Haemostasis Part II: Secondary Haemostasis

Haemostasis - Part II: Secondary Haemostasis

• Secondary haemostasis is a crucial part of the overall haemostatic process, following primary haemostasis.
• It involves a cascade of events to strengthen the platelet plug formed during primary haemostasis.
• The aim is to create a stable blood clot.

Preparation

• Students need to have completed the previous lecture on Haemostasis Part I to understand secondary haemostasis.
• Students should write out the pathways in a way that makes sense to them.

Aims and Objectives

• Students will be able to outline the processes of normal haemostasis.
• They will be able to explain the importance of effective haemostasis.
• They will be able to describe the major components of haemostatic mechanisms.
• They will be able to describe the mechanisms of secondary haemostasis.

Primary and Secondary Haemostasis

• Primary haemostasis: involves platelet response to vessel wall injury, platelet adhesion, and formation of a primary platelet plug.
• Secondary haemostasis: involves activation of the intrinsic and extrinsic coagulation pathways, activation of the common pathway, and fibrin strand formation strengthening the platelet plug.

Secondary Haemostasis

• A weak platelet plug requires strengthening by coagulation factors.
• Coagulation factors mainly comprise proenzymes, or zymogens.
• Most coagulation factors are synthesised in the liver.
• Factors II, VII, IX, and X are vitamin K-dependent.
• Proenzymes need activation to function. The active form of a coagulation factor is denoted by 'a'.

Secondary Haemostasis - 4 Stage Process

• Stage 1: Tissue factor is expressed or released.
• Stage 2: Activated platelets express phospholipid complexes, which provide binding sites for coagulation factors to become activated.
• Stage 3: Prothrombin is converted to thrombin.
• Stage 4: Fibrinogen is converted to fibrin, which strengthens the clot.

The Coagulation Cascade

• The coagulation cascade consists of three pathways: intrinsic, extrinsic, and common pathways.

Extrinsic Pathway

• Initiated by vascular injury.
• Tissue factor (TF) is exposed, binding to FVII to form FVIIa.
• FVIIa activates factor X forming factor Xa.

Intrinsic Pathway

• Initiated by contact with negatively charged surfaces (e.g., collagen, negatively charged phospholipids on platelets).
• This involves a cascade of activation events culminating in the activation of factor X.

Common Pathway

• Both the intrinsic and extrinsic pathways converge at the common pathway.
• Factor X is activated by either pathway (Xa).
• Xa along with other factors forms the prothrombinase complex.
• The prothrombinase complex converts prothrombin to thrombin.
• Thrombin cleaves fibrinogen to form fibrin, which polymerizes to form the blood clot.

What Happens to the Clot Afterwards?

• When the injury is healed, the clot is broken down by fibrinolysis.
• Tissue plasminogen activator (tPA) is an enzyme that converts plasminogen to plasmin.
• Plasmin then digests fibrin, producing small fragments known as d-dimer.
• Recombinant tPA and plasminogen activators are pharmacological treatments for thrombotic stroke.

Why Don't We Get Clots All The Time?

• Haemostasis is tightly controlled by both intrinsic and extrinsic pathways.
• Endogenous inhibitors of primary haemostasis include nitric oxide and prostacyclin (PGI2) produced in endothelial cells.
• Endogenous inhibitors of secondary haemostasis include:
  • Tissue factor pathway inhibitor (TFPI)
  • Antithrombin III
  • Protein C
• These inhibitors prevent unnecessary clot formation.

This quiz focuses on Secondary Haemostasis, which is essential for strengthening the platelet plug formed during primary haemostasis. Students will explore the processes that contribute to normal haemostasis, its importance, and the mechanisms involved in secondary haemostasis. Ensure you have completed Haemostasis Part I for better comprehension.