Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_35_библиотеки_им_акад_М_И_Перельмана

enzymes associated with the coagulation pathway [11]. These drugs are commonly prescribed following orthopedic surgeries of the lower extremities to prevent VTEs [2]. Warfarin is another anticoagulant that protectsagainst VTEs. Heparin is parenterally administered and warfarin can be orally administered. Since the coagulation pathway involves a vitamin K-dependent step, warfarin produces its anticoagu­lant activity through its ability to block the activation of vita­min K in the body [12].

• Factor Xa inhibitors Adiagram of the coagulation cascadedemonstrating the

The formation of Factors II, VII, IX, and X, all of which

Both reduced absorption of vitamin K and reduced synthe­sis of other factors necessary for coagulation by the diseased liver predisposes to the bleeding tendency often seen in patients with severe hepatic cirrhosis [36].

In pregnancy, thefetus obtains vitamin K from its mother through the placenta. The liver in the neonate has essentially no reserve of vitamin K, and deciency of vitamin K in human infants can lead to the hemorrhagic disease of vitamin K deciency bleeding (VKDB) of the newborn [37–39].

Rivaroxaban is used for thromboembolic prophylaxis, such as venous thromboembolism (VTE) prophylaxis after total knee replacement (TKR) or total hip replacement (THR). Rivaroxaban has also been used as secondary pre­vention after recent acute coronary syndrome (ACS) and for stroke prevention in patients who have atrial brillation [42]. When used for the prevention of venous thromboembolism following hip or knee replacements, extended therapy for at least 3months or longer is usually recommended [46]. In the presence of signicant renal or hepatic impairment, theuse of rivaroxaban may be contraindicated, or at least signicant reduction in the dosage may be needed [41, 46]. Clearance of rivaroxaban depends on the cytochrome P3A4 system. Use is not recommended in patients receiving concomitant sys­temic treatment with strong inhibitors of CYP3A4 and P-glycoprotein–azole-antimycotics (e.g., ketoconazole) or HIV protease inhibitors (e.g., ritonavir) because they may increase rivaroxaban plasma concentrations to a clinically relevant degree. Since rifampin strongly induces CYP3A4, co-administration with rifampin led to a decrease in effect and more rapid clearance of the administered dose. Co-administration with naproxen (500mg), aspirin (500mg followed by 100 mg), clopidogrel (300 mg followed by 75 mg), enoxaparin (40 mg), and warfarin (titrated to and INR of 2.0–3.0) did not affect the pharmacokinetics of rivar­oxaban [42].

major and non-major bleeding in total knee replacement patients in the phase 2 EXPERT trial, effective antithrom­botic activity was demonstrated at 15-mg and 40-mg doses, and these doses were well tolerated. In the phase 2 EXPLORE-Xa trial in patients with nonvalvular atrial bril­lation, betrixaban doses of 40, 60, and 80mg demonstrated the lowest occurrence of any bleeding events. The risk of bleeding was comparable to well-controlled warfarin in patients with atrial brillation at risk for stroke. The use of Betrixaban was associated with higher rates of diarrhea than with use of warfarin [52].

rudin is added to the cardiopulmonary bypass pump priming uid. Following administration of the initial dose, an acti­vated clotting time (ACT) can be used to monitor anticoagu­lation provided by bivalirudin. Adequate anticoagulation for cardiopulmonary bypass is documented by achieving an ACT of at least 500s and over 200s for a vascular surgery procedure such as an “off-pump” cardiopulmonary bypass. There is currently no “reversal agent” to terminate the action of bivalirudin, so termination of the anticoagulation effect depends on the patient’s intrinsic clearance mechanisms.