Use Of Low Molecular Weight Heparin Research Articles

Low molecular weight heparin prophylaxis for placenta-mediated complications in women with F2G20210A mutation

Introduction. A prothrombin-mutant genotype is a known risk factor in gestational complications.Aim — efficacy assessment in pregravid heparin prevention of pre-eclampsia (PE) and foetal growth retardation (FGR) in females with F2G20210A genotype and suprathreshold prothrombin activity.Patients and methods. A single-centre randomised controlled study enrolled 80 pregnant women carrying prothrombin F2G20210A. The inclusion criterion was a pregravid plasma prothrombin activity > 171 %. The study cohort consisted of 50 women (mean age 31.2 ± 3.7 years) receiving low molecular-weight heparin (LMWH) in menstrual cycle at weight-based elevated prevention doses. A comparison group comprised 30 pregnant women (mean age 31.3 ± 2.9 years) not receiving LMWH prophylaxis.Results. A pregravid start of LMWH treatment at high prophylactic doses in F2G20210A genotype carriers with prothrombin activity > 171 % allowed an absolute risk reduction (ARR) of PE by 46.7 % [p = 0.0001; number needed to treat (NNT): 2.1; 95 % confidence interval (CI) 3.4–1.56], severe PE by 30.7 % [p = 0.0001; NTT: 3.3; 95 % CI (6.7–2.2)] and FGR by 30.7 % [p = 0.0001; NTT: 3.3; 95 % CI (6.7–2.2)].Conclusion. Use of LMWH is justified in prevention of placenta-mediated complications in F2G20210A genotype carriers with a suprathreshold-high prothrombin activity.

Balancing Risk of Thromboembolism and Bleeding in Patients with Cancer: Selecting Anticoagulant Therapy Based on Recent Clinical Trials

Patients with cancer may experience venous thromboembolism (VTE), leading to various medical complications or death, more often than the population without cancer. Moreover, patients with cancer usually experience both higher rates of recurrent VTE and bleeding. For the past decade, low-molecular-weight heparin (LMWH) has been considered a standard therapy for VTE related to cancer; however, daily injections of LMWH have augmented the burden of neoplastic disease and decreased adherence to therapy in some patients. At present, direct oral anticoagulants (DOAC) such as factor Xa inhibitors (e.g., rivaroxaban, edoxaban, and apixaban) have been recommended as a new treatment modality, mostly because of their convenient use (i.e., the oral route of delivery) for the patient population with cancer. Notably, large recent randomised controlled trials that have compared DOACs with LMWH in patients with malignancies have revealed that DOACs represent a valuable alternative to LMWH for the therapy of VTE related to cancer. Despite their unique advantages, the DOACs may not be appropriate for some groups of patients with cancer due to their elevated risk of bleeding, among other factors. This mini-review presents the main findings from some recent randomised controlled trials, comparing the use of DOACs and LMWH for the management of VTE associated with malignancy. It highlights the efficacy, safety, and various other considerations of treatment and prophylaxis of VTE depending on the individual patient context. It provides current guidance on the selection of the optimal anticoagulant for comprehensive and personalised patient care.

Clinical Course of Covid-19 in Hematological Disorders

Hematology patients are extremely vulnerable to COVID-19 infection due to the immunosuppression arising from the direct effect of the disease and the medicines administered. Our purpose is to analyze the results of the patients that both have a hematological disease and receive treatment for COVID-19 infection in our hospital. Four hundred COVID-19 positive patients that received inpatient treatment between March 12, 2020 and October 1, 2020 in our center and got a diagnosis by using real -time polymerase chain reaction (RT-PCR) test were scanned retrospectively. Eighty one patients were included in the study. Nineteen patients had a hematological disease;62 had a chronic disease but didn't have a hematological disease. We found that the group with hematological disease had a high level of ferritin (p= 0.0001). While the use of steroids in COVID-19 treatments is more frequent in the group with hematological disease (p= 0.01), the use of LMWH (low molecular weight heparin) is more frequent in the group with no hematological diseases (p= 0.02). Intensive care treatment and mechanical ventilatory support were required more for the patients with hematological disease than the others (p= 0.03. p= 0.008). While the mortality rate is 42.1% in the patients with hematological disease, it is 9.7% in the patients with chronic disease (p= 0.003). In cox regression analysis, the study found that hematological diseases (HR: 4.02, 95% CI: 1.7-1844.5, p= 0.02), cardiac diseases (HR: 2.28, 95% CI: 1.2-77.9, p= 0.03), and intensive care treatment (HR: 4.60, 95% CI: 3.1-3115.0, p= 0.009) are significant risk factors. Hematological patients infected with COVID-19 have a more severe and mortal clinical manifestation than the patients with other chronical disease.

