Hematopoiesis 2

Name the TWO major hemostatic drugs.

1. Silver nitrate

2. Vitamin K

Name at least TWO anticoagulants and TWO antiplatelet drugs.

Anticoagulant: heparin, enoxaparin, warfarin, tPA

Antiplatelet: aspirin, clopidogrel

What factor is often the major target of the coagulation cascade since it is involved in each of the three pathways?

X (initialized the common pathway)

What are topical hemostatic drugs indicated for?

Capillary oozing

True or False: Lyophilized clotting factors involve structural matrix and clotting factors and require an intact hemostatic mechanism.

True!

What astringent hemostatic drug stops localized bleeding (nail trims; organs in surgery) in the form of a heavy metal through its potency for protein precipitation and damaged tissues?

Silver nitrate (Quik-Stop)

What other kind of drug is often added to topical hemostatic drugs? Give an example.

Vasoconstrictors

Epinephrine- helpful in cases of epistaxis

What are the THREE beneficial components found in plasma products?

1. Electrolytes

2. Antibodies

3. Protein (albumin)

What are the major coagulation factors found in plasma products?

II, VII, IX, and X

Are coagulation factors found in fresh plasma? Frozen plasma?

Fresh: yes (within 6 hours)

Frozen: no- albumin only (if after 6 hours)

What lasts for 4 hours in platelet-rich plasma (PRP)? 4-5 days?

4 hours: platelet activity

4-5 days: tissue regeneration

What is the mechanism of Vitamin K?

Reactivates factors II, VII, IX, X

What TWO major things can Vitamin K be used to treat in deficient conditions?

1. Rodenticide toxicity

2. Severe liver disease (cannot synthesize vitamin K)

What are the THREE major sources of Vitamin K and their sources?

1. K1: phytonadione- plant source

2. K2: menaquinone- animal source

3. K3: menadione- synthetic

What is the most rapid and preferential vitamin K source in acute use, especially in rodenticide toxicity?

K1 (phytonadione)

What vitamin K source is used in slow onset and chronic use cases, primarily as a dietary supplement?

K3 (menadione)

What hormone converts oxidized vitamin K into its reduced form?

What hormone converts reduced to oxidized vitamin K?

Epoxide reductase

Gamma carboxylase

Name the THREE major in vitro anticoagulants and the TWO in vivo.

Vitro: EDTA, citrate, heparin

Vivo: heparin, coumarin

What is the mechanism of EDTA and citrate?

Heparin?

Coumarin?

EDTA/citrate: Ca2+ removal

Heparin: effect coagulation factor proteins (C, S, Z)

Coumarin: impaired vitamin K

What is the most frequently used anticoagulants that is a naturally occurring polysulfated mucopolysaccharide stored throughout the body?

Heparin

True or False: Heparin is a major component of interstitial fluids and is stored in mast cell granules.

True!

What are the TWO groups of heparin products?

1. Unfractionated (UFH)

2. Low Molecular Weight Heparin (LMWH)

Which type of heparin is generally extracted from animal tissue (porcine intestine or bovine lung) and has a 8,000-40,000 Dalton molecular weight range?

Unfractionated

Which type of heparin yields lower molecular weights than the other type (<8,000 Daltons), but are more potent and more predictable?

What is the model drug for this type?

Low Molecular Weight Heparin (LMWH)

Enoxaparin

True or False: UFH is based on dose and is NOT interchangeable, while LMWH is based on units determined by bioassay.

False! UFH is based on UNITS determined by BIOASSAY, while LMWH is based on DOSE in mg are NOT interchangeable.

How do UFH and LMWH differ in their mechanism of action?

UFH: can block both thrombin (IIa) and factor Xa

LMWH: only blocks factor Xa (too small to block IIa)

True or False: LMWH must be monitored based on anti-X assay rather than prothrombin time, as is used for UFH.

True!

Heparin is limited to parenteral use because of what TWO major characteristics?

1. Large size

2. Polarity

True or False: You should avoid mixing heparin with any other drugs due to its large ionized chemical structure commonly leading to drug-drug interactions.

True!

Local and hepatic metabolism of heparin result in a short half-life of less than 2 hours for the —- type, while the half-life of the —- type is generally longer.

UFH

LMWH

What are the TWO major indications for using heparin?

1. Preventing/treating thrombosis (venous, arterial, FATE, etc.)

2. DIC as replacement therapy

What is the major side effect of heparin, associated with overdosing?

What can you use to monitor this?

Bleeding/hemorrhage

Prothrombin time test

What can you do to monitor anticoagulant activity of LMWH specifically?

Anti-Xa assay

Is thrombocytopenia more common with UFH or LMWH?

UFH

What is the relatively new drug that functions as an oral Xa inhibitor that is non-heparin based and heavily used in human medicine?

What is it primarily used for in dogs and cats?

Rivaroxaban

Thromboembolic disease (aortic thromboembolism prevention/treatment)

True or False: The optimal dose and dosing interval for thromboprophylaxis or the treatment of thrombotic disease requires further study.

True!

What is the major example of Vitamin K antagonists?

What is the mechanism of action?

Warfarin and other coumarin derivatives

Inhibit vitamin K reductase or epoxide reductase -> impair synthesis of II, VII, IX, and X

True or False: Vitamin K antagonists can only be used in vitro and have delayed time to effect (8-12 hours for factor VII and 4-6 days into therapy).

False! Vitamin K antagonists can only be used in VIVO (previously synthesized factors must be consumed, hence the delay) and have delayed time to effect (8-12 hours for factor VII and 4-6 days into therapy).

How can vitamin K antagonists create a potentially hypercoagulable state?

How can this be avoided?

Protein C decreases faster than the coagulation factors with use

Start with a low dose

True or False: Vitamin K antagonists have rapid oral absorption and are highly protein-bound, so there is a risk of drug interactions.

True!

Which vitamin K antagonist product has a 48-hour half-life and is clinically unpredictable?

Which is second generation with a 2-4 week half-life and is clinically relevant, especially in cases of rodenticide toxicity?

Coumarin derivates

Indandione derivatives

What is the major use of vitamin K antagonists like warfarin?

Treat/prevent thromboembolism

True or False: Warfarin is not recommended to use in both dogs and cats because of an unpredictable efficacy and toxicity, alongside with marked interindividual variation coupled with a narrow therapeutic index.

True!

What is formed from arachidonic acid and stimulates platelet aggregation and vasoconstriction, eventually forming a hemostatic plug?

Thromboxane A2 (TXA2)

What is the prototypic antiplatelet drug that works by inhibiting cyclooxygenases and is especially good at targeting TXA2, but is irreversible?

Aspirin (acetylsalicylic acid)

What is low dose aspirin used for clinically?

Prevent thromboembolic disease (cats with HCM especially)

True or False: Aspirin should not be used as a sole antithrombic for the treatment of cardiogenic thromboembolism in part because of limited efficacy, and no recommendation can be made for or against using for venous thromboembolism in dogs.

True!

Is aspirin toxicity more likely in cats or dogs?

How can you limit risk of toxicity?

Dogs

Always use low dose

How does the antiplatelet drug Clopidogrel work?

Inhibit platelet activating factor (P2Y or P2RY)

What are the TWO steps of activation of clopidogrel?

1. Activation in enterocytes/hepatocytes

2. Final cleavage in plasma

Is clopidogrel more effective in dogs or cats?

Is it more or less effective for venous thromboembolisms?

Cats

Less

True or False: Clopidogrel can be used as a sole therapy or combination therapy with LMWH or aspirin in the prevention of arterial thromboembolism in small animals.

True!

Stop!!

I could've dropped my croissant!!!