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Influence of Prescribed Blood Products on the Incidence of Deep Vein Thrombosis and Pulmonary Embolism in Surgical Patients.
Marušič, AP, Locatelli, I, Mrhar, A, Caprnda, M, Gaspar, L, Adamek, M, Kruzliak, P, Petrovič, D
Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis. 2017;(8):938-942
Abstract
Deep vein thrombosis (DVT) and pulmonary embolisms (PEs) are common complications after surgical procedures. The influence of prescribed blood products on the occurrence of DVT and PE was evaluated in postsurgical patients in this retrospective case-control study. The records of 286 surgical patients were analyzed: DVT (n = 52), PE (n = 92), and a control group (n = 142). The amounts of prescribed blood, blood products, and vitamin K were reviewed, together with appropriate prescribing of low-molecular-weight heparins. The influence of prescribed blood products on the occurrence of DVT or PE was analyzed using multinomial logistic regression. We demonstrated a significant difference between the test and control groups ( P < .05) in relation to receiving packed red blood cells. Treatment with red blood cells was associated with an increased risk of PE but not DVT. Patients who developed PE after surgery were hospitalized for longer (median 10 days) than patients with DVT (median 6 days). There was no difference between the test and control groups concerning treatment with fresh frozen plasma. Inadequate thromboprophylaxis significantly increased the likelihood of DVT. There is a connection between receiving packed red blood cells and occurrence of postoperative PE in surgical patients. Thus, patients receiving red blood cells should be monitored more closely after surgery, as they are more likely to develop PE postoperatively.
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The effect of parnaparin sodium on in vitro fertilization outcome: A prospective randomized controlled trial.
Lodigiani, C, Dentali, F, Banfi, E, Ferrazzi, P, Librè, L, Quaglia, I, Cafaro, L, Morenghi, E, Pacetti, V, Zannoni, E, et al
Thrombosis research. 2017;:116-121
Abstract
INTRODUCTION In-vitro and in-vivo models suggest the influence of low-molecular weight heparin on conception in infertile women undergoing in vitro fertilization procedures (IVF). In this randomized controlled trial we assessed whether a low-molecular weight heparin (parnaparin) could affect IVF outcomes. MATERIALS AND METHODS 271cycles were analyzed in 247 women having a first or subsequent IVF cycle at Fertility Center of Humanitas Research Hospital. Patients, without severe thrombophilia and hormonal or active untreated autoimmune disorders, were randomly allocated (1:1) to receive for the whole cycle parnaparin, or routine hormonal therapy only. The primary endpoint was the clinical pregnancy rate and the secondary endpoints included implantation rate and live birth rate. RESULTS The clinical pregnancy and the live birth rate were similar in treated and controls (21.5% vs. 26.7%, p=0.389; 18.5% vs. 20.6%, p=0.757). The abortion rate was 10.3% vs 22.9%, p=0.319, respectively. The subgroups analysis, ≤35, 36-38, 39-40years, showed the following: comparable clinical pregnancy rate (22.5% vs 38.8%, p=0.124; 21.8% vs 17.3%, p=0.631; 19.4% vs 23.3%, p=0.762 respectively) and live birth rate (16.3% vs 32.7%, p=0.099; 20.0% vs 13.5%, p=0.443; 19.4% vs 13.3%, p=0.731 respectively) in treated vs controls. Sensitivity analyses on women with ≥3 previous attempts and first enrolment only, and subgroup analyses according to trial conclusion conditioning a small sample size with low statistical power. CONCLUSIONS Our study excludes positive effect of parnaparin, once a day for the whole cycle, on clinical pregnancy rate in infertile women undergoing in vitro fertilization techniques.
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Rates of hospitalization among patients with deep vein thrombosis before and after the introduction of rivaroxaban.
Merli, GJ, Hollander, JE, Lefebvre, P, Laliberté, F, Raut, MK, Olson, WH, Pollack, CV
Hospital practice (1995). 2015;(2):85-93
Abstract
BACKGROUND Compared to warfarin, the non-vitamin K antagonist oral anticoagulant rivaroxaban may have advantages in treating patients with venous thromboembolism, because injectable bridging therapy and routine laboratory monitoring are not required. The objective of this study was to compare the rate of hospitalization in patients treated with rivaroxaban after its introduction with what it would have been before the introduction of rivaroxaban. METHODS A retrospective claims analysis was conducted using the MarketScan Hospital Drug Database from January 2011 to December 2013. Adult patients with a primary diagnosis of deep vein thrombosis (DVT) treated with rivaroxaban or low-molecular-weight heparin (LMWH) bridged to warfarin during the first day of an evaluation at a hospital were identified. Based on propensity-score methods, historical LMWH/warfarin patients (i.e., patients who received LMWH/warfarin before the approval of rivaroxaban) were matched 4:1 to rivaroxaban patients, and the rates of hospitalization were compared. RESULTS All rivaroxaban-treated patients (n = 134) in the database were well matched with four historical LMWH/warfarin-treated patients (n = 536). Among the rivaroxaban cohort, 60% of the patients were admitted to the hospital, compared to 82% of the historical patients treated with LMWH/warfarin in the matched cohort. The difference was statistically significant and corresponded to a 27% reduction in hospital admissions (rate ratio [95% confidence interval]: 0.73 [0.62-0.84]). Hospital admission rates adjusted for time-trend analyses also led to similar results. CONCLUSION The availability of rivaroxaban significantly reduced the hospitalization rate in patients with DVT treated with rivaroxaban compared to what it would have been if only LMWH/warfarin were available.
