The severity of trauma determines the immune response to PF4/heparin and the frequency of heparin-induced thrombocytopenia. [Prevention of thromboembolism with low molecular weight heparin (Fragmin) in obstetrics]. Can low molecular weight heparin replace unfractionated heparin during peripheral arterial reconstruction? An open label prospective randomized controlled trial. Liposomal heparin spray: a new formula in adjunctive treatment of superficial venous thrombosis. Prevention of venous thromboembolism after knee arthroscopy with low-molecular weight heparin (reviparin): Results of a randomized controlled trial. Fixed-dose, body weight-independent subcutaneous low molecular weight heparin Certoparin compared with adjusted-dose intravenous unfractionated heparin in patients with proximal deep venous thrombosis. An open-label randomized controlled trial of low molecular weight heparin compared to heparin and coumadin for the treatment of venous thromboembolic events in children: the REVIVE trial. Low-molecular-weight heparin versus unfractionated heparin in the treatment of patients with acute pulmonary thromboembolism. Haemostatic molecular markers in patients undergoing radical retropubic prostatectomy for prostate cancer and submitted to prophylaxis with unfractioned or low molecular weight heparin.
Heparin can induce heparin-induced thrombocytopenia (HIT). The combined effect of type of surgery (major vs minor) and heparin on this prothrombotic immune reaction to platelet factor 4 (PF4)/heparin was analyzed. In a randomized, double-blind study, trauma patients receiving low-molecular-weight (LMWH) or unfractionated heparin (UFH) for thrombosis prophylaxis were assessed for PF4/heparin-antibody seroconversion, HIT, and thrombosis according to type of surgery. The risk for seroconversion was higher than major versus minor surgery odds ratio, 7.98 [95% confidence interval, 2.06-31.00], P = .003, controlled for potential confounders, as was the risk for HIT (2.2% [95% confidence interval, 0.3%-4.1%] vs 0.0%, P = .010). During LMWH compared with UFH thromboprophylaxis, HIT (1 of 298 vs 4 of 316; P = .370) and PF4/heparin seroconversion (1.7% vs 6.6%; P = .002) were less frequent, driven by differences in patients undergoing major surgery (incidence of HIT: LMWH 0.8% vs UFH 4.0%; P = .180; seroconversion rates: 4.0% vs 17.0%; P = .001). After minor surgery, no case of HIT occurred. The severity of trauma and the need for major surgery strongly influence the risk of an anti-PF4/heparin immune response, which is then increased by UFH. In major trauma certoparin may be safer than UFH because it induces HIT-antibody seroconversion, and the corresponding risk of HIT, less frequently. A total of 130 obstetrical patients were treated with either low molecular weight (LMW) or unfractionated (UFH) heparin as part of prospective study comparing their efficacy in the prevention of thromboembolism. A single daily dose of 2500-5000 anti-Xa-units LMW heparin (Fragmin) or two to three daily doses of 5000 IU UFH (Liquemin) were given to two groups of 15 patients with therapeutic tocolysis and 50 patients with cesarean section. Patients with cesarean section were given 500 ml Dextran 60 i.v. during surgery followed by subcutaneous injection of heparin eight to ten hours after surgery. Heparin therapy was continued for ten days after surgery. None of the patients exhibited clinical signs of thrombosis. The majority of patients showed symptoms of local irritation at the site of heparin injection (69% of patients with LMW heparin; 80% of patients with UFH). Hematomas at the site of injection were significantly smaller when LMW heparin was used instead of UFH. A number of patients experienced headache after heparin application (10% of patients with LMW heparin; 13% of patients with UFH). There were no cases of post surgical haemorrhage. Comparison of daily profiles revealed a significantly higher anti-Xa-activity of LMW heparin compared to UFH. In contrast, other coagulation parameters were not different in the two experimental groups (antithrombin III, partial thrombin time, thrombin time). Hematologic parameters and liver enzymes were in the physiological range in both experimental groups and none of the patients exhibited signs of heparin induced thrombocytopenia.(ABSTRACT TRUNCATED AT 250 WORDS) This study was undertaken to evaluate the effect of low molecular weight heparin (LMWH) compared with unfractionated heparin (UFH) on the rate of occlusion and bleeding during peripheral vascular surgery.