Recent Trends in the Incidence of Heparin-Induced Thrombocytopenia: Data from the 2009-2014 National Inpatient Sample

BackgroundUse of Low-Molecular Weight Heparin (LMWH) has increased in the US hospitals after the release of generic enoxaparin in 2010. Quality improvement projects and various professional bodies have advocated the use of LMWH over unfractionated heparin because of its superiority over unfractionated heparin for VTE prevention and because of its decreased incidence of Heparin-induced thrombocytopenia (HIT). We used a large administrative database to assess the recent trends of HIT to assess the impact of these interventions in adult hospitalized patients.MethodsWe used the 2009-2014 National Inpatient Sample database, which is the largest publicly available all-payer inpatient database in the US, to identify patients ≥18 years with primary and secondary diagnoses of HIT (International Classification of Diseases, 9th Revision, Clinical-Modifications [ICD-9-CM] code 289.84). Annual incidence of HIT was calculated for each year 2009-2014, fitted into a log-linear model and compared using Monte Carlo permutation test to study the changes in trend. Statistical analyses were done using STATA version 13.0 and Joinpoint Regression Program version 4.5.0.1.ResultsA total of 129,761 adult patients with a diagnosis (both primary and secondary) of HIT were identified during the study period. The proportion of patients who developed HIT was unchanged at 0.06 cases per 100 admissions with an annual percent change (APC) of -2.1 which was statistically not significant (95% CI: -5.7 to 1.6, p=0.02) (Figure 1). Despite the increasing awareness and ease of testing for HIT, the annual incidence of HIT with thromboses (HITT) also remained unchanged (Figure 2). There was however, an increasing total cost of hospitalization from $132,535 in 2009 to $174,253 in 2014 (APC: 6.17, 95% CI: 4.1 to 8.3, p<0.05) even when adjusted for yearly inflation (Consumer Price Index, Bureau of Labor Statistics). However, overall inpatient mortality and length of stay remained unchanged at 9.5% and 13.7 days (Table 1).ConclusionDespite ongoing push towards use of LMWH and country-wide quality improvement projects to encourage the use of LMWH over UFH in hospitalized patients, our data shows that the incidence of HIT remains unchanged from 2009 to 2014. Similarly, the rates of HITT and outcomes (mortality and length of stay) remain unchanged. Given the rising healthcare costs of HIT admissions and flat incidence curves, the need for more effective preventative and early diagnostic strategies, along with cost effective management options are urgently warranted. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

How to use low-molecular-weight heparin to treat neonatal thrombosis in clinical practice.

Among children, neonates have the highest incidence of thrombosis due to risk factors such as catheter instrumentation, an evolving coagulation system and congenital heart disease. Low-molecular-weight heparins (LMWHs) are the most commonly used anticoagulants in neonates. Published guidelines delineate dosing and monitoring protocols for LMWH therapy in newborns. However, challenging clinical situations frequently present that warrant healthcare providers to think critically beyond the range of guidelines, and judiciously resolve specific problems. This review describes the use of LMWH in the neonatal population, including practical aspects such as route and site of administration, preparation from concentrated formulations and methods to minimize pain of subcutaneous injection. It is followed by a discussion on dosing, monitoring and outcomes of LMWH therapy in neonates. The risk of recurrence of thrombosis in neonates after LMWH therapy is approximately 3% based on a pooled analysis of studies reporting this outcome over the last 24 years. The article concludes with an overview of the side-effects of LMWH, including the risk of bleeding which is around 4% based on pooled analyses of more than 30 studies.

