Tinzaparin Research Articles

Efficacy and safety of once daily low molecular weight heparin (tinzaparin sodium) in high risk pregnancy

Low molecular weight heparin (LMWH) is widely regarded as the anticoagulant treatment of choice for the prevention and treatment of venous thromboembolism during pregnancy. However, previous studies have demonstrated that the pharmacokinetic profiles of LMWH vary significantly with increasing gestation. Consequently, it remains unclear whether LMWH regimens recommended for use in nonpregnant individuals can be safely extrapolated to pregnant women. The aims of this study were to assess the safety and the efficacy of tinzaparin sodium (Innohep) administered only once daily during pregnancy. A systematic retrospective review identified a cohort of 37 high-risk pregnancies which had been managed using tinzaparin 175 IU/kg once daily. In 26 cases, the index pregnancy had been complicated by development of an acute venous thromboembolism (17 deep vein thrombosis and nine pulmonary embolism). For each individual, case notes were examined and data extracted using a predetermined questionnaire. No episodes of recurrent venous thromboembolism were identified amongst this cohort of pregnancies managed using once daily LMWH administration. However, two unusual thrombotic complications were observed, including a parietal infarct in one patient, and a postpartum cerebral venous thrombosis in another. Once daily tinzaparin was well tolerated, with no cases of heparin-induced thrombocytopaenia, symptomatic osteoporosis, or foetal malformations. Tinzaparin dose modification based upon peak anti-Xa levels occurred in 45% of the cases examined. The present study is the largest study to have examined the clinical efficacy of once daily LMWH for use in pregnant women at high risk of venous thromboembolism. Our data support the safety and efficacy of antenatal tinzaparin at a dose of 175 IU/kg. In order to determine whether this once daily regimen provides equivalent (or indeed greater) thromboprophylaxis to twice daily LMWH regimens during pregnancy will require highly powered direct comparative studies.

Use of fondaparinux as an anticoagulant during hemodialysis: a preliminary study

To study the effect of fondaparinux, a new antithrombotic agent, as an anticoagulant during a 4-hour conventional hemodialysis session. materials and methods: Fondaparinux was administered as an anticoagulant to 16 chronic hemodialysis patients during a single 4-hour hemodialysis session at an intravenous bolus dose of 2.5 mg. Eight patients were using high-flux polyester polymer alloy (PEPA) dialyzers (Group A) and the remainder low-flux polysulfone dialyzers (Group B), whilst all had received conventional doses of tinzaparin sodium as an anticoagulant during the previous month. The dialyzers were primed with 1 l of normal saline containing 5,000 IU of unfractionated heparin. Blood samples for the measurement of INR, APTT (activated partial thromboplastin time) and anti-Xa levels were taken before the study dialysis session (pre), 5 min postdialysis (post), and before the next dialysis session (next). Mean fibrin/clot formation in the extracorporeal circuit and dialyzer was assessed macroscopically by visual inspection and was graded using a 4-point scale. Predialysis anti-Xa levels were 0.04 A+/- 0.03 IU/ml in Group A, and 0.025 A+/- 0.025 IU/ml in Group B (p = NS). Postdialysis anti-Xa levels were significantly higher than predialysis levels in both groups (Group A = 0.16 A+/- 0.04 IU/ml, Group B = 0.46 A+/- 0.12 IU/ml, p < 0.02 for both) and significantly higher in Group B compared to Group A (p < 0.025). Anti-Xa levels before the next dialysis session were 0.06 A+/- 0.04 IU/ml in Group A and 0.25 A+/- 0.06 IU/ml in Group B (p < 0.0001 between Groups A and B). APTT values were significantly higher in postdialysis than predialysis samples for both groups (higher by 27.0 A+/- 26.0% in Group A and 24.3 A+/- 31.9% in Group B). No significant differences were found when comparing APTT values in pre, post and next samples between Groups A and B. No differences were also found between pre, post and next samples for INR values, either within or between groups. Mean fibrin/ clot formation score in the extracorporeal circuit at the end of the study dialysis session was significantly higher in patients of Group A than those of Group B (p < 0.05). Dialysis had to be terminated before the completion of 4 hours in 2 patients of Group A because of the presence of extensive fibrin/clots in the circuit and dialyzer. Our findings indicate that fondaparinux sodium at an intravenous dose of 2.5 mg can be used successfully as an anticoagulant during a 4-hour conventional hemodialysis session in patients dialyzed with low-flux polysulfone dialyzers, but not in those dialyzed with high-flux dialyzers. However, anti-Xa levels in the former patients were still increased before the next dialysis session, potentially exposing the patients to an increased risk of bleeding.

