Dalteparin Research Articles

Impact of perioperative low-molecular-weight heparin therapy on clinical events of elderly patients with prior coronary stents implanted > 12 months undergoing non-cardiac surgery: a randomized, placebo-controlled trial

BackgroundLittle is known about the safety and efficacy of discontinuing antiplatelet therapy via LMWH bridging therapy in elderly patients with coronary stents implanted for > 12 months undergoing non-cardiac surgery. This randomized trial was designed to compare the clinical benefits and risks of antiplatelet drug discontinuation via LMWH bridging therapy.MethodsPatients were randomized 1:1 to receive subcutaneous injections of either dalteparin sodium or placebo. The primary efficacy endpoint was cardiac or cerebrovascular events. The primary safety endpoint was major bleeding.ResultsAmong 2476 randomized patients, the variables (sex, age, body mass index, comorbidities, medications, and procedural characteristics) and percutaneous coronary intervention information were not significantly different between the bridging and non-bridging groups. During the follow-up period, the rate of the combined endpoint in the bridging group was significantly lower than in the non-bridging group (5.79% vs. 8.42%, p = 0.012). The incidence of myocardial injury in the bridging group was significantly lower than in the non-bridging group (3.14% vs. 5.19%, p = 0.011). Deep vein thrombosis occurred more frequently in the non-bridging group (1.21% vs. 0.4%, p = 0.024), and there was a trend toward a higher rate of pulmonary embolism (0.32% vs. 0.08%, p = 0.177). There was no significant difference between the groups in the rates of acute myocardial infarction (0.81% vs. 1.38%), cardiac death (0.24% vs. 0.41%), stroke (0.16% vs. 0.24%), or major bleeding (1.22% vs. 1.45%). Multivariable analysis showed that LMWH bridging, creatinine clearance < 30 mL/min, preoperative hemoglobin < 10 g/dL, and diabetes mellitus were independent predictors of ischemic events. LMWH bridging and a preoperative platelet count of < 70 × 109/L were independent predictors of minor bleeding events.ConclusionsThis study showed the safety and efficacy of perioperative LMWH bridging therapy in elderly patients with coronary stents implanted > 12 months undergoing non-cardiac surgery. An alternative approach might be the use of bridging therapy with half-dose LMWH.Trial registrationISRCTN65203415.

Effect of co-administered dalteparin sodium and alteplase on clinical and biochemical parameters in postpartum patients with lower extremity deep venous thrombosis

Purpose: To investigate the clinical efficacy of co-administration of dalteparin sodium and alteplase in the treatment of postpartum lower extremity deep venous thrombosis.Methods: A total of 88 patients with postpartum lower extremity deep venous thrombosis admitted to Jiangxi Provincial People's Hospital of The First Affiliated Hospital of Nanchang Medical College, Nanchang, China from January 2020 to December 2022 were enrolled in this study and divided into study group (treated with dalteparin sodium and alteplase) and control group (treated with alteplase only), with 44 patients in each group. Clinical parameters (limb circumference, pigmentation and ulcer area), hemorheological parameters [D-Dimer (D_D), fibrinogen (FIB), centipoise (CP), red cell assembling index (RCAI)], inflammatory factors (hs-CRP, IL-6, THF-a, NMP-9) and cell adhesion factors {platelet endothelial cell adhesion molecule-1 (PECAM-1) and vascular cell adhesion molecule 1 (VCAM-1)} were determined and recorded.Results: Post-treatment, all the clinical and biochemical parameters in the study group were significantly improved compared with pre-treatment levels and the respective levels in the control group (p &lt; 0.05). The overall response rate (ORR) in the study group was 95.45 %, which was higher than the 79.55 % for the control group (p &lt; 0.05).Conclusion: Concomitant administration of dalteparin sodium and alteplase is more efficacious than treatment of with alteplase alone in the management of postpartum lower extremity deep venous thrombosis. However, further clinical trials on this combination therapy is required for the validation of findings obtained in this work.

