Low Molecular Weight Heparin Prophylaxis Research Articles

Thrombosis and Bleeding Risk Scores Are Strongly Associated with Mortality in Hospitalized Patients with COVID-19: A Multicenter Cohort Study.

Background: Internationally established guidelines mention pharmacological prophylaxis for all hospitalized COVID-19 patients. However, there are concerns regarding the efficacy and safety of anticoagulants. This study investigated the associations between thrombosis/bleeding risk scores and clinical outcomes. Methods: We conducted a retrospective review of adult patients admitted to two hospitals between 2021 and 2022. We analyzed clinical data, laboratory results, low molecular weight heparin (LMWH) use, thrombosis, bleeding, and 30-day survival. Results: Of the 160 patients, 69.4% were female, and the median age was 59 years. The rates of thrombotic complications and mortality were 12.5% and 36.3%, respectively. LMWH prophylaxis was administered to 73 of the patients (45.6%). The patients with high Padua prediction scores (PPS) and high IMPROVEVTE scores had a significantly higher risk of venous thromboembolism (VTE) compared to those with low scores (30.8% vs. 9.0%, p = 0.006 and 25.6% vs. 7.7%, p = 0.006). Similarly, elevated IMPROVEVTE and IMPROVEBRS scores were associated with increased mortality (hazard ratios of 7.49 and 6.27, respectively; p < 0.001). Interestingly, LMWH use was not associated with a decreased incidence of VTE when stratified by risk groups. Conclusions: this study suggests that COVID-19 patients with high thrombosis and bleeding risk scores have a higher mortality rate.

Thromboprophylaxis with Intermediate Dose Low Molecular Weight Heparin in Adults Undergoing Induction with L-Asparaginase for Acute Lymphoblastic Leukemia

Introduction Adolescents and young adults (AYA, defined as age 15-39 years) with acute lymphoblastic leukemia (ALL) have a poorer prognosis than their pediatric counterparts. To replicate the success of ALL treatment in children, pediatric-inspired regimens have been incorporated into the treatment of AYA and often include the use of L-asparaginase. Rates of thrombosis in adults receiving L-asparaginase for treatment of ALL have been reported to be as high as 34%, compared to only about 5% in pediatric patients. The risk of thrombosis is elevated primarily during the induction phase of treatment. Several strategies have been studied in adults, including antithrombin III replacement, fresh frozen plasma replacement, and prophylactic dosing of anticoagulation, however no clear guidelines exist on how to prevent thrombosis in these high-risk patients. To prevent L-asparaginase-induced thrombotic events, our institution implemented a standard practice of 1mg/kg/day of low molecular weight heparin (LMWH), a dose in-between prophylactic and therapeutic dosing, administered to all adults with ALL who were treated with L-asparaginase during induction chemotherapy. In this current study, we report data from patients who have been treated with this strategy from 2012 to present, focusing on the antithrombotic efficacy and safety of 1mg/kg/day LMWH in this population. Methods This retrospective chart review included 62 patients who received prophylactic anticoagulation with the LMWH enoxaparin (1mg/kg/day) while undergoing induction chemotherapy with L-asparaginase for ALL at the Oregon Health &amp; Science University from 2012 to present. Anticoagulation with enoxaparin was initiated with the first dose of L-asparaginase and continued until the day of discharge or day 30 of induction. The primary outcome was the incidence of thrombosis within the first 30 days of L-asparaginase administration. Minor and major bleeding events, as defined by the International Society of Thrombosis and Haemostasis (ISTH), were recorded. Statistical analysis with univariate regression models was performed to evaluate the association of thrombotic events with demographic, disease and treatment variables. Results Sixty-two patients received 1mg/kg/day LMWH prophylaxis during ALL induction between January 2012 and June 2023 (43 with B-ALL and 19 with T-ALL). Median age at induction was 25.7 years (range 18-39 years). A majority of patients (83.9%) received the maximum dose of 2500mg/m 2 of L-asparaginase. Four patients (6.5%; 95% CI 1.8%-15.7%) experienced a thrombotic event within the first 30 days of induction with L-asparaginase; 3 of the events were catheter-associated and were treated supportively or with catheter removal, and 1 patient developed a distal lower extremity deep vein thrombosis related to myositis. Median time to thrombosis was 13.5 days (range 11-22 days). There were no significant associations between development of thrombotic events with age, gender, B- or T-cell precursor, or dose of L-asparaginase. No thrombosis-related deaths or major bleeding events occurred. Conclusions Prophylactic anticoagulation with intermediate dose 1mg/kg/day LMWH in adults with ALL undergoing induction chemotherapy with L-asparaginase is a safe and an effective strategy to prevent serious thrombotic events. Our institutional rate of 6.5% of patients experiencing thrombotic events during induction with L-asparaginase, with all of the events being clinically low risk, compares favorably to historically reported rates in adults and approaches the low rates reported in children. Further prospective research is warranted.

