PharmD Program: Hematopoietic Disorders and Thrombosis

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Questions and Answers

What is the main hazard associated with warfarin?

Osteoporosis

Reversible alopecia

Haemorrhage (correct)

Teratogenic effects

Which of the following is a contraindication for the use of warfarin?

Prosthetic heart valves

Pregnancy (correct)

Pulmonary embolism

Atrial fibrillation

What is the mechanism of action of warfarin?

It stimulates the production of clotting factors

It directly inhibits thrombin formation

It enhances the activity of plasminogen

It competitively inhibits vitamin K epoxide reductase component 1 (correct)

What is the difference between heparin and low-molecular-weight heparins (LMWHs) in terms of thrombocytopenia?

LMWHs are less likely to cause thrombocytopenia Signup and view all the answers

What is the indication for using aspirin in patients with coronary artery disease?

To prevent myocardial infarction in patients at high risk Signup and view all the answers

What is the role of vitamin K in coagulation?

It is required for the carboxylation of clotting factors Signup and view all the answers

Which of the following is a side effect of heparin?

All of the above Signup and view all the answers

What is the treatment for haemorrhage caused by warfarin?

All of the above Signup and view all the answers

Which of the following fibrinolytics is NOT 'clot selective'?

Aprotinin Signup and view all the answers

What is the primary indication for the use of tissue plasminogen activator?

Acute myocardial infarction Signup and view all the answers

What is the main side effect of fibrinolytic therapy that requires treatment with fresh plasma or coagulation factors?

Bleeding Signup and view all the answers

Which of the following iron preparations is absorbed the least?

Ferrous fumarate Signup and view all the answers

What is the main advantage of hydroxocobalamin over cyanocobalamin?

It does not cause unwanted effects Signup and view all the answers

In which of the following conditions is folic acid supplementation recommended?

Pregnant women Signup and view all the answers

What is the primary mechanism of action of fibrinolytic drugs?

Catalysis of tissue plasminogen activator Signup and view all the answers

Which of the following is NOT a indication for the use of fibrinolytic drugs?

Chronic peripheral artery disease Signup and view all the answers

What is the primary mechanism of action of heparin?

Binding to antithrombin III and accelerating the inhibition of clotting factors Signup and view all the answers

What is the main difference between the action of heparin and low molecular weight heparin (LMWHs)?

LMWHs act primarily on factor Xa, whereas heparin acts on thrombin Signup and view all the answers

What is the consequence of heparin binding to antithrombin III?

Heparin is released and binds to another antithrombin III molecule Signup and view all the answers

What is the main hazard of heparin therapy?

Haemorrhage Signup and view all the answers

What type of thrombi are anti-platelet drugs and fibrinolytic drugs primarily used to treat?

Platelet-rich thrombi Signup and view all the answers

What is the effect of heparin on the inhibition of clotting factors?

It increases the rate of inhibition by 1000 times Signup and view all the answers

What is the mechanism of action of antithrombin III?

It accelerates the inhibition of clotting factors by heparin Signup and view all the answers

What is the primary difference between the treatment of arterial thrombi and venous thrombi?

Arterial thrombi are treated with anti-platelet drugs, while venous thrombi are treated with anticoagulants Signup and view all the answers

Study Notes

Thrombosis and Anemia

The main drugs used for platelet-rich arterial thrombi are antiplatelet drugs and fibrinolytic drugs.
The main drugs used to prevent or treat venous thrombi are:
- Injectable anticoagulants (heparin)
- Oral anticoagulants (warfarin)

Mechanism of Action of Heparin

Heparin binds to antithrombin III, leading to conformation changes and rapid interaction with protease (activated clotting factors).
Once it binds and activates antithrombin, heparin is released intact for renewed binding to more antithrombin, leading to a continuous anticoagulant effect.
Heparin accelerates the rate of neutralization of certain activated coagulation factors (XIIa, XIa, Xa, IXa, and IIa) by antithrombin.
Low Molecular Weight Heparin (LMWHs) increase the action of antithrombin III on factor Xa but not its action on thrombin.

Side Effects of Heparin

Haemorrhage (main hazard): treated by stopping therapy and, if necessary, giving antidote protamine sulfate IV.
Heparin-induced thrombocytopenia (HIT). Management: discontinue heparin and use alternative drugs like LMWHs.
Osteoporosis
Reversible alopecia
Hypersensitivity due to animal source (rare)

Mechanism of Action of Warfarin

Warfarin is the main vitamin K antagonist.
It competitively inhibits vitamin K epoxide reductase component 1, thus inhibiting the reduction of vitamin K epoxide to its active form.
Leads to inhibition of vit K-dependent carboxylation of clotting factors II, VII, IX, X.
Acts only in vivo and have no effect in vitro.

Side Effects of Warfarin

Teratogenic, causing disordered bone development.
Haemorrhage (main hazard). Treated by administration of vitamin K, or fresh plasma or coagulation factor concentrates (for life-threatening bleeding).

Antiplatelets

Aspirin: adverse effects mainly on the gastrointestinal tract (gastric ulcer).
Prevention of myocardial infarction in patients at high risk.
Following coronary artery bypass grafting.
For acute indications (thrombotic stroke in evolution, acute myocardial infarction) treatment.

Thrombolytic Agents

This group causes rapid degradation of thrombi by catalyzing conversion of plasminogen to plasmin.
Plasmin can’t be used due to naturally occurring plasmin inhibitors in plasma.
Examples: streptokinase, urokinase, tissue plasminogen activator (e.g., alteplase, reteplase).
Side effects: bleeding treated by fresh plasma or coagulation factors.
Aminocarporic acid is used as an antidote for t-PA, while aprotinin is used for streptokinase.

Treatment of Thrombotic Disorders

Acute myocardial infarction, within 12 hours of onset (the earlier, the better).
Acute thrombotic stroke within 3 hours of onset.
Acute arterial thromboembolism.
Life-threatening deep vein thrombosis and pulmonary embolism.

Anemia

Food rich in iron includes meat, vegetables, and grains.
Oral iron: ferrous sulfate, ferrous gluconate, ferrous fumarate (only 25% absorbed) for 3-6 months to correct anemia and replenish iron stores.
Parenteral iron: iron dextran, iron sucrose complex, given IM or IV infusion for patients who cannot tolerate or absorb oral iron.
Side effects:
- Oral iron: nausea, epigastric discomfort, diarrhea, constipation, black stool
- Parenteral iron: local pain, tissue staining, flushing

Vitamin B12

Preparations: cyanocobalamine injection, hydroxycobalamine injection
IM daily for 1-2 weeks
Patients with pernicious anemia require life-long therapy, with maintenance injections every 3 months following a loading dose
Hydroxocobalamin does not cause unwanted effects

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Description

This quiz covers the mechanisms of action of anticoagulants, anti-platelets, and thrombolytic agents, as well as their uses in hematopoietic disorders and thrombosis. Presented by Dr. Khalid Mohamad.