Posterior Fossa Hemorrhage Following the Use of Low-Molecular-Weight Heparin: Lessons Learned and Recommendations for the Treatment and Prophylaxis of Postoperative Venous Thromboembolism.

IntroductionVenous thromboembolism (VTE) is the most common preventable cause of morbidity and mortality among neurosurgery patients. Several studies have concluded that the use of chemical prophylaxis among patients undergoing a craniotomy reduces the incidence of VTE, and it is presumed to be safe. However, these studies do not differentiate between a supratentorial and posterior fossa craniotomy. Furthermore, the prophylactic or therapeutic use of low-molecular-weight heparin (LMWH) has been reported to increase the risk of intracranial hemorrhage. In this study, we describe the clinical details and outcomes for all patients who underwent posterior fossa craniotomy and developed posterior fossa hemorrhage secondary to postoperative use of LMWH during the study period. We also propose recommendations pertaining to postoperative heparin use after posterior fossa surgeries.MethodsData were retrospectively collected for patients presenting with posterior fossa hemorrhage following anticoagulant use among those who previously underwent posterior fossa craniotomy by the senior author (R.W.P.) from January 1, 2011, through December 31, 2018.ResultsWe identified five patients who experienced postoperative hemorrhage while receiving LMWH in the initial setting of posterior fossa craniotomy. After hemorrhaging, four patients had low Glasgow Outcome Scale (GOS) scores (≤3) and failed to return to their baseline neurological status. These four patients had a Glasgow Coma Scale (GCS) score of 15/15 in the immediate postoperative period and received heparin within 72 hours of surgery.ConclusionsBased on our findings, there is a possible association between the increased risk of hemorrhage and the early postoperative use of LMWH. The debilitating outcomes among the majority of these patients warrant the cautious use and further investigation of postoperative LMWH to appropriately quantify the risk. Further comparative studies with a larger sample size are required to provide insight into the pathophysiology of our findings.

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.

Do differences in baseline clinical severity of ovarian cancer patients with thrombosis predict treatment with rivaroxaban versus low molecular-weight heparin?

e18748 Background: Prescribers use direct oral anticoagulants and low molecular-weight heparin (LMWH) for the acute treatment and secondary prevention of cancer-associated thrombosis (CAT). We sought to identify predictors impacting the use rivaroxaban versus LMWH for CAT in patients with ovarian cancer. Methods: Using US Surveillance, Epidemiology and End Result-Medicare linked data from 2013-2016, we evaluated adults with ovarian cancer, undergoing hospitalization/emergency department admission for CAT and prescribed rivaroxaban or LMWH for outpatient anticoagulation. Univariate analysis was performed to examine the association between covariates and clinicians’ choice to use rivaroxaban or LMWH. Variables with a p-value &lt; 0.20 upon univariate analysis were deemed significant and subsequently included into a stepwise, backwards multivariable logistic regression model to obtain adjusted odd ratios (ORs) of treatment assignment. Results: Of the 125 ovarian cancer patients included in our analysis, 26% received rivaroxaban and 74% LMWH. All patients had stage 3 or 4 ovarian cancer, 36% were ≥75 years-of-age, 78% were white, and 18% were below the poverty line (p ≥ 0.25). Upon univariate analysis, rural community, time between cancer diagnosis and VTE ≥ 1 year, index VTE without evidence of pulmonary embolism, and CKD ≥ stage 3 were found to be significant predictors of rivaroxaban use when compared to LMWH (p ≤ 0.14 for all). Upon multivariable regression, CKD ≥ stage 3 (OR = 3.13) was shown to be independently associated with rivaroxaban versus LMWH use (p≤0.01). Conclusions: In routine practice, patients were more likely to receive rivaroxaban if they had CKD and lived in a rural area. These differences in prescribing practices may be due to less availability of LMWH in rural areas and less tolerance of injections in CKD patients. Univariate analysis also suggest that low VTE burden (i.e., DVT only) and VTE event ≥ 1 year after cancer diagnosis were also associated with rivaroxaban use over LMWH, which may be due to LMWH therapy as the long-established standard of care for patients with cancer. Large observational studies are needed to confirm these results. [Table: see text]

