Low Molecular Weight Heparin Prophylaxis 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.

Comparison of the Safety of Prophylactic Anticoagulants After Intracranial Surgery.

Venous thromboembolism (VTE) represents a rare but preventable postoperative complication. Unfractionated heparin (UH) and low-molecular-weight heparin (LMWH) are used to prevent VTE, but comparative studies of their safety and efficacy in the neurosurgical context are limited. To determine the relative safety and efficacy of UH and LMWH for prophylaxis after cranial surgery. We performed a retrospective analysis of 3204 elective intracranial surgical admissions in 2901 patients over the period 2013 to 2018. From chart review, we extracted demographic and clinical features, including diagnosis and procedure, drugs administered, and the occurrence of VTE events. To compare postoperative outcomes, we performed propensity score matching of patients receiving different drugs, and reviewed postoperative cranial imaging. To contextualize our results, we selected 14 prior neurosurgical studies of VTE prophylaxis to compare our outcomes to the existing literature. In our sample of 3204 admissions, the overall rate of VTE was 0.8% (n=27). Rates of VTE were not statistically different in matched cohorts receiving UH and LMWH (1.7%vs 1.0%, respectively); however, LMWH was associated with a higher rate of clinically significant intracranial hemorrhage (ICH) (3.4%vs 0.5%, P=.008). Literature review and meta-analysis supported these findings. Across studies, UH and LMWH were associated with similar rates of VTE. Studies in which patients received LMWH reported significantly higher rates of ICH (4.9% higher, P=.005). We find that LMWH and UH show similar efficacy in preventing VTE; however, LMWH is associated with higher rates of ICH.

Low-Molecular Weight Heparin is Superior to Unfractionated Heparin for Elderly Trauma Patients

Several studies have demonstrated that low-molecular weight heparin (LMWH) is superior to unfractionated heparin (UFH) in trauma patients. The superiority of either one has not been established for the elderly. In this study, we compared LMWH to UFH in elderly trauma patients. A retrospective analysis of the American College of Surgeons' Trauma Quality Improvement Program database was performed for patients aged ≥65 y. Propensity score matching was performed to minimize confounders between the two groups. Outcomes included venous thromboembolic (VTE) and bleeding events. Overall, 93,987 patients were identified (mean age 77.1 ± 7.3 y, females 55,035 [58.6%]), of which 67,738 (72.1%) patients received LMWH and 26,249 (27.9%) received UFH. After Propensity score matching, LMWH was associated with a lower incidence of deep venous thrombosis (1.7% versus 2.1%, P=0.007) and pulmonary embolisms (0.6% versus 1%, P< 0.001). LMWH was also associated with fewer bleeding complications (transfusions: 2.8% versus 3.5%, P< 0.001, procedures: 0.7% versus 0.9%, P=0.007). Sub-analyses showed that differences in VTE rates were identified in patients with mild injuries (Injury Severity Score [ISS] <16, 0.6% versus 1.9%, P< 0.001). Differences in bleeding complications were identified in patients with injuries of mild (ISS <16, transfusions: 3% versus 3.8%, P< 0.001, surgeries: 0.3% versus 0.4%, P= 0.015) and moderate severity (ISS 16-24, transfusions: 1.9% versus 2.7%, P= 0.038, surgeries: 1% versus 1.7%, P= 0.013). LMWH prophylaxis is superior to UFH for VTE prevention among elderly trauma patients. LMWH prophylaxis is associated with fewer bleeding complications compared to UFH in patients with injuries of mild or moderate severity.

Findings from a multicentre, observational study on reproductive outcomes in women with unexplained recurrent pregnancy loss: the OTTILIA registry.

