What laboratory tests and treatments are recommended for patients suspected of having a blood clotting disorder?

Laboratory Tests and Treatments for Blood Clotting Disorders

For patients suspected of having a blood clotting disorder, first-line laboratory testing should include activated partial thromboplastin time (aPTT), prothrombin time (PT), complete blood count with platelet count, and von Willebrand factor (VWF) assays, followed by appropriate second-line testing and treatment based on initial results. 1

Initial Diagnostic Approach

First-Line Laboratory Tests

• Complete blood count (CBC) with platelet count - Essential for identifying thrombocytopenia or other blood cell abnormalities 2, 1
• Coagulation screening:
  • Activated partial thromboplastin time (aPTT) - Evaluates intrinsic and common pathways 2, 1
  • Prothrombin time (PT) - Evaluates extrinsic and common pathways 2, 1
  • Fibrinogen levels (Clauss and/or derived) - Performed by 90% of specialists in first-line testing 2
• Von Willebrand factor (VWF) assays - Performed by 84% of specialists 2, 1
• Factor VIII, IX, and XI assays - Performed by 62% of specialists 2
• Additional recommended tests:
  • ABO blood group - Performed by 70% of specialists (affects VWF levels) 2, 1
  • Iron studies - Performed by 69% of specialists 2
  • Thyroid function testing - Performed by 45% of specialists 2

Clinical Assessment

• Use a standardized Bleeding Assessment Tool (BAT) - 80% of specialists use these, with ISTH BAT being most common (73%) 2, 1
• Collect thorough family history of bleeding 1
• Document medication use, especially over-the-counter drugs and NSAIDs 1
• Assess for hypermobility, which can be associated with bleeding disorders 2, 1

Second-Line Testing

If first-line tests are normal but bleeding symptoms persist, proceed with:

• Platelet function testing (light transmission aggregometry) - Performed by 60% of specialists 2
• Additional factor assays:
  • Factor II (52%), Factor V (55%), Factor VII (54%), Factor X (53%), Factor XIII (60%) 2
• Specialized testing:
  • Platelet flow cytometry (42%) 2
  • Genetic testing (48%) 2
  • Fibrinolysis assays (38%) 2
  • Thrombin generation assay (28%) 2
  • Thromboelastography/rotational thromboelastometry 2

Interpretation of Test Results

Abnormal PT

• Indicates potential deficiency in vitamin K-dependent factors (II, VII, IX, X) or factor V 3
• May indicate liver disease, vitamin K deficiency, or anticoagulant use

Abnormal aPTT

• Isolated prolongation suggests deficiency in factors VIII, IX, or XI 4
• Slightly prolonged aPTT with moderate decrease in factor VIII may indicate von Willebrand disease or hemophilia A carrier state 4

Abnormal Platelet Count

• Low platelet count alone suggests peripheral destruction, immunothrombocytopenia, or bone marrow production abnormality 3
• Monitor thrombocytopenia closely; discontinue certain medications if platelet count falls below 100,000/mm³ 5

Von Willebrand Disease Testing

• Core VWF panel should include VWF antigen (VWF:Ag), VWF ristocetin cofactor activity (VWF:RCo), factor VIII coagulant activity (FVIII:C), and VWF:RCo/VWF:Ag ratio 1
• A VWF:RCo/VWF:Ag ratio <0.5-0.7 suggests qualitative VWF defects 1

Treatment Approaches

For Von Willebrand Disease

• First-line therapy: Desmopressin (DDAVP) 0.3 μg/kg IV for mild to moderate Type 1 VWD 1
• For Type 2B, Type 3, and severe forms: VWF-containing factor concentrates 1
• Minimum target levels: VWF activity ≥50 IU/dL for adequate hemostasis; ≥80 IU/dL for history of severe bleeding 1
• Avoid DDAVP in Type 2B VWD as it may worsen thrombocytopenia 1

For Surgical Management

• For minor surgery: Tranexamic acid (TXA) is preferred (used by 79% of specialists) 2
• For major surgery: TXA (91% overall, 59% alone, 32% combined with DDAVP) 2
• Target levels for major procedures: VWF:RCo ≥80-100 IU/dL 1

For Bleeding Disorders of Unknown Cause (BDUC)

• 75% of specialists formally register patients with convincing bleeding history even without detectable laboratory abnormalities 2
• Various diagnostic labels are used, with "Unclassified bleeding disorder" (31%) and "BDUC" (28%) being most common 2

Special Considerations

Monitoring During Treatment

• Routine monitoring should include:
  • Complete blood counts (including platelet count)
  • Serum creatinine levels
  • Stool occult blood tests 5
• Standard coagulation tests (PT, aPTT) are relatively insensitive for monitoring certain anticoagulants like fondaparinux 5
• Anti-Factor Xa assay with appropriate calibrator can be used for monitoring specific anticoagulants 5

Thrombophilia Testing

• Consider testing for factor V Leiden, prothrombin gene mutation, hyperhomocysteinemia, and antiphospholipid antibodies in patients with:
  • Idiopathic venous thromboembolism at young age
  • Recurrent thrombosis
  • Thromboses at unusual sites
  • Family history of thrombotic disorders 6

Vaccine-Induced Immune Thrombocytopenia and Thrombosis (VITT)

• For suspected VITT, perform D-dimer measurement, coagulation screen including Clauss fibrinogen assay, and blood film 2
• If thrombocytopenia is present or clinical suspicion is high, refer to secondary care immediately 2
• Treatment includes intravenous immunoglobulin and non-heparin based anticoagulants 2

Common Pitfalls and Caveats

• Routine coagulation tests may be insensitive for certain anticoagulants; use specific assays when appropriate 5
• Anticoagulant effects may persist for 2-4 days after discontinuation in patients with normal renal function, and longer in renal impairment 5
• Patients weighing less than 50kg have increased bleeding risk with certain anticoagulants 5
• VWF levels are influenced by blood type (type AB have 60-70% higher levels than type O) and can be elevated during pregnancy, stress, and hyperthyroidism 4
• Repeated testing may be necessary, as some patients with VITT have normal platelet counts initially but develop thrombocytopenia within 2-3 days 2