Anticoagulants - CVPR

Question 1

An injectable, rapidly acting anticoagulant that is often used acutely to interfere with the formation of thrombi. If unfractionated, it is a mixture of straight-chain, anionic glycosaminoglycans with a wide range of molecular weights. It is strongly acidic because of the presence of sulfate and carboxylic acid groups.

Answer 1

Heparin (UFH)

Question 2

MOA: its anticoagulant effect is a consequence of binding to antithrombin III, with the subsequent rapid inactivation of coagulation factors. Antithrombin III is an α globulin that inhibits serine proteases of thrombin (factor IIa) and factor Xa. In the absence of this, antithrombin III interacts very slowly with thrombin and factor Xa. When this drug binds to antithrombin III, a conformational change occurs that catalyzes the inhibition of thrombin about 1000-fold. A unique pentasaccharide sequence permits their binding to antithrombin III.

Answer 2

Heparin

Question 3

Therapeutic use: These are used to limit the expansion of thrombi by preventing fibrin formation. These agents are used for the treatment of acute venous thromboembolism (DVT or PE). Also used for prophylaxis of postoperative venous thrombosis in patients undergoing surgery (for example, hip replacement) and those with acute MI. These drugs are the anticoagulants of choice for treating pregnant women, because they do not cross the placenta, due to their large size and negative charge.

Answer 3

Heparin and LMWH

LMWHs do not require the same intense monitoring as heparin, thereby saving laboratory costs and nursing time. These advantages make LMWHs useful for both inpatient and outpatient therapy. ​

Question 4

This DOAC has high oral bioavailability when taken with food. Following an oral dose, the peak plasma level is achieved within 2–4 hours; the drug is extensively protein-bound. It is a substrate for the cytochrome P450 system and the P-glycoprotein transporter. Drugs inhibiting both CYP3A4 and P-glycoprotein (eg, ketoconazole) result in increased drug effect. One-third of the drug is excreted unchanged in the urine and the remainder is metabolized and excreted in the urine and feces. The drug half-life is 5–9 hours in patients age 20–45 years and is increased in the elderly and in those with impaired renal or hepatic function.

Answer 4

Rivaroxaban

Question 5

This DOAC has an oral bioavailability of 50% and prolonged absorption, resulting in a half-life of 12 hours with repeat dosing. The drug is a substrate of the cytochrome P450 system and P-glycoprotein and is excreted in the urine and feces. As with rivaroxaban, drugs inhibiting both CYP3A4 and P-glycoprotein, as well as impairment of renal or hepatic function, result in increased drug effect.

Answer 5

Apixaban

Question 6

This DOAC is approved for prevention of embolic stroke in patients with atrial fibrillation without valvular heart disease, prevention of venous thromboembolism following hip or knee surgery, and treatment of venous thromboembolic disease (VTE). Depending on clinical presentation and risk factors, patients with VTE are treated for 3–6 months. It is also approved for prolonged therapy in selected patients to reduce recurrence risk at the treatment dose.

Answer 6

Rivaroxaban

Question 7

This DOAC is approved for prevention of stroke in nonvalvular atrial fibrillation, for prevention of VTE following hip or knee surgery, and for treatment and long-term prevention of VTE. The recommended duration of therapy in hip and knee replacement is the same as for rivaroxaban.

Answer 7

Apixaban

Question 8

Why would you not want to use a drug like Fondaparinux if your patient was perhaps needing to go to the OR?

Answer 8

Fondaparinux is small and therefore has a long half-life making it not a good choice for operative patients.

Question 9

Why would you want to use LMWH in pregnant patients as opposed to Unfractionated heparin?

Answer 9

Unfractionated heparin would bind to osteoblasts causing increased bone breakdown. LMWH doesn’t have as much binding to osteoblasts.

Question 10

Which parenteral anticoagulants would you consider not using if the patient has a reduced kidney function and why?

Answer 10

LMWH and Fondaparinux because they are small and are renally eliminated as opposed to unfractionated heparin that is large and eliminated by macrophages.