Current approaches to the use of antiplatelet and anticoagulant drugs in pregnant women with thrombocytopenia caused by hemostasis activation

Introduction. At present, hemostasis disorders still hold one of the lead places in the pathogenesis of reproductive losses associated with high risk of miscarriage and remain one of the major causes for developing serious obstetric complications. Relevance, efficacy and safety of using drugs containing acetylsalicylic acid (ASA) and low molecular weight heparins (LMWH) in pregnant women with thrombocytopenia comorbid with intravascular coagulation activation remain pressing issues. The study of thrombocytopenia pathogenesis during pregnancy and search for new methods of hemostasis correction are accounted for by high risk of developing diverse perinatal complications and necessity to conduct prophylactic measures for their prevention.Aim: to study hemostasis changes and clinical outcomes in pregnant women with thrombocytopenia, to substantiate the use of antiplatelet agents and anticoagulants in pregnant women with activated intravascular blood coagulation for preventing development of thromboembolic and placenta-associated complications of pregnancy.Materials and Methods. A multicenter prospective study was conducted by enrolling 299 pregnant women at a gestational age of22.85 [22.00; 25.00] weeks, whose average age was 31.06 [27.75; 35.00] years. There were distinguished three groups: main group (n = 124) consisted of pregnant women with lowered platelet count and activated intravascular blood coagulation, who received ASA preparations and LMWH in prophylactic doses for 4 weeks; pregnant comparison groups (n = 125) received no such drugs; control group (n = 50) consisted of women with normal platelet counts during physiological pregnancy. All patients underwent clinical, anamnestic and laboratory examination, and the clinical outcomes of pregnancy were assessed.Results. It was found that use of ASA (a combined drug: ASA 75 mg + magnesium hydroxide 15.2 mg/day) and LMWH (enoxaparin sodium) in pregnant women from the main group were noted to improve hemostasis parameters: via markedly increased platelet count, decreased fibrinogen level, prothrombin index as well as normalized antithrombin III level (p &lt; 0.01). It was also found during treatment that the D-dimer level and the rate (83.6 ± 2.3 % and 72.4 ± 2.7 %) and the degree (86.4 ± 2.7 % and 74.4 ±2.8 %) of platelet aggregation in the main group (in contrast with comparison group) were significantly decreased (p &lt; 0.01). The frequency of detected chronic placental insufficiency was significantly higher (p &lt; 0.01) in the comparison group (n = 50; 41.32 %) vs. the main group after receiving ASA and LMWH (n = 20; 16.52 %). The incidence of moderate (p = 0.016) and severe (p = 0.018) preeclampsia was significantly higher in the comparison group vs. the main group. While comparing the volume of blood loss during delivery, there were no differences between the main group and the comparison group (p = 0.46); it was noted only a statistically significant difference compared to the control group (p = 0.04), in which the lowest blood loss was found (337.9 [200.0; 600.0] ml) in comparison with the other two groups (p1,3 = 0.05; p2,3 = 0.04). It should be noted that the volume of blood loss in all groups remained within the physiological permissible range.Conclusion. Our clinical and laboratory study allowed to substantiate relevance of using ASA and LMWH drugs in pregnant women with thrombocytopenia comorbid with confirmed activation of intravascular blood coagulation, for prevention of thromboembolic and placenta-associated complications of pregnancy as well as proved safety of such drugs during pregnancy.

