Increasing dosages of low-molecular-weight heparin in hospitalized patients with Covid-19.

We conducted an observational cohort study in adult patients consecutively admitted for the respiratory illness Covid-19 to our hub hospital from March 9 to April 7, 2020. The high observed rate of venous thromboembolism prompted us to increase the prophylactic doses of enoxaparin from 40 mg daily up to 1 mg/kg twice daily in patients admitted to intensive care units (ICU), 0.7 mg/kg twice daily in high-intensity of care wards and 1 mg/kg daily in low-intensity of care wards. Patients on high enoxaparin doses were compared to those who received prophylaxis with the standard dosage. Efficacy endpoints were mortality, clinical deterioration, and the occurrence of venous thromboembolism, safety endpoint was the occurrence of major bleeding. Of 278 patients with Covid-19, 127 received prophylaxis with high enoxaparin doses and 151 with standard dosage. At 21 days, the incidence rate of death and clinical deterioration were lower in patients on higher doses than in those on the standard dosage (hazard ratio 0.39, 95% confidence interval 0.23-0.62), and the incidence of venous thromboembolism was also lower (hazard ratio 0.52, 95% confidence interval 0.26-1.05). Major bleeding occurred in four of 127 patients (3.1%) on the high enoxaparin dosage. In conclusion, in the cohort of patients with Covid-19 treated with high enoxaparin dosages we observed a 60% reduction of mortality and clinical deterioration and a 50% reduction of venous thromboembolism compared to standard dosage prophylaxis. However, 3% of patients on high enoxaparin dosages had non-fatal major bleeding.

Evaluation of the anticoagulant effect of low-molecular-weight heparins based on the anti-Xa level during haemodialysis.

AIM: Evaluate the relationship between anti-Xa activity and anticoagulant effect, and ascertain whether accumulation of low-molecular-weight heparins (LMWH) occurs during haemodialysis. METHODS: There was an observational, single-centre study among participants who received the LMWH dalteparin, enoxaparin or nadroparin. A standard haemodialysis session lasted 4 hours. All included participants had anti-Xa activity measures at 0.5 and 4 hours. Extracorporeal circuit (ECC) clotting was evaluated by visual inspection of the haemodialyser and bubble trap after each haemodialysis session. The same person was tested at three consecutive haemodialysis sessions. RESULTS: Overall, 90 participants were enrolled and 259 haemodialysis sessions assessed. There was no significant difference in the mean anti-Xa activity at 0.5 and 4 hours for three consecutive sessions, so LMWH accumulation did not occur. There were 69 (26.6%) sessions in which, ECC clotting was visible. Compared with the group where circuit clotting did not occur, the LMWH dose and anti-Xa activity in the group where circuit clotting occurred were significantly lower. At 0.5 hour, anti-Xa <0.88 IU/mL had significantly higher odds of ECC clotting than that at ≥0.88 IU/mL. At 4 hours, anti-Xa <0.35 IU/mL had significantly higher odds of ECC clotting than that at ≥0.35 IU/mL. CONCLUSION: We found that over three haemodialysis sessions, no significant accumulation of LMWH was evident in subjects receiving a LMWH dose of between 2000 and 5000 IU for regular. Anti-Xa activity measurement can be used to adjust the dosage of LMWH and predict the anticoagulant effect during haemodialysis.

Low-molecular-weight heparin biosimilars: potential implications for clinical practice. Australian Low-Molecular-Weight Heparin Biosimilar Working Group (ALBW).

A working group of clinicians and scientists was formed to review the clinical considerations for use of low-molecular-weight heparin (LMWH) biosimilars. LMWH are biological molecules of significant complexity; the full complexity of chemical structure is still to be elucidated. LMWH biosimilars are products that are biologically similar to their reference product and rely on clinical data from a reference product to establish safety and efficacy. The complex nature of LMWH molecules means that it is uncertain whether a LMWH biosimilar is chemically identical to its reference product; this introduces the possibility of differences in activity and immunogenicity. The challenge for regulators and clinicians is to evaluate the level of evidence required to demonstrate that a LMWH is sufficiently similar to the reference product. The consensus opinion of the working group is that prior to clinical use a LMWH biosimilar should have proven efficacy and safety, similar to the reference product with prospective studies, which should be confirmed with a proactive post-marketing pharmacovigilance programme.

[Are 55 cents always better value than 90 cents for venous thromboembolism prophylaxis? Comparison of three low-molecular-weight heparins with regard to economics and guideline compliance]. / Sind bei der venösen Thrombembolieprophylaxe 55 Cent immer günstiger als 90 Cent? - Vergleich von 3 niedermolekularen Heparinen hinsichtlich Wirtschaftlichkeit und Leitlinien-Compliance.

