Comparison of efficacy of nadroparin and fondaparinux sodium for prevention of deep vein thromboembolism in lower extremities after total hip arthroplasty and total knee arthroplasty: a retrospective study of 592 patients.

OBJECTIVES: To compare the efficacy of nadroparin and fondaparinux sodium for prevention of deep vein thromboembolism (DVT) in lower extremities after total hip arthroplasty (THA) and total knee arthroplasty (TKA). METHODS: A total of 592 patients were enrolled in the study. Clinical data of patients who underwent total hip arthroplasty (THA) and total knee arthroplasty (TKA) in our hospital from December 2021 to September 2022 were retrospectively collected, which mainly included patients' general information, surgery-related information, and DVT-related information. The patients were categorized into the nadroparin group(n = 278) and the fondaparinux sodium group(n = 314) according to the types of anticoagulants used. Anticoagulant therapy began 12-24 h after operation and continued until discharge. DVT prevalence between two groups was compared. The Statistical Package for Social Sciences (SPSS) software version 25 (SPSS, Armonk, NY, USA) was used for statistical analysis. RESULTS: The prevalence of DVT in the nadroparin group and the fondaparinux sodium group was 8.3% (23/278) and 15.0% (47/314), respectively(p = 0.012). Statistical analysis showed that nadroparin group showed a lower prevalence of thrombosis than fondaparinux group (OR = 1.952, P = 0.012). Subgroup analyses showed that nadroparin group had a lower prevalence of DVT than fondaparinux group in some special patients groups such as female patients (OR = 2.258, P = 0.007), patients who are 65-79 years old (OR = 2.796, P = 0.004), patients with hypertension (OR = 2.237, P = 0.042), patients who underwent TKA (OR = 2.091, P = 0.011), and patients who underwent combined spinal-epidural anesthesia (OR = 2.490, P = 0.003) (P < 0.05). CONCLUSION: Nadroparin may have an advantage over fondaparinux sodium in preventing DVT in lower extremities after THA and TKA.

The effect of renal impairment and obesity on anti-Xa peak and trough levels in patients receiving therapeutic doses of nadroparin: a comparison with control patients.

PURPOSE: Anti-Xa peak level monitoring is recommended during LMWH treatment in renal impairment or obesity. The trough level has been proposed as marker for bleeding. We studied the influence of renal impairment and obesity on anti-Xa levels. METHODS: Peak and trough levels were collected during therapeutic nadroparin treatment in patients with renal impairment, obese patients, and controls. 27 patients (n = 68 samples) were evaluated and combined with published data (n = 319 samples from 35 patients) using population pharmacokinetic (popPK) modelling. RESULTS: Median peak level was 0.44 and 0.95 IU/mL in renal impairment with and without dose reduction and 0.60 and 0.43 IU/mL in obesity and controls, respectively. Trough levels were < 0.5 IU/mL in all patients with renal impairment with dose reduction and in 5/6 control patients. In the popPK model, total body weight and eGFR were covariates for clearance and lean body weight for distribution volume. Model-based evaluations demonstrated peak levels below the therapeutic window in controls and increased levels in renal impairment. Dose reductions resulted in a different effect on peak and trough levels. Obese patients (BMI up to 32 kg/m2) had similar levels upon weight-based dosing. CONCLUSION: In renal impairment, anti-Xa peak levels after dose reduction are comparable to those in controls. Weight-based dosing is suitable for obese patients. Aiming for peak levels between 0.6 and 1.0 IU/mL in these patients would result in overexposure compared to controls. Considering the association of trough levels and bleeding risk and our findings, trough monitoring seems to be a suitable parameter to identify nadroparin accumulation.

Low-Molecular-Weight Heparins (LMWH) and Synthetic Factor X Inhibitors Can Impair the Osseointegration Process of a Titanium Implant in an Interventional Animal Study.

