Enhanced anticoagulant activity of enoxaparin in patients with ESRD as measured by thrombin generation time (original) (raw)
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PLoS ONE, 2014
Background: Anticoagulation therapy is usually required in patients with chronic kidney disease (CKD) for treatment or prevention of thromboembolic diseases. However, this benefit could easily be offset by the risk of bleeding. Objectives: To determine the incidence of adverse outcomes of anticoagulants in hospitalized patients with CKD, and to compare the rates of major bleeding events between the unfractionated heparin (UFH) and enoxaparin users. Methods: One year prospective observational study was conducted in patients with CKD stages 3 to 5 (estimated GFR, 10-59 ml/min/1.73 m 2) who were admitted to the renal unit of Dubai Hospital. Propensity scores for the use of anticoagulants, estimated for each of the 488 patients, were used to identify a cohort of 117 pairs of patients. Cox regression method was used to estimate association between anticoagulant use and adverse outcomes. Results: Major bleeding occurred in 1 in 3 patients who received anticoagulation during hospitalization (hazard ratio [HR], 4.61 [95% confidence interval [CI], 2.05-10.35]). Compared with enoxaparin users, patients who received anticoagulation with unfractionated heparin had a lower mean [SD] serum level of platelet counts (139.95 [113]610 3 /mL vs 205.56 [123] 610 3 /mL; P,0.001), and had a higher risk of major bleeding (HR, 4.79 [95% CI, 1.85-12.36]). Furthermore, compared with those who did not receive anticoagulants, patients who did had a higher in-hospital mortality (HR, 2.54 [95% CI, 1.03-6.25]); longer length of hospitalization (HR, 1.04 [95% CI, 1.01-1.06]); and higher hospital readmission at 30 days (HR, 1.79 [95% CI, 1.10-2.91]). Conclusions: Anticoagulation among hospitalized patients with CKD was significantly associated with an increased risk of bleeding and in-hospital mortality. Hence, intensive monitoring and preventive measures such as laboratory monitoring and/or dose adjustment are warranted.
Blood Coagulation & Fibrinolysis, 2012
Low molecular weight heparins (LMWHs) are used for prevention and management of vascular thrombosis. In general, monitoring of anticoagulant activity is not required, however, certain populations may be susceptible to overdosing or underdosing. As anti-activated factor X(anti-Xa) activity testing is not readily available, it was our aim to investigate the usefulness of thromboelastography (TEG; Haemoscope Corporation, Skokie, Illinois, USA) for the assessment of coagulation in patients on LMWH. All patients admitted to the coronary care unit on therapeutic dose of enoxaparin were included (1 mg/kg twice daily). Blood samples were collected 4 h after the morning dose of enoxaparin once the participant had received at least three doses. When anti-Xa activity was classified as low (0-0.5), correct (0.5-1.0) or high (>1.0), the distribution of reaction time (R) and dose per kg showed little association with anti-Xa activity. The difference between mean R for the high anti-Xa group and the correct anti-Xa group was statistically nonsignificant using two-sample t-test (P U 0.26). A linear regression model showed no evidence of association between dose per kg and anti-Xa (P U 0.95). However, there was evidence of positive association between dose per kg and R (P U 0.011) wherein a 10% increase in dose per kg was associated with an increase in R of 2.7 (95% confidence interval 0.6-4.7). There was no evidence of association between R and anti-Xa (P U 0.38). TEG was unable to be used to predict anti-Xa activity. However, TEG R was prolonged in more than 90% patients and correlated with dose of enoxaparin. As enoxaparin dose correlated poorly with anti-Xa activity, a more global test might be necessary to adjust dosing of LMWH in sick, hospitalized patients.
