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thrombocytopenia

Abnormal decrease in number of the blood platelets. Classification: 1) mild: 100,000-150,000/uL 2) moderate: 50,000-100,000/uL 3) severe: <50,000/uL Etiology: 1) congenital a) in-utero forms - autoimmune thrombocytopenia - infections - viremia - bacteremia - other infections - drugs - thrombocytopenia with absent radius syndrome - vascular malformations b) hereditary forms - isolated familial thrombocytopenia - Wiskott-Aldrich syndrome - Fanconi syndrome - Alport's syndrome - Bernard-Soulier disease - Glanzmann thrombasthenia - von Willebrand's disease, platelet type - May-Hegglin anomaly - Chediak-Higashi syndrome - thrombocytopenia absent radius syndrome - gray platelet syndrome [3] 2) diminished platelet production a) metabolite deficiency - vitamin B12 deficiency - folate deficiency b) pharmacologic agents (common) - acetazolamide - aspirin - carbamazepine - chlorpropamide - chlorthalidone - estrogens - gold salts - indomethacin - isoniazid - methyldopa - phenylbutazone - phenytoin & other hydantoins - quinine (TTP) - others, many c) physical/toxic agents - radiation - chemotherapy - alcohol (common) d) myelophthisis - granuloma - tumor - myelofibrosis e) infection - viral infection - CMV, HIV1 infection, parvovirus B19,, hepatitis C infection, EBV, rubella, mumps, varicella - HIV1-induced thrombocytopenia - protozoan - malaria, Leishmaniasis - rickettsia - tuberculosis f) diminished/defective megakaryocytes - myelodysplastic syndrome - myeloproliferative disease - malignancies - CML, CLL, Hodgkin's disease, non-Hodgkin's lymphoma, hairy cell leukemia - small cell lung cancer metastases to bone marrow - aplastic anemia - paroxysmal nocturnal hemoglobinuria - Fanconi anemia - collagen-vascular disease - systemic lupus erythematosus - myelofibrosis [3] - graft vs host disease g) liver failure, portal hyperfunction h) chronic hemolysis - thalassemia major - hemoglobin C disease - hereditary spherocytosis i) sarcodosis 3) increased platelet destruction a) immune-mediated - immune thrombocytopenic purpura (ITP) - drug-induced - heparin* - quinidine - quinine - beta-lactam antibiotics: moxalactam, penicillin - sulfonamides: trimethoprim-sulfamethoxazole [13] - valproic acid - vancomycin [13] - post-transfusion purpura - antiphospholipid syndrome - alloimmune - bacterial sepsis without DIC - some infections - non-specific systemic allergic events - thrombocytopenia with apparent cause [3] b) microangiopathic - microangiopathic hemolytic anemia (schistocytes on peripheral smear) - disseminated intravascular coagulation (DIC)* - thrombotic thrombocytopenic purpura (TTP)* - hemolytic uremic syndrome - eclampsia, HELLP syndrome - localized intravascular coagulation - giant cavernous hemangioma - dissecting aortic aneurysm - malignant hypertension - renal graft allorejection - intravascular foreign bodies - vascular malformations - burns c) hypersplenism d) massive transfusion e) hypothermia f) gestational thrombocytopenia g) artificial heart valves h) snake venoms 4) sequestion due to splenic pooling, splenomegaly 5) pseudothrombocytopenia * Marks thrombocytopenias considered medical emergencies. Pathology: - isolated thrombocytopenia in most patients is not due to bone marrow disease or stem cell disorder [3] Genetics: - defects in MASTL are the cause of thrombocytopenia type 2 Clinical manifestations: 1) symptoms: a) mild: platelet count: 100,000-150,000/uL - usually asymptomatic b) moderate: platelet count: 50,000-100,000/uL - easy bruisability - excessive bleeding during trauma c) severe: platelet count: <50,000/uL - excessive bleeding during surgery with platelet count: < 30,000 - platelet count: <10,000-20,000 - risk of spontaneous bleeding d) spontaneous bleeding, especially mucosal bleeding due to thrombocytopenia tend to occur immediately after trauma e) non-specific symptoms - do not distinguish thrombocytopenia as a cause from coagulation disorders - hematoma - ecchymosis - purpura - organ bleeding f) headache in the setting of severe thrombocytopenia may be a symptom of intracranial bleeding 2) signs: a) petechiae are much more often a sign of platelet disorders than a sign of microvascular disease b) hemorrhagic petechiae or bullae on mucous membranes may indicate a high risk of clinically significant bleeding c) bleeding from mucous membranes confers an increased risk of spontaneous intracranial hemorrhage 3) onset: a) drug-induced thrombocytopenia: 5 days b) immune thrombocytopenia: > 5 days [11] Laboratory: 1) complete blood count (CBC) with differential 2) peripheral blood smear - platelet clumps & low platelet count suggest pseudothrombocytopenia (EDTA-anticoagulated blood) - schistocytes suggests microangiopathic hemolytic anemia 3) partial thromboplastin time (PTT) 4) prothrombin time (PT) 5) fibrin split products 6) serum chemistries [3] a) liver function tests b) thyroid function tests c) basic metabolic panel d) serum vitamin B12 e) serum folate 7) HIV1 testing & hepatitis C serology [3] 8) bone marrow biopsy a) suspected myelodysplasia b) thrombocytopenia refractory to therapy (ITP) * also see ARUP consult [7] Radiology: - CT for evaluation of splenomegaly (hypersplenism) Complications: - major bleeding including intracranial hemorrhage associated with thrombocytopenia [5] - bleeding risk greater for platelet counts < 5000/uL than > 80,000/uL, but no clear pattern of decreasing risk with increasing platelet counts [5] - platelet transfusion not associated with diminished next day bleeding [5] Differential diagnosis: 1) isolated thrombocytopenia; blood platelets < 50,000/uL - immune thrombocytopenic purpura 2) thrombocytopenia & schistocytes on peripheral smear a) disseminated intravascular coagulaion (DIC) b) thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS) c) HELLP syndrome 3) thrombocytopenia & platelet clumps on peripheral smear - pseudothrombocytopenia 4) thrombocytopenia, disorder in 2 cell lines, tear drop cells -> myelodysplasia 5) thrombocytopenia, anemia, leukopenia & lymphocytosis - aplastic anemia 6) pancytopenia, macrocytosis, hypersegmented neutrophils - vitamin B12 deficiency, folate deficiency 7) drug-induced thrombocytopenia - heparin-induced thrombocytopenia (most common drug) 8) post-tranfusion purpura 5-10 days after blood transfusion [3] 9) cirrhosis: splenic sequestration due to splenomegaly 10) platelet count is normal in von Willebrand disease Management: 1) thrombocytopenias requiring emergency treatment a) heparin-induced thrombocytopenia b) disseminated intravascular coagulation (DIC) c) thrombotic thrombocytopenic purpura (TTP) 2) platelet transfusions a) prophylactic platelet transfusion in patients with hematologic malignancy & platelet counts <10,000/uL (<20,000/uL in febrile patients) [3,4] b) each unit or transfused platelets should increase the platelet count by 5000-10,000/uL in the absence of active platelet destruction c) premedication to avoid febrile & allergic reactions - hydrocortisone - diphenhydramine (Benadryl) - acetaminophen (Tylenol) d) contraindications to platelet transfusions: - thrombotic thrombocytopenic purpura (TTP) - hemolytic uremic syndrome (HUS) - post-transfusion purpura 3) specific treatment for specific causes of thrombocytopenia - thrombopoietin receptor agonist - glucocorticoids for immune-mediated thrombocytopenia (idiopathic thrombocytopenia) [3] - not indicated for chemotherapy-induced thrombocytopenia [3] - thrombotic thrombocytopenia - discontinuation of offending drug should result in platelet recovery [3] 4) asymptomptomatic patients with idiopathic thrombocytopenia & platelet count > 30,000/uL need only observation [3] - glucocorticoids for symptomatic idiopathic thrombocytopenia & platelet count < 30,000/uL 5) activity a) < 10,000/mm3: no exercise or active physical therapy b) 10,000-20,000/mm3 a) no resistance training b) aerobic exercise ok c) > 30,000: exercise not restricted

