Thrombocytopenia After Acute Infection: The Answer is Immune Thrombocytopenic Purpura (ITP)
The correct answer is A: Immune Thrombocytopenic Purpura (ITP), because acute viral infections trigger autoantibody formation against platelet glycoproteins, leading to immune-mediated platelet destruction that typically presents as isolated thrombocytopenia following the infectious episode. 1, 2
Why ITP is the Correct Answer
Pathophysiologic Link Between Infection and ITP
Acute viral infections are well-established triggers for secondary ITP, with the thrombocytopenia developing during or immediately after infections such as varicella-zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), parvovirus B19, hepatitis A virus (HAV), and rubella. 1, 2
The mechanism involves immune system activation by viral antigens that cross-react with platelet surface glycoproteins (particularly GPIIb-IIIa and GPIb-IX), resulting in autoantibody production and subsequent platelet destruction through antibody-dependent cellular phagocytosis, complement-mediated cytotoxicity, and cytotoxic T-lymphocyte activity. 3, 4, 5
In children, approximately two-thirds of ITP cases follow a recent viral infection or vaccination, with spontaneous remission occurring in 60-74% within 6 months, whereas adult post-infectious ITP tends toward chronicity. 6, 2
Clinical Presentation After Acute Infection
Post-infectious ITP presents as isolated thrombocytopenia (platelet count <100 × 10⁹/L) with otherwise normal complete blood count, appearing 1-4 weeks after the acute infectious illness resolves. 7, 6, 8
Physical examination reveals only bleeding manifestations (petechiae, purpura, mucosal bleeding); the presence of splenomegaly, hepatomegaly, or lymphadenopathy would exclude primary ITP and suggest alternative diagnoses such as ongoing infection, lymphoproliferative disease, or autoimmune conditions. 1, 7
Peripheral blood smear shows normal-sized or mildly enlarged platelets without schistocytes, giant platelets, or abnormal white cells—findings that distinguish ITP from inherited thrombocytopenias, thrombotic microangiopathies, and bone marrow disorders. 7, 8
Why the Other Options Are Incorrect
B. Glanzmann Thrombasthenia – Inherited Platelet Function Disorder
Glanzmann thrombasthenia is a congenital disorder caused by mutations in genes encoding GPIIb-IIIa, resulting in defective platelet aggregation with normal or near-normal platelet counts, not thrombocytopenia. 7
This condition presents from birth with mucocutaneous bleeding despite adequate platelet numbers; it does not develop acutely after infections and would have been evident earlier in life. 7
C. Hereditary Cyclooxygenase Deficiency – Congenital Platelet Function Defect
Hereditary cyclooxygenase deficiency is an extremely rare inherited disorder affecting platelet function (impaired thromboxane A₂ synthesis) but does not cause thrombocytopenia; platelet counts remain normal. 7
Like Glanzmann thrombasthenia, this is a lifelong condition present from birth, not an acquired disorder triggered by acute infection. 7
D. Von Willebrand Disease – Coagulation Factor Deficiency
Von Willebrand disease is an inherited bleeding disorder caused by quantitative or qualitative defects in von Willebrand factor, which affects platelet adhesion and factor VIII stability but does not cause thrombocytopenia. 7
Platelet counts are normal in von Willebrand disease; bleeding occurs due to impaired platelet-vessel wall interaction and prolonged aPTT (in severe cases), not low platelet numbers. 7
This condition is congenital and would have manifested earlier in life with excessive bleeding after minor trauma, dental procedures, or menorrhagia—not as acute-onset thrombocytopenia following infection. 7
Diagnostic Approach to Post-Infectious Thrombocytopenia
Essential Initial Workup
Confirm true thrombocytopenia by repeating the platelet count in a citrate or heparin tube and obtaining a peripheral blood smear reviewed by a hematopathologist to exclude EDTA-dependent pseudothrombocytopenia, which occurs in approximately 0.1% of samples. 7, 8
Verify isolated thrombocytopenia through complete blood count with differential; any unexplained anemia, leukopenia, or leukocytosis mandates bone marrow examination to exclude malignancy, myelodysplastic syndrome, or aplastic anemia. 1, 7
Mandatory Testing in Adults
HIV antibody testing is required in all adults with suspected ITP, regardless of risk factors, because HIV-associated thrombocytopenia is clinically indistinguishable from primary ITP and may precede other HIV manifestations by years. 1, 7
