Exam 7 L.5 Flashcards Preview

Small Animal Medicine > Exam 7 L.5 > Flashcards

Flashcards in Exam 7 L.5 Deck (22):
1

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
-calcium
-surface membranes of platelets

2

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

3

PTT time

Assesses intrinsic and common pathways

4

PT time

Assesses extrinsic and common pathways

5

Common pathway

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

6

Remember

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

7

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

8

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

9

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

10

The vitamin K -dependent clotting factors

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

11

Heparin-how does it work?

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

12

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!!

13

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

14

Hemophilia A

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

15

Tertiary hemostasis

Fibrinolysis
-goal is to reestablish blood flow through vessels

16

Fibrinoysis

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

17

Fibrinolysis

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)

18

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!!!

19

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

AND

Loss of control/restriction

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

20

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)

21

Most common inherited coagulation disorders

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

22

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)