Secondary hemostasis disorders Flashcards
What is secondary hemostasis
Secondary hemostasis is the formation of an organized fibrin clot via activation of coagulation factors and cofactors
The main pathway for initiation of the coagulation cascade is the tissue factor pathway (formerly the extrinsic pathway)
The main function of the contact activation pathway (formerly intrinsic pathway) is to amplify the coagulation cascade
Describe the different steps of the secondary hemostasis (coagulation phase)
Step 1: the coagulation cascade is initiated by exposure of tissue factor TF, which is present in sub-endothelial tissue
Step 2: TF binds to activated factor VII
- this complex then activates factor X
- activated factor X (which represents the start of the “common” pathway) combines with factor V, calcium and platelet phospholipids to form the “prothrombinase complex”
Step 3: the prothrombinase complex causes the conversion of prothrombin (factor II) to thrombin (activated factor II)
Step 4: thrombin converts fibrinogen to fibrin, activates factor XIII that strengthens the fibrin mesh, and promotes platelet activation
Step 5: thrombin activates proteins C and S, which in turn, inactivate factors V and VIII
What could you say about activated clotting time
This is a moderately sensitive screening test for deficiencies of all factors of clotting cascade, except for factor VII
Apart from severe thrombocytopenia, problems with primary hemostasis will not affect this test
Normal ACT for cats < 165s
What could you say about prothrombin time
It is a measure of the extrinsic and common coagulation pathways
It will be prolonged by problems with coagulation factors VII, X, V, II or I
If the PT is prolonged and the APTT is normal, early rodenticide toxicity should e suspected
What could you say about activated partial thromboplastin time
It is a measure of the intrinsic and common coagulation pathways
Explain why liver disease and exocrine pancreatic insufficiency can cause coagulopathies
Liver disease can cause coagulopathies either due to problems with manufacture of coagulation factors or due to poor viatmin K absorption secondary to cholestasis
EPI can also result in coagulopathy likely through vitamin K malabsorption
Explain the role of vitamin K in hemostasis
Clotting factors II, VII, IX and X as well as the anticoagulant proteins C and S are dependent on vitamin K for normal function
The liver manufactures these proteins as non-functional precursors
- to become functional vitamin K is required to carboxylate the amino acid glutamate on the precursor proteins
What is the origin and the metabolism of vitamin K in the body
Vitamin K is derived from the diet and also synthesis by intestinal bacteria
- it is then absorbed along with fat and stored within hepatocytes
To participate in activation of clotting factors, vitamin K must be in a “hydroquinone” form
- the gut-derived form is usually “quinone”
- quinone is converted to hydroquinone via a reductase reaction
Once the hydroquinone has been used in the carboxylation of the clotting factors, it is converted into the inactive epoxide form
- epoxide is then recycled to quinone via an epoxide reductase reaction
What is the site of action of vitamin K antagonist rodenticides
They inhibit epoxide reductase, which limits the regeneration of hydroquinone and consequently halts the carboxylation of clotting factor precursors
How frequent is anticoagulant rodenticides intoxication in cats? How cats can be poisoned?
Rodenticide toxicity is relatively rare in cats
Cats can become poisoned by ingestion of intoxicated mice and rats
- especially with the more potent second-generation coumarins
What would be your treatment plan for cat known or suspected of anticoagulant rodenticide ingestion
Emesis and possible charcoal administration for recent ingesttion
Phytonadione (vit K1) can then be given at 1.25-2.5 mg/kg, PO, q12h with a fatty meal
What is the mechanism explaining vitamin-K dependent coagulopathy in Devon Rex cats
This is a hereditary disorder reported in Australia and the UK
Affected cats have a deficiency of the epoxide reductase enzyme
What is the treatment for vitamin-K dependent coagulopathy in Devon Rex cats
Coagulopathy is usually first picked up when the cat is neutered, although spontaneous hemorrhage may also occur
These cats need vitamin K1 supplementation for life
What is the most common congenital factor deficiency in the cat
Factor XII deficiency is the most common congenital deficiency in the cat
- it is an incomplete autosomal dominant disorder in DSH and DLH
It results in a prolonged aPTT (and ACT), but a normal PT
Because generation of fibrin does not require Factor XII in vivo, affected cats do not have a clincally significant coagulopathy