Epidural Hematoma Secondary to Removal of an Epidural Catheter After a Total Knee Replacement

Varitimidis, Sokratis E. MD1; Paterakis, Konstantinos MD1; Dailiana, Zoe H. MD1; Hantes, Michalis MD1; Georgopoulou, Stavroula MD1 Author Information

4 Efficacy and safety of once-daily therapeutic dose low molecular weight heparin (tinzaparin sodium) in high-risk pregnancy

4 Efficacy and safety of once-daily therapeutic dose low molecular weight heparin (tinzaparin sodium) in high-risk pregnancy

Efficacy and Safety of Tinzaparin Sodium as a Bridging Agent for Patients on Oral Anticoagulant Undergoing General Surgery: Clinical Experience with the First 100 Consecutive Patients.

The aim of the present prospective study was to test the efficacy and safety of a bridging protocol in patients under oral anticoagulants (OA) who need to undergo general surgery. One hundred consecutive patients receiving oral anticoagulant accenocoumarol for various cardiovascular disorders entered the study. Patients underwent 107 scheduled operations (among them 41 cholecystectomies, 24 colectomies, 13 hernia repairs and 9 ERCPs, the 7 followed by cholecystectomy), receiving the low molecular weight heparin (LMWH) tinzaparin sodium as the bridging agent. At least 4 days prior to the operation the OA was replaced with tinzaparin at a daily dose of 175 anti-Xa IU per kg of body weight. Patients received no LMWH on the day of the operation and the OA was co-administered with tinzaparin on the second post-operative day and for at least 2 days. When target INR (2.5 to 3) was achieved, tinzaparin administration was stopped. Lower limbs color duplex was performed pre-operatively and on the 2nd, 8th–10th and 20th–30th post-operative day. Complete anticoagulation profile, intra-operative bleeding and post-operative blood loss, large haematoma development (over 5 cm in diameter), deep vein thrombosis (DVT) and 30-day morbidity and mortality were thoroughly recorded. During the 30-day period 1 patient died (from sepsis), 9 developed wound infections and three underwent re-operations (two for anastomotic leaks and one for duodenal perforation following ERCP). None of these events was related to the bridging process. There were no proximal DVTs. Three asymptomatic distal vein thromboses (2 posterior tibial and one peroneal ) were identified on post-operative duplex scan. No large wound haematomas were seen. One colorectal surgery patient had a drain blood loss of 460 ml on the first and 140 ml on the second post-operative day, requiring blood transfusion; tinzaparin administration was delayed for three days in this case. Finally, in 17 cases we had difficulties in adjusting INR levels to the desired range; in these cases tinzaparin administration was prolonged for 2–5 days. We conclude that our bridging protocol, using therapeutic doses of the LMWH tinzaparin sodium as the bridging agent, is both safe and effective for replacing OAs in patients undergoing general surgery operations.

Results from tinzaparin sodium pharmacokinetic studies in paediatric patients show that dose requirements are age dependent,

Results from tinzaparin sodium pharmacokinetic studies in paediatric patients show that dose requirements are age dependent,

Comparison of two low-molecular weight heparins (LMWHs), tinzaparin and bemiparin, during hemodialysis

The anticoagulant effects of two LMWHs, tinzaparin sodium and bemiparin sodium, were compared during two study dialysis (SD) sessions (SD1 with tinzaparin and SD2 with bemiparin) in ten chronic hemodialysis patients. Prior to SD1, patients had received 3,500 IU of tinzaparin in each dialysis session for two weeks. After SD1, they were switched to 3,500 IU of bemiparin for two weeks and the second study dialysis session (SD2) was carried out. Patients used the same dialyzers during the whole study period and no changes were made in any of the other hemodialysis parameters. Blood samples for the measurement of PT, aPTT and anti-Xa activity were taken before the study dialysis sessions (sample 0), and again at two and four hours after the initiation of dialysis (samples 2-h and 4-h, respectively). PT values showed no change between the SD1 and SD2 sessions, but aPTT values were significantly higher in the 2-h and 4-h samples of the SD1 session compared to corresponding values in SD2 samples (p < 0.005). Anti-Xa activity was higher in the 2-h and 4-h samples of the SD2 session compared to the SD 1 session (p = 0.005 and p = 0.012, respectively). At four hours, only patients receiving bemiparin had a mean anti-Xa activity higher than 0.40 IU/mg (mean 0.51 +/- 0.76). However, fibrin/clot formation in the extracorporeal circuit during each study period as assessed by visual inspection, did not differ significantly between sessions. It is concluded that the anticoagulant profile of bemiparin sodium during hemodialysis treatment is superior to that of tinzaparin.

