Introduction To Haemostasis

INTRODUCTION TO HAEMOSTASIS

Objectives • Define haemostasis • Overview of the coagulation cascade • Coagulation factors and their common names • Common routine tests in coagulation

What is HAEMOSTASIS? • It is the cessation of blood loss from a damaged vessel. It is the process by which blood clot is formed through a series of event in the blood. • A thrombus is an intravascular clot formed during life

Haemostasis contd • • • •

Blood vessel (vascular wall) Platelets Coagulation factors Plasma proteins

Process of Haemostasis • Vascular Spasm - The smooth muscle in blood vessel walls contracts immediately the blood vessel is broken. This response reduces blood loss for some time, while the other hemostatic mechanisms become active. • Platelet Plug Formation - When blood platelets encounter a damaged blood vessel they form a "platelet plug" to help to close the gap in the broken blood vessel. • Blood Clotting (Coagulation) • Dissolution of Clot by Plasmin (Fibrinolysis)

Platelet Kinetics • Platelets are produced in blood cell formation (thrombopoiesis) in bone marrow, by budding off from megakaryocytes. • The physiological range for platelets is 150-400 x 109 per litre. • Around 1 x 1011 platelets are produced each day by an average adult. • The lifespan of circulating platelets is 7-10 days. • This process is regulated by thrombopoietin, a hormone usually produced by the liver and kidney. • Each megakaryocyte produces between 5,000 and 10,000 platelets. • Old platelets are destroyed by the spleen and by Kupffer cells in the liver

Platelet Structure

Platelet Structure contd

Platelet Glycoproteins (GPs) or Receptors • GP Ia – Adhesion to collagen • GP Ib –Adhesion of von willebrand factor • GP IIb/IIIa (fibrinogen receptor) –plateletplatelet aggregation

Formation of primary haemostatic plug • Platelet activation • Shape change • Platelet release reaction (granule secretion) • Synthesis of Thromboxane A2 • Platelet adhesion • Platelet aggregation

What is Coagulation cascade ? • Coagulation is initiated almost instantly after an injury to the blood vessel damages the endothelium (lining of the vessel). Platelets immediately form a hemostatic plug at the site of injury; this is called primary hemostasis. Secondary hemostasis occurs simultaneously—proteins in the blood plasma, called coagulation factors, respond in a complex cascade to form fibrin strands which strengthen the platelet plug • Biological amplification system which is initiated by tissue damage or vascular injury, with resultant sequential activation of coagulation factors in which thrombin is generated.

Coagulation cascade

Coagulation cascade

Coagulation factors and their common names • • • • • • • • • • • • •

Factor I - fibrinogen Factor II - prothrombin Factor III - tissue thromboplastin (tissue factor) Factor IV - ionized calcium ( Ca++ ) Factor V - labile factor or proaccelerin Factor VI - unassigned Factor VII - stable factor or proconvertin Factor VIII - antihemophilic factor Factor IX - plasma thromboplastin component, Christmas factor Factor X - Stuart-Prower factor Factor XI - plasma thromboplastin antecedent Factor XII - Hageman factor Factor XIII - fibrin-stabilizing factor

Fibrinolysis • Tissue plasminogen activator released from ECs activates plasminogen; • Plasminogen is converted to plasmin • Plasmin breaks down Fibrin into fibrin degradation products (FDPs)

Inhibitors of coagulation factors • Tissue factor pathway inhibitor inhibits VIIa and extrinsic pathway • Antithrombin inhibits IIa, IXa, XIIa, XIa, Xa • Proteins C and S inhibits Va and VIIIa • Tissue plasminogen activator inhibitor (tPAI)-inhibits fibrinolysis

Common routine tests in coagulation • Prothrombin time (PT) • Activated partial thromboplastin time (aPTT) • Thrombin time (TT) • Fibrinogen quantitation • Factor assays

SUMMARY • Haemostasis is an important mechanism in controlling blood loss • Coagulation cascade includes the extrinsic, intrinsic and common pathway • Coagulation Factors and their common names • Inhibitors of coagulation provide protective mechanisms for unchecked blood coagulation