Low Molecular Weight Heparin Research Articles

Impact of antiplatelets, anticoagulants and cyclic nucleotide stimulators on neutrophil extracellular traps (NETs) and inflammatory markers during COVID-19.

While the association between coronavirus disease-19 (COVID-19) and neutrophils extracellular traps (NETs) is recognized, uncertainties remain regarding its precise onset, timing of resolution and target therapy. To assess changes in inflammatory and NET markers during the first week of COVID-19 hospitalization, and the association with disease severity. "In vitro" experiments investigated the effect of antiplatelets, anticoagulants, and cyclic nucleotide stimulators on NETs release. Prospective cohort study, changes in interleukin (IL)-6, IL-8, IL-17, TNF-α, RANTES, PF4, and citrullinated-H3 (citH3) levels within each outcome group was evaluated using ANOVA. Differences between moderately ill, critically ill, and non-survivors were determined using Kruskal-Wallis and logistic regression. Healthy neutrophils were stimulated with phorbol-12-myristate-13-acetate (PMA) or COVID-19 sera and treated with unfractionated heparin (UFH), low molecular weight heparin (LMWH), aspirin (ASA), ticagrelor, cinaciguat, sildenafil, and milrinone. The proportion of NETosis was assessed using IncuCyte Cell Imager. Of the 125 patients, 40.8% had moderate COVID-19, 40.8% had critical COVID-19 but recovered, and 18.4% died. From admission to hospitalization day 8, IL-6 levels decreased in moderately and critically ill, but not in non-survivors, while citH3 levels increased in critically ill and non-survivors. IL-6, IL-8, and TNF-α levels were associated with critical and fatal COVID-19. The release of NETs by neutrophils stimulated with PMA or COVID-19 sera was decreased in the presence of ASA, UFH, LMWH and cyclic nucleotide stimulators in a dose-dependent manner. In the first week of hospitalization, NET markers rose later than inflammatory markers in severe COVID-19 cases. Cyclic nucleotide stimulators, ASA and heparin may emerge as treatment approaches as they may modulate NETosis.

Real world application of the 2023 ACR/EULAR antiphospholipid antibody syndrome classification criteria in a pharmacist directed anticoagulation clinic.

To determine the number of patients that met classification for antiphospholipid antibody syndrome (APS) after applying the 2023 American College of Rheumatology and the European Alliance for Associations of Rheumatology (ACR/EULAR) classification criteria, to identify reasons patients did not meet the new criteria, and determine the number of patients who were single, double, or triple positive based on laboratory criteria. A single center, retrospective chart review of patients with APS on anticoagulation managed by ambulatory care clinical pharmacists. Data collected included patient demographics, type of anticoagulation, and clinical and laboratory criteria for APS as defined by the 2023 ACR/EULAR criteria. Data is presented using descriptive statistics. A total of 51 patients previously diagnosed with APS were included. There were 42 patients on warfarin (82.3%), 4 patients on direct oral anticoagulants (19%), 3 patients on low molecular weight heparin (5.8%), and 2 patients on fondaparinux (3.9%). Of the 51 patients, 12 (23.5%) met classification criteria, 33 (64.7%) did not meet classification criteria and 6 (11.7%) had insufficient data. Of the 27 patients that did not meet criteria, 13 patients did not meet the laboratory criteria (39.4%), 6 patients did not meet the clinical criteria (18.2%) and 14 patients did not meet both laboratory and clinical criteria (42.4%). Of the 12 patients that met classification criteria, 2 patients were triple positive (16.7%), 3 were double positive (25%), and 7 were single positive (58.3%). Results from this study indicate that APS continues to be a complex disease state with challenges in diagnosis and classification. Since only a small number of patients in our clinic continued to meet the classification criteria, opportunities for patient re-evaluation of management strategies at our institution could be considered.

Abstract 4116285: Safety and Efficacy of Early Direct Oral Anticoagulants Versus Low Molecular Weight Heparin in Patients with Ischemic Stroke and Immobility: A Multi-National Database Study

Background: Low molecular weight heparin (LMWH) is the preferred anticoagulant for venous thromboembolism (VTE) prophylaxis in patients with ischemic stroke and reduced mobility. However, some patients may have indications for early direct oral anticoagulants (DOACs) and are continued on this therapy rather than transitioning to LMWH. Whether outcomes differ between these groups is unknown. We compared the safety and efficacy of early DOACs versus LMWH from a large retrospective database. Methods: Patients within the TriNetX Research Network receiving either DOACs or LMWH within 72 hours of ischemic stroke and a Modified Rankin Scale of 4-5 were included. A 1:1 propensity score matching analysis was performed using 27 covariables including demographic information, comorbidities, and medications. Chi-square and independent t -tests were used in bivariable analyses. Outcomes were all-cause mortality, VTE, intracranial and extracranial hemorrhage at 30 and 90 days. Results: Of 5,492 propensity-matched patients, mean age was 73±13, and 43% were male. Mortality in the DOAC group was significantly lower than in the LMWH group at 30 days (RR=0.59, 95% CI: 0.51-0.69) and 90 days (RR=0.63, 95% CI: 0.56-0.71). Risk of VTE was not significantly different at 30 days (RR=0.80, 95% CI: 0.43-1.50) or 90 days (RR=0.74, 95% CI: 0.45-1.22). Risk of intracranial hemorrhage was not significantly different at 30 days (RR=0.81, 95% CI: 0.36-1.80) or 90 days (RR=0.62, 95% CI: 0.34-1.15). Conclusions: In patients with acute ischemic stroke and reduced mobility, early use of DOACs was associated with lower mortality compared to early use of LMWH.

