Haemostasis: Balancing Bleeding and Clotting in the Human Body 🩸

 Haemostasis is the body's finely tuned process of maintaining blood flow while preventing excessive bleeding or clot formation. It operates through a delicate equilibrium of pro-coagulant and anti-coagulant proteins, ensuring that blood remains fluid under normal conditions but can rapidly clot when injury occurs.

The Three Phases of Haemostasis

1️⃣ Vasoconstriction & Injury Response

• When a blood vessel is injured, local vasoconstriction occurs to minimize blood loss.
• Collagen and tissue factor are exposed, signaling platelets to respond.

2️⃣ Primary Haemostasis: Platelet Plug Formation

• Platelets adhere to exposed von Willebrand factor (vWF), initiating adhesion.
• Activated platelets release ADP and thromboxane A2, triggering further platelet aggregation.
• Platelets form a temporary plug through fibrinogen bridges, stabilizing the site of injury.
• This process kickstarts the coagulation cascade.

3️⃣ Secondary Haemostasis: Coagulation Cascade Activation

• The intrinsic and extrinsic pathways lead to the activation of Factor X, initiating the common pathway.
• Factor X converts prothrombin (Factor II) into thrombin (Factor IIa), a key enzyme in clot formation.
• Thrombin transforms fibrinogen (Factor I) into insoluble fibrin, reinforcing the clot.
• Factor XIII cross-links fibrin strands, stabilizing the clot further.

The Intrinsic vs. Extrinsic Pathways: How Does Clotting Begin?

🩸 Intrinsic Pathway: Triggered when Factor XII contacts negatively charged collagen on damaged endothelium. Platelets release Factor VIII, which combines with Factor IX, ultimately activating Factor X.

🩸 Extrinsic Pathway: Initiated when Factor VII exits circulation following injury. Tissue factor (Factor III) binds Factor VII, activating Factor X.

🔬 Key Test Indicators:

• Prothrombin Time (PT) measures the extrinsic pathway.
• Activated Partial Thromboplastin Time (aPTT) assesses intrinsic pathway function.
• D-dimer levels indicate ongoing fibrinolysis, helping assess clot breakdown activity

Fibrinolysis: Clearing Clots Once Healing Begins

Once tissue repair is complete, plasminogen is converted into plasmin, degrading the fibrin clot into soluble fragments.

💊 Tranexamic acid inhibits plasmin formation, reducing excessive bleeding in clinical settings.

D-dimers are protein fragments produced after fibrinolysis – can be used to screen for increased fibrinolytic activity

Clotting Regulators: Preventing Unchecked Thrombosis

Several proteins help regulate haemostasis, preventing excessive clot formation:

✅ Antithrombin – Inhibits thrombin and several clotting factors.

✅ Protein C & Protein S – Work together to degrade Factors Va and VIIIa, slowing clotting.

✅ Tissue Factor Pathway Inhibitor – Inhibits the TF-VIIa complex to prevent excessive Factor X activation.

💡 Clinical Correlations: When Haemostasis Fails

🔴 Bleeding Disorders:

• Von Willebrand Disease (VWD): Deficiency or dysfunction of vWF leads to prolonged bleeding, commonly affecting mucosal surfaces.
• Haemophilia A & B: Factor VIII or IX deficiencies impair the intrinsic pathway, causing deep tissue and joint bleeding.

🩸 Clotting Disorders:

• Factor V Leiden Mutation: A genetic predisposition to thrombosis due to resistance to Protein C regulation.
• Antiphospholipid Syndrome: Autoimmune condition increasing thrombotic risk through abnormal antibody-mediated clot formation.

Assessing Bleeding & Clotting Disorders: Key Questions & Investigations

When evaluating a patient for a bleeding or clotting disorder, a structured approach is crucial. The history provides essential diagnostic clues, while laboratory investigations confirm the underlying pathology.

Key Questions for Bleeding Disorders

1️⃣ Is there evidence of a bleeding problem?

