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Phys. Exam 2 Hemostasis
exam 2 hemostasis and fibrolysis
70
Physiology
Graduate
10/12/2010

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Term
What are the 3 stages of coagulation and the 2 stages of fibrinolysis?
Definition
Coagulation:
1. vascular phase
2. platelet phase
3. coagulation phase- activation of clotting system and clot formation

Fibrinolysis:
4. Clot retraction: contraction of blood clot
5. Clot destruction: enzymatic break down of clot by plasmin
Term
Coagulation is a set of reactions that causes blood to go from a liquid to a ___. It is a defense mechanism against blood loss.
Definition
- gel
Term
Coagulation is initiated by ___ stimuli arising from vascular injury, triggering the ___ and ___ pathways leading to the final three steps. List these final three steps.
Definition
- external
- extrinsic
- intrinsic
1. Prothrombin activator is formed
2. Prothrombin is converted to thrombin
3. Thrombin assists the forming of fibrinogen into a fibrin mesh.
Term
Last 3 steps in coagulation:
- Prothrombin ___ is formed.
- Prothrombin is converted to ___.
- ___ facilitates the joining of ___ into a ___ network
Definition
- activator
- Thrombin
- Thrombin, fibrinogen, fibrin
Term
stimuli to lining of vessel> ___ and other thrombogenic substances exposed> ___ adhere forming a plug>>___ clot forms
Definition
- collagen
- platelets
- fibrin
Term
Primary hemostasis is the time of ___ ____ and is mediated by ___ ___ ___ aka ___. This factor is made by ___ cells and ___.
Definition
- platelet adhesion
- von Willebrand Factor (vWF) aka velcro
- endothelial cells and megakaryocytes
Term
platelet secretion is also called:
Definition
release reaction
Term
platelet secretion aka the release reaction rapidly proceeds ___.
Definition
adhesion
Term
During platelet secretion granules release their contents which are: . The release of the substances results in production of a ____ complex.
Definition
- ADP
- calcium
- vasoactive substances

results in production of phospholipid complex and shape change
Term
During platelet aggregation platelet adherence is promotoded by ___, ___, and ___. This results in a ___ ___ which is reversible. Thrombin converts fibrinogen to fibrin which is reversible.
Definition
- ADP, TxA2, and thrombin
- primary plug
Term
Prothrombin can be activated by the ___ or ___ pathway.
Definition
- intrinsic
- extrinsic
Term
explain intrinsic pathway of activating prothrombin.
Definition
endothelium ruptures and collagen is exposed
Term
explain extrinsic pathway of activating prothrombin:
Definition
- tissue cell trauma causes release of tissue factor, tissue factor acts with calcium
Term
coagulation sequence:

collagen or tissue factor and calcium>> platelets aggregate>> release PF3>>>factor X gets activated >>factor X complexes with calcium ions, PF3, and factor V to form the prothrombin activator complex.
Definition
Term
what makes up the prothrombin activator complex?
Definition
- activated factor X complexed with PF3, calcium, and factor V
Term
give 3 physiological examples of limited proteolysis:
Definition
- digestive enzyme activation
- proinsulin>>insulin
- activation of capsases
Term
Briefly describe in coagulation phase 1 and 2:
Definition
Coagulation phase 1: 2 pathways to prothrombin activation

