Blood clotting, or coagulation, is a complex physiological process that prevents excessive bleeding (hemostasis) when a blood vessel is injured.
It involves platelets, clotting factors, and the coagulation cascade to form a stable fibrin clot.
Phases of Blood Clotting
1) Vascular Spasm (Vasoconstriction):
Immediate narrowing of the blood vessel to reduce blood flow.
2) Platelet Plug Formation (Primary Hemostasis):
Platelet Adhesion: Platelets stick to exposed collagen in damaged blood vessels.
Platelet Activation: Platelets release chemicals (ADP, thromboxane A2) to attract more platelets.
Platelet Aggregation: Platelets form a temporary plug.
3) Coagulation Cascade (Secondary Hemostasis):
Sequential activation of clotting factors leads to the formation of a fibrin mesh that stabilizes the platelet plug.
4) Clot Retraction and Repair:
The clot contracts to reduce size and facilitate tissue repair.
5) Clot Dissolution (Fibrinolysis):
Plasmin breaks down the clot once healing is complete.
Coagulation Pathways
Intrinsic Pathway (Contact Activation):
Activated by damage inside blood vessels.
Factors: XII → XI → IX → VIII → X.
Extrinsic Pathway (Tissue Factor Pathway):
Activated by external trauma releasing tissue factor (TF).
Factors: TF → VII → X.
Common Pathway:
Both pathways converge at Factor X, activating thrombin.
Thrombin converts fibrinogen into fibrin, forming the final clot.
Key Clotting Factors
Factor I: Fibrinogen – Converted to fibrin.
Factor II: Prothrombin – Converted to thrombin.
Factor III: Tissue factor (TF) – Activates extrinsic pathway.
Factor IV: Calcium – Essential cofactor in clotting.
Factor VIII and IX: Deficiencies cause Hemophilia A and B.
Factor XIII: Cross-links fibrin to stabilize the clot.
Disorders of Blood Clotting
1) Bleeding Disorders (Hypocoagulable States):
Hemophilia (A - Factor VIII, B - Factor IX deficiency).
Von Willebrand Disease: Defective platelet adhesion.
Thrombocytopenia: Low platelets.
Liver Disease: Impaired clotting factor synthesis.
Vitamin K Deficiency: Affects Factors II, VII, IX, X.
2) Excessive Clotting Disorders (Hypercoagulable States):
Deep Vein Thrombosis (DVT): Clots in deep veins.
Pulmonary Embolism (PE): Clot migration to lungs.
Disseminated Intravascular Coagulation (DIC): Widespread clotting followed by bleeding.
Thrombophilia: Genetic predisposition (e.g., Factor V Leiden).
Diagnosis
1) Coagulation Tests:
PT (Prothrombin Time): Extrinsic pathway, monitors warfarin.
INR: Standardized PT value.
aPTT (Activated Partial Thromboplastin Time): Intrinsic pathway, monitors heparin.
Thrombin Time (TT): Fibrinogen conversion assessment.
2) Platelet Tests:
Count and Bleeding Time: Platelet number and function.
3) Special Tests:
D-Dimer: Detects clot breakdown products (DVT, PE).
Fibrinogen Levels: Checks for deficiencies.
Factor Assays: Identifies specific deficiencies.
Treatment
1) Bleeding Disorders:
Replacement Therapy: Clotting factors (Factor VIII for Hemophilia A).
Desmopressin (DDAVP): Releases von Willebrand factor.
Vitamin K Supplementation: For deficiencies.
Platelet Transfusion: In thrombocytopenia.
2) Clotting Disorders (Hypercoagulability):
Anticoagulants:
Heparin: Immediate effect (intrinsic pathway).
Warfarin: Long-term use (extrinsic pathway).
DOACs: Apixaban, Rivaroxaban.
Thrombolytics (Fibrinolytics): Alteplase for DVT, PE, stroke.
Antiplatelets: Aspirin, Clopidogrel to prevent aggregation.
Compression Therapy: Prevents clotting in immobile patients.
Complications
Bleeding: From anticoagulants or clotting factor deficiencies.
Thromboembolism: Migrating clots causing PE, stroke.
Organ Damage: Hypoperfusion due to clots.
Prognosis
Early Treatment: Improves survival and outcomes.
Chronic Conditions: Require long-term management.
Advances in Therapy: Improved outcomes for high-risk patients.