Hepatitis C virus serology must be obtained in all adults, as chronic HCV can cause secondary ITP that resolves with successful antiviral therapy. 1, 7
Helicobacter pylori testing (urea breath test or stool antigen assay, not serology) should be performed in adults, particularly in high-prevalence regions, because eradication therapy normalizes platelet counts in a subset of ITP patients. 1, 7
When Bone Marrow Examination is Mandatory
Age ≥60 years—to exclude myelodysplastic syndrome, leukemia, or other malignancies that increase in prevalence with age. 1, 7
Systemic constitutional symptoms (fever, unexplained weight loss, night sweats, bone pain)—these findings suggest underlying marrow pathology or lymphoproliferative disease. 1, 7
Abnormal CBC parameters beyond isolated thrombocytopenia (unexplained anemia, leukopenia, leukocytosis)—pancytopenia or additional cytopenias exclude primary ITP. 1, 7
Atypical peripheral smear findings (schistocytes suggesting thrombotic microangiopathy, giant platelets indicating inherited thrombocytopenia, immature white cells raising concern for leukemia, or leukocyte inclusion bodies seen in MYH9-related disease). 7
Organomegaly or lymphadenopathy on physical examination—these findings exclude primary ITP and mandate investigation for secondary causes. 1, 7
Minimal or no response to first-line ITP therapies (IVIg, corticosteroids, anti-D immunoglobulin)—treatment failure warrants bone marrow evaluation to confirm the diagnosis. 7
Management Principles for Post-Infectious ITP
Observation vs. Treatment Decision
Treatment decisions are based on bleeding severity, not platelet count alone; patients with no bleeding or only mild skin manifestations (petechiae, purpura) should be observed regardless of platelet number. 1, 6, 8
In children with post-infectious ITP, observation alone is recommended for those with platelet counts ≥30 × 10⁹/L and no or minor mucocutaneous bleeding, because spontaneous remission occurs in 60-74% within 6 months and the risk of serious bleeding (including intracranial hemorrhage at 0.1-0.5%) is extremely low. 1, 6
Treatment is indicated only when clinically significant bleeding occurs (persistent epistaxis requiring intervention, oral or gastrointestinal bleeding, menorrhagia), platelet count falls below 10 × 10⁹/L with any bleeding, or invasive procedures are planned. 1, 6
First-Line Treatment Options When Needed
For children requiring treatment, intravenous immunoglobulin (IVIg) 0.8-1 g/kg as a single dose is preferred over corticosteroids because it produces less immunosuppression during acute viral infection and achieves rapid platelet increase within 24-48 hours. 6, 2
Short-course corticosteroids (prednisone 1-2 mg/kg/day for 7-14 days) are an alternative first-line option but should be used cautiously in the setting of acute infection due to concerns about suppressing the inflammatory response needed to clear the pathogen. 6, 2
Anti-D immunoglobulin (50-75 μg/kg) is effective only in Rh(D)-positive, non-splenectomized patients and requires Rh(D) blood group typing before administration. 1, 6
Critical Pitfalls to Avoid
Never diagnose ITP without personal review of the peripheral blood smear by a hematopathologist, because automated counters miss pseudothrombocytopenia, giant platelets (inherited thrombocytopenias), and schistocytes (thrombotic microangiopathy with >90% mortality if untreated). 7, 8
Never omit HIV and hepatitis C testing in adults with suspected ITP, even in low-risk populations, because these infections can masquerade as primary ITP for years before other manifestations appear. 1, 7
Avoid prolonged corticosteroid therapy in children due to significant toxicities including growth suppression, immunosuppression, metabolic effects, and increased infection risk—limit corticosteroids to short courses (7-14 days) only when treatment is absolutely necessary. 1, 6
Do not prescribe medications that impair platelet function (aspirin, NSAIDs, antiplatelet agents) in patients with thrombocytopenia, as these drugs increase bleeding risk even with moderate platelet counts (50-100 × 10⁹/L). 7
Recognize that platelet transfusions are generally ineffective in ITP due to rapid immune-mediated destruction of transfused platelets and should be reserved only for life-threatening hemorrhage (intracranial bleeding, severe gastrointestinal bleeding) in combination with IVIg and corticosteroids. 6