Background and objectives: Cementless total hip arthroplasty is a common surgical procedure and perioperative thromboprophylaxis is used to prevent deep vein thrombosis or pulmonary embolism. Osseointegration is important for long-term implant survival, and there is no research on the effect of different thromboprophylaxis agents on the process of osseointegration. Materials and Methods: Seventy rats were allocated as follows: Group I (control group), Group II (enoxaparin), Group III (nadroparin), and Group IV (fondaparinux). Ovariectomy was performed on all subjects, followed by the introduction of an intramedullary titanium implant into the femur. Thromboprophylaxis was administered accordingly to each treatment group for 35 days postoperatively. Results: Group I had statistically significantly lower anti-Xa levels compared to treatment groups. Micro-CT analysis showed that nadroparin had lower values compared to control in bone volume (0.12 vs. 0.21, p = 0.01) and percent bone volume (1.46 vs. 1.93, p = 0.047). The pull-out test showed statistically significant differences between the control group (8.81 N) compared to enoxaparin, nadroparin, and fondaparinux groups (4.53 N, 4 N and 4.07 N, respectively). Nadroparin had a lower histological cortical bone tissue and a higher width of fibrous tissue (27.49 µm and 86.9 µm) at the peri-implant area, compared to control (43.2 µm and 39.2 µm), enoxaparin (39.6 µm and 24 µm), and fondaparinux (36.2 µm and 32.7 µm). Conclusions: Short-term administration of enoxaparin, nadroparin, and fondaparinux can reduce the osseointegration of titanium implants, with nadroparin having the most negative effect. These results show that enoxaparin and fondaparinux are preferred to be administered due to a lesser negative impact on the initial implant fixation.

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.

Correlation between activated partial thromboplastin time and anti-Xa activity in patients who received low-molecular weight heparin as anticoagulation for haemodialysis.

Plasma anti-Xa activity, the recommended test to monitor low-molecular weight heparin (LMWH) therapy, is not readily available in many laboratories. In our clinical trials on the use of LMWH as anticoagulation for haemodialysis, a consistent prolongation of APTT in addition to the elevated anti-Xa activity was observed in the patients after LMWH administration. Hence, the paired anti-Xa activity and APTT data were re-analyzed. The APTT ratio, which was the proportional change in APTT from the baseline value after LMWH administration, was found to have a strong correlation with anti-Xa activity (coefficient of determination, R 2 = 0.72, P < 0.001). In the receiver operating characteristic analysis, the APTT ratio was also found to be an excellent predictor of therapeutic anti-Xa activity ≧0.5 IU/mL (area under curve = 0.93, P < 0.001). The sensitivity was 88% and the specificity was 83.3% when an APTT ratio ≧1.4 was used as the cut point to predict the achievement of therapeutic anti-Xa activity. Our results illustrated that APTT is a potentially useful screening test to assess the degree of anticoagulation achieved by LMWH during haemodialysis, if the testing for plasma anti-Xa activity is not available.

Nadroparin for the prevention of venous thromboembolism in nonsurgical patients: a systematic review and meta-analysis.

