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

Initial Workup for Suspected Bleeding Disorders

The initial workup for a patient with suspected bleeding disorder should include a thorough clinical evaluation with bleeding assessment tool (BAT), complete blood count with platelet count, prothrombin time (PT), activated partial thromboplastin time (aPTT), and von Willebrand factor (VWF) screening tests. 1, 2

Clinical Evaluation

• Personal and Family Bleeding History:

  • Unexplained or extensive bruising
  • Epistaxis (nosebleeds)
  • Menorrhagia (heavy menstrual bleeding)
  • Bleeding during childbirth
  • Excessive bleeding following invasive procedures or dental extractions
  • Family history of bleeding disorders

• Bleeding Assessment Tool (BAT):

  • Use of a standardized BAT is strongly recommended (preferably ISTH-BAT) 1
  • BAT scores help identify patients needing further investigation
  • Abnormal BAT scores should influence both first-line and second-line testing 1

• Physical Examination:

  • Assess for bleeding manifestations
  • Look for syndromic features (hearing loss, heart/face/bone abnormalities, skin discoloration)
  • Evaluate for hypermobility (present in 55% of evaluations) 1

• Medication History:

  • Document use of medications that affect platelet function (NSAIDs, antiplatelet drugs)
  • Record over-the-counter medication use (88% of clinicians do this) 1

First-Line Laboratory Tests

1. Complete Blood Count (CBC) with platelet count

   • Evaluates for thrombocytopenia and other cell line abnormalities
   • Examine blood smear for platelet size/morphology abnormalities

2. Coagulation Screening Tests:

   • Prothrombin Time (PT) - evaluates extrinsic pathway
   • Activated Partial Thromboplastin Time (aPTT) - evaluates intrinsic pathway
   • These are performed by 100% of clinicians as first-line tests 1

3. Von Willebrand Disease (VWD) Screening:

   • VWF antigen (VWF:Ag)
   • VWF ristocetin cofactor activity (VWF:RCo)
   • Factor VIII coagulant activity (FVIII:C)
   • Performed by 84% of clinicians as first-line tests 1, 2

4. Additional First-Line Tests:

   • Fibrinogen level (Clauss method) - performed by 90% of clinicians 1
   • ABO blood group (affects VWF levels) - performed by 70% of clinicians 1, 2
   • Iron studies - performed by 69% of clinicians 1

Interpretation of First-Line Tests

• Prolonged PT: Suggests deficiency in factors VII, X, V, II, or fibrinogen 2
• Prolonged aPTT: Suggests deficiency in factors XII, XI, IX, VIII, or common pathway factors 2
• Abnormal VWF tests: May indicate von Willebrand disease 2

VWD Type	VWF:RCo	VWF:Ag	FVIII	VWF:RCo/VWF:Ag Ratio
Type 1	<30	<30	↓/Normal	>0.5-0.7
Type 2	<30	<30-200	↓/Normal	<0.5-0.7 (usually)
Type 3	<3	<3	↓↓↓	-

Second-Line Tests (if First-Line Tests Normal)

If first-line tests are normal but clinical suspicion remains high:

1. Platelet Function Testing:

   • Light transmission aggregometry (LTA) with multiple agonists (epinephrine, ADP, collagen, arachidonic acid, ristocetin)
   • Performed by 60% of clinicians as second-line test 1
   • Assess for platelet granule release (ATP/ADP secretion, α-granule markers) 1

2. Additional Coagulation Factor Assays:

   • Factors II, V, VII, X, XI, XIII
   • Performed by 52-60% of clinicians as second-line tests 1

3. Specialized Tests:

   • Platelet flow cytometry (for surface glycoproteins) - 42% of clinicians 1
   • Genetic testing - 48% of clinicians 1
   • Fibrinolysis assays - 38% of clinicians 1
   • Thrombin generation assay - 28% of clinicians 1

Common Pitfalls and Considerations

• Normal PT/aPTT does not rule out a bleeding disorder as these tests only monitor the initiation phase of coagulation (first 4% of thrombin production) 2
• VWF levels are influenced by:
  • ABO blood type (type O has lower levels than type AB)
  • Stress, exercise, inflammation, pregnancy, estrogen use 2
• Up to 60-70% of patients with mild-moderate bleeding symptoms may have a bleeding disorder of unknown cause (BDUC) even after initial testing 2, 3
• Consider hematology consultation when:
  • Initial testing is abnormal
  • High clinical suspicion despite normal testing
  • Abnormal bleeding assessment tool score 2

By following this systematic approach to the initial workup of suspected bleeding disorders, clinicians can efficiently identify the most common bleeding disorders and determine which patients require further specialized testing.