Dose Of Low Molecular Weight Heparin Research Articles

Meta-analysis of the impact of continuous anticoagulation therapy with low-dose heparin or low molecular weight heparin on the prognosis of patients with acute respiratory distress syndrome

The effects of low-dose heparin and low molecular weight heparin on the efficacy and prognosis of patients with acute respiratory distress syndrome (ARDS) were systematically evaluated. Chinese and English databases such as Wanfang data, VIP database, China National Knowledge Infrastructure (CNKI), China Biomedical Literature Service system (SinoMed), American National Medical Library database (PubMed), Netherlands Medical Abstracts database (Embase) and Cochrane library database were searched for the randomized controlled trials (RCTs) of heparin or low molecular weight heparin in the treatment of ARDS. The search time is from July 1999 to June 2020. The control group was given routine treatment, while the experimental group was given heparin 5-10 U×kg-1×h-1, or low molecular heparin subcutaneous injected 2 500-5 000 U once every 12 hours for 7 days on the basis of the routine treatment. The main outcome were 28-day mortality, arterial oxygen saturation (SaO2), acute physiology and chronic health evaluation II (APACHE II), length of stay in (intensive care unit) ICU and mechanical ventilation time, and the secondary outcome indexes were C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), lung injury score, respiratory frequency, activated partial thromboplastin time (APTT) and prothrombin time (PT) after 7 days' treatment. The two researchers collected data and evaluated the quality of the literature according to the Cochrane 5.1. The stability of the Meta-analysis results was tested by sensitivity analysis, and the publication bias was included in the funnel chart analysis. Fourteen Chinese literatures were included, with a total of 894 cases, including 454 cases in the experimental group and 440 cases in the control group. The results of Meta-analysis showed that the 28-day fatality rate in the experimental group was significantly lower than that in the control group [relative risk (RR) = 0.54, 95% confidence interval (95%CI) was 0.38-0.76, P = 0.000 4], and 7-day SaO2 significantly increased [heparin: mean difference (MD) = 48.27, 95%CI was 29.95-66.59, P < 0.000 01]. Low molecular weight heparin: MD = 56.67, 95%CI was 41.22-71.13, P < 0.000 01]. Compared with the control group, the APACHE II score (MD = -4.28, 95%CI was -5.15 to -3.42, P < 0.000 01), the lung injury score (MD = -1.19, 95%CI was -1.35 to -1.03, P < 0.000 01) and the respiratory rate (MD = -4.76, 95%CI was -6.26 to -3.26, P < 0.000 01) in the experimental group were significantly lower than those in the control group after 7 days' treatment. The time of staying in ICU (MD = -4.85, 95%CI was -6.94 to -2.76, P < 0.000 01) and the time of mechanical ventilation (MD = -2.93, 95%CI was -3.34 to -2.52, P < 0.000 01) in the experimental group were lower than those in the control group. After 7 days' treatment, the levels of IL-6 (MD = -38.50, 95%CI was -59.01 to -17.99, P < 0.000 01), TNF-α (MD = -16.24, 95%CI was -31.11 to -1.38, P < 0.000 01) and CRP (MD = -5.5, 95%CI was -6.47 to -4.27, P < 0.000 01) were significantly lower in the experimental group than those in the control group. However, after 7 days' treatment, there were no significant differences in APTT (MD = -0.55, 95%CI was -1.61 to 0.51, P = 0.27) or PT (MD = -0.41, 95%CI was -1.48 to 0.66, P = 0.45). For the indicators with high heterogeneity, Meta-analysis was carried out again by excluding any study, and the overall effect value did not change significantly, suggesting that the results were relatively robust. Funnel chart analysis was carried out on the indexes with more than 10 articles included in the literature. The results showed that the literature had publication bias, but the bias was small. Continuous anticoagulation therapy with low dose heparin and low molecular weight heparin can improve the prognosis and reduce the mortality of patients with ARDS.

The effectiveness of early anticoagulant treatment in Covid-19 patients.

