thrombocytopenia
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Introduction
Abnormal decrease in number of the blood platelets.
Classification
Etiology
- congenital
- in-utero forms
- autoimmune thrombocytopenia
- infections
- viremia
- bacteremia
- other infections
- drugs
- thrombocytopenia with absent radius syndrome
- vascular malformations
- 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]
- in-utero forms
- diminished platelet production
- metabolite deficiency
- pharmacologic agents (common)
- physical/toxic agents
- radiation
- chemotherapy
- alcohol (common)
- myelophthisis
- granuloma
- tumor
- myelofibrosis
- infection
- diminished/defective megakaryocytes
- liver failure, portal hyperfunction
- chronic hemolysis
- sarcodosis
- increased platelet destruction
- immune-mediated
- immune thrombocytopenic purpura (ITP)
- drug-induced
- post-transfusion purpura
- antiphospholipid syndrome
- alloimmune
- bacterial sepsis without DIC
- some infections
- non-specific systemic allergic events
- thrombocytopenia with apparent cause[3]
- microangiopathic
- hypersplenism
- massive transfusion
- hypothermia
- gestational thrombocytopenia
- artificial heart valves
- snake venoms
- immune-mediated
- sequestion due to splenic pooling, splenomegaly
- 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
- symptoms:
- mild: platelet count: 100,000-150,000/uL - usually asymptomatic
- moderate: platelet count: 50,000-100,000/uL
- 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
- spontaneous bleeding, especially mucosal bleeding due to thrombocytopenia tend to occur immediately after trauma
- non-specific symptoms
- do not distinguish thrombocytopenia as a cause from coagulation disorders
- hematoma
- ecchymosis
- purpura
- organ bleeding
- headache in the setting of severe thrombocytopenia may be a symptom of intracranial bleeding
- signs:
- petechiae are much more often a sign of platelet disorders than a sign of microvascular disease
- hemorrhagic petechiae or bullae on mucous membranes may indicate a high risk of clinically significant bleeding
- bleeding from mucous membranes confers an increased risk of spontaneous intracranial hemorrhage
- onset:
- drug-induced thrombocytopenia: 5 days
- immune thrombocytopenia: > 5 days[11]
Laboratory
- complete blood count (CBC) with differential
- peripheral blood smear
- platelet clumps & low platelet count suggest pseudothrombocytopenia (EDTA-anticoagulated blood)
- schistocytes suggests microangiopathic hemolytic anemia
- partial thromboplastin time (PTT)
- prothrombin time (PT)
- fibrin split products
- serum chemistries[3]
- HIV1 testing & hepatitis C serology[3]
- bone marrow biopsy
- suspected myelodysplasia
- thrombocytopenia refractory to therapy (ITP)
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]
- bleeding risk greater for platelet counts < 5000/uL than > 80,000/uL, but no clear pattern of decreasing risk with increasing platelet counts[5]
Differential diagnosis
- isolated thrombocytopenia; blood platelets < 50,000/uL
- thrombocytopenia & schistocytes on peripheral smear
- thrombocytopenia & platelet clumps on peripheral smear
- thrombocytopenia, disorder in 2 cell lines, tear drop cells -> myelodysplasia
- thrombocytopenia, anemia, leukopenia & lymphocytosis
- pancytopenia, macrocytosis, hypersegmented neutrophils
- drug-induced thrombocytopenia
- heparin-induced thrombocytopenia (most common drug)
- post-tranfusion purpura 5-10 days after blood transfusion[3]
- cirrhosis: splenic sequestration due to splenomegaly
- platelet count is normal in von Willebrand disease
Management
- thrombocytopenias requiring emergency treatment
- platelet transfusions
- prophylactic platelet transfusion in patients with hematologic malignancy & platelet counts <10,000/uL (<20,000/uL in febrile patients)[3][4]
- each unit or transfused platelets should increase the platelet count by 5000-10,000/uL in the absence of active platelet destruction
- premedication to avoid febrile & allergic reactions
- contraindications to platelet transfusions:
- 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]
- thrombopoietin receptor agonist
- asymptomptomatic patients with idiopathic thrombocytopenia & platelet count > 30,000/uL need only observation[3]
- glucocorticoids for symptomatic idiopathic thrombocytopenia & platelet count < 30,000/uL
- activity
- < 10,000/mm3: no exercise or active physical therapy
- 10,000-20,000/mm3
- no resistance training
- aerobic exercise ok
- > 30,000: exercise not restricted
More general terms
More specific terms
- 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
Additional terms
- disseminated intravascular coagulation (DIC)
- hemolytic uremic syndrome (HUS)
- hereditary disorders associated with thrombocytopenia
- paroxysmal nocturnal hemoglobinuria (PNH, Marchiafava-Micheli syndrome)
- pseudothrombocytopenia
References
- ↑ Saunders Manual of Medical Practice, Rakel (ed), WB Saunders, Philadelphia, 1996, pg 590-94
- ↑ Harrison's Principles of Internal Medicine, 13th ed. Companion Handbook, Isselbacher et al (eds), McGraw-Hill Inc. NY, 1995, pg 829-39
- ↑ 3.00 3.01 3.02 3.03 3.04 3.05 3.06 3.07 3.08 3.09 3.10 3.11 3.12 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 - ↑ 4.0 4.1 Stanworth SJ et al. A no-prophylaxis platelet-transfusion strategy for hematologic cancers. N Engl J Med 2013 May 9; 368:1771 PMID: https://www.ncbi.nlm.nih.gov/pubmed/23656642
Slichter SJ. Eliminate prophylactic platelet transfusions? N Engl J Med 2013 May 9; 368:1837. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23656650 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1212772 http://www.nejm.org/doi/full/10.1056/NEJMe1302974 - ↑ 5.0 5.1 5.2 5.3 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: https://www.ncbi.nlm.nih.gov/pubmed/28679741
- ↑ Gauer RL, Braun MM. Thrombocytopenia. Am Fam Physician 2012 Mar 15; 85:612 PMID: https://www.ncbi.nlm.nih.gov/pubmed/22534274 Free full text
- ↑ 7.0 7.1 ARUP Consult: Thrombocytopenic Disorders The Physician's Guide to Laboratory Test Selection & Interpretation https://arupconsult.com/content/thrombocytopenic-disorders
- ↑ 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: https://www.ncbi.nlm.nih.gov/pubmed/23845922 PMCID: PMC3728035 Free PMC article
- ↑ Aster RH, Bougie DW Drug-Induced Immune Thrombocytopenia N Engl J Med 2007; 357:580-587 PMID: https://www.ncbi.nlm.nih.gov/pubmed/17687133 https://www.nejm.org/doi/full/10.1056/NEJMra066469
- ↑ 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: https://www.ncbi.nlm.nih.gov/pubmed/17329697 Free article https://www.nejm.org/doi/full/10.1056/NEJMoa065066
- ↑ 11.0 11.1 NEJM Knowledge+ Question of the Week. Jan 12, 2021 https://knowledgeplus.nejm.org/question-of-week/1082/
- ↑ 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
- ↑ 13.0 13.1 13.2 NEJM Knowledge+ Hematology
Gauer RL, Whitaker DJ. Thrombocytopenia: Evaluation and Management. Am Fam Physician. 2022 Sep;106(3):288-298. PMID: https://www.ncbi.nlm.nih.gov/pubmed/36126009
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