Laboratory Tests for Blood Clotting Disorders
Initial screening for blood clotting disorders should include complete blood count (CBC), prothrombin time (PT), activated partial thromboplastin time (aPTT), and von Willebrand factor (VWF) screening tests. 1
Initial Screening Tests
First-line Laboratory Tests
- Complete Blood Count (CBC) - Evaluates platelet count and morphology
- Prothrombin Time (PT) - Assesses extrinsic and common pathway
- Activated Partial Thromboplastin Time (aPTT) - Evaluates intrinsic and common pathway
- Thrombin Time (TT) - Measures fibrinogen to fibrin conversion
These initial tests are considered grade C recommendations according to the NHLBI guidelines and can suggest whether coagulation factor deficiency or thrombocytopenia might be potential causes of clinical bleeding 1.
Von Willebrand Disease Screening
If mucocutaneous bleeding history is strong, initial VWF assays should include:
- VWF antigen (VWF:Ag)
- VWF ristocetin cofactor activity (VWF:RCo)
- Factor VIII coagulant activity (FVIII)
These three tests are grade B recommendations and should be performed together as they not only establish the diagnosis but also suggest the type and severity of VWD if present 1.
Second-line Testing
If initial screening tests are normal but clinical suspicion remains high for a bleeding disorder:
Platelet Function Testing
Light Transmission Aggregometry (LTA) with agonists:
- Epinephrine
- ADP
- Collagen
- Arachidonic acid
- Ristocetin 1
Platelet Granule Release Assessment:
- ATP/ADP release (lumiaggregometry)
- α-granule markers 1
Flow Cytometry for platelet surface glycoproteins:
- GPIIb/IIIa (CD41)
- GPIIIa (CD61)
- GPIb (CD42b)
- GPIb/IX (CD42a) 1
Additional Coagulation Factor Assays
If initial tests suggest factor deficiency, specific factor assays may be ordered:
- Factor II, V, VII, X (extrinsic pathway)
- Factor VIII, IX, XI (intrinsic pathway)
- Factor XIII
- Fibrinogen (Clauss method) 1
Third-line Testing
For cases that remain undiagnosed but with strong clinical suspicion:
- VWF Multimer Analysis - Only if initial VWF testing identifies abnormal results 1
- Expanded Flow Cytometry - Additional glycoproteins (GPIa/IIa, GPIV, GPVI) 1
- Thrombin Generation Assay
- Clot Retraction Test
- Transmission Electron Microscopy - For platelet granule assessment 1
- Genetic Testing - For suspected hereditary disorders 1
Important Considerations
Test Limitations
- The PFA-100 and skin bleeding time tests are not recommended due to insufficient specificity/sensitivity 1.
- An isolated prolonged PT is extremely rarely clinically significant 2.
- Approximately one-third of isolated prolonged aPTT cases are clinically insignificant 2.
Pre-analytical Variables
- Medications affecting platelet function should be discontinued 7-10 days before testing
- Repeated platelet studies should be separated by at least 1 month 1
- Proper sample collection and handling is critical for accurate results
Common Pitfalls
- Over-reliance on screening tests: Normal screening tests do not rule out all bleeding disorders
- Misinterpretation of isolated abnormalities: Not all prolonged clotting times indicate clinically significant bleeding risk
- Failure to correlate with clinical history: Laboratory results must be interpreted in the context of the patient's bleeding history
- Inappropriate timing of tests: Testing during acute bleeding episodes or while on anticoagulants can affect results
Remember that the diagnostic approach should be guided by the patient's clinical presentation and bleeding history, with laboratory testing selected accordingly to maximize diagnostic yield and minimize unnecessary testing.