Pharmacokinetics of dalteparin and nadroparin for thromboses in children with oncological diseases

Objective: evaluate the pharmacokinetics and pharmacodynamics of nadroparin and dalteparin in thrombosis that occurred in children with malignant neoplasms. Materials and methods: The results of 52 pharmacokinetic studies involving 34 patients with oncological diseases, whose treatment was complicated by venous thrombosis, were analyzed. The median age of patients was 14.5 (7–18) years. Depending on the daily dose and the type of heparin administered, the results of pharmacokinetic studies were divided into 6 groups. Dalteparin sodium: against the background of chemo-induced thrombocytopenia, subcutaneous administration of dalteparin at a dose of 51.0 (40.0–72.0) anti-Xa IU/kg every 12 hours – 6 observations; subcutaneous injection every 12 hours at a dose of 100.5 (91.0–141.0) anti-Xa IU/kg – 18 observations; long-term continuous intravenous infusion at a constant rate at a daily dose of 201.0 (180.0–265.0) anti-Xa IU/kg - 6 observations. Nadroparin calcium: 62.0 (53.0-71.0) anti-Xa IU/kg every 12 hours - 6 observations; 93.5 (80.0–117.0) anti-Xa IU/kg every 12 hours – 10 observations; subcutaneous injection at a dose of 203.0 (170.0–236.0) anti-Xa IU/kg once a day - 6 observations. Results: We confirmed that in the acute period of thrombosis in children, the most optimal way to administer low molecular weight heparin is intravenous infusion of dalteparin sodium at a constant rate. Subcutaneous injection of 50% of the daily dose of LMWH at intervals of 12 hours is preferable to a single injection of 100% of the daily dose every 24 hours. There were no significant advantages of nadroparin compared with dalteparin when using anticoagulants in comparable doses in case of venous thrombosis, which complicated the treatment of children with malignant neoplasms. Conclusion: Control over the adequacy of the dose of LMWH can be performed at any stage of treatment. The specific anti-Xa activity of nadroparin and dalteparin needs to be checked before the next subcutaneous injection and between 3 and 4 hours after administration. An increase in chronometric indicators of blood coagulation indirectly reflects the presence of an anticoagulant in the blood, but does not allow an objective assessment of the achievement of a therapeutic effect.

Effectiveness of different antithrombotic agents in combination with tranexamic acid for venous thromboembolism prophylaxis and blood management after total knee replacement: a prospective randomized study

BackgroundTranexamic acid (TXA) has been widely applied in total knee arthroplasty (TKA) to significantly reduce perioperative blood loss and improve knee function recovery in patients after surgery. The choice of antithrombotic agents for venous thromboembolism (VTE) prevention after TKA is controversial. Therefore, this study aimed to compare the effects of different antithrombotic agents on patients after primary unilateral TKA in the context of applied TXA.MethodsA total of 180 patients undergoing primary unilateral TKA from October 2020 to December 2021 were included in this study. All patients were given an intraoperative drip of 60 mg/kg TXA. Thereafter, patients were divided into three groups (n = 60 each). Baseline data were comparable among the three groups. The average follow-up time was 3.02 ± 0.09 months. Group 1 enrolled patients receiving oral rivaroxaban (RA) at 10 mg, Group 2 included patients who received subcutaneous Dalteparin sodium at 2500 IU, while Group 3 included patients taking oral aspirin (ASA) at 100 mg. Patients in all the three groups received treatment once a day for 30 days at 12 h postoperatively. The primary outcomes in this study were post-treatment drainage volume and thrombotic complication rate. The secondary outcomes included hematologic parameters, transfusion rate, intraoperative blood loss, total blood loss (TBL), and bleeding complication rate.ResultsThe average drainage volume after treatment was significantly lower in Group 3 than in Group 1 and Group 2 (205.2 ± 69.0 vs 243.4 ± 72.5 vs 295.4 ± 72.5 ml, P < 0.001), and there was a significant difference between Group 1 and Group 2 (243.4 ± 72.5 mL vs 295.4 ± 72.5 mL, P < 0.001). The blood transfusion rate of Group 2 dramatically increased compared with Group 1 and Group 3 (20.0% vs 6.7% vs 5.0%, P = 0.01). The bleeding complication rate in Group 1 apparently increased relative to Group 2 and Group 3 (26.7% vs 10.0% vs 8.3%, P = 0.008). Besides, there was no significant difference in the thrombotic complication rate among the three groups.ConclusionUnder the background of TXA application, ASA, RA, and Dalteparin sodium were all effective on preventing VTE after TKA. In addition, ASA effectively reduced post-treatment Hemoglobin (Hb) loss, drainage volume, TBL, transfusion rate, and bleeding complications compared with RA and Dalteparin sodium.Trial registrationThe trial was registered at the Chinese Clinical Trial Registry (ChiCTR2200060169). Date of Registration: 21/05/2022.

