The Differential Diagnosis of Thromobocytopenia

Abstract

Background: Thrombocytopenia is defined as a platelet count below 150 000/μL. It increases the risk of bleeding, often due to an existing underlying condition. A meticulous diagnostic evaluation is needed so that specific treatment can be initiated and complications avoided.

Methods: This review is based on clinical studies up to June 2025 that were retrieved by a selective search with pertinent key words in the MEDLINE/PubMed database, and on current guidelines.

Results: Thrombocytopenia often arises in association with pregnancy (7-10 %), immune-mediated diseases such as idiopathic thrombocytopenic purpura (ITP), certain drugs (e.g., heparin-induced thrombocytopenia [HIT] in as many as 1% of patients treated with unfractionated heparin), infections, and systemic and hematologic diseases. The diagnostic evaluation is by an algorithm involving the clinical history, a complete blood count, and other, specific tests. Emergencies such as thrombotic microangiopathy (TMA) and disseminated intravascular coagulation require rapid therapeutic intervention. The treatment depends on the cause and severity of thrombocytopenia; it can include the discontinuation of precipitating drugs, the use of immunosuppressive drugs or thrombopoietin receptor agonists in immune-mediated cases, and specific measures against infection, TMA, or malignant diseases. Prophylactic platelet transfusion can be considered if the platelet count drops below 10 000-20 000/μL, or below 50 000/μL before an intervention or operation, but not in cases of ITP or thrombotic thrombocytopenic purpura (TTP).

Conclusion: The treatment depends on the clinical manifestations, platelet count, and underlying cause.

Figure

Algorithm for the evaluation of thrombocytopenia Red boxes indicate emergencies (red flags, immediate transfer to an emergency room is necessary): yellow boxes indicate pathological findings or diseases that do not constitute an immediate emergency; green boxes indicate physiological or benign findings. ADAMTS-13, a disintegrin and metalloproteinase with thrombospondin motifs 13; ALAT, alanine aminotransferase; ANA, antinuclear antibodies; APS, antiphospholipid syndrome; ASAT, aspartate aminotransferase; CMV, cytomegalovirus; COVID-19, coronavirus disease 2019; CRP, C-reactive protein; DIC, disseminated intravascular coagulation; EBV, Epstein-Barr virus; EDTA, ethylenediaminetetraacetic acid; eGFR, estimated glomerular filtration rate; HIT, heparin-induced thrombocytopenia; aHUS, atypical hemolytic-uremic syndrome; HUS, hemolytic-uremic syndrome; ITP, immune thrombocytopenia; LDH, lactate dehydrogenase; MRI, magnetic resonance imaging; PET-CT, positron emission tomography-computerized tomography; TMA, thrombotic microangiopathy; TTP, thrombotic thrombocytopenic purpura; VITT, vaccine-induced immune thrombotic thrombocytopenia; vWF, von Willebrand factor