A Randomized Trial Comparing 2 Low-Molecular-Weight Heparins for the Outpatient Treatment of Deep Vein Thrombosis and Pulmonary Embolism

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. 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. 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%. 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.

Tinzaparin sodium is effective as thromboprophylaxis and thrombosis treatment during pregnancy

Tinzaparin sodium is effective as thromboprophylaxis and thrombosis treatment during pregnancy

Tinzaparin sodium: a review of its pharmacology and clinical use in the prophylaxis and treatment of thromboembolic disease.

Tinzaparin sodium (tinzaparin; innohep) is a low molecular weight heparin (LMWH) formed by the enzymatic degradation of porcine unfractionated heparin (UFH). In clinical trials, once-daily subcutaneous (SC) tinzaparin was effective and generally well tolerated in the prophylaxis and treatment of thromboembolic disease. SC tinzaparin 75 anti-Xa IU/kg/day showed similar thromboprophylactic efficacy to adjusted-dosage oral warfarin in patients undergoing total hip arthroplasty; in patients undergoing knee replacement, the incidence of deep vein thrombosis (DVT) was significantly lower with tinzaparin. The drug had similar efficacy to equivalent-dosage SC enoxaparin sodium in orthopaedic surgery. In patients undergoing general surgery, SC tinzaparin 3500 anti-Xa IU/day was of equivalent thromboprophylactic efficacy to SC UFH 5000IU twice daily. Encouraging preliminary results have been obtained with tinzaparin in the prevention of DVT in patients with complete motor paralysis. In the initial treatment of acute proximal DVT and pulmonary embolism, SC tinzaparin 175 anti-Xa IU/kg/day was at least as effective as adjusted-dosage intravenous (IV) UFH. In the outpatient treatment of venous thromboembolism, tinzaparin has demonstrated similar efficacy to dalteparin sodium (dalteparin) and warfarin. Tinzaparin was effective in preventing clotting in haemodialysis circuits; the anticoagulant efficacy of tinzaparin in patients undergoing haemodialysis was similar to that of SC dalteparin and similar to or less than (although in this case the tinzaparin dose was too low for sufficient anticoagulant efficacy) that of IV UFH. Advantages of tinzaparin over UFH and warfarin include ease of administration and lack of need for laboratory monitoring. Tinzaparin is more cost effective than UFH in the treatment of established thromboembolic disease, and home-based treatment with tinzaparin may offer greater cost benefits than hospital-based therapy. Tinzaparin is well tolerated, including in elderly patients and those with renal impairment receiving long-term treatment. Incidences of major bleeding complications were low and reports of heparin-induced thrombocytopenia were infrequent in clinical studies. In conclusion, tinzaparin is a valuable LMWH in the prophylaxis and management of thromboembolic disease.

Tenecteplase

Each month, subscribers to The Formulary® Monograph Service receive five to six researched monographs on drugs that are newly released or are in late Phase III trials. The monographs are targeted to your Pharmacy and Therapeutics Committee. Subscribers also receive monthly one-page summary monographs on the agents that are useful for agendas and pharmacy/nursing in-services. A comprehensive target drug utilization evaluation (DUE) is also provided each month. The monographs are published in printed form and on diskettes that allow customization. Subscribers to the The Formulary Monograph Service also receive access to a pharmacy bulletin board called The Formulary Information Exchange (The F.I.X). All topics pertinent to clinical pharmacy are discussed on The F.I.X. Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. If you would like information about The Formulary Monograph Service or The F.I.X., call The Formulary at 800-322-4349. The October 2000 Formulary monographs are argatroban, tinzaparin sodium, balsalazide, methylphenidate extended-release tablets, and eflornithine hydrochloride cream. The DUE is on argatroban.

