Clinical guidelines for prevention and treatment of CAT in Japan and other countries.

Cancer-associated thrombosis (CAT) is an important prognostic factor for an increasing number of cancer patients. Understanding of CAT among cancer care providers has grown in recent years, and guidelines for the prevention and treatment of CAT have been published in Japan and around the world. In this article, we introduce these major guidelines and discuss differences we identified between the Japanese guidelines and those of other countries, with a focus on problems and issues. Insurance coverage of low-molecular-weight heparin and indications for primary prevention with direct oral anticoagulants in particular require urgent consideration.

Evaluation of the Safety and Efficacy of Enoxaparin Once-Daily Versus Twice-Daily Dosing for Prophylaxis in Pediatric Patients.

OBJECTIVES: Enoxaparin for the prevention of venous thromboembolism (VTE) in pediatric patients is -typically dosed twice a day. The use of once-daily dosing like that used in adult patients is limited because of a lack of safety and efficacy data. The aim of this study was to evaluate the safety and efficacy of -once-daily versus twice-daily dosing of enoxaparin for pediatric VTE prophylaxis based on incidence of thrombotic and bleeding events. METHODS: This was a 3-year retrospective chart review of enoxaparin received for VTE prophylaxis at -Cohen Children's Medical Center, New Hyde Park, NY. Exclusion criteria were age 18 years or older, and renal dysfunction. RESULTS: A total of 177 enoxaparin courses (81 in the once-daily and 96 in the twice-daily group) were included. The median dose in the once-daily group was 0.68 mg/kg/dose with dose capping at 40 mg/dose in 70% of patients. One patient in the once-daily group had a VTE, whereas no patients in the twice-daily group experienced a VTE. One major bleeding event occurred in the once-daily group (p = 0.46); however, minor bleeding events were comparable between the 2 groups (p = 0.69). CONCLUSIONS: Once-daily enoxaparin prophylaxis appears to be safe and effective based on minimal -differences in incidence of thrombotic and bleeding events when compared to twice-daily dosing. Based on this study, it may be reasonable to consider once-daily enoxaparin dosing for prophylaxis, especially in older children. A larger multicenter cohort study evaluating once-daily dosing for prophylaxis is warranted to validate the safety and efficacy specifically for risk-based dosing strategies.

Characterization of the Benefits and Risks of Therapeutic Anticoagulation in Patients Admitted with Severe COVID-19 (CRITAC).

Background: Severe COVID-19 is associated with increased rates of thrombotic complications. Recent provincial recommendations in British Columbia have suggested providing thromboprophylaxis with therapeutic anticoagulation for hospital inpatients with severe COVID-19 who do not have a high risk of bleeding. Objectives: To characterize the rates of major bleeding, thrombotic events, complications from COVID-19, and adverse effects among patients with severe COVID-19 treated with therapeutic anticoagulation. Methods: This retrospective chart review involved patients with laboratory-confirmed COVID-19 who were admitted to 3 sites within a local health authority between April 1 and December 31, 2021, and received therapeutic anticoagulation for thromboprophylaxis. Results: After screening of 1036 patients, 72 patients were included in the study. The mean age of participants was 54 years, 63% (n = 45) were male, and 92% (n = 66) were receiving supplemental oxygen by nasal prongs on admission. The primary outcome, major bleeding, was experienced by 1 patient (1%). Increasing oxygen requirements resulting in progression to high-flow nasal cannula occurred in 11 patients (15%), and 5 patients (7%) required admission to the intensive care unit. One patient (1%) experienced a thrombotic event, and 1 patient (1%) had a minor bleed. The mean duration of hospitalization was 10 (standard deviation 10.8) days. One death occurred during the study period, and no cases of heparin-induced thrombocytopenia were observed. Conclusions: In this study of hospital inpatients with severe COVID-19 who were deemed to be at low risk of bleeding and who received therapeutic anticoagulation, there were low rates of both major bleeding and thrombotic events.

