- Slides: 58
Introduction to Haemostasis Ahmad Sh. Silmi Hematologist Msc, FIBMS
Course Objectives • Identify the factors that influence the effectiveness of hemostatic processes. • Describe the mechanisms that are involved in the arrest of blood flow from a damaged vessel. • Identify key aspects associated with primary and secondary hemostasis. • Explain the role of various coagulation components in hemostatic processes. • Define the extrinsic, intrinsic, and common pathways that are part of the coagulation cascade, identifying the coagulation factors that are associated with each pathway. • Describe the function of various laboratory tests in evaluating hemostasis. • Identify common coagulation disorders, their symptomology, and subsequent treatment. • Explain the role of the prothrombin time and activated partial thromboplastin time in monitoring anticoagulation therapy.
Course outline Part one • An Introduction to the Fundamentals of Coagulation • Which of the following would NOT impact the effectiveness of hemostatic processes? – Primary Hemostasis • Introduction to Hemostatic Mechanisms • Primary Hemostasis: The Vascular System and Platelet Involvement • Primary Hemostasis: Platelet Production • Primary Hemostasis: Characteristics of the Platelet • Primary Hemostasis: Platelet Function • Summary of Primary Hemostasis • Which of the following processes does NOT occur during primary hemostasis?
Course outline Part one Cont. – Overview of Secondary Hemostasis • Overview of Secondary Hemostasis • Secondary Hemostasis: Fibrin Formation via the Coagulation Cascade • Consequences Linked to Deficiencies in Coagulation Factors • What is the ultimate goal of secondary hemostasis? • Coagulation Factors in the Coagulation Cascade • Secondary Hemostasis: The Extrinsic Pathway • Secondary Hemostasis: The Intrinsic Pathway • Secondary Hemostasis: The Common Pathway • Secondary Hemostasis: Coagulation Factor Characteristics • Factor VII is part of which coagulation pathway? – The Fibrinolytic System • The Fibrinolytic System • Regulation of hemostatic mechanisms
Course outline Part Two – Coagulation Disorders • • Coagulation Disorders: Inherited Coagulation Disorders: Acquired Coagulation Disorders: Platelet Disorders Coagulation Disorders and Liver Disease – Anticoagulation Therapy • • Anticoagulation Therapy Heparin Therapy Oral Anticoagulant Therapy Other
Let us Begin……
HEMOSTASIS Ø Haemostasis or Hemostasis (Greek: aimóstasis, from aíma "blood" + stásis "stagnation") is a complex process which continually ensures: § prevention of spontaneous blood loss and § stops hemorrhage caused by damage of vascular system Ø Most times this includes the changing of blood from a fluid to a solid state and then to fluid state. 7
Function of Haemostasis ¨ Arrests bleeding ¨ Keeps blood in fluid state ¨ Repair and reestablish the blood flow through the injured vessels ¨ Remove haemostatic plug n If any of the above functions is exaggerated or impaired it will cause either thrombosis or hemorrhage respectively; so hemostasis is a balance between thrombosis and hemorrhage 8
Without this balance, the individual may experience either excessive bleeding (poor clot formation or excessive Fibrinolysis) Vaso-occlusion (uncontrolled formation of thrombin in vascular system, occluding vessels and depriving organs of blood). asilmi
HEMOSTASIS n There are certain conditions associated with excessive bleeding are referred to as: Hypo-coagulable states. Such as, Hemophilia or deficiency in one of the plasma coagulation proteins such as factors VIII. Acquired conditions such as DIC, Liver and Kidney diseases. n In addition to Coagulation promotion, vessel injury initiates Fibrinolysis through endothelial cell release of tissue Plasminogen activators (t. PAS). This is to ensure that excessive coagulation does not occur. n asilmi
HEMOSTASIS n n Role of Coagulation in Hemostasis Coagulation: Is the process where by on vessel injury, Plasma protein, Tissue factors and Calcium interact on the surface of the platelets to form a Fibrin clot. Platelets provide a surface for the coagulation reaction, and interact with fibrin to form a stable platelet fibrin clot. asilmi
HEMOSTASIS n Tissue factors (except Ca and Tissue Thromboplastin) normally circulate in the plasma as inactive proteins. n On activation some factors form enzymatic proteins known as Seiren Proteases that activate other specific factors in the coagulation sequence. n Other conditions are related to uncontrolled thrombosis are called Hyper-coagulable state. This is related to an appropriate formation of thrombi in the vascular vessels that occlude normal blood flow. asilmi
Mechanism of Hemostasis n Haemostasis involves a series of delicately balanced physical and biochemical changes following an injury to a blood vessel. n As the most immediate response, the blood vessel constrict n Then platelets adhere and aggregate at the site of the injury and form a plug 13
Mechanism of Hemostasis n These activated platelets secretes substances that initiate the coagulation factors which interact serially, forming a fibrin network or clot in which white cells, red cells and platelets are trapped and form a solid plug of blood ( coagulation) which seals off the injury vessel completely. n Finally slow lysis of the clot, fibrinolysis, begins and the site of the injury is repaired. 14
Components of normal hemostasis n Tissue vessels Tissular coagulation factor Platelets n Thrombocytic factors Platelet Coagulation (activator & inhibitors) Humoral ( plasma factors) n Fibrinolysis (activater & inhibitors) 15
The effectiveness or failure of haemostatic mechanism to control bleeding depends on : – The type & degree of injury. – The size & ability of injured vessel to contract. – The pressure within the vessel & surrounding tissues. – The availability & activity of the platelets. – The quantity & functional ability of blood clotting factors. – The absence of inhibitors.
