11: Hemostasis

what is hemostasis?

process by which blood vessels are repaired after injury

3 players in hemostasis

endothelium, platelets, coagulation cascade

pathologic correlates to hemostasis

thrombosis and hemorrhage

thrombosis

blood clot in uninjured vessel

hemorrhage

blood loss at site of injury, secondary to vascular damage

4 stage sequence of hemostasis IN ORDER

1. vasoconstriction, 2. primary hemostasis, 3. secondary hemostasis, 4. formation of permanent plug

what causes vasoconstriction? (step 1 of hemostasis)

release of endothelin by endothelial cells

what does endothelin do?

limits escape of RBCs and proteins from damaged vessels

goal of primary hemostasis (step 2 of hemostasis)

form platelet plug

PPP

primary (hemostasis) platelet plug

cells involved in primary hemostasis (step 2)

collagen, endothelium, vWF, fibrinogen, platelets

what do platelets contain?

ADP and thromboxane A2

mechanism of primary hemostasis (step 2)

platelets attach to exposed ECM via vWF, change shape, release secretory granules (ADP/thromboxane A2), plug is formed

vWF

von Willebrand factor

what do ADP and thromboxane A2 do? (secretory granules released by platelets in primary hemostasis)

cause vasoconstriction and promote further platelet aggregation

what receptor do platelets use to bind to vWF in primary hemostasis?

Gp1b receptor

what happens when platelets change shape in primary hemostasis?

they are increasing their SA

what does thrombin cleave on platelets in primary hemostasis?

PAR-1

what surface receptor do activated platelets express in primary hemostasis?

Gp2b-3a

alpha granules secreted by platelets in primary hemostasis

PDGF and vWF

PDGF

platelet derived growth factor

dense granules secreted by platelets in primary hemostasis

ADP and thromboxane A2

what does surface receptor Gp2b-3a bind in primary hemostasis?

fibrinogen

what does fibrinogen do when it binds to platelets?

help platelets stick together

secondary hemosasis

activation of coagulation cascade, cementing platelets into plug

tissue factor in secondary hemostasis

thromboplastin

what secretes tissue factor in secondary hemostasis?

adjacent endothelial cells

what initiates the coagulation cascade? (secondary hemostasis)

tissue factor (thromboplastin)

goal of secondary hemostasis

form FIBRIN PLUG

what does thrombin do in the coagulation cascade (secondary hemostasis)?

converts fibrinogen to fibrin (insoluble protein)

what holds together the coagulation cascade (secondary hemostasis)?

calcium ions

what factors are used by the intrinsic pathway? (secondary hemostasis)?

12, 11, 9, 8

mechanisms of intrinsic pathway (secondary hemostasis)?

factor 12 activates 11, kallikrein formed, activates 9. factor 8 gets activated by thrombin.

what 2 factors of the intrinsic pathway (secondary hemostasis) initiate the COMMON PATHWAY?

factors 8 and 9

what factor is used by the extrinsic pathway (secondary hemostasis)?

7

factor 7 (tissue factor)

only present in activated endothelium

how is common pathway activated by the extrinsic pathway (secondary hemostasis)?

factor 7 and Ca together activate factor 10, initiates common pathway

factors in the common pathway (secondary hemostasis)?

10, 5, 2, 1

common pathway mechanism (secondary hemostasis)?

factor 10 activates 2 into 2a, which cleaves factors 1 and 5

factor 2a (common pathway) (secondary hemostasis)

thrombin

factor 1 (common pathway) (secondary hemostasis)

fibrinogen

factor 1a (common pathway) (secondary hemostasis)

fibrin

what does fibrin (factor 1a) do in the common pathway? (secondary hemostasis)

adds to platelet plug, making it a solid clot

what is the end results of the coagulation cascade?

fibrin plug

is formation of fibrin plug acute or chronic?

ACUTE! (occurs 2nd to vascular injury)

what is fibrosis?

scar tissue that is part of the healing process, and is CHRONIC

are fibrin and fibrosis the same thing?

NO

what factors are dependent on vitamin K?

10, 9, 7, 2 (remember 1972)

what pathway is the first to fail with anti-coagulant toxicity?

extrinsic pathway (factor 7)

3 different coagulation tests

PT, PTT, Russell's Viper Venom

pathway of PT

extrinsic pathway

what does PT stand for (extrinsic)?

prothrombin time

pathway of PTT

intrinsic

what does PTT stand for (intrinsic)?

partial thromboplastin time

pathway of Russell's Viper Venom Test

common pathway (measures factor 10)

what does BMBT stand for?

buccal mucosal bleeding time

what does BMBT assess?

primary and secondary hemostasis (how long it takes for a standard cut on buccal mucosa to stop bleeding)

von Willebrands disease

defect in primary hemostasis ONLY (platelets don't adhere to ECM)

excessive thrombosis

too much blood coagulation

hemorrhaging

too little blood coagulation

what does DIC stand for?

disseminated intravascular coagulation

what is DIC?

abnormal/excessive generation of thrombin and fibrin in blood, causing increase platelet aggregation and clotting, leads to systemic thrombosis and hemorrhages

what causes release of tissue factor?

massive tissue destruction, sepsis, endothelial injurt

when tissue factor is released, what is activated?

plasmin

what does plasmin o?

causes fibrinolysis

what happens when thrombin, fibrin, and platelet aggregation are INHIBITED?

BLEEDING