Coagulation phase 2: Pathway to Thrombin
Term
prothrombin activator catalyzes the transformation of ___ to ___ and also helps polymerize fibrin into a fibrin clot.
Definition
- prothrombin
- thrombin
Term
what two important sequences does fibrin have that allows for its polymerization?
Definition
- Gly-His-Arg
- Gly-Pro-Arg
Term
the cross-linking mechanism of fibrin clot is catalyzed by ___ __.
Definition
- factor XIII
Term
List the 4 components that limit fibrin formation:
Definition
- tissue factor pathway inhibitor
- serine protease inhibitors
- protein C system
- fribrinolytic system
Term
The tissue factor pathway inhibitor inhibits ___ ___ ___ ___ and thereby inhibits ___ formation.
Definition
- factor VIIa tissue factor
- thrombin formation
Term
Serine protease inhibitors neutralize ___ and ___ ___, thereby inhibiting ___ formation and activity.
Definition
- thrombin
- factor Xa
Term
Protein C system causes proteolysis of factors __ and ___, which inhibits ___ formation.
Definition
- Va and VIIIa
- thrombin
Term
Fibrinolytic system causes proteolysis of ___ and removes the excess fibrin clot.
Definition
- fibrin
Term
What system regulates Secondary (excess) coagulation?
Definition
- Fibrinolytic System
Term
The major effector of the fibrinolytic system is ___.
Definition
- plasmin
Term
___ converts plasminogen to ___. This enzyme requires ___ as a cofactor.
Definition
-tPA
- plasmin
- fibrin
Term
plasmin binds to ___ and degrades ___.
Definition
- fibrin
- clots
Term
the fibrinolytic system puts the breaks on blood coagulation by breaking down ___ and ___ protelytically with ___.
Definition
- fibrinogen
- fibrin
- plasmin
Term
Activators of plasminogen are present in the ____, ___ of blood vessels, and in the ___. These activators are proteolytic enzymes.
Definition
- plasma
- endothelium of blood vessels
- urine
Term
The urine plasminogen activator, called ____, does not require ___ as a cofactor like the other plasminogen activators do.
Definition
- urokinase
- fibrin
Term
Urokinase may be the endothelial factor which has filtered through the renal glomeruli or it may be formed in the renal tubules. Urokinase is currently used for what?
Definition
- thrombolytic agent for treatment of myocardial infarction
Term
list the plasminogen activators:
Definition
- urokinase
- streptokinase
- tissue plasminogen activators (tPAs)
Term
tPAs and urokinase can be used as ____ factors to counteract acute MIs.
Definition
- antithrombotic
Term
plasmin breaks up fibrin and fibrinogen. the break down products of fibrin feed back and inhibit the formation of more fibrin.
Definition
Term
3 main functions of the fibrinolytic system:
Definition
1. brake on the clotting system
2. causes dissolution of fibrin which could block circulatory flow
3. cleans up fibrin debris as blood passes through capillaries
Term
small amounts of plasminogen are being ___ activated to plasmin within circulation. however, circulating plasmin is usually absent in detectable quantities b/c:
Definition
- continuously

absent b/c:
- anti plasminogen activators (inhibitors of activators) are usually in the plasma
Term
In patients with shock, undergoing thoracic surgery, or in eclampsia with pregnancy, ____ ___ may occur b/c there are too many antiplasmins in the plasma preventing plasmin from working.
Definition
- fibrinolytic crisis
Term
Fibrin acts as an ____ by binding to thrombin.
Definition
- anticoagulant
Term
3 ways fibrin is an anticoagulant:
Definition
- binds thrombin preventing thrombin from having positive feed back effects on coagulation
- prevents thrombin from speeding up production of prothrombin activator via factor V
- prevents thrombin from accelerating the intrinsic pathway by activation of platelets
Term
free thrombin, not absorbed by fibrin, may be inactivated by ____ __.
Definition
- antithrombin III
Term
Heparin is an ___ that inhibits __ activity after combining with ___ ___ ___.
Definition
- anticoagulant
- thrombin
- antithrombin III
Term
Coumadin and dicoumarol are ____ that are ____ ___.
Definition
- anticoagulants
- vitamin K antagonists
Term
aspirin works as an ___ b/c it has ___ ___ activity.
Definition
- antiocoagulant
- anti-platelet activity
Term
Vitamin K aka ___ promotes blood coagulation via aiding in synthesis of factors II, VII, IX, and X. What are two vitamin K antagonists and thus anticoagulants?
Definition
- thiamine