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Pharmacokinetics of Certoparin During In Vitro and In Vivo Dialysis.
Krieter, DH, Fink, S, Dorsch, O, Harenberg, J, Melzer, N, Wanner, C, Lemke, HD
Artificial organs. 2015;(11):951-9
Abstract
The efficacy and safety of certoparin in the prophylaxis of clotting during hemodialysis have recently been proven. Different to other low-molecular weight heparins (LMWHs), certoparin does not accumulate in maintenance dialysis patients for unknown reasons. The purpose of the present study was to examine the impact of the dialysis procedure on the removal of certoparin. In a subgroup of the MEMBRANE study consisting of 12 patients, the pharmacokinetics of certoparin during hemodialysis was determined by means of the anti-Xa activity. In addition, the elimination of certoparin into continuously collected dialysate was assessed. Further, in vitro experiments with human blood-simulating high-flux hemodialysis and hemofiltration were performed to quantify the elimination and the sieving coefficients SK of the two LMWHs certoparin and enoxaparin compared with unfractionated heparin (UFH). The surrogate marker middle molecules inulin and myoglobin served as reference solutes during the experiments. Finally, the adsorption of (125) iodine-radiolabeled certoparin onto the synthetic dialysis membrane was quantified. The clinical study reconfirmed the absence of bioaccumulation of certoparin with anti-Xa activities between <0.01 and 0.02 IU/mL after 24 h. A short plasma half-life time of 2.0 ± 0.7 h was determined during hemodialysis. Of the total certoparin dose injected intravenously prior to hemodialysis, only 2.7% was eliminated into dialysate. The in vitro experiments further revealed only 6% of certoparin to be adsorbed onto the dialysis membrane. The anti-Xa activities of certoparin and enoxaparin slowly declined during in vitro hemofiltration to 87.3 ± 5.5 and 82.5 ± 9.4% of baseline, respectively, while inulin and myoglobin concentrations rapidly decreased. The anti-Xa activity of UFH remained unchanged. The SK of both LMWH and UFH was very low in hemofiltration and particularly in hemodialysis with values ≤0.1. The elimination kinetics during hemodialysis suggests strong protein-binding of certoparin. Different from LMWH significantly cleared by the kidneys, the relatively short half-life time of certoparin of only 2 h during hemodialysis allows a more reliable control of the anti-coagulatory effects and decreases the risk of bleeding complications. Dialytic removal does not significantly contribute to the clearance of certoparin in maintenance dialysis patients.
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Daily administration of low molecular weight heparin increases Hepatocyte Growth Factor serum levels in gynaecological patients: pharmacokinetic parameters and clinical implications.
Surbone, A, Fuso, L, Passera, R, Ferrero, A, Marchese, C, Martino, C, Luchin, A, Di Renzo, MF, Zola, P
BMC research notes. 2012;:517
Abstract
BACKGROUND Hepatocyte Growth Factor (HGF) enhances cytotoxicity of paclitaxel (PTX) and cisplatin (CDDP) in human ovarian cancer cells. Because of potential pitfalls of HGF exogenous administration, we investigated whether HGF serum concentration might be alternatively raised in vivo by administering low molecular weight heparin (LMWH). METHODS The main HGF pharmacokinetic parameters were evaluated following acute and chronic LMWH treatment. First, women, operated on for gynaecological tumors, were treated with a single dose of calcium nadroparin and studied for 12 hours. Next, women operated on for benign or malignant gynaecological tumors were treated daily with calcic nadroparin for one month. Subsequently, the biological activity of the measured HGF serum levels was tested in assays of ovarian cancer cell sensitization to drugs. RESULTS In the short-term treated group, median HGF AUCss, Cmax and Caverage were about four-fold that of the control group, whereas Cmin was three-fold. In the patients treated chronically median HGF serum levels rose about six-fold in the first week, and decreased but remained significantly higher after one month. The pharmacokinetic of nadroparin-dependent HGF increase were similar in the two groups. The HGF concentrations measured after both acute and chronic treatment were found to be effective in sensitising ovarian cancer cells to chemotherapeutics. CONCLUSIONS This study raises the possibility of using LMWH to increase HGF serum concentration and to take advantage of its biological activities. In particular, nadroparin might be used as a chemo-potentiating agent in epithelial cell ovarian carcinoma through its action on HGF serum concentration. TRIAL REGISTRATION ClinicalTrials.gov ID: NCT01523652.