Comparative analysis of the efficacy of direct oral anticoagulant rivaroxaban and low molecular weight heparin in the treatment of tumor patients with venous thromboembolism

Objective: To explore the effectiveness and safety of direct oral anticoagulant rivaroxaban and low molecular weight heparin (LMWH) in the treatment of tumor patients with venous thromboembolism (VTE). Methods: A retrospective analysis was conducted on 296 patients diagnosed with tumor associated VTE in the Shanghai Pulmonary Thromboembolism Database from December 2020 to September 2022. Patients were grouped according to the prescription of anticoagulant drugs. Thirteen baseline variables [age, gender, smoking history, physical state (PS) score, tumor type, tumor stage, tumor treatment method, hemoglobin, platelets, D-dimer, creatinine, alanine aminotransferase, and VTE site] were matched. After matching, 100 cases were assigned to rivaroxaban group, including 64 males and 36 females, aged [M (Q1, Q3)] 70 (62,74) years old; There were 100 cases in the LMWH group, including 69 males and 31 females, aged 68 (60,73) years old. Kaplan-Meier method was used to plot survival curves. The differences between the rivaroxaban group and LMWH group in 6-month cumulative VTE recurrence rate, clinically significant bleeding rate, and all-cause mortality rate were analysed using log-rank test. Results: There were no statistically significant differences between the rivaroxaban group and the LMWH group in the 6-month cumulative VTE recurrence rate [13.5% (95%CI: 6.4%-20.1%) vs 7.5% (95%CI: 2.0%-12.7%), P=0.171], bleeding incidence rate [9.2% (95%CI: 3.3%-14.8%) vs 6.2% (95%CI: 1.3%-10.9%), P=0.438] and all-cause mortality rate [8.0% (95%CI: 2.5%-13.2%) vs 10.0% (95%CI: 3.9%-15.7%), P=0.602]. Conclusion: The anticoagulant efficacy and safety of rivaroxaban and LMWH are comparable in tumor patients with VTE.

Establishment and validation of a predictive model for lower extremity deep vein thrombosis in patients with traumatic pelvic fractures

BackgroundPatients with traumatic pelvic fracture (TPF) are at high risk for developing deep vein thrombosis (DVT). However, there is still no unified standard on how to distinguish high-risk groups for DVT in patients with TPF and how to accurately use anticoagulants at present.ObjectivesThis observational study aimed to establish a DVT risk nomogram score (DRNS) model for TPF patients, and to explore the value of the DRNS model as a clinical guideline in the prevention of DVT with low molecular weight heparin (LMWH).MethodsIndependent risk factors of lower extremity DVT were screened through Lasso regression and logistic regression. A DRNS model was established per this.ResultsThe independent risk factors of DVT included combined femoral fractures, age ≥ 40 years old, BMI (body mass index) ≥ 24 kg/m2, ISS score, fibrinogen concentration, and the minimum concentration of ionized calcium within 48 h after admission. The optimal cutoff value for DRNS was 78.5. In the low-risk population of DVT (DRNS < 78.5), there was no statistical significance of variation about the incidence of DVT progression between the LMWH once a day (qd) group and the LMWH once every 12 h (q12h) group, with P = 0.323. In the high-risk population of DVT (DRNS ≥ 78.5), the incidence of DVT progression in the LMWH qd group was significantly higher than that in the LMWH q12h group, with P = 0.002.ConclusionsThe DRNS model based on independent risk factors of DVT could stratify the risk of DVT for TPF patients, and it was able to provide more precise DVT drug prevention plans for clinicians.

Low molecular weight heparins promote migration and invasion of trophoblast cells through regulating the PI3K/AKT signaling pathway.