What evaluation and care is offered to women after unexplained recurrent pregnancy loss (RPL) or intra-uterine foetal death (IUFD) and what are the reproductive outcomes? Women are assessed for thrombophilia and often treated with low-molecular weight heparin (LMWH) and/or low-dose aspirin (ASA). Randomized controlled trials (RCTs) on possible efficacy of heparins and/or aspirin have been inconclusive due to limited power to detect a difference and patient heterogeneity. Prospective multicentre cohort study performed in 12 hospitals in three countries between 2012 and 2019. All consecutive pregnant women with recurrent PL (≥3 losses or 2 losses in the presence of at least one euploid foetal karyotype) or at least one IUFD. Eligible women may have undergone thrombophilia testing before conception, at the discretion of local providers. The possible assignment of women to treatments (such as LMWH) was not decided a priori but was determined based on the responsible provider's current practice. Aims of the study were: (i) to evaluate factors associated with pregnancy outcome; (ii) to compare clinical management strategies in women with and without a subsequent successful pregnancy; and (iii) to evaluate characteristics of women who may benefit from antithrombotic therapy. A propensity score matching method was used to balance the differences in baseline characteristics. A matched sample of 265 pregnant women was analysed, with all undergoing thrombophilia screening; 103 out of 119 (86.6%) with and 98/146 (67.1%) without thrombophilia were prescribed with LMWH and/or ASA. Overall, live-births were recorded in 204 cases (77%), PL or IUFD in 61 (23%) pregnancies. Logistic regression showed a significant interaction between thrombophilia and treatment with LMWH (P = 0.03). Findings from sensitivity analysis showed odds ratio (OR) for pregnancy loss in women with inherited or acquired thrombophilia in absence of any treatment was 2.9 (95% CI, 1.4-6.1); the administration of LMWH (with or without ASA) was associated with higher odds of live-birth (OR, 10.6; 95% CI, 5.0-22.3). Furthermore, in women without thrombophilia, the odds of live-birth was significantly and independently associated with LMWH prophylaxis (alone or in association with ASA) (OR, 3.6; 95% CI, 1.7-7.9). While the propensity score matching allows us to balance the differences in baseline characteristics, it does not eliminate all confounding. Antithrombotic prophylaxis during pregnancy may be effective in women with otherwise unexplained PL or IUFD, and even more useful in those with thrombophilia. The study was funded by Italian Ministry of Health (Ricerca Corrente 2018-2020). Dr G.P. has received research grant support from Bristol Myers Squibb/Pfizer Alliance, Janssen, Boston Scientific Corporation, Bayer, and Portola and consultant fees from Amgen and Agile Therapeutics. Dr E.G. has received consultant fees from Italfarmaco and Sanofi. All other authors declare that they have no conflict of interest. NCT02385461.

Individually Tailored By-Passing Therapy for the Management of Breakthrough Bleeds in Hemophilia Patients with Inhibitors Receiving Prophylaxis with Emicizumab

Background: Emicizumab is a recombinant, humanized, bispecific, monoclonal antibody that bridges activated factor IX and factor X to restore the function of deficient factor VIII, which is needed for effective hemostasis. Treatment of bleeding in patients with hemophilia A and inhibitors involves by-passing agents such as recombinant activated factor VII (rFVIIa) and activated prothrombin complex concentrate (APCC). These molecules are also used for the management of breakthrough bleeds in patients on prophylaxis with emicizumab. There may be risks in combining two procoagulant drugs. In addition, there is no validated laboratory assay to evaluate the combined effect of emicizumab with a by-passing agent. We have previously reported that thrombin generation assay (TGA) may represent a surrogate marker for monitoring by-passing therapies.Methods: After obtaining informed consent of two patients with severe hemophilia A and high titer of inhibitors included in phase 3 HAVEN 1 trial evaluating emicizumab prophylaxis, TGA was performed to determine in vitro individual response of patients to 5 different dosages of APCC (15 -25 - 45 - 75 - 100 U/kg) and rFVIIa (45 - 90 - 150 -200 - 270 µg/kg), while on emicizumab prophylaxis. Thrombin generation was measured according to the recent recommendations published by the ISTH FVIII/FIX subcommittee.Results: A dose dependent increase of thrombin generation was observed with both by-passing agents, rFVIIa and APCC, in platelet rich- and platelet poor-plasma. However, very low dosages of APCC i.e. 15 to 25 U/kg were sufficient to fully normalize thrombin generation in our two patients.One patient experienced an acute spontaneous arterial bleeding while on prophylaxis regimen with emicizumab 1.5 mg/kg weekly. He had presented a dissection of an aberrant renal artery supplying the inferior pole of the left kidney responsible for a perirenal hematoma of 16x10x7 cm. The patient was suffering from arterial dysplasia, he also had high blood pressure and dyslipidemia. As the individual response of the patient to by passing agents was determined before the bleeding event, he could benefit from personally tailored by-passing therapy with APCC. He had a single “high dose” of 24 U/kg followed by 15 U/kg every 12 hours during 2 weeks and then 15 U/kg every 24 hours during one additional week, for a total treatment duration of 3 weeks. Thrombin generation capacity was 2039 nM.min with APCC 24 U/kg and 1488 nM.min with APCC 15 U/kg. Normal thrombin generation capacity is 1487±372 nM.min (mean±2SD) as determined in 100 healthy volunteers (2). The patient safely recovered with no thrombotic complication during the 3 weeks of APCC treatment. No low molecular weight heparin prophylaxis was prescribed during the treatment with APCC. HAVEN 1 study reported 9% of thrombotic complications in patients who had received multiple infusions of APCC. The coagulation capacity of patients receiving combined emicizumab and by-passing therapy may be very different. This case illustrates that global haemostasis assays may help physician to determine the individual profile of patients with by-passing agents and emicizumab and to tailor their by-passing therapy when treating breakthrough bleeding.Conclusion: The use of an objective laboratory criterion, such as thrombin generation capacity, may be helpful to guide by-passing therapy in patients receiving emicizumab prophylaxis. In vitro spiking experiments, easy to perform, may represent valuable information for the choice of dosages that may effectively achieve haemostasis and not represent a high risk of thrombosis. Thus, individually tailored by-passing therapy may help to limit adverse events that may occur when emicizumab is used in combination with other procoagulant molecules. DisclosuresDargaud:Stago: Honoraria; CSL Behring: Honoraria, Research Funding; BMS: Honoraria, Research Funding; LFB: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Baxalta/Shire: Honoraria, Research Funding; Alnylam: Research Funding; Octapharma: Honoraria, Research Funding; Bayer: Honoraria, Research Funding. Negrier:LFB: Honoraria, Speakers Bureau; Baxalta: Honoraria, Speakers Bureau; Bayer: Honoraria, Research Funding, Speakers Bureau; Baxter: Research Funding; Pfizer: Honoraria, Research Funding, Speakers Bureau; Biogen/SOBI: Honoraria, Research Funding, Speakers Bureau; Octapharma: Honoraria, Research Funding, Speakers Bureau; Novo Nordisk: Honoraria, Research Funding, Speakers Bureau; Inspiration: Research Funding; CSL Behring: Honoraria, Research Funding, Speakers Bureau; Alnylam: Research Funding.

