Haemostasis Problems: A Logical Approach

PATHCHAT Edition No. 17
Please contact your local Ampath pathologist for more information.

Introduction

🔹 Haemostasis is a delicate balance between procoagulant and anticoagulant mechanisms in the body.

• Disruptions in this balance lead to either bleeding disorders or thrombotic disorders.
• Both conditions can be life-threatening or debilitating.
• Early diagnosis and targeted treatment significantly improve patient outcomes.

🔹 Diagnostic Challenges:

• Bleeding disorders can be complex and difficult to diagnose.
• Thrombosis risk factors can be genetic or acquired.
• Proper laboratory testing and clinical evaluation are critical.

Full Bleeding Tendency Screen

🔹 Who Needs This Test?

• Patients with unexplained or excessive bleeding.
• Patients with easy bruising (without trauma).
• Those with prolonged bleeding from wounds.
• Patients with nosebleeds, heavy menstrual bleeding, GI bleeding.
• Spontaneous bleeds into joints or tissues.

🔹 Pre-Test Clinical Evaluation (British Guidelines Approach):
Before ordering tests, consider:

1. Is there truly a bleeding tendency?
2. Is there a family history of bleeding disorders?
3. Is it a platelet disorder? (e.g., nosebleeds, petechiae).
4. Is it a clotting factor disorder? (e.g., muscle/joint bleeding).
5. What medications is the patient taking?
6. Are there underlying medical conditions (renal, liver, or haematologic diseases)?

🔹 Recommended Laboratory Tests:
✅ Step 1: Basic Screening

• Full Blood Count (FBC) & Platelets – Assess blood cell counts & platelet morphology.
• Bleeding Time – Evaluates vascular & platelet function.
• PT/INR, aPTT & Thrombin Time (TT) – Evaluate coagulation factors.

✅ Step 2: If PT/aPTT is Abnormal

• Factor VIII Assay – Detects Haemophilia A.
• Von Willebrand Factor (vWF) Antigen & Activity – Detects Von Willebrand Disease (VWD).
• Platelet Aggregation Studies – Tests response to ADP, collagen, ristocetin.

✅ Step 3: If Bleeding Disorder is Still Unexplained

• Factor XIII Screening – Assesses fibrin clot stability.
• Plasmin Inhibitor & Tissue Plasminogen Activator (tPA) – Tests for fibrinolysis issues.
• Multimer Analysis (UFS lab) – Classifies Von Willebrand Disease subtypes.

📌 A final diagnosis is made based on test results & clinical history in consultation with a haematologist.

Full Thrombotic Screen

🔹 Who Needs This Test?

• Patients with deep vein thrombosis (DVT), pulmonary embolism (PE), or stroke.
• Young patients with unexplained thrombosis.
• Patients with recurrent thrombosis or thrombosis at unusual sites (e.g., mesenteric vein).
• Patients with thrombosis while on anticoagulants.

🔹 Recommended Laboratory Tests:
✅ Step 1: Basic Screening

• Full Blood Count (FBC) & Platelets – Assesses blood cell counts & platelet morphology.
• PT/INR, aPTT & Thrombin Time (TT) – Evaluates coagulation status.
• Fibrinogen Levels – Elevated levels are linked to thrombosis.

✅ Step 2: If Hypercoagulability is Suspected

• Antithrombin III, Protein C & Protein S Levels – Naturally occurring anticoagulants.
• Activated Protein C Resistance (APCR) / Factor V Leiden Mutation – Most common genetic cause of thrombosis.
• Prothrombin 20210A Mutation – Second-most common genetic risk factor for thrombosis.
• Lupus Anticoagulant / Antiphospholipid Antibodies – Autoimmune-associated clotting disorders.
• Homocysteine Levels – Assessed for thrombosis risk, though controversial.

✅ Step 3: Advanced Testing (For Persistent Unexplained Cases)

• tPA Pre- & Post-Stasis, Plasminogen Activator Inhibitor (PAI-1) – Rare fibrinolytic disorders.
• Factor VIII & vWF Levels – Elevated levels linked to arterial thrombosis.
• ADAMTS13 Levels – Low levels may indicate increased stroke risk.

📌 Important Considerations:

• Heparin therapy must be discontinued for at least 10 days before testing.
• Protein C & S are vitamin K-dependent and are reduced by warfarin therapy.
• Once anticoagulation therapy is started, hypercoagulability assays become unreliable.

Understanding Haemostasis: Common Pathway Disruptions

🔹 Types of Haemostasis Disorders:

✅ 1. Bleeding Disorders (Prolonged Bleeding)

• Intrinsic Pathway Defect → Prolonged aPTT
  • Factor VIII, IX, XI, XII deficiencies (e.g., Haemophilia A & B).
• Extrinsic Pathway Defect → Prolonged PT
  • Factor VII deficiency.
• Common Pathway Defect → Prolonged PT & aPTT
  • Factor I (Fibrinogen), II (Prothrombin), V, X, XIII deficiencies.

✅ 2. Thrombosis Disorders (Excessive Clotting)

• Inherited Risk Factors:
  • Factor V Leiden Mutation – Most common genetic cause.
  • Prothrombin 20210A Mutation – Increases clotting risk.
  • Antithrombin III, Protein C, or Protein S Deficiency – Impaired anticoagulation.
• Acquired Risk Factors:
  • Lupus Anticoagulant / Antiphospholipid Syndrome – Autoimmune-related clotting.
  • High Factor VIII or vWF Levels – Linked to stroke & arterial thrombosis.

Key Takeaways for Clinicians

✅ A structured approach is essential for diagnosing bleeding or thrombotic disorders.
✅ Laboratory testing should be guided by clinical history and symptom presentation.
✅ A comprehensive screening is recommended for patients with unexplained clotting or bleeding.
✅ Anticoagulant therapy affects test results – timing of testing is critical.
✅ Consult a haematologist for accurate diagnosis and test selection.

References

1. Hoffbrand A.V., Petit J.E. (2012). Essential Haematology (6th Edition). Wiley Blackwell.
2. Hoffbrand A.V. et al. (2005). Postgraduate Haematology (6th Edition). Wiley Blackwell.
3. Ratnoff O.C. et al. (1996). Disorders of Haemostasis (3rd Edition). WB Saunders.
4. Sonneveld M.A.H. et al. (2014). Von Willebrand Factor and ADAMTS13 in Arterial Thrombosis: A Systematic Review and Meta-Analysis. Blood Reviews, 28:167–178.