|Year : 2015 | Volume
| Issue : 2 | Page : 437-441
A comparative study between fondaparinux, a low-molecular-weight heparin, and recombinant hirudin in thromboembolic prophylaxis after major abdominal surgery in the surgical intensive care unit
Magda F Yehyia, Hatem A Atalla, Ezzeldin S Ibrahim, Sadek A Sadek, Hager H Mohammady MSc
Department of Anaesthesia and Critical care, Faculty of Medicine, Menoufia University, Menoufia Governorate, Egypt
|Date of Submission||30-Aug-2014|
|Date of Acceptance||14-Oct-2014|
|Date of Web Publication||31-Aug-2015|
Hager H Mohammady
Department of Anaesthesia and Critical Care, Faculty of Medicine, Menoufia University, Shebin El-kom, Menoufia Governorate
Source of Support: None, Conflict of Interest: None
Evaluation of the safety and the efficacy of different anticoagulants in thromboembolic prophylaxis after major abdominal surgeries.
Thromboembolic events are serious complications after major abdominal surgeries, and there are different modalities to prevent them.
Materials and methods
Sixty patients who underwent major abdominal surgery were assigned in a randomized, double-blinded manner and classified into three groups: group A (n = 20) was started on enoxaparin at a daily dose of 40 mg. Group B (n = 20) was given recombinant hirudin 15 mg twice daily. Group C (n = 20) was given fondaparinux 2.5 mg subcutaneously daily. The duration of treatment was 5-12 days. The efficacy of the three drugs was compared by the occurrence of DVT (assessed by Doppler ultrasound) or fatal and nonfatal pulmonary embolism (by computed tomography). The safety was assessed by postoperative bleeding in terms of the number of transfused whole blood units, plasma expanders, or packed red blood cells and fatal bleeding.
Results showed that enoxparin, fondaparinux, and recombinant hirudin were equally effective in the prevention of thromboembolism. The least risk of postoperative bleeding was noticed in patients receiving enoxparin in comparison with patients receiving fondaparinux or recombinant hirudin.
Enoxaparin, hirudin, and fondaparinux are equally effective in protection against thromboembolic events in patients undergoing major abdominal surgeries; however, enoxaparin is superior to the others regarding safety.
Keywords: enoxaparin, fondaparinux, recombinant hirudin, thromboembolic prophylaxis
|How to cite this article:|
Yehyia MF, Atalla HA, Ibrahim ES, Sadek SA, Mohammady HH. A comparative study between fondaparinux, a low-molecular-weight heparin, and recombinant hirudin in thromboembolic prophylaxis after major abdominal surgery in the surgical intensive care unit. Menoufia Med J 2015;28:437-41
|How to cite this URL:|
Yehyia MF, Atalla HA, Ibrahim ES, Sadek SA, Mohammady HH. A comparative study between fondaparinux, a low-molecular-weight heparin, and recombinant hirudin in thromboembolic prophylaxis after major abdominal surgery in the surgical intensive care unit. Menoufia Med J [serial online] 2015 [cited 2020 Apr 6];28:437-41. Available from: http://www.mmj.eg.net/text.asp?2015/28/2/437/163898
| Introduction|| |
Major abdominal surgical procedures place patients at risk for venous thromboembolism (VTE), including DVT and pulmonary embolism. Complications of DVT include postphlebitic syndrome or death from pulmonary embolism. Therefore, prophylaxis with anticoagulant medications, and the adjunctive use of mechanical devices, is essential  .
Enoxaparin, the first low-molecular-weight heparin, has been shown to be a safe and effective form of thromboprophylaxis, and is recommended as the first-line therapy together with UFH by the latest practice guidelines relevant to major abdominal surgery  .
The pentasaccharide fondaparinux is the first drug from a new class of synthetic compounds, which has no components from animals, acts through specific inhibition of factor Xa, and has no direct activity against thrombin. Postoperative fondaparinux improved the risk benefit ratio for VTE prophylaxis significantly  .