P361 No increased postoperative risk of venous thromboembolism in patients with Ulcerative Colitis undergoing colectomy after tofacitinib exposure

Abstract Background Colectomy for ulcerative colitis (UC) has been associated with postoperative morbidity and mortality, including venous thromboembolism (VTE). Patients with inflammatory bowel diseases (IBD) have a 2 to 4-fold increased risk for developing VTE, as compared to non-IBD patients. Due to recent concerns on increased VTE associated with tofacitinib exposure, we aimed to evaluate the 180-day postoperative VTE risk in UC patients undergoing colectomy after tofacitinib use in comparison to patients failing biologicals and undergoing the same surgery. Methods This retrospective cohort study included all UC patients who underwent colectomy between 2014 and 2020 in our tertiary IBD center. All medical charts were reviewed, and clinically relevant information extracted, including indication for colectomy, development of postoperative VTE (deep venous thrombosis, pulmonary or extra-pulmonary embolisms) within 180 days of surgery, low-molecular weight heparin (LMWH) prophylaxis and perioperative therapy exposure (steroids within 1 month prior to surgery, biologicals or tofacitinib within 3 months prior to surgery). Results One-hundred seven UC patients (49.5% women, median [IQR] age 38.0 [27.0 – 53.0] years) underwent colectomy due to refractory disease (n=93), dysplasia or carcinoma (n=12) or polyposis (n=2) (Table 1). Thirty-six (33.6%) patients were operated urgently. At the time of surgery, 44 (41.1%) were on steroids, 38 (35.5%) on anti-TNF agents, 27 (25.2%) on vedolizumab/etrolizumab, 6 (5.6%) on anti-IL12/23 agents and 12 (11.2%) on tofacitinib. All patients received antithrombotic prophylactic LMWH postoperatively. During the 180-day postoperative period, 3 (2.8%) patients developed an intra-abdominal thrombosis, none of them had a history of VTE. Two thromboses were found by coincidence on CT scans which were performed in light of postoperative fever and inflammatory blood tests, the other patient was symptomatic. All 3 patients had been exposed to vedolizumab: one had an underlying malignancy (colon adenocarcinoma), the 2 others also had been exposed to corticosteroids prior to colectomy. No VTE was seen in the patients who underwent colectomy while on tofacitinib. Conclusion The overall risk for UC patients to develop VTE after colectomy is low with adequate antithrombotic prophylactic therapy. In particular, we did not observe any VTE in our colectomy patients who were exposed to tofacitinib prior to surgery. The three patients who developed VTE despite LMWH had additional risk factors (concomitant steroid use, active cancer).

Use of low-molecular weight heparin, transfusion and mortality in COVID-19 patients not requiring ventilation.

