Rivaroxaban versus nadroparin for thromboprophylaxis following thoracic surgery for lung cancer: A randomized, noninferiority trial.

The benefit of rivaroxaban in thromboprophylaxis after oncologic lung surgery remains unknown. To evaluate the efficacy and safety of rivaroxaban, patients who underwent thoracic surgery for lung cancer were enrolled, and randomly assigned to rivaroxaban or nadroparin groups in a 1:1 ratio; anticoagulants were initiated 12-24 h after surgery and continued until discharge. Four hundred participants were required according to a noninferiority margin of 2%, assuming venous thromboembolism (VTE) occurrence rates of 6.0% and 12.6% for patients in the rivaroxaban and nadroparin groups, respectively. The primary efficacy outcome was any VTE during the treatment and 30-day follow-up periods. The safety outcome was any on-treatment bleeding event. Finally, 403 patients were randomized (intention-to-treat [ITT] population), with 381 included in per-protocol (PP) population. The primary efficacy outcomes occurred in 12.5% (25/200) of the rivaroxaban group and 17.7% (36/203) of the nadroparin group (absolute risk reduction, -5.2%; 95% confidence interval [CI], [-12.2-1.7]), indicating the noninferiority of rivaroxaban in ITT population. Sensitivity analysis was performed in the PP population and yielded similar results, confirming the noninferiority of rivaroxaban. In the safety analysis population, the incidence of any on-treatment bleeding events did not differ significantly between the groups (12.2% for rivaroxaban vs. 7.0% for nadroparin; relative risk [RR], 1.9; 95% CI, [0.9-3.7]; p = .08), including major bleeding (9.7% vs. 6.5%; RR, 1.6 [95% CI, 0.9-3.7]; p = .24), and nonmajor bleeding (2.6% vs. 0.5%; RR, 5.2 [95% CI, 0.6-45.2]; p = .13). Rivaroxaban for thromboprophylaxis after oncologic lung surgery was shown to be noninferior to nadroparin.

Clinical study on low-molecular weight heparin infusion as anticoagulation for nocturnal home haemodialysis.

AIM: This study was conducted to evaluate low-molecular weight heparin (LMWH) as anticoagulation for nocturnal home haemodialysis (NHHD). While its longer half-life may cause drug accumulation in frequent dialysis, the essential need of a supplementary intra-dialytic bolus for the sleeping patients also renders LMWH's use impractical. METHODS: The recruited patients, who were on alternate-day 8 h haemodialysis, were randomized to receive either nadroparin or unfractionated heparin (UFH) for a week. They underwent crossover to receive the alternate anticoagulant in the next week. A nadroparin infusion regimen was adopted to enhance its practicability, which consisted of a loading dose of 35 IU/kg and a continuous infusion of 10 IU/kg per hour for 6 h. RESULTS: A total of 12 NHHD patients were recruited. With nadroparin infusion, the mean anti-Xa levels at the 2nd , 4th , 6th and 8th hours of dialysis were 0.46 ± 0.11, 0.55 ± 0.14, 0.61 ± 0.15 and 0.45 ± 0.15 IU/mL respectively. Comparing to UFH, which offered satisfactory anticoagulation according to the activated partial thromboplastin time, nadroparin-treated dialysis achieved similar thrombus scores and dialyser urea/creatinine clearances at the end of haemodialysis. During the post-dialysis period, one patient demonstrated residual LMWH effect (anti-Xa level 0.09 IU/mL) on the next day, whereas none had detectable anti-Xa activities 2 days afterwards upon next dialysis. CONCLUSIONS: Low-molecular weight heparin infusion is practical and effective as anticoagulation for NHHD. It can be safely used in an alternate-day haemodialysis schedule. A close monitoring for LMWH accumulation is recommended if long dialysis is performed daily.

