Safety and Efficacy of Tinzaparin Anticoagulation during Nocturnal Hemodialysis

2019 ◽  
Vol 50 (4) ◽  
pp. 255-261 ◽  
Author(s):  
Ann Bugeja ◽  
Sophie Harris ◽  
Brendan McCormick ◽  
Pierre-Antoine Brown ◽  
Channing Liberty ◽  
...  
Keyword(s):  
Unfractionated Heparin ◽  
Retrospective Cohort ◽  
Low Molecular Weight ◽  
Bleeding Events ◽  
Safety And Efficacy ◽  
Ottawa Hospital ◽  
Nocturnal Hemodialysis ◽  
Extracorporeal Dialysis ◽  
Extended Duration ◽  
Antifactor Xa

Background: The safety and efficacy of low-molecular-weight heparin in the prevention of extracorporeal dialysis circuit clotting among in-center extended duration nocturnal hemodialysis (INHD) patients are unknown. The aim of this study was to determine the safety and efficacy of 2 doses of tinzaparin, among INHD patients receiving 6–8 h hemodialysis, 3 times per week. Methods: We conducted a retrospective cohort study to examine antifactor Xa levels at time 0, 2 h, 4 h mid-hemodialysis (mid-HD), 6 h, and at end of each INHD session for 4 weeks and to determine extracorporeal dialysis circuit clotting and bleeding events after switching from unfractionated heparin to tinzaparin, using a standard protocol of tinzaparin delivery at the initiation and midpoint of HD. Results: All 16 patients in The Ottawa Hospital INHD program were converted to tinzaparin and followed for 177 INHD sessions. Mean antifactor Xa level at 2 h of HD was 0.41 ± 0.21 (SD) IU/mL, at 4 h (mid-HD) 0.19 ± 0.17 IU/mL, at 6 h 0.44 ± 0.21 IU/mL, and at dialysis end 0.26 ± 0.14 IU/mL. Antifactor Xa levels were undetectable at the start of INHD, suggesting no tinzaparin accumulation. Five patients required an increase in tinzaparin due to extracorporeal dialysis circuit clotting. There were no bleeding events. One patient required a switch to fondaparinux due to an adverse reaction. Conclusion: Tinzaparin was safe and efficacious for most INHD patients without accumulation or bleeding. The conversion from unfractionated heparin to tinzaparin required an increased tinzaparin dose for 31% of INHD patients.

Novel Design of Peptides to Reverse the Anticoagulant Activities of Heparin and other Glycosaminoglycans

2001 ◽  
Vol 85 (03) ◽  
pp. 482-487 ◽  
Author(s):  
Joel Gradowski ◽  
James San Antonio ◽  
Jose Martinez ◽  
Barbara Schick
Keyword(s):  
Molecular Weight ◽  
Unfractionated Heparin ◽  
Low Molecular Weight Heparin ◽  
Factor Xa ◽  
Low Molecular Weight ◽  
Heparin Binding ◽  
Antifactor Xa ◽  
Novel Design

SummaryPatients undergoing anticoagulation with unfractionated heparin, low molecular weight heparin, or danaparoid may experience excess bleeding which requires reversal of the anticoagulant agent. Protamine is at present the only agent available for reversal of unfractionated heparin. Protamine is not effective in patients who have received low molecular weight heparin or danaparoid. We have developed a series of peptides based on consensus heparin binding sequences (Verrecchio et al., J Biol Chem 2000; 275: 7701-7707) that are capable of neutralizing the anti-thrombin activity of unfractionated heparin in vitro, the antifactor Xa activity of unfractionated heparin, Enoxaparin (Lovenox) and danaparoid (Orgaran) in vitro and the anti-Factor Xa activity of Enoxaparin in vivo in rats. These peptides may serve as alternatives for Protamine reversal of UFH and may be useful for neutralization of enoxaparin and danaparoid in humans.

