Reduction of painful vaso-occlusive crisis of sickle cell anaemia by tinzaparin in a double-blind randomized trial. Low molecular weight heparin and prevention of postoperative thrombosis in abdominal surgery. Clinical assessment of low molecular weight heparin effects in peripheral vascular disease. Subcutaneous low-molecular-weight heparin compared with continuous intravenous heparin in the treatment of proximal-vein thrombosis. Randomized, placebo-controlled trial of low molecular weight heparin in active ulcerative colitis. The effect of low molecular weight heparin on survival in patients with advanced malignancy. [Efficacy of a very low molecular weight heparin fragment (CY 222) compared to standard heparin in patients with deep venous thrombosis. A randomized study]. Randomized, controlled trial of low molecular weight heparin vs. no deep vein thrombosis prophylaxis for major colon and rectal surgery in Asian patients. A prospective double-blind trial of a low molecular weight heparin once daily compared with conventional low-dose heparin three times daily to prevent pulmonary embolism and venous thrombosis in patients with hip fracture.
A randomized double-blind clinical trial was performed to test the safety and efficacy of a low-molecular-weight heparin, tinzaparin (Innohep), for the management of acute painful vasoocclusive crisis characteristic of sickle cell anemia (SCA). We studied 253 patients with acute painful crisis but with no other complications of SCA, randomized to treatment or control groups. In the treatment group, 127 patients received tinzaparin at 175 IU/kg, subcutaneous once daily, along with supportive care including morphine analgesia; in the control group, 126 patients received placebo and the same supportive care. The maximal experimental treatment period was seven days. Analysis revealed a statistically significant reduction in number of days with the severest pain score, overall duration of painful crisis, and duration of hospitalization (p < 0.05 for each comparison of tinzaparin vs. placebo). The decline in pain intensity was sharper for tinzaparin-treated patients, and complications consisted of two minor bleeding events that were reported and treated by cessation of tinzaparin. This investigation demonstrated that tinzaparin, administered at its approved treatment regimen, reduced the severity and duration of acute crisis of SCA. In a prospective, double-blind, randomized multicenter trial the efficacy and safety of low molecular weight heparin and unfractionated heparin were compared for the prevention of postoperative deep vein thrombosis in patients undergoing abdominal surgery. Six hundred and seventy-three patients were randomly allocated to the two prophylaxis groups; 20 of these, however, did not undergo surgery and did not receive any prophylaxis. Of the remaining 653 patients 323 received one subcutaneous injection of 3,000 anti-Xa units of low molecular weight heparin and 330 received subcutaneously 5,000 U heparin three times a day. Treatment was initiated 2 h preoperatively and continued for 7 to 10 days. The occurrence of DVT was determined by the 125I-labelled fibrinogen uptake test and phlebography. Venous thrombosis was diagnosed in 24 of 323 patients (7.4%) treated with low molecular weight heparin and in 26 of 330 patients (7.9%) treated with low-dose heparin. DVT of proximal veins was detected in four patients of the low molecular weight heparin group and in three patients of the low-dose heparin group. During the observation period three pulmonary emboli - one fatal and two non-fatal - occurred in patients receiving prophylaxis with low-dose heparin. No pulmonary embolism was found in patients treated with low molecular weight heparin. Both prophylactic schemes were well tolerated. Intra- and postoperative blood loss, incidence of wound hematoma, frequency and volume of intra- and postoperative blood transfusion were similar in both groups with a slight advantage for the low molecular weight heparin group.(ABSTRACT TRUNCATED AT 250 WORDS) This study was carried out, using the double-blind method vs placebo, on 36 patients suffering from stage II peripheral vascular disease (PVD) according to Leriche, to check the clinical and hemorrheologic effects of the administration of a new low molecular weight heparin (LMWH). After a one-month washout period, the patients were randomly assigned either to the group treated with the LMWH (15,000 aXaU/day sc) or to the group treated with indistinguishable placebo. At the start of the study and after three and six months of treatment, clinical, instrumental, and laboratory tests were performed to assess local and systemic efficacy and tolerance. The LMWH under study caused a statistically significant increase in claudication time, with a parallel increase in the absolute claudication distance and in the interval free of pain. The drug also led to a significant increase in activated partial thromboplastin time, the values of which, however, remained within the normal limits, and to a marked reduction in blood viscosity. No significant variation was observed in the tolerability parameters in the two treatment groups, and no local or systemic adverse reactions occurred. Low-molecular-weight heparin has a high bioavailability and a prolonged half-life in comparison with conventional unfractionated heparin. Limited data are available for low-molecular-weight heparin as compared with unfractionated heparin for the treatment of deep-vein thrombosis.