It is still debated whether prophylactic doses of low-molecular- weight heparin (LMWH) are always effective in preventing Venous Thromboembolism (VTE) and mortality in COVID-19. Furthermore, there is paucity of data for those patients not requiring ventilation. We explored mortality and the safety/efficacy profile of LMWH in a cohort of Italian patients with COVID-19 who did not undergo ventilation. From the initial cohort of 422 patients, 264 were enrolled. Most (n = 156, 87.7%) received standard LMWH prophylaxis during hospitalization, with no significant difference between medical wards and Intensive Care Unit (ICU). Major or not major but clinically relevant hemorrhages were recorded in 13 (4.9%) patients: twelve in those taking prophylactic LMWH and one in a patient taking oral anticoagulants (p: n.s.). Thirty-nine patients (14.8%) with median age 75 years. were transfused. Hemoglobin (Hb) at admission was significantly lower in transfused patients and Hb at admission inversely correlated with the number of red blood cells units transfused (p < 0.001). In-hospital mortality occurred in 76 (28.8%) patients, 46 (24.3%) of whom admitted to medical wards. Furthermore, Hb levels at admittance were significantly lower in fatalities (g/dl 12.3; IQR 2.4 vs. 13.3; IQR 2.8; Mann–Whitney U-test; p = 0.001). After the exclusion of patients treated by LMWH intermediate or therapeutic doses (n = 32), the logistic regression showed that prophylaxis significantly and independently reduced mortality (OR 0.31, 95% CI 0.13–0.85). Present data show that COVID-19 patients who do not require ventilation benefit from prophylactic doses of LMWH.

Low-molecular-weight heparin versus unfractionated heparin in pediatric traumatic brain injury.

The incidence of venous thromboembolism (VTE) in patients with traumatic brain injury (TBI) has increased significantly. The Eastern Association for the Surgery of Trauma recommends using low-molecular-weight heparin (LMWH) over unfractionated heparin (UH) in pediatric patients requiring VTE prophylaxis, although this strategy is unsupported by the literature. In this study, the authors compare the outcomes of pediatric TBI patients receiving LMWH versus UH. The authors performed a 4-year (2014-2017) analysis of the pediatric American College of Surgeons Trauma Quality Improvement Program. All trauma patients (age ≤ 18 years) with TBI requiring thromboprophylaxis with UH or LMWH were potentially eligible for inclusion. Patients who had been transferred, had died in the emergency department, or had penetrating trauma were excluded. Patients were stratified into either the LMWH or the UH group on the basis of the prophylaxis they had received. Patients were matched on the basis of demographics, injury characteristics, vital signs, and transfusion requirements using propensity score matching (PSM). The study endpoints were VTE, death, and craniotomy after initiation of prophylaxis. Univariate analysis was performed after PSM to compare outcomes. A total of 2479 patients met the inclusion criteria (mean age 15.5 ± 3.7 years and 32.0% female), of which 1570 (63.3%) had received LMWH and 909 (36.7%) had received UH. Before PSM, patients receiving UH were younger, had a lower Glasgow Coma Scale score, and had a higher Injury Severity Score. Patients treated in pediatric hospitals were more likely to receive UH (12.9% vs 9.0%, p < 0.001) than patients treated in adult hospitals. Matched patients receiving UH had a higher incidence of VTE (5.1% vs 2.9%, p = 0.03). LMWH prophylaxis in pediatric TBI appears to be more effective than UH in preventing VTE. Large, multicenter prospective studies are warranted to confirm the superiority of LMWH over UH in pediatric patients with TBI. Moreover, outcomes of VTE prophylaxis in the very young remain understudied; therefore, dedicated studies to evaluate this population are needed.

Successful Non-surgical Treatment of an Acute Calculous Cholecystitis in a Myeloma Patient with Covid-19: Case Report.

COVID-19 has a wide spectrum of clinical phenotypes. While fever and cough are the most common symptoms, abdominal pain is rarely reported. We report the first case of COVID-19 pneumonia in an elderly patient with multiple myeloma (MM), complicated by acute calculous cholecystitis (ACC). A 73-year-old gentleman with underlying IgG kappa MM, presented with fever, cough and dyspnoea. His nasopharyngeal swab was positive for SARS-CoV-2. Piperacillin/tazobactam and oral hydroxychloroquine were started in addition to granulocyte colony-stimulating factor (GCSF) support due to neutropenia. Patient deteriorated on day 5, requiring high flow oxygen support. Dexamethasone, low molecular weight heparin prophylaxis and one dose of intravenous immunoglobulin were given. Despite negative swab on day 10, he developed ACC on day 17. With antibiotics and supportive care, patient showed full recovery without any surgical intervention. It remains elusive whether the gallbladder might be vulnerable to COVID-19, necessitating further validation via prospective studies.