• History of easy bruising, epistaxis, gum bleeding, or prolonged menstrual bleeding?
• Excessive bleeding after surgery, trauma, or dental procedures?

2️⃣ What is the location of bleeding?

• Mucosal bleeding (nose, gums, GI tract)? → Suggests platelet dysfunction or von Willebrand disease.
• Joint or deep tissue bleeding? → Often seen in haemophilia or coagulation factor deficiencies.

3️⃣ What is the timing of bleeding relative to a haemostatic challenge?

• Immediate bleeding post-injury → More likely platelet-related.
• Delayed bleeding (hours to days) → Suggests coagulation factor deficiency (e.g., haemophilia).

4️⃣ Medication history?

• Use of aspirin, NSAIDs, anticoagulants (warfarin, DOACs), or herbal supplements that affect haemostasis?

5️⃣ Family history of bleeding disorders?

• Consider haemophilia, von Willebrand disease, or rare inherited platelet disorders.

Key Investigations for Bleeding Disorders

🔬 Basic Tests:

✅ Full Blood Count (FBC) → Assess platelets and haemoglobin.

✅ Peripheral Blood Film → Look for platelet abnormalities or microcytic anaemia (suggestive of chronic blood loss).

✅ Standard Coagulation Screen:

• Activated Partial Thromboplastin Time (aPTT) → Tests intrinsic pathway (Factors VIII, IX, XI, XII).
• Prothrombin Time (PT) → Tests extrinsic pathway (Factors VII, X, V, II, I).
• Thrombin Time (TT) → Assesses fibrinogen function.
• International Normalized Ratio (INR) → Evaluates warfarin therapy or liver dysfunction.

✅ Fibrinogen levels → Identifies fibrinogen deficiency or consumption (e.g., DIC).

🔬 Specialty Tests:

✅ Von Willebrand Factor Antigen & Activity Assays → Diagnose VWD.

✅ Platelet Function Assays (PFA-100) → Evaluate platelet dysfunction.

✅ Mixing Studies → Differentiate factor deficiencies from inhibitors (e.g., lupus anticoagulant).

✅ Thrombophilia Workup (if suspect hypercoagulability) → Includes Factor V Leiden, Protein C/S, Antithrombin, Lupus Anticoagulant.

Key Questions for Clotting Disorders

1️⃣ Is there evidence of a clotting problem?

• History of deep vein thrombosis (DVT), pulmonary embolism (PE), or recurrent pregnancy loss?
• Unexplained stroke, myocardial infarction, or organ ischemia at a young age?

2️⃣ What are the risk factors?

• Immobility, malignancy, smoking, or estrogen exposure (OCP, pregnancy)?
• Recent surgery, trauma, or prolonged hospitalization?

3️⃣ Family history of clotting disorders?

• Any relatives with DVT, PE, Factor V Leiden mutation, or other thrombophilia?

4️⃣ Medication history?

• Use of hormonal contraceptives, chemotherapy, or pro-thromb🩸🩸🩸🩸tic medications?

Key Investigations for Clotting Disorders

🔬 Basic Tests:

✅ FBC (platelet count) → Elevated platelets may indicate essential thrombocythemia, while low platelets may suggest DIC.

✅ D-dimer → Elevated in active clot formation (DVT/PE screening, DIC assessment).

✅ Standard Coagulation Screen (PT, aPTT, TT, INR) → Helps assess clotting pathway abnormalities.

🔬 Thrombophilia Screen (if clinically indicated):

✅ Factor V Leiden mutation → Most common inherited thrombophilia.

✅ Prothrombin Gene Mutation 20210A → Increases thrombotic risk.

✅ Protein C, Protein S, and Antithrombin III levels → Deficiencies lead to increased clotting tendency.

✅ Lupus Anticoagulant & Anticardiolipin Antibodies → Diagnose antiphospholipid syndrome.

✅ Anti-beta 2 Glycoprotein I Antibodies → Supports APS diagnosis.