Hemostasis and Platelet Physiology Lecture Notes

These flashcards provide a comprehensive review of hemostasis, including vascular components, endothelial functions, platelet physiology, and the coagulation cascade based on lecture notes.

Hemostasis

Derived from Greek meaning “The stoppage of blood flow”; the process that retains blood within the vascular system, localizes reactions to injury sites, and re-establishes blood flow through repair.

Maintenance of circulatory hemostasis

Achieved through the process of balancing bleeding (hemorrhage) and clotting (thrombosis).

Extravascular Component

Involves tissues surrounding a vessel; hemostatic ability depends on the bulk, type, and tone of the surrounding tissue.

Thromboplastin

A component released by intact tissues when vessels are injured to aid in hemostasis.

Vascular Component

Involves the blood vessels (capillaries, arteries, veins, arterioles, and venules) in which blood flows.

Tunica Intima

The inner tubular cavity of a blood vessel consisting of a single layer of endothelium thickened by subendothelial connective tissue and elastic fiber.

Tunica Media

The thickest coat of a blood vessel, composed of smooth muscle and elastic fibers.

Tunica Adventitia

The outer layer of a blood vessel consisting of fibrous connective tissue containing autonomic nerve endings.

Endothelium

A squamous epithelium functioning in the formation of clots and the prevention of clot lysis.

Collagen and Elastin

Regulates the permeability of the inner vessel wall and provides the principal stimulus to thrombosis following injury to a blood vessel.

Plasminogen Activator

A substance that activates plasminogen to ensure the rapid lysis of fibrin clots.

Prostacyclin ($PGI_2$)

Synthesized from prostaglandin precursors via the eicosanoid pathway; inhibits platelet aggregation and adhesion and acts as a vasodilator.

Intravascular Component

Key components are platelets and biochemical procoagulants in the plasma.

Vasoconstriction

The contraction of the blood vessel wall to control bleeding and prevent exsanguination, promoted by epinephrine and serotonin.

EX_TRINSIC COAGULATION PATHWAY

Initiated by the release of tissue thromboplastin (Factor III) from an injured vessel.

INTRINSIC COAGULATION PATHWAY

Initiated by the activation of Factor XII through contact with exposed collagen.

Nitric Oxide

Induces smooth muscle relaxation (vasodilation), inhibits platelet activation, and promotes angiogenesis.

Tissue Factor Pathway Inhibitor (TFPI)

Controls the activation of the extrinsic coagulation pathway by limiting the TF:VIIa:Xa complex.

Thrombomodulin

Absorbs thrombin and, with the help of EPCR, catalyzes the activation of the Protein C pathway.

Protein C

Downregulates coagulation by digesting activated factors V and VIII, thereby inhibiting thrombin formation.

Heparan Sulfate

A glycosaminoglycan that enhances the activity of antithrombin to inhibit thrombin.

CD39

An enzyme that converts ADP to AMP, preventing platelets from aggregating.

13-Hode (Hydroxyoctadecadienoic acid)

Derived from the lipoxygenase pathway; helps prevent the adhesion of platelets.

Von Willebrand Factor (VWF)

A large multimeric glycoprotein stored in Weibel-Palade bodies that acts as a bridge binding platelets to exposed subendothelial collagen.

ADAMTS13

Secreted from endothelial cells; it cleaves large VWF multimers into shorter chains to support normal platelet adhesion.

P-selectin

An adhesion molecule that promotes platelet and leukocyte binding.

Tissue Plasminogen Activator (TPA)

Secreted by endothelial cells to activate fibrinolysis by converting plasminogen to plasmin to digest fibrin.

Plasminogen Activator Inhibitor-1 (PAI-1)

A control protein that inhibits plasmin generation and fibrinolysis.

Thrombin Activatable Fibrinolysis Inhibitor (TAFI)

Activated by thrombin bound to thrombomodulin; slows fibrinolysis and increases the tendency for thrombosis.

Primary Hemostasis

The short-lived initial response to vascular injury involving vessels and platelets to form a platelet plug.

Secondary Hemostasis

The delayed, long-term response involving the interaction of plasma clotting factors to form a stable fibrin mesh.

Platelets

Anucleated, light blue cytoplasm cells with fine red-purple granules; average diameter of $2$ to $4 \text{ um}$.

Platelet Adhesion

The property by which platelets roll and cling to nonplatelet surfaces, mediated by GP Ib/IX/V receptors and VWF.

Platelet Aggregation

The property by which platelets bind to one another using GP IIb/IIIa receptors, $Ca^{+2}$, and fibrinogen.

Glanzmann Thrombasthenia

A disease characterized by a lack of the GP IIb/IIIa receptor on platelets.

Thromboxane $A_2$ ($TxA_2$)

A vasoconstrictor and mediator of the platelet release reaction that stimulates aggregation by releasing $Ca^{2+}$ from dense tubules.

Aspirin

Prevents clot formation by inhibiting the enzyme cyclooxygenase, which is necessary for Thromboxane production.

Platelet Release Reaction

The discharge of granule contents (Factor V, VWF, Factor VIII, fibrinogen, $Ca^{2+}$, ADP) essential to clotting and repair.

Serotonin

A substance stored in platelet dense granules that helps the blood vessel to constrict.

Substrate

A classification of clotting factor that acts as a material for another factor; Factor I (Fibrinogen) is the most significant.

Cofactor

Clotting factors like V, VIII, HMWK, and Prekallikrein that hasten the reaction of enzymes.

Serine Protease

Enzymes synthesized as inactive zymogens with serine at their active site; includes factors II, VII, IX, X, XI, and XII.

Transglutaminase

An enzyme that catalyzes the transfer of amino groups; Factor XIII is the only clotting factor in this category.

Contact Group

Factors XII, XI, HMWK, and Prekallikrein; requires contact with a negative charge (collagen in vivo, glass in vitro) for activation.

Prothrombin Group

Factors II, VII, IX, and X; these are Vitamin K dependent for the carboxylation of glutamic acid.

Fibrinogen Group

Factors I, V, VIII, and XIII; they are consumed whenever a clot is formed and are absent in serum.

Prothrombin (Factor II)

The inert precursor of thrombin with a half-life of almost $3$ days; 70\text{%} is consumed during clotting.

Thrombin (Factor IIa)

The main enzyme of coagulation; it cleaves fibrinopeptides A and B, activates cofactors V and VIII, and initiates platelet aggregation.

Factor III (Tissue Factor)

Lipoprotein complex from tissues (brain, lung, placenta) capable of converting prothrombin to thrombin.

Factor IV (Calcium)

An ionized mineral necessary for the activation of thromboplastin and the conversion of prothrombin to thrombin.

Extrinsic Tenase Complex

A complex composed of Factor VIIa, Factor III (Tissue Factor), and $Ca^{+2}$.

Intrinsic Tenase Complex

A complex composed of Factor IXa, Factor VIIIa, $Ca^{+2}$, and PF3 (phospholipid).

Prothrombinase Complex

A complex composed of Factors Xa, Va, $Ca^{+2}$, and PF3 that acts directly on prothrombin (Factor II) to produce thrombin (IIa).

Common Pathway

The final stage of coagulation beginning with the activation of Factor X and ending with stabilized fibrin.

aPTT (Activated Partial Thromboplastin Time)

A laboratory test used to evaluate the intrinsic and common pathways of coagulation.

PT/INR (Prothrombin Time)

A laboratory test used to evaluate the extrinsic and common pathways of coagulation.