antagonists:
- Dicumarol
- Warfarin
Term
vitamin K is cofactor in synthesis of ___ from ____.
Definition
- gamma- carboxyglutamate
- glutamate
Term
Prothrombin binds ___ ions at sites of modified ___ ___ ___ residues (done by vitamin K) and thus promotes formation of thrombin and subsequently the formation of ___ from ___.
Definition
- calcium
- gamma carboxy glutamate residues
- fibrin
- fibrinogen
Term
In the instrinsic system what factors activate factor X? Factor X is what goes on to form the prothrombin activator complex with calcium, factor V, and PF3.
Definition
- factors IXa and VIII activate factor X in the intrinsic system
Term
in the extrinsic system, what factors activate factor X?
Definition
- factor VII
Term
The intrinsic and extrinsic systems are inactivated by ___. This substance binds ___ ___ which activates proteolytic enzymes.
Definition
- heparin
- antithrombin III
- proteolytic enzymes
Term
What are three treatment options to reduce clotting?
Definition
- anticoagulants
- antiplatelet drugs
- thrombolytics
Term
what are two treatments to facilitate clotting?
Definition
- replacement factors (VIII, IXa, etc.)
- plasminogen inhibitors
Term
compromise of what organ will result in insufficient clotting factors?
Definition
- liver
Term
Hemophilias A have deficiency of what?
Definition
- deficient factor VIII
Term
Hemophilia B have a deficiency of:
Definition
Factor IX deficiency
Term
Hemophilia C have a deficiency of :
Definition
Factor XI deficiency
Term
another hemophilia disease is :
Definition
von Willebrand's disease
Term
liver dysfunction
Definition
- deficient vitamin K
- deficient procoagulants
Term
A ___is a clot that develops and persists in an unbroken vessel. it can block circulation leading to tissue death.
Definition
- Thrombus
Term
An ___ is a thrombus freely floating in the bloodstream. pulmonary emobli can't get oxygen. cerebral emboli> stroke.
Definition
- embolism
Term
bleeding time is most general test of ___ ___.
Definition
- platelet function
Term
Prothrombin time (PT) is measure of the function of the ___ pathway. it is also a good indicator for prognonsis of those with hepatocellular disease.
Definition
- extrinsic
Term
Partial Thromboplastin time (PTT) measures the function of the ___ pathway.
Definition
- intrinsic
Term
thrombin time tests for abnormalities in ____.
Definition
- fibrinogen
Term
fibrin stability test checks for ___ ___.
Definition
factor XIII
Term
look at slide 33 for widespread disseminated intervascular coagulation DIC
Definition
Term
- DIC: No injury occuring, but coagulation system gets triggered. Widespread microvascular thrombosis- small clots form all over coagulation system without an injury site. So no positive purpose for this. Plasmin and fibrinolisis will occur and fibrin clots degraded and cycle just keeps going. As cycling continues, coagulation factors and platelets get depleted so if challenge for system arises via an injury the system can’t do its job anymore b/c its depleted by DIC.
Definition
Term
major disorders associated with DIC:
Definition
OBSTETRIC
Abruptio placentae
Retained dead fetus
Septic abortion
Toxemia

INFECTIONS
Gram negative sepsis
Meningococcemia
Rocky Mountain spotted fever
Histoplasmosis
Aspergillosis
Malaria

NEOPLASMS
Carcinomas of pancreas, prostate
lung and stomach
Acute promyelocytic leukemia
MASSIVE TISSUE INJURY
Trauma
Burns
Extensive surgery

MISCELLANEOUS
Acute intravascular hemolysis
Snakebite
Giant hemangioma
Shock
Heat stroke
Vasculitis
Aortic aneurism
Liver disease
Term
. Continuous veno-venous hemodialysis (HD) with IV bicarbonate infusion was initiated due to the patient’s renal failure. Low dose IV heparin, antithrombin III, and multiple packed red blood cell transfusions were administered for ongoing DIC and hemolytic anemia.
Definition
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