                The study was an open label, prospective, randomized trial, carried out by 20 Swedish surgical and vascular surgical departments that report to the Swedish Vascular Registry (SWEDVASC). Study subjects included patients undergoing peripheral vascular procedures, except carotid surgery. Of the 849 patients included, 817 were followed up to 30 days. LMWH (40 mg of enoxaparin) or UFH (5000 IU heparin) was given intravenously immediately before clamping. The same formulation in diluted form was used for vascular rinsing. Main outcome measures included patent reconstruction at day 1, perioperative blood loss, and the percentage of patients requiring protamin. Further, 30-day data for mortality, repeat operation, and recurrent occlusion are reported.
                The mortality rate at 30 days was 2.7%, with no difference between groups. The patency rate at 1 day was 91.2% to 98.4%, depending on diagnosis and type of reconstruction. No difference was recorded between study groups (0.6 < P < 1.0). At 30 days the patency rate was 83.1% to 100% (0.2 < P <.9). Median blood loss was 350 mL (interquartile range [IQR], 200-800 mL) in the LMWH group and 425 mL (IQR, 200-900 mL) in the UFH group (P =.02). Protamin was given to significantly fewer patients in the LMWH group (P =.001). LMWH was comparable to UFH during peripheral vascular reconstruction in terms of 1-day and 30-day graft patency, operative blood loss, and hemorrhagic complications. Protamine was required less often after LMWH. In this randomized trial LMWH was as effective as UFH in preventing thrombosis without excess bleeding or hemorrhagic complications. The objective of this study was to assess the efficacy and safety of liposomal heparin spray-a new formula of topical heparin delivery. This was a randomized, multicenter, controlled open clinical trial with 2 parallel groups. Forty-six outpatients with clinical signs of superficial venous thrombosis (SVT) were treated with either topical liposomal heparin spraygel (LHSG) (Lipohep Forte Spraygel, 4 puffs of 458 IU tid (n = 22) or with low-molecular-weight heparin (LMWH) (Clexane 40 mg once a day (n = 24), administered subcutaneously (sc). Main outcome measures were efficacy parameters (improvement of local symptoms-pain control and planimetric evaluation of erythema size, duplex Doppler assessment of thrombus regression) and safety parameters (documentation of adverse events, with particular reference to deep vein thrombosis [DVT] by duplex sonography, and patients' and investigators' assessment of drug tolerance). Patients' and investigators' subjective assessment of efficacy of treatment and change in basic biochemical parameters were defined as secondary outcome measures. Statistical analysis was performed with use of Wilcoxon test, Mann-Whitney U-test and Chi-square test. Regression of SVT-related symptoms, including pain, erythema, and thrombus presence, was shown as comparable in LHSG and LMWH groups. These results were corroborated by efficacy assessment by investigators and patients. Three cases of deep venous thrombosis in heparin spraygel and 1 in heparin sc group were reported. No significant adverse reactions were observed in the spraygel group, but 1 serious allergic reaction was observed in the LMWH group. Tolerance of new formula heparin was assessed as good. Heparin spraygel-a new topical mode of heparin application, seems a promising method of heparin delivery. This initial study has demonstrated comparable efficacy and safety of LHSG and LMWH in local treatment of SVT. These findings should be confirmed by further extensive study that will reach appropriate statistical power to support such conclusion, for despite heparin treatment, significant risk of DVT was demonstrated in both groups. Deep venous thrombosis (DVT) is a common, important complication of major orthopaedic surgery, particularly knee arthroplasty. Knee arthroscopy is increasingly performed on an outpatient basis. Few reports have elucidated the incidence of venous thromboembolism (VTE) in patients undergoing arthroscopic surgery receiving no prophylaxis. The objective of the present trial was to evaluate the risk of VTE in those patients and to determine efficacy and safety of a low-molecular weight heparin (LMWH) in preventing VTE.
                This is the first controlled randomized trial using objective diagnostic methods with blinded outcome assessment to reveal the incidence of VTE in outpatient arthroscopy and determine efficacy and safety of a LMWH (reviparin sodium) in preventing VTE in these patients.