Pregnant women confront a high risk of mortality due to preeclampsia (PE), which also results in severe challenges for newborns. Due to their efficient properties and minimal side effects, low molecular weight heparins (LMWHs) are extensively utilized by optimizing their molecular size. Nevertheless, there have been no reports regarding the alleviating effect of LMWHs on PE and the molecular mechanism underlying it. To examine the therapeutic impact of LMWHs on PE, we initially created a PE rat model and assessed the advantages of LMWHs on PE through Western blot, immunofluorescence, TUNEL, 24-h proteinuria determination, and other techniques. Furthermore, we examined the in vitro molecular mechanism of LMWHs therapy on PE using CCK-8, Transwell, Flow cytometry, Wound healing assay, and other techniques. LMWHs, when used in vivo, reduced the rise in blood pressure and 24-h proteinuria in rat models of PE. Additionally, they prevented trophoblast cell apoptosis in these rat models. In vitro, LMWHs demonstrated a significant ability to enhance the migration and invasion of HTR-8 and JEG-3 cells. Mechanistically, LMWHs mitigate the development of PE by activating the PI3K/AKT signaling pathway. According to our findings, the activation of the PI3K/AKT signaling pathway by LMWHs appears to provide relief for PE. Therefore, we have compelling evidence supporting the use of LMWHs as an efficient treatment for PE.

The Unusual Presentation of Non-ST Elevation Myocardial Infarction Following Acute Carbon Monoxide Poisoning in an Elderly Female: A Case Report

Carbon monoxide (CO) poisoning is a leading cause of poisoning-related deaths, particularly affecting organs with high oxygen demands such as the heart and brain. Cardiac complications, including non-ST elevation myocardial infarction (NSTEMI), can occur due to CO poisoning but are not frequently reported in the elderly. We present the case of an 82-year-old female with a medical history of diabetes, hypertension, dyslipidemia, and previous ischemic heart disease. She was brought to the emergency department after being found drowsy in a closed room with a burning charcoal heater. The initial assessment revealed a carboxyhemoglobin level of 33.5%, which decreased to 9.3% after high-flow oxygen therapy and hyperbaric oxygen therapy (HBOT). Laboratory tests indicated elevated troponin levels, and an ECG showed asymmetrical T-wave inversion and ST depression. Despite the improvement in carboxyhemoglobin, the patient experienced persistent chest pain and rising troponin levels. She was treated with dual antiplatelet therapy and low molecular weight heparin as per acute coronary syndrome protocol, leading to a gradual improvement and a subsequent discharge in a stable condition. This case highlights the potential for CO poisoning to induce NSTEMI in elderly patients. A prompt diagnosis and appropriate management, including the use of HBOT, were crucial for the patient’s recovery.

Successful delivery in a cornual pregnancy after expectant management with traditional Chinese medicine and low-molecular-weight heparin: A case report.

Horn pregnancy is a rare subtype of ectopic pregnancy that presents a diagnosis and treatment challenge due to its nonspecific symptoms and high risk of rupture. A 32-year-old woman without vaginal pregnancy with history of right corner who presented with painless vaginal bleeding. A transvaginal ultrasound revealed a pregnancy sac implanted in the left corner of the uterus, confirming the diagnosis of a cornual pregnancy. Treatment options include pharmacological or surgical interventions, and anticipatory treatment is rarely recommended. Conservative treatment was chosen after extensive consultation, and the patient was treated with low molecular weight heparin and traditional Chinese medicine. Subsequent ultrasound tests showed stable fetal development and a successful cesarean section. This case highlights the success of combining low molecular weight heparin with traditional Chinese medicine in the treatment of cornual pregnancy. Factors affecting horn pregnancy, diagnostic challenges, and treatment considerations are discussed. Further research is necessary to determine the best management strategy and to ensure safe delivery for patients with impaired fertility but a strong desire to conceive.

Enoxaparin Failure in Patient With Cerebral Venous Sinus Thrombosis and Prothrombin G20210A Mutation: Case Report.

Cerebral venous sinus thrombosis (CVST) is a rare, serious, and complex cerebrovascular disease. The prothrombin G20210A mutation is the second most common inherited thrombophilia and is considered to be one of the etiologies of CVST. The optimal heparinoid medication for treatment remains a topic of debate. This case report describes a young woman with CVST who did not respond to low-molecular-weight heparin (LMWH). The patient was initially treated with LMWH; however, her symptoms and clot burden in the sagittal sinus worsened, and coagulation studies showed no evidence of therapeutic anticoagulation despite good compliance. Unfractionated heparin was then initiated, and the patient's symptoms improved dramatically within 24 hours, along with the recanalization of the cerebral venous sinuses. Genetic testing revealed a heterozygous mutation in the prothrombin gene (G20210A). This mutation is a known risk factor for CVST. However, it is unclear why the patient did not respond to LMWH but responded appropriately to unfractionated heparin. This case report highlights the potential for LMWH resistance in patients with CVST and prothrombin gene mutations. These findings also emphasize the importance of close monitoring of coagulation parameters and clinical response in patients with CVST receiving LMWH.