Effects of five treatment regimens on blood loss and blood transfusion in total knee arthroplasty: a preliminary study in China
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OBJECTIVE: Our study is aimed to explore effects of five treatment regimens on blood loss and blood transfusion rate in total knee arthroplasty (TKA) patients. METHODS: 191 TKA patients were divided into the rivaroxaban, nadroparin, and tranexamic acid groups (n = 37 each) as well as into the affected-limb-position and tourniquet group (n = 40 each). A 3-month follow-up after operation was needed for all patients. The total blood loss, hidden blood loss, and dominant blood loss were recorded, and hemoglobin and red blood cell changes, pain and knee swelling degrees, hospital for special surgery (HSS), and American knee society (KSS) knee scores were observed. RESULTS: When compared with the rivaroxaban, nadroparin, and tourniquet groups, TKA patients' dominant blood loss, hidden blood loss, total blood loss, rate and volume of blood transfusion in the tranexamic acid and affected-limb-position groups were significantly decreased. While 7 days after operation, the hemoglobin and red blood cells in the tranexamic acid and affected-limb-position groups were significantly increased. At 1 month and 3 months after operation, when compared with the rivaroxaban, nadroparin, and tourniquet groups, the HSS and KSS scores in the tranexamic acid and affected-limb-position groups were all increased. In comparison with the rivaroxaban, nadroparin, and tourniquet groups, the D-Dimers after operation in the tranexamic acid and affected-limb-position groups were significantly lower. CONCLUSION: These results demonstrated that for TKA patients, the tranexamic acid and affected-limb-position could obviously reduce the blood loss and blood transfusion rate.
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Nadroparin carries a potentially high risk of inducing cutaneous delayed-type hypersensitivity responses.

BACKGROUND: Heparins are widely used for the prophylaxis/treatment of thromboembolic events. As adverse effects, heparin-induced skin lesions occur frequently (in 7.5-39% of patients). Skin lesions may be the only clinical manifestation of life-threatening immune-mediated heparin-induced thrombocytopenia, but are commonly caused by a delayed-type hypersensitivity response [heparin-induced delayed-type hypersensitivity (HIHS)]. Risk factors have not been prospectively identified. OBJECTIVES: To identify possible risk factors for heparin-induced skin lesions from three independent clinical trials in a combined analysis. METHODS: A pooled analysis from prospective studies was performed, and possible risk factors were included in a multiple logistic regression analysis. RESULTS: Obesity (body mass index of > 25), prolonged anticoagulant therapy, prior heparin exposure and younger age (< 55 years) were confirmed as independent risk factors for HIHS. The choice of anticoagulant preparation had the greatest influence. On comparison of dalteparin, enoxaparin, fondaparinux, unfractionated heparin, and nadroparin, the latter was associated with the highest risk of eliciting HIHS (odds ratio of 30.2, 95%CI: 11.7-77.9). CONCLUSIONS: The high risk associated with nadroparin has been validated in controlled trials, and this emphasizes the singularity of each heparin preparation in terms of allergenicity and that individualized anticoagulation is required.

Effects of ultrapure hemodialysis and low molecular weight heparin on the endothelial surface layer.

BACKGROUND: Chronic kidney disease patients show changes in the endothelial surface layer (ESL). Whether hemodialysis (HD) itself or low molecular weight heparins (LMWH) induce ESL alterations is unknown. METHODS: We studied the ESL in 20 HD patients with Sidestream Dark Field Imaging [measuring perfused boundary region (PBR)] and measurement of ESL constituents in plasma during HD in 2 studies. LMWH was administered at the start of HD in study A, and 120 min after the start of HD in study B. Mean platelet volume (MPV) and platelet large cell ratio (P-LCR) were also measured. RESULTS: Syndecan-1 increased significantly 30 min after LMWH administration. sP-Selectin increased 120 min after HD start, and MPV and P-LCR decreased significantly during HD. No significant changes of PBR, sE-Selectin, sICAM-1, or sVCAM-1 were perceived. CONCLUSIONS: HD caused a significant increase in Syndecan-1 without a change in PBR. The administration of LMWH appeared to precede the rise in Syndecan-1.

Fatal intrahepatic hemorrhage after nadroparin use for total hip arthroplasty.

