Zheng XL, Vesely SK, Cataland SR, et al. ISTH guidelines for the diagnosis of thrombotic thrombocytopenic purpura. J Thromb Haemost. 2020 Jul 17. doi: 10.1111/jth.15006. Epub ahead of print. PMID: 32914582.
Zheng XL, Vesely SK, Cataland SR, et al. ISTH guidelines for treatment of thrombotic thrombocytopenic purpura. J Thromb Haemost. 2020 Jul 15. doi: 10.1111/jth.15010. Epub ahead of print. PMID: 32914526.
Neunert C, Terrell DR, Arnold DM, et al. American Society of Hematology 2019 guidelines for immune thrombocytopenia. Blood Adv. 2019 Dec 10;3(23):3829-3866. doi: 10.1182/bloodadvances.2019000966. Erratum in: Blood Adv. 2020 Jan 28;4(2):252. PMID: 31794604; PMCID: PMC6963252.
Arnold DM, Kukaswadia S, Nazi I, et al. A systematic evaluation of laboratory testing for drug-induced immune thrombocytopenia. J Thromb Haemost. 2013 Jan;11(1):169-76. doi: 10.1111/jth.12052. PMID: 23121994; PMCID: PMC4991941.
Definition, Etiology, PathogenesisTop
Disorders of platelets may be caused by low platelet counts (thrombocytopenia), high platelet counts (thrombocytosis), or abnormal platelet function.
1. Thrombocytopenia is usually defined as a platelet count <150,000/microL. It may be classified as:
a) Immune: Primary or secondary immune thrombocytopenia (ITP); drug-induced immune thrombocytopenia (eg, quinine/quinidine, sulfonamides, vancomycin, abciximab, antibiotics); heparin-induced thrombocytopenia (HIT), which can be associated with thrombosis. Secondary ITP can be caused by infections (HIV, hepatitis C, Helicobacter pylori), concomitant autoimmune diseases (eg, systemic lupus erythematosus, antiphospholipid syndrome), and non-Hodgkin lymphoma, among others.
b) Nonimmune: Thrombotic microangiopathies, including thrombocytopenic purpura (TTP) and hemolytic-uremic syndrome (HUS), sepsis, disseminated intravascular coagulation (DIC), Kasabach-Merritt syndrome, and others.
a) Inherited: Rare, sometimes familial, it may present in childhood. Examples include Bernard-Soulier syndrome, Fanconi anemia, Alport syndrome.
b) Acquired: More frequent, it may be caused by drugs (myelosuppressive agents, linezolid, interferons, and many others), alcohol abuse and other toxins, viral infections, cobalamin and/or folate deficiency, bone marrow disorders (leukemia, aplastic anemia, lymphoid neoplasm, myelodysplastic syndrome, cancer metastasis, myelofibrosis), bone marrow infiltration (Gaucher disease, tuberculosis), radiation, amegakaryocytic thrombocytopenia, or cyclic thrombocytopenia (regular decreases in platelet counts every 21-39 days, most frequently in young women).
3) Thrombocytopenia caused by sequestration of platelets: Hypersplenism; rarely at other sites, such as large hemangiomas.
4) Thrombocytopenia caused by dilution developing after massive transfusion or fluid resuscitation.
5) Physiologic thrombocytopenia of pregnancy, also called gestational thrombocytopenia (platelet counts are usually >70,000/microL; the condition requires no treatment and resolves spontaneously after delivery).
6) Pseudothrombocytopenia is a laboratory artifact caused by in vitro platelet agglutination (clumping) in the blood collected in a tube containing ethylenediaminetetraacetic acid (EDTA). It can cause significant underestimation of platelet counts. Examination of the blood film should be done for any patient with thrombocytopenia to exclude platelet clumping. Most automated analyzers will recognize platelet clumping and not report a falsely reduced level. Platelet counts are often accurate when the blood is collected in tubes containing heparin or citrate.
2. Thrombocytosis is defined as a platelet count >400,000/microL:
1) Primary thrombocytosis (essential thrombocythemia) is a myeloproliferative neoplasm (see Primary Myelofibrosis).
2) Secondary (reactive) thrombocytosis may be caused by surgery, solid tumors, iron deficiency anemia, hemolytic anemia, chronic inflammatory or infectious diseases, acute blood loss, or splenectomy. It is usually asymptomatic, causes no bleeding or thrombosis, and resolves after successful treatment of the underlying condition.
3. Qualitative disorders of platelet function cause prolonged bleeding times and impaired platelet aggregation as assessed using aggregometry in patients with normal or slightly decreased platelet counts:
1) Inherited: Rare abnormalities of platelet surface receptors (eg, Bernard-Soulier syndrome, Glanzmann thrombasthenia), membrane, cytoskeleton, or degranulation.
2) Acquired: Most commonly drug-induced (acetylsalicylic acid, ticlopidine, clopidogrel, prasugrel, ticagrelor, glycoprotein IIb/IIIa antagonists, fibrinolytic agents, or other drugs) or caused by uremia, myeloproliferative neoplasms, acute leukemia, or monoclonal gammopathy.
Note: In patients with severe bleeding due to a qualitative platelet disorder, tranexamic acid or desmopressin 0.3 microg/kg may be effective. Platelet concentrates may be considered for patients who do not respond adequately to medical treatments. Repeated doses of desmopressin are limited by tachyphylaxis and hyponatremia. Data from clinical trials are lacking.
Cutaneous and mucosal bleeding: petechiae on the skin of extremities, trunk (rarely the face), and oral mucosa; gingival bleeding; epistaxis; menorrhagia and urinary and/or genital bleeding. Life-threatening gastrointestinal or intracranial hemorrhages may occur, and excessive bleeding after tissue injury may be observed. In patients with thrombocytopenia bleeding usually occurs with platelet counts <20,000/microL.