The Impact of Obesity on Pain Perception During and After Subcutaneous Injections: A Cross-Sectional Analysis

(1) Background: The administration of subcutaneous (SC) injectables is among the most frequent procedures a nurse performs in daily practice. The needle for the injection must pass through the skin barrier to reach the SC space, where the drug will be deposited. This procedure can cause pain to the patient and local lesions. Local fat measurement can be performed by measuring the skin fold. Previous studies have found higher levels of pain in people with obesity receiving SC insulin, and this study thus aimed to measure pain levels during and after an SC injection of low-molecular-weight heparin (LMWH) and identify how age, gender, and obesity may modulate the level of pain during and after the procedure. (2) Methods: This was a cross-sectional study, and the variables included age, gender, body mass index (BMI), BMI quartile, abdominal skin folds (ASFs), ASF quartile, and pain level during and after injection. A caliper was used to measure ASFs, height and weight were used to calculate BMI, and the Visual Analog Scale (VAS) was used to measure pain. (3) Results: The sample amounted to 202 participants, which was not considered representative of the study population. The average age was 64.3 years, and females predominated (62.40%). Of these participants, 42.5% were obese, and 29.1% were overweight. The average pain levels were low during (1.4) and after injection (1.9), highlighting the absence of pain during injection in 29.7% and after injection in 34.2%. (4) Conclusions: Obesity was associated with increased pain, but when adjusted for age, the pain was no longer significant. Females and young participants showed a significant relationship with pain during injection. Age, gender, and obesity had a statistically significant relationship with pain level. Participants with obesity (according to BMI and ASF) showed the highest levels of pain during and after injection. After injection, there was an increase in pain in most cases, possibly due to the discomfort caused by the drug itself, an aspect considered in the drug’s technical data sheet as a frequent adverse effect (&gt;1/10 to &lt;1/100). However, the drug volume does not seem to be related to pain in this study.

International Normalized Ratio measurement during perioperative anticoagulation bridging with Low Molecular Weight Heparin in patients undergoing heart valve replacement surgery

BackgroundSurgical procedures in anticoagulated patients require specific attention due to increased bleeding risk. Preoperative anticoagulation interruption in high-risk patients is often necessary. Bridging anticoagulation with low-molecular-weight heparin (LMWH) minimizes thromboembolic risk, but its effect on INR measurement is not well established, necessitating careful monitoring and individual assessment. ObjectivesInvestigating the effect of heparin bridging on INR measurements in anticoagulated patients on vitamin K antagonist (VKA) and by in vitro spiking experiments. Methods38 anticoagulated patients on VKA undergoing valve replacement surgery were studied using two plasma-based INR assays and one whole blood point-of-care INR method on multiple timepoints after postoperatively resuming VKA. Furthermore, we compared INR levels in pooled plasma of both normal and VKA-treated individuals, with seven spiked concentrations of LMWH or unfractionated heparin (UFH) in four INR assays. ResultsIn LMWH-bridged anticoagulated patients, the INR results obtained with HemosIL® RecombiPlasTin® and point-of-care Coaguchek are significantly higher compared to STA® Hepato Prest, within 3 days after restart of VKA. After spiking of LMWH or UFH in various concentrations into pooled plasma, only STA® Hepato Prest assay shows no interference in INR measurement within the therapeutic range (1.0-2.0 international units/mL) in both VKA and normal plasma. All other assays have substantial interference, with the Thromborel® S assay being the most heparin-sensitive assay. ConclusionDifferences between INR methods are seen within 72 hours after restarting VKA in post-operative patients who receive LMWH-bridging. In vitro experiments using LMWH and UFH show the interference of heparin in multiple INR methods, even with concentrations below suppliers-stated heparin interference limits.

TREATMENT OF EARLY-ONSET FETAL GROWTH RESTRICTION WITH LOW MOLECULAR WEIGHT HEPARIN DOES NOT PROLONG GESTATION: A RANDOMIZED CLINICAL TRIAL

Although there is a biological basis for it, there is scarce evidence on the effect of heparin in ameliorating placental insufficiency and maximizing gestational age at delivery among fetal growth restriction (FGR) pregnancies. To explore the effectiveness of treatment using low molecular weight heparin (LMWH) at a prophylactic dose started at the time of diagnosis in prolonging gestation in pregnancies with early-onset fetal growth restriction (FGR). This was a phase III, multicenter, triple-blind, parallel-arm randomized clinical trial conducted in two university hospitals in Spain. Singleton pregnancies qualifying for early-onset placental FGR according to the adapted Delphi consensus (20+0-31+6 weeks at diagnosis with umbilical artery Doppler with absent/reversed diastolic flow; or estimated fetal weight <10th percentile plus pulsatility index (PI) of umbilical artery Doppler >95th percentile; or estimated fetal weight <10th percentile plus mean PI of uterine artery Doppler >95th) were randomized to receive either subcutaneous treatment with bemiparin 3500 IU/0.2 mL/day or a placebo from inclusion at diagnosis to the time of delivery. The primary outcomes were prolongation of pregnancy from inclusion to live birth (days) and gestational age at live birth (days). 49 patients were included (23 in the LMWH group and 26 in the placebo group). In the LMWH group, the median prolongation of pregnancy was 42 days, while in the placebo group it was 41.5 days (median difference 0.5 days [95% CI -22.7 to 6.3] (p=0.667) and in the LMWH group, the median gestational age at delivery was 35.1 weeks, while in the placebo group, it was 34.6 weeks (median difference 0.5 weeks [95% CI -3.4 to 1.2] (p=0.639). The use of prophylactic dose LMWH started at the time of diagnosis does not prolong pregnancy in individuals with early-onset fetal restriction.