Low-molecular-weight heparins have become the predominant choice for deep venous thrombosis prophylaxis and treatment. However, their use may cause bleeding complications. Intrahepatic bleeding is exceptional and only very few cases have been described. The authors present a unique case of fatal intrahepatic hematoma complicating nadroparin use in a 65-year-old woman with a hepatic cyst who was admitted to hospital for unilateral total hip arthroplasty. At autopsy, hemoperitoneum (2,000 ml of blood and clots) was evident. A ruptured sub-capsular hematoma involving the right lobe of the liver was observed. The hemorrhage within the cyst induced by the nadroparin use was likely responsible for the subsequent hepatic hematoma, liver rupture, and death. This case highlights the need for pathologists and surgeons to be aware of the possibility of intrahepatic hematoma in patients who have received low-molecular-weight heparins, undergone major surgery and present postoperative hemodynamic instability, especially in those with preoperative diagnosis of hepatic cyst.

Hemorrhage induced by antithrombotic agents: new insights from a real-world pharmacovigilance study.

BACKGROUND: Hemorrhage represents the most common and serious side effect of antithrombotic agents. Many studies have compared the risk of bleeding between different antithrombotic agents, but analysis of time-to-onset for hemorrhage induced by these drugs is yet sparse. METHODS: We conducted a retrospective study based on the adverse drug reaction reports on antithrombotic agents collected by the Henan Adverse Drug Reaction Monitoring Center. We assessed the reporting odds ratio to determine the disproportionate reporting signals for bleeding and the Weibull shape parameter was used to evaluate the time-to-onset data. RESULTS: In the signal detection, crude low molecular weight heparin-hemorrhage was found as a positive signal. The hemorrhage for most antithrombotic agents was random failure profiles. In particular, the hazard of hemorrhage decreased over time for warfarin and clopidogrel and increased for alteplase, nadroparin, and dipyridamole. CONCLUSION: We found that the risk of bleeding in patients taking Crude low molecular weight heparins was significantly higher compared to other antithrombotic agents, but with a small magnificence, which may be attributed to the severely irrational use of this medication under improper management. Statistics in days, results showed that the risk of bleeding decreased over time for warfarin and clopidogrel and increased for alteplase, nadroparin, and dipyridamole.

Aspirin plus heparin or aspirin alone in women with recurrent miscarriage.

BACKGROUND: Aspirin and low-molecular-weight heparin are prescribed for women with unexplained recurrent miscarriage, with the goal of improving the rate of live births, but limited data from randomized, controlled trials are available to support the use of these drugs. METHODS: In this randomized trial, we enrolled 364 women between the ages of 18 and 42 years who had a history of unexplained recurrent miscarriage and were attempting to conceive or were less than 6 weeks pregnant. We then randomly assigned them to receive daily 80 mg of aspirin plus open-label subcutaneous nadroparin (at a dose of 2850 IU, starting as soon as a viable pregnancy was demonstrated), 80 mg of aspirin alone, or placebo. The primary outcome measure was the live-birth rate. Secondary outcomes included rates of miscarriage, obstetrical complications, and maternal and fetal adverse events. RESULTS: Live-birth rates did not differ significantly among the three study groups. The proportions of women who gave birth to a live infant were 54.5% in the group receiving aspirin plus nadroparin (combination-therapy group), 50.8% in the aspirin-only group, and 57.0% in the placebo group (absolute difference in live-birth rate: combination therapy vs. placebo, -2.6 percentage points; 95% confidence interval [CI], -15.0 to 9.9; aspirin only vs. placebo, -6.2 percentage points; 95% CI, -18.8 to 6.4). Among 299 women who became pregnant, the live-birth rates were 69.1% in the combination-therapy group, 61.6% in the aspirin-only group, and 67.0% in the placebo group (absolute difference in live-birth rate: combination therapy vs. placebo, 2.1 percentage points; 95% CI, -10.8 to 15.0; aspirin alone vs. placebo -5.4 percentage points; 95% CI, -18.6 to 7.8). An increased tendency to bruise and swelling or itching at the injection site occurred significantly more frequently in the combination-therapy group than in the other two study groups. CONCLUSIONS: Neither aspirin combined with nadroparin nor aspirin alone improved the live-birth rate, as compared with placebo, among women with unexplained recurrent miscarriage. (Current Controlled Trials number, ISRCTN58496168.)

