What is the diagnosis for an adult patient with anemia (low hemoglobin) and thrombocytopenia (low platelet count) and no prior medical history?

Diagnostic Approach to Low Hemoglobin and Low Platelets

The combination of anemia and thrombocytopenia requires immediate evaluation for thrombotic microangiopathy (TMA), including atypical hemolytic uremic syndrome (aHUS) and thrombotic thrombocytopenic purpura (TTP), as these are life-threatening emergencies requiring urgent intervention. 1

Immediate Emergency Department Workup

Any patient presenting with anemia plus thrombocytopenia must have haptoglobin, indirect bilirubin, and LDH levels measured immediately to assess for microangiopathic hemolytic anemia. 1

First-Line Laboratory Tests

• Peripheral blood smear examination to confirm true thrombocytopenia (excluding pseudothrombocytopenia from platelet clumping), assess for schistocytes (>1% suggests TMA), and evaluate red cell morphology. 1, 2, 3
• Complete blood count with differential to document severity of cytopenias and assess white blood cell count—pancytopenia (low hemoglobin, platelets, AND white cells) suggests bone marrow failure like aplastic anemia rather than peripheral destruction. 2, 3, 4
• Direct Coombs test to distinguish immune from non-immune hemolytic anemia. 1
• ADAMTS13 activity level must be obtained urgently if TMA is suspected—severely deficient activity (<10 IU/dL) indicates TTP. 1

Critical Diagnostic Triad for TMA

The presence of all three features defines TMA and requires immediate specialist consultation: 1

• Non-immune hemolytic anemia (negative Coombs, elevated LDH, reduced haptoglobin, ± schistocytes)
• Thrombocytopenia (platelets <150,000/μL or 25% reduction)
• Organ involvement (typically renal: hematuria, proteinuria, elevated creatinine)

Important caveat: The absence of schistocytes should NOT exclude TMA diagnosis due to low test sensitivity—if clinical suspicion is high, proceed with TMA workup regardless. 1

Differential Diagnosis Algorithm

If Isolated Bicytopenia (Normal WBC Count)

Primary considerations: 5, 6, 7

• TMA syndromes (aHUS, TTP, STEC-HUS)—most urgent
• Immune thrombocytopenia (ITP) with concurrent anemia from bleeding—however, ITP diagnosis requires normal hemoglobin and WBC, making it unlikely if significant anemia is present 1, 4
• Drug-induced thrombocytopenia with bleeding-related anemia—obtain detailed medication history including heparin, quinidine, sulfonamides, GPIIb-IIIa inhibitors, chemotherapy 2, 5
• Antiphospholipid syndrome—can cause both thrombosis and thrombocytopenia 7
• Iron deficiency-associated thrombocytopenia (IDAT)—uncommon but important, as platelet count typically 21-80 × 10⁹/L, often misdiagnosed as ITP, and responds rapidly to iron therapy within 4-39 days 8

If Pancytopenia (Low Hemoglobin, Platelets, AND WBC)

Primary considerations: 4, 5

• Aplastic anemia—requires bone marrow biopsy showing hypocellular marrow with fatty replacement 4
• Bone marrow infiltration (leukemia, lymphoma, metastatic disease)—though acute leukemia typically presents with elevated WBC, not leukopenia 4
• HIV infection—perform testing if risk factors present, as HIV commonly causes pancytopenia 2, 4
• Medication-induced bone marrow suppression 4, 5

Risk Stratification by Platelet Count

Severe Thrombocytopenia (<20 × 10⁹/L)

• Hospital admission required for newly diagnosed patients—high risk of serious bleeding including spontaneous intracranial hemorrhage. 1, 3, 5
• Platelet transfusion recommended when counts <10 × 10⁹/L or with active hemorrhage. 5

Moderate Thrombocytopenia (20-50 × 10⁹/L)

• May have mild skin manifestations (petechiae, purpura, ecchymosis). 5
• Outpatient management acceptable if established diagnosis with no significant bleeding, but requires expedited hematology follow-up within 24-72 hours. 3

Mild Thrombocytopenia (>50 × 10⁹/L)

• Generally asymptomatic with spontaneous serious bleeding rare (<5%). 3, 5
• Safe for most procedures: central venous catheter placement at >20 × 10⁹/L, lumbar puncture at >50 × 10⁹/L. 1, 3

Additional Targeted Testing Based on Clinical Context

• Stool testing for verocytotoxin-producing E. coli (VTEC) if diarrhea present—STEC-HUS typically appears 4-5 days after diarrhea onset. 1
• HIV testing in patients with risk factors, as HIV is commonly associated with thrombocytopenia. 2, 3, 4
• Liver and renal function tests to exclude secondary causes and assess organ involvement. 4
• Coagulation studies (PT/aPTT) to evaluate for disseminated intravascular coagulation. 3
• Bone marrow aspiration and biopsy if persistent thrombocytopenia >6-12 months, unresponsive to therapy, or atypical features suggesting alternative diagnosis. 2, 3, 4

Common Pitfalls to Avoid

• Failing to confirm true thrombocytopenia through peripheral smear—pseudothrombocytopenia from EDTA-induced platelet clumping occurs in 0.1% of adults. 3
• Delaying ADAMTS13 testing when TMA is suspected—this must be sent urgently as TTP requires immediate plasma exchange. 1
• Premature platelet transfusion in TTP—avoid until TTP is excluded, as transfusion may worsen thrombosis. 6
• Missing medication-induced causes, especially heparin-induced thrombocytopenia which causes both thrombocytopenia AND thrombosis. 2, 3, 5
• Overlooking iron deficiency as a cause of thrombocytopenia—IDAT presents with lower platelet counts (median 30.5 × 10⁹/L) but higher mean platelet volume (MPV 8.2 fL) compared to ITP, and recovers rapidly with iron therapy. 8