Goueli- Biochemistry of Coagulation Flashcards by Sarah Carlson

What is hemostasis?

Physiological blood clotting in response to injury or vascular leak

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What is thrombosis?

Patholgoic blood clotting

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What is hemorrhage?

Pathologic bleeding

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What are the 4 phases of hemostasis?

Vascular constriction- limits flow of blood to area of injury
Platelets aggregate at site of injury forming loose platelet plug
Fibrin mesh form and entraps the plug
Clot is dissolved in order for normal blood flow to resume

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What are the three types of granules platelets contain?

Electron dense granules
alpha granule
lysosomal granules

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What is a normal platelet level?

150–450,000

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Platelet level <10,000

increased risk of spontaneous hemorrhage

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platelet level <50,000

INcreased difficulty clotting if you’re already bleeding

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What is the ideal platlet count for procedures?

For neurosurgical procedures?

50,000

above 100,000

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What are the fundamental mechanisms involved in platelet function during blood coagulation

Adhesion
aggregation
secretion

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How does primary homeostasis (adhesion) occur?

Platelets adhere to exposed collage at injured site–> release contents of granules–> aggregate

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What mediates the adhesion of platelets to collagen exposed on endothelial cell surfaces?

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What Gp binds directly to exposed collagen?

GpVI

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What does vWF do?

Acts as a bridge between a specific glycoprotein complex on the surface of platelets and collagen fibrils

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Where is vWF produced and stored?

alpha-granules

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What does vWF bind to at the site of injury?

subnedothelial collagen 2. glycoprotein IB on the platelet surface
Factor 8

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What happens in vWF def?

Reduced levels of Factor 8

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What happens in Gp1B def?

Bernard Soulier syndrome

Qualitative defect in platelet–> protein can’t bind to vWF

tx–give someone else’s platelets

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Schistocytes in a blood smear is a sign of….

microangiopathic hemolytic anemia

What are the two most important hallmarks of TPP?

Profound thrombocytopenia

Microangiopathic hemolytic anemia (red cell fragmentation)

TPP is d/t a def in…

ADAMTS13

Def is acquired OR hereditatory

What happens when a platelet binds to collagen?

It causes the platelet to change shape from a flat disc to a spherical cell–>

exposes Gp complex binding sites to fibrinogen and vWF

The binding of platelets leads to the release of arachidonic acid. What does arachidonic acid do?

Leads to an increase in the production and release of TXA2.

What is TXA2?

Potent vasoconstrictor

Induces platelet aggregation

What does fibrinogen do?

Circulates in the blood Binding of fibrinogen allows platelets to adhere to one another--> soft clot

What are the two pathways that lead to the formation of a fibrin clot and what do they do?

Intrinsic and extrinsic converge on a common pathway that promotes clot formation

Where are most coagulation factors synthesized?

the liver

How do you generate fibrin?

By promoting thrombin activity

What happens in the extrinsic pathway?

factors 9a and 10a assemble w/ cofactors (8a and 10a) on the surface of the aggregated platelet--> generation of large amounts of 10-a and thrombin (IIa)--> conversion of fibrinogen to fibrin

What activates the extrinsic pathway? the intrinsic?

It responds to release of TF Hyperlipidemic states or bacterial infiltration

The intrinsic pathway requires what clotting factors? It ultimately leads to....

Factors 8,9,10,11,12 Converstion of factor 10 to 10a

What is factor 8a?

A cofactor in the clotting cascade that is activated by thrombin

What occurs in the common pathway?

Factor 5 a binds to specific receptors on surfaces of activated platelets and forms complex w/ prothrombin and factor 10a. Factor 10a converts prothrombin to thrombin

What regulates thrombin?

Thrombin inhibitors!

What are the thrombin inhibitors?

Antithrombin III (can also inhibit factors 9,10, 11, 12

What potentiates the activity of thrombin?

heparin

What does thrombin do to Protein S and C?

Thrombin forms a complex w/ another protein to convert protein C to protein Ca. Protein S and APC degrade factors 5a and 8a and decrease thrombin production. Proteins C and S put the breaks on coagulation

What is fibrinolysis?

Degradation of fibrin in a clot by plasmin

What factors require Vit K gamma carboxylation for optimal function?

Factors 2,7,9,10, C and S **takes place in the hepatocyte before release of the clotting factor

What happens if you're def in vit K?

you'll have an issue w/ clotting/bleeding

What is warfarin?

Anticoagulant Has structure resembling vit K

What does warfarin do?

Competes w/ fvit K preventing gamma carboxylation of glutamate residues in Factors 2,7,9,10, C adn S

What happens to the noncarboxylated blood clotting precursors?

They increase in both blood and plasma but can't promote blood coagulation because they can't bind Ca and therefore can't bind to the phospholipid membrane for activation

What else does warfarin block?

Proteins S and C--so you can't turn down coagulation *primary reason why there needs to be a "bridge w/ heparin"

How do heparins work?

Anticoagulant They bind to and activate ATIII which leads to thrombin inactivation Also block activity of factors 8a, 9a, 10a