Acenocoumarol in Prophylaxis of DVT
Deep vein thrombosis (DVT) and pulmonary embolism (PE) are life-threatening complications following major surgery as well as medical conditions necessitating prolonged immobility.49
The clinical efficacy studies with acenocoumarol have shown the drug to be effective in the prophylaxis of DVT.50,51
- Prevention of Thrombosis
- Prophylaxis of DVT
- Safety and Cost-Effectiveness
Prevention of thrombosis after hip arthroplasty: A prospective study of preoperative oral anticoagulants
Swierstra BA et al., Acta Orthop Scand. 1988 Apr;59(2):139-43.
101 patients undergoing total hip replacement
Prospective, randomized study
The patients were randomly allocated to receive one of the following regimens:
- Group A: Acenocoumarol at a dose of 3 mg one day before the surgery and on the day of the surgery; thereafter the dose of acenocoumarol was adjusted to yield an international normalized ratio (INR) of 2.1.
- Group B: Acenocoumarol was given at a dose of 3 mg on preoperative days 4 and 3 and on days 2 and 1, the dose was adjusted to yield an INR of 1.5-1.6 during the operation. Thereafter, the dose was adjusted to yield an INR of 2.1.
The drug was continued for 10 days in both the groups.
Venous thrombosis was diagnosed on the basis of radionuclide venography with 99mTc-labeled macroaggregates of albumin, performed about 10 days after the operation. The presence or absence of hot spots after 20 min was the most important criterion for the diagnosis.
There was no difference between the two groups in the incidence of proximal localized deep venous thrombosis (11/51 and 12/50 respectively for groups A and B). Blood loss did not depend on the level of peroperative anticoagulation. There were no postoperative hemorrhagic complications. No fatal pulmonary embolism occurred during the study. After discontinuation of the oral anticoagulants because of a negative venogram, nonfatal pulmonary embolism occurred in 3 out of 55 patients.
Oral anticoagulants controlled by the British comparative thromboplastin versus low-dose heparin in prophylaxis of deep vein thrombosis
Taberner DA et al., Br Med J 1978; 1: 272-274.
145 patients >40 years undergoing major gynecologic surgery
Randomized, controlled, comparative study
The patients were randomly allocated to receive one of the following:
- Group 1: Acenocoumarol at a dose of 6 mg at least 5 days before the surgery to achieve a prothrombin ratio (PR) of 2–2.5. After the surgery, the dose was monitored to achieve a PR of between 2–4. The drug was continued for 14 days and then withdrawn gradually over a period of 3 days.
- Group 2: Low dose heparin (5000 U) was administered twice-daily subcutaneously beginning 2 hours before surgery and continued for 7 days.
- Group 3: Saline was used at a dose of 0.2 mL SC, beginning 2 hours before surgery and continued for 7 days.
131I fibrinogen scan was carried out immediately after surgery and on a daily basis for 7 days.
The incidence of DVT was significantly lower with acenocoumarol and low-dose heparin compared to the saline group. The fall in hemoglobin levels and excessive hemorrhage was comparable in all the 3 groups.
The study showed that oral anticoagulant prophylaxis stabilised preoperatively and low-dose heparin was equally effective in preventing deep vein thrombosis in a moderate-risk group. Immediate preoperative prothrombin ratios of 2.0-2.5 and postoperative ratios of 2.0-4.0 with the BCT gave adequate protection without increased hemorrhagic risk.
BCT, British comparative thromboplastin.
Safety and cost-effectiveness of Acitrom® for DVT prophylaxis in critically ill patients requiring prolonged mechanical ventilation - A preliminary experience
Azim A et al., J Anaesth Clin Pharmacol 2010; 26(3): 360-62.
45 neurological patients requiring prolonged mechanical ventilation, of whom the data on 39 patients was evaluable.
All the patients underwent DVT probability risk assessment and received low molecular weight heparin along with acenocoumarol 2 mg/day for five days, followed by dosing adjustments until international normalized ratio (INR) of 2–3 was achieved. After achieving the INR, heparin was stopped and patients were maintained on acenocoumarol only.
Therapy was monitored with INR, bleeding complications and lower limbs Doppler.
Mean duration of mechanical ventilation and intensive care unit (ICU) stay was 38.57±9.23 and 47.73±16.22 days respectively. None of the patient had any complication related to acenocoumarol therapy or any evidence of symptomatic or asymptomatic (Doppler) DVT during ICU stay or during follow-up of 3 months. The cost of acenocoumarol (Acitrom®) including the cost of INR monitoring was only Rs.330 [Indian rupees] for a thirty day therapy.
Adjustment of acenocoumarol dosage
|INR||Change in dosage of acenocoumarol|
|<1.3||Add 1 mg/day to the current dose and repeat INR after 1 week|
|1.4–2.0||Add 0.5 mg/day to the current dose and repeat INR after 1 week|
|2.1–3.0||Maintain current dose|
|3.1–3.5||Decrease current dose by 0.5 mg/day and repeat after 1 week|
|3.6–4.0||Decrease current dose by 1 mg/day and repeat after 1 week|
|>4.0||Stop the drug for 3 days and repeat INR. If INR remains >4.0, discontinue therapy. If INR <4.0 on repeated measurement then to follow as above.|
INR, international normalized ratio.
Acenocoumarol (Acitrom®) appears to be a suitable alternative to other available therapies for the prevention of deep vein thrombosis at least in this particular subgroup of critically ill patients.