Cerebral venous thrombosis and Covid 19: Literature review

Introduction: Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) was first detected in December 2019 in the city of Wuhan, China, and has since taken on worldwide proportions. It is known that individuals with Coronavirus disease-19 (COVID-19) have systemic clinical manifestations. Among the multisystemic effects, cerebral venous thrombosis (CVT) is responsible for high mortality rates. In this sense, understanding the association between CVT and SARS-CoV-2 infection directly impacts the disease's morbidity and mortality. Methodology: Literature review in the PubMed and Embase databases, with the following search terms: “COVID-19”, “SARS-CoV-2”, “Venous thromboembolism”, “Thrombosis”, “Cerebral Venous Thrombosis”, “Intracranial Sinus Thrombosis” and “Cranial Sinus Thrombosis”. The selected articles were written in English, which addressed the various aspects of COVID-19. Results and discussion: CVT are a rare complication of COVID-19, with an incidence between 0.02 to 1% of hospitalized patients. However, it can reach about 75% of mortality in affected individuals. Pathophysiology seems to be associated with the state of hypercoagulability and the systemic inflammatory process resulting from viral infection. Thus, recent studies show a consensus on the early anticoagulation of patients affected by the virus, to reduce mortality in these cases. However, the differences between the types of anticoagulation, Low Molecular Weight Heparin (LMWH), Unfractionated Heparin (UFH), Dabigatran have not yet been well established, although there is a predilection for the use of LMWH. Also, thrombectomy is a therapeutic intervention option that should be evaluated, due to the risk of additional endothelial injury from the use of stent retrievers. Conclusion: Although it has a relatively low incidence, CVT aggravates the condition and increases the risk of death for patients with COVID-19. Because of this, early diagnosis and evaluation of therapeutic options for CVT are essential for the development of clinical management.

"Part of the Ritual": Exploring Patient and Physician Decision Making Regarding Anticoagulation Use in Obstetric Antiphospholipid Syndrome.

Antiphospholipid syndrome is associated with recurrent pregnancy loss. Low-molecular-weight heparin (LMWH) and/or aspirin (ASA) prophylaxis during pregnancy to prevent future loss is based on limited trial data with mixed results. Given the clinical equipoise, we sought to understand how patients and physicians navigate the decision-making process for use of LMWH and/or ASA in pregnancy. We interviewed 10 patients and 10 thrombosis physicians in Ottawa, Canada from January 2017 to March 2018. Patients who had ≥1 late pregnancy loss or ≥2 early losses and persistently positive antiphospholipid antibodies based on the revised Sapporo/Sydney criteria were identified in the a Thrombosis Clinic. Patients were also identified by the TIPPS Study screening logs of excluded patients. Data collection and analysis occurred iteratively, in keeping with constructivist grounded theory methodology. Our analysis generated three themes, present across both patient and physician interviews, which captured a patient-led decision-making experience: (1) managing high stakes, (2) accepting uncertainty, and (3) focusing on safety. Patients and physicians acknowledged the high emotional burden and what was at stake: avoiding further pregnancy loss. Patients responded to their situation by taking action (i.e., using LMWH injections became a "ritual"), whereas physicians reacted by removing themselves from the final decision by "[leaving] it up to the patient." Our findings should be considered when designing future research on studying the role for LMWH/ASA in this population, as it suggests that the perceived benefits of treatment go beyond improving pregnancy rates. Rather, patients described potential benefit from the process of taking action, even in the absence of a guaranteed good outcome.

Effectiveness and safety of direct oral anticoagulants in patients with cancer associated venous thromboembolism

IntroductionReal-world evidence on the effects of direct oral anticoagulants (DOACs) in patients with cancer associated venous thromboembolism (VTE) is limited. Thus, our population-based cohort study aimed to assess the effectiveness and safety of DOACs compared to the standard of care low-molecular-weight heparin (LMWH) in this vulnerable population. Materials and methodsUsing linked administrative healthcare databases from the province of Québec, Canada, we identified patients with incident VTE from 2012 to 2015 and a cancer diagnosis in the year before the VTE, who initiated treatment with anticoagulants within 30 days after the VTE. Using an active comparator new-user design with an as-treated exposure definition, we compared use of DOACs with use of LMWH. Cox proportional hazards models estimated adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of recurrent VTE, major bleeding, and all-cause mortality. In secondary analyses, we stratified by age and sex. ResultsOverall, 4438 patients with cancer associated VTE initiated treatment with anticoagulants (513 DOACs, 2698 LMWH). During a median follow-up of 0.3 years, and compared with LMWH, DOACs were associated with a decreased risk of recurrent VTE (HR, 0.54; 95% CI, 0.36–0.82) and major bleeding (HR, 0.54; 95% CI, 0.31–0.96). We also observed a decreased risk of all-cause mortality with DOACs compared with LMWH (HR, 0.14; 95% CI, 0.09–0.22). Age and sex did not modify the associations. ConclusionsDOACs were associated with improved effectiveness and safety compared with LMWH in patients with cancer related VTE. Unmeasured confounding probably contributed to our findings on all-cause mortality.

