What initial lab tests are recommended for patients presenting with clotting abnormalities?

Initial Laboratory Tests for Clotting Abnormalities

The recommended initial laboratory tests for patients presenting with clotting abnormalities include complete blood count (CBC) with platelet count, prothrombin time (PT), activated partial thromboplastin time (aPTT), and von Willebrand factor (VWF) screening tests (VWF antigen, ristocetin cofactor activity, and factor VIII coagulant activity). 1

First-Line Testing

Core Tests (Performed by 100% of specialists)

• Complete blood count (CBC) with platelet count
• Prothrombin time (PT)
• Activated partial thromboplastin time (aPTT)

Additional First-Line Tests

• Fibrinogen levels (Clauss and/or derived) (performed by 90% of specialists) 1
• Von Willebrand factor (VWF) screening panel (performed by 84% of specialists) 1
  • VWF antigen (VWF:Ag)
  • Ristocetin cofactor activity (VWF:RCo)
  • Factor VIII coagulant activity (FVIII:C)
• Factor VIII, IX, and XI assays (performed by 62% of specialists) 1
• Blood smear examination (to assess platelet size/structure and other cell abnormalities) 1
• ABO blood group (performed by 70% of specialists) 1

Interpretation of First-Line Results

Abnormal PT

• Indicates potential deficiencies in the extrinsic pathway (factors VII, X, V, II, or fibrinogen)
• May suggest vitamin K deficiency, liver disease, or factor deficiencies 2

Abnormal aPTT

• Indicates potential deficiencies in the intrinsic pathway (factors VIII, IX, XI, XII)
• May suggest hemophilia, von Willebrand disease, or presence of inhibitors 2
• When isolated with a bleeding history, strongly suggests hemophiliac states 2

Abnormal Platelet Count

• Low count may indicate peripheral destruction, immunothrombocytopenia, or bone marrow issues 2
• Note: Mildly reduced platelet count should not exclude testing for inherited platelet function disorders 1

Abnormal VWF Tests

• VWF:RCo/VWF:Ag ratio <0.5-0.7 suggests qualitative VWF defects 3
• Low VWF with normal multimer pattern suggests Type 1 VWD
• Low VWF with abnormal multimer pattern suggests Type 2 VWD

Second-Line Testing (If First-Line Tests Are Normal or Inconclusive)

Platelet Function Testing

• Light transmission aggregometry (LTA) with multiple agonists (epinephrine, ADP, collagen, arachidonic acid, ristocetin) 1
• Platelet granule release assessment (ATP/ADP secretion, α-granule markers) 1
• Platelet flow cytometry to assess surface glycoproteins (GPIIb/IIIa, GPIb/IX) 1

Additional Coagulation Factor Assays

• Factors II, V, VII, X (performed by >50% of specialists) 1
• Factor XIII (performed by 60% of specialists) 1

Specialized Tests

• Thrombin time (TT) and reptilase time (RT) (to detect abnormal fibrin formation) 4
• Fibrinolysis assays (performed by 38% of specialists) 1
• Thrombin generation assay (performed by 28% of specialists) 1

Common Pitfalls and Caveats

1. Pre-analytical Variables: Ensure proper sample collection to avoid pseudothrombocytopenia or sample activation 3

2. Medication Effects: Review medication history for drugs affecting platelet function or causing drug-induced thrombocytopenia 3

3. Isolated Epinephrine Response: An isolated defective response to epinephrine in LTA is common and should only prompt further investigation when accompanied by other abnormalities or strong clinical suspicion 1

4. Physiological Variables: VWF levels can be influenced by blood type (type O has lower levels than type AB), pregnancy, stress, and thyroid function 5

5. Timing of Testing: Avoid testing during acute bleeding episodes or immediately after transfusion therapy

6. Test Selection Logic: The most appropriate laboratory tests should be ordered based on clinical assessment, pertinent history, and family history 5

By following this systematic approach to laboratory testing, clinicians can efficiently diagnose the underlying cause of clotting abnormalities and develop appropriate management strategies.