Physiology Chapter 5: Hemostasis

Platelets

• Formed in bone marrow, with a count of 150-400,000/µl
• 30% sequestered in spleen, with a diameter of 2-4 µm and a lifespan of 8-12 days, no nucleus
• Active cytoplasm with enzyme synthesis
• Membrane receptors for thrombin, ADP, and serotonin
• Storage of calcium and adhesion proteins (VWF, fibronectin, collagen, fibrinogen)
• Synthesis of prostaglandins, coat of glycoproteins for adhesion to injured areas
• Granules containing ADP, serotonin, and ATP, phospholipids for activation of intrinsic pathway
• α-granules containing fibrinogen, PDGF, VWF, fibronectin, and fibrin stabilizing factor

Hemostasis

• Refers to the stoppage of bleeding (hemo = blood, stasis = standing)
• Three stages: blood vessel spasm, platelet plug formation, and blood coagulation

Stage 1: Blood Vessel Spasm

• Triggered by pain receptors, local myogenic spasm, and local release of thromboxane A2 and serotonin
• Results in smooth muscle contraction in blood vessels to minimize blood flow from the wound site

Stage 2: Platelet Plug Formation

• Triggered by exposure of platelets to collagen
• Results in platelet adhesion, activation, and aggregation to form a plug
• Steps of platelet plug formation: adhesion, secretion, and aggregation

Stage 3: Blood Coagulation

• Triggered by cellular damage and blood contact with foreign surfaces
• Results in the formation of a blood clot through a series of reactions
• Two pathways: extrinsic (tissue factor pathway) and intrinsic (contact activation pathway)

Coagulation Cascade

• Involves seven separate steps
• Requires contact with tissue factors external to the blood or exposure to collagen
• Intrinsic pathway involves factor XII activation
• Extrinsic pathway involves tissue thromboplastin release from traumatized tissue

Serum and Plasma

• Serum: liquid remaining after blood has clotted
• Plasma: liquid remaining when clotting is prevented with an anticoagulant

Fate of Blood Clots

• Plasmin digests blood clots
• Platelet-derived growth factor stimulates smooth muscle cells and fibroblasts to repair damaged blood vessel walls

Prevention of Blood Clotting

• Smooth lining of blood vessels discourages platelet accumulation and clotting factors
• Fibrin absorbs thrombin and prevents clotting reaction from spreading
• Cells like basophils and mast cells secrete heparin (an anticoagulant)
• Dynamic blood flow

Abnormal Blood Clotting

• Thrombus: abnormal intravascular clot attached to a vessel wall
• Emboli: freely floating clots
• Factors causing thromboembolism include roughened vessel surfaces, imbalances in clotting-anticlotting systems, slow-moving blood, and release of tissue thromboplastin

Coagulation Defects

• Vitamin C deficiency: lack of stable collagen (in elderly, alcoholics)
• Hepatic failure: most clotting factors are made in the liver
• Vitamin K deficiency: required for prothrombin, VII, IX, and X
• Hemophilia: excessive bleeding due to deficiency of clotting factors
• Thrombocytopenia: bleeding from small capillaries and blood vessels due to low platelet count

Anti-Hemostatic Drugs

• Heparin: potentiates antithrombin III
• Aspirin: inhibits thromboxane A2 production and platelet activation
• Clopidogrel: irreversible inhibitor of ADP receptor on platelet membranes
• Warfarin: decreases blood clotting by blocking vitamin K epoxide reductase
• Streptokinase: plasminogen activator

Tests for Hemostasis

• Platelet disorder tests: bleeding time (increased in thrombocytopenia)
• Coagulation disorder tests: clotting time, partial thromboplastin time (PTT), and prothrombin time (PT)

This quiz covers the physiology of hemostasis, focusing on platelets, their formation, structure, and functions.