Anti-factor Xa level monitoring of low-molecular-weight heparin for prevention of venous thromboembolism in critically ill patients (AXaLPE): protocol of a randomised, open-label controlled clinical trial

IntroductionWhether and when to monitor the amount of anti-factor Xa (aFXa) activity in critically ill patients with complex diseases to prevent venous thromboembolism (VTE) remain unclear. This study is a...

P454 No increased postoperative risk of venous thromboembolism nor infectious complications after JAK inhibitor exposure in patients with ulcerative colitis undergoing colectomy

Abstract Background Total colectomy for ulcerative colitis (UC) is associated with postoperative morbidity, including venous thromboembolism (VTE), in patients who already have a 2 to 4-fold risk for thromboembolic events. In light of recent concerns on increased major adverse events associated with JAK inhibitor exposure, we aimed to evaluate the postoperative VTE risk as well as other (non)infectious complications in UC patients undergoing colectomy after JAK inhibitor use. Methods This retrospective cohort study included all UC patients who underwent colectomy between 2013 and 2021 in our tertiary IBD center, and documented the 180-day postoperative non-infectious and infectious risks (table 1). Clinically relevant information included patient demographics, comorbidities, family history of IBD, personal history of VTE, intake of oral anticonception, smoking behaviour, disease characteristics including indication for colectomy, preoperative serum laboratory values, perioperative drug exposure (table 2) and surgical characteristics including low-molecular weight heparin (LMWH) prophylaxis (table 3). Results One-hundred seventy-nine UC patients (43.6% women, median [IQR] age 42.0 [28.5 – 56.2] years) underwent colectomy due to refractory disease (n=154) or suspected dysplasia or carcinoma (n=25). Forty-nine patients (27.4%) were operated urgently. In the twelve weeks prior to surgery, 55 (30.7%) patients had received anti-TNF agents, 40 (22.3%) anti-adhesion therapy, 16 (8.9%) anti-IL12/23, 2 (1.1%) investigational agents and 36 (20.1%) JAK inhibitors. Preoperatively, 27 patients (15.1%) were administered a moderate to high dose of systemic corticosteroids. All patients received antithrombotic prophylactic LMWH postoperatively, except for two patients who developed a gastrointestinal bleeding. During the 180-day postoperative period, a total of 3 patients (1.7%; mean age 51 years, 1 female) developed an intra-abdominal thrombosis, found by coincidence on CT scan. In all patients risk factors were identified, e.g. inflammatory state, cancer, high dose of corticosteroids. No VTE was seen in the patients who underwent colectomy while on JAK inhibitor. Only two out of 36 JAK inhibitor treated patients (5.6%) developed an infectious complication, while the overall risk of developing an infectious complication was 19.5%. Conclusion The overall risk for UC patients to develop VTE after colectomy is low with adequate antithrombotic prophylactic therapy. We did not observe any VTE in patients who were exposed to JAK inhibitors prior to surgery, nor did we see an increased risk on short-term infectious complications in this patient group. All patients who developed VTE despite LMWH had additional risk factors.