Anticoagulant thromboprophylaxis with low molecular weight heparin is widely used in nonsurgical settings. To obtain best estimates of the effects of nadroparin for the prevention of venous thromboembolism (VTE) in nonsurgical patients, we conducted a systematic review and meta-analysis. Data sources were Medline, Embase, and Cochrane Library supplemented with conference abstracts, without language restrictions. Selection criteria were randomized controlled trials with nadroparin at prophylactic dose in adult nonsurgical patients. Main efficacy outcomes were major VTE (the composite of symptomatic deep vein thrombosis, symptomatic pulmonary embolism, asymptomatic proximal deep vein thrombosis and VTE-related death) and symptomatic VTE. The main safety outcome was major bleeding. We expressed treatment effects as risk ratios. Ten studies (4 vs. placebo or no treatment, 4 vs. UFH, 1 vs. fondaparinux and 1 vs. warfarin) enrolling a total of 7658 patients were included. In comparison with placebo, nadroparin reduced major VTE by about one-half (RR 0.48, 95% CI 0.24-0.97) with a consistent effect on symptomatic VTE (RR 0.69, 95% CI 0.46-1.05) and no increase in major bleeding (RR 1.51, 95% CI 0.40-5.79). In comparison with other pharmacological prophylaxis, nadroparin was similarly efficacious for prevention of major VTE (RR 1.14, 95% CI 0.63-2.10) and symptomatic VTE (RR 1.10, 95% CI 0.51-2.35) and produced similar effects on major bleeding (RR 0.60, 95% CI 0.25-1.50). Five studies were open label, and for three of these the adjudication method was not described or not blinded. In nonsurgical populations at risk of VTE, nadroparin reduced VTE by about one half compared with placebo or no treatment and appeared similarly effective and safe as other prophylactic anticoagulants.

Influence of Fondaparinux Versus Nadroparin Calcium Thromboprophylaxis on Clinical Parameters Following Total Knee Arthroplasty

Fondaparinux has been shown to be as effective as low molecular weight heparin in orthopedic surgery, with no cases of heparin induced thrombocytopenia proven until today. The main goal of this prospective randomized controlled trial was to define whether thromboprophylaxis in patients with primary osteoarthritis of the knee undergoing total knee arthroplasty (TKA) influences clinical parameters in the same manner in patients receiving fondaparinux as in those receiving nadroparin during the first 7 postoperative days. Sixty patients with primary knee osteoarthritis underwent unilateral TKA performed by the same surgeon and were randomized into two groups of 30 patients receiving either fondaparinux or nadroparin thromboprophylaxis. Patients were compared according to the duration of operation, perioperative blood loss, laboratory results and clinical evaluation of the edema during the early postoperative period. No differences were found between the groups in the mean duration of surgery, perioperative blood loss, and most of laboratory results. The level of urea was significantly lower in the nadroparin group on the first and second postoperative day. No cases of heparin induced thrombocytopenia, deep vein thrombosis or pulmonary embolism were noted during the study. Study results showed both fondaparinux and nadroparin to have the same influence on clinical parameters during the first 7 postoperative days in patients undergoing TKA.

Microvascular effects of the low molecular weight heparins in a colorectal xenograft model: an intravital microscopy study.

BACKGROUND: Low molecular weight heparins (LMWHs) are the cornerstone of the prevention of thromboembolic events in surgical patients. Recent clinical data suggest that LMWHs might improve survival of cancer patients, independent of their anticoagulant effect. The anti-cancer mechanism of LMWHs is incompletely understood, but may include effects on tumor angiogenesis. We assessed the effects of LMWHs on tumor angiogenesis and microcirculation in a mouse colorectal xenograft model using in vivo microscopy in window chambers. METHODS: HT29 human colorectal cancers were implanted in dorsal skinfold window chambers in athymic mice. Animals (n = 8 per group) were treated with 200 IU of nadroparin, enoxaparin, or saline for 8 d. Repeated intravital fluorescence microscopy was performed to calculate functional microcirculatory parameters as follows: number (N) and length (L) of microvessels, vascular area fraction (AF), and red blood cell velocity. Microvessel density, microvessel fractal dimension, and pericyte coverage were assessed histologically. RESULTS: Active angiogenesis was observed in control animals, resulting in a significant increase in N, L, and AF. In nadroparin- and enoxaparin-treated animals, however, AF did not change significantly over time and N and L remained significantly lower than untreated animals on day 7. Compared with control animals, nadroparin- and enoxaparin-treated animals showed a significantly lower microvessel density, but a higher pericyte coverage index, indicating a more mature microvessel network. CONCLUSIONS: The LMWHs nadroparin and enoxaparin inhibit tumor angiogenesis and result in microvessel normalization in this in vivo observed colorectal xenograft model.

