Hemostasis: Blood coagulation and fibirinolysis - Part 2 Flashcards
In general, the aim of the third step of Hemostasis, Blood Coagulation (secondary hemostasis), is what?
Convert soluble fibrinogen to insoluble fibrin
The conversion of fibrinogen to fibrin requires what?
Thrombin
The formation of Thrombin occurs via which 2 pathways?
1) Intrinsic
2) Extrinsic
Tissue injury initiates the release of what to being the extrinsic pathway.
Tissue factor (Factor III or Thromboplastin)
Thromboplastin is also known as what?
Factor III (Tissue factor) - initiator of Extrinsic pathway.
Factor VII, which is part of the extrinsic pathway, is activated by what?
Tissue factor (Thromboplastin / Factor III)
Factor VIIa and tissue factor, in the presence of ____ and ____ activate _______.
Calcium
Platelet phospholipids
Factor X.
Rough endothelial surface, due to pathological processes, lead to the exposure of collagen, which initiates what in the Instrinsic pathway?
Factor XII (Hageman factor)
What is factor XII, the first factor initiated in the Intrinsic pathway, also known as?
Hageman factor
Factor XIIa, a factor in the Intrinsic pathway, activated what?
XI –> XIa
Factor XIa of the intrinsic pathway activates what?
IX —> IXa
Thrombin (IIa) activates what in the intrinsic pathway?
VIII –»> VIIIa
What in the intrinsic pathway activates factor X
IXa,
VIIIa,
platelet phospholipids and Ca2+
What does Thrombin (IIa) activate in the common pathway?
V –> Va;
Firbinogen (I) —-> Fibrin (Ia);
XIII–> XIIIa
What does Xa combine with in the common pathway? To form what?
Va,
Tissue phospholipids,
Ca2+
- Forms prothrombinase complex
What does the prothrombinase complex do in the common pathway?
Splits prothromin (II) to thrombin (IIa)
What factor forms Fibrin?
Thrombin (IIa)
What is the role of Factor XIIIa?
- Covalently cross links fibrin monomers to form cross-linked fibrin
- Converts the fibrin polymer (soft clot) to a stable polymer (hard clot)
Fibrinogen is a ____ that is synthesized by the ____.
Plasma protein
liver
The fibrin monomers _______ and are linked to each other via _______, forming the ________.
Aggregate;
Hydrogen bonds;
Fibrin polymer (soft clot)
Specifically, to form the covalent bond, XIIIa acts to do what?
Amino group of lysine on one fibrin molecule + amide nitrogen of glutamine on another fibrin molecule = covalent bond
Factor XIIIa is a…
Highly specific transglutaminase
Ultimate aim of hemostasis is the conversion of ____ to ____ and stabilization of _____ which requires ___.
Firbinogen
Fibrin (4c)
Fibrin (6c)
Thrombin (IIa)
LAB TESTS: defect in clotting cascade results in ______
increased clotting time
LAB TESTS: An extrinsic pathway defect results in:
Increased prothrombin time (INR)
LAB TESTS: An intrinsic pathway defect results in:
Increased APTT
Vitamin K is required for the hepatic synthesis of what?
Prothrombin (Factor II) VII IX X Proteins C and S
Which amino acid residues of Proteins C and S are acted upon by Vitamin K dependent gamma-carboxylation?
Glutamic acid
What is the coenzyme for gamma-carboxylase?
Vitamin K
gamma-carboxylation forms mature clotting factors that contains _____ and is capable of subsequent activation?
Gamma-carboxyglutamate (Gla)
Gamma-carboxylation allows Ca2+ binding because of what?
2 adjacent negatively charged carboxylate groups
Once gamma-carboxylation allows Ca2+ binding because of two adjacent negatively charged carboxylate groups, The clotting factor-Ca2+ complex can then bind to what?
phospholipids on the platelet membrane
What is INR (Prothrombin time)?
A very sensitive indicator of vitamin K deficiency