Bifunctional Dalteparin/Enoxaparin coated nanosilver formulation to prevent bloodstream infections during hemodialysis

Catheter-related bloodstream infections (CRBSI) are the major concern of patients undergoing hemodialysis. The current study formulates bifunctional low molecular weight heparin (LMWH) coated nanosilver as an effective anticoagulant and antimicrobial/anti-biofilm agent. Nanosilver formulations were prepared using a microwave-assisted green synthesis approach and stabilized with pharmaceutically approved LMWH such as dalteparin (DL) and enoxaparin (EX) along with unfractionated heparin (HP) as a control. The obtained heparinized (HP/DL/EX) nanosilver was monodisperse, and the size ranged between 15 and 25 nm. DL/EX predominantly stabilized the nanosilver by primarily engaging their negatively charged sulfate groups. The obtained DL/EX coated nanosilver are hemocompatible, showed two times increase in their anticoagulation activity, and are highly potent in inhibiting/eradicating both mono- and polymicrobial biofilms. Henceforth, the observed biocompatible and enhanced bifunctional characteristics of DL/EX coated nanosilver can be used to replace the systemic antibiotics and can be an alternative catheter lock solution to prevent CRBSI in hemodialysis therapy.

КЛИНИЧЕСКИЕ И ПРАВОВЫЕ АСПЕКТЫ ПРИМЕНЕНИЯ НИЗКОМОЛЕКУЛЯРНЫХ ГЕПАРИНОВ В ПЕДИАТРИИ

The acceptability and effectiveness of low-molecular-weight heparin (LMWH) use in paediatrics has been confirmed by established Russian and foreign clinical practice. However, at present, the only LMWHs that are legally allowable for children are those with the international nonproprietary name of «dalteparin sodium», since this is directly stated in it’s Package Insert Leaflet (PIL). Prescribing the rest of the LMWHs for children will, in fact, be an off-label prescription. In addition, there are currently no standards of medical care, procedures for its delivery and regulations on the organization of medical care that would allow for the possibility of assigning LMWHs to children. This situation makes it difficult to introduce into the Russian pediatric practice the choice of administration of LMWHs in children where necessary. The use of LMWH in pediatrics may become available even without making changes to PIL, but subject to the establishment of such a recommendation in the new clinical guidelines. The latter is the only legal mechanism in force allowing legal and legally secure off-label appointment.

Pharmacokinetics of low molecular weight heparins in thrombosis, complicate the treatment of children with cancer