Coronavirus disease 2019 (Covid-19) is an emerging, fast-spreading and worldwide infectious disease that would be deteriorated with the precipitation of systemic or local thrombosis. The aim of current study was evaluating the effects of early anticoagulant treatment in hospitalized Covid-19 patients. The present retrospective and comparative cohort study investigated 413 hospitalized Covid-19 patients treated with or without Low Molecular Weight Heparin (LMWH) (n = 187 and 226, respectively) in the Covid Clinics of Gulhane Education and Research Hospital in Ankara, Turkey, between March 18 and May 03, 2020. The treatment groups were consisted of the patients evaluated before and after The Covid-19 Treatment Guide update on April 12, 2020 that included the anticoagulant treatment thereafter. The mean age of all 413 patients (204 male and 209 female) at disease onset was 50.6 ± 16.7 years. The LMWH-treated patients had significantly higher coagulation markers such as d-dimer and platelet count than LMWH-untreated patients (p values < 0.05). The inflammatory markers, ferritin, interleukin-6 and procalcitonin were significantly increased in LMWH-untreated patients (p values < 0.05). The presence of any comorbidity was significantly more common in LMWH-treated patients compared to LMWH-untreated group (39.6% vs 19.9%, respectively; p < 0.001). Hypertension and diabetes mellitus were the most frequent comorbidities in both groups. The number of intensive care unit (ICU) transfer and longer length of hospital stay were more commonly observed in LMWH-untreated patients (p values <0.05). Early anticoagulant treatment with relatively higher doses of LMWH may improve the clinical outcome of Covid-19 patients and shorten the length of hospital stay.

Effect of short-term low molecular weight heparin on patency following successful salvage of arteriovenous access with recurrent thrombosis.

This study aims to investigate the effect of low molecular weight heparin (LMWH) in maintaining the patency of arteriovenous (AV) access with recurrent thrombosis. Following successful thrombectomy, 66 patients with recurrent thrombosis were included in the study. The primary, assisted primary and secondary patency rates of patients who received LMWH (n = 24) were compared with those who did not receive anticoagulant (n = 42) using Kaplan-Meier analysis. Cox-regression analysis was performed to investigate potential predictors of patency rates. The mean dose of enoxaparin used was 40 ± 13.1 mg or 0.74 ± 0.2 mg/kg daily for a median duration of 14 (IQR 7,28) days. The mean trough anti-Xa concentrations measured after two doses of LMWH was 0.17 ± 0.13 IU/mL. Kaplan-Meier analyses for mean primary, assisted primary and secondary patency rates of LMWH vs no anticoagulation groups were 149 (95% CI: 91 - 207) vs 87 (95% CI: 42-132) days (P < .006), 230 (95% CI: 142-320) vs 107 (95% CI: 62-150) days (P = .01) and 438 (299-579) vs 294 (95% CI: 197-392) days (P = .08) respectively. LMWH remained a significant protective predictor of primary (HR: 0.49; 95% CI: 0.25-0.86; P = .02) and assisted primary patency rates (HR: 0.51; 95% CI: 0.27-0.98; P = .04) after adjusting for patient age, access age, type of AV access, presence of peripheral vascular disease and haemoglobin levels. LMWH may improve short and mid-term patency rates for AV accesses with recurrent thrombosis.

North American Physician Practice Patterns in the Management of Anticoagulation in Pregnancy.

Background: During pregnancy and in the postpartum period women are at increased risk of venous thromboembolism (VTE) owing to hypercoagulability and mechanical issues, as well as nonpregnancy conditions including inherited and acquired thrombophilia. Although guidelines exist for the use of thromboprophylaxis in this setting, there are differences in the specifics of the recommendations among expert societies. We assessed the current practice patterns of North American providers in the prevention of pregnancy-associated VTE in women with thrombophilia. Methods: A survey was created and distributed with case studies and questions addressing VTE prevention during the antepartum and postpartum periods. Results: Surveys were completed by 28% of adult providers queried, with broad geographic representation. There was consistent use of a prophylactic dose of low-molecular weight heparin (LMWH) ante- and postpartum for individuals with low-risk thrombophilia and past estrogen-provoked VTE but a lack of a consensus of anticoagulant (AC) use and dose in individuals with higher risk thrombophilia. There was variability in the dose selection and monitoring of AC when using induction versus spontaneous labor, with 47% of providers switching from LMWH to unfractionated heparin for those not having a scheduled delivery, and there were differences in the duration of postpartum prophylaxis based upon delivery mode. Conclusion: In this survey of North American experienced specialists' responses to a variety of commonly encountered scenarios of thrombophilia and pregnancy and the management of AC were not always consistent with published guidelines.