Related

disseminated intravascular coagulation (DIC) hemolytic uremic syndrome (HUS) hereditary disorders associated with thrombocytopenia paroxysmal nocturnal hemoglobinuria (PNH, Marchiafava-Micheli syndrome) pseudothrombocytopenia

Specific

Evan's syndrome HELLP syndrome heparin-induced thrombocytopenia; heparin-associated antibody syndrome (HIT) HIV-induced thrombocytopenia immune or idiopathic thrombocytopenic purpura (ITP) macrothrombocytopenia neonatal alloimmune thrombocytopenia thrombocytopenia of pregnancy (gestational thrombocytopenia) thrombotic thrombocytopenic purpura (TTP) X-linked dyserythropoietic anemia & thrombocytopenia X-linked thrombocytopenia with beta-thalassemia; thrombocytopenia, platelet dysfunction, hemolysis, & imbalanced globin synthesis

General

platelet disorder; thromboasthenia sign/symptom

Database Correlations

OMIM 188000

References

  1. Saunders Manual of Medical Practice, Rakel (ed), WB Saunders, Philadelphia, 1996, pg 590-94
  2. Harrison's Principles of Internal Medicine, 13th ed. Companion Handbook, Isselbacher et al (eds), McGraw-Hill Inc. NY, 1995, pg 829-39
  3. Medical Knowledge Self Assessment Program (MKSAP) 11, 16, 17, 18, 19. American College of Physicians, Philadelphia 1998, 2012, 2015, 2018, 2022. - Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022
  4. Stanworth SJ et al. A no-prophylaxis platelet-transfusion strategy for hematologic cancers. N Engl J Med 2013 May 9; 368:1771 PMID: 23656642 - Slichter SJ. Eliminate prophylactic platelet transfusions? N Engl J Med 2013 May 9; 368:1837. PMID: 23656650 http://www.nejm.org/doi/full/10.1056/NEJMoa1212772 http://www.nejm.org/doi/full/10.1056/NEJMe1302974
  5. Uhl L, Assmann SF, Hamza TH et al. Laboratory predictors of bleeding and the effect of platelet and RBC transfusions on bleeding outcomes in the PLADO trial. Blood 2017 Sep 7; 130:1247 PMID: 28679741
  6. Gauer RL, Braun MM. Thrombocytopenia. Am Fam Physician 2012 Mar 15; 85:612 PMID: 22534274 Free full text
  7. ARUP Consult: Thrombocytopenic Disorders The Physician's Guide to Laboratory Test Selection & Interpretation https://arupconsult.com/content/thrombocytopenic-disorders
  8. Arnold DM, Nazi I, Warkentin TE et al Approach to the diagnosis and management of drug-induced immune thrombocytopenia. Transfus Med Rev. 2013 Jul;27(3):137-45 PMID: 23845922 PMCID: PMC3728035 Free PMC article
  9. Aster RH, Bougie DW Drug-Induced Immune Thrombocytopenia N Engl J Med 2007; 357:580-587 PMID: 17687133 https://www.nejm.org/doi/full/10.1056/NEJMra066469
  10. Von Drygalski A, Curtis BR, Bougie DW et al. Vancomycin-induced immune thrombocytopenia. N Engl J Med 2007 Mar 1; 356(9):904-10 PMID: 17329697 Free article https://www.nejm.org/doi/full/10.1056/NEJMoa065066
  11. NEJM Knowledge+ Question of the Week. Jan 12, 2021 https://knowledgeplus.nejm.org/question-of-week/1082/
  12. Hackethal V Why Clotting Happens When Platelets Are Low. A hematologist explains the counterintuitive concept of clots with low platelets. MedPage Today April 23, 2021 https://www.medpagetoday.com/special-reports/exclusives/92243
  13. NEJM Knowledge+ Hematology - Gauer RL, Whitaker DJ. Thrombocytopenia: Evaluation and Management. Am Fam Physician. 2022 Sep;106(3):288-298. PMID: 36126009