Objective: to evaluate the pharmacokinetics of nadroparin and dalteparin in thrombosis complicating the treatment of children with malignant neoplasms.Materials and methods. The results of 52 pharmacokinetic studies performed in 34 patients with malignant neoplasms, whose treatment was complicated by venous thrombosis, were analyzed. The age of the patients is from 7 to 18 years, he median is 14.5 years. Depending on the value of daily dose and type of heparin administered, the results of pharmacokinetic studies were divided into 6 groups. Dalteparin sodium: during period of chemotherapy induced thrombocytopenia, subcutaneous injection at a dose of 51.0 (40.0-72.0) anti Xa IU/kg every 12 hours - 6 studies; subcutaneous injection every 12 hours at a dose of 100.5 (91.0-141.0) anti Xa IU/kg - 18 observations; long-term continuous administration at a constant rate at a daily dose of 201.0 (180.0-265.0) anti Xa IU/kg - 6 pharmacokinetic observations. Nadroparin calcium: 62.0 (53.0-71.0) anti Xa IU/kg every 12 hours - 6 studies; 93.5 (80.0-117.0) anti Xa IU/kg every 12 hours - 10 observations; subcutaneous injection at a dose of 203.0 (170.0-236.0) anti Xa IU/kg once a day - 6 pharmacokinetic observations.Results. At steady-state, the area under the pharmacokinetic curve (AUC) of dalteparin and nadroparin, regardless of the mode of administration, depended on the maximum specific activity and half-life. No relationship was found for dalteparin between AUC and endogenous creatinine clearance. In contrast to dalteparin, the AUC after administration of na-droparin was closely related to endogenous creatinine clearance. The increase in chronometric indices indirectly reflected the presence of an anticoagulant in the blood, but did not allow an objective assessment of therapeutic effect achievement, recorded by the degree of thrombin generation inhibition.Conclusion. There were no significant advantages of nadroparin compared with dalteparin when using in comparable doses in the case of venous thrombosis, complicated the treatment of children with malignant neoplasms. Subcutaneous administration of 50 % nadroparin calcium daily dose with 12 hours interval is preferred over a single administration of 100 % daily dose every 24 hours. It is mandatory to monitor the administration of low molecular weight heparins in children with oncological diseases in order to make a decision on the adequacy of anticoagulant dose to the therapeutic range.

Cryptic brain abscess ‐ do not forget hereditary hemorrhagic teleangiectasia!

Cryptic brain abscess ‐ do not forget hereditary hemorrhagic teleangiectasia!

Дозирование низкомолекулярных гепаринов и анти-фактор Xa активность у пациентов с новой коронавирусной инфекцией COVID-19.

Дозирование низкомолекулярных гепаринов и анти-фактор Xa активность у пациентов с новой коронавирусной инфекцией COVID-19.

Comparison of low-molecular-weight heparins in thromboprophylaxis of major orthopaedic surgery – randomized, prospective pilot study

AimTo compare the clinical effectiveness of the two most commonly used LMWHs, dalteparin (DALT) and enoxaparin (ENOX), in thromboprophylaxis of elective total hip replacement (THR) or total knee replacement (TKR).Material and methodsTo the prospective, randomized study were included 66 adult patients qualified to undergo THR or TKR (age 63 ± 12 years, 44 women). The patients were randomized to daily in-hospital subcutaneous prophylaxis with 5,000 I.U. of DALT or 40 mg of enoxaparin. Clinical and laboratory data were collected before surgery, and on 1st and 5th days after surgery.ResultsThirty-four patients were randomized to prophylaxis with ENOX and 32 with DALT. The groups did not differ significantly in age, sex, creatinine and most of the laboratory parameters. The compared groups had similar surgical parameters, but more patients in the ENOX group received red blood cell infusion (17(50%) vs 8(25%); p < 0.05). The Lee–White coagulation time mildly decreased in ENOX and DALT following the surgery (p = ns). There was a shortening of Duke’s bleeding time in DALT after the surgery and it became significantly quicker than that in ENOX on Day 5 (p = 0.03).ConclusionThe observed difference in Duke’s bleeding time and exceeding blood loss during the surgery on the enoxaparin demands confirmation, as it can be important information for clinical management.

Medications used disproportionately during pregnancy: Priorities for research on the risks and benefits of medications when used during pregnancy.

