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Open Medicine (Warsaw, Poland) 2020To compare the clinical effectiveness of the two most commonly used LMWHs, dalteparin (DALT) and enoxaparin (ENOX), in thromboprophylaxis of elective total hip...
AIM
To 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 METHODS
To 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.
RESULTS
Thirty-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%); < 0.05). The Lee-White coagulation time mildly decreased in ENOX and DALT following the surgery ( = 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 ( = 0.03).
CONCLUSION
The 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.
PubMed: 33336060
DOI: 10.1515/med-2020-0213 -
Frontiers in Cardiovascular Medicine 2020Venous thromboembolism (VTE) is highly prevalent in cancer patients. Recent guidelines recommend considering direct oral anticoagulants (DOACs) for the treatment of...
Venous thromboembolism (VTE) is highly prevalent in cancer patients. Recent guidelines recommend considering direct oral anticoagulants (DOACs) for the treatment of cancer-associated thrombosis (CAT). However, direct head-to-head comparisons among DOACs are lacking, and almost no net clinical benefit (NCB) analysis has been performed in patients with CAT. We systematically searched PubMed, EMBASE, Cochrane Library, and ClinicalTrials.gov for randomized controlled trials (RCTs) reporting on recurrent VTE, major bleeding, or clinically relevant bleeding events in patients with CAT who received DOACs and low-molecular-weight heparins. Relative risks (RRs) and 95% confidence intervals (95% CIs) were calculated using a random-effect model. Surface under the cumulative ranking curve (SUCRA) values were calculated, and a trade-off analysis was performed to estimate the NCB. Overall, four RCTs involving 2,894 patients were enrolled. DOACs were more effective than dalteparin in reducing the risk of recurrent VTE (RR: 0.62, 95% CI: 0.44-0.87), with a comparative risk of major bleeding (RR: 1.33, 95% CI: 0.84-2.11) and an increased risk of clinically relevant bleeding (RR: 1.45, 95% CI: 1.05-1.99). No significant difference was observed among individual anticoagulants in terms of recurrent VTE and major bleeding. With respect to the ranking of each anticoagulant for the primary outcome, edoxaban (SUCRA: 69.2) was more effective than dalteparin (SUCRA: 60.7), rivaroxaban (SUCRA: 60.7), and apixaban (SUCRA: 25.5) in reducing VTE recurrence. For major bleeding, apixaban (SUCRA: 76.3) had the highest cumulative ranking probability, followed by edoxaban (SUCRA: 66.4), dalteparin (SUCRA: 28.8), and rivaroxaban (SUCRA: 28.5). Similar results were observed for clinically relevant bleeding. In terms of both benefit and safety outcomes, DOACs, especially edoxaban, seemed to confer a better NCB profile than dalteparin. DOACs are a safe and effective alternative therapy to dalteparin in patients with CAT. Among them, edoxaban might provide a good risk-to-benefit balance. However, because of the lack of head-to-head studies, further investigations are needed to confirm our findings.
PubMed: 33304929
DOI: 10.3389/fcvm.2020.586020 -
Critical Care (London, England) Nov 2020A substantial proportion of critically ill COVID-19 patients develop thromboembolic complications, but it is unclear whether higher doses of thromboprophylaxis are...
BACKGROUND
A substantial proportion of critically ill COVID-19 patients develop thromboembolic complications, but it is unclear whether higher doses of thromboprophylaxis are associated with lower mortality rates. The purpose of the study was to evaluate the association between initial dosing strategy of thromboprophylaxis in critically ill COVID-19 patients and the risk of death, thromboembolism, and bleeding.
METHOD
In this retrospective study, all critically ill COVID-19 patients admitted to two intensive care units in March and April 2020 were eligible. Patients were categorized into three groups according to initial daily dose of thromboprophylaxis: low (2500-4500 IU tinzaparin or 2500-5000 IU dalteparin), medium (> 4500 IU but < 175 IU/kilogram, kg, of body weight tinzaparin or > 5000 IU but < 200 IU/kg of body weight dalteparin), and high dose (≥ 175 IU/kg of body weight tinzaparin or ≥ 200 IU/kg of body weight dalteparin). Thromboprophylaxis dosage was based on local standardized recommendations, not on degree of critical illness or risk of thrombosis. Cox proportional hazards regression was used to estimate hazard ratios with corresponding 95% confidence intervals of death within 28 days from ICU admission. Multivariable models were adjusted for sex, age, body mass index, Simplified Acute Physiology Score III, invasive respiratory support, and initial dosing strategy of thromboprophylaxis.
