D’YOUVILLE COLLEGE
BIOLOGY 108/508 - HUMAN ANATOMY & PHYSIOLOGY II
LECTURE # 15
BLOOD V
HEMOSTASIS
11.
Platelets and Hemostasis:
• platelets (thrombocytes): bits of granulated cytoplasm formed by
fragmentation of megakaryocytes from bone marrow (fig. 17 - 12); formation
regulated by thrombopoietin; normal platelet count is approximately 300,000/l.
- platelets contain serotonin, platelet-derived growth factor (PDGF), ADP,
Ca2+, & various enzymes
- participate in plug formation, vascular spasm response, coagulation
cascade, clot retraction
• hemostasis: 'stoppage of blood' = mechanisms that prevent blood loss; three
main steps (fig. 17 - 13) -- vascular spasm (vasoconstriction), platelet plug formation,
& clotting (coagulation) of blood, processes that involve participation of platelets,
procoagulants, & anticoagulants (control activity of procoagulants)
• vascular spasm (vasoconstriction): myogenic (direct response to injury to
vascular smooth muscle), neurogenic (reflexes triggered by pain receptors), and
humoral components (serotonin & thromboxane)
• hemostatic (platelet) plug formation:
- platelet aggregation - occurs as platelets get sticky upon exposure to
collagen fibers, platelets clump, forming plug, and adhere to collagen (potentiated
by von Willebrand factor - links collagen & platelets)
- degranulation - occurs concurrently with aggregation, releasing of
platelet contents to prolong vascular spasm, promote further aggregation
• procoagulants: (synthesis of several, in liver, requires vitamin K); some
important ones are (table 17 - 3):
- factor I: fibrinogen
- factor II: prothrombin
- factor III: thromboplastin
- factor IV: calcium ion
- factor VIII: antihemophilic globulin
- also factors XII (Hageman), V, & X
Bio 108/508
lec. 15 - p. 2
• coagulation cascade (fig. 17 - 14):
- formation of prothrombin activator: involves two pathways, both
extensively involving calcium ion, & both activating factor X (facilitated by V)
- 1) extrinsic -- faster, initiated by tissue thromboplastin
- 2) intrinsic -- slower, but more complete; initiated by platelet factor 3
(derived from platelet membranes), & requiring interaction of larger number of
clotting factors (all from plasma); may also be initiated by Hageman factor in
response to contact with negatively charged surfaces
- activation of prothrombin: conversion of prothrombin to thrombin
(powerful enzyme of clotting -- catalyzes own formation)
- fibrin formation and polymerization (fig. 17 - 15): catalyzed by
thrombin, fibrinogen (soluble) is converted to fibrin, which polymerizes, forming
insoluble meshwork (stabilizes platelet plug & traps formed elements in mesh -->
gels blood)
• clot retraction - contractile proteins from platelets draw fibrin meshwork
tighter, expressing serum, & consolidating clot
• clot dissolution:
- plasminogen system (profibrinolysin) activated (by Hageman factor,
thrombin, etc.) to plasmin (fibrinolysin) to dissolve clot
• anticoagulants:
- help keep procoagulants in check in healthy vessels: heparin (from mast
cells) & antithrombin (plasma protein) inhibit thrombin and other components of
intrinsic pathway; swift blood flow (normal) dilutes clotting factors; healthy
endothelial cells produce substances that inhibit platelets and procoagulants
• disorders: failure of balance between procoagulant and anticoagulant
activity
- thromboembolic conditions (intravascular clots) result from heightened
activity of procoagulants; danger lies in occlusion of blood vessels, by clots or by
pieces of clot (emboli)
- bleeding disorders arise from deficiency of platelets (thrombocytopenia),
or procoagulant deficiencies (notably hemophilias), or from overuse of
anticoagulant therapy with heparin or warfarin (coumadin)