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Emergency anticoagulation treatment for cirrhosis patients with portal vein thrombosis and acute variceal bleeding.
Maruyama, H, Takahashi, M, Shimada, T, Yokosuka, O
Scandinavian journal of gastroenterology. 2012;(6):686-91
Abstract
OBJECTIVE To determine the safety and efficacy of anticoagulation treatment for portal vein thrombosis in cirrhosis patients with acute variceal bleeding, with patient eligibility determined by contrast ultrasonography findings. MATERIALS AND METHODS This prospective study included 23 consecutive cirrhosis patients (63.8 ± 11.8 years old, 12 males and 11 females) with emergency admission for acute variceal bleeding with or without portal vein thrombus. Eligibility for anticoagulation treatment was determined by positive intra-thrombus enhancement on contrast ultrasonography (perflubutane microbubble agent, 0.0075 mL/kg) performed before endoscopy. Low-molecular-weight heparin was administered after hemostasis was achieved by band ligation. Repeated band ligation or injection sclerotherapy combined with argon plasma coagulation was performed for variceal disappearance. RESULTS Hemostasis was achieved in all 10 patients with active bleeding. Five of these patients had portal vein thrombus, and all showed positive intra-thrombus enhancement on contrast ultrasonography. Anticoagulation treatment of these five patients resulted in complete recanalization of the portal vein within 2-11 days. There were no significant differences in the number of endoscopic treatment sessions or the length of hospital stay between the groups with and without thrombosis, and no complications including rebleeding were reported. Long term, none of the patients who continued oral anticoagulation treatment had recurrence of thrombosis (4/5). Variceal recurrence occurred only in the non-thrombosis group (2/18) during the follow-up period (median: 351 days). CONCLUSIONS Early anticoagulation treatment in cirrhosis patients with portal vein thrombosis and acute variceal bleeding may be safe, tolerated, and effective in cases with positive intra-thrombus enhancement on contrast ultrasonography.
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Low molecular weight heparin (LMWH) increases the efficacy of cisplatinum plus gemcitabine combination in advanced pancreatic cancer.
Icli, F, Akbulut, H, Utkan, G, Yalcin, B, Dincol, D, Isikdogan, A, Demirkazik, A, Onur, H, Cay, F, Büyükcelik, A
Journal of surgical oncology. 2007;(6):507-12
Abstract
BACKGROUND In this non-randomized study we aimed to assess the efficacy of the addition of low molecular weight heparin (LMWH) to gemcitabine (GEM) plus cisplatinum (CDDP) combination chemotherapy on survival by prevention of thromboembolic complications in patients with advanced pancreatic cancer (APC). PATIENTS AND METHODS Between November 1999 and February 2004, 69 consecutive patients with APC were treated with GEM (800 mg/m2, day 1, day 8) plus CDDP (35 mg/m2, day 1, day 8) every 21 days +/-LMWH (nadroparine calcium, 2,850 IU/day until disease progression). Ten out of 35 patients in LMWH group and 10 out of 34 patients in chemotherapy alone group had primary inoperable locally advanced disease and the rest of the patients had metastatic disease. RESULTS Total response rate was 58.8% (11.7% CR) for the patients treated with LMWH and 12.1% for those treated without LMWH (P = 0.0001). LMWH group had a better median time to progression (TTP) and survival when compared to control group (7.3 vs. 4.0 months, P = 0.0001; 13.0 vs. 5.5 months, P = 0.0001). The toxicity was similar and acceptable in both groups. CONCLUSION Addition of LMWH to GEM plus CDDP combination significantly improved the response and survival in patients with APC and the current schedule deserves to be tested in phase III trials.
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Effects of low molecular weight heparin on the frequencies of intradialytic arrhythmias in hemodialysis patients.