Effect of conventional hemodialysis on the apixaban plasma concentration.

PURPOSE: Apixaban is a factor Xa inhibitor used in patients undergoing hemodialysis treatment. The objective of this study is to investigate the effect of hemodialysis on apixaban plasma concentrations. METHODS: This observational study is on patients treated with apixaban 2.5 mg twice daily on conventional hemodialysis with standard low-molecular-weight heparin (LMWH) anticoagulation (nadroparin 3800-7600 IU). Plasma blood samples were collected before starting dialysis (t1), 2 h after starting dialysis (t2), and directly after dialysis (t3). Apixaban concentration was measured before and after dialysis. Anti-Xa activity was measured for all three samples. RESULTS: A significant difference was observed between the apixaban concentration before and after dialysis (mean before dialysis 141.03 ng/mL; mean after dialysis 102.71 ng/mL; p = 0.003). Nonetheless, both apixaban plasma concentrations and anti-Xa levels remained within the reference range. Anti-Xa levels had a strong correlation with the apixaban concentrations (r = 0.935, p = 0.000). Thus, anti-Xa activity might be used as a surrogate for apixaban plasma concentration. CONCLUSION: There seems to be no need for dose adjustments of apixaban; co-administration of LMWH next to apixaban might also be unnecessary.

Is the current therapeutic dosage of nadroparin adequate for neonates and infants under 8 months with thromboembolic disease? a population pharmacokinetic study from a national children's medical center.

Objectives: Nadroparin, a low-molecular-weight-heparin is commonly used off-label in neonates and infants for thromboembolic events prevention. However, the recommended dosing regimen often fails to achieve therapeutic target ranges. This study aimed to develop a population pharmacokinetic (PK) model of nadroparin to determine an appropriate dosing regimen for neonates and infants less than 8 months. Methods: A retrospective chart review was conducted on patients treated with nadroparin at Children's Hospital of Fudan University between July 2021 and December 2023. A population PK model was developed using anti-Xa levels, and its predictive performance was evaluated internally. Monte Carlo simulations were performed to design an initial dosing schedule targeting anti-Xa levels between 0.5 and 1 IU/mL. Results: A total of 40 neonates and infants aged less than 8 months with gestational age ranging from 25 to 41 weeks treated with nadroparin were enrolled in the study for analysis. A one-compartment PK model with first order absorption and elimination was adequately fitted to the data. Creatinine clearance was identified as a significant factor contributing to inter-individual variability in clearance. The typical population parameter estimates of clearance, distribution volume and absorption rate in this population were 0.211 L/h, 1.55 L and 0.495 h-1, respectively. Our findings suggest that current therapeutic doses of nadroparin (150-200 IU/kg q12 h) may result in subtherapeutic exposure, thus higher doses might be required. Conclusion: The present study offers the first estimation of PK parameters for nadroparin in preterm or term neonates and infants less than 8 months utilizing the model. Our findings have potential implications for recommending initial personalized dosages, particularly among patient populations exhibiting similar characteristics.

Large variation in anti-factor Xa levels with nadroparin as thromboprophylaxis in COVID-19 and non-COVID-19 critically ill patients.

