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Flashcards in Exam 7 L.5 Deck (22):

Secondary hemostasis

1) end result: generation of thrombin which forms a cross-linked fibrin clot
2) consists of: series of enzymatic reactions (coagulation cascade) involving:
-coagulation factors
-surface membranes of platelets


Pathways of secondary hemostasis

1) extrinsic: tissue factor and factor VII
2) intrinsic: factors XII, XI, IX, and VIII
3) common: factors X, V, II, I, and XIII
4) culminates in the generation of thrombin:
-cleaves fibrinogen to form fibrin
-fibrin is cross-linked to form the fibrin clot


PTT time

Assesses intrinsic and common pathways


PT time

Assesses extrinsic and common pathways


Common pathway

Fibrinogen is cleaved by thrombin ==> fibrin, which is then cross-linked to form a clot by FXIIIa



1) Extrinsic pathway starts the intrinsic pathway!
-Extrinsic is initiated via tissue factor (i.e. vascular injury)
2) factor 12 doesn't do anything to stimulate clotting in the animal, it only stimulates clotting in the test tube*
4) the coagulation cascade is initiated by TISSUE FACTOR
5) the intrinsic pathway amplifies the coagulation cascade
6) the coagulation cascade is propagated by the platelet


Keeping secondary hemostasis in check

1) physiologic:
-extrinsic pathway: tissue factor pathway inhibitor (TF PI)
-intrinsic and common pathway: anti-thrombin, protein C and S (vitamin K -dependent)
2) therapeutic: heparin- acts via anti-thrombin; warfarin-vitamin K antagonist

Note: thrombin is self-limiting, when activated it also starts a negative feedback pathway on itself


Inherited coagulation disorders

1) F VIII deficiency: hemophilia A
-**most common CF deficiency**
2)F IX deficiency: hemophilia B
3) vitamin K recycling enzymes: Devon Rex cats


Acquired coagulation disorders

1) toxicity: anticoagulant rodenticides (vitamin K antagonism)
2) DIC: inflammation, bacterial sepsis, cancer (clotting factors get used up)
3) liver disease: decreased production of clotting factors
4) drugs


The vitamin K -dependent clotting factors

Clotting factors II, VII, IX, X
-note: anticoagulant rodenticides antagonize vitamin K


Heparin-how does it work?

Heparin binds to anti-thrombin, allowing it to inhibit FII and FX


Coagulation disorders due to disruption of inhibition

1) consumption of inhibitors: sepsis, DIC
2) loss: protein losing disorders (loss of anti-thrombin)
-anti-thrombin is a similar size as albumin (if you are losing or not absorbing albumin, the same is likely happening with anti-thrombin)
3) decreased production: liver disease/failure

remember: any time you lose albumin you likely lose anti-thrombin!
-- Thus, you are predisposed to forming clots!!


How to identify a disorder of secondary hemostasis

1) clinical signs:
-bleeding into body cavities
-large bruises/hematomas
-joint bleeds
-prolonged bleeding after surgery or trauma
2) screening tests
-coagulation assays: PT, PTT


Hemophilia A

1) inherited factor VIII deficiency
2) X-linked (males affected)
3)**most common hereditary coagulopathy**


Tertiary hemostasis

-goal is to reestablish blood flow through vessels



1) fibrin clot breakdown
2) by plasmin
3) plasmin is activated by tPA
4)*endpoint is release of degradation products*
-D dimers: from cross-linked fibrin (if present, D dimers mean there were clots)
-fibrin(ogen) degradation products (FDP's): from soluble fiber or fibrinogen



Injury to endothelial cells activates tPA (tissue plasminogen activator), tPA activates plasminogen to plasmin, and the plasmin then breaks down cross-linked fibrin to D-dimers (and fibrin/fibrinogen to FDPs)


Inhibitors of fibrinolysis

1) physiologic:
-anti-plasmin (inhibits plasmin)
-plasminogen activator inhibitor (inhibits tPA)
2) therapeutic:
- aminocaproic acid, tranexamic acid ==> they both promote clot formation!!!


What happens in DIC?

Excessive activation of hemostasis (likely via tissue factor!! - Too many cells showing tissue factor!****) ==> Too much thrombin** ==> excessive clotting (thrombosis)
1) consumes platelets
2) consumes coagulation factor
3) consumes inhibitors


Loss of control/restriction

==== Systemic, uncontrolled thrombin generation ==> thrombosis ==> hemorrhage (end-stage, as all clotting factors are used up)


Diagnosis of diagnosis of DIC

Defects in tests of all pathways of hemostasis
1) primary hemostasis: low platelets
2) secondary hemostasis: coagulation tests prolonged, fibrinogen may be low or normal
3) Fibrinolysis: D dimers or FDP (high)
4) inhibitors: anti-thrombin (low)


Most common inherited coagulation disorders

1) vWD: primary hemostasis
2) hemophilia A: secondary hemostasis


Most common acquired coagulation disorders

1) thrombocytopenia: primary hemostasis
-counts <30,000/uL at risk of spontaneous hemorrhage
2) rodenticide toxicosis (secondary hemostasis)
3) DIC (all hemostatic components)