scholarly journals A direct comparison of prophylactic low-molecular-weight heparin versus unfractionated heparin in neurosurgery: A meta-analysis

2019 ◽  
Vol 10 ◽  
pp. 202 ◽  
Author(s):  
Mohamed Macki ◽  
Mohamed Fakih ◽  
Sharath Kumar Anand ◽  
Raviteja Suryadevara ◽  
Jaafar Elmenini ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Unfractionated Heparin ◽  
Outcome Measures ◽  
Low Molecular Weight Heparin ◽  
Meta Analysis ◽  
Forest Plot ◽  
Low Molecular Weight ◽  
Safety And Efficacy ◽  
Major Complications ◽  
Neurosurgical Patients

Background: Several studies have confirmed the role of prophylactic low-molecular-weight heparin (LMWH) for venous thromboembolism (VTE) in neurosurgery; however, a paucity of literature has assessed its safety and efficacy versus prophylactic unfractionated heparin (UFH). The objective is to present a meta-analysis directly comparing prophylactic LMWH to UFH for the prevention of VTE in neurosurgery. Materials and Methods: Relevant studies that directly compared LMWH to UFH for prophylaxis of VTE in neurosurgery and/or spine surgery were identified by MEDLINE and EMBASE searches plus a scrutiny of references from the original articles and reviews. Three randomized trials were included in the meta-analysis. Efficacy and safety were ascertained per three primary outcome measures: VTE, minor complications (decline in hemoglobin/hematocrit), and major complications. Forest plot analysis provided odds ratio (OR), 95% confidence intervals (CIs), and P-values. Results: Of the 429 patients in the pooled analysis, the postoperative VTE rate of 5.6% (12/213) after LMWH chemoprophylaxis was equivalent to 3.7% (8/216) after UFH chemoprophylaxis (OR = 1.42, 95% CI 0.62–3.75, P = 0.308). Minor complications of 4.7% versus 4.6%, respectively, were nearly equal (OR = 1.01, 95% CI 0.41– 2.50, P = 0.929). All four major complications included intracranial hemorrhages: three after LMWH (1.4%) and one after UFH (0.5%) (OR = 2.32, 95% CI 0.34–16.01, P = 0.831). Tests for heterogeneity were nonsignificant in all three outcome measures. Conclusion: Rates of VTE, minor complications, and major complications were equivalent between prophylactic LMWH and UFH in neurosurgery. Further, randomized clinical trials comparing the two heparin products are required to elucidate superior safety and efficacy in neurosurgical patients.

Assessment of venous thromboembolism treatment in patients with cancer on low molecular weight heparin, warfarin, and the direct oral anticoagulants

2017 ◽  
Vol 25 (2) ◽  
pp. 261-268 ◽  
Author(s):  
Ellen M Uppuluri ◽  
Kelly R Burke ◽  
Christina Mactal Haaf ◽  
Nancy L Shapiro
Keyword(s):  
Molecular Weight ◽  
Venous Thromboembolism ◽  
Low Molecular Weight Heparin ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Low Molecular Weight ◽  
Bleeding Events ◽  
Safety And Efficacy ◽  
Patients With Cancer ◽  
Relationship Of