Contexte: Les cas graves de COVID-19 sont associés à des taux accrus de complications thrombotiques. De récentes recommandations provinciales en Colombie-Britannique proposent de fournir une thromboprophylaxie avec anticoagulation thérapeutique aux patients hospitalisés atteints d'une forme grave de COVID-19 qui ne présentent pas un risque élevé de saignement. Objectifs: Caractériser les taux d'hémorragies majeures, d'événements thrombotiques, de complications découlant de la COVID-19 et d'effets indésirables chez les patients atteints de COVID-19 sévère traités par anticoagulation thérapeutique. Méthodes: Cette revue rétrospective des dossiers portait sur des patients atteints de COVID-19 confirmée en laboratoire qui ont été admis dans 3 sites au sein d'une autorité sanitaire locale entre le 1er avril et le 31 décembre 2021 et qui ont reçu une anticoagulation thérapeutique pour la thromboprophylaxie. Résultats: Après la présélection de 1036 patients, 72 ont été inclus dans l'étude. L'âge moyen des participants était de 54 ans, 63 % (n = 45) étaient des hommes et 92 % (n = 66) recevaient un supplément d'oxygène par sonde nasale à l'admission. Le critère de jugement principal, une hémorragie majeure, a été observé chez 1 patient (1 %). Une augmentation des besoins en oxygène entraînant une progression vers une canule nasale à haut débit s'est produite chez 11 patients (15 %) et 5 patients (7 %) ont dû être admis à l'unité de soins intensifs. Un patient (1 %) a présenté un événement thrombotique et 1 patient (1 %) a eu un saignement mineur. La durée moyenne d'hospitalisation était de 10 jours (écart type 10,8). Un décès est survenu au cours de la période d'étude et aucun cas de thrombocytopénie induite par l'héparine n'a été observé. Conclusions: Dans cette étude portant sur des patients hospitalisés atteints d'une forme grave de COVID-19, considérés comme présentant un faible risque de saignement et ayant reçu une anticoagulation thérapeutique, les taux d'hémorragies majeures et d'événements thrombotiques étaient faibles.

The effect of serum triglyceride levels and different lipid-lowering methods on the prognosis of hypertriglyceridemic acute pancreatitis: a single-center 12-year retrospective study by propensity score matching.

AIM: To investigate the impact of triglyceride on hypertriglyceridemic acute pancreatitis (HTG-AP) and different lipid-lowering methods on triglyceride-lowering efficiency and HTG-AP. METHODS: The patients with HTG-AP from January 2012 to December 2023 in Civil Aviation General Hospital were analyzed, retrospectively. Patients were divided and compared according to whether their triglycerides were below 5.56 mmol/L at 48 and 72 h of admission. The patients were divided into control group, insulin group, and low molecular weight heparin (LMWH)+bezafibrate group based on the different methods of lipid-lowering. Propensity score matching (PSM) was employed to balance the baseline characteristics. RESULTS: There was no correlation between the severity of HTG-AP and the triglyceride at admission. The incidence of severity, local complications, and persistent organ failure (POF) were significantly decreased in patients with 48-h and 72-h triglyceride attainment. Following PSM, the incidence of infectious pancreatic necrosis (IPN) (3.3% vs. 13.3%) was significantly reduced in insulin group compared with control group (p < .05). Compared with control group, LMWH + bezafibrate group had higher lipid reduction efficiency, and the incidence of IPN (0.9% vs. 10.1%) and POF (8.3% vs. 19.3%) was significantly decreased (p < .05). There was no significant difference in the efficiency of lipid-lowering, complications, and POF between LMWH + bezafibrate group and insulin group (p > .05). CONCLUSION: The severity of HTG-AP is not associated with the triglyceride levels at admission. However, rapid reduction of triglyceride levels can lower the incidence of local complications and respiratory failure. Compared with conservative treatment, insulin and LMWH + bezafibrate can both reduce the incidence of IPN in patients with HTG-AP.

Low-molecular-weight heparin and preeclampsia - does the sword cut both ways? Three case reports and review of literature.

BACKGROUND: Low-molecular-weight heparins (LMWH) are the most commonly used anticoagulants during pregnancy. It is considered to be the drug of choice due to its safety in not crossing placenta. Considering the beneficial effect in the improvement of microcirculation, prophylactic application of LMWH in patients with preeclampsia became a trend. However, the bleeding risk related with LMWH in preeclampsia patients has seldomly been evaluated. This current study aimed to identify the potential risks regarding LMWH application in patients with preeclampsia. CASE SUMMARY: Herein we present a case series of three pregnant women diagnosed with preeclampsia on LMWH therapy during pregnancy. All the cases experienced catastrophic hemorrhagic events. After reviewing the twenty-one meta-analyses, the bleeding risk related with LMWH seems ignorable. Only one study analyzed the bleeding risk of LMWH and found a significantly higher risk of developing PPH in women receiving LMWH. Other studies reported minor bleeding risks, none of these were serious enough to stop LMWH treatment. Possibilities of bleeding either from uterus or from intrabdominal organs in preeclampsia patients on LMWH therapy should not be ignored. Intensive management of blood pressure even after delivery and homeostasis suture in surgery are crucial. CONCLUSION: Consideration should be given to the balance between benefits and risks of LMWH in patients with preeclampsia.

A systematic review and meta-analysis of the effectiveness of primary thromboprophylaxis in acute lymphoblastic leukemia during early-phase therapy including asparaginase or its prolonged form.