The Saudi Consensus for the Management of Cancer-Associated Thromboembolism: A Modified Delphi-Based Study.

Background Cancer is a well-known risk factor of preventable thromboembolic disease. This study aims to provide guidance on the prevention and management of cancer-associated thrombosis (CT) that tailors prophylactic and therapeutic options for medical and surgical oncology patients presenting to health care settings in Saudi Arabia. Methods The present consensus was developed in concordance with the modified Delphi-based approach, which incorporates a face-to-face meeting between two voting rounds to gain experts' feedback on the proposed statements. All experts were either oncologists, hematologists, or hemato-oncologist with an active clinical and research profile in hemato-oncology. Results The experts highlighted that the comparatively high incidence of inherited thrombophilia among the Saudi population may account for a higher CT burden in the Kingdom than in other parts of the world. However, due to the lack of literature that assesses CT in Saudi Arabia, primary venous thromboembolism prophylaxis should be tailored according to a valid risk assessment of cancer patients and should be implemented in routine practice. For hospitalized medical oncology patients, the experts agreed that prophylaxis with low-molecular-weight heparin (LMWH) should be offered, regardless of the presence of acute illness. For ambulatory medical oncology patients, LMWH or direct oral anticoagulants (DOACs) prophylaxis should be offered for high-risk patients. Concerning surgical patients, they agreed that all oncology patients undergoing surgery should be offered thromboprophylaxis. In terms of secondary prophylaxis, the experts recommended continuing a prophylactic dose of anticoagulant (LMWH or DOAC), for an appropriate period depending on the cancer type and stage. Finally, they also provided a set of statements on management of CT in Saudi Arabia. Conclusion The present modified Delphi-based study combined the best available evidence and clinical experience with the current health care policies and settings in Saudi Arabia to build a consensus statement on the epidemiology, prevention, and management of CT.

A retrospective study on the use of low-molecular-weight heparin for prevention of pregnancy-related recurrent venous thromboembolism and obstetrical complications.

The risk of venous thromboembolism (VTE) is increased during pregnancy and it is further increased together with pregnancy complications in women with personal history of VTE and thrombophilia abnormalities. It is unclear how the use of low-molecular-weight heparin (LMWH) may prevent such complications. To evaluate the potential benefits and risks of the use of LMWH for prevention of pregnancy-related VTE and obstetrical complications in the first pregnancy after a previous VTE. This retrospective cohort study includes fertile women referred to the Thrombosis Center from January 2000 to September 2018 for a thrombophilia work-up, after having had at least one previous VTE and one pregnancy thereafter. Data on pregnancy-related recurrent VTE, pregnancy outcomes and the use of LMWH were collected. Among 208 women, no thrombosis or major bleeding was recorded in 138 pregnancies conducted with LMWH, whereas 10 VTE (14%) were recorded in 70 pregnancies conducted without. Nine women (90%) with recurrent VTE had had a previous hormone-related event. The incidence of miscarriage was lower in pregnancies with LMWH than in those without (11% vs. 26%, relative risk 0.4, 95% confidence interval: 0.2-0.8), whereas late obstetrical complications and terminations were similar in the two groups. The prevalence of terminations was doubled in women with thrombophilia (12%) than in those without (6%). LMWH prophylaxis during pregnancy appears to be effective and safe for the prevention of recurrent VTE and may reduce the incidence of miscarriage.

Thromboembolic Events in Patients Undergoing Neoadjuvant Chemotherapy and Radical Cystectomy for Muscle-Invasive Bladder Cancer: A Study of Renal Impairment in Relation to Potential Thromboprophylaxis.