Should pregnant women with anticoagulant prophylaxis benefit from scheduled delivery?

When vaginal delivery is considered in women with low-molecular-weight heparin (LMWH) treatment, epidural analgesia is contraindicated for 12-24h after the last injection. We evaluated the proportion of epidural analgesia depending on whether this is scheduled delivery (labor induction after stopping LMWH) or unscheduled delivery (stopping LMWH at labor onset). Retrospective hospital study running from 2015 to 2017. Inclusion criteria for patients with LMWH treatment were: singleton pregnancy, gestational age ≥ 38weeks of gestation and possible vaginal delivery. The primary endpoint was the epidural analgesia rate. Secondary endpoints included risks for caesarean section, deep vein thrombosis, and postpartum hemorrhage. Among 129 patients, 54 had scheduled delivery (41.9%). In practice, only 44 of them had labor induction (81.5%) and 54 of the 75 patients in the unscheduled delivery group had spontaneous delivery (72.0%). There was no significant difference in the rate of epidural analgesia between the "scheduled" and "unscheduled" groups (52/54 (96.3%) vs. 66/75 (88.0%) (p = 0.12)), and no difference in the secondary endpoints. High access rates to epidural analgesia are observed in both scheduled and unscheduled deliveries. Scheduled delivery does not appear to be a really advantageous strategy for women with LMWH prophylaxis.

Children and Young Adults Admitted to a NYC Children's Hospital Had a Similar Rate of Severe COVID-19 Coagulopathy As That Reported in Older Adults

The coagulopathy associated with COVID-19 has not been previously described in children and young adults. We reviewed the clinical and laboratory characteristics of children and young adults admitted for COVID-19 to an urban Children's Hospital in New York City, focusing on coagulation and venous thromboembolism.Clinical and laboratory data were analyzed from 54 patients aged 2 months to 30 years treated by the Pediatric Hematology service at a single Children's Hospital between January 1 and May 31, 2020. Information was obtained from hospital records with IRB approval.There was a moderate male predominance, with 32 (59%) males and 22 (41%) females. There were 28 (52%) patients younger than 18 years and 26 (48%) patients 18 - 30 years old. 26% of patients identified as Black, and 57% as Hispanic/Latino, similar to the community demographics in the Bronx in the 2019 census. Obesity was the most prevalent comorbid condition, with 19 (35%) patients having BMI of 30 or higher. There were also 12 (22%) patients with sickle cell anemia.There were 28 (52%) patients in this cohort with severe and critical illness, as based on established criteria, and 25 (46%) patients required increased ventilatory support. This was defined by the need for > 5L nasal cannula, high-flow nasal cannula, non-rebreather, or intubation. 11 patients (20%) had documented venous thromboembolism (VTE). Four patients died of COVID-19 complications at ages 2 months, 11, 14 and 18 years old. The VTE rate was similar in those patients under 18 years of age (5 of 28, 18%) and those 18 - 30 years of age (6 of 26, 23%). Most (94%) patients had a D-Dimer > 0.5 (upper limit of normal) at admission and 57% developed peak D-Dimer > 5 ug/mL during their admission.Elevated D-dimer > 5 was a risk factor for VTE with 3 of 23 (13%) and 7 of 17 (41%) patients developing VTE with D-dimer < 5 and > 5, respectively (OR 4.7, p=0.042). Patients requiring increased ventilatory support had a 36% rate of VTE as compared to 1 of 28 (4%) of those without (OR 15.2, p=0.003). Six of 24 patients on prophylactic anticoagulation developed VTE. One patient developed a pulmonary embolism 10 days post discharge from the hospital. No patients on anti-Xa-based low molecular weight heparin prophylaxis developed VTE. None of 12 patients with sickle cell anemia developed VTE, had peak D-Dimer > 5 ug/mL or required increased ventilatory support.Hospitalized children and young adults with COVID-19 in our cohort developed a coagulopathy similar to that of older adults, characterized by elevated D-Dimer and high rate of VTE. This is in contrast to the published pediatric series out of China and Singapore that described mild illness and did not comment on VTE rates. Presence of elevated D-dimer or need for increased ventilatory support were significant risk factors for thrombosis. Patients with sickle cell anemia had a lower risk of VTE and less severe illness. Anti-Xa monitored thromboprophylaxis may aid in preventing or ameliorating the COVID-19 coagulopathy in children and young adults. Institutional anticoagulation guidelines were developed based on these observations.DisclosuresDavila:Spire Learning: Speakers Bureau; ATHN: Other: Grant Funding. O'Brien:Bristol Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees.

