Immune Thrombocytopenia

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])

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

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

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

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

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