To identify medications used disproportionately more or less among pregnant women relative to women of childbearing age. Medication use among pregnant women in New South Wales, Australia was identified using linked perinatal and pharmaceutical dispensing data from 2006 to 2012. Medication use in women of childbearing age (including pregnant women) was identified using pharmaceutical dispensing data for a 10% random sample of the Australian population. Pregnant social security beneficiaries (n = 111 612) were age-matched (1:3) to female social security beneficiaries in the 10% sample. For each medication, the risk it was dispensed during pregnancy relative to being dispensed during an equivalent time period among matched controls was computed. Medications were mapped to Australian pregnancy risk categories. Of the 181 included medications, 35 were statistically significantly more commonly dispensed to pregnant women than control women. Of these, 23 are categorised as posing no increased risk to the foetus. Among medications suspected of causing harm or having insufficient safety data, the strongest associations were observed for hydralazine, ondansetron, dalteparin sodium and ranitidine. Use was less likely during pregnancy than control periods for 127 medications, with the strongest associations observed for hormonal contraceptives and progestogens. Most medications found to be used disproportionately more by pregnant women are indicated for pregnancy-related problems. A large number of medications were used disproportionately less among pregnant women, where avoidance of some of these medications may pose a greater risk of harm. For many other medications avoided during pregnancy, current data are insufficient to inform this risk-benefit assessment.

FDA approval summary: Dalteparin for the treatment of symptomatic venous thromboembolism in pediatric patients.

On May 16, 2019, the U.S. Food and Drug Administration (FDA) approved dalteparin sodium for the treatment of symptomatic venous thromboembolism (VTE) to reduce the risk of recurrence in pediatric patients 1month of age and older. Approval was primarily based on FDA review of a single-arm trial evaluating dalteparin administered subcutaneous twice daily in 38 pediatric patients with symptomatic VTE. Efficacy was based on the achievement of therapeutic plasma anti-Xa levels. The FDA concluded that dalteparin has efficacy and acceptable safety for pediatric patients.

Dalteparin anticoagulation in paediatric home haemodialysis.

The aim of this study was to investigate whether dalteparin is a safe and effective anticoagulant for paediatric home haemodialysis (HD) and to assess the determinants of dosing. Data were collected for all children (< 18years) undergoing home HD from 2011 to 2017 at one large paediatric nephrology centre in the UK. All children had anticoagulation with dalteparin sodium according to a standardised protocol. Dalteparin safety was assessed by monitoring for accumulation, adequate clearance of dalteparin and adverse events. Dalteparin efficacy was assessed through monitoring for clot formation in dialysis circuits. Potential determinants of dalteparin dosing were assessed. Eighteen children were included, their median age at start was 12years, and 50% were male. Eighty-three percent of children had four home HD sessions each week, with a median total dialysis hours of 20h/week. Thirty-three percent of children had nocturnal home HD. Median dalteparin dose at 12-month follow-up was 40IU/kg (range 8-142IU/kg). Factors associated with higher dalteparin dosing requirements included a younger age of the child (p < 0.01), a lower blood flow rate (p < 0.01) and the use of a central venous line for dialysis access (p = 0.038). No children had evidence of bioaccumulation of dalteparin or inadequate clearance. No significant bleeding or adverse events were reported. Dalteparin is a safe and effective anticoagulant when used for paediatric home HD. In this study, there was no evidence of bioaccumulation or significant adverse events. Further research is required to directly compare dalteparin with unfractionated heparin (UFH) and evaluate anticoagulant choice for paediatric home HD.

Role of dalteparin sodium on the growth of cancer cells and tumor-associated angiogenesis in A549 human lung cancer cell line and grafted mouse model.