Markedly increased risk of postoperative bleeding complications during perioperative bridging anticoagulation in general and visceral surgery

BackgroundIncreasing numbers of patients receiving oral anticoagulants are undergoing elective surgery. Low molecular weight heparin (LMWH) is frequently applied as bridging therapy during perioperative interruption of anticoagulation. The aim of this study was to explore the postoperative bleeding risk of patients receiving surgery under bridging anticoagulation.MethodsWe performed a monocentric retrospective two-arm matched cohort study. Patients that received perioperative bridging anticoagulation were compared to a matched control group with identical surgical procedure, age, and sex. Emergency and vascular operations were excluded. The primary endpoint was the incidence of major postoperative bleeding. Secondary endpoints were minor postoperative bleeding, thromboembolic events, length of stay, and in-hospital mortality. Multivariate analysis explored risk factors of major postoperative bleeding.ResultsA total of 263 patients in each study arm were analyzed. The patient cohort included the entire field of general and visceral surgery including a large proportion of major oncological resections. Bridging anticoagulation increased the postoperative incidence of major bleeding events (8% vs. 1%; p < 0.001) as well as minor bleeding events (14% vs. 5%; p < 0.001). Thromboembolic events were equally rare in both groups (1% vs. 2%; p = 0.45). No effect on mortality was observed (1.5% vs. 1.9%). Independent risk factors of major postoperative bleeding were full-therapeutic dose of LMWH, renal insufficiency, and the procedure-specific bleeding risk.ConclusionPerioperative bridging anticoagulation, especially full-therapeutic dose LMWH, markedly increases the risk of postoperative bleeding complications in general and visceral surgery. Surgeons should carefully consider the practice of routine bridging.

COVID-19-Associated Coagulopathy: Safety and Efficacy of Prophylactic Anticoagulation Therapy in Hospitalized Adults with COVID-19

Background:COVID-19-associated coagulopathy increases mortality in patients with COVID-19 infection. The International Society of Thrombosis and Hemostasis (ISTH) has published a guidance document recommending thromboprophylaxis with low-molecular weight heparin (LMWH) for all hospitalized patients with COVID-19. Despite standard dose LMWH thromboprophylaxis, arterial and venous thrombotic events occur in up to 30-40% of COVID-19 patients admitted to the intensive care unit (ICU). It is not known if patients with coagulopathy from COVID-19 benefit from higher levels of prophylactic anticoagulation therapy. No data exist regarding the comparative safety or efficacy of intermediate dose versus standard prophylactic dose LMWH.Study Design and Methods:This is a multi-center, randomized, open-label study (NCT04360824) comparing standard prophylactic dose enoxaparin (40 mg SC daily if BMI < 30 kg/m2; 30 mg SC twice daily or 40 mg SC twice daily if BMI ≥ 30 kg/m2) versus intermediate-weight adjusted dose enoxaparin (1 mg/kg SC daily if BMI < 30 kg/m2 or 0.5 mg/kg SC twice daily if BMI ≥ 30 kg/m2) in hospitalized patients with laboratory-confirmed SARS-CoV-2 infection who are either admitted to an intensive care unit or have a modified ISTH Overt DIC score ≥ 3.Objectives:The primary endpoint is to compare all-cause 30-day mortality of patients treated with standard prophylactic dose versus intermediate-dose enoxaparin. The secondary endpoints are to determine whether the use of standard prophylactic dose versus intermediate dose enoxaparin impacts major bleeding, arterial thrombosis, venous thrombosis, time to intubation or transfusion of blood products. The exploratory endpoints are to determine the effects of SARS-CoV-2 infection on laboratory coagulation parameters to better understand the mechanism of COVID-19 coagulopathy compared to healthy control subjects; parameters include citrullinated histone H3 (H3Cit), a component of neutrophil extracellular traps. The null hypothesis is that intermediate dose enoxaparin (intervention arm) will have a mortality rate that is not less than standard prophylactic dose enoxaparin (standard of care arm). Assuming a true margin of 20%, a sample size of 82 patients in each arm of the study is required to have 80% power when testing for a difference.Baseline Data:Three centers are currently enrolling patients. As of August 1, 2020, we have enrolled 52 patients (28 males and 24 females) with a median age of 61 years (range 24-80). 51% were Caucasian, 36% Hispanic, and 16% other ethnicities. Median BMI was 31 kg/m2 (range 20-52). Baseline D-Dimer was elevated in 95% of participants with a median of 2.23 mg/mL (range 0.39-40.32). The majority of participants had normal baseline PT, PTT, and platelet levels. All patients had fibrinogen levels over 100 mg/dL with a median of 607 mg/dL. Plasma H3Cit was elevated significantly in patients with COVID-19 (n = 21) vs healthy control subjects (n = 10) (6.48 vs 1.09 ng/mL, P = 0.001).Conclusion:Baseline data for the first 52 patients enrolled confirm the presence of multiple risk factors for thrombosis such as elevated BMI, D dimer, and plasma markers of neutrophil extracellular traps. In contrast to initial reports from China, the prevalence of thrombocytopenia and hypofibrinogenemia was very low in our cohort. Hispanics represented 36% of our study population, compared with 19% of overall COVID-19 infections in the region, suggesting a higher severity of illness in this subpopulation. The enrollment of this trial is ongoing with the addition of sites that have larger African American populations. As safety and efficacy data mature, this study will help clarify the optimum dose of prophylactic enoxaparin to prevent COVID-19 associated coagulopathy.DisclosuresNo relevant conflicts of interest to declare.