Low and Highly Variable Exposure to Prophylactic LMWH Nadroparin in Critically Ill Patients: Back to the Drawing Board for Prophylactic Dosing?

BACKGROUND AND OBJECTIVE: Low-molecular-weight heparins are routinely administered to patients in the intensive care unit to prevent venous thromboembolisms. There is considerable evidence that low-molecular-weight heparin doses should be personalised based on anti-Xa levels, but pharmacokinetic data in intensive care unit patients are lacking. This study aimed to characterise the pharmacokinetics and associated variability of the low-molecular-weight heparin nadroparin in critically ill patients. METHODS: Critically ill adult patients who were admitted to the intensive care unit and received nadroparin for prophylaxis of venous thromboembolism were included in a study. Population pharmacokinetic analysis was performed by means of parametric non-linear mixed-effects modelling (NONMEM). RESULTS: A total of 30 patients were enrolled with 12 patients undergoing continuous veno-venous hemodialysis and 18 patients not undergoing continuous veno-venous hemodialysis. Very high variability in pharmacokinetics was observed with an inter-individual variability in the volume of distribution of 63.7% (95% confidence interval 46.5-90.6), clearance of 166% (95% confidence interval 84.7-280) and relative bioavailability of 40.2% (95% confidence interval 29.5-52.6). We found that standard doses of 2850 IE and 5700 IE of nadroparin resulted in sub-prophylactic exposure in critically ill patients. CONCLUSIONS: Low exposure and highly variable pharmacokinetics of nadroparin were observed in intensive care unit patients treated with a prophylactic dose. It can be debated whether nadroparin is currently dosed optimally in intensive care unit patients and our findings encourage the investigation of higher and tailored dosing of nadroparin in the critically ill.

Thrombophylaxis and bleeding complications after cesarean section.

OBJECTIVE: To evaluate the safety of different regimes of thromboprophylaxis with low molecular weight heparins (LMWHs) in women undergoing cesarean section. DESIGN: Retrospective single-center cross-sectional study. SETTING: University Medical Center, The Netherlands. POPULATION: All women that delivered by cesarean section in the Erasmus Medical Center, Rotterdam, between January 2004 and December 2007 received thromboprophylaxis. We included women who received thromboprophylaxis according to the routine administration schedule at that time. METHODS: Three different consecutive regimes of thromboprophylaxis were used. In the first period, women received dalteparin 5000IU pre- and postoperatively (group A), in the second period, nadroparin 5700IU was administered pre- and postoperatively (group B), and in the third period, nadroparin 2850IU was administered not earlier than 6-12 hours postoperatively (group C). Detailed information on individual characteristics, cesarean section and postpartum period were extracted from patient files. MAIN OUTCOME MEASURES: Postoperative bleeding complications. RESULTS: A total of 1527 women were eligible and included. In group B, significantly more women experienced bleeding complications (necessitating either conservative treatment or re-laparotomy) compared with the other two groups (19/574 women in group B vs. 9/647 in group A and 1/306 in group C). After adjusting for potential confounders (maternal age, body mass index, and occurrence of preeclampsia/hemolysis, elevated liver enzymes and low platelet count) these effects remained significant (p=0.005). The incidence of thromboembolism was not different in the three groups. CONCLUSIONS: Different regimes of thromboprophylaxis in women with cesarean section influenced the occurrence of bleeding complications.

Localized and Generalized Skin Adverse Drug Reactions to Nadroparin Calcium Injection in 6 Cases of Pregnant Women.