Stroke and Thromboprophylaxis in the Era of COVID-19

Stroke and Thromboprophylaxis in the Era of COVID-19

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.

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.

Risk factors of postoperative deep vein thrombosis (DVT) under low molecular weight heparin (LMWH) prophylaxis in patients with thoracolumbar fractures caused by high-energy injuries.

To determine the incidence of DVT and to evaluate the risk factors of DVT under LMWH prophylaxis in patients with thoracolumbar fractures caused by high‑energy injuries postoperatively. A total of 534 patients from January 2016 to November 2019 were included in this retrospective study. Medical record data, including demographic data, perioperative variables, and laboratory results, were collected. LMWH prophylaxis was used for DVT in all the patients. The incidence and risk factors of DVT after surgery were identified by logistic regression analysis and receiver operating characteristic (ROC) curve analysis. The overall incidence of postoperative DVT was 18.91% (101/534). Three patients (0.56%) had proximal DVT and ninety-eight (18.35%) patients had distal DVT. The incidence of postoperative DVT in patients with thoracic fractures was 26.80% and 15.50% with lumbar fractures. The multivariate analysis showed that six risk factors increased the incidence of postoperative DVT, including advanced age, decreased lower extremity motor, blood transfusion, duration of bed rests, fibrinogen (FIB), and D-dimer. The ROC analysis indicated that the diagnostic value of D-dimer was highest whose area under the ROC curves (AUC) value was 0.754. Despite LMWH prophylaxis, the risk of postoperative DVT is still very high, especially in thoracic fracture. Advanced age, decreased lower extremity motor, blood transfusion, duration of bed rests, FIB, and D-dimer are risk factors for DVT. Moreover, the diagnostic value of D-dimer is the highest among these factors.

Low molecular weight heparin for prevention of central venous catheter-related thrombosis in children.

The prevalence of children diagnosed with thrombotic events has been increasing in the last decades. The most common thrombosis risk factor in neonates, infants and children is the placement of a central venous catheter (CVC). It is unknown if anticoagulation prophylaxis with low molecular weight heparin (LMWH) decreases CVC-related thrombosis in children. This is an update of the Cochrane Review published in 2014. To determine the effect of LMWH prophylaxis on the incidence of CVC-related thrombosis and major and minor bleeding complications in children. Further objectives were to determine the effect of LMWH on occlusion of CVCs, number of days of CVC patency, episodes of catheter-related bloodstream infection (CRBSI), other side effects of LMWH (allergic reactions, abnormal coagulation profile, heparin-induced thrombocytopaenia and osteoporosis) and mortality during therapy. The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL databases and World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 7 May 2019. We undertook reference checking of identified trials to identify additional studies. We included randomised controlled trials (RCTs) and quasi-randomised trials comparing LMWH to no prophylaxis (placebo or no treatment), or low-dose unfractionated heparin (UFH) either as continuous infusion or flushes (low-dose UFH aims to ensure the patency of the central line but has no systemic anticoagulation activity), given to prevent CVC-related thrombotic events in children. We selected studies conducted in children aged 0 to 18 years. Two review authors independently identified eligible studies, which were assessed for study methodology including bias, and extracted unadjusted data where available. In the data analysis step, all outcomes were analysed as binary or dichotomous outcomes. The effects of interventions were summarised with risk ratios (RR) and their respective 95% confidence intervals (CI). We assessed the certainty of evidence for each outcome using the GRADE approach. One additional study was included for this update bringing the total to two included studies (with 1135 participants). Both studies were open-label RCTs comparing LMWH with low-dose UFH to prevent CVC-related thrombosis in children. We identified no studies comparing LMWH with placebo or no treatment. Meta-analysis found insufficient evidence of an effect of LMWH prophylaxis in reducing the incidence of CVC-related thrombosis in children with CVC, compared to low-dose UFH (RR 0.68, 95% CI 0.27 to 1.75; 2 studies; 787 participants; low-certainty evidence). One study (158 participants) reported symptomatic and asymptomatic CVC-related thrombosis separately and detected no evidence of a difference between LMWH and low-dose UFH (RR 1.03, 95% CI 0.21 to 4.93; low-certainty evidence; RR 1.17, 95% CI 0.45 to 3.08; low-certainty evidence; for symptomatic and asymptomatic participants respectively). There was insufficient evidence to determine whether LMWH impacts the risk of major bleeding (RR 0.27, 95% CI 0.05 to 1.67; 2 studies; 813 participants; low-certainty evidence); or minor bleeding. One study reported minor bleeding in 53.3% of participants in the LMWH arm and in 44.7% of participants in the low-dose UFH arm (RR 1.20, 95% CI 0.91 to 1.58; 1 study; 158 participants; very low-certainty evidence), and the other study reported no minor bleeding in either group (RR: not estimable). Mortality during the study period was reported in one study, where two deaths occurred during the study period. Both were unrelated to thrombotic events and occurred in the low-dose UFH arm. The second study did not report mortality during therapy per arm but showed similar 5-year overall survival (low-certainty evidence). No additional adverse effects were reported. Other pre-specified outcomes (including CVC occlusion, patency and CRBSI) were not reported. Pooling data from two RCTs did not provide evidence to support the use of prophylactic LWMH for preventing CVC-related thrombosis in children (low-certainty evidence). Evidence was also insufficient to confirm or exclude a difference in the incidence of major and minor bleeding complications in the LMWH prophylaxis group compared to low-dose UFH (low and very low certainty respectively). No evidence of a clear difference in overall mortality was seen. Studies did not report on the outcomes catheter occlusion, days of catheter patency, episodes of CRBSI and other side effects of LMWH (allergic reactions, abnormal coagulation profile, heparin-induced thrombocytopaenia and osteoporosis). The certainty of the evidence was downgraded due to risk of bias of the included studies, imprecision and inconsistency, preventing conclusions in regards to the efficacy of LMWH prophylaxis to prevent CVC-related thrombosis in children.