Recent studies on patients with muscle-invasive bladder cancer (MIBC) undergoing neoadjuvant chemotherapy (NAC) have shown an association between NAC and thromboembolic events (TEE) prior to radical cystectomy (RC). Recent studies suggest that central venous access catheters (CVAs) may induce TEEs, and low-molecular-weight heparin (LMWH) has been mentioned as possible prophylaxis. However, other studies have shown a high incidence of decreased renal function in these patients. The purpose of this study was to determine the portion of MIBC patients with NAC-induced TEEs who had decreased preoperative renal function for whom LMWH potentially would not be beneficial as prophylaxis. We identified 459 cystectomized MIBC patients from two Swedish medical centers from 2009 to 2021. The inclusion criterion of cT2-T4aN0M0 resulted in 220 eligible patients, who were further divided into NAC-administered (n = 187) and NAC-eligible (n = 33), the tentative control group. Values of renal function before, during, and after each NAC cycle were retrospectively collected from individual medical records. Amongst the NAC-administered patients with TEE (n = 29), 41% (95% CI 23.5-61.1%) of patients had decreased renal function. Thus, a substantial portion of NAC-administered patients who developed TEEs had reduced renal function and would have been less likely to have benefited from renal clearance-dependent LMWH prophylaxis.

Thrombin Generation Is Differentially Affected By Anticoagulants in Patients with Acute Lymphoblastic Leukemia - an Ex-Vivo Study

Background: Venous thromboembolism (VTE) is a frequent complication in patients with acute lymphoblastic leukemia (ALL). Low molecular weight heparin (LMWH) reduces the risk of VTE in ALL, but is not well tolerated in children. VTE rates remain unacceptably high in adults despite LMWH prophylaxis. Thus, novel strategies for VTE prevention are warranted. In the primary analysis of the PREVAPIX-ALL trial there was no statistically significant reduction in VTE among children treated with the oral factor Xa inhibitor, apixaban, compared to no anticoagulation (AC). Comparative data on activity of different anticoagulants are needed to guide planning of VTE prophylaxis trials. Aims: To characterize and compare the ex-vivo effect of LMWH (enoxaparin), oral direct factor Xa inhibitors (apixaban, rivaroxaban) and oral direct thrombin inhibitor (dabigatran etexilate) in ALL patients' samples using thrombin generation (TG). Methods: A prospective observational cohort study of 46 children with newly-diagnosed ALL, treated with the L-asparaginase (ASP)-based BFM protocol, at a tertiary medical center. Patients on therapeutic-dose AC at baseline were excluded. Blood samples were drawn before ASP treatment (ALL-Day0) and 7 days after (ALL-Day7). Normal pooled plasma (NP) was collected from healthy adult volunteers. Samples were spiked ex-vivo with enoxaparin [0.2 U/mL], apixaban [39 ng/mL], rivaroxaban [39 ng/mL] and dabigatran [150 ng/mL] or vehicle (i.e., control). AC concentrations chosen based on 50% peak reduction (for Xa inhibitors) or 200% LT prolongation (for dabigatran) in NP. Subsequently, TG was performed initiated using 5 pM tissue factor in the presence of 4 µM phospholipids using Calibrated Automated Thrombogram method in these samples. Results are expressed as peak height (PH) and lag time (LT) and relative reduction or prolongation (% difference in PH or LT, respectively) in plasma samples spiked with anticoagulants compared to control. Reduction in PH reflects enoxaparin, apixaban and rivaroxaban activity, while LT prolongation indicates dabigatran activity. This report focuses on measures reflecting the activity of each drug. Descriptive statistics were used to show the median [interquartile range (IQR)] for continuous variables and percentages for categorical data. T-Test / Mann-Whitney U test and paired T-test / Wilcoxon test used to compare between paired and non-paired samples, respectively. Results: Selected sample characteristics are as follows: median age, 7.75 years [IQR 3.73-11.93]; 19 (41%) females; median BMI, 16.8 [IQR 15.5-19.9]; B-cell precursor immunophenotype in 33 (71.7%) and T-cell in 13 (28.3%); prior VTE in 1 (2%). Median PH [IQR] in control samples (without AC) was 256.6 [252.6-265.3] nmol/l, 396.0 [347.2-464.7] nmol/l and 354.4 [307.1-407.4] nmol/l in NP, ALL-Day0 and ALL-Day7 respectively. Median LT [IQR] in control samples was 2.7 [2.5-2.83] nmol/l, 1.8 [1.7-2.3] nmol/l and 1.7 [1.6-2] nmol/l in NP, ALL-Day0 and ALL-Day7 respectively. Median % differences in PH and LT between samples spiked with different anticoagulants and controls are shown in Figure 1A and Figure 1B, respectively. Enoxaparin, apixaban and rivaroxaban reduced PH in NP, ALL-Day0 and ALL-Day7 samples (p<0.0005). There was less reduction in PH with enoxaparin, apixaban and rivaroxaban in ALL-Day0 samples than in NP (p=0.029, p<0.0005, p<0.0005 respectively), suggesting reduced anticoagulant activity in ALL patients compared to subjects without ALL. LT was prolonged with dabigatran in NP, ALL-Day0 and ALL-Day7 samples (p<0.05). Dabigatran resulted in a similar LT prolongation in ALL-Day0 and NP (p=0.677), suggesting a preserved AC effect in ALL. There was less LT prolongation in ALL-Day7 (134% [123-175%] than in ALL-Day0 (180% [134-238]; p=0.031). This reflects an ongoing dabigatran effect after ASP, albeit to a lesser degree. Conclusions: Our ex-vivo results suggest limited anticoagulant activity of enoxaparin and lack of anticoagulant activity of apixaban and rivaroxaban (both factor Xa inhibitors) in preventing VTE in ALL, in line with prior clinical data. In contrast, dabigatran etexilate, an oral direct thrombin inhibitor not previously tested in ALL, exhibited preserved anticoagulant activity in ALL patients, even after exposure to ASP. This may suggest that dabigatran should be investigated in clinical studies for the unmet need of VTE prophylaxis in ALL. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Evaluation of Retinal Microvascular Impairment after COVID-19 and its Clinical Correlates Using Optical Coherence Tomography Angiography.