RESULTS
A total of 152 patients were included: 67 received low-, 48 medium-, and 37 high-dose thromboprophylaxis. Baseline characteristics did not differ between groups. For patients who received high-dose prophylaxis, mortality was lower (13.5%) compared to those who received medium dose (25.0%) or low dose (38.8%), p = 0.02. The hazard ratio of death was 0.33 (95% confidence intervals 0.13-0.87) among those who received high dose, and 0.88 (95% confidence intervals 0.43-1.83) among those who received medium dose, as compared to those who received low-dose thromboprophylaxis. There were fewer thromboembolic events in the high (2.7%) vs medium (18.8%) and low-dose thromboprophylaxis (17.9%) groups, p = 0.04.
CONCLUSIONS
Among critically ill COVID-19 patients with respiratory failure, high-dose thromboprophylaxis was associated with a lower risk of death and a lower cumulative incidence of thromboembolic events compared with lower doses.
TRIAL REGISTRATION
Clinicaltrials.gov NCT04412304 June 2, 2020, retrospectively registered.
Topics: APACHE; Aged; Anticoagulants; COVID-19; Critical Illness; Dalteparin; Female; Humans; Intensive Care Units; Male; Middle Aged; Retrospective Studies; SARS-CoV-2; Sweden; Thrombosis; Tinzaparin
PubMed: 33225952
DOI: 10.1186/s13054-020-03375-7 -
Acta Anaesthesiologica Scandinavica Mar 2021Mortality rates in COVID-19 patients in need of mechanical ventilation are high, with wide variations between countries. Most studies were retrospective, and results may... (Observational Study)
Observational Study
BACKGROUND
Mortality rates in COVID-19 patients in need of mechanical ventilation are high, with wide variations between countries. Most studies were retrospective, and results may not be generalizable due to differences in demographics, healthcare organization and surge capacity. We present a cohort of mechanically ventilated COVID-19 patients from a resource-rich, publicly financed healthcare system.
METHODS
Prospective study from a tertiary hospital. Consecutive SARS-CoV-2 positive adult patients admitted to the ICU for mechanical ventilation from 10 March 2020 to 04 May 2020 were included. Triage and treatment were protocolized. High-dose dalteparin was adjusted by D-dimer. Demographics, treatments and high-resolution physiological variables were collected. Outcomes were 30-day and hospital mortality. Data are medians (quartiles).
RESULTS
Of the 1484 persons in the hospital catchment area testing positive for SARS-CoV-2, 201 (13.5%) were hospitalized. Thirty-eight (19%) patients were mechanically ventilated, of whom five (13%) died. Of the 163 patients treated with supplemental oxygen, eight (5%) died. In ventilated patients (75% males, age 61 (53-70) years), severe, moderate and mild ARDS was present in 25%, 70% and 5%. Tidal volume ≤8 mL/kg ideal bodyweight was achieved in 34 (94%) patients. Proning and neuromuscular blockers were used in 19 (54%) and 20 (61%) patients. Duration of ventilation was 12 days (8-23). D-dimer peaked at 3.8 mg/L (2.1-5.3), and maximum dalteparin dose was 15 000 IU/24 h (10 000-15 000). Despite organizational changes, a high degree of adherence to treatment protocols was achieved.
CONCLUSION
In a prospective cohort study of mechanically ventilated COVID-19 patients treated in a resource-rich, publicly financed healthcare system, mortality was considerably lower than previously reported in retrospective studies.
Topics: Anticoagulants; COVID-19; Cohort Studies; Critical Care; Dalteparin; Female; Fibrin Fibrinogen Degradation Products; Humans; Inpatients; Intensive Care Units; Lung; Male; Middle Aged; Prospective Studies; Respiration, Artificial; SARS-CoV-2; Tertiary Care Centers; Time; Treatment Outcome; COVID-19 Drug Treatment
PubMed: 33128800
DOI: 10.1111/aas.13726 -
PloS One 2020To prevent bio-accumulation of low molecular weight heparins (LMWHs) in patients with decreased kidney function, dosage reduction and anti-Xa monitoring has been...