Hemostasis n n The hemostatic components remain inert in the presence of intact vascular tissue or endothelium Following injury, each component must function optimally.
Vessel wall, Blood flow & Coagulation Substances asilmi
In Case if there is an Endothelial Injury (Bleeding must be prevented at site of injury) asilmi
Flow must be Maintained asilmi
Virchow Law There are three haemostatic components: • 1 - The extra-vascular (The tissues surrounding blood vessels) involved in Hemostasis when local vessel is injured. It plays a part in Hemostasis by providing back-pressure on the injured vessel through swelling and trapping of escaped blood. asilmi
HEMOSTASIS The three haemostatic components n n 2 - The vascular (The blood vessels through which blood flow) it depends on the size, amount, of smooth muscle within their walls and integrity of the endothelial cell lining. 3 - The intra-vascular (The platelets and plasma proteins that circulate within the blood vessels). These components are involved in Coagulation (clot or thrombus formation) or Fibrinolysis (clot or thrombus dissolution). asilmi
Phases Three –phase process I. Primary hemostasis II. Coagulation (secondary hemostasis) III. Fibrinolysis (Tertiary hemostasis)
Phases cont’d I. Primary hemostasis q Involves q Blood vessels (vascular vasoconstriction phase and release of tissue or exogenous factors) q Thrombocytes (plate or endothelial –thrombocyte phase, plate aggregation and release of plate factors). q After 3 to 5 minutes , blood flow is arrested with the formation of a plate plug.
Phases cont’d II. Coagulation q Involves q Plasma coagulation factors (plasma phase) q Plate factor 3 provides for definitive hemostasis q Takes 5 to 10 minutes by formation of fibrin q q Reinforces the plate plug.
Phases cont’d III Fibrinolysis q Essential final step in any hemostasis mechanism, q Enabling in 48 to 72 hours, and a q Return to normal by destroying fibrin and healing the injured vessel. 27
I. Primary hemostasis Ø Is a result of a three –way interaction between: Ø Vascular wall Ø Platelets Ø plasma coagulation factors Ø Triggered by v Small injuries to blood vessels v The plasma coagulation factors desquamation (damaging of epithelial cells in pinpricks)
Primary hemostasis Ø Involves: § Vasoconstriction § Platelet adhesion § Platelet aggregation § Platelet secretion 29
HEMOSTASIS n n Role of Blood Vessels in Hemostasis Blood flows through the vascular system to and from all parts of the body. The vascular system consists of capillaries, arteries, and veins. Blood normally carried within vessels whose physical capabilities include Contraction (narrowing) and Dilation, which are controlled by the smooth muscle of the vessel media. asilmi
HEMOSTASIS n Vasoconstriction and Vasodilatation provide the means for control blood flow rate and blood pressure. n Substances released from the endothelial cells and subendothelial smooth muscles also contribute to normal blood flow and prevent abnormal formation of clot. asilmi
Vascular NO functions n n n NO inhibits platelets' and leucocytes' adhesion to endothelial cells. It inhibits platelet aggregation It facilitates the dissolution of small platelet aggregates. NO affect the fibrinolytic activity by regulating the release of t-PA & PAI-1. The crucial role of vascular NO in the control of blood fluidity has been demonstrated by the regulation of the bleeding time in humans. 41
Arachidonic acid Cyclo-oxygenase Cyclic Endoperoxides ENDOTHELIAL CELL Prostacyclin synthetase Prostacyclin (PGI 2) Inhibits plt aggregation Vasodilator PLATELET Thromboxane synthetase Thromboxane (Tx. A 2) Enhances plt aggregation Vasoconstrictor
Mediators of Vascular relaxation 46
Summary of Important Vascular Function asilmi
Vascular Endothelium Function Prostacyclin Vasodilation, inhibition of platelet aggregation Thromboxane A 2 From platelets, constrict muscular arteries ELAMs, ICAMs von Willebrand factor 49 Cytokines induce synthesis to promote leukocyte adhesion Promote platelet-collagen adhesion to exposed subendothelium
Vascular Endothelium Function Tissue factor pathway inhibitor Anticoagulant- Inhibits coagulation extrinsic pathway Thrombomodulin Anticoagulant- Inhibits coagulation by activating protein C system Tissue plasminogen activator Anticoagulant- Inhibits coagulation by activating fibrinolysis Heparan sulfate proteoglycans Anticoagulant- Inhibits coagulation by activating antithrombin Tissue factor 50 Procoagulant- Inflammatory cytokines (IL-1, TNF) induce expression
Upon conclusion one can aske the following question 53