Therapeutic dosing of low-molecular-weight heparin may decrease mortality in patients with severe COVID-19 infection.

ABSTRACTBACKGROUND: Venous thromboembolism or extensive thrombosis is relatively common in patients with severe COVID-19 infection and has been associated with increased mortality. During the current COVID-19 pandemic, several prophylactic doses and types of low-molecular-weight heparin (LMWH) are being used worldwide; however, there are no high-quality studies or recommendations for an optimal prophylactic LMWH dose.OBJECTIVES: Investigate the relationship between coagulation parameters and the LMWH dose, and mortality and ICU admission in hospitalized patients with severe COVID-19 pneumonia.DESIGN: Retrospective.SETTING: Tertiary care hospital.PATIENTS AND METHODS: Data on clinical features, coagulation parameters and anticoagulant medications of inpatients with severe COVID-19 were collected for the period between 11 March 2020 and 31 April 2020.MAIN OUTCOME MEASURES: Mortality and ICU admission for prophylactic dose LMWH (0.5 mg/kg twice daily) and therapeutic dose LMWH (1 mg/kg twice daily).SAMPLE SIZE: 154 cases.RESULTS: Ninety-eight (63.6%) patients were treated with the LMWH prophylactic dose and 56 (36.4%) patients were treated with the therapeutic dose. Forty-four (44.9%) of 98 patients using the prophylactic dose LMWH died, while 10 (17.9%) of 56 patients using the therapeutic dose LMWH died (P=.001). Mortality was 6.4-fold higher in the prophylactic dose LMWH users than in the therapeutic dose LMWH users (OR=6.5, 95% CI: 2.4–17.6, P<.001).CONCLUSIONS: Therapeutic dosing of LMWH may decrease mortality in patients with severe COVID-19 infected pneumonia. More aggressive thromboprophylaxis regimens using higher doses of heparin should be evaluated in prospective studies.LIMITATIONS: Lack of information about bleeding complications. LMWH was not compared with other anticoagulant therapies. There was no comparison between our two groups on the APACHE score. Used different doses of LMWH in different clinics in our hospital. Single-center, retrospective study.CONFLICT OF INTEREST: None.

Dosage of Anticoagulants in Obesity: Recommendations Based on a Systematic Review.

Anticoagulants are frequently used as thromboprophylaxis and in patients with atrial fibrillation (AF) or venous thromboembolism (VTE). While obesity rates are reaching epidemic proportions worldwide, the optimal dosage for obese patients has not been established for most anticoagulants, including low-molecular-weight heparin (LMWH), non-vitamin K antagonist oral anticoagulants (NOAC), and pentasaccharides (fondaparinux). The aim of the present systematic review was to summarize the current knowledge and provide recommendations on dosage of LMWH, NOAC, and fondaparinux in obese patients (body mass index [BMI] ≥ 30 kg/m2 or body weight ≥ 100 kg). Based on a systematic search in PubMed and Embase, a total of 72 studies were identified. For thromboprophylaxis with LMWH in bariatric surgery (n = 20 studies), enoxaparin 40 mg twice daily, dalteparin 5,000 IE twice daily, or tinzaparin 75 IU/kg once daily should be considered for patients with BMI ≥ 40 kg/m2. For thromboprophylaxis with LMWH in nonbariatric surgery and in medical inpatients (n = 8 studies), enoxaparin 0.5 mg/kg once or twice daily or tinzaparin 75 IU/kg once daily may be considered in obese patients. For treatment with LMWH (n = 18 studies), a reduced weight-based dose of enoxaparin 0.8 mg/kg twice daily should be considered in patients with BMI ≥ 40 kg/m2, and no dose capping of dalteparin and tinzaparin should be applied for body weight < 140 kg. As regards NOAC, rivaroxaban, apixaban, or dabigatran may be used as thromboprophylaxis in patients with BMI < 40 kg/m2 (n = 4 studies), whereas rivaroxaban and apixaban may be administered to obese patients with VTE or AF, including BMI > 40 kg/m2, at standard fixed-dose (n = 20 studies). The limited available evidence on fondaparinux (n = 3 studies) indicated that the treatment dose should be increased to 10 mg once daily in patients weighing > 100 kg.

