PharmD Program: Hematopoietic Disorders and Thrombosis

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