To investigate the effects of dalteparin sodium on the expression of vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR), and hypoxia-inducible factor 1α (HIF-1α) in A549 human lung cancer (LC) cell line and a human A549-grafted nude mouse model. A549 human lung adenocarcinoma cell line was divided into control group, treated using normal saline (NS); and dalteparin sodium groups, receiving 5, 15, 50, and 150 IU/ml of dalteparin sodium, respectively. Human A549-grafted nude mouse was induced through subcutaneous (SC) injection of A549 (5 × 106/0.2 ml) into the right armpit, and randomly assigned into control group (n = 6) receiving intraperitoneal (i.p.) injection of NS, cisplatin (DDP) group (n = 6, 3 mg/kg DDP alone, i.p., for 3 days), low molecular weight heparin (LMWH) group (n = 6) receiving SC injection of 1500 IU/kg dalteparin sodium for 35 days, and DDP plus LMWH group (n = 6, 3 mg/kg DDP, i.p., for 3 days, followed by SC injection of 1500 IU/kg dalteparin sodium for 35 days). Significant difference was noted in the messenger RNA expression of VEGF, VEGFR, and HIF-1α after treating with heparin with a concentration of 15, 50, or 150 IU/ml in the A549 cell line at 24 and 48 h, respectively. In the human A549-grafted nude mouse model, a significant reduction was noted in the expression of VEGF, VEGFR, and HIF-1α in the tumor mass harvested from the mice receiving administration of dalteparin sodium plus DDP. Dalteparin sodium had the inhibitory effects on the growth of human LC A549 cells in vitro and A549 LC xenograft model, which could be enhanced when administrated together with DDP.

An Adjustable Dalteparin Sodium Dose Regimen for the Prevention of Clotting in the Extracorporeal Circuit in Hemodialysis: A Clinical Trial of Safety and Efficacy (the PARROT Study).

Background:Dalteparin sodium, a low-molecular-weight heparin, is indicated for prevention of clotting in the extracorporeal circuit during hemodialysis (HD). Product labeling recommends a fixed single-bolus dose of 5000 international units (IU) for HD sessions lasting up to 4 hours, but adjustable dosing may be beneficial in clinical practice.Objective:The aim of the PARROT study was to investigate the safety and efficacy of an adjustable dose of dalteparin in patients with end-stage renal disease requiring 3 to 4 HD sessions per week.Design:A 7-week, open-label, multicenter study with a single treatment arm, conducted between October 2013 and March 2016.Setting:Ten sites in Canada.Patients:A total of 152 patients with end-stage renal disease requiring 3 to 4 HD sessions per week.Measurements:The primary outcome was the proportion of HD sessions completed without premature termination due to inadequate anticoagulation.Methods:All participants initially received a dose of 5000 IU dalteparin, which could be adjusted at subsequent HD sessions when clinically indicated, by increment or decrement of 500 or 1000 IU, with no specified dose limits.Results:Patients were followed for 256 patient-months. Nearly all (99.9%; 95% confidence interval [CI]: 99.7-100) evaluable HD sessions were completed without premature clotting. Dose was adjusted for more than half (52.3%) of participants, mostly owing to clotting or access compression time >10 minutes. Median dalteparin dose was 5000 IU (range: 500-13 000 IU). There were no major bleeds, and minor bleeding was reported in 2.3% of all HD sessions. There was no evidence of bioaccumulation.Limitations:This short-term study, with a single treatment arm, was designed to optimize dalteparin dose using a flexible dosing schedule; it was not designed to specifically evaluate dalteparin dose minimization, provide a direct comparison of dalteparin versus unfractionated heparin, or provide information on long-term safety for flexible dalteparin dosing. Patients were excluded if they were at high risk of bleeding, including those on anticoagulants and those on antiplatelet agents other than aspirin <100 mg/d.Conclusions:Overall, an adjustable dalteparin sodium dose regimen allowed safe completion of HD, with clinical benefits over fixed dosing.Trial Registration:ClinicalTrials.gov NCT01879618, registered June 13, 2013.

Sequencing the oligosaccharide pool in the low molecular weight heparin dalteparin with offline HPLC and ESI–MS/MS

Low molecular weight heparins (LMWHs) are widely used anticoagulant drugs. The composition and sequence of LMWH oligosaccharides determine their safety and efficacy. The short oligosaccharide pool in LMWHs undergoes more depolymerization reactions than the longer chains and is the most sensitive indicator of the manufacturing process. Electrospray ionization tandem mass spectrometry (ESI–MS/MS) has been demonstrated as a powerful tool to sequence synthetic heparin oligosaccharide but never been applied to analyze complicated mixture like LMWHs. We established an offline strong anion exchange (SAX)-high performance liquid chromatography (HPLC) and ESI–MS/MS approach to sequence the short oligosaccharides of dalteparin sodium. With the help of in-house developed MS/MS interpretation software, the sequences of 18 representative species ranging from tetrasaccharide to octasaccharide were obtained. Interestingly, we found a novel 2,3-disulfated hexauronic acid structure and reconfirmed it by complementary heparinase digestion and LC–MS/MS analysis. This approach provides straightforward and in-depth insight to the structure of LMWHs and the reaction mechanism of heparin depolymerization.

