What are the typical complete blood count (CBC) findings in thrombotic microangiopathy (TMA)?

Typical CBC Findings in Thrombotic Microangiopathy

The hallmark CBC findings in TMA are thrombocytopenia (platelets <150,000/mm³ or a 25% reduction from baseline) and anemia with evidence of hemolysis, though the complete triad may not always be present initially. 1

Core Hematologic Abnormalities

Platelet Count

• Thrombocytopenia is a defining feature, with platelet counts typically <150,000/mm³ or showing a 25% reduction from the patient's baseline value 1
• The degree of thrombocytopenia varies by TMA subtype—TTP and HUS typically show more severe thrombocytopenia compared to hypertension-induced TMA, which presents with only moderate thrombocytopenia 1
• Platelet consumption occurs due to formation of platelet-rich thrombi in the microcirculation 1, 2

Hemoglobin/Anemia

• Non-immune hemolytic anemia is characteristic, with the direct Coombs test being negative 1, 2
• Anemia results from mechanical fragmentation of red blood cells as they pass through damaged small vessels containing platelet-rich thrombi and fibrin networks 1, 2
• The severity of anemia varies, but it should be disproportionate to any bleeding if present 1

Red Blood Cell Morphology

• Schistocytes (fragmented red blood cells) are the pathognomonic finding on peripheral blood smear 2
• Other fragmented forms include burr cells and helmet cells 2
• Important caveat: Schistocytes >1% strongly support TMA diagnosis, but their absence does not exclude early TMA due to the test's low sensitivity 1
• In hypertension-induced TMA, only few schistocytes may be present compared to TTP or HUS 1

White Blood Cell Count

• The WBC count is typically normal in primary TMA syndromes 1
• An abnormal WBC count (leukocytosis, leukopenia, or abnormal differential) should prompt investigation for secondary causes such as infection, malignancy, or systemic disease 1

Supporting Laboratory Evidence Beyond CBC

While not strictly CBC findings, these tests are essential when TMA is suspected based on CBC abnormalities:

Markers of Hemolysis

• Elevated lactate dehydrogenase (LDH) 1, 2
• Reduced or absent haptoglobin levels 1, 2
• Elevated indirect bilirubin 1
• These tests should be ordered immediately when anemia plus thrombocytopenia are detected 1

Reticulocyte Count

• Elevated reticulocyte count reflects the bone marrow's compensatory response to hemolysis 1
• Helps distinguish hemolytic anemia from production defects 1

Clinical Context and Pitfalls

Incomplete Presentation

• In approximately 50% of cases at onset, not all three clinical signs (hemolytic anemia, thrombocytopenia, renal involvement) are clearly present 1
• This incomplete presentation can delay diagnosis, making it critical to maintain high clinical suspicion when even two components are present 1

Distinguishing TMA Subtypes

• The severity of CBC abnormalities helps differentiate TMA etiologies: TTP and HUS show more severe thrombocytopenia and more numerous schistocytes compared to malignant hypertension-associated TMA 1
• Urgent ADAMTS13 activity testing is mandatory when TMA is suspected to identify TTP (activity <10%) 1, 2
• Testing for antiphospholipid antibodies and complement studies guides further management 1, 2

Red Flags for Alternative Diagnoses

• Anemia disproportionate to bleeding or thrombocytopenia severity suggests alternative causes 1
• Leukocyte abnormalities, excessive giant or small platelets, or inclusion bodies on smear indicate inherited thrombocytopenias or other disorders 1
• Moderate to massive splenomegaly, lymphadenopathy, or constitutional symptoms suggest lymphoproliferative disease, HIV, or systemic lupus erythematosus rather than primary TMA 1

Technical Considerations

• Exclude pseudothrombocytopenia due to EDTA-dependent platelet agglutination before pursuing TMA workup 1
• Peripheral smear review by a qualified hematologist or pathologist is paramount for accurate diagnosis 1