PURPOSE: Critically ill COVID-19 and non-COVID-19 patients receive thromboprophylaxis with the LMWH nadroparin. Whether a standard dosage is adequate in attaining the target anti-FXa levels (0.20-0.50 IU/ml) in these groups is unknown. METHODS: This study was a prospective, observational study in the ICU of a large general teaching hospital in the Netherlands. COVID-19 and non-COVID-19 patients admitted to the ICU who received LMWH in a prophylactic dosage of 2850 IU, 5700 IU or 11400 IU subcutaneously were eligible for the study. Anti-FXa levels were determined 4 h after administration. Relevant laboratory parameters, prespecified co-variates and clinical data were extracted from the electronic health record system. The primary goal was to evaluate anti-FXa levels in critically ill patients on a prophylactic dosage of nadroparin. The second goal was to investigate whether covariates had an influence on anti-FXa levels. RESULTS: A total of 62 patients were included in the analysis. In the COVID-19 group and non-COVID-19 group, 29 (96%) and 12 patients (38%) reached anti-FXa levels above 0.20 IU/ml, respectively. In the non-COVID-19 group, 63% of the patients had anti-FXA levels below the target range. When adjusted for nadroparin dosage a significant relation was found between body weight and the anti-FXa level (p = 0.013). CONCLUSION: A standard nadroparin dosage of 2850 IU sc in the critically ill patient is not sufficient to attain target anti-FXa levels in the majority of the studied patient group. We suggest a standard higher dosage in combination with body-weight dependent dosing as it leads to better exposure to nadroparin. CLINICAL TRIALS REGISTRATION: Retrospectively registered, ClinicalTrials.gov ID NTC 05926518 g, date of registration 06/01/23, unique ID 2020/1725.

Case Report: A successful outcome of nadroparin calcium therapy for cerebral venous sinus thrombosis in a child with acute lymphoblastic leukemia.

Background: The appearance of cerebral venous sinus thrombosis (CVST) in childhood acute lymphocytic leukemia (ALL) is a rare life-threatening disease that can cause significant morbidity, neurological sequelae, and potentially poor outcomes. Case presentation: We present the case of a 13-year-old boy with ALL who developed CVST and intrinsic hemorrhage approximately 30 days after receiving chemotherapy with vincristine, dexamethasone, daunorubicin, and pegylated-asparaginase (PEG-Asp). He complained of a severe headache and then developed a generalized seizure at night. T1- and T2-weighted magnetic resonance imaging (MRI) and cerebral magnetic resonance venography sequences revealed superior sagittal sinus thrombosis and intrinsic hemorrhagic changes in the bilateral frontoparietal lobes. He received nadroparin calcium as the anticoagulant treatment and was switched to Erwinia asparaginase (Erwinia Asp) rather than PEG-Asp. Oxcarbazepine and clonazepam were started with good seizure control. Intrathecal treatment was delayed until 1 month later. Anticoagulation treatment was stopped for 24 h before and 6 h after lumbar puncture. Platelet transfusion was administered to ensure the platelet count remained at >50 × 109/L. Oral acetazolamide (500-1,000 mg, daily) was administered to relieve headache and reduce intracranial pressure. Three months later, brain MRI showed a complete resolution of or significant improvement in the filling defect. Nadroparin calcium was administered for 1 week after switching to Erwinia Asp to prevent clot recurrence. He completed the 6-month chemotherapy and is doing well with no neurological sequelae and no recurrence of bleeding or thrombosis. Conclusions: Nadroparin calcium therapy appears to be safe and effective for pediatric CVST with ALL. The reintroduction of Erwinia Asp should be accompanied by anticoagulant therapy with nadroparin calcium.

Fondaparinux versus nadroparin for prevention of venous thromboembolism after elective hip and knee arthroplasty.

OBJECTIVE: To evaluate the efficacy and safety of fondaparinux compared with nadroparin for prevention of venous thromboembolism after arthroplasty. PATIENTS AND METHODS: One hundred fifteen patients were randomized into 2 treatment groups. Patients were given fondaparinux in Group I and nadroparin in Group II. Measurements were performed on Days 1, 5, and 21. The wound area was assessed with a subjective visual analog scale. RESULTS: The blood counts, clinical biochemical tests, and coagulation tests (ie, thrombin time, partial thromboplastin time, activated partial thromboplastin time, fibrinogen, prothrombin time-International Normalized Ratio, and antithrombin III activity) did not show statistically significant differences between Group I and Group II. In both study groups, anti-factor Xa activities increased significantly on the fifth and 21st day. The scores of the subjective visual analog scale showed significance on Day 21. CONCLUSIONS: Our results confirm the safety and efficacy of both fondaparinux and nadroparin for prophylaxis after major orthopedic surgery.