Analysis of Pregnancy Outcomes in Patients Exhibiting Recurrent Miscarriage With Concurrent Low-Titer Antiphospholipid Antibodies.

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by thrombotic events and adverse pregnancy outcomes, often associated with elevated antiphospholipid antibodies (aPLs). The 2023 ACR/EULAR criteria for APS necessitate persistent medium to high titers of aPLs for laboratory confirmation. However, the impact of persistently low-titer aPLs in recurrent miscarriage (RM) patients remains controversial. This study aims to analyze the effect of treatment on pregnancy outcomes and maternal-fetal complications in patients with low-titer aPLs. The study encompassed 252 pregnancies in 237 RM patients tested for aPLs at the Third Hospital of Guangzhou Medical University from January 2018 to July 2022. Patients were divided into two groups based on aPLs titers: 86 with low-titer aPLs (92 pregnancies) and 151 aPLs-negative (160 pregnancies). Of the low-titer group, 71 received treatment, while 21 and all aPLs-negative patients did not. Seventy-one treated patients with low-titer aPLs were divided into two groups. Group A (n = 15) received a standard treatment regimen that included low-dose aspirin (LDA) and low-molecular-weight heparin (LMWH). In contrast, Group B (n = 56) received a multidrug regimen, which included hydroxychloroquine (HCQ) and/or glucocorticoids (GC) and/or intravenous immunoglobulin (IVIG) in addition to the standard treatment of LDA and LMWH. Pregnancy outcomes and maternal-fetal complications were subsequently compared. The highest positivity rates were for aCL-IgM (76.2% in the untreated low-titer aPLs group and 81.7% in the treated low-titer aPLs group), followed by aβ2GPI-IgM (23.8% in the untreated low-titer aPL group and 11.4% in the treated low-titer aPLs group), and LA (5.6% in the untreated low-titer aPLs group and 3.3% in the treated low-titer aPLs group). Single antibody positivity was 90.5% in the untreated low-titer aPL group and 87.3% in the treated low-titer aPLs group, with double positivity at 9.5% in the untreated low-titer aPLs group and 12.7% in the treated low-titer aPLs group. No triple positivity was detected. The treated low-titer aPLs group had more previous miscarriages (p < 0.05) and a higher ANA positivity rate (p < 0.05) than the aPLs-negative group. Additionally, the treated low-titer aPLs group had lower complement levels than the aPLs-negative group. Immunoglobulin IgM levels were higher in both the untreated and treated low-titer aPL groups compared to the aPLs-negative group (p < 0.05). Post treatment, the live birth rate in the low-titer group significantly exceeded that of the untreated group (67.6%vs. 33.3%; p = 0.005). The miscarriage rate was notably lower in untreated low-titer patients compared to aPLs-negative patients (32.4%vs. 66.7%; p = 0.005). No significant differences were observed in maternal or fetal complications between the groups. In the standard treatment group (Group A), there were 8 (53.3%) live births, whereas the multidrug treatment group (Group B) had 40 (71.4%) live births, a significantly higher rate than in the standard treatment group, although the difference lacked statistical significance. The study indicates that untreated RM patients with low-titer positive aPLs have a higher recurrence of miscarriage compared to the aPLs-negative RM group. However, recurrence significantly decreases following appropriate intervention, suggesting the benefits of treatment for RM patients with low-titer aPLs.

Treatment and long term follow-up results in patients with pulmonary vascular thrombosis related to COVID-19.

Pulmonary embolism is a complication of COVID-19 infection. The aim of this study is to assess prognosis and treatment response, including incidences of chronicity, relapse, and mortality among outpatients diagnosed with COVID-19-related pulmonary embolism between 2020 and 2022. A total of 101 patients with pulmonary embolism, started on anticoagulation during or within a month of COVID-19 infection, were included after testing positive by PCR. Data about comorbidities, Pulmonary Embolism Severity Index scores, PE diagnostic modalities, biochemical parameters, and transthoracic echocardiographic findings at diagnosis and at 24-month follow-up were collected. Cardiac catheterization parameters were recorded and compared between groups at diagnosis and at the 24-month follow-up. Groups were comparable with respect to gender, age, body mass index, and comorbidity score. Use of Q-SPECT for diagnosis was found significantly higher in patients with COVID-19-related pulmonary embolism (P < .001). The incidence of deep vein thrombosis was similar. In the study group, 43.6% of patients received anticoagulants for 3 months, with 49.1% using low molecular weight heparin and 50.9% using direct oral anticoagulants. At 24 months, rate of patients continuing treatment was comparable between groups. Specific pulmonary artery blockage value was found to be higher in patients with chronic thromboembolic pulmonary hypertension compared to those who demonstrated a response to pulmonary embolism treatment (P = .009). No adverse effects of anticoagulant therapy were observed during course of treatment. Over 24-month follow-up period, mortality, relapse, chronic thromboembolic hypertension and thromboembolic disease was observed in 2%, 2.2%, 4.9%, and 9.9% of patients, respectively.