Background Direct oral anticoagulants (DOACs) are not recommended for venous thromboembolism (VTE) treatment in patients with cancer because their safety and efficacy have not been compared to low molecular weight heparin (LMWH) in large trials. Routine anti-Xa monitoring in cancer patients on LMWH is also not recommended due to limited data correlating anti-Xa levels and outcomes. Objective Compare the safety and efficacy of DOACs to LMWH and warfarin and assess the relationship of anti-Xa monitoring and outcomes in patients with cancer taking LMWH in an urban university setting. Methods This retrospective, cohort study analyzed the recurrence of VTE and number of bleeding events in patients with cancer. Results There were 131 patients included in the analysis. There was no difference seen in the rate of recurrent VTEs between the LMWH, warfarin and DOAC groups (9.3%, 5.9%, 9.1%, p = 0.89). There was also no difference in the rate of bleeding between groups (10.5%, 14.7%, 9.1%, p = 0.576). There was an increased rate of mortality seen in the LMWH group (26.7% vs. 2.9% vs. 18.2%, p = 0.006). There was no difference seen in recurrent VTE (10.3% vs. 8.5%, p = 0.53) or bleeding (10.3% vs. 10.7%, p = 0.661) between the monitored and unmonitored LMWH patients. Conclusion Results of this analysis suggest DOACs may be as safe and effective as LMWH and warfarin for the treatment of VTE in patients with cancer, and there may be no clinical benefit to routine anti-Xa monitoring in patients on LMWH treatment. However, larger studies are needed to confirm these observations.

Unfractionated Heparin and CY 216: Pharmacokinetics and Bioavailabilities of the Antifactor Xa and IIa Effects after lntravenous and Subcutaneous Injection in the Rabbit

1989 ◽  
Vol 61 (03) ◽  
pp. 348-353 ◽  
Author(s):  
L Briant ◽  
C Caranobe ◽  
S Saivin ◽  
P Sié ◽  
B Bayrou ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Unfractionated Heparin ◽  
Subcutaneous Injection ◽  
Low Molecular Weight Heparin ◽  
Activity Ratio ◽  
Biological Activities ◽  
Pharmacokinetic Parameters ◽  
Low Molecular Weight ◽  
Time Intervals ◽  
Antifactor Xa

SummaryThis report compares the pharmacokinetics and the bioavailabilities of the antifactor Xa and of the antifactor II a activities generated by intravenous (IV) and subcutaneous (SC) injections of increasing doses of unfractionated heparin (UH) and of a low molecular weight heparin (CY 216). Rabbits were injected with 500, 1,000, 2,500 and 5,000 antifactor Xa u/kg of both heparins and their biological activities were followed at various time intervals. After IV injection the clearance of the antifactor Xa activities was independent of the dose and the clearance of UH was significantly higher than that of CY 216; after SC injection the bioavailability estimated from the antifactor Xa effect was consistently over 100% for CY 216 while that of UH increased from 27% at the lowest dose to 93% at the highest dose. The pharmacokinetic parameters estimated by the antifactor IIa activity of UH were superimposable to those calculated with the antifactor Xa activity. For CY 216 no direct comparison between the two activities was made since the dose injected expressed in antifactor IIa units was 3.4 times lower. UH and CY 216 were therefore injected intravenously to other animals at equivalent and increasing doses expressed in antifactor IIa units (50-5,000 u/kg). The pharmacokinetic parameters calculated from the curves of the antifactor IIa activities were basically identical except at the two lower doses (50 and 100 u/kg) for which UH was cleared faster than CY 216. These results indicate that the antifactor IIa activity generated by an injection of CY 216 disappears faster than the corresponding antifactor Xa activity and therefore that the antifactor Xa/antifactor IIa activity ratio of CY 216 progressively increases after SC or IV injection.

Markers of Hemostatic System Activation in Acute Deep Venous Thrombosis-Evolution during the First Days of Heparin Treatment

1993 ◽  
Vol 70 (06) ◽  
pp. 0909-0914 ◽  
Author(s):  
Keyword(s):  
Molecular Weight ◽  
Venous Thrombosis ◽  
Deep Venous Thrombosis ◽  
Unfractionated Heparin ◽  
Low Molecular Weight Heparin ◽  
Factor Xa ◽  
Low Molecular Weight ◽  
Dose Adaptation ◽  
Heparin Treatment ◽  
Lung Scan