                There were 262 patients undergoing elective knee arthroscopy prospectively randomized to receive either no treatment or reviparin once daily subcutaneously for 7 to 10 days. The blindly assessed primary outcome measure was the incidence of DVT detected by compression color-coded sonography. Both groups were comparable with regard to demographics and baseline characteristics.
                239 patients were evaluable (122 no treatment, 117 receiving LMWH). 6 DVT were detected - 5 in the control group (5/117 - 4.1%) and only one in the active treatment group (1/116 - 0.85%). This particular patient had a low level of protein C and a subnormal level of protein S. The odds ratio of 4.95 approximates a relative risk reduction of about 80%. Treatment with reviparin was safe and well tolerated. There was no major bleeding, four patients with minor bleedings. One patient had a transitory fall in platelet count below 100 giga-particles/L without any clinical symptoms.
                Patients undergoing knee arthroscopy have a moderate risk of VTE and effective prophylaxis can be achieved with LMWH (reviparin). Subcutaneous body weight-adjusted low molecular weight heparin (LMWH) has been proven as effective and safe as intravenous aPTT-adjusted unfractionated heparin (UFH) for the treatment of patients with acute deep venous thrombosis (DVT). In this study we evaluate the efficacy of the initial treatment of proximal DVT with a fixed-dose, body weight-independent application of the LMWH Certoparin with a six month follow-up. In a prospective, multicentre, randomized, active-controlled study 1220 patients with objectively diagnosed proximal DVT were randomly assigned to subcutaneous 8000 U anti-factor Xa of Certoparin twice daily for 10 to 14 days or intravenous aPTT-adjusted UFH for 5 to 8 days. Both regimen were followed by oral anticoagulation for 6 months. The primary end point was the rate of symptomatic and objectively confirmed thromboembolic events within 6 months. The aim of the study was to demonstrate the non-inferiority of the Certoparin regimen as compared to UFH. The per-protocol analysis revealed 22 (3.8%) thromboembolic events in the Certoparin group and 24 (4.3%) in patients assigned to UFH within 6 months, thereby proving the non-inferiority (p<0.01), confirmed by intent-to-treat analysis (p<0.001). Major bleeding occurred in 6 and 7 patients started on Certoparin or UFH during the treatment period. Thromboembolic events were equally distributed in body weight categories with < 50, 50-80 and >80 kg as followed: 0, 3.6% and 4.1% of patients for the Certoparin group and 0, 4.6% and 4.2% of patients for the UFH group. The same was true for major bleeding complications with 0, 2.9% and 1.5% for Certoparin and 0, 3.5% and 4.2% for UFH. Overall mortality was 1.9% in the Certoparin group and 2.7% in the UFH group. Fixed-dose body weight-independent subcutaneous LMWH Certoparin is at least as efficacious and safe as intravenous aPTT-adjusted UFH for the initial treatment of acute proximal DVT. This effect is maintained during a 6-months follow-up of treatment with oral anticoagulation. Venous thromboembolic events (VTE) are serious complications in children and for which the standard of care, unfractionated heparin followed by oral anticoagulation (UFH/OA), is problematic. The objective of REVIVE was to compare the efficacy and safety of a low molecular weight heparin (reviparin-sodium) to UFH/OA for the treatment of VTE in children.
                This multicenter, open-label study, with blinded central outcome adjudication, randomized patients with objectively confirmed VTE to receive either reviparin-sodium or UFH/OA. Dose adjustments were made using nomograms. The efficacy outcome was based on recurrent VTE and death due to VTE during the 3-month treatment period. The safety outcomes were major bleeding, minor bleeding and death. Due to slow patient accrual, REVIVE was closed prematurely.
                At 3 months, with reviparin-sodium, 2/36 patients (5.6%) had recurrent VTE or death compared to 4/40 patients (10.0%) receiving UFH/OA (odds ratio=0.53; 95% CI=(0.05, 4.00); Fisher's exact test: 2P=0.677). There were 7 major bleeds, 2/36 (5.6%) in the reviparin-sodium group and 5/40 (12.5%) in UFH/OA group (odds ratio=0.41; 95% confidence interval 0.04, 2.76); Fisher's exact test: P=0.435). There were 5 deaths during the study period, 1 (2.8%) in the reviparin-sodium group and 4 (10.0%) in the UFH/OA group. All five deaths were unrelated to VTE but one was due to an intracranial hemorrhage in the UFH/OA group.