OA08 Ocrelizumab in pregnancy in a patient with juvenile onset systemic lupus erythematosus

Abstract Introduction Juvenile-onset systemic lupus erythematosus (jSLE) is a multisystem autoimmune disease that results in increased disease activity compared to adult-onset SLE. jSLE in pregnancy results in a greater incidence of disease flares as well as adverse pregnancy outcomes. Management of SLE in pregnancy is particularly difficult due to lack of safety data for immunosuppressant medications and is therefore limited. Ocrelizumab is a humanised monoclonal antibody that selectively targets CD20 B cells and is approved for the treatment of multiple sclerosis. Despite never being trialled in a patient with active SLE in pregnancy, this case demonstrates its use with a successful outcome. Case description An 18-year-old female was diagnosed at age 14 with juvenile onset systemic lupus erythematosus with the presence of a photosensitive malar rash, arthralgia, alopecia, aphthous ulcers and headache. At the time of diagnosis her investigations revealed ANA 1:5120 with homogenous pattern, high dsDNA, low C3 and C4, thrombocytopenia, antibodies to Smith, Ro, RNP, anti-Rib-P, strongly positive lupus anticoagulant antibodies and low titre anti-cardiolipin IgG and IgM. Previous treatment included methotrexate, mycophenolate mofetil and cyclosporin which were discontinued either due to patient choice, inefficacy or adverse reaction. Azathioprine was contraindicated due to low TMPT. Rituximab was trialled and although effective had to be stopped due to adverse reaction. Unfortunately, she experienced a primigravida pregnancy loss at 15-20 weeks secondary to active SLE and pre-eclampsia. Shortly after this, she developed a rare case of anti-fascin antibody neuropathy and was treated with ocrelizumab. Six months later during her second pregnancy, she was treated with hydroxychloroquine 400 mg, aspirin 150 mg, folic acid 5 mg and low molecular weight heparin prophylaxis which were continued throughout the pregnancy. Due to concerns of active lupus at 13 weeks due to facial rash and fatigue, prednisolone was commenced at 10 mg daily and continued. After careful consideration, Ocrelizumab was given in the second trimester at 17 and 19 weeks’ gestation. Following this, symptoms remained under control and disease activity was low with normal C3/C4 and dsDNA levels without significant proteinuria. A newborn baby was delivered at 38 weeks by caesarean section without complication or foetal abnormalities. Both the mother and baby remain under close follow- up but have not demonstrated adverse outcomes at 3 months postpartum. Discussion This case demonstrates the use of Ocrelizumab in the second trimester of a high-risk pregnancy complicated by active jSLE. At present, there is no license for use of Ocrelizumab in SLE and no safety data on its use in pregnancy. However, there was a good outcome for this patient which resulted in no antenatal or postpartum complications and the successful birth of a healthy newborn without foetal abnormalities. Ocrelizumab is used for the treatment of early relapsing-remitting multiple sclerosis (RRMS) and is increasingly used by neurologists in women of childbearing age despite being unlicensed for use in pregnancy. Concerns of its use in pregnancy surround B cell depletion in the neonate which while tends to be transient, causes significant concern regarding long term immunological development and response to vaccination. B cell depleting therapies are widely used in the context of active and refractory SLE and therefore use of Ocrelizumab has been evaluated in cases of SLE in two phase III clinical trials. The first study examined the efficacy of Ocrelizumab in SLE without renal involvement (BEGIN) and the second recruited patients with lupus nephritis (BELONG). The BEGIN study was terminated early due to lack of response and the BELONG study was terminated due to a significant increase in serious infections (in the Ocrelizumab plus mycophenolate treatment group). However, results on disease activity were positive with complete renal response being achieved non-statistically more frequently in the Ocrelizumab treated patients versus placebo. Real world evidence shows the importance of achieving disease control in SLE around pregnancy to prevent adverse outcomes. The decision for the use of Ocrelizumab therefore needs to be balanced carefully against potential harm to the baby either from direct foetal exposure to the drug, or from gestation in an immunocompromised mother. Key learning points • Pre-pregnancy counselling is of paramount importance in severe cases of active SLE and when possible, pregnancy should be postponed in these instances until disease activity is stabilised with contraception counselling offered to those on teratogenic immunosuppressive agents. • A multidisciplinary approach to the management of complex SLE in pregnancy in essential with obstetrician, midwife, maternal medicine physician and rheumatologist input. • The benefit of potentially life-saving immunosuppressive treatment should be carefully balanced against the poor outcomes of active SLE in pregnancy and decisions should be made on a case-by-case basis.