SummaryFibrin D-Dimer (D-Di), prothrombin activation fragment (F 1+2) and thrombin-antithrombin III complexes (TAT) were measured using ELISA procedures in the plasma of patients with an acute deep venous thrombosis (DVT), at presentation and on days 2, 6 and 10 after initiation of heparin treatment. Patients were randomly allocated into two treatment groups: 44 patients received adapted doses of continuous intravenous unfractionated heparin (UH) whereas 47 received 1 mg/kg every twelve hours of a low molecular weight heparin (enoxaparin) subcutaneously. A phlebography and a perfusion lung scan were performed before inclusion and on day 10. Failure of therapy (n = 9) was defined by venogram worsening or confirmed pulmonary embolism. Improvement (n = 44) or stationary state (n = 38) were defined by venogram evolution in the absence of new leg scan defects.At presentation, D-Di, F 1 + 2 and TAT were above cut-off values in 97, 66 and 89% of patients respectively. D-Di levels correlated with the extent of venous thrombosis whereas TAT and F 1 + 2 did not. Mean levels of D-Di decreased sharply during the first days of treatment but were still abnormal on day 10. A secondary increase of D-Di on days 6 or 10 by more than 3 μg/ml occurred in 4 of the 9 patients who developed a thromboembolic recurrence but in none of the 72 patients who had a more favorable outcome. F 1 + 2 and TAT time-courses were not related to clinical evolution. In the Enoxaparin group, there was no relationship between antifactor Xa activities and any biological markers. TAT and F 1 + 2 levels fell on day 2 and remained stable until day 10. In contrast, in the UH group, TAT and F 1 + 2 did not significantly decrease on day 2, probably due to a delay in dose adaptation, but they declined slowly until day 10.In conclusion, D-Di displays a higher sensitivity than F 1 + 2 or TAT for the diagnosis of D\T. D-Di, but not TAT or F 1 + 2, follow-up seems to be of potential value for early detection of recurrency. Hemostatic activation is controlled earlier by fixed doses of a low molecular weight heparin, irrespective of the plasma anti-factor Xa activities, than by unfractionated heparin at adapted doses.

Effects of Unfractionated and Low Molecular Weight Heparins on Platelet Thromboxane Biosynthesis “In Vivo”

1994 ◽  
Vol 72 (06) ◽  
pp. 942-946 ◽  
Author(s):  
Raffaele Landolfi ◽  
Erica De Candia ◽  
Bianca Rocca ◽  
Giovanni Ciabattoni ◽  
Armando Antinori ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Unfractionated Heparin ◽  
Low Molecular Weight Heparin ◽  
Primary Source ◽  
In Vivo Studies ◽  
Low Molecular Weight ◽  
Heparin Administration ◽  
To Receive

SummarySeveral “in vitro” and “in vivo” studies indicate that heparin administration may affect platelet function. In this study we investigated the effects of prophylactic heparin on thromboxane (Tx)A2 biosynthesis “in vivo”, as assessed by the urinary excretion of major enzymatic metabolites 11-dehydro-TxB2 and 2,3-dinor-TxB2. Twenty-four patients who were candidates for cholecystectomy because of uncomplicated lithiasis were randomly assigned to receive placebo, unfractionated heparin, low molecular weight heparin or unfractionaed heparin plus 100 mg aspirin. Measurements of daily excretion of Tx metabolites were performed before and during the treatment. In the groups assigned to placebo and to low molecular weight heparin there was no statistically significant modification of Tx metabolite excretion while patients receiving unfractionated heparin had a significant increase of both metabolites (11-dehydro-TxB2: 3844 ± 1388 vs 2092 ±777, p <0.05; 2,3-dinor-TxB2: 2737 ± 808 vs 1535 ± 771 pg/mg creatinine, p <0.05). In patients randomized to receive low-dose aspirin plus unfractionated heparin the excretion of the two metabolites was largely suppressed thus suggesting that platelets are the primary source of enhanced thromboxane biosynthesis associated with heparin administration. These data indicate that unfractionated heparin causes platelet activation “in vivo” and suggest that the use of low molecular weight heparin may avoid this complication.

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