Aging clinical and experimental research, 2017
The aim of this study was to evaluate the activity of anti-activated factor X (anti-Xa) in patients with different degrees of chronic renal failure (CRF), treated with therapeutic doses of low molecular weight heparin. This prospective study evaluated the effect of age, renal function, BMI, gender, in determining the efficacy and safety of treatment with enoxaparin, evaluated by assessing the anti-Xa. The therapeutic anticoagulant range was set between 0.20 and 0.70 U/mL. Two hospital geriatric units. 98 patients (64 men, 34 women, mean age 82 years) with CRF, treated with enoxaparin at therapeutic dosage, for deep vein thrombosis or acute coronary syndrome. Anti-Xa was assessed 4 h after the third administration of LMWH using Chromogenix test. Renal function was assessed by calculating creatinine clearance according to Cockcroft formula. The dose of enoxaparin ranged between 53 and 200 U/kg; total 4000-16000 U/day. The mean anti-Xa was 0.41 U/mL (95% CI 0.36-0.45). Multiple regress...
American Journal of Clinical Pathology, 2013
We examined the concordance of heparin levels measured by a chromogenic anti-Xa assay and the activated partial thromboplastin time (APTT) during unfractionated heparin therapy (UFH) and the biochemical basis for differences between these measures. We also investigated the endogenous thrombin potential (ETP) as a possible measure of anticoagulation. Paired measures of anti-Xa and APTT were performed on 569 samples from 149 patients on UFH. The anti-Xa values and the APTT were concordant in only 54% of measurements. One hundred twelve samples from 59 patients on UFH were assayed for APTT, anti-Xa, factor II, factor VIII, and ETP. Supratherapeutic APTT values but therapeutic anti-Xa results had decreased factor II activity. Subtherapeutic APTT but therapeutic anti-Xa values had high factor VIII activity. ETP correlated with anticoagulation status and UFH dose. In conclusion, factor II and VIII activity contributes to discordance between APTT and anti-Xa results. ETP measurements may provide an additional assessment of anticoagulation status.
American Heart Journal, 2009
Background The STACKENOX study assessed the cumulative anticoagulation effect of administering stack-on intravenous unfractionated heparin (UFH) to subjects already receiving enoxaparin. Methods Seventy-two healthy subjects aged 40 to 60 years received subcutaneous enoxaparin (1 mg/kg every 12 hours) for 2.5 days (steady state) and were randomized to receive a 70 IU/kg intravenous UFH bolus 4, 6, or 10 hours after the final enoxaparin dose. Anticoagulation levels were assessed in subjects receiving enoxaparin alone and after the UFH bolus by monitoring activated clotting time (ACT), anti-Xa and anti-IIa activities, and thrombin generation (endogenous thrombin potential [ETP]). Results After the final enoxaparin dose, ETP levels decreased by 40%; anti-Xa and anti-IIa activities increased, as expected; and ACT levels did not indicate any anticoagulation effect. Stack-on UFH at 4, 6, or 10 hours after the last enoxaparin dose significantly increased anti-Xa and anti-IIa activities (P b .0001) to well above accepted therapeutic levels and resulted in total inhibition of thrombin generation for ≥2 hours; ACT levels remained within the range commonly observed in subjects receiving UFH. Conclusions The administration of stack-on UFH to subjects already receiving recommended enoxaparin dosing may result in over-anticoagulation, and should be avoided. Activated clotting time assessment did not detect the over-anticoagulation resulting from co-administration of enoxaparin and UFH.
Nephrology Dialysis Transplantation, 2003
Background. The interest of low molecular weight heparins (LMWH) regarding bleeding risk is controversial in renal failure patients. In haemodialysis patients, there are very few data on the pharmacokinetics of LMWH after the end of the session. The aim of the study was to evaluate the duration of anticoagulation after bolus administration of the LMWH enoxaparin at the start of haemodialysis. Methods. The pharmacokinetics of enoxaparin were studied during the 48 h following a single bolus injection at the start of the dialysis session in 30 chronic haemodialysis patients. Pharmacokinetics were determined using a population approach (Non Linear Mixed Effects Modelling). Results. A single injection of enoxaparin at 60 U IU/kg (4000 ± 455 IU) led to an anti-Xa activity higher than 1.2 IU/ml during the first 2 h of the session, and between 0.4 and 1.2 IU during the third and fourth hours. After the end of the session, anti-Xa activity remained higher than 0.4 IU/ml up to 10 h after injection, and higher than 0.1 IU/ml up to 24 h. The pharmacokinetic model showed that only weight improved the predicted vs observed anti-Xa activity plot. The model was used to simulate single and multiple dosing with decreased enoxaparin doses. Whatever the procedure, anti-Xa activity remained high (>0.22 ± 0.99 UI/ml) up to 12 h after the start of the dialysis session. Conclusions. These results suggest that haemodialysis patients receiving the LMWH enoxaparin during dialysis are at risk of bleeding up to 10 h after the injection.