Miyauchi, H, Matsumoto, Y, Futenma, A, Amano, I, Miyauchi, J, Matsuo, S
Renal failure. 2006;(6):469-74
Abstract
Arrhythmia is known to cause sudden death in hemodialysis patients. Heparin administration releases lipoprotein lipase from the capillary endothelial cell surface, resulting in an increase in the plasma levels of free fatty acids; higher levels of free fatty acids may affect the occurrence of arrhythmias. This study assessed whether the occurrence of arrhythmias during hemodialysis could be suppressed by replacing unfractionated heparin with low molecular weight heparin. Ten dialysis patients who had supraventricular premature contraction and/or ventricular premature contraction were monitored by the Holter electrocardiograph system during hemodialysis. To investigate the effect of each form of heparin on plasma lipid metabolism, the lipoprotein lipase and lipid levels before and during hemodialysis were measured. The occurrence of arrhythmias was significantly suppressed in hemodialysis using low molecular weight heparin, as compared with hemodialysis using unfractionated heparin. Lower lipoprotein lipase and free fatty acids levels were also observed in hemodialysis using low molecular weight heparin. The authors concluded that hemodialysis using low molecular weight heparin instead of unfractionated heparin could be effective in protecting hemodialysis patients with arrhythmias against arrhythmia-related cardiac events.
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A randomized trial comparing 2 low-molecular-weight heparins for the outpatient treatment of deep vein thrombosis and pulmonary embolism.
Wells, PS, Anderson, DR, Rodger, MA, Forgie, MA, Florack, P, Touchie, D, Morrow, B, Gray, L, O'Rourke, K, Wells, G, et al
Archives of internal medicine. 2005;(7):733-8
Abstract
BACKGROUND Low-molecular-weight heparins (LMWHs) are now standard therapy for the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE). No published trials have compared LMWHs, and few studies have examined outpatient therapy for PE. Only tinzaparin sodium has demonstrated superiority to unfractionated heparin in a clinical trial. METHODS We compared 2 LMWH products, tinzaparin and dalteparin sodium, for the treatment of acute DVT and PE in a randomized, controlled clinical trial of consecutive outpatients presenting to a venous thromboembolism service at 4 tertiary-care hospitals. Patients were treated with subcutaneous tinzaparin sodium, 175 IU/kg every 24 hours, or subcutaneous dalteparin sodium, 200 IU/kg every 24 hours, for at least 5 days. Warfarin sodium therapy was started simultaneously and continued for 90 days. The primary end point was efficacy (recurrence of venous thromboembolism); safety (bleeding) was a composite end point. RESULTS Two hundred fifty-four patients received tinzaparin (39 with PE and 215 with DVT) and 251 received dalteparin (51 with PE and 200 with DVT). Most patients had an active malignancy or idiopathic DVT/PE. The outcome events occurred in 11 (4.4%; 95% confidence interval [CI], 2.2%-7.7%) and 15 patients (5.9%; 95% CI, 3.3%-9.5%) in the dalteparin and tinzaparin groups, respectively, including 9 and 10 recurrences, respectively, and 2 and 5 major hemorrhages, respectively (P = .44). The 95% CI on the difference of -1.5% was -5.3% to 2.4%. CONCLUSIONS Tinzaparin and dalteparin are safe and effective for the outpatient treatment of DVT or PE. Our finding of no differences between the LMWHs based on major clinical end points means that practical issues can be the deciding factor on which drug to use.
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Low-molecular-weight heparin versus low-dose aspirin in women with one fetal loss and a constitutional thrombophilic disorder.
Gris, JC, Mercier, E, Quéré, I, Lavigne-Lissalde, G, Cochery-Nouvellon, E, Hoffet, M, Ripart-Neveu, S, Tailland, ML, Dauzat, M, Marès, P
Blood. 2004;(10):3695-9
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Abstract
The prospective evaluation of the effect of thromboprophylaxis in women with one unexplained pregnancy loss from the 10th week of amenorrhea was performed. A total of 160 patients with heterozygous factor V Leiden mutation, prothrombin G20210A mutation, or protein S deficiency were given 5 mg folic acid daily before conception, to be continued during pregnancy, and low-dose aspirin 100 mg daily or low-molecular-weight heparin enoxaparin 40 mg was taken from the 8th week. Twenty-three of the 80 patients treated with low-dose aspirin and 69 of the 80 patients treated with enoxaparin had a healthy live birth (odds ratio [OR], 15.5; 95% confidence interval [CI], 7-34, P <.0001). Enoxaparin was superior to low-dose aspirin in each subgroup defined according to the underlying constitutional thrombophilic disorder. An associated protein Z deficiency and/or positive antiprotein Z antibodies were associated with poorer outcomes. The neonate weight was higher in the women successfully treated with enoxaparin, and neonates small for gestational age were more frequent in patients treated with low-dose aspirin. No significant side effects of the treatments could be evidenced in patients or newborns. As there is no argument to prove that low-dose aspirin may have been deleterious, these results support enoxaparin use during such at-risk pregnancies.