10. Clotting Cascade & its Role in CV Diseases Flashcards
Coagulation physiology
Coagulation system along with endothelial cells & platelets maintains blood in fluid state within blood vessels
Endothelial cells
Synthesises & secretes substances that can act as either procoagulants (P) or anticoagulants (A)
Platelets
- Blood cells that help with blood clotting to stop bleeding
- Inactive form circulates in the blood which rushes to area of injury & activates to form a clot
- Receptors are present on platelets for all substances secreted by endothelial cells
- Platelet membrane hold receptors for many substances involved in haemostasis - primary or secondary
Primary haemostasis
Formation of platelet plug:
- Adhesion
- Activation
- Aggregation
Friable & unstable clot is formed
Secondary haemostasis
Formation of a more stable blood clot:
Intrinsic pathway:
- Caused by damaged surface which exposes endothelial collagen
Extrinsic pathway:
- Caused by trauma
Common pathway:
- Involves prothrombin, thrombin, fibrinogen, fibrin & Xa
Fibrinolysis
Plasminogen (inactive)
- Made in liver
- Circulates in bloodstream
- Incorporated in thrombus during clot formation
- Tissue plasminogen activator (tPA) allows plasmin formation
Plasmin (active):
- Activated form of plasminogen
- An enzyme
- Converts fibrin clot to fibrin degradation product
Coagulation dysregulation
Associated disease conditions:
- Thrombosis - arterial or venous
- Haemophilia -> Bleeding disorders -> von Willebrand disease or Vitamin K deficiency
Why does thrombosis occur?
Thrombosis is the formation of a solid mass of blood within the circulatory system
Abnormalities of the vessel wall:
- Atheroma
- Direct injury
- Inflammation
Abnormalities of blood flow:
- Stagnation
- Turbulence
Abnormalities of blood components:
- Smoking
- Post-partum
- Post-op
Arterial thrombosis
- Typically from rupture of atherosclerotic plaque
- Involves left heart chambers, arteries
- Associated with acute coronary syndrome, Ischaemic stroke, ischaemia
- Consists of mainly platelets
- Treated with anti platelet agents (ASA, clopidogrel)
Venous thrombosis (VTE)
- Typically from a combination of factors from Virchow’s triad
- Involves venous sinusoids of muscles & valves in veins
- Associated with DVT & PE
- Consists of mainly fibrin
- Treated with anticoagulants (heparins, warfarins)
DVT vs PE
- DVT in lower extremities
- PE occurs due to embolisation of the thrombus to pulmonary vasculature
Virchow’s triad
Conditions associated with Virchow’s triad predispose to thrombus formation
- Endothelia damage
- Hypercoagulability - tendency to clot
- Stasis
Deep vein thrombosis: Signs & symptoms + Treatment
Signs & symptoms:
- Swelling of the lower leg
- Tenderness of calf muscle
- Localised redness & warmth
- Mild fever
- Lower leg veins may become more prominent (darker & raised) & sometimes the skin becomes darker
Treatment:
- Anticoagulants - Warfarin
- Thrombolytics - Alteplase (tPA)
- Compression stockings
Pulmonary embolism: Signs & Symptoms + Treatment
Signs & symptoms: Most common
- Shortness of breath
- Chest pain
- Cough that may produce blood (haemoptysis)
Signs & symptoms: Less common
- Leg pain or swelling, usually in calf
- Clammy/discoloured skin
- Excessive sweating
- Fever
- Rapid or irregular heartbeat
- Light-headedness or dizziness
Treatment:
- Anticoagulants - Warfarin, heparin, rivaroxaban
- Thrombolytic agents
Arterial thrombosis
Primary trigger is the rupture of an atherosclerotic plaque, causing a complete or partial vessel occlusion