COVID‐19 associated coagulopathy and thromboembolic disease: Commentary on an interim expert guidance

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) is the causative pathogen of a new infectious disease, COVID-19, that first occurred in late December 2019 in the city of Wuhan in Hubei Province, China. It has since spread globally, resulting in a WHO declared pandemic, with as yet (17/4/20) more than two million confirmed cases and about 150.000 confirmed deaths. As for every new disease, clinicians, hospitals and governments struggle to find optimal clinical and public health measures to contain its spread and burden. For this, information from scientific research is crucial and fortunately we see a rapidly accumulating output of studies.

WeMPiC protocol to prevent Deep Venous Thrombosis in patients with neurosurgical diseases

Background: Deep Venous Thrombosis is a common yet difficult problem to prevent in neurosurgical patients. Recent trials did not find sufficient evidence to support use of graduated compression stockings, however we believe, this inefficiency may be due to the method of application which needs to be modified. We have been following a patient specific mechanical prophylaxis protocol, nicknamed WeMPiC. This study aims to evaluate the effectiveness of WeMPiC protocol.&#x0D; Methods: An observational cohort study was performed including consecutive patients admitted to neurosurgical ICU who were bedridden for &gt;7 days between April 2014 and September 2017. We developed WeMPiC protocol of early weaning off, early mobilization, limb physiotherapy and alternate two hours on and off application of thigh length graduated compression stockings. Lower limbs compression ultrasound studies were performed on alternate days.&#x0D; Results: One hundred thirty-one patients were included in the study. Mean age of patients was 53.7+ 20.6 years. Of these patients, 52.7% had stroke (91% had hemorrhages), 32.1% had head injury and 7.6% each had spine problem and brain tumor each. five (3.8%) developed deep venous thrombosis on the 4th and 6th day of ICU stay, mainly in popliteal veins (2.3%) and femoral veins (1.5%). Deep venous thrombosis was associated with younger age (47 years, p=0.005), ICU stay (13 days, p=0.014), Wells’ score (4.6, p&lt;0.0001) and Poor Glasgow Coma Score at presentation (9, p=0.004). Power of study calculated for the cohort incidence of 3.8% was 100%. Cost benefit of $336 with WeMPiC protocol was seen as compared to the Low molecular weight heparin prophylaxis over four weeks.&#x0D; Conclusions: Compared to incidence of 12.1% in CLOTS 3 trial among the unexposed patients, we report a risk reduction of 8.3% with WeMPiC protocol which is cost effective and highly applicable in resource constraint scenarios.