Background: Despite the increasing number of skin adverse drug reactions caused by nadroparin calcium have been reported, mostly, little is known regarding of their details of clinical characteristics, especially for generalized skin adverse drug reactions. We sought to evaluate localized and generalized characteristics of the skin adverse drug reaction to nadroparin calcium injection in pregnant women. Methods: A retrospective study was conducted on 6 pregnant women, who experienced localized and generalized skin adverse drug reactions during long-term nadroparin calcium injection. The patients' clinical and imaging information were retrieved from medical records. The skin prick test, patch test, and intradermal test were performed after they stopped lactation. Causality assessment of suspected adverse drug reactions was performed on these cases. Results: The average total dose of nadroparin calcium injection in the 6 cases was 64.17 ± 22.66. Localized skin adverse drug reaction, manifested as erythema at the injection point, appeared after 47.5 ± 17.4 days of subcutaneous injection of nadroparin calcium. Generalized urticaria-like lesions, progressing from the injection site on the abdomen, appeared in 5.17 ± 3.60 days after the first appearance of localized reaction, while laboratory test results revealed essential peripheral blood eosinophilia. All rashes in the 6 cases subsided in 2-5 weeks after drug withdrawal. After delivery, 5 of 6 cases received complete skin tests to evaluate drug hypersensitivity. Results presented positive in the intradermal test within 7 days. Both the skin prick test and skin patch test were negative. Localized skin reactions and generalized urticaria-like adverse drug reactions were considered as definitely and probably caused by nadroparin calcium injection, respectively. Conclusion: Subcutaneous injection of nadroparin calcium in pregnant women appears to be at risk of localized and generalized urticaria-like adverse drug reaction. It is important to follow up the pregnant woman during nadroparin calcium injection for evaluating adverse drug reactions. Timely detection of symptoms is pivotal in early diagnosis and treatment of adverse drug reactions.

[Hyperkalemia due to low-molecular-weight heparin]. / Hyperkaliëmie bij laag-molecuulgewicht heparine.

BACKGROUND: The cause of hyperkalemia is frequently iatrogenic. Patient's prescriptions should therefore be checked in the analysis of the hyperkalemia. Low-molecular-weight heparin is not often suspected to cause this. CASE DESCRIPTION: A 64-year-old man, hospitalized because of a complicated clinical course of pancreatitis, developed an acute severe hyperkalemia. Further analysis was susceptive for hypoaldosteronism, which was confirmed with biochemical testing. The only drug that could cause hyperkalemia in this case was nadroparin, which was prescribed because of vena lienalis and a superior mesenteric vein thrombosis. A rechallenge with nadroparin showed a rapid rise in serum potassium, confirming our suspicion. CONCLUSION: In the diagnostic work-up of hyperkalemia, hypoaldosteronism should be considered in patients using LMWH. In particular when other risk factors for hyperkalemia are present, monitoring of potassium could be advised in patients receiving these agents.

Critical appraisal of evidence for anti-Xa monitoring and dosing of low-molecular-weight heparin in renal insufficiency.

INTRODUCTION: Several guidelines advise to monitor therapeutic LMWH therapy with peak anti-Xa concentrations in renal insufficiency with subsequent dose adjustments. A better understanding of the clinical association between peak anti-Xa concentrations and clinical outcomes is mandatory, because misunderstanding this association could lead to erroneous, and potentially even harmful, LMWH dose adjustments. AREAS COVERED: We reviewed the evidence of the widely applied therapeutic window for anti-Xa peak concentrations and report on the evidence for pharmacokinetic dose reduction in renal insufficiency, limitations of peak and trough anti-Xa concentration monitoring. EXPERT OPINION: The added value of peak anti-Xa monitoring in patients with renal insufficiency, receiving a dose reduced for pharmacokinetic changes, is not supported by data. Enoxaparin and nadroparin should be adjusted to 50-65% and 75-85% of the original dose for patients with a creatinine clearance (CrCL) of <30 ml/min and 30-60 ml/min, respectively. Tinzaparin should be adjusted to around 50% of the original dose for patients with a CrCL of <30 ml/min. In case anti-Xa monitoring is applied, trough concentration anti-Xa monitoring is preferred over peak monitoring, aiming at a maximum concentration of 0.4 IU/mL for once-daily dosed tinzaparin and 0.5 IU/mL for twice-daily dosed enoxaparin and nadroparin.