Elevated eosinophil count is related with lower anti-factor Xa activity in COVID-19 patients.

Despite prophylactic anticoagulant treatments, thrombotic complications may develop in patients with coronavirus disease 2019 (COVID-19). This study aimed to evaluate the factors influencing anti-factor Xa activity in COVID-19 patients receiving low molecular weight heparin (LMWH). We prospectively evaluated 80 COVID-19 patients, diagnosed using polymerase chain reaction test, who were admitted to our clinic and administered LMWH; LMWH (enoxaparin) was applied according to the weight, D-dimer levels, and clinical condition of patients. Anti-factor Xa activity in blood, drawn 4 h after the 3rd dose of LMWH, was measured and an activity of < 0.2 IU/mL was considered subprophylactic. Patients were followed up clinically, and anti-factor Xa activity was re-examined before discharge. Groups 1 and 2 included 13 and 67 patients with subprophylactic (mean ± SD: 0.18 ± 0.06) and prophylactic (mean ± SD: 0.43 ± 0.23) anti-factor Xa activity, respectively. The proportion of eosinophils in patients was significantly higher in group 1 than in group 2 (mean ± SD; 2.96 ± 2.55 vs 0.90 ± 1.28; p = 0.001). At the time of discharge, the eosinophilic proportion of patients was significantly higher (eosinophil %, mean ± SD; 3.06 ± 1.49 vs 2.07 ± 1.92; p = 0.001), but the activated partial thromboplastin time was significantly lower (22.34 ± 1.38 vs 24.38 ± 3.58; p = 0.01) in group 1 than in group 2. Of 14 patients with eosinophil content > 4%, 6 were in group 1 ((6/13) 46.2%), while 8 were in group 2 ((8/63) 11.9%); (p = 0.009), and all had a D-dimer level < 1 μg/mL (p = 0.03). ROC analysis for the presence of anticoagulation at subprophylactic level revealed an area under curve of 0.79 (95% CI: 0.64–0.93); p = 0.001). In conclusion; Elevated eosinophil count is related to lower anti-factor Xa activity in patients with COVID-19 receiving LMWH. The clinical significance of the subprophylactic anti-factor Xa activity should be studied in COVID-19 patients (NCT04507282).

Adding a Preoperative Dose of LMWH may Decrease VTE Following Bariatric Surgery.

Bariatric procedures are the most effective management for obesity. There is no standard venous thromboembolism (VTE) prophylaxis for both dosing and duration of anticoagulation following laparoscopic sleeve gastrectomy. Our purpose was to assess the optimum regimen for VTE prophylaxis in bariatric procedures and to reduce the incidence of perioperative bleeding. This is a prospective randomized study which involved 100 morbidly obese patients, subdivided into two groups; group A received postoperative low molecular weight heparin (LMWH) prophylaxis alone starting from day 1 to day 15 in dose 1mg/kg/day in a maximum dose 120mg/day, and group B received both pre- and postoperative LMWH; at night of surgery 12h preoperatively and postoperative starting from day 1 to day 15 with the same dose. All patients underwent mesenteric and bilateral lower limbs duplex 15days postoperative using Philips iU machine and linear (L9-3), convex (C5-1) and sector (S5-1) probes. Regarding postoperative VTE, we found statistically significant increase in postoperative VTE in patients of group A (four cases) without any case complicated with VTE in patients of group B (P value = 0.041). Regarding postoperative bleeding, we found statistically insignificant percent of cases complicated with postoperative bleeding in group B compared to group A (P value 0.315). Preoperative as well as a postoperative prophylactic anticoagulant as LMWH is recommended to prevent perioperative VTE. There was an insignificant increase in postoperative bleeding in patients who received preoperative prophylactic anticoagulants.

Focus on coronavirus disease 2019 associated coagulopathy.

Focus on coronavirus disease 2019 associated coagulopathy.

