Peripheral Smear Evaluation for Thrombocytopenia
The peripheral blood smear must be examined by a qualified hematologist or pathologist to identify platelet clumping (pseudothrombocytopenia), assess platelet size and morphology, and detect abnormal cells that indicate specific causes of thrombocytopenia. 1
First Priority: Exclude Pseudothrombocytopenia
- Look for platelet clumping or aggregates, which indicates EDTA-dependent pseudothrombocytopenia—the most common laboratory artifact that can lead to unnecessary workup and treatment. 1, 2
- If clumping is present, immediately redraw blood in sodium citrate or heparin tubes to obtain an accurate platelet count. 3, 2
- This step prevents potentially serious consequences from treating a laboratory artifact as true thrombocytopenia. 2
Platelet Morphology Assessment
Platelet Size
- Large platelets (megathrombocytes) suggest increased platelet turnover from peripheral destruction, as seen in immune thrombocytopenia (ITP), or may indicate inherited thrombocytopenias like Bernard-Soulier syndrome or MYH9-related disease. 1
- Excessive numbers of giant or small platelets strongly suggest inherited thrombocytopenia rather than acquired causes. 1
- In typical ITP, expect to see "a few large platelets" with no other abnormalities. 1
Red Blood Cell Morphology
- Schistocytes (fragmented red cells) are a critical red flag indicating thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS), or other thrombotic microangiopathies requiring immediate intervention. 1, 4
- The presence of schistocytes mandates urgent evaluation including ADAMTS13 testing, LDH, haptoglobin, and direct antibody test. 4
- Spherocytes may indicate autoimmune hemolytic anemia with concurrent immune thrombocytopenia (Evans syndrome). 1
White Blood Cell Abnormalities
- Leukocyte inclusion bodies suggest MYH9-related disease, an inherited thrombocytopenia. 1
- Blasts or immature white cells indicate bone marrow pathology such as acute leukemia, myelodysplastic syndrome, or bone marrow infiltration. 1
- Atypical lymphocytes may suggest viral infection or lymphoproliferative disorders. 1
Integration with Complete Blood Count
- Isolated thrombocytopenia (normal hemoglobin and white blood cell count) narrows the differential to ITP, drug-induced thrombocytopenia, or early HIV/HCV infection. 1, 5
- Anemia disproportionate to bleeding suggests hemolysis, bone marrow failure, or nutritional deficiency requiring reticulocyte count assessment. 1, 4
- Pancytopenia (low platelets, hemoglobin, and white cells) indicates bone marrow failure, aplastic anemia, or bone marrow infiltration and mandates bone marrow examination. 1
Common Pitfalls to Avoid
- Failing to personally review the smear or relying solely on automated counts can miss pseudothrombocytopenia, leading to unnecessary invasive testing or treatment. 1, 3
- Missing schistocytes delays diagnosis of life-threatening thrombotic microangiopathies where plasma exchange must be initiated emergently. 4
- Overlooking subtle platelet size abnormalities can miss inherited thrombocytopenias, leading to inappropriate ITP treatment including unnecessary splenectomy. 1
- Not correlating smear findings with clinical context—for example, thrombocytopenia with thrombosis (not bleeding) suggests heparin-induced thrombocytopenia or antiphospholipid syndrome rather than ITP. 1, 4
Specific Smear Findings by Diagnosis
Immune Thrombocytopenia (ITP)
- Few large platelets with otherwise normal red and white cell morphology. 1
- No schistocytes, no blasts, no abnormal white cells. 1
Thrombotic Microangiopathies (TTP/HUS)
- Schistocytes are the hallmark finding requiring immediate recognition. 1, 4
- May see polychromasia indicating hemolysis. 1
Heparin-Induced Thrombocytopenia (HIT)
- Smear typically shows normal platelet morphology without specific diagnostic features. 1
- Diagnosis relies on clinical scoring (4T score) and antibody testing, not smear findings. 1