q3: primary hemostasis, secondary hemostasis

initiated by the exposure of platelets to the subendothelial connective tissue components blood vessels (Collagen, microfilaments, basement membranes).

Primary hemostasis

First phase of hemostasis in which the blood vessels contract to seal the wound and platelets and von Willebrand factor fill the open space by forming a platelet plug.

Primary hemostasis

Primary vascular response

Vasoconstriction

synthesis of stromal components

Angiogenesis

vascular tone regulation

Coagulation

special metabolic functions (blood vessel will undergoes vasodilation)

Inflammation

Inhibits Platelet activation

Prostacyclin (PGI2)

A vasodilator that is synthesized through the eicosanoid pathway

Prostacyclin (PGI2)

Stimulates vasodilation

ATP

Endothelial surface receptor for thrombin

Thrombomodulin

Binds and inactivates thrombin and enhances anticoagulant and fibrinolytic action of protein C found in the plasma

Thrombomodulin

Coats the endothelial cell surface and weakly enhances activity of anti-thrombin III

Heparan Sulfate

Converts plasminogen to plasmin, which plays important role in fibrinolysis

TPA

Protein secreted by endothelium into subendothelium; required for plt adhesion

Von Willevbrand factor (vWF)

The Storage site of vwf in endothelium

Weibel Palade bodies

The Storage site of vwf in platelets or megakaryocytes

alpha granules

has been described as a "carpet" on which activated platelets assemble

Von Willevbrand factor (vWF)

It transports the procoagulant factor VIII.

Von Willevbrand factor (vWF)

Reversible; seals endothelial gaps, some secretion of growth factors, in arterioles

Platelet Adhesion

Platelets roll and cling to nonplatelet surfaces

Platelet Adhesion

Requirements: VWF, exposed subendothelial collagen or fibronectin, & GP Ib/IIb or the GP Ib/IX/V complex

Platelet Adhesion

Platelet adhesion to subendothelial connective tissues, especially collagen, occurs within __ minutes after a break in the endothelium.

1 to 2

Morphological and functional change in plates; irreversible

Platelet Activation

Cyclooxygenase (from the platelets) metabolizes arachidonic acid to form prostaglandin enderoperoxides, which are converted to thromboxane A2 (a vasoconstrictor and a platelet stimulator, causing platelet secretion and aggregation)

Platelet Activation

inhibits cyclooxygenase pathway (remission after 7 to 10days)

Aspirin

Platelets discharge the contents of their granules

Platelet Secretion

Irreversible; occurs during aggregation, platelet contents are secreted, essential to coagulation

Platelet Secretion

Following activation, platelet undergoes a shape change most probably caused by contraction of microtubules

Platelet Secretion

From a disk shape to spherical shape with the extrusion of numerous pseudopods

Platelet Secretion

Platelet granules move to the center of the platelets and fuse with the open canalicular system connected to the outside of the platelet; in this way the content of the granules are extruded to the outside

Platelet Secretion

Platelets adhere to each other (Platelet to platelet)

Platelet Aggregation

Irreversible; occurs during aggregation, platelet contents are secreted, essential to coagulation

Platelet Aggregation

Simultaneously with platelet release, platelet stimulating agents (collagen, ADP, epinephrine, thrombin) bind to the platelets, causing then to adherence to one another

Platelet Aggregation

Platelet stimulating agents such as collagen, ADP, epinephrine, thrombin binds to platelets, causing them to adhere to one another. Fibrinogen binds to GP IIb/

IIIa receptors on adjacent platelets and joins them together in the presence of ionized calcium

Platelet Aggregation

Fibrinogen is necessary as cofactor for

platelet aggregation

provides the basis of consolidation and stabilization of platelet/hemostatic plug

Fibrinogen

Coagulation factors are mostly produced by the

liver

originally thought as activated Factor Va, but is non-existent

Factor VI

Numeral: I

Preferred name: __

Fibrinogen

Numeral: II

Preferred name: __

Prothrombin

Numeral: III

Preferred name: __

Tissue factor

Numeral: IV

Preferred name: __

Calcium

Numeral: V

Preferred name: __

Proaccelerin

Numeral: VII

Preferred name: __

Proconvertin

Numeral: VIII

Preferred name: __

Antihemophilic factor (AHF)

Numeral: IX

Preferred name: __

Plasma thromboplastin component (PTC)