Retinal vascular complications have been described in patients with coronavirus disease 2019 (COVID-19). This study aimed to analyze retinal microvascular changes and their correlations with clinical findings. This case-controlled study was conducted in a university hospital. The right eyes of 52 otherwise healthy patients recovered from COVID-19 and 42 healthy controls were examined with optical coherence tomography angiography. Mann-Whitney U test was used to compare vessel density (VD) and foveal avascular zone (FAZ) parameters. Associations with treatment choices, pneumonia, and laboratory findings were analyzed. Twenty-nine patients (56%) and 18 healthy controls (43%) were men. Mean age of the COVID-19 group was 39.00±13.04 years. Twenty-two patients had pneumonia, 18 (35%) received hydroxychloroquine (HCQ), 17 (33%) received HCQ plus low-molecular-weight heparin (LMWH), and 10 (19%) received favipiravir. The patient group had lower parafoveal VD in the superficial capillary plexus (SCP) and lower parafoveal VD and perifoveal VD in the deep capillary plexus (DCP) than controls (p=0.003, p=0.004, p=0.001). FAZ area did not differ significantly (p=0.953). Perifoveal VD in the DCP was also significantly lower in the HCQ+LMWH group than the HCQ group (p=0.020) and in the presence of pneumonia (p=0.040). C-reactive protein (CRP) and ferritin levels were negatively correlated with perifoveal VD in the DCP (r=-0.445, p=0.023; r=-0.451, p=0.040). Ferritin was also negatively correlated with parafoveal VD in the SCP (r=-0.532, p=0.013). Parafoveal and perifoveal VD was found to be lower in the COVID-19 group. Presence of pneumonia, need for LMWH prophylaxis, and levels of CRP and ferritin were found to be negatively associated with retinal VD. Large-scale studies are needed to evaluate the clinical importance.