                In a multicenter, double-blind clinical trial, we compared fixed-dose subcutaneous low-molecular-weight heparin given once daily with adjusted-dose intravenous heparin given by continuous infusion for the initial treatment of patients with proximal-vein thrombosis, using objective documentation of clinical outcomes.
                Six of 213 patients who received low-molecular-weight heparin (2.8 percent) and 15 of 219 patients who received intravenous heparin (6.9 percent) had new episodes of venous thromboembolism (P = 0.07; 95 percent confidence interval for the difference, 0.02 percent to 8.1 percent). Major bleeding associated with initial therapy occurred in 1 patient receiving low-molecular-weight heparin (0.5 percent) and in 11 patients receiving intravenous heparin (5.0 percent), a reduction in risk of 91 percent (P = 0.006). This apparent protection against major bleeding was lost during long-term therapy. Minor hemorrhagic complications were infrequent. Ten patients receiving low-molecular-weight heparin (4.7 percent) died, as compared with 21 patients receiving intravenous heparin (9.6 percent), a risk reduction of 51 percent (P = 0.049).
                Low-molecular-weight heparin is at least as effective and as safe as classic intravenous heparin therapy under the conditions of this study and more convenient to administer. The simplified therapy provided by low-molecular-weight heparin may allow patients with uncomplicated proximal deep-vein thrombosis to be cared for in an outpatient setting. In several open and 1 controlled trial, unfractionated heparin was effective in the treatment of active ulcerative colitis (UC). Low molecular weight heparin (LMWH) had a similar effect in several open studies.
                We studied the efficacy, safety, and tolerability of LMWH in mild to moderately active UC in a randomized, double-blind, placebo-controlled trial. In all, 29 patients with a mild or moderate recurrence of UC during salicylate treatment were randomized to receive either reviparin 3,436 IU (n = 15) subcutaneously twice daily or placebo (n = 14). The study period was 8 weeks. Treatment was discontinued if there was no improvement at 4 weeks or at any disease progression. Primary outcome measure was clinical improvement at 8 weeks measured by the Colitis Activity Index (CAI) and the Clinical Symptoms Grading (CSG, based on the CAI). Endoscopic and histologic grading and quality of life as measured by the Inflammatory Bowel Disease Questionnaire (IBDQ) were secondary outcome measures. Patients were closely monitored for adverse events.
                Twenty of 29 patients finished the 8-week treatment period (reviparin versus placebo: 11 versus 9; P = 0.70). There was no difference in CSG, CAI, endoscopic and histologic grading, or IBDQ. Treatment was well tolerated and no serious adverse events occurred.
                In this study, treatment with LMWH showed no significant clinical advantage compared to placebo in mild to moderately active UC. Studies in cancer patients with venous thromboembolism suggested that low molecular weight heparin may prolong survival. In a double-blind study, we evaluated the effect of low molecular weight heparin on survival in patients with advanced malignancy without venous thromboembolism.
                Patients with metastasized or locally advanced solid tumors were randomly assigned to receive a 6-week course of subcutaneous nadroparin or placebo. The primary efficacy analysis was based on time from random assignment to death. The primary safety outcome was major bleeding.
                In total, 148 patients were allocated to nadroparin and 154 patients were allocated to placebo. Mean follow-up was 1 year. In the intention-to-treat analysis the overall hazard ratio of mortality was 0.75 (95% CI, 0.59 to 0.96) with a median survival of 8.0 months in the nadroparin recipients versus 6.6 months in the placebo group. After adjustment for potential confounders, the treatment effect remained statistically significant. Major bleeding occurred in five (3%) of nadroparin-treated patients and in one (1%) of the placebo recipients (P = .12). In the a priori specified subgroup of patients with a life expectancy of 6 months or more at enrollment, the hazard ratio was 0.64 (95% CI, 0.45 to 0.90) with a median survival of 15.4 and 9.4 months, respectively. For patients with a shorter life expectancy, the hazard ratio was 0.88 (95% CI, 0.62 to 1.25).
