What is the initial workup for a patient presenting with a suspected bleeding disorder?

Initial Workup for Suspected Bleeding Disorders

The initial laboratory evaluation for patients with suspected bleeding disorders should include a complete blood count (CBC) with platelet count, prothrombin time (PT), activated partial thromboplastin time (aPTT), von Willebrand factor antigen (VWF:Ag), von Willebrand factor ristocetin cofactor activity (VWF:RCo), and factor VIII coagulant activity (FVIII). 1

Step 1: Clinical Assessment

Before laboratory testing, perform a thorough clinical evaluation:

• Use a standardized bleeding assessment tool (BAT) to quantify bleeding severity
• Document specific bleeding manifestations:
  • Unexplained or extensive bruising
  • Epistaxis
  • Menorrhagia
  • Bleeding during childbirth
  • Excessive bleeding following invasive procedures or dental extractions
• Assess medication history (drugs affecting platelet function)
• Review family history of bleeding disorders
• Evaluate for syndromic features (hearing loss, heart/face/bone abnormalities, skin discoloration)

Step 2: First-Line Laboratory Tests

Order these initial tests for all patients with suspected bleeding disorders:

1. Complete blood count (CBC) with platelet count
2. Prothrombin time (PT)
3. Activated partial thromboplastin time (aPTT)
4. Von Willebrand factor screening:
   • VWF antigen (VWF:Ag)
   • VWF ristocetin cofactor activity (VWF:RCo)
   • Factor VIII coagulant activity (FVIII)
5. Blood smear examination

Important caveat: Normal PT and aPTT do not exclude bleeding disorders such as von Willebrand disease, which often presents with normal coagulation screening tests 1. This highlights the importance of including specific VWF testing in the initial evaluation.

Step 3: Interpretation and Further Testing

Based on initial results:

If abnormal platelet count or morphology:

• Evaluate for thrombocytopenia causes
• Consider inherited platelet function disorders (IPFD) even with mildly reduced platelet count 2
• Examine blood smear for platelet size/structure abnormalities

If abnormal PT/aPTT:

• Evaluate for coagulation factor deficiencies
• Consider mixing studies to differentiate factor deficiency from inhibitor

If abnormal VWF tests:

• Abnormal VWF:Ag, VWF:RCo, or FVIII suggests von Willebrand disease
• Calculate VWF:RCo/VWF:Ag ratio (ratio <0.5-0.7 suggests Type 2 VWD)
• Consider VWF multimer analysis for further classification 1

If normal initial tests but high clinical suspicion:

• Proceed to platelet function testing:
  • Light transmission aggregometry (LTA) with multiple agonists (epinephrine, ADP, collagen, arachidonic acid, ristocetin) 2
  • Platelet granule release assessment (ATP/ADP secretion, α-granule markers) 2
  • Flow cytometry for platelet surface glycoproteins 2

Step 4: Specialized Testing When Indicated

If initial results are inconclusive or normal despite strong clinical suspicion:

• Expanded flow cytometry
• Thrombin generation assay
• Clot retraction test
• Transmission electron microscopy for platelet granule assessment 1
• Genetic testing in selected cases

Important Considerations

1. Pre-analytical factors affecting results:

   • Discontinue medications affecting platelet function 7-10 days before testing
   • Patient factors (stress, exercise, inflammation, pregnancy, estrogen) can elevate VWF/FVIII levels
   • ABO blood type influences VWF levels

2. Diagnostic challenges:

   • Up to 60-70% of patients with mild-moderate bleeding may have a bleeding disorder of unknown cause (BDUC) despite normal initial testing 3
   • Single testing is not recommended; repeat if results are borderline

3. When to consult hematology:

   • Abnormal initial testing
   • Normal testing but high clinical suspicion based on bleeding history
   • Need for specialized testing or interpretation

4. Tests to avoid for initial screening:

   • Bleeding time and PFA-100 lack sensitivity and specificity for routine screening 1

By following this systematic approach, clinicians can effectively evaluate patients with suspected bleeding disorders while avoiding common diagnostic pitfalls.