Introduction
Bemiparin is a low molecular weight heparin (LMWH) used in Europe for 10 years (1). Doctors prescribe it for the diagnosis of acute deep vein thrombosis (DVT) with pulmonary embolism (PE) or without it. They also use it for the prevention of venous thromboembolism (VTE) in patients undergoing general or orthopedic surgery and for clot prevention in the extracorporeal system during hemodialysis.
European VTE prevention guidelines indicate that 160 people experience DVT and 60 experience PE per 100,000 population per year (2). VTE is also associated with high mortality (3), making thrombosis prevention particularly important for patients at moderate or high risk of VTE. Studies confirm the benefits of non-fractionated heparin (NFH) (4). This article reviews the key aspects of using LMWH for long-term VTE prevention and treatment in the general population and specific patient groups (elderly patients, patients with renal insufficiency).
Properties of Bemiparin
Scientists synthesize LMWHs from NFH through depolymerization, and new generation LMWHs, including bemiparin, result from this process (6). These compounds feature a longer biological half-life and show more selectivity for the Xa clotting factor compared to NFH (1).
The main properties of the new generation LMWHs are:
- Lower molecular weight compared to other LMWHs and NFH (bemiparin 3.6 kDa vs. 4.5 kDa enoxaparin and 15 kDa NFH)
- Stronger anti-Xa / anti-IIa action (bemiparin 8:1 vs. 3.3–5.3:1 enoxaparin and 1:1 NFH)
- Longer half-life (bemiparin 5.2–5.4 hours vs. 4–4.4 hours enoxaparin and 0.5–1 hour NFH) (7)
A higher ratio of anti-Xa / anti-IIa action is achieved because the bemiparin molecule has fewer pentasaccharide chains responsible for thrombin affinity, but it does not affect the Xa clotting factor (6, 8).
In a study by Da Pozzo et al. (9), researchers found that bemiparin inhibits angiogenesis in vitro. They believe that bemiparin also has antioxidant effects (10). Another study showed that bemiparin reduced subendothelial matrix platelet coverage during blood flow more than dalteparin and NFH (11, 12).
VTE Prevention and Treatment with Bemiparin
Bemiparin is used for VTE prevention and treatment. Clinical studies have compared bemiparin with NFH for VTE prevention and treatment.
VTE Prevention in General Surgery
In a multicenter, randomized, double-blind study, researchers compared bemiparin 2,500 IU/d and NFH 5,000 IU 2 k/d in patients undergoing abdominal organ surgery with a low or moderate risk of VTE (12). Patients received anticoagulants for 7 days. Neither group experienced cases of VTE, PE, or death, but the NFH group required more frequent blood component transfusions and reoperations due to bleeding. The NFH group also had more wound hematomas.
Hematomas at the injection site were more frequent and larger in the NFH group compared to the bemiparin group. One patient in the bemiparin group experienced clinically insignificant moderate thrombocytopenia. The study results indicate that the 2,500 IU/d dose of bemiparin is as effective as NFH for VTE prevention but causes fewer major and minor bleedings (12).
VTE Prevention in Orthopedic Surgery
Patients undergoing orthopedic surgery are at increased risk of VTE. Navarro-Quilis et al. (13) found that thrombosis prevention with bemiparin is more cost-effective than with enoxaparin for patients undergoing knee arthroplasty. In a multicenter, controlled, double-blind, randomized study involving 381 patients, researchers compared bemiparin (3,500 IU, first dose 6 hours after surgery) with enoxaparin (40 mg, first dose 12 hours before surgery). Doctors administered anticoagulants for 10+2 days. Both drugs were equally effective in evaluating primary outcomes, which included symptomatic and/or venographically confirmed DVT 10+2 days after surgery, symptomatic PE, and death from any cause. The frequency of VTE in the bemiparin group was 32.1%. In the enoxaparin group, it was 36.9%.
No differences appeared in secondary outcomes, such as other distal or proximal DVT or PE, and bleeding episodes. Major and minor bleeding occurred in 3 patients in the bemiparin group. In the enoxaparin group, it occurred in 4 patients. However, hematomas at the injection site were more common in the enoxaparin group. They occurred in 32.5% of cases vs. 22.7% in the bemiparin group (p=0.03). Researchers demonstrated that administering bemiparin 6 hours after surgery is as effective and safe as administering enoxaparin 12 hours before surgery. This applies to thrombosis prevention in patients undergoing orthopedic surgery.
