What is the workup for chronic thrombocytopenia?

Workup for Chronic Thrombocytopenia

The workup for chronic thrombocytopenia begins with history, physical examination, complete blood count, and peripheral blood smear evaluation by a qualified hematologist or pathologist—this core evaluation is sufficient for most patients under 60 years without atypical features. 1

Essential Initial Evaluation

History Taking

• Medication review: Document all current and recent medications, particularly heparin, quinidine/quinine, sulfonamides, and alcohol use, as these commonly cause thrombocytopenia 1
• Bleeding history: Assess for mucocutaneous bleeding, prior surgeries, and pregnancies to gauge hemostatic function 1
• Infection risk factors: Identify HIV risk factors, recent viral illnesses, and immunization history 1
• Systemic symptoms: Screen for fever, weight loss, night sweats, arthralgias, or rash suggesting autoimmune disease or lymphoproliferative disorders 1
• Family history: Ask about inherited thrombocytopenias including Wiskott-Aldrich syndrome, MYH9-related disease, and Bernard-Soulier syndrome 1
• Transfusion history: Recent transfusions raise possibility of posttransfusion purpura 1

Physical Examination

• Bleeding manifestations only: Physical examination should be normal aside from petechiae, purpura, or ecchymosis 1
• Splenomegaly: Mild splenomegaly may occur in younger patients, but moderate or massive splenomegaly indicates alternative diagnosis such as lymphoproliferative disease or portal hypertension 1
• Lymphadenopathy or hepatomegaly: These findings suggest underlying HIV, systemic lupus erythematosus, or lymphoproliferative disease rather than primary immune thrombocytopenia 1

Laboratory Studies

Complete Blood Count

• Isolated thrombocytopenia: ITP is characterized by isolated thrombocytopenia with otherwise normal CBC 1
• Anemia assessment: If anemia is present, it should be proportional to bleeding duration; obtain reticulocyte count to distinguish production failure from hemolysis 1
• Leukocyte evaluation: Normal white blood cell count and morphology; abnormalities suggest alternative diagnosis 1

Peripheral Blood Smear (Mandatory)

• Platelet morphology: Platelets should be normal or slightly larger than normal; consistently giant platelets (approaching RBC size) suggest inherited thrombocytopenia 1
• Exclude pseudothrombocytopenia: EDTA-dependent platelet agglutination must be ruled out by examining smear or repeating count in citrate or heparin tube 1
• Red blood cell morphology: Schistocytes indicate thrombotic thrombocytopenic purpura-hemolytic uremic syndrome, not ITP 1
• Leukocyte inclusions: Döhle-like bodies suggest MYH9-related disease 1

Mandatory Serologic Testing in Adults

All adult patients with suspected chronic thrombocytopenia require HIV and hepatitis C virus testing regardless of risk factors or geographic location. 1

• HIV testing: Thrombocytopenia may precede other HIV symptoms by years; control of infection can result in complete hematologic remission 1
• Hepatitis C virus testing: HCV-associated thrombocytopenia is clinically indistinguishable from primary ITP 1
• Helicobacter pylori testing: Use urea breath test or stool antigen test (not serology) in adults where eradication may have clinical impact 1

Bone Marrow Examination: When Required

Bone marrow examination (both aspirate and biopsy) is indicated in patients older than 60 years, those with systemic symptoms or abnormal physical findings, or when splenectomy is considered. 1

Specific Indications

• Age >60 years: Mandatory to exclude myelodysplastic syndromes, leukemias, or other malignancies 1
• Systemic symptoms: Fever, weight loss, bone pain, or constitutional symptoms 1
• Abnormal blood counts: Any abnormality beyond isolated thrombocytopenia (anemia not proportional to bleeding, leukopenia, leukocytosis) 1
• Atypical smear findings: Schistocytes, leukocyte inclusion bodies, or dysplastic features 1
• Treatment failure: Persistent thrombocytopenia lasting >6-12 months or unresponsive to IVIg 1
• Pre-splenectomy evaluation: Consider in some cases before splenectomy 1

Bone Marrow Testing Components

• Morphologic assessment: Both aspirate and biopsy required 1
• Flow cytometry: Particularly helpful for identifying chronic lymphocytic leukemia-associated ITP 1
• Cytogenetic testing: Should be considered to exclude clonal disorders 1

Additional Testing Based on Clinical Context

Tests of Potential Utility

• Quantitative immunoglobulin levels: Consider in children with ITP, especially those with persistent or chronic disease, to exclude common variable immunodeficiency 1
• Direct antiglobulin test: May be useful in selected cases 1
• Blood group Rh(D) typing: Important if anti-D immunoglobulin therapy is being considered 1
• Pregnancy test: In women of childbearing potential 1

Tests NOT Routinely Recommended

• Antiplatelet antibody assays: Platelet-associated IgG is elevated in both immune and non-immune thrombocytopenia; glycoprotein-specific antibody testing not routinely recommended 1
• Antiphospholipid antibodies: Only test if symptoms of antiphospholipid syndrome present; found in 40% of typical ITP patients but does not affect treatment response 1
• Antinuclear antibodies: May predict chronicity in childhood ITP but not routinely indicated 1
• Platelet survival studies: Not useful 1
• Bleeding time: Not useful 1
• Serum complement levels: Not useful 1

Algorithmic Approach to Chronic Thrombocytopenia Workup

Step 1: Confirm True Thrombocytopenia

• Repeat CBC in citrate or heparin tube to exclude pseudothrombocytopenia 1
• Review peripheral blood smear by qualified hematologist or pathologist 1

Step 2: Determine if Isolated Thrombocytopenia

• If isolated: Proceed with ITP workup 1
• If not isolated: Consider bone marrow examination and broader differential diagnosis 1

Step 3: Age-Based Stratification

• Age <60 years with typical features: History, physical, CBC, smear, HIV, HCV, H. pylori testing sufficient; bone marrow NOT required 1
• Age ≥60 years: Bone marrow examination mandatory regardless of other features 1

Step 4: Assess for Atypical Features

• If any atypical features present (splenomegaly, lymphadenopathy, systemic symptoms, abnormal smear): Proceed to bone marrow examination 1
• If all typical: Bone marrow examination not required in patients <60 years 1

Critical Pitfalls to Avoid

• Missing pseudothrombocytopenia: Always examine peripheral smear and consider repeating count in different anticoagulant 1
• Failing to test for HIV/HCV: These infections can present identically to primary ITP and require different management 1
• Overlooking drug-induced thrombocytopenia: Quinidine, heparin, sulfonamides, and alcohol are common culprits 1
• Assuming ITP in patients >60 years without bone marrow: Myelodysplastic syndrome with isolated thrombocytopenia is a critical missed diagnosis with different prognosis and treatment 1, 2
• Ignoring constitutional symptoms: Fever, weight loss, or lymphadenopathy mandate investigation for lymphoproliferative or autoimmune disease 1
• Not considering inherited thrombocytopenias: Family history and platelet size on smear provide critical clues 1
• Performing unnecessary tests: Antiplatelet antibodies, platelet survival studies, and bleeding times do not change management 1