BACKGROUND
To prevent bio-accumulation of low molecular weight heparins (LMWHs) in patients with decreased kidney function, dosage reduction and anti-Xa monitoring has been suggested. The aim of this study was to investigate the effect of pre-emptive dosage reduction of LMWH on anti-Xa levels. Furthermore, we investigated the association between anti-Xa levels and bleeding, thrombotic events and mortality.
METHODS
In this single center study, we followed 499 patients with decreased renal function in whom anti-Xa levels were measured. We observed how many patients had anti-Xa levels that fell within the reference range, with a standard protocol of a pre-emptive dosage reduction of LMWH (25% reduction in patients with an estimated glomerular filtration rate (eGFR) between 30 and 60 ml/min/1.73m2 and a reduction of 50% in patients with an eGFR below the 30 ml/min/1.73m2). Furthermore, Cox proportional hazard analyses were used to estimate hazard ratios to investigate the association between anti-Xa levels and major bleeding, thrombotic events and mortality within three months of follow-up.
RESULTS
In a cohort of 499 patients (445 dalteparin and 54 nadroparin users), a pre-emptive dosage reduction of LMWH led to adequate levels of anti-Xa in only 19% of the patients (12% for the dalteparin users and 50% for nadroparin users). We did not find an association between anti-Xa levels and bleeding, thrombosis or mortality.
CONCLUSION
Pre-emptive dosage reduction of LMWH leads to low anti-Xa levels in a large proportion, but this was not associated with bleeding, thrombosis or mortality.
Topics: Aged; Cohort Studies; Dose-Response Relationship, Drug; Factor Xa Inhibitors; Female; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Kidney; Male; Middle Aged; Thrombosis
PubMed: 33001983
DOI: 10.1371/journal.pone.0239222 -
European Journal of Hospital Pharmacy :... Jul 2022Low-molecular-weight heparins are widely used in clinical practice for the treatment or prophylaxis of venous thromboembolism (VTE). As these drugs are eliminated mainly...
OBJECTIVES
Low-molecular-weight heparins are widely used in clinical practice for the treatment or prophylaxis of venous thromboembolism (VTE). As these drugs are eliminated mainly by renal means, any renal function impairment may lead to higher plasma concentrations and increase the risk of bleeding. This study aims to evaluate whether in clinical practice there is an increase in the occurrence of bleeding in patients with renal insufficiency (RI) during treatment or prophylaxis with dalteparin, and to analyse the risk factors potentially influencing the appearance of such bleeding events.
METHODS
Patients were sampled from the Universitary Severo Ochoa Hospital, Leganés, Spain. This was a retrospective cohort study with a 1 year inclusion period, conducted at a Spanish university hospital with 400 beds, on patients undergoing treatment or prophylaxis for VTE with dalteparin for a minimum of 3 days. The main outcome measure was the number of patients who had bleeding events, independently of their severity, during dalteparin administration in patients with RI.
RESULTS
367 patients were included in the study. Bleeding occurred in 17.9% of patients in the group with RI and in 7.3% of patients with normal renal function (NRF). Most haemorrhages in both cohorts were grade 2 on the WHO scale (64.7% in the RI group and 69.2% in the NRF group). Logistic regression analysis allowed the presence of RI (MDRD-4 (Modification of Diet in Renal Disease) <50 mL/min) to be identified as a risk factor.
CONCLUSION
Patients with RI treated with dalteparin face a higher risk of bleeding than those with NRF, which seems to make it necessary to monitor and seek new dosage adjustments for these patients.Impact on practice statements: This study yields new data on dalteparin in RI, which has not been widely studied before.
Topics: Anticoagulants; Dalteparin; Humans; Renal Insufficiency; Retrospective Studies; Venous Thromboembolism
PubMed: 32920531
DOI: 10.1136/ejhpharm-2020-002262 -
Journal of Critical Care Dec 2020The aim of this study was to investigate potential markers of coagulopathy and the effects of thromboprophylaxis with low-molecular-weight heparin (LMWH) on... (Observational Study)
Observational Study
PURPOSE
The aim of this study was to investigate potential markers of coagulopathy and the effects of thromboprophylaxis with low-molecular-weight heparin (LMWH) on thromboelastography (TEG) and anti-factor Xa in critically ill COVID-19 patients.