Effects of Routine Antithrombotic-Adjusted Dose of Rivaroxaban and Nadroparin Calcium on Tendon Healing of Rats: An Experimental Study.

Introduction Achilles tendon injury necessitates thromboembolism prophylaxis after repair. This study aimed to investigate the effects of antithrombotic-adjusted prophylactic doses of nadroparin calcium and rivaroxaban on Achilles tendon healing. Materials and Methods Twenty-four young adult male Wistar Albino type rats were randomly divided into three groups. All rats underwent a full-thickness surgical incision of the Achilles tendon, followed by primary repair. After the procedure, group 1 was determined as the control group and received no medication. Group 2 received 2.03 mg/kg rivaroxaban daily via gastric lavage once daily, and group 3 was given subcutaneous 114 IU AXa nadroparin calcium once daily for 28 days. After euthanization, the degrees of inflammation, neovascularization, fibroblastic activity, and collagen fiber sequencing were examined and scored for histopathological evaluation. The Statistical Package for Social Science (SPSS) version 21.0 for Windows software (SPSS, Inc., Chicago, Illinois, United States) was used for all statistical analyses. The number of inflammatory cells, capillary vessels, and fibroblasts, which met the parametric tests' assumptions, were compared between three independent groups by one-way analysis of variance. The significance level was set at p- value < 0.05. Results Histological examination of the group 1 sample showed the presence of inflammatory cells, an increase in the number of fibroblasts, and sequencing of collagen fibers scattered. The presence of inflammatory cells, remarkable increases in the number of fibroblasts, the presence of mature collagen fibers, and regular sequencing of collagen fibers regular were shown in groups 2 and 3. There were statistically significant differences between the groups regarding the number of inflammatory cells and fibroblasts. In group 2, the number of inflammatory cells was lower than in groups 1 and 3. Elsewhere, the number of fibroblasts was higher in group 1 compared than in groups 2 and 3. Conclusion Both rivaroxaban and nadroparin calcium in their daily dosage have a beneficial effect on Achilles tendon healing.

The right time to measure anti-Xa activity in critical illness: pharmacokinetics of therapeutic dose nadroparin.

Background: Peak anti-Xa activity of low-molecular-weight heparin nadroparin is measured 3 to 5 hours after subcutaneous injection. In critically ill patients, physiological changes and medical therapies may result in peak activities before or after this interval, possibly impacting dosing. Objectives: The primary objective was to determine the percentage of critically ill patients with adequately estimated peak activities drawn 3 to 5 hours after subcutaneous administration of a therapeutic dose of nadroparin. Adequate was defined as a peak activity of ≥80% of the actual peak anti-Xa activity. If ≥80% of patients had adequately estimated peak activities in the 3- to 5-hour interval, measurement in this interval was regarded as acceptable. The secondary objective was to determine the pharmacokinetic profile of nadroparin. Methods: In this single-center, prospective study, we evaluated anti-Xa activities in patients admitted to a general intensive care unit. After ≥4 equal doses of nadroparin, anti-Xa activity was measured according to a 12- to 24-hour sampling scheme. Results: In 25 patients, anti-Xa activities drawn between 3 and 5 hours after administration ranged 80% to 100% of the actual peak activity. Compared to the threshold level of an adequate estimation in at least 20 patients (≥80%), measuring anti-Xa activities in the 3- to 5-hour interval is an acceptable method (1-tailed binomial test; P < .02). We found a large interindividual variability for nadroparin exposure (mean ± SD area-under-the-curve0-12h, 10.3 ± 4.8 IU·h/mL) and delayed elimination (t1/2 range, 4.0-120.9 hours) despite adequate renal function. Conclusion: In critically ill patients, measuring anti-Xa activity in a 3- to 5-hour interval after subcutaneous injection of therapeutic nadroparin is an acceptable method to estimate the actual peak anti-Xa activity.

Rare complication of nadroparin injections: Skin necrosis and heparin-induced thrombocytopenia syndrome.

We described a rare case of nadroparin-induced skin necrosis with thrombocytopenia. LMWH therapy is used in thrombosis prophylaxis, it is important to recognize that skin necrosis can be a part of HIT early in its course and change heparin or LMWH to non-heparin anticoagulants such as direct thrombin III inhibitors or anti-Xa anticoagulants.

Sequential Therapy of Nadroparin and Rivaroxaban in the Initial Treatment of Patients With Acute Pulmonary Embolism.

Background: Sequential low molecular weight heparin (LMWH) plus warfarin, LMWH plus edoxaban, and LMWH plus dabigatran regimens have already shown efficacy and safety in the treatment of acute pulmonary embolism (PE). The efficacy and safety of sequential LMWH plus rivaroxaban regimen in the treatment of acute PE have been understudied. Methods: A retrospective study was performed to explore the efficacy and safety of sequential therapy regimens of subcutaneous LMWH (nadroparin 86 IU/kg every 12 h for a week) followed by oral rivaroxaban (20 mg once daily for 3 months) for the management of patients with established acute PE without hemodynamic instability, compared with those of nadroparin plus dabigatran and nadroparin plus warfarin. Results: The number of patients with total resolution of PE were 238 (80.1%), 220 (78.0%), and 166 (62.6%), in the nadroparin + rivaroxaban, nadroparin + dabigatra, and nadroparin + warfarin groups, respectively. (p = 0.001) The prevalence of DVT at the 3-month follow-up visit was 18 (6.1%), 14 (5.0%), and 11 (4.2%), in the aforementioned three groups, respectively. (p = 0.559) The NT-proBNP level (pg/ml) at the 3-month follow-up visit was 122.5 (97.4-158.9), 131.7 (102.2-166.3), and 357.8 (275.4-433.2) in the three groups, respectively. (p = 0.001) The D-dimer level (ng/ml) at the 3-month follow-up visit was 387.3 (310.9-465.2), 432.5 (382.4-489.6), and 854.0 (721.5-993.7) in the three groups, respectively (p < 0.001). The number of patients with major bleeding events was 3(0.9%), 6(1.8%), and 18 (5.5%) in the three groups, respectively (p < 0.001). Conclusion: The regimen of sequential subcutaneous nadroparin at body-weight adjusted dose for a week followed by oral rivaroxaban at a dose of 20 mg once daily for 3 months is effective and safe in the initial treatment of patients with acute pulmonary embolism.

Arterial Versus Venous Port Site Administration of Nadroparin for Preventing Thrombosis of Extracorporeal Blood Circuits in Patients Receiving Hemodiafiltration Treatment.

INTRODUCTION: Administration of low-molecular-weight heparins (LMWHs) is necessary for preventing extracorporeal circuit thrombosis during hemodialysis. A substantial amount of LMWH is removed with online hemodiafiltration (OL-HDF) when administered through the inlet site of the extracorporeal circuit. Consequently, administration of LMWH at the outlet site appears to be more efficient. In this study we aimed to compare the effects of nadroparin calcium (NAD) administered through the outlet versus the inlet port site in postdilution OL-HDF and assess the NAD dose reduction. METHODS: Forty-nine hemodialysis patients were included in 3 consecutive 6-week studies as follows: phase I, inlet port line; phase II, outlet port line; and phase III, outlet port line with reduced dose. We evaluated clotting in the hemodialyzer and venous bubble trap, the dialysis dose (K t/V), and substitution volume. RESULTS: Thirty four percent, 63%, and 66% were categorized as "white" during phases I, II, and III, respectively. During phases I, II, and III, 75%, 93%, and 95% of the venous bubble traps were "clean," and 9%, 0.6%, and 0.4% of the dialyzers clotted, respectively. Average NAD dose was 0.43 ml during phase I and 0.3 ml during phase II. During phase III, the LMWH dose was reduced by 33% to 50% in 15 patients. In phase III, Kt/V improved from 1.64 to 1.75 and substitution volume increased from 20.18 to 21.96 L. CONCLUSIONS: When using OL-HDF, a single administration of NAD at the outlet port line allows for a significant dose reduction and was associated with improved dialysis performance.