BACKGROUND: Four low-molecular-weight heparins with different dosage regimens are allowed for venous thromboembolism prophylaxis in patients with a high risk of thromboembolism in Germany. If comparison is made purely on the basis of drug costs, multi-dose vials are the favourable solution. We try to answer the question whether the choice of low-molecular-weight heparin influences the compliance with the S2 guideline "Inpatient and outpatient thromboembolism prophylaxis in surgery and perioperative medicine." Beyond that we ask if multi-dose administration is superior to the pre-filled syringe when total costs are calculated on the basis of procedure and technical application. PATIENTS AND METHODS: After training the nursing and medical staff in guideline-compliant implementation of thromboembolism prophylaxis with pre-filled certoparin safety syringes (03/09-05/09) or nadroparin (06/09-08/09) and enoxaparin (02/10-04/10) from multi-dose vials, we calculated the total costs on the basis of procedure and technical application. Furthermore, the satisfaction of the nursing staff was interrogated and the proportion of non-guideline-compliant prescriptions was determinated prospectively on the basis of a total of 388 patient files. RESULTS: When total costs are calculated on the basis of procedure and technical application, the costs for nadroparin are 1.16 €/0.3 mL, 1.30 €/0.4 mL and 1.58 €/0.6 mL, for enoxaparin 1.04 €/20 and 1.42 €/40, and for certoparin 1.25 €/pre-filled safety syringe. The pre-filled certoparin safety syringe made a very good overall impression on the nursing staff (versus sufficient for nadroparin and enoxaparin). Guideline-compliance was achieved in 100 % with body weight- and risk-independent certoparin, in 79.4 % with risk-adapted enoxaparin, and in 66.4 % with body weight- and risk-dependent nadroparin. CONCLUSION: The complexity of the dosage regimen of a low-molecular-weight heparin has a decisive influence on guideline-compliance. By calculating total costs on the basis of procedure and technical application multi-dose vials only offer a price advantage in patients with a low or moderate risk of thromboembolism compared with pre-filled safety syringes in the venous thromboembolism prophylaxis of orthopaedic and trauma surgery patients.

Factors that influence prescribing within a therapeutic drug class.

RATIONALE, AIMS AND OBJECTIVES: The decision to prescribe one drug instead of another within the same therapeutic class may be influenced by a variety of drug-related, direct, or indirect factors; but little is known about which considerations are most important in such choices. The low-molecular-weight heparins (LMWHs) represent a class of drugs that are commonly used and for which therapeutic equivalence has been debated in the literature. The purpose of this study was to identify and compare factors perceived by doctors and clinical pharmacists to be influential in prescribing decisions among LMWHs. METHODS: Doctors and clinical pharmacists were interviewed to elicit information and to rank factors that influence the prescribing and use of LMWHs in community hospitals in the United States. For each factor, the mean and median of the rating were determined along with the frequency distribution across ratings. The non-parametric Mann-Whitney U-test was used to examine differences between doctors and clinical pharmacists. RESULTS: Both groups considered efficacy, formulary status, and policies restricting drug use to be highly influential in the decision to use one LMWH instead of another. Compared to clinical pharmacists, doctors rated personal experience as more influential, whereas they rated drug cost and prescribing guidelines lower. CONCLUSIONS: These findings suggest that doctors and clinical pharmacists differentiate between LMWHs based on differences between products and because of hospital administrative programs (such as drug formularies). This information may be of value in designing programs to alter medication use.

Low-molecular-weight heparins: are they interchangeable?

Unfractionated heparin (UFH) has been used as an antithrombotic agent in the treatment of various clinical entities for over 60 years. Low-molecular-weight heparin (LMWH) com- pounds have gradually replaced UFH for these indications as they have several advantages, including subcutaneous administration and the lack of need for laboratory monitoring. Ever since their introduction, there has been discussion about whether LMWH compounds differ in their efficacy and safety. The best answer is given by direct comparison of two or more preparations; however, such trials are very scarce. Comparison using classical meta-analysis is limited as only a small number of trials with the respective low-molecular-weight heparin compounds are available. The objective of the present analysis has been to use a novel way of plotting the odds ratios of the different studies to compare the efficacy and safety of different LMWH compounds in the initial treatment of patients with venous thromboembolism. Classical meta-analysis revealed reductions in safety and efficacy of 30--40% in favour of LMWHs. Contrasting the log odds ratios of efficacy and safety indicated that there is no conclusive evidence that LMWHs have intrinsic different safety and efficacy profiles.

Heparinas de bajo peso molecular en la cardiopatía isquémico-metabólica: resultados en 24 casos / Heparins of low molecular weight in the metabolic-isqchemic cardiophatis: in 42 cases results

Se estudian clínica y electrocardiograficamente 42 casos consecutivos de cardiopatías isquémicas metabólicas (CIM), a los cuales se les administró, por estar en crisis de descompensación de su enfermedad (CIM subaguda), una heparina de bajo peso molecular, la dalteparina sódica o Fragmín a dosis de 5.000 UI subcutáneamente una vez al día por 8 días (promedio). El máximo tiempo de control fue de 3 meses. A este tratamiento se sumó un antiagregante plaquetario de acción inhibidora de los receptores de TXA2 (Indobufeno) a dosis oral entre 400 y 600 mg. al día y un inhibidor de la formación de nuevos radicales libres de oxígeno a dosis oral de 60 mg. diarios. Los controles hicieron cada 7 días ambulatoriamente, durante el primer mes hasta el tercero. El promedio de edad fue de 64.2 años. Los resultados fueron altamente favorables, tanto clinica como electrocardiográficamente, llegándose, en la mayoría de los casos que presentaron zona inactivable a la desaparición de la misma. Igual comportamiento se observó con la lesión de la isquemia electrocardiográfica. Dado los buenos resultados se concluye que con este medicamento, mediante el esquema propuesto, se logra una verdadera "trombectomía química farmacológica", con escasos efectos colaterales indeseables menores. La FC se estabilizó en la mayoría de los casos entre 70 y 90 lpm, lo cual mejora el pronóstico de estos enfermos. Se plantea en la discusión el mecanismo de acción del Fragmín, y los otros medicamentos empleados. En ningún caso hubo reacción o efectos indeseables