ECULIZUMAB DOSE ADJUSTMENTS DURING PREGNANCIES IN PAROXYSMAL NOCTURNAL HEMOGLOBINURIA: A SINGLE CENTER EXPERIENCE.

Paroxysmal nocturnal hemoglobinuria (PNH) has always been considered a relative contraindication for pregnancy. The use of eculizumab has reduced morbidity and mortality of fetus and mother. Dose adjustments are often required due to emerging breakthrough hemolysis, no standard recommendations are currently available in this setting. Here we report our single hematology center experience on breakthrough hemolysis and eculizumab dose adjustments during PNH pregnancies. Clinical data of four pregnancies from three PNH patients are reported. Two of them were already on standard dosage eculizumab when pregnancies were diagnosed. Their baseline PNH clone sizes were 89.5% and 97.5% on granulocytes and 38% and 90% on erythrocytes, respectively. In both cases low molecular weight heparin-prophylaxis was started when pregnancy was diagnosed. The third 26 year old patient with a baseline PNH clone of 8.8% started treatment at the beginning of her 2 nd trimester. The 26 year old patient was stable on 900 mg Eculizumab until 12 weeks post-partum. The other two developed breakthrough hemolysis during their third trimesters. Eculizumab dosing was increased initially from 900mg bi-weekly to 900 mg weekly and subsequently to 1200 mg biweekly. The 28 year old patient with the largest clone underwent two pregnancies and required even a 1200mg weekly dosage in her first pregnancy until four weeks post-partum. All four babies were delivered without complications. Eculizumab dose adjustments up to 1200 mg biweekly as well as interval shortening from bi-weekly to weekly administration seems effective and safe in breakthrough hemolysis control during pregnancy in PNH. Dose escalations did not impact on birth or development of the babies.

A nationwide prospective multicenter study of external ventricular drainage: accuracy, safety, and related complications.

External ventricular drainage (EVD) catheters are associated with complications such as EVD catheter infection (ECI), intracranial hemorrhage (ICH), and suboptimal placement. The aim of this study was to investigate the rates of EVD catheter complications and their associated risk factor profiles in order to optimize the safety and accuracy of catheter insertion. A total of 348 patients with urgently placed EVD catheters were included as a part of a prospective multicenter observational cohort. Strict definitions were applied for each complication category. The rates of misplacement, ECI/ventriculitis, and ICH were 38.6%, 12.2%, and 9.2%, respectively. Catheter misplacement was associated with midline shift (p = 0.002), operator experience (p = 0.031), and intracranial length (p < 0.001). Although mostly asymptomatic, ICH occurred more often in patients receiving prophylactic low-molecular-weight heparin (LMWH) (p = 0.002) and those who required catheter replacement (p = 0.026). Infectious complications (ECI/ventriculitis and suspected ECI) occurred more commonly in patients whose catheters were inserted at the bedside (p = 0.004) and those with smaller incisions (≤ 1 cm) (p < 0.001). ECI/ventriculitis was not associated with preinsertion antibiotic prophylaxis (p = 0.421), catheter replacement (p = 0.118), and catheter tunneling length (p = 0.782). EVD-associated complications are common. These results suggest that the operating room setting can help reduce the risk of infection, but not the use of preoperative antibiotic prophylaxis. Although EVD-related ICH was associated with LMWH prophylaxis for deep vein thrombosis, there were no significant clinical manifestations in the majority of patients. Catheter misplacement was associated with operator level of training and midline shift. Information from this multicenter prospective cohort can be utilized to increase the safety profile of this common neurosurgical procedure.