                Although limited by small sample size, REVIVE provides valuable information on the incidence of recurrent VTE, major bleeding and problematic issues associated with therapy of VTE in children. Low-molecular-weight heparin (LMWH) appears to be as effective as unfractionated heparin (UFH) for both treatment and prophylaxis of deep vein thrombosis (DVT), but limited data are available for its use in acute pulmonary thromboembolism (PTE).
                To determine whether enoxaparin, a LMWH, was clinically as efficient and safe as UFH in patients with a diagnosis of acute PTE.
                After exclusion of those with massive forms, 59 patients with acute PTE were randomly assigned to either subcutaneous enoxaparin given twice daily (1 mg/kg/dose) or adjusted dose intravenous UFH. Oral anticoagulant treatment was begun on the second day and was given for at least 6 months. We compared the treatment regimens at day 8 and day 90 with respect to a combined end point of major bleeding, recurrent venous thromboembolism (VTE), and death.
                In the first 8 days of treatment, 1 of 30 patients assigned to receive UFH (3.3%) reached one of the end points (recurrence), as compared with none of 29 patients assigned to enoxaparin. Statistically this difference was not significant (p = 0.508). By day 90, 3 patients assigned to UFH (10%) had symptomatic recurrent VTE, as compared with 1 patient assigned to enoxaparin (3.4%). There was neither major bleeding nor death in the study groups. There was an absolute difference of 6.4 percentage points between the two treatment groups, but the difference was statistically not significant (p = 0.318).
                Initial subcutaneous treatment with enoxaparin appeared to be as effective and safe as UFH in acute PTE.
                Copyright 2002 S. Karger AG, Basel Deep vein thrombosis and subsequently pulmonary embolism are the most common causes of increased post-operative morbidity and mortality in patients with pelvic or abdominal cancer. Aim of the study was to evaluate variations in coagulative parameters induced by two accepted primary prophylaxis patterns: standardized low doses of unfractioned heparin (UFH) or single doses of low molecular weight heparin (LMWH) in cancer patients submitted to radical retropubic prostatectomy.
                Fifty patients (45-75 yr) were randomly assigned two groups. Group 1 received UFH (5000 units s.c. x 3 daily); group 2 received calcium nadroparin (single daily dose of 0.3 ml s.c.). In both groups prophylaxis began preoperatively and was maintained throughout the entire hospital-stay. Blood cell, platelet count, coagulative system exploring tests, thrombotic molecular markers, and physiological inhibitors of coagulation were determined at baseline conditions and on the first and seventh day after surgery.
                Preoperative values of fibrinogen, F1+2 fragment, TAT and D-dimer resulted over normal range in both groups. A significant increase of these markers was observed also during the post-operative period. PT, aPTT, ATIII, PC, total and free PS showed the most substantial changes on the 1st post operative day, though their values ranged within normal levels on the three sampling times. The levels of haemostatic markers demonstrated a baseline hypercoagulability, probably related to cancer and thrombin activation caused by prostatectomy. Despite this thrombophylic state, neither of the two groups presented symptomatic bleeding or thromboembolic complications.
                These results prove that a single daily dose of nadroparin has been safe and efficient as a thrice-daily dose of UFH, with a better risk/benefit relationship.
There was a lower incidence of HIT and HIT complicated by VTE in postoperative patients undergoing thromboprophylaxis with LMWH compared with UFH. This is consistent with the current clinical use of LMWH over UFH as front-line heparin therapy. However, conclusions are limited by a scarcity of high quality evidence. We did not expect the paucity of RCTs including HIT as an outcome as heparin is one of the most commonly used drugs worldwide and HIT is a life-threatening adverse drug reaction. To address the scarcity of clinically-relevant information on the topic of HIT as a whole, HIT should be included as an outcome in future RCTs of heparin, and HIT as an adverse drug reaction should be considered in clinical recommendations regarding monitoring of the platelet count for HIT.