Trough anti-Xa activity after intermediate dose nadroparin for thrombosis prophylaxis in critically ill patients with COVID-19 and acute kidney injury.

Our objective was to assess the incidence of drug bioaccumulation in critically ill COVID-19 patients with AKI receiving intermediate dose nadroparin for thrombosis prophylaxis. We conducted a Prospective cohort study of critically ill COVID-19 patients. In patients on intermediate dose nadroparin (5700 IU once daily) we assessed the incidence of bioaccumulation (trough anti-Xa level > 0.2 IU/mL) stratified according to presence of AKI. We quantified this association using multilevel analyses. To assess robustness of our observations, we explored the association between AKI and anti-Xa activity in patients receiving high dose nadroparin (> 5700 IU). 108 patients received intermediate dose nadroparin, of whom 24 had AKI during 36 anti-Xa measurements. One patient with AKI (4.2% [95%CI 0.1-21%]) and 1 without (1.2% [95%CI 0.03-6.5%]) developed bioaccumulation (p = 0.39). Development of AKI was associated with a mean increase of 0.04 (95%CI 0.02-0.05) IU/ml anti-Xa activity. There was no statistically significant association between anti-Xa activity and AKI in 51 patients on high dose nadroparin. There were four major bleeding events, all in patients on high dose nadroparin. In conclusion, Bioaccumulation of an intermediate dose nadroparin did not occur to a significant extent in critically ill patients with COVID-19 complicated by AKI. Dose adjustment in AKI may be unnecessary.

Chemotherapy-associated thromboembolic risk in cancer outpatients and effect of nadroparin thromboprophylaxis: results of a retrospective analysis of the PROTECHT study.

BACKGROUND: Cancer patients receiving chemotherapy are at increased risk of thrombosis. Nadroparin has been demonstrated to reduce the incidence of venous and arterial thrombotic events (TEs) by about 50% in cancer outpatients receiving chemotherapy. The aims of this retrospective analysis were to evaluate the thromboembolic risk and the benefit of thromboprophylaxis according to type of chemotherapy. METHODS: Cancer outpatients were randomly assigned to receive subcutaneous injections of nadroparin or placebo. The incidence of symptomatic TEs was assessed according to the type of chemotherapy. Results were reported as risk ratios with associated 95% CI and two-tailed probability values. RESULTS: 769 and 381 patients have been evaluated in the nadroparin and placebo group, respectively. In the absence of thromboprophylaxis, the highest rate of TEs was found in patients receiving gemcitabine- (8.1%) or cisplatin-based chemotherapy (7.0%). The combination of gemcitabine and cisplatin or carboplatin increased the risk to 10.2%. Thromboprophylaxis reduced TE risk by 68% in patients receiving gemcitabine; with a further decrease to 78% in those receiving a combination of gemcitabine and platinum. CONCLUSIONS: This retrospective analysis confirms that patients undergoing chemotherapy including gemcitabine, platinum analogues or their combination are at higher risk of TEs. Our results also suggest that outpatients receiving chemotherapy regimens including these agents might achieve an increased benefit from thromboprophylaxis with nadroparin. CLINICAL TRIAL REGISTRATION NUMBER: NCT 00951574.

Anticoagulation for cerebral venous sinus thrombosis.