Risk of pregnancy-related venous thromboembolism and obstetrical complications in women with inherited type I antithrombin deficiency: a retrospective, single-centre, cohort study

Inherited quantitative (type I) deficiency of plasma antithrombin is associated with a high risk of venous thromboembolism, which further increases in pregnancy. Inherited thrombophilia also increases the risk of obstetrical complications, but data on maternal and fetal outcomes in women with antithrombin deficiency are scarce. The aim of this study was to evaluate the risk of pregnancy-associated venous thromboembolism and obstetrical complications in women with type I antithrombin deficiency. In this single-centre, retrospective cohort study, women who had been referred to our Hemophilia and Thrombosis Centre, Milan, Italy for a thrombophilia work-up from Jan 1, 1980, to Jan 1, 2018, with type I antithrombin deficiency and who had had at least one pregnancy were included. Women with type II anthithrombin deficiency were excluded from the study. Data on pregnancy-associated venous thromboembolism, pregnancy outcomes, and the use of low-molecular-weight heparin (LMWH) were collected to evaluate the risk of pregnancy-associated venous thromboembolism and obstetrical complications with or without use of LMWH. 126 women had been referred to the hospital, of whom 88 (70%) had had at least one pregnancy. Eight were excluded because of referral for venous thromboembolism during pregnancy or the puerperium, resulting in 80 (63%)women evaluated for the risk of venous thromboembolism. One woman was excluded because of referral for obstetrical complications, resulting in 87 (69%) evaluated for risk of obstetrical complications. We observed three events of venous thromboembolism in 43 pregnancies in women treated with LMWH (7·0%, 95% CI 1·8-17·8), and 17 events in 146 pregnancies in women who did not receive LMWH (11·6%, 7·2-17·6; relative risk [RR] 0·6, 95% CI 0·2-1·9; p=0·57). The risk of venous thromboembolism without LMWH was 5·4% (95% CI 0·9-16·7) in women with a negative family history of venous thromboembolism, and 11·8% (6·4-19·6) in those with a positive family history of venous thromboembolism. Of the 87 women evaluated for the risk of obstetrical complications, miscarriages occurred in 6 (13%) of 45 pregnant women treated with LMWH and 32 (20%) of 161 women who did not receive LMWH (terminations excluded). Late obstetrical complications occurred in 11 (24%) of women treated with LMWH and nine (6%) in those who did not receive LMWH (RR 4·4, 95% CI 1·9-9·9; p=0·0006). Our results confirm that women with type I antithrombin deficiency have a high risk of first or recurrent venous thromboembolism during pregnancy. The risk of venous thromboembolism is highest in women with a positive family history of the condition, but still relevant in those with a negative family history, suggesting that LMWH prophylaxis should also be considered in these patients. None.

Effect of prophylactic anticoagulation on incidence of venous thromboembolism in testicular germ cell tumor patients.

422 Background: Testicular germ cell tumors (GCTs) are among the most common solid tumors in young males. With the availability of highly effective treatment, improving patients’ quality of life has gained more focus in recent years. Venous thromboembolism (VTE), commonly occurring in GCT patients, is associated with increased morbidity and mortality. Prophylactic anticoagulation has been shown to decrease the risk of VTE in cancer patients. In this retrospective study we evaluated the effect of low molecular weight heparin (LMWH) prophylaxis during hospitalization on incidence of VTE and outcome in GCT patients treated with first-line chemotherapy. Methods: Study population included 394 chemotherapy-naive GCT patients treated with first-line chemotherapy at the National Cancer Institute, Bratislava, Slovakia from January 2000 to December 2017. VTE was defined as any venous thrombosis or pulmonary embolism, confirmed by imaging, occurring during first-line chemotherapy. No visceral thromboses were observed. Results: Forty-one out of 394 patients (10.4%) were diagnosed with VTE on initial staging and were excluded from the analysis. Final cohort included 353 patients. LMWH prophylaxis was administered to 104 patients (29.5%), 249 patients (70.5%) did not receive prophylaxis. We observed 14 (4.0%) VTE events. The difference in VTE incidence between patients with and without prophylaxis was not statistically significant (5.8% vs. 3.2% p = 0.37). We have observed a trend to longer overall survival in patients without prophylaxis (HR = 0.61, 95%CI = 0.32-1.13, p = 0.08). Patients with extragonadal GCT receiving VTE prophylaxis had significantly shorter survival compared to patients without prophylaxis (HR = 0.29, 95%CI = 0.08-1.12, p = 0.04). Conclusions: LMWH prophylaxis was not associated with decreased VTE incidence. Moreover, it was associated with shorter survival in extragonadal GCTs. Taking into account these data, LMWH prophylaxis during hospitalization should not be used in GCT patients receiving chemotherapy.