Haemostasis - Part II: Secondary Haemostasis

Haemostasis - Part II: Secondary Haemostasis

• Secondary haemostasis involves strengthening the platelet plug by coagulation factors.
• Coagulation factors are mainly proenzymes (zymogens).
• Most coagulation factors are created in the liver.
• Factors II, VII, IX, and X require Vitamin K for synthesis.
• Proenzymes need activation to work.
• The active form of a factor is denoted by 'a' (e.g., FVIIa).

Aims and Objectives

• The lecture aims to describe the processes of normal haemostasis.
• Students will be able to explain the significance of effective haemostasis.
• Students will be able to explain the main components of haemostatic mechanisms.
• Students will be able to explain the mechanisms of secondary haemostasis.

Primary and Secondary Haemostasis

• Primary haemostasis:
  • Platelets react to vessel injury.
  • Platelets adhere to the vessel wall.
  • A primary platelet plug forms.
• Secondary haemostasis:
  • Activation of intrinsic and extrinsic coagulation pathways.
  • Activation of common pathway.
  • Fibrin strand formation and strengthening of the platelet plug.
• All phases are integrated and often occur simultaneously.

Secondary Haemostasis Details

• Weak platelet plugs need strengthening by coagulation factors.
• Coagulation factors are mostly proenzymes (zymogens)
• The most coagulation factors are synthesized in the liver.
• The factors are vitamin K-dependent, namely factors II, VII, IX, and X.
• Proenzymes need activation to work and the active form of a coagulation factor has 'a' as a suffix. (e.g., FVIIa).

Secondary Haemostasis Four-Stage Process

• Stage 1: Tissue factor is expressed or released.
• Stage 2: Activated platelets express phospholipid complexes with a negative charge, allowing coagulation factors to bind and become activated.
• Stage 3: Conversion of prothrombin to thrombin.
• Stage 4: Conversion of fibrinogen to fibrin.

The Coagulation Cascade

• The coagulation cascade involves three pathways:
  • Extrinsic pathway.
  • Intrinsic pathway.
  • Common pathway.
• These pathways help understand how medications prevent blood clots and aid in in vitro diagnostic tests.

Extrinsic Pathway

• Initiated by vascular injury (physical, inflammation, atherosclerotic plaques).
• Tissue factor (TF) is exposed.
• TF binds to FVII, activating it (FVIIa).
• TF-FVIIa complex activates factor X (FX).
• Factor X (FXa) joins the common pathway.

Intrinsic Pathway

• Initiated by contact with negatively charged surfaces (e.g., collagen, negatively charged phospholipids).
• Factor XII becomes activated.
• The activation of factors in a cascade along the pathway.
• Factor X (FX) participates in the common pathway .

Common Pathway

• Both the intrinsic and extrinsic pathways lead to factor X activation.
• Factor Xa, along with factor Va and calcium ions (Ca2+), activates prothrombin.
• Prothrombin converts to thrombin.
• Thrombin catalyzes the conversion of fibrinogen to fibrin.
• Fibrin forms a mesh that strengthens the platelet plug, forming a blood clot.

Clot Breakdown/Fibrinolysis

• After injury heals, clots are removed by fibrinolysis.
• Tissue plasminogen activator (tPA) is released from endothelial cells.
• tPA converts plasminogen into plasmin.
• Plasmin digests fibrin, resulting in small fragments called d-dimers.
• Recombinant tPA is a valuable treatment for thrombotic strokes.

Preventing Clots

• Haemostasis is tightly controlled.
• Endogenous inhibitors of primary haemostasis include nitric oxide and prostacyclin.
• Endogenous secondary haemostasis inhibitors include tissue factor pathway inhibitor (TFPI), antithrombin III, and protein C.
• These inhibitors prevent inappropriate clot formation.

This quiz delves into the critical processes of secondary haemostasis, enhancing the platelet plug through coagulation factors. It covers the roles of these proenzymes, their synthesis in the liver, and the importance of Vitamin K in their activation. Students will explore the mechanisms that contribute to effective haemostasis and its significance.