Treatment of sepsis-induced coagulopathy : Results of aGermany-wide survey in intensive care units

HintergrundIm Rahmen von Sepsis und septischem Schock kommt es aufgrund der engen Verflechtung von Gerinnung und Entzündung häufig zu einer Koagulopathie. Die sepsisinduzierte Koagulopathie (SIC) stellt hierbei die schwerste, potenziell fatale Form dar. Aufgrund fehlender Evidenz beschränken sich die aktuellen Sepsis-Leitlinien auf Empfehlungen zur medikamentösen Prophylaxe einer venösen Thromboembolie (VTE), während die Behandlung einer SIC nicht thematisiert wird.MethodenUm den Status quo der VTE-Prophylaxe sowie der SIC-Behandlung auf deutschen Intensivstationen zu erheben, wurde von Oktober 2019 bis Mai 2020 eine deutschlandweite Onlineumfrage unter ärztlichen Leitern von Intensivstationen durchgeführt. Diese wurde ab April 2020 durch einen zusätzlichen Fragenblock ergänzt, der sich mit der VTE-Prophylaxe sowie der SIC-Behandlung bei Coronaviruskrankheit(COVID)-19-Patienten befasste.ErgebnisseDie Umfrageergebnisse zeigen eine ausgeprägte Heterogenität in der klinischen Praxis bezüglich Prophylaxe von VTE und Therapie der SIC. Ein systematisches Screening auf SIC findet in den meisten Intensivstationen nicht statt. Bei COVID-19-Patienten fällt v. a. auf, dass bei drei Viertel der teilnehmenden Intensivstationen die gelebte Praxis der medikamentösen VTE-Prophylaxe nicht von Non-COVID-19-Patienten abweicht.SchlussfolgerungDie Heterogenität der in der Umfrage gesammelten Antworten legt nahe, dass es einer systematischen Aufarbeitung dieses Themenfeldes bedarf, um zukünftig über klinische Interventionsstudien die individualisierte Patientenversorgung mit der gebotenen Evidenz zu unterlegen.Zusatzmaterial onlineDie Online-Version dieses Beitrags (10.1007/s00101-021-00916-9) enthält eine Zusammenstellung weiterer Aspekte zum Beitrag und den zugrunde liegenden Fragebogen. Beitrag und Zusatzmaterial stehen Ihnen auf www.springermedizin.de zur Verfügung. Bitte geben Sie dort den Beitragstitel in die Suche ein, das Zusatzmaterial finden Sie beim Beitrag unter „Ergänzende Inhalte“.

The Association of Low Molecular Weight Heparin Use and In-hospital Mortality Among Patients Hospitalized with COVID-19.

PurposeTo determine the association between low molecular weight heparin (LMWH) use and mortality in hospitalized COVID-19 patients.MethodsWe conducted a retrospective study of patients consecutively enrolled from two major academic hospitals exclusively for COVID-19 in Wuhan, China, from January 26, 2020, to March 26, 2020. The primary outcome was adjusted in-hospital mortality in the LMWH group compared with the non-LMWH group using the propensity score.ResultsOverall, 525 patients with COVID-19 enrolled with a median age of 64 years (IQR 19), and 49.33% men. Among these, 120 (22.86%) were treated with LMWH. Compared with the non-LMWH group, the LMWH group was more likely to be older and male; had a history of hypertension, diabetes, coronary heart disease (CHD), or stroke; and had more severe COVID-19 parameters such as higher inflammatory cytokines or D-dimer. Compared with non-LMWH group, LMWH group had a higher unadjusted in-hospital mortality rate (21.70% vs. 11.10%; p = 0.004), but a lower adjusted mortality risk (adjusted odds ratio [OR], 0.20; 95% CI, 0.09–0.46). A propensity score-weighting analysis demonstrated similar findings (adjusted OR, 0.18; 95% CI, 0.10–0.30). Subgroup analysis showed a significant survival benefit among those who were severely (adjusted OR, 0.07; 95% CI, 0.02–0.23) and critically ill (adjusted OR, 0.32; 95% CI, 0.15–0.65), as well as among the elderly patients’ age > 65, IL-6 > 10 times upper limit level, and D-dimer > 5 times upper limit level.ConclusionsAmong hospitalized COVID-19 patients, LMWH use was associated with lower all-cause in-hospital mortality than non-LMWH users. The survival benefit was particularly significant among more severely ill patients.