A specific thrombin inhibitor such as recombinant hirudin stems from its direct action on both free and fibrin-bound thrombin; it requires no plasma cofactor in the inhibition of thrombus growth  .
| Aim of the work|| |
We used low-molecular-weight heparin as a comparison drug and evaluated the antithrombotic efficacy and safety of fondaparinux and hirudin as compared with those of a standard regimen of enoxparin in patients undergoing major abdominal surgical procedures.
| Materials and methods|| |
After obtaining guidance and approval from the Department of Ethics Committee, 60 patients who underwent major abdominal surgeries and were admitted in the surgical ICU were enrolled for the study. Written informed consent was obtained from each patient before his or her enrollment in the trial. Patients of both sexes were eligible if they were between 18 and 60 years old, weighed at least 50 kg, and were scheduled for major abdominal surgical procedures. We excluded patients who had any hemostatic or bleeding disorder, patients with active bleeding (gastrointestinal ulceration, hemorrhagic stroke), intracranial or intraocular bleeding within the previous 3 months, uncontrolled hypertension, or renal impairment, pregnant women, patients who had undergone nephrectomy or kidney transplantation, and patients with known allergy to recombinant hirudin, low-molecular-weight heparin, or fondaparinux.
A total of 60 patients were divided into three groups: group A was given enoxparin (clexane; Aventis pharma) 40 mg in 0.4 ml water subcutaneously 12 h postoperatively with a daily dose on a regular basis. Group B was given recombinant hirudin (Thrombex; Novartis pharma) 15 mg subcutaneously twice daily, with the first dose given 30 min before the start of the surgery. Group C was given fondaparinux (Arixtra; GSK pharma) 2.5 mg in 0.25 ml water subcutaneously 6 h postoperatively, and then every 24 h.
Placebo prefilled injections were given to complete the double-blind design. The day of surgery was defined as day 1. Treatment was scheduled to last up to days 5-12, and the primary efficacy outcome was assessed between days 5 and 12.
The primary efficacy outcome was VTE (DVT, fatal, or nonfatal pulmonary embolism or both) up to day 12. Patients were examined for deep-vein thrombosis by Doppler compression sonography of both legs within 48 h of intensive care unit admission, twice weekly, and if VTE was clinically suspected. Symptomatic pulmonary embolism was confirmed by echocardiography and spiral computed tomography.
Perioperative blood loss was defined as bleeding recorded up to 12 h after the start of the surgery, and postoperative blood loss as that recorded from 12 h after the start of surgery up to postoperative day 6. Transfusion with whole blood, concentrates of red cells, and plasma expanders was recorded. Serious bleeding episodes were defined as a need for perioperative transfusion of more than 5 U of whole blood or concentrates of red cells, a need for transfusion of 7 U at any time after the start of the surgery, or a total blood loss of more than 3500 ml. Any adverse events such as retroperitoneal, intracranial, or intraspinal hematoma were recorded.
It was performed using the statistical package for social science. Descriptive statistical analysis (range, mean, and SD), paired Student's t-test, and analysis of variance (F-test) were performed. Statistical significance was considered when P value was less than 0.05.
| Results|| |
Demographic data, characteristics, and the duration of surgery showed no significant difference among the three groups [Table 1]. Regarding the frequency of venous thromboembolic events, there was no significant difference among the three groups [Table 2].
Postoperative blood loss was significantly more in the fondaparinux and the hirudin groups in comparison with the enoxaparin group [Table 3] and [Figure 1]. Transfusion requirements in the three studied groups showed no significant difference among the three groups [Table 4] and [Table 5].
|Figure 1: Distribution of the studied groups regarding the mean and SD of the amount of bleeding|
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Regarding the detected cases of thrombocytopenia, there was no significant statistical difference between the three groups [Table 5], and only one case was found in group A.
|Table 5 Distribution of the groups regarding the amount of PRBCs, blood units, and the occurrence of thrombocytopenia|
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| Discussion|| |
VTE is a common complication in patients undergoing surgery. In patients undergoing general surgery without prophylaxis, the rates of DVT and fatal PE range from 15 to 30% and from 0.2 to 0.9%, respectively  . Many trials have evaluated the efficacy and the safety of anticoagulants for prophylaxis after major abdominal surgery  . The modalities that have clearly reduced the risk of DVT and PE as per evidence-based studies include LDUH and low-molecular-weight heparin  .