Asian Journal of Medicine and Health
Background: Maintaining the patency of the extracorporeal circuit (ECC) is required. The cost and long-term effect of anticoagulants on hemodialysis (HD) patients' parameters are still matters of concern. We aimed to study the effect of shifting to enoxaparin instead of unfractionated heparin (UFH) during HD and evaluate its efficacy, safety, and benefits. Design and methodology: This study was conducted at Arar hospital, Kingdom of Saudi Arabia (KSA), and included 86 end-stage renal disease (ESRD) patients on HD for six months starting from October 2017. All patients had been on UFH as an anticoagulant during hemodialysis sessions before they were shifted to equivalent doses of enoxaparin sodium (Clexan®) as a therapeutic upgrade to start with. The patients’ files were examined retrospectively for the period of UFH therapy and then all patients were observed prospectively for at least 6 months while on Clexane. The occurrence of clotting in the dialysis sets were recorded and t...
Nephron, 1995
The nephrotic syndrome (NS) canies one of the highest risks of thrombotic complications. Consequently, over the last 15 years, some nephrologists have treated patients at risk (i.e. those with albuminemia <20 gA and membranous nephropathy) with anticoagulants: either subcutaneous heparin (Kakkar protocol) or antivitamin K. Lowmolecular-weight heparin (LMWH) has a longer plasma half-life and better bioavailability than standard heparin and can thus be administered as a single daily injection. LMWH also carries a lower risk of hemorhage. we prospectively studied the safety and efficacy of the LMWH Enoxaparin for preventive anticoagulation in NS. In a preliminary study, 10 adult nephrotic patients with biological markers of thrombosis risk (severe hypoalbuminemia and/or anomalies of the fibrinolytic pathway and/or deficiency in coagulation inhibitors) were given 40 mg (4,000 U) of Enoxaparin daily for at least 3 months; 3 patients were treated for 3 months, 1 for 6 months and 6 for 12 months. patients were assessed for silent thrombosis, using renal vein Doppler ultrasonography, lower leg vein Doppler ultrasonography and lung ventilation-perfusion scintigraphy, before entry to the trial and subsequently at 3-month intervals. As LWMH caused no obvious side effects and no thrombosis was oliserved during the pilot study, we then placed 55 adult nephrotic patients free of thrombosis on the same treatment. Patients were seen according to the usual calendar required by their individual illnesses. At each examination, patients were assessed for clinical signs and symptoms of thrombosis and side effects; plasma D-dimer and urinary fibrin-fibrinogen degradation products were also measured at each visit. Twenty-five of the 55 patients (minimal-change disease, n= 15;membranous nephropathy,n=2; systemic lupus erythematosus, n=2; otherforms of glomerulonephritis, n= 6) received LMWH for less than 4 months. No side effects or thrombosis were observed, with the exception of I patient who had local intolerance to Enoxaparin but not to Teldeparin. The other 30 patients (membranous nephropathy, n=14; segmental glomerulosclerosis, n=13; other nephropathies, n=3) received LMWH for at least 6 months (median, 13 months;range, 6-48 months). No side-effects or thrombosis were observed. Enoxaparin caused no changes in bone density in patients at risk of osteoporosis, as determined by absorptiometry. The self-administered LMWH therapy was well accepted by patients, most of whom found it straightforward and painless. The results of this prospective study suggest that the LMWH Enoxaparin given at a dose appropriate for adult NS patients with a high thombotic risk is safe, effective and easily self-administered. The incidence of bleeding was low. Our findings provide arguments for the adoption of LMWH as first-line preventive anticoagulation in NS. k|,î),x , à,,,râi*.,,Pffi1îïl: