5112BMBMOL Coagulation 2025

Haematology and Transfusion Overview

Title: Haematology and Transfusion

• Focus: Coagulation

• Instructor: Dr. Adam Linley, Senior Lecturer in Haematology

• Location: 8.01 James Parsons Building

• Email: a.j.linley@ljmu.ac.uk

Learning Outcomes

1. Understanding the purpose of the coagulation pathway: Grasp the significance of the coagulation pathway in maintaining hemostasis and preventing hemorrhage in various clinical scenarios.

2. Identifying the properties of the factors involved: Familiarize with the roles, characteristics, and structures of each coagulation factor.

3. Learning about the activation processes: Comprehend how coagulation factors are activated during the hemostatic response.

4. Recognizing the control mechanisms of the coagulation pathway: Identify intrinsic and extrinsic regulation mechanisms that prevent excessive clot formation.

Coagulation: Key Concepts

• Critical Process: Coagulation is essential for preventing blood loss through the complex process of thrombus formation at sites of vascular injury, triggering a response that leads to bleeding cessation.

• Interactions: The coagulation pathway is characterized by interactions among various proteins, co-factors, and cellular elements that work in concert to form a stable clot. These elements include platelets, clotting factors, and plasma proteins.

• Balance: The delicate equilibrium between coagulation and anticoagulation processes is crucial for maintaining hemostasis; disruptions can lead to bleeding disorders or thrombosis.

The Coagulation Cascade

• Initiation: The coagulation cascade is initiated by vascular injury, which exposes tissue factor (TF) and colagen allowing for the rapid recruitment and activation of coagulation factors through contact activation.

• Key Factors: Involves several critical coagulation factors including:

  • Factor IX (Christmas factor)

  • Factor X (Stuart-Prower factor)

  • Factor XI (Plasma thromboplastin antecedent)

  • Factor VIII (Antihemophilic factor)

  • Thrombin (Factor IIa)

  • Fibrinogen (Factor I).

• End Product: The culmination of the cascade results in the formation of stable fibrin and fibrin polymers from fibrinogen through thrombin activation, creating a mesh that solidifies the clot.

Coagulation Factors

• Roman Numerals: Coagulation factors are designated by Roman numerals (I, II, V, VII, VIII, IX, X, XI, XII), primarily existing as zymogens (inactive forms that require activation).

• Active Forms: Upon activation, these factors are converted into active serine proteases that participate in subsequent stages of the coagulation process.

• Exceptions: Notably, FVIII and FV function as glycoprotein cofactors, while FXIIIa acts as a transglutaminase facilitating cross-linking of fibrin to stabilize the clot.

Role of Calcium (Ca2+)

• Importance: Calcium ions (Ca2+) are indispensable for the orientation and interaction of coagulation factors, essential for proper functioning during the coagulation processes.

• Modification: Factors undergo vitamin K dependent gamma-carboxylation in the liver, which is essential for their activity and interaction.

• Clinical Relevance: Numerous anticoagulants target this modification, such as warfarin, highlighting the importance of vitamin K in coagulation management.

Phospholipids in Coagulation

• Function: Phospholipids are critical in promoting the activity of coagulation factors, primarily sourced from activated platelets.

• Mechanism: Upon vascular injury, platelets release phospholipids that enhance the activity of coagulation factors, thereby accelerating the cascade.

Thrombin: A Central Player

• Effects: Thrombin has multifaceted roles including:

  • Promotion of platelet aggregation and the release of additional coagulation factors.

  • Activation of FV, FXI, cleavage of FVIII from von Willebrand factor (vWF).

  • Conversion of fibrinogen to fibrin and activation of FXIII for clot stabilization.

• Anticoagulation Role: Thrombin also plays a critical role in the activation of Protein C, which is important for controlling the clotting cascade.

Inhibitors of Coagulation

• Key Proteins: Significant proteins such as Protein C and Protein S are dependent on vitamin K and function to inhibit FV and FVIIIa, providing a regulatory response to prevent excessive clotting.

• Function: This regulation is vital to maintain balance and prevent pathological clotting that can lead to thrombosis or embolism.

Fibrinolysis

• Process: Fibrinolysis is the physiological process of breaking down fibrin, which is facilitated by plasmin; plasminogen serves as its inactive precursor.

• Importance: This process ensures that once a clot has fulfilled its purpose, it is degraded to restore normal blood flow and prevent occlusion.

Anticoagulation Therapy

• Warfarin: A vitamin K antagonist that inhibits gamma-carboxylation of coagulation factors, effectively prolonging clotting time. It is commonly used in the treatment of deep vein thrombosis (DVT) and monitored through prothrombin time (PT) assessments.

• Heparin: A naturally occurring mucopolysaccharide that enhances the action of antithrombin, serving as an effective anticoagulant. Heparin must be administered intravenously and its efficacy is monitored by activated partial thromboplastin time (APTT).

Bleeding Disorders

• Haemophilia A: Characterized by a deficiency in Factor VIII, leading to symptoms such as excessive bleeding after injuries, easy bruising, and joint pain due to bleeding into joints.

• Haemophilia B: Similar to Haemophilia A, this disorder arises from a deficiency of Factor IX, presenting with comparable bleeding issues.

• Von Willebrand Disease (vWD): This bleeding disorder is characterized by a deficiency or dysfunction of von Willebrand factor (vWF), which plays a crucial role in platelet adhesion. Patients may experience spontaneous bleeding from cuts, nosebleeds, and excessive bleeding from surgical procedures.

Summary of Key Comparisons

• Haemophilia A: Low Factor VIII, primarily transmitted through X-linked inheritance.

• Haemophilia B: Low Factor IX, follows a similar X-linked inheritance pattern.

• Von Willebrand Disease: Low vWF, predominantly exhibits an autosomal dominant inheritance pattern.