Effects of different anticoagulants on coagulation function in hemodialysis patients

Objective To investigate the effect of different anticoagulant drugs on the changes of coagulation index and the incidence of hemorrhage in hemodialysis patients. Methods 40 patients with hemodialysis were selected as study objects, according to the random number table method they were divided into three groups, 20 cases received heparin in A group, 10 cases received low molecular heparin in B group; 10 cases received argatroban in C group.At the same time, 10 healthy persons were selected as control group.The activated glass bead clotting time (gbACT), blood velocity (CR), platelet function (PF), prothrombin fragment 1+ 2 (PF1+ 2) and the surface of platelet alpha granule membrane protein (GMF-140) were observed and analyzed in all patients. Results Compared with the control group, the CR, PF, PF1+ 2 and GMF-140 before taking to machine in A group were significantly increased, which were (31.1±5.5)sig/min, (3.1±0.5), (478.2±74.3)pmol/L, (36.9±6.6)pmol/L, respectively, gbACT was significantly prolonged [(196.1±27.3)s]. In A group, compared with before taking to machine, the CR, PF, PF1+ 2 and the GMF-140 before taking off machine were significantly decreased, which were (10.6±3.2)sig/min, (1.8±0.4), (400.1±85.5)pmol/L, (30.9±6.8)pmol/L, respectively, gbACT was significantly prolonged[(252.5±50.4)s], there were statistically significant differences (F=112.64, 28.38, 81.40, 18.11, 21.63 0.05, all P<0.05); B group compared with the control group, the CR, PF, PF1+ 2 and GMF-140 before taking to machine were significantly increased, which were (29.5±6.6)sig/min, (2.9±1.2), (475.5±97.0)pmol/L, (37.5±7.0)pmol/L, respectively, gbACT was significantly prolonged[(193.9±32.8)s]. In B group, the CR and PF1+ 2 before taking off machine were significantly decreased, which were (22.3±6.8), (407.8±90.3)pmol/L, respectively, gbACT was significantly prolonged [(207.5±31.5)s], there were statistically significant differences (F=9.11, 57.81, 5.99, 16.37, all P<0.05); C group compared with the control group, the CR, PF, PF1+ 2 and GMF-140 before taking to machine were significantly increased, which were (26.1±3.3)sig/min, (2.5±0.5), (443.5±64.1)pmol/L, (32.2±8.3)pmol/L, respectively, before taking off machine, the CR[(23.7±4.1)] was higher than (18.5±3.6) of the control group, there were statistically significant differences (F=11.14, 3.04120.30, 8.63, all P<0.05).40 hemodialysis patients were successfully treated without the occurrence of elevated venous pressure during and after treatment pipeline no or slight residual blood, puncture time and no significant prolongation. Conclusion Unfractionated heparin has strong anti-clotting effect, during and after hemodialysis has greater risk of bleeding, dalteparin has anticoagulant effect, but there is greater risk of bleeding during hemodialysis, the use of argatroban helps to improve the condition of bleeding. Key words: Hemodialysis; Anticoagulant drugs; Heparin; Heparin sodium; Aplus

Pharmacodynamic properties and bioequivalence of dalteparin sodium subcutaneous injection in healthy Chinese male subjects

