Basic Principles of Hemostasis

Objectives: Describe the 4 steps of hemostasis Describe platelets, their normal count, development, and functions. Describe the process of coagulation & the role of Vit K in it Define normal coagulation time List the natural anti-coagulants present in blood Define hemophilia and list possible symptoms of hemophilia Explain normal bleeding time and define Purpura

Steps of Hemostasis 1. Vascular spasm (vasoconstriction) 2. Platelet plug formation 3. Clot formation (blood clotting) 4. Clot retraction

Platelets Platelets (Thrombocytes) Count 150,000-400, 000 /μL Origin: megakaryocytes in bone marrow develop under influence of “Thrombopoeitin” Disc shape- with vesicles 2-4 μ in size No nucleus Residues of ER, Golgi apparatus Mitochondria Enzyme systems Contain granules which secrete chemicals: i. Serotonin; ii. endothelial growth factor; iii. Prostaglandins; iv. phospsholipids (membrane) v. Fibrin stabilizing factor vi. Platelet Derived Growth factor Natural destruction by macrophages in spleen Platelets

Functions of platelets: Help in hemostasis (stoppage of bleeding) by 1. producing vasoconstriction 2. becoming sticky (activated) to form a platelet plug to close small holes in blood vessels 3. initiate coagulation Clinical implications Low dose Aspirin reduces platelet adhesiveness: Rationale for use in “blood thinning” Low platelet count (< 50,000/μL) causes bleeding disorder Simple investigation: Bleeding time measurement by finger prick. Normal bleeding time 3-6 minutes Disease when platelet count is low: Thrombocytopenic purpura

Vascular spasm Contraction of vascular smooth muscle because of i. muscle damage; ii. serotonin from platelets Platelet plug formation 1. Platelet adhesion to damaged endothelium 2. Platelet release reaction: ADP: increase platelet adhesiveness (stickiness) 3. Serotonin & TXA2 : vasoconstriction 4. Platelets stick to one another to form a plug: Adhesion which is good enough to stop a small puncture from bleeding (Prostacyclin from endothelium opposes (يعارض) stickiness)

Blood coagulation: factors involved

Principles of Hemostasis Blood coagulation Prothrombin activator PROTHROMBINASE) (Factor Xa + Ca++ + Phospholipid + Factor V) Vit K -Source: dietary, large intestine bacteria -Fat soluble; -Synthesis of prothrombin, factors VII, IX, X, Protein C Prothombin thrombin Thrombin: Accelerates prothrombinase formation fibrinogen fibrin F XIII Serum (straw yellow in colour) = blood – clotting factors Clot retraction + RBC = clot

+ 1 PROTHROMBINASE THROMBIN 2 STRENGTHENED 3 FIBRIN THREADS Tissue trauma Tissue factor (TF) Blood trauma Damaged endothelial cells expose collagen fibers (a) Extrinsic pathway (b) Intrinsic pathway Activated XII Ca2+ platelets Platelet phospholipids Activated X Activated PROTHROMBINASE V Prothrombin (II) THROMBIN Loose fibrin threads STRENGTHENED FIBRIN THREADS Activated XIII Fibrinogen (I) XIII (c) Common pathway 1 2 3 +

(Prothrombin activator) Prothrombinase (Prothrombin activator)

Breakup/limitation of clot: Fibrinolysis Clot contains Plasminogen Thrombin, Active Factor XII Tissue –plasminogen activator (pTA) activate Plasmin clot lysis (clot breaks up Prostacyclin Inhibits platelet adhesiveness

Natural anticoagulants: A. Endothelial surface factors B. Anticoagulants present in the blood which remove THROMBIN C. Anticoagulants may be used 1. Smoothness of endothelial wall: so has glycocalyx which repels clotting factors 1. Fibrin itself 2. Antithrombin III -antithrombin (α globulin) + heparin -removes activated factors XII, XI, X -removes thrombin 2. Protein C :inactivates factors V and VIII 3. Thrombomodulin- a protein bound to endothelium -combines with thrombin to reduce clotting. In patients: i. Heparin ii. Vit K antagonists Outside the body: Heparin Calcium antagonists 4. This combination also activates Protein C

Normal coagulation time: 3-7 minutes (finger prick method) Clinical implications Coagulation disorders : i. not enough coagulations factors--? (Hemophilia (factor VIII deficiency) transmitted by female to males. Only males suffer) ii. Not enough Vit K -

Summary Steps of hemostasis Platelets and their role in hemostasis Normal bleeding time and its abnormality Coagulation factors The clotting cascade and formation of prothrombinase Natural anti-coagulation Anticoagulation in treatment Normal clotting time and abnormalities