BACKGROUND: Treatment of cerebral venous sinus thrombosis with anticoagulants has been controversial. Anticoagulants may prevent new venous infarcts, neurologic deterioration and pulmonary embolism but may also promote haemorrhages. OBJECTIVES: To assess the effectiveness and safety of anticoagulant therapy in patients with confirmed cerebral venous sinus thrombosis. SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register (last searched August 2010), MEDLINE (1950 to August 2010), EMBASE (1980 to August 2010) and the Cochrane Central Register of Controlled Trials (The Cochrane Library, 2011 Issue 1). In an effort to identify further published, unpublished and ongoing trials we searched ongoing trials registers and reference lists of relevant articles, and contacted authors. SELECTION CRITERIA: Unconfounded randomised controlled trials in which anticoagulant therapy was compared with placebo or open control in patients with cerebral venous sinus thrombosis (confirmed by intra-arterial contrast, or venography with magnetic resonance, or venography with computed tomography imaging). DATA COLLECTION AND ANALYSIS: Two review authors independently extracted outcomes for each of the two treatment groups (anticoagulant treatment and control). The outcome data for each patient were analysed in the treatment group to which the patient was originally allocated (intention-to-treat analysis). We calculated a weighted estimate of the treatment effects across trials (relative risk, absolute risk reduction). MAIN RESULTS: We included two small trials involving 79 patients. One trial (20 patients) examined the efficacy of intravenous, adjusted dose unfractionated heparin. The other trial (59 patients) examined high dose, body weight adjusted, subcutaneous, low-molecular weight heparin (nadroparin). Anticoagulant therapy was associated with a pooled relative risk of death of 0.33 (95% confidence interval (CI) 0.08 to 1.21) and of death or dependency of 0.46 (95% CI 0.16 to 1.31). The absolute reduction in the risk of death or dependency was 13% (95% CI 30% to -3%). No new symptomatic intracerebral haemorrhages were observed. One major gastro-intestinal haemorrhage occurred after anticoagulant treatment. Two control patients (placebo) had a diagnosis of probable pulmonary embolism (one fatal). AUTHORS' CONCLUSIONS: Based upon the limited evidence available, anticoagulant treatment for cerebral venous sinus thrombosis appeared to be safe and was associated with a potentially important reduction in the risk of death or dependency which did not reach statistical significance.

Clinical safety and anticoagulation efficacy of low-molecular-weight heparins in chronic hemodialysis patients: a single medical center experience.

BACKGROUND: In many countries low-molecular-weight heparins (LMWHs) are increasingly used for hemodialysis (HD). Low-range activated clotting time (ACT-LR) values and anti-Xa activity had been used to monitor the degree of anticoagulation caused by LMWH. However, the facilities are not easily available at most hospitals. Such data are limited in Taiwan. METHODS: A total of 76 patients receiving maintenance HD were prospectively enrolled. The HD patients were randomized to receive either nadroparin or enoxaparin and checked the ACT-LR values and anti-Xa activity. We aimed to analyze ACT-LR values and anti-Xa activity along with the clotting of the dialyzer or bleeding events associated with two LMWHs after they were administered. We also aimed to determine the dose necessary to reach maximum safety and efficacy. RESULTS: We found no significant differences in LMWH dosage, ACT-LR values, and anti-Xa activity between the two groups. There were no significant differences in bleeding/adverse events and extracorporeal circuit thrombosis between the two groups. Most of the bleeding and adverse events were subcutaneous minor bleeding. No major bleeding or mortality was found. We found significant differences in mean dosage, cost, bleeding/adverse effect, and extracorporeal circuit thrombosis between excessive and reduced nadroparin dosage groups. CONCLUSION: LMWH is not still routinely used due to its high cost in Taiwan. In our clinical experience, nadroparin and enoxaparin exhibited high levels of safety and efficacy in chronic HD patients. Reduced LMWHs dosage could promote patient's safety and decreased HD cost in HD patients with excessive dosage of LMWHs.

An unusual adverse effect of nadroparin injections: Calcinosis cutis.

In 1988, Tumiati et al described the first case of calcinosis cutis related to a calcium-containing heparin. Since then, only 18 cases have been reported in the literature; they usually have an altered calcium-phosphate product, an elevated parathyroid hormone (PTH), or both. We report a 33-year-old patient who developed calcinosis cutis at sites of nadroparin injections without any disturbance of calcium-phosphate product, PTH, or vitamin D. The pathogenesis of calcinosis cutis secondary to nadroparin injections remains controversial; Proposed causes included metastatic, dystrophic, iatrogenic, or multifactorial etiologies. This is the first case of multiple nodules of calcinosis cutis without alterations of calcium-phosphate product, PTH, or vitamin D, which supports an iatrogenic mechanism. We also suggest that calcinosis cutis could be more frequent than we thought and is probably an underdiagnosed entity.