1. Dalteparin sodium (DS) is a low molecular weight heparin that is widely used in the treatment of thromboembolism. The purpose of this study was to compare the pharmacodynamic properties and bioequivalence of the two formulations of DS with subcutaneous injection in healthy Chinese male subjects.2. In this randomized, open-label, two-period crossover study, a total of 24 male subjects were recruited to receive single subcutaneous doses of test and reference DS injection in two different sequences (12 subjects each) with a seven-day washout period. Plasma samples were obtained at different time points after administration of the injection and measured by chromogenic substrate assay. The pharmacodynamic parameters including Emax, AUEC0–T, AUEC0–∞ and Tmax were analyzed to evaluate the bioequivalence of two DS formulations.3. The relative bioequivalence was 107.7 ± 15.5 and 106.6 ± 29.8 for Anti-Xa and Anti-IIa, two major active metabolites of DS, respectively. The 90% confidence intervals (CIs) of the geometric mean ratio (test/reference) of Emax, AUEC0–T and AUEC0–∞ were 98.71–104.40%, 101.95–112.13% and 102.38–112.10% for Anti-Xa, and 100.88–110.42%, 95.76–112.62% and 92.24–111.32% for Anti-IIa, respectively, and all of the 90% CIs were within 80–125%. The T1/2 of reference and test were 2.88 ± 1.21 h and 2.76 ± 0.97 h for Anti-Xa, 1.87 ± 0.62 h and 1.96 ± 1.52 h for Anti-IIa.4. Based on the pharmacodynamic parameters and FDA Guidance on DS and regulatory criteria for bioequivalence, the test and reference formulations were bioequivalent in healthy Chinese male subjects.

Low-dose aspirin plus low-molecular-weight heparin for the prevention of pre-eclampsia: yes, no or maybe.

Low-dose aspirin plus low-molecular-weight heparin for the prevention of pre-eclampsia: yes, no or maybe.

Difficult questions of Kawasaki syndrome treatment

Aim. To summarize the existing literature data and to optimize protocols of anticoagulant therapy for Kawasaki syndrome.&#x0D; Methods. A review of treatment results in 10 patients with Kawasaki syndrome, where an individual approach to anticoagulation led to a positive result, and surgical treatment was not required, is presented.&#x0D; Results. In 5 of 6 patients with timely diagnosis and treatment according to the protocol, transient ectasia of coronary arteries with further normalization of their size within 4-7 months of follow up was detected. In one child on the 12th day of the disease small aneurysms of the right and left coronary arteries were identified. They disappeared after 7 months from the debut of the disease. In 3 patients, diagnosis and treatment have been delayed. In this group, a giant aneurysm of the proximal left anterior descending branch of the left coronary artery with the signs of thrombosis was discovered in a child aged 9 months on the 45th day of the disease. Anticoagulation with heparin with further switching to dalteparin sodium (Fragmin) was accompanied by adequate anticoagulation to the 3rd day of treatment. Aneurysms decreased to 2-4 mm without signs of thrombosis after 24 months of treatment with warfarin in combination with acetylsalicylic acid (Aspirin). In a girl of 1 year and 4 months of age, on the 20th day of the disease, it was complicated by exudative pericarditis with high risk for tamponade, which required a pericardial puncture and catheterization, and a giant aneurysm of the right coronary artery with the signs of thrombosis was found on the 45th day of the disease. Adequate anticoagulation was reached on the 3rd day of treatment with dalteparin sodium (Fragmin). Long-term use of warfarin in combination with acetylsalicylic acid (Aspirin) was continued. At follow-up at 4 months aneurysm of the right coronary artery has not decreased, but the size and the density of the blood clot reduced significantly. A year later, the aneurysm decreased to 5-6 mm without signs of thrombosis. At the next case of a 3 year old child, who was treated according to the treatment standards, ectasia of the right and left coronary arteries was revealed on the 14th day of treatment, disappearing after of long-term use of acetylsalicylic acid (Aspirin).&#x0D; Conclusion. At further development of standards and following up antithrombotic treatment in patients with the complicated forms of Kawasaki disease, the possibility of individual treatment adjustment based on the detection of thrombophilia genetic markers, which increase the risk for thrombotic complications, should be considered.