                A brief course of subcutaneous low molecular weight heparin favorably influences the survival in patients with advanced malignancy and deserves additional clinical evaluation. Low molecular weight heparin fractions have been demonstrated as efficient as low doses of standard heparin in preventing post-operative deep-vein thrombosis. Several clinical studies are, now, carrying out in patients with acute deep-vein thrombosis in order to assess efficacy and safety of low molecular weight heparin fractions as compared to standard heparin. In a randomised study including patients with deep-vein thrombosis treated either with low molecular weight heparin or with subcutaneously standard heparin, we demonstrated an effectiveness, in terms of thrombus reduction, of low molecular weight heparin as well as standard heparin. However, low molecular weight heparin seemed to be safer than standard heparin. Routine deep venous thrombosis prophylaxis is controversial in Asian patients, because deep venous thrombosis incidence was considered negligible. Because of recent reports of significantly higher incidences, a randomized, controlled trial was conducted to assess the effectiveness and complications of enoxaparin prophylaxis (low molecular weight heparins) in major colorectal surgery.
                Three hundred twenty consecutive patients were randomly assigned to control or low molecular weight heparins groups. Patients in the low molecular weight heparins group were given perioperative enoxaparin starting 12 hours before surgery. The surgeon (blinded) assessed for difficulties related to possible enoxaparin administration. Independent blinded observers performed daily clinical assessments and Doppler studies (at the 3rd and 5th postoperative day). Deep venous thrombosis was confirmed by duplex ultrasound, and pulmonary embolism was confirmed by lung scans or postmortem examinations.
                Deep venous thrombosis developed in 5 of 169 (3 percent) controls and 0 of 134 low molecular weight heparins patients (P = 0.045). Three of the deep venous thrombosis patients had pulmonary embolism, which was fatal in one patient. The surgeons were unable to perceive any increased surgical difficulties in the low molecular weight heparins group. The bleeding-related complications were significantly higher in the low molecular weight heparins patients (controls, n = 3 (1.8 percent); low molecular weight heparins, n = 9 (6.7 percent)). However, apart from one subdural hematoma and two abdominal hemorrhages needing re-exploration, which also occurred in one of the controls, these complications were minor bruises at the wounds, drains, or injection sites.
                Deep venous thrombosis prophylaxis is needed in Asian patients undergoing major colorectal surgery. In a randomized, prospective, double-blind trial, the effect of conventional low-dose heparin (5,000 units every 8 hours) was compared with that of a low molecular weight fragment (2165 LMWH, Kabi Vitrum AB, starting 2,500 units 2 hr before surgery, and then 5,000 units subcutaneously every morning for 9 days). A total of 90 patients admitted because of hip fracture fulfilled the inclusion criteria and were analyzed for development of pulmonary embolism and deep vein thrombosis: 46 patients were included in the low molecular weight heparin (LMWH) group, and 44 in the conventional heparin group. Two and three, respectively, died before diagnostic tests were performed. In the remaining patients a ventilation-perfusion lung scan was performed 8 days after intervention. In the first 57 patients studied a bilateral ascending venography was performed on the ninth day only if clinical symptoms suggested a deep venous thrombosis. Because of the rate of venous thrombosis detected in those patients was unexpectedly low, venography was requested in the remaining 33 patients, even if the screening tests were negative. Pulmonary embolism occurred in six patients, all in the LMWH group. Deep vein thrombosis occurred in 14 patients in the LMWH group and in six patients in the conventional heparin group. Both differences are statistically significant. Mortality did not differ between the groups, nor did haemorrhagic complications. Our findings suggest that, in patients with hip fracture, LMWH is not useful at the dosage used.
Based on the results of one study, evidence is incomplete to support or refute the effectiveness of low-molecular-weight heparins in people with sickle cell disease. Vaso-occlusive crises are extremely debilitating for sufferers of sickle cell disease; therefore well-designed placebo-controlled studies with other types of low-molecular-weight heparins, and in participants with different genotypes of sickle cell disease, still need to be carried out to confirm or dismiss the results of this single study.