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.

Low molecular weight heparin in COVID-19 patients prevents delirium and shortens hospitalization.

BackgroundCOVID-19 patients present with delirium during their hospitalization.AimsTo assess the incidence of delirium in hospitalized COVID-19 patients and analyze the possible association with demographic, clinical, laboratory, and pharmacological factors.MethodsCOVID-19 patients were assessed for clinical signs of delirium and administered the assessment test for delirium and cognitive impairment (4AT) and the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) scales.ResultsOut of the 56 patients of our cohort, 14 (25.0%) experienced delirium. The use of low molecular weight heparin (LMWH) (enoxaparin 1 mg/kg/daily) was less frequent in patients with delirium (p = 0.004) and was accompanied by lower C reactive protein (CRP) levels (p = 0.006).DiscussionThe use of LMWH was associated with absence of delirium, independently of comorbidities and age.ConclusionsThe use of LMWH may help preventing the occurrence of delirium in COVID-19 patients, with possible reduction of length of stay in the hospital and sequelae.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10072-020-04887-4.

Edoxaban Vs. Low Molecular Weight Heparin As Anticoagulant Therapy in Hospitalized Patients with Atrial Fibrillation and COVID-19 Infection

BackgroundDuring SARS-CoV-2 pandemic, the anticoagulant management in patients with atrial fibrillation (AF) was simplified to the use of low molecular weight heparin (LMWH) in different international guidelines. These recommendations were based for the possible drug interactions between oral anticoagulants and the experimental coronavirus disease 2019 (COVID-19) therapies. However, not all direct oral anticoagulants (DOACs) have the same risk of drug-drug interactions. The metabolism of edoxaban by CYP3A4 is less than 4% being one of the DOACs that poses less of drug-drug interactions risk with the therapy used against the COVID-19 (http://www.covid19-druginteractions.org/). Unfortunately, the current information about the use of DOACs in hospitalized patients with COVID-19 infection is very scarce.ObjectiveTo determine whether the effectiveness (major thromboembolic events) and safety (bleedings) of edoxaban or low molecular weight heparin (LMWH) were different among patients with AF that had been hospitalized for COVID-19 infection in Catalonia, Spain.MethodsObservational and multicenter study with a retrospective analysis that consecutively included from March 5th to April 27st 2020 hospitalized patients with the diagnosis of non-valvular AF who received anticoagulant treatment with LMWH or edoxaban concomitantly with the empirical therapy used for COVID-19 infection. The initiation or continuation of anticoagulant treatment with edoxaban was performed according to medical criteria and with close monitoring for possible interactions. The use of LMWH was carried out with therapeutic and intermediate doses. The minimum follow-up was 30 days or until death. Thromboembolic events, hemorrhagic events, length of hospitalization and death from all causes were analyzed. Clinical and analytical factors were compared between both cohorts.ResultsA total of 232 patients (mean age 80.3±7.7 years, 50.0% men, CHA2DS2-VASc 4.1±1.4; HAS-BLED 2.6±1.0) were included. Regarding treatment for COVID-19 during hospitalization, the majority of patients were taking azithromycin (98.7%), hydroxychloroquine (89.7%) and ritonavir/lopinavir (81.5%). The biodemographic, analytical characteristics are summarized in the table 1. With regard to outcomes, mean duration of hospitalization was 14.6±7.2 days and mean total time of follow-up (since admission to last visit) was 31.6±13.4 days. 12.9% of patients required admission in the intensive care unit, 18.5% of patients died and 9.9% had a bleeding complication (34.8% major bleeding). Whereas peak mean D-dimer was higher in those patients taking LMWH (1691.7±2240.8 vs 3249.4±5146.3 µg/L; P=0.003). Except for the duration of hospitalization that was longer in those patients taking LMWH (13.3±6.5 vs 16.0±7.7 days; P=0.005), the rest of outcomes similarly occurred in patients treated with edoxaban or LMWH (Table 1).ConclusionsApproximately one out of 5 hospitalized COVID-19 patients with AF anticoagulated with edoxaban or LMWH died and one out of 10 presented a bleeding complication. Mortality rates, arterial and venous thromboembolic complications and bleedings did not significantly differ between groups. However, the duration of hospitalization was significantly lower with edoxaban. In our clinical practice, edoxaban had a similar therapeutic profile to LMWH and may provide additional benefit. Further studies are needed to determine whether the possible interaction between edoxaban and the antiviral treatment used empirically for COVID-19 is clinically relevant.DisclosuresOlivera:Boehringer Ingelheim: Consultancy, Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; BAYER: Consultancy; Daiichi Sankyo: Consultancy, Speakers Bureau. Campoy:boehringer ingelheim: Consultancy; Daiichi Sankyo: Speakers Bureau. Sierra:Jazz Pharmaceuticals: Research Funding; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Daiichi Sankyo: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Astellas: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead-Kite: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Cerezo:Daiichi Sankyo: Consultancy, Speakers Bureau.

