Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content + Download Section PDF Listen ++ For further information, see CMDT Part 14-04: Increased Platelet Destruction + Key Features Download Section PDF Listen +++ +++ Essentials of Diagnosis ++ Isolated thrombocytopenia (rule out pseudothrombocytopenia by review of peripheral smear) Assess for any new causative medications and HIV and hepatitis B and C infections, and Helicobacter pylori infections Immune thrombocytopenia is a diagnosis of exclusion +++ General Considerations ++ Immune thrombocytopenia is an autoimmune condition in which pathogenic antibodies bind platelets, accelerating their clearance from circulation The disorder is primary (idiopathic) in most adult patients, although it can be secondary, ie associated with Autoimmune disease (such as systemic lupus erythematosus) Lymphoproliferative disease (such as lymphoma) Medications (see Table 14–7) Infections (such as HIV, hepatitis C, Epstein-Barr, and Zika virus infections) Targets of antiplatelet antibodies include glycoproteins IIb/IIIa and Ib/IX on the platelet membrane, although antibodies are demonstrable in only two-thirds of patients In addition to production of antiplatelet antibodies, HIV and hepatitis C virus may lead to thrombocytopenia through additional mechanisms (for instance, by direct suppression of platelet production [HIV] and cirrhosis-related decreased thrombopoietin production and secondary splenomegaly [hepatitis C virus]) ++Table Graphic Jump LocationTable 14–7.Selected medications causing drug-associated thrombocytopenia.1View Table||Download (.pdf) Table 14–7. Selected medications causing drug-associated thrombocytopenia.1 Class Examples Chemotherapy Most agents Antiplatelet agents Abciximab, eptifibatide, tirofiban Anagrelide Ticlopidine Antimicrobial agents Adefovir, indinavir, ritonavir Fluconazole Isoniazid Linezolid Penicillins Rifampin Sulfa drugs Vancomycin Cardiovascular agents Amiodarone Atorvastatin, simvastatin Captopril Digoxin Hydrochlorothiazide Procainamide Gastrointestinal agents Cimetidine, famotidine Neuropsychiatric agents Carbamazepine Haloperidol Methyldopa Phenytoin Analgesic agents Acetaminophen Diclofenac, ibuprofen, naproxen, sulindac Anticoagulant agents Heparin Low-molecular-weight heparin Immunomodulator agents Interferon-alpha Rituximab Immunosuppressant agents Mycophenolate mofetil Tacrolimus Other agents Immunizations Iodinated contrast dye 1See also https://www.ouhsc.edu/platelets/. + Clinical Findings Download Section PDF Listen +++ +++ Symptoms and Signs ++ Mucocutaneous bleeding may be present, depending on the platelet count Clinically relevant spontaneous bruising, epistaxis, gingival bleeding, or other types of hemorrhage generally do not occur until the platelet count has fallen below 10,000–20,000/mcL Additional disease-specific findings may be present in persons with secondary immune thrombocytopenia (such as due to collagen vascular disease, HIV or HCV infection, or lymphoproliferative malignancy) +++ Differential Diagnosis ++ Thrombotic thrombocytopenic purpura Acute leukemia Myelodysplastic syndrome Disseminated intravascular coagulation Early aplastic anemia Drug toxicity (eg, heparin, sulfonamides, thiazides, quinine) Alcohol abuse Hypersplenism Systemic lupus erythematosus + Diagnosis Download Section PDF Listen +++ +++ Laboratory Tests ++ Isolated thrombocytopenia with platelet count < 100,000/mcL, often < 25,000/mcL If bleeding has occurred, anemia may also be present Serologic testing to exclude hepatitis virus B and C and HIV infections Megakaryocyte morphologic abnormalities and hypocellularity or hypercellularity are not characteristic of immune thrombocytopenia, but patients with ITP often have increased numbers of bone marrow megakaryocytes In the absence of such findings, otherwise asymptomatic patients with unexplained isolated thrombocytopenia of recent onset may be considered to have immune thrombocytopenia +++ Imaging Studies ++ If there are clinical findings suggestive of a lymphoproliferative malignancy, a CT scan should be performed +++ Diagnostic Procedures ++ Bone marrow should be examined in patients With unexplained cytopenias in two or more lineages Older than 40 years with isolated thrombocytopenia Who did not respond to primary immune thrombocytopenia-specific therapy + Treatment Download Section PDF Listen +++ +++ Medications ++ A short course of corticosteroids with or without IVIG or anti-D (WinRho) are mainstay of initial treatment (Figure 14–1) Anti-D (WinRho) or IVIG temporarily increases platelet counts (duration, up to 3 weeks or longer) Serial IVIG or anti-D treatment (platelet counts < 30,000/mcL) may allow adult patients to delay or avoid splenectomy Adding rituximab may improve initial response rate but rituximab plus corticosteroids is associated with increased toxicity Short course of high-dose dexamethasone is also an option for initial treatment Platelet transfusions may be given concomitantly if active bleeding is present Rituximab leads to clinical responses in about 50% of adults with corticosteroid-refractory chronic immune thrombocytopenia Romiplostim (administered at 1–10 mcg subcutaneously weekly), eltrombopag (taken as 25–75 mg orally daily), and avatrombopag (taken orally daily) Approved for use in adult patients with chronic immune thrombocytopenia who have not responded durably to corticosteroids, IVIG, or splenectomy Typically taken indefinitely to maintain the platelet response Can be used as second-line therapy Fostamatinib Syk inhibitor Used to treat patients who do not respond to corticosteroids, TPO-mimetics, or rituximab Moderate-dose oral prednisone or intermittent infusions of IVIG are standard treatment options for pregnancy-associated immune thrombocytopenia ++ Figure 14–1. Management of immune thrombocytopenia (ITP), a simplified overview. Note: All patients with ITP need to be managed by a hematologist because of the nuanced decision making required. Graphic Jump LocationView Full Size||Download Slide (.ppt) +++ Surgery ++ Splenectomy Durable response rate of over 50% Consider for severe cases of thrombocytopenia that fail to respond durably to initial treatment or are refractory to second-line agents Patients should receive pneumococcal, Haemophilus influenzae type b, and meningococcal vaccination at least 2 weeks before splenectomy If available, laparoscopic splenectomy is preferred +++ Therapeutic Procedures ++ Only individuals with platelet counts < 25,000–30,000/mcL or those with significant bleeding should be treated The goal of management of pregnancy-associated immune thrombocytopenia is a platelet count > 10,000–30,000/mcL in the first trimester, > 30,000/mcL during the second or third trimester, or > 50,000/mcL prior to cesarean section or vaginal delivery + Outcome Download Section PDF Listen +++ +++ Follow-Up ++ Monitor patients for progression +++ Complications ++ Major initial concern is cerebral hemorrhage, a risk when platelet count is < 5000/mcL Fatal bleeding is rare, even at very low platelet counts +++ Prognosis ++ Prognosis for remission is good Most patients relapse after reduction of the corticosteroid dose Disease is usually initially controlled with prednisone; splenectomy offers definitive therapy Chronic thrombocytopenia will develop in most adult patients with newly diagnosed ITP +++ When to Refer ++ All patients with ITP should be referred to a hematologist for evaluation at the time of diagnosis +++ When to Admit ++ Patients with major hemorrhage or very severe thrombocytopenia associated with bleeding should be admitted and monitored in-hospital until the platelet count has stably risen to > 20,000–30,000/mcL and hemodynamic stability has been achieved + References Download Section PDF Listen +++ + +Bussel J et al. Fostamatinib for the treatment of adult persistent and chronic immune thrombocytopenia: results of two phase 3, randomized, placebo-controlled trials. Am J Hematol. 2018 Jul;93(7):921–30. [PubMed: 29696684] + +Chaturvedi S et al. Splenectomy for immune thrombocytopenia: down but not out. Blood. 2018 Mar 15;131(11):1172–82. [PubMed: 29295846] + +Neunert C et al. American Society of Hematology 2019 guidelines for immune thrombocytopenia. Blood Adv. 2019 Dec 10;3(23):3829–66. [PubMed: 31794604] + +Neunert C et al. Severe bleeding events in adults and children with primary immune thrombocytopenia: a systematic review. J Thromb Haemost. 2015 Mar;13(3):457–64. [PubMed: 25495497] + +Yang R et al. Therapeutic options for adult patients with previously treated immune thrombocytopenia—a systematic review and network meta-analysis. Hematology. 2019 Dec;24(1):290–9. [PubMed: 30661482]