Coagulation

1. enzyme precursors

2. Cofactors

3. Substrates

3 categories of coagulation factors

Fibrinogen (factor I) - soluble protein acted upon by the main coagulation enzyme thrombin (factor IIa) to form fibrin (elastic-thread-like protein that forms a mesh to trap platelets and cells)

What is the main coagulation substrate.

• Extrinsic - tissue factor pathway, started by tissue factor (TF) found in the membranes of cells in the tissues

• Intrinsic - contact activation pathway, coagulation factors circulating in the bloodstream

Two main pathways of the coagulation cascade (where each factor activates another factor)

Prothrombin test (PT)

Test used to evaluate extrinsic pathway function and monitor coumarin therapy

Activated partial thromboplastin test (APTT)

Test used to evaluate intrinsic pathway and monitor heparin therapy

• Initiating the coagulation process

• Producing large amounts of thrombin on the surface of activated platelets

The extrinsic pathway is responsible for __________. The intrinsic pathway is responsible for __________.

1. Vasoconstriction

2. Primary platelet plug

3. Secondary hemostatic plug (clot)

4. Fibrinolysis

4 responses when a vessel is injured

von Willebrand factor (vWF)

Damage to the blood vessel endothelial cells (ECs) exposes a gluelike substance called ________, which causes platelets to stick to the damage tissue

convert fibrinogen to soluble fibrin strands for clot formation

Primary role of thrombin

Amplification

When more thrombin is needed to create fibrin (stabilizes the platelet plug). Thrombin amplifies its own production by activating a sequence of coagulation factors

propagation

When large amounts of thrombin needed to create fibrin are propagated on the surface of activated platelets as more and more of them are drawn to the injury

1. Dissolving clots that form w/in intact vessels

2. Removing hemostatic clots as the tissue heals

2 functions of fibrinolysis

• Synthesizes coagulation factors (prothrombin, fibrinogen)

• Bile salts to absorb vit K (needed to synthesize some of the coagulation factors)

• Mast cells (tissue basophils) produce heparin (anticoagulant)

Role of the liver in hemostasis

pathological, widespread clotting and fibrinolysis. Coagulation factors are consumed and bleeding occurs

Describe disseminated intravascular coagulation (DIC)

• D-dimer

• Factor assays

• Fibrin degradation products (FDP)

• Partial thromboplastin time (PTT or aPTT)

• Platelet function assay (PFA)

• Prothrombin time (PT)

List tests of the hemostatic process