Role of Low Molecular Weight Heparin in the Management of Unexplained Recurrent Pregnancy Loss: A Review of Literature.

Recurrent pregnancy loss remains a significant challenge in gynecological practice, accounting for about 2%-4% of pregnancies. In some patients, the etiology is unknown. Unexplained recurrent pregnancy loss (URPL) refers to the spontaneous loss of three or more consecutive pregnancies without an identifiable risk factor, accounting for about 40%-50% of pregnancy losses. The review aims to understand the role of low molecular weight heparin (LMWH) in the treatment of URPL. Articles for this review have been found in the PubMed database, and studies published more than ten years before the review excluded. The articles were reviewed to determine the effect of LMWH on live birth rates, reduced late pregnancy complications, and adverse drug reactions following its use. Many studies show improved live birth rates in women treated with LMWH compared to the control, while some studies show no improvement. There was no statistically significant difference in reducing late pregnancy complications, such as preeclampsia, intrauterine growth restriction, preterm labor, and low birth weight, in either study and control groups. Adverse drug reaction was rare among women treated with LMWH and, if present, was mild and self-limiting, thus making it a safe therapy. More studies, preferably large multicenter randomized controlled trials, need to be conducted on the use of LMWH to establish a consensus guideline on the treatment of URPL.

The Potential of Low Molecular Weight Heparin to Mitigate Cytokine Storm in Severe COVID-19 Patients: A Retrospective Cohort Study.

On March 11, 2020, the World Health Organization declared its assessment of coronavirus disease 2019 (COVID‐19) as a global pandemic. However, specific anti‐severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2) drugs are still under development, and patients are managed by multiple complementary treatments. We performed a retrospective analysis to compare and evaluate the effect of low molecular weight heparin (LMWH) treatment on disease progression. For this purpose, the clinical records and laboratory indicators were extracted from electronic medical records of 42 patients with COVID‐19 (21 of whom were treated with LMWH, and 21 without LMWH) hospitalized (Union Hospital of Huazhong University of Science and Technology) from February 1 to March 15, 2020. Changes in the percentage of lymphocytes before and after LMWH treatment were significantly different from those in the control group (P = 0.011). Likewise, changes in the levels of D‐dimer and fibrinogen degradation products in the LMWH group before and after treatment were significantly different from those in the control group (P = 0.035). Remarkably, IL‐6 levels were significantly reduced after LMWH treatment (P = 0.006), indicating that, besides other beneficial properties, LMWH may exert an anti‐inflammatory effect and attenuate in part the “cytokine storm” induced by the virus. Our results support the use of LMWH as a potential therapeutic drug for the treatment of COVID‐19, paving the way for a subsequent well‐controlled clinical study.

Stroke and Thromboprophylaxis in the Era of COVID-19

Stroke and Thromboprophylaxis in the Era of COVID-19