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Hemostasis and Blood Coagulation
Terms in this set (61)
What is hemostasis?
The process by which the body prevents blood loss
What are the four major mechanisms of Hemostasis?
- Platelet plug formation
- Vascular constriction
- Blood coagulation
- Fibrous tissue growth
From where are platelets derived?
As fragments from megakaryocytes
What is the function of the glycoprotein surface coat of platelets?
- It prevents adherence to normal endothelium
- Causes platelets to aggregate to collagen that is exposed following a blood vessel injury
What facilitates the adherence of platelets to damaged vesicular endothelium?
von Willebrandt Factor
What impact does adherence to collagen have on actin and myosin isoproteins in platelets?
It causes them to forcibly contract and release serotonin and thromboxane A (TxA)
What do serotonin and TxA simulate?
What additional substance is secreted when the platelets contract?
What is the function of ADP?
It leads to the formation of the platelet plug
What is the first step in preventing blood loss?
The formation of a platelet plug
Where are the majority of clotting factors synthesized?
In the liver
In what form are clotting factors synthesized?
Most are synthesized as zymogens (inactive forms of protein) with serene protease activity
What stimulates and increases the activity of many of the clotting factors?
What are the two cascades of blood clotting?
Intrinsic and Extrinsic pathways
What is the end point of both blood clotting cascades?
Activation of Stuart Factor (X)
What will activated Stuart Factor initiate?
The final stage of clot formation
What initiates clotting?
The contact system
What are the 4 glycoproteins that make up the contact system?
- Hageman Factor (XII)
- Plasma thromboplastin antecedent (PTA or factor XI)
- High Molecular weight kininogen (MHK)
What does adsorption to an exposed surface or activated platelets stimulate?
Hageman factor and HMK
Activated Hageman factor and HMK...
... activate Prekallikrein to Kallikrein
... additional Hageman factor
(1st positive feedback cycle of cascade!)
Activated Hageman factor and HMK also activates...
... cleaves and activates christmas factor (IX)
Activated Christmas factor..
... activates Stuart Factor (X)
In the extrinsic pathway, activated Hageman factor cleaves...
... proconvertin (VII) to its active form
Does HMK influence the activity of Hageman factor in the extrinsic pathway?
Activated proconvertin (VII) and tissue factor III catalyze...
... the activation of Stuart Factor
What is the primary function of activated Stuart factor?
To cleave the protein prothrombin into thrombin
How does Stuart factor activate prothrombin?
It cleaves prothrombin in two locations on the cleavage domain in order to separate the A and B chains
How does thrombin act as a positive feedback signal?
- It assists in the activation of proconvertin in the extrinsic pathway
- Activates both proaccelerin and anti hemophilic factor in the intrinsic pathway
What is the role of proaccelerin?
It increases the activity of Stuart factor
(which will increases the cleavage of prothrombin)
What is the role of anti hemophilic factor?
It increases the activity of christmas factor
(which will increases the cleavage of prothrombin)
What activates fibrin stabilizing factor (FSF)?
What is the role of fibrin stabilizing factor?
It is necessary to harden clots
What is the primary role of thrombin?
It cleaves fibrinogen into fibrin
(allowing fibrin cross linking to form a soft clot)
What modulates the interaction between Stuart factor and prothrombin?
A binding domain on the A chain of prothrombin
(it contains a large number of gamma-carboxyglutamates)
What causes gamma-carboxyglutamates in the A chain of prothrombin?
Post-transcriptional modification of glutamate residues
What enzyme is responsible for the modification of glutamate residues?
What is utilized by gamma-glutamyl carboxylase?
The reduced form of vitamin K
(results in a carboxylated glutamate while vitamin K is oxidized to an epoxide form)
What returns the epoxide form of Vitamin K back to its original form?
Vitamin K epoxide Reductase
How are the phylloquinone and menaquinone forms of vitamin K obtained?
Either from diet or from gut bacteria (in the quinone form, therefore vitamin k epoxide reductase is necessary)
What are two inhibitors of vitamin K epoxide reductase?
As anti-coagulants, what is the function of warfarin and dicoumarol?
They impede clot formation
Which form of vitamin K inhibits G6PDH?
K3 Synthetic (Menadione)
How does thrombin cleave fibrinogen?
It targets cleavage sites on each alpha and beta subunit to convert fibrinogen to fibrin
What allows numerous fibrin molecules to adhere to one another and form a soft clot?
The exposure of binding sites when fibrinogen is converted to fibrin
What converts a soft clot into a hard clot?
FSF by covalently linking the individual fibrin molecules
What is the role of antithrombin?
It inhibits all active proteases of the clotting cascade except proconvertin
What increases the activity of antithrombin?
Where are high concentrations of heparin found?
In mast cells
What cleaves protein C?
What is the role of activated protein C?
It breaks down proaccelerin and anti hemophilic into non active forms
What causes Hemophilia A?
Sex-linked deficiency of anti hemophilic factor (VIII)
What causes Hemophilia B?
Deficiency in christmas factor (IX)
What is the most common disorder of coagulation?
von Willebrand's disease
Describe type 1 of von Willebrand's disease.
- few sign or symptoms except during trauma
Describe type 2 of von Willebrand's disease
- All subtypes experience some level of clotting deficiency
Describe type 3 of von Willebrand's disease.
- Most severe
- complete dysfunction of protein
- severe mucosal bleeding, bleeding into joints
What is pseudo-vWD?
Referred to as type 4
- normal vWF, platelet receptor dysfunctional
What is the major issue associated with thrombocytopenia?
The lack of formation of platelet plugs
What is the most common cause of thrombocytpenia?
Production of antibodies to platelets
(could be autoimmune or the result of transfusion)
THIS SET IS OFTEN IN FOLDERS WITH...
Cell: Block 3: Lymphatic
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