MATERIAL AND METHODS
We conducted a prospective study in 31 consecutive adult intensive care unit (ICU) patients. TEG with and without heparinase and anti-factor Xa analysis were performed. Standard thromboprophylaxis was given with dalteparin (75-100 IU/kg subcutaneously).
RESULTS
Five patients (16%) had symptomatic thromboembolic events. All patients had a maximum amplitude (MA) > 65 mm and 13 (42%) had MA > 72 mm at some point during ICU stay. Anti-factor Xa activity were below the target range in 23% of the patients and above target range in 46% of patients. There was no significant correlation between dalteparin dose and anti-factor Xa activity.
CONCLUSIONS
Patients with COVID-19 have hypercoagulability with high MA on TEG. The effect of LMWH on thromboembolic disease, anti-factor Xa activity and TEG was variable and could not be reliably predicted. This indicates that standard prophylactic doses of LMWH may be insufficient. Monitoring coagulation and the LMWH effect is important in patients with COVID-19 but interpreting the results in relation to risk of thromboembolic disease poses difficulties.
Topics: Adult; Anticoagulants; Blood Coagulation; Blood Coagulation Disorders; Critical Illness; Dalteparin; Factor Xa Inhibitors; Female; Heparin, Low-Molecular-Weight; Humans; Intensive Care Units; Male; Middle Aged; Prospective Studies; Risk; Thrombelastography; Venous Thromboembolism; COVID-19 Drug Treatment
PubMed: 32920503
DOI: 10.1016/j.jcrc.2020.08.026 -
Journal of Thrombosis and Haemostasis :... Dec 2020Inflammation with leukocyte activation is a hallmark of cancer-associated thrombosis (CAT), and elevated leukocytes predict venous thromboembolism in cancer outpatients....
BACKGROUND
Inflammation with leukocyte activation is a hallmark of cancer-associated thrombosis (CAT), and elevated leukocytes predict venous thromboembolism in cancer outpatients. In a recent trial, rivaroxaban was more efficacious than dalteparin in preventing CAT recurrence.
OBJECTIVES
In a proof-of-concept study, we aimed to provide a mechanistic basis for improved efficacy of rivaroxaban compared to low molecular weight heparin in CAT treatment.
METHODS
We studied the effects of rivaroxaban, dalteparin, and tinzaparin at peak and trough levels on tumor cell-induced procoagulant activity and platelet aggregation in the presence or absence of the cationic leukocyte-derived enzyme, myeloperoxidase (MPO). Furthermore, pro-inflammatory conditions were generated by stimulating whole blood with lipopolysaccharide (LPS) or phorbol-myristate-acetate (PMA), before measuring thrombin generation in plasma supernatants.
RESULTS
All three anticoagulants inhibited thrombin generation, fibrin clot formation, and platelet aggregation induced by the tissue factor-expressing prostate carcinoma cell line, 22Rv1. Pre-incubation with MPO partially attenuated the anticoagulant activity of dalteparin and tinzaparin, but not rivaroxaban, at trough levels. The effect of MPO did not involve the enzyme's catalytic properties, but required its structural integrity, as indicated by heat denaturation. In plasma obtained from LPS- or PMA-stimulated whole blood, elevated MPO antigen levels inversely correlated with the ability of tinzaparin to inhibit 22Rv1-induced thrombin generation.
CONCLUSIONS
Myeloperoxidase release may partially attenuate the anticoagulant activity of trough levels of dalteparin and tinzaparin in the context of paraneoplastic leukocyte activation. However, this effect is likely not sufficient to explain the improved efficacy of rivaroxaban, and possibly other oral factor Xa inhibitors, in CAT treatment.
Topics: Anticoagulants; Factor Xa Inhibitors; Heparin, Low-Molecular-Weight; Humans; Male; Neoplasms; Peroxidase; Rivaroxaban
PubMed: 32865287
DOI: 10.1111/jth.15075