Venous thromboembolism and bleeding in critically ill COVID-19 patients treated with higher than standard low molecular weight heparin doses and aspirin: A call to action

BackgroundCritically ill COVID-19 patients have a clear pattern of inflammation and hypercoagulable state. The main aim of the study was to evaluate the outcome of severe COVID-19 patients basing on prothrombotic risk factors (i.e. D-dimer). We also evaluated the impact of different doses of low molecular weight heparin (LMWH) on the incidence of bleedings. MethodsThe data of forty-two patients admitted to the Intensive Care Unit (ICU) were retrospectively analyzed. On ICU admission, patients with D-dimer < 3000 ng/mL (Group 1) received enoxaparin 4000 UI (6000 UI, if body mass index >35) subcutaneously b.i.d. and patients with D-dimer ≥ 3000 ng/mL (Group 2) received enoxaparin 100 UI/kg every 12 h. Aspirin was administered to all patients once a day. ResultsBoth groups presented a high incidence of perivascular thrombosis (40.9% in Group 1 and 30% in Group 2). Patients of Group 2 suffered a higher incidence of venous thromboembolism (VTE) than Group 1 (65% vs 13.6%, p = 0.001). One patient (4.5%) of Group 1 and three patients (15%) of Group 2 suffered from minor bleeding; no patient had major bleeding. Group 2 had a longer ICU and hospital stay than Group 1 (11.5 ± 5.6 vs 9.0 ± 4.8 and 30 ± 4.9 vs 21 ± 2.3, p < 0.05, respectively) as well as increased ICU mortality (25% vs 9.1%). ConclusionsMore severe critically ill COVID-19 patients have a high incidence of VTE and worse outcome, despite the use of heparin at the therapeutic dose. However, the use of heparin did not increase the incidence of bleeding complications.

Guidance for the Management of Patients with Vascular Disease or Cardiovascular Risk Factors and COVID-19: Position Paper from VAS-European Independent Foundation in Angiology/Vascular Medicine.

COVID-19 is also manifested with hypercoagulability, pulmonary intravascular coagulation, microangiopathy, and venous thromboembolism (VTE) or arterial thrombosis. Predisposing risk factors to severe COVID-19 are male sex, underlying cardiovascular disease, or cardiovascular risk factors including noncontrolled diabetes mellitus or arterial hypertension, obesity, and advanced age. The VAS-European Independent Foundation in Angiology/Vascular Medicine draws attention to patients with vascular disease (VD) and presents an integral strategy for the management of patients with VD or cardiovascular risk factors (VD-CVR) and COVID-19. VAS recommends (1) a COVID-19-oriented primary health care network for patients with VD-CVR for identification of patients with VD-CVR in the community and patients' education for disease symptoms, use of eHealth technology, adherence to the antithrombotic and vascular regulating treatments, and (2) close medical follow-up for efficacious control of VD progression and prompt application of physical and social distancing measures in case of new epidemic waves. For patients with VD-CVR who receive home treatment for COVID-19, VAS recommends assessment for (1) disease worsening risk and prioritized hospitalization of those at high risk and (2) VTE risk assessment and thromboprophylaxis with rivaroxaban, betrixaban, or low-molecular-weight heparin (LMWH) for those at high risk. For hospitalized patients with VD-CVR and COVID-19, VAS recommends (1) routine thromboprophylaxis with weight-adjusted intermediate doses of LMWH (unless contraindication); (2) LMWH as the drug of choice over unfractionated heparin or direct oral anticoagulants for the treatment of VTE or hypercoagulability; (3) careful evaluation of the risk for disease worsening and prompt application of targeted antiviral or convalescence treatments; (4) monitoring of D-dimer for optimization of the antithrombotic treatment; and (5) evaluation of the risk of VTE before hospital discharge using the IMPROVE-D-dimer score and prolonged post-discharge thromboprophylaxis with rivaroxaban, betrixaban, or LMWH.

Inadequate prophylactic effect of low-molecular weight heparin in critically ill COVID-19 patients.

PurposeThe 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 MethodsWe 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).ResultsFive 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.ConclusionsPatients 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.

Retrospective study of hematologic complications in patients with slow-flow vascular malformations undergoing sclerotherapy.