Venous thromboembolism in adolescents and young adults with acute lymphoblastic leukemia treated on a pediatric-inspired regimen

Asparaginase (ASP)-containing regimens for acute lymphoblastic leukemia (ALL) are associated with venous thromboembolism (VTE). We evaluated the prevalence, risk factors, role of prophylaxis and clinical impact of VTE among adolescents and young adult (AYA) patients (15–50 years) treated on Dana-Farber Cancer Institute (DFCI) ALL protocols. The 1- and 2-year cumulative incidence of VTE were 31.9% (95% CI: 27.0%, 36.9%) and 33.5% (95% CI: 28.5%, 38.5%) respectively, with most events occurring during ASP-based consolidation phase (68.6%). VTE was more frequent in patients with overweight/obese vs. normal BMI (39.2% vs. 29.0%, p = 0.048). In a 1-year landmark analysis, the 4-year overall survival was 91.5%, without difference between patients with vs. without VTE (93.8% vs. 90.0%, p = 0.93). Relapse and non-relapse mortality rates were also similar. Among patients treated at Dana-Farber/Harvard Cancer Center, cerebral sinus vein thrombosis occurred in 3.6% of patients (8.5% of VTE events) in comparison to pulmonary embolism (32.9%) and deep vein thromboses (58.6%, 24.4% line-associated). In a Cox regression model for VTE free-time, elevated BMI was associated with shorter VTE free-time (HR 1.94 [95% CI 1.13-3.35], p = 0.018), while low molecular weight heparin (LMWH) prophylaxis as time-varying covariate was not. In conclusion, we found that VTE was frequent in AYAs treated on DFCI ALL protocols but did not impact survival outcomes. Overweight/obese BMI increased risk for VTE.

Risk Factors for Stroke in Patients with Nephrotic Syndrome: Experience from Two Centers in Poland

Objective. Patients with nephrotic syndrome (NS) have an increased risk of developing acute ischemic stroke (aIS) and intracranial hemorrhage (ICH). However, the informations on the risk factors for these outcomes are unknown. The aim of this study was therefore to determine the risk factors for stroke among patients with NS. Methods. A multicentric retrospective cohort of patients who developed aIS or ICH, following a diagnosis of NS between 2010 and 2021 was assembled. NS patients who did not develop stroke at follow-up were assembled as non-matched controls from the same study period. Cox regression yielding a hazard ratio (HR) with a 95% confidence interval was applied to investigate the potential risk factors for stroke among patients with NS. A meta-analysis on the current litterature was also performed. Results. With a mean follow-up of 6 years, a total of 45 patients with NS were included of which 14 were diagnosed with aIS and 4 with ICH at follow-up. Significant risk factors for stroke in patients with NS were diabetes mellitus (DM) (HR 2.85, 95%CI 1.10-7.49; p-value = 0.03), diabetic nephropathy (HR 2.74, 95% CI 1.06-7.07; p-value = 0.038) smoking (HR 8.29, 95% CI 2.20-31.2; p-value = 0.002), prior arterial thromboembolic events (ATEs) (HR 2.86, 95% CI 1.09-7.53: p-value = 0.03) and age > 55 years old (HR 4.84, 95% CI 1.48-15.8; p-value = 0.009). Administration of low molecular weight heparin (LMWH) (HR 0.88, 95% CI 0.22-3.43; p-value = 0.848) did not affect the risk-estimates for developing stroke in patients with NS. Meta-analysis including 1091 patients revealed prior ATEs, diabetes, hypertension and smoking to be risk factors for ATEs among patients with NS. Conclusion. In this study we found older age, DM, prior ATEs and smoking to increase the risk of developing stroke in patients with NS, while notably LMWH had no protective effects. Our findings may serve as an aid for physicians in managing and identifying high-risk patients for stroke in this subpopulation.

The Effect of Intermittent Pneumatic Compression Device Combined with Low-Molecular-Weight Heparin on the Prevention of Deep Vein Thrombosis in Elderly Patients after Femoral Neck Fracture Surgery.

Aims/Background Femoral neck fractures in elderly patients carry a high risk of developing deep vein thrombosis (DVT) due to prolonged immobilization and surgical intervention. This study examines the effectiveness of combining intermittent pneumatic compression (IPC) with low-molecular-weight heparin (LMWH) for preventing DVT in elderly patients following femoral neck fracture surgery. Methods A total of 150 elderly patients with femoral neck fractures, admitted between January 2022 and January 2024, were retrospectively selected, and their clinical data were analyzed. Based on the treatment methods, the patients were divided into a control group (n = 71) and a study group (n = 79). The control group received LMWH treatment, while the study group received a combination of LMWH and IPC. The incidence of DVT, surgical outcomes, hip joint function, coagulation function indicators, hemodynamic indicators, and serum pro-inflammatory factors were compared between the two groups. Results The results showed that the incidence of DVT in the study group was lower than in the control group (p = 0.017). There were no significant differences between the two groups in terms of intraoperative blood loss, postoperative drainage volume, or Harris scores (p > 0.05). After the intervention, the study group demonstrated higher levels of average velocity (Va), peak blood flow velocity (Vp), and blood flow (BF) compared to the control group (p < 0.05). Additionally, the activated partial thromboplastin time (APTT) and prothrombin time (PT) were longer, while the D-dimer (D-D) level was lower in the study group (p < 0.05). The study group also exhibited lower levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-8 (IL-8) (p < 0.05). Conclusion The results indicate that combining IPC with LMWH effectively reduces the incidence of postoperative DVT in elderly patients with femoral neck fractures, improves venous blood flow in the lower limbs, reduces vascular inflammation, and ensures safety.