Expert Review: Prevention of Obstetrical Venous Thromboembolism

(Am J Obstet Gynecol. 2021;225:228–236) Approximately 9% to 10% of maternal deaths are related to thrombotic pulmonary embolism. The American College of Obstetricians and Gynecologists (ACOG), the Royal College of Obstetricians and Gynaecologists (RCOG), the American College of Chest Physicians (ACCP), the American Society of Hematology, the National Partnership for Maternal Safety, and the Society for Maternal-Fetal Medicine have all published dissimilar recommendations for obstetrical venous thromboembolism (VTE) prophylaxis. Several additional studies have concluded mechanical prophylaxis alone was ineffective during childbirth and during recovery and sequential compression devices were only in use 17% to 21% of the time. While the use of mechanical prophylaxis has become more common, the mortality rate for VTE has not decreased. The United Kingdom implemented guidelines in 2004 for low–molecular-weight heparin prophylaxis and has shown a 40% reduction in maternal deaths from VTE. However, cost, lack of evidence, and safety concerns are included in the argument against heparin prophylaxis. This review focuses on guidelines for heparin prophylaxis during antepartum hospitalizations and following cesarean deliveries (CD).

Low-molecular-weight heparin prophylaxis is not associated with decreased incidence of venous thromboembolism in testicular germ cell tumor patients receiving chemotherapy

Venous thromboembolism (VTE), commonly occurring in patients with testicular germ cell tumors (GCTs), is associated with increased morbidity and mortality. Prophylactic anticoagulation has been shown to decrease the risk of VTE in patients with malignancies. The objective was to evaluate the effect of low-molecular-weight heparin (LMWH) prophylaxis on the incidence of VTE and outcome in patients with GCT treated with first-line chemotherapy. In this retrospective study, 353 chemotherapy-naive GCT patients were treated with first-line chemotherapy at the National Cancer Institute, Bratislava, Slovakia (2000-2017). Median follow-up was 71 months. VTE was defined as any venous thrombosis or pulmonary embolism, confirmed by imaging, occurring during first-line chemotherapy. Exclusion criteria were LMWH use before starting chemotherapy and VTE on initial staging. We observed 14 (4.0%) VTE events. No visceral thromboses were observed. The difference in VTE incidence between patients with and without prophylaxis was not statistically significant (5.8% vs. 3.2%, p=0.37). We observed a trend toward longer overall survival in patients without prophylaxis (hazard ratio = 0.61, 95% confidence interval = 0.32-1.13, p=0.08). Patients with extragonadal GCT receiving VTE prophylaxis had significantly shorter survival (hazard ratio = 0.29, 95% confidence interval = 0.08-1.12, p=0.04). This effect was most likely driven by a higher incidence of treatment-related deaths in patients with extragonadal GCT receiving LMWH (p=0.06). LMWH prophylaxis was not associated with decreased VTE incidence. Moreover, there was a higher incidence of treatment-related deaths in patients with extragonadal tumor location. Low-molecular-weight heparin prophylaxis during hospitalization should not be used routinely in patients with testicular germ cell tumors receiving chemotherapy.

Progression of Intracranial Hemorrhage After Chemical Prophylaxis Using Low-Molecular-Weight Heparin in Patients With Traumatic Brain Injury.

Chemical prophylaxis using low-molecular-weight heparin (LMWH) is considered a standard of care for venous thromboembolism in trauma patients. Our center performs a head computed tomography (CT) scan 24 hours after initiation with prophylactic LMWH in the setting of a known traumatic brain injury (TBI). The purpose was to determine the overall incidence of ICH progression after chemoprophylaxis in patients with a TBI. This retrospective study was performed at a Level I trauma center, from 1/1/2014 to 12/31/2017. Study patients were drawn from the institution's trauma registry based on Abbreviated Injury Score codes. 778 patients met all inclusion criteria after initial chart review. The proportion of patients with an observed radiographic progression of intracranial hemorrhage after LMWH was 5.8%. 3.1% of patients had a change in clinical management. Observed radiographic progression after LMWH prophylaxis and the presence of SDH on initial CT, the bilateral absence of pupillary response in the emergency department, and a diagnosis of dementia were found to have statistically significant correlation with bleed progression after LMWH was initiated. Over a 4-year period, the use of CT to evaluate for radiographic progression of traumatic intracranial hemorrhage 24 hours after receiving LMWH resulted in a change in clinical management for 3.1% of patients. The odds of intracranial hemorrhage progression were approximately 6.5× greater in patients with subdural hemorrhage on initial CT, 3.1× greater in patients with lack of bilateral pupillary response in ED, and 4.2× greater in patients who had been diagnosed with dementia.

