Exam 7 L.5

Question 1

Secondary hemostasis

Answer 1

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
- calcium
- surface membranes of platelets

Question 2

Pathways of secondary hemostasis

Answer 2

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

Question 3

PTT time

Answer 3

Assesses intrinsic and common pathways

Question 4

PT time

Answer 4

Assesses extrinsic and common pathways

Question 5

Common pathway

Answer 5

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

Question 6

Remember

Answer 6

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*
3) IT’S ALL ABOUT THROMBIN
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

Question 7

Keeping secondary hemostasis in check

Answer 7

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

Question 8

Inherited coagulation disorders

Answer 8

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

Question 9

Acquired coagulation disorders

Answer 9

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

Question 10

The vitamin K -dependent clotting factors

Answer 10

Clotting factors II, VII, IX, X

-note: anticoagulant rodenticides antagonize vitamin K

Question 11

Heparin-how does it work?

Answer 11

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

Question 12

Coagulation disorders due to disruption of inhibition

Answer 12

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!!

Question 13

How to identify a disorder of secondary hemostasis

Answer 13

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

Question 14

Hemophilia A

Answer 14

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

Question 15

Tertiary hemostasis

Answer 15

Fibrinolysis

-goal is to reestablish blood flow through vessels

Question 16

Fibrinoysis

Answer 16

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

Question 17

Fibrinolysis

Answer 17

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)

Question 18

Inhibitors of fibrinolysis

Answer 18

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

Question 19

What happens in DIC?

Answer 19

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

AND

Loss of control/restriction

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

Question 20

Diagnosis of diagnosis of DIC

Answer 20

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)

Question 21

Most common inherited coagulation disorders

Answer 21

1) vWD: primary hemostasis

2) hemophilia A: secondary hemostasis

Question 22

Most common acquired coagulation disorders

Answer 22

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