Numeral: X

Preferred name: __

Stuart-Prower factor

Numeral: XI

Preferred name: __

Plasma thromboplastin antecedent

Numeral: XII

Preferred name: __

Hageman factor

Numeral: XIII

Preferred name: __

Fibrin stabilizing factor

Numeral: HMWK

Preferred name: __

Fitzgerald factor

Numeral: Pre Kallikrein

Preferred name: __

Fletcher factor

AKA Prethrombin

Prothrombin / II

AKA Tissue thromboplastin

Tissue factor / III

AKA Ionized calcium

Calcium / IV

AKA Labile factor / Accelerator globulin

Proaccelerin / V

AKA Stable factor / Serum prothrombin conversion accelerator (SPCA), Autoprothrombin I

Proconvertin / VII

AKA Antihemophilic factor A

Antihemophilic globulin (AHG)

Platelet cofactor I

Antihemophilic factor (AHF) / VIII

AKA Christmas factor

Antihemophilic factor B

Platelet cofactor II

Plasma thromboplastin component (PTC) / IX

AKA Stuart factor

Prower factor

Autoprothrombin III

Thrombokinase

Stuart-Prower factor / X

AKA Antihemophilic factor C

Plasma thromboplastin antecedent / XI

AKA Glass factor

Contact Factor

Hageman factor / XII

AKA Laki- Lorand factor

Fibrinase

Plasma transglutaminase

Fibrinoligase

Fibrin stabilizing factor / XIII

AKA Contact activation cofactor

William's factor

Flaujeac Factor

Fitzgerald factor / HMWK

Zymogens/Enzyme precursors (7)

Factor II, VII, IX, X, XI, XII, PK

Serine Proteases (7)

Factor IIa, VIIa, IXa, Xa, XIa, XIIa, Kallikrein

Cofactor (4)

Factor V, VIII, III, HMWK

Fibrinogen group (4)

Factors I, V, VIII, XIII

Thrombin sensitive

Fibrinogen group

Consumed during coagulation

Fibrinogen group

Absent in serum

Fibrinogen group

Not absorbed by barium sulfate or aluminum hydroxide

Fibrinogen group

Increases in inflammation, pregnancy, stress and fear, oral contraceptives

Fibrinogen group

Largest group and most concentrated group

Fibrinogen group

Calcium dependent

Fibrinogen group

Prothrombin group (4)

Factors IX, X, VII, II

Vitamin K dependent

Prothrombin group

Not consumed during coagulation

Prothrombin group

Absorbed by barium sulfate or aluminum hydroxide (Note: Not seen in absorbed plasma)

Prothrombin group

Increases in pregnancy, and oral contraceptives

Prothrombin group

Calcium dependent

Prothrombin group

Contact group (4)

Factor XII, XI, HMKW, PK

Not consumed during coagulation

Contact group

Not absorbed by barium sulfate or aluminum hydroxide

Contact group

Calcium independent

Contact group

Intrinsic (6)

Factors: VIII, IX, XI, XII, HMWK, PK

Extrinsic (2)

Tissue factor (III) and Factor VII

Common (5)

Factors: I, II, V, X, XIII

Negative charge molecules

In vivo = collage; In vitro= silica glass surface

Intrinsic

Tissue thromboplastin or tissue factor

Extrinsic

Tenase enzymes (intrinsic and extrinsic tenase)

Common

thrombin cleaves fibrinopeptides A and B to form fibrin monomer. Fibrin monomers polymerize due to the affinity of thrombin-cleaved positively charged E domains for negatively charged D domains of other monomers. Factor XIIIa catalyzes the covalent cross-linking of gamma chains of adjacent D domains to form an insoluble stable fibrin clot

Stabilized fibrin clot formation

generation of prothrombin complex

a. Stage 1

b. Stage 2

c. Stage 3

a. Stage 1

conversion of prothrombin to thrombin

a. Stage 1

b. Stage 2

c. Stage 3

b. Stage 2

conversion of fibrinogen to fibrin

a. Stage 1

b. Stage 2

c. Stage 3

c. Stage 3

Thought of as a complex series cascading reactions involving development of enzymes from their precursor (zymogens, procoagulants, proenzymes).

coagulation cascade

Most of the substances necessary for coagulation are present in an inert form and must be converted to an activated state.

coagulation cascade

As one enzyme is formed it the becomes available to convert the next zymogen to its activated enzyme.

coagulation cascade

Intrinsic tenase (4)

IXa, VIIIa, Calcium, Plt phospholipid (PF3)

Extrinsic tenase (4)

VIIa, Tissue factor, Calcium, Plt phospholipid (PF3)