In this study, we compared low-molecular-weight heparin (enoxaparin) with a thrombin inhibitor (hirudin) and a specific factor Xa inhibitor (fondaparinux) in patients undergoing major abdominal surgery.
The main efficacy outcome was thromboembolic events (DVT and PE), which showed no significant statistical difference among the three groups (same efficacy) despite the fact that PE occurred in two cases in the enoxparin group (10% of cases) and DVT occurred in two cases (10% of cases) in the same group, whereas one case of DVT (5% of cases) occurred in the fondaparinux group. This may be attributed to our small sample size in comparison with other studies. However, this is consistent with the study by Agnelli et al.  , because among the 2048 patients evaluated for efficacy, the rate of VTE was 4.6% (47 of 1027) with fondaparinux compared with 6.1% (62 of 1021) with dalteparin (low-molecular-weight heparin).
Although different results have been reported in the field of orthopedic surgery, fondaparinux has been shown to be highly effective in the prevention of DVT among elective hip replacement patients. Lassen et al.  randomly assigned 2309 consecutive patients aged 18 years or older who were undergoing elective hip-replacement surgery to once-daily subcutaneous injections of either 2.5 mg fondaparinux, starting postoperatively, or 40 mg enoxaparin, starting preoperatively. They assessed the primary efficacy outcome in 1827 (79%) of the 2309 patients. By day 11, VTEs was recorded in 37 (4%) of the 908 patients assigned to fondaparinux and in 85 (9%) of the 919 patients assigned to enoxaparin. The two groups did not differ in the frequency of death or clinically relevant bleeding. Their conclusion was that drugs that act through the specific inhibition of factor Xa, such as fondaparinux, could be more effective than low-molecular-weight heparins in the prevention of VTE in patients undergoing hip-replacement surgery.
In contrast, Bauer et al.  showed that patients undergoing knee surgery receiving fondaparinux achieved equal reduction in the risk of VTE compared with enoxaparin. Many other orthopedic studies , proved that fondaparinux showed better efficacy than enoxaparin. They concluded that the unique mechanism of action of fondaparinux, its rapid onset of action, and its highly reproducible and predictable linear pharmacokinetics are important reasons for its better efficacy compared with enoxaparin. Two other studies by Eriksson and colleagues , showed a controversial result and found that recombinant hirudin was superior to enoxaparin in its efficacy in preventing thromboembolic complications. They explained the better effect of hirudin to be due to its administration immediately before surgery and two times daily thereafter. The mode of action of this specific inhibitor of thrombin may also have accounted for its superiority to enoxaparin.
Regarding the safety in using enoxaparin, fondaparinux, and hirudin, our results showed that enoxaparin was the best, with the least postoperative bleeding compared with hirudin and fondaparinux.
In contrast, the results of trials on patients undergoing hip surgery [9, 11, 14] showed that fondaparinux did not increase the risk and the amount of bleeding in comparison with enoxaparin. Eriksson et al.  conducted a double-blinded study, wherein 1711 consecutive patients undergoing surgery for fracture of the upper third of the femur were randomly assigned to receive subcutaneous doses of either 2.5 mg of fondaparinux once daily initiated postoperatively or 40 mg of enoxaparin once daily initiated preoperatively, for at least 5 days. The main safety outcomes were major bleeding and mortality from all causes. The duration of follow-up was 6 weeks. There were no significant differences between the two groups in the incidence of death or clinically relevant bleeding.
Our results did not match with those of Eriksson et al.  regarding the treatment regimens by enoxaparin and hirudin as they were equally safe without any significant difference in relation to the amount of blood loss and did not require specific laboratory monitoring.
Our study showed that there were no significant statistical differences among the three groups with regard to the type and the number of blood products given. These results are contradictory to those of Lassen et al.  Eriksson et al.  , and Turpie et al.  who studied patients undergoing hip surgery, and found that the fondaparinux group showed a lesser number of blood products transfused in comparison with the enoxaparin group.
| Conclusion|| |
Enoxaparin, hirudin, and fondaparinux were equally effective in protection against thromboembolic events in patients undergoing major abdominal surgeries; however, enoxaparin is superior to fondaparinux or hirudin in relation to safety, due to the lesser amount of postoperative bleeding.
| Acknowledgements|| |
Conflicts of interest
There are no conflicts of interest..
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]