Unfractionated heparin or low molecular weight heparin in patients with acute pulmonary embolism: a meta-analysis of randomized controlled trials

Abstract Introduction There is limited data on the use of unfractionated heparin (UFH) and low molecular weight heparin (LMWH) in patients admitted for acute pulmonary embolism (PE). Current ESC guidelines preferred LMWH over UFH based on extrapolated data. We aimed to compare UFH and LMWH in patients with acute PE using randomized controlled trials (RCTs). Methods A comprehensive literature search was performed from inception to 02/01/2024 of the PubMed database. Studies of adult patients comparing UFH to LMWH were evaluated for short-term (7-to-12 days) mortality, long-term mortality (90-days to 180-days), short-term (7-to-12 days) and long-term major bleeding (90-days to 180-days). Odds ratio (OR) with 95% confidence intervals (CI) were calculated using DerSimonian-Laird method. Results Of a total 2400 studies, nine RCTs with 1,996 subjects (1025 UFH and 971 LMWH) were included with mean age of 62.9 years and 48.5% males. There was no difference in short-term (OR= 0.89 [95% CI 0.44-1.82]; p=0.75; I2=0%; 6 trials) and long-term mortality (OR= 0.77 [95% CI 0.50-1.21]; p=0.26; I2=0%; 6 trials) with use of LMWH or UFH (Figure Panel A and B). Similarly, there was no difference in short-term (OR= 0.70 [95% CI 0.38-1.32]; p=0.27; I2=0%; 9 trials) and long-term major bleeding (OR= 0.92 [95% CI 0.53-1.60]; p=0.77; I2=0%; 6 trials) with use of LMWH or UFH (Figure Panel C and D). Overall, there was no evidence of publication bias using either funnel plot or eggers test (p &amp;gt; 0.05). Conclusions In this meta-analysis of 9 RCTs, there was similar efficacy and safety of UFH and LMWH in patients admitted for acute PE. However, future large-scale trials are needs to confirm these findings.

Complication comparison in intermediate-to-high risk venous thromboembolism patients, treated with high vs standard dose apixaban and rivaroxaban after low molecular weight heparin

Abstract Background In patients with intermediate-to-high risk venous thromboembolism (VTE), current guidelines recommend initial treatment with low molecular weight heparin (LMWH), followed by an oral anticoagulant. However, the studies supporting these guidelines have only focused on the use of Edoxaban and Dabigatran after 5 days of LMWH treatment. To date there are no studies supporting similarly implemented guidelines for Apixaban and Rivaroxaban. Purpose To investigate the incidence of bleeding complications and thrombosis in intermediate-to-high risk VTE patients, when treated with either lead-in high or standard dose Rivaroxaban or Apixaban, following initial LMWH treatment. Methods Through a real-life retrospective study of 844 intermediate-to-high risk VTE patients, 584 were initially treated with LMWH and subsequently Apixaban or Rivaroxaban and divided into two groups. The first group of 514 patients, received high dose Apixaban or Rivaroxaban (10mg x 2 for 7 days and 15mg x 2 for 21 days respectively) before being reduced to their standard doses. The remaining 70 patients, instead transitioned directly to the standard doses (5mg x 2 and 20mg x 1 respectively) from LMWH. All patients started treatment between 2018 and 2023, and all complications were recorded until one year following initiation of treatment. Treatment complications include recurrent VTE, separated into deep vein thrombosis and pulmonary embolism, and bleeding complications in the form of fatal, non-fatal, minor and a drop in haemoglobin. The recurrence of VTE and incidence of bleeding complications were evaluated as the primary efficacy outcome and safety outcome respectively. Results Overall, 4.7% of patients treated with initial high dose Apixaban or Rivaroxaban suffered major bleeding complications as opposed to 2.9% treated with the standard dose (p=&amp;lt;0.05). Out of all complications, 5 were fatal, all of which were part of the high dose group and included 3 cerebral and 2 gastrointestinal bleeds. However, minor bleeding complications were more frequent in the standard dose group, presenting in 26.1% of patients, while, paradoxically, the high dose group had similar complications in only 15.8% of patients (p=&amp;lt;0.05). Although treated with a higher dose, 6/478 (1,26%) incurred a recurrent thrombus within a year of treatment, while the standard dose group had no cases of recurrence, though this was not a statistically significant result. Conclusion Directly transitioning from LMWH to standard dose Apixaban/Rivaroxaban in intermediate-to-high risk VTE, leads to a statistically significant reduced incidence of major bleeding complications, without an increased risk of recurrent thrombosis.