Slow-flow vascular malformations (SFVM) are associated with localized intravascular coagulopathy (LIC), which is characterized by elevated D-dimer and, when severe, hypofibrinogenemia. LIC results in intralesional clotting and hemorrhage and increases risk for significant thrombotic and bleeding complications. Sclerotherapy has been a suggested potential trigger for LIC worsening to disseminated intravascular coagulopathy. Hematologic complications of sclerotherapy in SFVM, along with low-molecular-weight heparin (LMWH) used to prevent worsening LIC, are largely unstudied. Medical records of patients with SFVM and LIC who underwent sclerotherapy at Cincinnati Children's Hospital Medical Center from July 2008 to December 2016 were reviewed for periprocedural hematologic complications. LMWH dose, frequency, and course length were evaluated. Fifty-nine patients with SFVM and LIC underwent 281 sclerotherapy procedures, of which 86% were in children. Eighty-five percent of patients received periprocedural LMWH, although at various doses and course lengths. No thrombotic complications occurred in children. One adult on LMWH developed pulmonary emboli after sclerotherapy. No major bleeding complications occurred postoperatively. In four patients, fibrinogen dropped below 100mg/dL post-sclerotherapy, requiring cryoprecipitate. One patient required packed red blood cell (RBC) transfusion for sclerotherapy-induced hemolysis. No intraoperative bleeding or thrombotic events occurred. LMWH use, at subtherapeutic dosing, was common in this patient population and did not appear to increase risk of significant bleeding before, during, or after sclerotherapy. In children with SFVM, bleeding and thrombotic complications after sclerotherapy appear rare. Although safe, prospective studies are needed to evaluate the efficacy of LMWH to prevent worsening coagulopathy with procedures.

Preliminary Experience With Low Molecular Weight Heparin Strategy in COVID-19 Patients.

BackgroundHeparin administration in COVID-19 patients is recommended by expert consensus, although evidence about dosage, duration and efficacy are limited. We aim to investigate the association between different dosages of low molecular weight heparin (LMWH) and mortality among COVID-19 hospitalized patients.Methods and ResultsRetrospective study of 450 laboratory-confirmed COVID-19 patients admitted to Sant’Orsola Bologna Hospital from March 01 to April 10, 2020. Clinical, laboratory and treatment data were collected and analyzed. The in-hospital mortality between COVID-19 patients treated with standard prophylactic LMWH dosage vs. intermediate LMWH dosage was compared. Out of 450 patients, 361 received standard deep vein thrombosis (DVT) prophylaxis enoxaparin treatment (40-60mg daily) and 89 patients received intermediate enoxaparin dosage (40–60 mg twice daily) for 7 days. No significant differences in the main demographic characteristics and laboratory testings at admission were observed in the two heparin regimen subgroups, except for older age and prevalence of hypertension in the group treated with “standard” prophylaxis LMWH dosage. The intermediate LMWH administration was associated with a lower in-hospital all-cause mortality compared to the “standard” prophylactic LMWH dosage (18.8% vs. 5.8%, p = 0.02). This difference remained significant after adjustment with the propensity score for variables that differed significantly between the dosage groups (OR= 0.260, 95% CI 0.089–0.758, p=0.014).ConclusionsIntermediate LMWH dosage seems to be associated with lower incidence of mortality compared to standard DVT prophylaxys in hospitalized COVID-19 patients. Our study paves the way to further pathophysiological investigations and controlled studies of anticoagulation therapy in Covid-19 disease.

A critical review of the pathophysiology of thrombotic complications and clinical practice recommendations for thromboprophylaxis in pregnant patients with COVID-19.

Those who are infected with Severe Acute Respiratory Syndrome‐related CoronaVirus‐2 are theoretically at increased risk of venous thromboembolism during self‐isolation if they have reduced mobility or are dehydrated. Should patients develop coronavirus disease (COVID‐19) pneumonia requiring hospital admission for treatment of hypoxia, the risk for thromboembolic complications increases greatly. These thromboembolic events are the result of at least two distinct mechanisms – microvascular thrombosis in the pulmonary system (immunothrombosis) and hospital‐associated venous thromboembolism. Since pregnancy is a prothrombotic state, there is concern regarding the potentially increased risk of thrombotic complications among pregnant women with COVID‐19. To date, however, pregnant women do not appear to have a substantially increased risk of thrombotic complications related to COVID‐19. Nevertheless, several organizations have vigilantly issued pregnancy‐specific guidelines for thromboprophylaxis in COVID‐19. Discrepancies between these guidelines reflect the altruistic wish to protect patients and lack of high‐quality evidence available to inform clinical practice. Low molecular weight heparin (LMWH) is the drug of choice for thromboprophylaxis in pregnant women with COVID‐19. However, its utility in non‐pregnant patients is only established against venous thromboembolism, as LMWH may have little or no effect on immunothrombosis. Decisions about initiation and duration of prophylactic anticoagulation in the context of pregnancy and COVID‐19 must take into consideration disease severity, outpatient vs inpatient status, temporal relation between disease occurrence and timing of childbirth, and the underlying prothrombotic risk conferred by additional comorbidities. There is currently no evidence to recommend the use of intermediate or therapeutic doses of LMWH in thromboprophylaxis, which may increase bleeding risk without reducing thrombotic risk in pregnant patients with COVID‐19. Likewise, there is no evidence to comment on the role of low‐dose aspirin in thromboprophylaxis or of anti‐cytokine and antiviral agents in preventing immunothrombosis. These unanswered questions are being studied within the context of clinical trials.