Tinzaparin vs. Nadroparin Safety and Efficacy in Neurosurgery.

BACKGROUND: An outbreak of African swine fever (ASF) in China in 2020 has led to an unprecedented shortage of nadroparin. Most patients, especially those kept in hospital for surgery, are currently treated with prophylactic anticoagulation (AC). In search of alternatives for nadroparin (fraxiparine), we found no sufficient data on alternatives for neurosurgical patients, such as tinzaparin of European origin. We compared nadroparin and tinzaparin concerning adverse events (bleeding versus thromboembolic events) in neurosurgical patients. METHODS: Between 2012 and 2018, 517 neurosurgical patients with benign and malignant brain tumors as well as 297 patients with subarachnoid hemorrhage (SAH) were treated in the Department of Neurosurgery, University Hospital Leipzig, receiving prophylactic anticoagulation within 48 h. In 2015, prophylactic anticoagulation was switched from nadroparin to tinzaparin throughout the university hospital. In a retrospective manner, the frequency and occurrence of adverse events (rebleeding and thromboembolic events) in connection with the substance used were analyzed. Statistical analysis was performed using Fisher's exact test and the chi-squared test. RESULTS: Rebleeding rates were similar in both nadroparin and tinzaparin cohorts in patients being treated for meningioma, glioma, and SAH combined (8.8% vs. 10.3%). Accordingly, the rates of overall thromboembolic events were not significantly different (5.5% vs. 4.3%). The severity of rebleeding did not vary. There was no significant difference among subgroups when compared for deep vein thrombosis (DVT) or pulmonary embolism (PE). CONCLUSION: In this retrospective study, tinzaparin seems to be a safe alternative to nadroparin for AC in patients undergoing brain tumor surgery or suffering from SAH.

Effectiveness and Safety of Nadroparin Therapy in Preterm and Term Neonates with Venous Thromboembolism.

INTRODUCTION: Optimal neonatal nadroparin dosages to treat venous thromboembolism (VTE) are unknown. OBJECTIVE: To evaluate therapeutic nadroparin dosages to reach therapeutic target ranges (TTR: 0.5-1.0 International Unit (IU)/mL) and the effectiveness and safety of nadroparin in neonatal VTE. METHODS: Retrospective study including neonates with VTE on nadroparin in a tertiary center between 2007 and 2018. Two groups were distinguished: neonates before (group 1) and after (group 2) switch to higher starting dosages in 2014. RESULTS: Sixty-one neonates (44 preterm, 17 term) with 64 VTEs were included. TTR was reached in 32/64 (50%) VTEs (group 1: 35.7%; group 2: 61.1%). Median nadroparin dosage to reach TTR was 197 (97.9-330.3) IU/kg/12 h. No therapy-related deaths occurred. Recurrent VTE developed in 6 (9.8%) neonates. Complete clot resolution was observed in 31/41 (75.6%) VTEs. TTR was reached in 58.1% VTEs with complete clot resolution. No major bleeding occurred. Non-major clinically relevant bleedings occurred in 3/64 (4.7%) VTEs, consisting of large hematomas due to the use of subcutaneous catheters. CONCLUSIONS: High nadroparin dosages are needed to reach TTR in neonates, which seem to be safe. Clot resolution may occur without reaching TTR. Subcutaneous catheters may cause important bleeding complications.