Routine use of LMWH prophylaxis is associated with a lower incidence of venous thromboembolic events following an ankle fracture

BackgroundVenous thromboembolic events (VTE) are well-known and serious complications following a trauma to the lower extremities. There is an ongoing debate on the benefit of low-molecular-weight heparin (LMWH) as prophylaxis following ankle fracture treatment. We examined the association between the incidence of VTE and the use of LMWH-prophylaxis following an ankle fracture, as well as factors affecting the risk of VTE. MethodsIn this retrospective cohort study, data on ankle fractures and fracture treatment from the Swedish Fracture Register was linked to data from the Swedish National Patient Register and the Swedish Prescribed Drug Register. Patients with VTE and patients who received LMWH prophylaxis were identified. The treating orthopedic departments were sent a questionnaire about their guidelines regarding the use of LMWH prophylaxis. Results222 cases of diagnosed VTE were identified among 14,954 ankle fractures. Orthopedic departments with higher-than-average use of LMWH prophylaxis among non-operatively treated ankle fractures had a lower incidence of VTE (OR 0.60, CI 0.39–0.92). Among operatively treated patients, departments with a guideline for the routine use of LMWH prophylaxis also had lower incidence of VTE (OR 0.56, CI 0.37–0.86). A later onset of VTE was seen among patients prescribed LMWH prophylaxis, with a mean of 56 days to onset (CI 44–67), compared to 39 days (CI 33–45) in patients without prescribed prophylaxis. During the first two weeks following injury, there was only one case of VTE in patients with prescribed LMWH, compared to 39 cases of VTE among patients without prescribed prophylaxis. ConclusionsRoutine use of LMWH in patients with operatively treated ankle fractures was associated with a lower incidence of VTE. A more frequent use of LMWH among patients with non-operatively treated ankle fractures were associated with a lower incidence of VTE. The onset occurred later among patients with LMWH-prophylaxis who still suffered a VTE.

Early versus delayed thromboprophylaxis with LMWH in pelvic-acetabular trauma- a prospective study

BackgroundDelayed presentation of pelvic-acetabular fractures is a common scenario in developing countries and there is usually a delay of more than 24 h in their presentation. ObjectivesWe aim to comparatively analyse early(<24 h) versus delayed (>24 h) thromboprophylaxis with low molecular weight heparin (LMWH) in prevention of deep venous thrombosis (DVT) in Pelvic Acetabular fractures. MethodsPatients of pelvic-acetabular fractures who presented during 1 year of study period were divided into 2 groups after exclusion of patients with contraindications for thromboprophylaxis. Group A included patients who received LMWH prophylaxis within 24 h of injury. Group B included patients who received LMWH prophylaxis after 24 h of injury. All patients underwent CT venography at day 14 and were followed up with doppler ultrasound on 4th and 8th week. Results110 patients with pelvic-acetabular fractures were included after exclusion of 61 patients. 4 out of 29 patients in group A (13.8%) and 12 out of 81 patients (14.8%) in group B developed DVT. There was no significant difference in incidence of DVT between Group A and B (P value-0.893). ConclusionThere was no difference between early and delayed thromboprophylaxis with LMWH in pelvic-acetabular trauma.

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 &gt; 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 &gt; 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.