Tenecteplase

Each month, subscribers to The Formulary® Monograph Service receive five to six researched monographs on drugs that are newly released or are in late Phase III trials. The monographs are targeted to your Pharmacy and Therapeutics Committee. Subscribers also receive monthly one-page summary monographs on the agents that are useful for agendas and pharmacy/nursing in-services. A comprehensive target drug utilization evaluation (DUE) is also provided each month. The monographs are published in printed form and on diskettes that allow customization. Subscribers to the The Formulary Monograph Service also receive access to a pharmacy bulletin board called The Formulary Information Exchange (The F.I.X). All topics pertinent to clinical pharmacy are discussed on The F.I.X. Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. If you would like information about The Formulary Monograph Service or The F.I.X., call The Formulary at 800-322-4349. The October 2000 Formulary monographs are argatroban, tinzaparin sodium, balsalazide, methylphenidate extended-release tablets, and eflornithine hydrochloride cream. The DUE is on argatroban.

The Economic Impact of Treating Deep Vein Thrombosis with Low-Molecular-Weight Heparin: Outcome of Therapy and Health Economy Aspects

Subcutaneous low-molecular-weight heparin (LMWH) is at least as safe and effective as classical intravenous heparin therapy for the treatment of proximal vein thrombosis. Anticoagulant monitoring and intravenous administration are not required with LMWH treatment, therefore this therapy may offer economic advantages. An economic evaluation of these therapeutic approaches was performed comparing the costs and effectiveness. The evaluation was aimed at helping decision-makers to maximize the health of the population served, subject to available resources. The American-Canadian Thrombosis Study was a multicentre, randomized, double-blind clinical trial that compared treatment by initial continuous intravenous infusion of heparin (followed by 3 months of warfarin therapy) with a once-daily dose of subcutaneous LMWH, tinzaparin sodium (followed by 3 months of warfarin treatment) in patients with acute proximal deep vein thrombosis. In the LMWH-treated group, the cost incurred for 100 patients was $399,403 (Canadian) or $335,687 (US) with a frequency of objectively documented recurrent venous thromboembolism of 2.8%. In the intravenous heparin-treated group, the cost incurred for 100 patients was $414,655 (Canadian) or $375,836 (US), with a frequency of objectively documented recurrent venous thromboembolism of 6.9%. These results show a cost saving of $15,252 (Canadian) or $40,149 (US) with the use of LMWH. Multiple sensitivity analyses did not alter the findings of the study which indicated that LMWH therapy is at least as safe and effective but less costly than intravenous heparin treatment. The potential for outpatient therapy in up to 37% of patients who are receiving LMWH would substantially augment the cost-saving. The cost-effectiveness findings presented in this paper are based on the assumption that all costs are covered by a single payer. Outpatient management in many countries will shift the healthcare costs from the healthcare payer to the patient, increasing the economic burden to the patient.

Dose titration study of tinzaparin, a low molecular weight heparin, in patients on chronic hemodialysis.

The minimal necessary dose of Innohep (IH) (MNDI) (Innohep [tinzaparin], Leo Pharmaceutical Corp., Ballerup, Denmark) was examined in 40 patients switched from conventional heparin ([CH], Leo Pharmaceutical Corp.) to IH and in 13 patients already treated with IH. Clotting in the venous chamber and in the dialyzer was evaluated on a 4 point scale by visual inspection. IH was administrated as a bolus injection into the arterial side of the dialyzer at the beginning of dialysis sessions. The initial dose of IH was 50% of the total dose of CH used before the study (in respective IU). According to clotting in the venous chamber or dialyzer, the dose of IH was titrated by stepwise changes of 500 IU to the lowest possible dose until 3 subsequent dialysis sessions without clotting were obtained. The total dose of CH (bolus and infusion) before switching was 6,162 +/- 2,100 IU. The bleeding time from the cannulation site after dialysis, in 24 patients with A-V fistulas, was 7.1 +/- 2.8 min(triplicates). Eight patients were excluded before achieving the MNDI, 3 due to bleeding not clearly related to heparinization (1 due to gingival bleeding, 1 to epistaxis, and 1 to sugillations), 1 due to alopecia, 2 due to a need of more than 10,000 IU of IH, and 2 patients due to cessation of treatment resulting from anxiety. After switching over, the MNDI amounted to 66 +/- 26% in respective IU. The conversion IH/CH ratio correlated significantly to the blood flow rate and the type of dialyzer. When compared on 3 subsequent sessions before and after switching to IH, no differences were found in the bleeding time after decannulation and in clotting in the venous chamber while dialyzer clotting fell on the visual scale from an average of 0.36 to 0.19 (p < 0.01). No total clot formation was observed during the study. The MNDI correlated positively to the body weight, blood flow rate, and time on dialysis (with the respective coefficients of correlation of r being 0.58, 0.44, and 0.30, p < 0.05) and was also influenced by the type of dialyzer. The average MNDIs for the Hemoflow-FS hollow-fiber (Fresenius, Bad Homburg, Germany), Lundia PRO plate (Gambro, Lund, Sweden), and Polyflux hollow fiber (Gambro) were 2,571, 3,727, and 5,020 IU (p < 0.01, ANOVA). In patients on chronic hemodialysis, IH given as a bolus of 4,250 IU effectively prevented extracorporeal clotting during dialysis, similarly to CH. However, a considerable individual variation in MNDIs not related to the need for CH was observed, and this necessitates individual dosage adjustments to obtain the optimal prevention of clotting with minimal bleeding risk.