Effect of low or high doses of low‐molecular‐weight heparin on thrombin generation and other haemostasis parameters in critically ill patients with COVID‐19

The clinical picture of the coronavirus 2 (SARS-CoV-2)/COVID-19-related acute respiratory syndrome is often associated with a coagulopathy. An elevated D-dimer has been linked with an unfavorable prognosis in COVID-19 patients.

Real-World Data on Thromboprophylaxis in Active Cancer Patients: Where Are We? Are We Getting There?

Background: Cancer patients are at high risk for cancer-associated thrombosis (CAT). CAT is the second leading cause of death in these patients but it can be preventable with thromboprophylaxis. Patients and Methods: An observational, prospective, multicenter study aiming to record CAT management in clinical practice was conducted by the Hellenic Society of Medical Oncology (HeSMO). Results: A total of 426 active cancer patients (mean age 65.3 years, mean BMI: 26.1 kg/m2) who received thromboprophylaxis, were included from 18 oncology units. Tumor types were lung 25.1%, pancreas 13.9%, breast 8.7%, stomach 8.5%, ovarian 7.8%, and others 36%, while 69% had metastases. A total of 71% had a Khorana score ≤2 and 61% received High Thrombotic Risk Chemotherapy Agents (HTRCAs, e.g., platinum). For thromboprophylaxis patients received mainly Low Molecular Weight Heparins (LMWHs), on higher than prophylactic doses in 50% of cases. Overall, 16 (3.8%) thrombotic events and 6 (1.4%) bleeding events were recorded. Notably, patients on higher doses of LMWHs compared to patients who received standard prophylactic doses had 70% lower odds to develop thrombotic events (OR: 0.3, 95% CI: 0.10–1.0, p = 0.04). Conclusion: CAT is an important issue in oncology. Along with the Khorana score, factors as metastases and use of HTRCAs should also be taken into consideration. Thromboprophylaxis for active cancer patients with LMWHs, even on higher doses is safe and efficient.

Management and outcomes of cancer patients with venous thromboembolism presenting with thrombocytopenia

IntroductionTreatment of venous thromboembolism (VTE) in cancer patients with thrombocytopenia is challenging due to perceived higher risk of bleeding. Material and methodsWe used the RIETE registry to compare the 10- and 30-day outcomes in cancer patients with acute VTE, according to platelet count at baseline. ResultsAs of December 2018, 15,337 cancer patients with VTE were included: 166 (1.1%) had <50 × 109 platelets/L (severe thrombocytopenia), 711 (4.6%) had 50–99 × 109/L (mild thrombocytopenia) and 14,460 (94.3%) had ≥100 × 109/L (normal count). Most patients in all subgroups received initial therapy with low-molecular-weight heparin (LMWH), but 62% of those with severe thrombocytopenia received <150 IU/kg/day LMWH, 42% received <100 IU/kg/day. The mortality rate progressively decreased with increasing platelet counts (12%, 9.4% and 3.3% respectively at 10 days, 27%, 18% and 9.4% at 30 days), but the major bleeding rates did not (1.2%, 2.5% and 1.3% respectively at 10 days, 2.4%, 4.4% and 2.2% at 30 days). On multivariable analysis, patients with severe thrombocytopenia had a similar risk for major bleeding at 10 days (OR 0.84; 95%CI 0.20–3.49) and at 30 days (OR 0.90; 95%CI 0.32–2.49), but those with mild thrombocytopenia were at increased risk both at 10 days (OR 2.11; 95%CI 1.27–3.49) and at 30 days (OR 1.91; 95%CI 1.29–2.84). ConclusionsCancer patients with acute VTE and baseline thrombocytopenia often receive initial lower-than recommended doses of LMWH. Although caution is required, this practice seems to be safe in patients with severe thrombocytopenia. Nonetheless, there was an inverse correlation between baseline platelet count and mortality.