Additionally, postoperative administration of bemiparin may reduce the risk of spinal hematoma. In another prospective, open-label, multicenter study, researchers treated 7,959 patients with foot immobilization with a cast or during surgery. These surgeries included knee joint replacement, hip joint replacement, femoral neck surgery after fracture, and other limb surgeries, knee arthroscopy, and spine surgeries (14).
For thrombosis prophylaxis, doctors administered bemiparin for an average of 28 days. Researchers gave 3,500 IU/d to 84.9% of patients and 2,500 IU/d to 15.1% of patients. They recorded cases of symptomatic VTE (DVT or PE), major bleeding, deaths, thrombocytopenia, and other adverse reactions. They found a low frequency of VTE at 0.91%. Non-fatal major bleeding occurred in 0.17% of cases. The mortality rate was low, at 0.37%. Mild to moderate thrombocytopenia appeared in 0.51% of cases. The dosage of bemiparin, other medications used, age, and obesity did not influence the development of VTE and bleeding frequency. The results showed that 3-4 weeks of thrombosis prophylaxis with bemiparin during leg immobilization or orthopedic procedures in clinical practice carry a low risk of DVT, bleeding, and other adverse events.
Acute VTE Treatment with Bemiparin
In a multicenter, prospective, randomized trial conducted by V. Kakkar, researchers compared the effectiveness of acute VTE treatment and its long-term management with bemiparin or UFH (5). After 14 days of venography, they found that bemiparin significantly reduced thrombus size compared to UFH (5). The FLEBUS study (15) confirmed that treating with bemiparin resulted in a low frequency of recurrent VTE (0.3%) and rare bleeding (1 major and 3 minor - 1.1%). Finally, in a multicenter, prospective, cohort study ESFERA, researchers compared bemiparin to vitamin K antagonists (VKA) for long-term 98-day thrombosis prophylaxis. They found that bemiparin could be a safer and more cost-effective alternative to VKA for long-term DVT treatment (16).
Long-term VTE Treatment
Doctors prescribe LMWH for long-term VTE treatment when oral anticoagulants are contraindicated. The effectiveness of LMWH and the frequency of bleeding complications are similar to those when using warfarin (17). Several studies comparing long-term treatment with bemiparin to long-term treatment with UFH (5, 15, 16) revealed no significant differences in the frequency of recurrent VTE and bleeding after long-term treatment with bemiparin (5).
Treatment of Specific Patient Populations with VTE
Specific patient populations include elderly patients and those with kidney failure. Clinical trials rarely include these patients, leading to a lack of reliable evidence on medication suitability. Clinical trial data show that doctors often underdose anticoagulants for elderly people due to concerns about their comorbidities and general condition (18). Elderly patients should receive anticoagulants when indicated, with stricter treatment control. For patients with kidney failure, doctors recommend LMWH and fondaparinux over UFH because they cause fewer cases of thrombocytopenia and bleeding (18).
Several studies indicate no need to adjust bemiparin doses for prophylaxis in patients with mild to moderate kidney failure, but insufficient data exists on dose adjustment for patients with severe kidney failure (19, 20). Doctors can safely use UFH even with low creatinine clearance.
Pharmacoeconomic Benefit of Treating with Bemiparin
Another study found that 6 weeks of thrombosis prophylaxis with bemiparin after alternate knee joint surgery may cost less than prescribing enoxaparin (24). Researchers confirmed these results, finding that preoperative bemiparin is as effective and safe as postoperative enoxaparin in protecting patients undergoing knee replacement surgery from venous thromboembolism (13).
Conclusion
Bemiparin is an LMWH with certain characteristics compared to other LMWHs. Doctors use it for the prevention of dangerous blood clots that form in the deep veins of the legs and/or lungs during orthopedic surgeries (hip, knee, or other bone surgeries), general surgery, and dialysis procedures. They also use it for the treatment of VTE. Studies show that doctors can administer bemiparin to elderly patients and those with mild to moderate renal insufficiency. Due to its pharmacokinetic properties, doctors administer this anticoagulant once daily.