Tinzaparin sodium as ???effective and safe??? as heparin in PE

Tinzaparin sodium as ???effective and safe??? as heparin in PE

Subcutaneous Low-Molecular-Weight Heparin vs Warfarin for Prophylaxis of Deep Vein Thrombosis After Hip or Knee Implantation

Postoperative venous thrombosis and pulmonary embolism present a major clinical threat to patients undergoing total hip or knee arthroplasty. We performed an economic evaluation of warfarin sodium and subcutaneous low-molecular-weight heparin sodium prophylaxis comparing cost and effectiveness. A consecutive series of 1436 patients who underwent hip or knee arthroplasty comparing these 2 regimens in a randomized trial with objective documentation of outcomes provided the opportunity to perform economic evaluations for Canada and the United States. Deep vein thrombosis was documented in 231 (37.4%) of 617 patients given warfarin and in 185 (31.4%) of 590 patients given low-molecular-weight heparin (P = .03). In Canada, warfarin and low-molecular-weight heparin (tinzaparin sodium) incurred costs per 100 patients of $11,598 and $9,197, respectively, providing a cost savings of $2,401 for the low-molecular-weight heparin group. The drug cost of low-molecular-weight heparin (tinzaparin) was $6 per day and for warfarin was $0.32 per day. Sensitivity analysis showed that low-molecular-weight heparin is more costly if drug costs are increased by 1.5-fold (ie, the cost of tinzaparin is increased from $6 per day to $8.82 per day or more). In the United States, the analysis was also not definitive; low-molecular-weight heparin was more costly than warfarin at drug costs of $15 and $2.01 per day, respectively. Our findings indicate that the decision to use low-molecular-weight heparin or warfarin prophylaxis in patients undergoing major joint replacement surgery is a finely tuned trade-off. Prophylaxis with low-molecular-weight heparin is equally or more effective than the more complex prophylaxis with warfarin. Major bleeding is uncommon but less frequent with warfarin use. The most significant parameters that influence the comparative cost-effectiveness are the cost of the drug, the cost of international normalized ratio monitoring, and the costs associated with major bleeding. The analysis also demonstrates that the results are health care system dependent (Canada vs US). In Canada, low-molecular-weight heparin (tinzaparin) is less costly because it avoids the need for international normalized ratio monitoring. In the United States, the drug cost for low-molecular-weight heparin will likely be the principal determinant of relative cost-effectiveness.

Tinzaparin sodium cuts cost of DVT treatment

Tinzaparin sodium cuts cost of DVT treatment

Binding of low molecular weight heparin (Tinzaparin sodium) to bovine endothelial cells in vitro

Heparinase depolymerized low molecular weight (LMW) heparin (Tinzaparin sodium, Logiparin®) was radiolabelled by catalytic tritiation to high specific radioactivity and the binding to fetal bovine heart endothelial (FBHE) cells was studied at 4°C and 37°C. The binding was found to be time dependent and saturable. Two classes of binding sites could be distinguished from Scatchard analysis at both temperatures: One with high affinity (K D = 0.027 μM at 4°C, K D = 0.012 μM at 37°C) and another with very low affinity (K D = 69 μM at 4°C and 37 μM at 37°C). The binding reversibility was affected by the temperature indicating internalization of a fraction of the bound LMW heparin. At 4°C only 11% of the specifically bound heparin was bound irreversibly. At 37°C the non displaceable fraction accounted for 28 % of the specifically bound LMW heparin. This work demonstrates that tinzaparin sodium binds specifically to endothelial cells. This binding may be useful in interpreting pharmacokinetic properties of this low molecular weight heparin.