined immunodeficiency". J Allergy Clin Immunol. 120 (2): 423–8. doi:10.1016/j.jaci.2007.02.047. PMID 17481714.
  35. Sarkar RN, Banerjee S, Dey S, Saha A, Bhattacharjee P, Banerjee TK; et al. (2009). "Haematological presentation of systemic lupus erythematosus". J Assoc Physicians India. 57: 767–8. PMID 20329445.
  36. Song S (2011). "A case report: Concurrent chronic myelomonocytic leukemia and T-cell large granular lymphocytic leukemia-type clonal proliferation as detected by multiparametric flow cytometry". Cytometry B Clin Cytom. 80 (2): 126–9. doi:10.1002/cyto.b.20565. PMID 21337493.
  37. Villano JL, Letarte N, Yu JM, Abdur S, Bressler LR (2012). "Hematologic adverse events associated with temozolomide". Cancer Chemother Pharmacol. 69 (1): 107–13. doi:10.1007/s00280-011-1679-8. PMID 21614470.
  38. Le Hô H, Barbarot N, Desrues B (2010). "[Pancytopenia in disseminated tuberculosis: Think of macrophage activation syndrome]". Rev Mal Respir. 27 (3): 257–60. doi:10.1016/j.rmr.2010.02.005. PMID 20359619.
  39. Klimaszyk D, Łukasik-Głebocka M (2011). "[Pancytopenia in the course of acute valproic acid poisoning--case report]". Przegl Lek. 68 (8): 539–42. PMID 22010461.
  40. Eom TH, Lee HS, Jang PS, Kim YH (2013). "Valproate-induced panhypogammaglobulinemia". Neurol Sci. 34 (6): 1003–4. doi:10.1007/s10072-012-1153-3. PMID 22797722.
  41. Tun NT, Shukla S, Krishnakurup J, Pappachen B, Krishnamurthy M, Salib H (2014). "An unusual cause of pancytopenia: Whipple's disease". J Community Hosp Intern Med Perspect. 4. doi:10.3402/jchimp.v4.23482. PMC 3992356. PMID 24765256.
  42. 42.0 42.1 42.2 42.3 Chirnomas SD, Kupfer GM (2013). "The inherited bone marrow failure syndromes". Pediatr Clin North Am. 60 (6): 1291–310. doi:10.1016/j.pcl.2013.09.007. PMC 3875142. PMID 24237972.
  43. 43.0 43.1 43.2 Da Costa L, Moniz H, Simansour M, Tchernia G, Mohandas N, Leblanc T (2010). "Diamond-Blackfan anemia, ribosome and erythropoiesis". Transfus Clin Biol. 17 (3): 112–9. doi:10.1016/j.tracli.2010.06.001. PMC 3699172. PMID 20655265.
  44. 44.0 44.1 Nelson ND, Bertuch AA (2012). "Dyskeratosis congenita as a disorder of telomere maintenance". Mutat Res. 730 (1–2): 43–51. doi:10.1016/j.mrfmmm.2011.06.008. PMC 3208805. PMID 21745483.
  45. Palovcak A, Liu W, Yuan F, Zhang Y (2017). "Maintenance of genome stability by Fanconi anemia proteins". Cell Biosci. 7: 8. doi:10.1186/s13578-016-0134-2. PMC 5320776. PMID 28239445.
  46. Du W, Erden O, Pang Q (2014). "TNF-α signaling in Fanconi anemia". Blood Cells Mol Dis. 52 (1): 2–11. doi:10.1016/j.bcmd.2013.06.005. PMC 3851925. PMID 23890415.
  47. 47.0 47.1 Myers KC, Bolyard AA, Otto B, Wong TE, Jones AT, Harris RE; et al. (2014). "Variable clinical presentation of Shwachman-Diamond syndrome: update from the North American Shwachman-Diamond Syndrome Registry". J Pediatr. 164 (4): 866–70. doi:10.1016/j.jpeds.2013.11.039. PMC 4077327. PMID 24388329.
  48. Andolina JR, Morrison CB, Thompson AA, Chaudhury S, Mack AK, Proytcheva M; et al. (2013). "Shwachman-Diamond syndrome: diarrhea, no longer required?". J Pediatr Hematol Oncol. 35 (6): 486–9. doi:10.1097/MPH.0b013e3182667c13. PMC 3514592. PMID 22935661.


Template:WikiDoc Sources