Lecture 10 - Hemostasis Part 2 Flashcards
Secondary hemostasis: the main goal is to produce a VERY stable ______ _____ and
the way to do it is binding ______ to the _______ _____ formed during the primary
hemostasis). Remember that for Hemostasis (or clot formation) to occur the initiating step is to have= vascular ______. The parallel activation of _______ and coagulation system occurs at sites of vascular ______.
Secondary hemostasis: the main goal is to produce a VERY stable platelet plug and
the way to do it is binding FIBRIN to the platelet plug (formed during the primary
hemostasis). Remember that for Hemostasis (or clot formation) to occur the initiating
step is to have= vascular injury. The parallel activation of platelets and coagulation
system occurs at sites of vascular injury.
The process of coagulation is dependent upon:
1. Coagulation factors
* Synthesized in the _____
* _______ and ____-______ factors
2. Cells (4)
- Coagulation factors
* Synthesized in the liver
* Enzymatic and non-enzymatic factors - Cells
* Fibroblasts
* Platelets
* Endothelial cells
* Leukocytes
List the enzymatic factors required for the coagulation cascade.
1, 1a, 2, 2s, 7a, 9a, 10a, 11a, 12a
9a = christmas factor
7a = proconvertin
10a = stuart factor
List the non-enzymatic factors required for the coagulation cascade.
5a, 8a, Factor 3/Thromboplastin/Tissue factor
List the Vitamin-K dependent coagulation factors.
Which of these factors has the shortest half life?
For activation dependent on Vitamin K
* Factors II, VII, IX, X
* Factor VII (shortest half-life)
Vitamin K is needed for production of activated coagulant Factors ___, ___, ___, ___
(and ?) –remember most clotting factors
are produced in the ______ (by _____).
So if the patient has ______ disease or failure, you will see a decreased production of clotting factors due to progressive loss of _________ (coagulation tests can be indirect tests of _____ function).
2, 7, 9 10
anticoagulant Prot. C & S
LIVER
hepatocytes
hepatocytes
liver
Inactive precursors (__________) are made functional by Vit. ___-dependent ___ translational _______ of _______ acid residues on the molecules. This process is facilitated by the Vitamin ___ epoxide reductase enzyme. _______ inhibit this enzyme.
procoagulants, K, post, carboxylation, Glutamine
K
Coumarins
An increase in clotting factors remaining in their inactive state is caused by?
Vitamin K Antagonism
What causes Vitamin K Antagonism?
- Coumarin-containing compounds: rodenticides, warfarin, moldy sweet clover
- Fat malabsorption: cannot absorb fat soluble Vit. K
Tissue factor/Thromboplastin starts the ______ cascade after injury.
extrinsic
Coagulation factor IV (4) is called ______ and is needed for the coagulation cascade enzymatic factors to work.
Calcium
Coagulation factor X is called _______ ______ factor and starts the common pathway + cleaves coagulation factor II.
Stuart-Prower
Coagulation factor XII is called the ______ factor and plays a minor role in fibrinolysis.
Hageman
The extrinsic pathway is INITIATED by _______ tissue/cells who consequently release ______ factor which is expressed on ________ at site of vascular injury to activate the ________ path. By expression of this factor, Factor ____ is activated. Then factor ____ in the presence of ____, ____, activates factor _____ to factor ____ to Begin
common pathway. This generates small amounts of _______.
THIS IS THE FIRST STEP of _______ Hemostasis: initiation of ______ generation
____ Factor + ___ = => formation of Factor ___ activation complex.
damaged, Tissue, Fibroblasts, EXTRINSIC, 7, VIIa, TF, Ca2++, F10, 10a, Thrombin, Secondary, Thrombin, Tissue, 7, 10
The intrinsic pathway begins when Factor ____ is exposed to collagen or other negatively charged substances (3?), activating Factor ___ –> ____.
Now Factor ___ activates Factor ___ into Factor ___. With a _______ Ion, Factor _____ activates Factor ___.
Now Factors ___ and ____, along with _______, form a complex to activate Factor ___. The end
The intrinsic pathway begins when F12 is exposed to collagen or other negatively
charge substances (like PLT, phosphates, endotoxins), activating F12. The F12a is activated
Now F12a activates F11 into F11a. With a Calcium Ion, F11a activates F9
Now F9a, F8a and Ca2+ form a complex to activate F10
Note: Factor IX can also be activated by the ?
TF-VIIa complex (cross- over from extrinsic pathway)
F8 is found in the _____ and is often activated by ?
blood, Thrombin (FIIa)
Factor VIII
* Usually circulates as a ___-_______ complex with ______
* The _____ bound to F8 does not participate in the _______ pathway of coagulation
* Functions in hemostasis by promoting
platelet _____ and ______
non-covalent, vWF, vWF, Intrinsic, adhesion, aggregation
The common pathway begins with the activation of factor 10 via _______ or _____ pathways. Now Factor 10a, along with ______, activates Factor ___ to ___.
Now activated ____, _____ bind with Ca to form a complex that promotes activation of
__________ to activated _______. Then, Factor _____ cleaves Fibrinogen (F1) into ______. The last and final step is?
Intrinsic, extrinsic
Now 10a together with Thrombin (2a) from extrinsic pathway activates 5 to 5a
Now activated 10a, 5a bind with Ca to form a complex that promotes activation of
Prothrombin (F2) to activated F2a=thrombin
Now thrombin (F2a) cleaves Fibrinogen (F1) into fibrin (F1a).
F13a (needs Calcium and this cross-links w fibrin strands of the soft clot to form a
hard clot.
The common pathway is the last and final step of the secondary hemostasis
At the same time as the coagulation cascade, the fibrinolytic system is operating.
Fibrin, Factor 1a, is degraded in fibrin _________ products by ______ that originates from fibrin bound _______ in liver.
Removal of fibrin clots is necessary for wound ______ and reestablishment of ______,
also prevents ______.
degradation
PLASMIN, plasminogen, healing, circulation, thrombosis
As a stable fibrin clot is formed then thrombin production ________ and _______ dominates
decreases, fibrinolysis
The fibrin clot is removed by the proteolytic action of ______, which comes from its precursor: ________ (produced in ____
and circulates in _____).
plasmin, Plasminogen, liver, plasma
Name the procoagulant tests.
Name the anticoagulant tests.