Asparaginase is essential in the initial management of acute lymphoblastic leukemia (ALL) but frequently leads to venous thromboembolism (VTE). Using anticoagulants for primary VTE prevention has been studied with no consensus. We conducted a systematic literature search in PubMed, Scopus, and Web of science and performed random-effect meta-analysis using Mantel-Haenszel method in RevMan 5.4 to analyze primary pharmacological thromboprophylaxis during asparaginase treatment in early-phase (induction, consolidation, or intensification phase) therapy in patients with ALL with all ages and followed with subgroup analysis by age. Meta-analysis of 13 articles describing the effect of antithrombin supplementation in 1375 patients showed that antithrombin prophylaxis decreases the risk of VTE by 43% (RR, 0.57; 95% CI, 0.38 - 0.83; p=0.004), with mild heterogeneity (I2=35%, p=0.10) and moderate certainty by GRADE. 8 articles included for meta-analysis of low-molecular weight heparin (LMWH) treatment in 612 patients showed that it decreased the risk of VTE by nearly 40% (RR, 0.61; 95% CI, 0.45 - 0.81; p=0.00081), with minimal heterogeneity (I2=14%, p=0.31) but low certainty. Subgroup analysis showed that only prophylaxis with antithrombin supplementation significantly decreased the VTE rate in adult patients with moderate certainty. In pediatric patients, one nonrandomized prospective study showed that LMWH combined with antithrombin has a better thromboprophylaxis effect than antithrombin alone. In the PREVAPIX-ALL trial, prophylaxis with direct factor Xa inhibitor Apixaban did not benefit children younger than 18 years except for cases of obesity. We concluded that thromboprophylaxis with antithrombin is effective in ALL patients older than 18 years during the early phase of therapy, and LMWH combined with antithrombin supplementation might be effective for pediatric patients with ALL. Apixaban is effective in pediatric ALL patients with obesity and needs further study in other high-risk patients.

Periprocedural Bridging Therapy in Patients With Mechanical Heart Valves.

Mechanical heart valves (MHVs) are thrombogenic and require lifelong anticoagulation with vitamin K antagonists (VKAs) such as warfarin. Periprocedural bridging with unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) aims to reduce the risk of thromboembolic events in patients. Currently, there are no definitive class I recommendations for anticoagulation management in patients with MHVs. In this report, we present the case of a 77-year-old female who was perioperatively bridged with enoxaparin and subsequently developed an acute thrombus.

Impact of perioperative low-molecular-weight heparin therapy on clinical events of elderly patients with prior coronary stents implanted > 12 months undergoing non-cardiac surgery: a randomized, placebo-controlled trial.

BACKGROUND: Little is known about the safety and efficacy of discontinuing antiplatelet therapy via LMWH bridging therapy in elderly patients with coronary stents implanted for > 12 months undergoing non-cardiac surgery. This randomized trial was designed to compare the clinical benefits and risks of antiplatelet drug discontinuation via LMWH bridging therapy. METHODS: Patients were randomized 1:1 to receive subcutaneous injections of either dalteparin sodium or placebo. The primary efficacy endpoint was cardiac or cerebrovascular events. The primary safety endpoint was major bleeding. RESULTS: Among 2476 randomized patients, the variables (sex, age, body mass index, comorbidities, medications, and procedural characteristics) and percutaneous coronary intervention information were not significantly different between the bridging and non-bridging groups. During the follow-up period, the rate of the combined endpoint in the bridging group was significantly lower than in the non-bridging group (5.79% vs. 8.42%, p = 0.012). The incidence of myocardial injury in the bridging group was significantly lower than in the non-bridging group (3.14% vs. 5.19%, p = 0.011). Deep vein thrombosis occurred more frequently in the non-bridging group (1.21% vs. 0.4%, p = 0.024), and there was a trend toward a higher rate of pulmonary embolism (0.32% vs. 0.08%, p = 0.177). There was no significant difference between the groups in the rates of acute myocardial infarction (0.81% vs. 1.38%), cardiac death (0.24% vs. 0.41%), stroke (0.16% vs. 0.24%), or major bleeding (1.22% vs. 1.45%). Multivariable analysis showed that LMWH bridging, creatinine clearance < 30 mL/min, preoperative hemoglobin < 10 g/dL, and diabetes mellitus were independent predictors of ischemic events. LMWH bridging and a preoperative platelet count of < 70 × 109/L were independent predictors of minor bleeding events. CONCLUSIONS: This study showed the safety and efficacy of perioperative LMWH bridging therapy in elderly patients with coronary stents implanted > 12 months undergoing non-cardiac surgery. An alternative approach might be the use of bridging therapy with half-dose LMWH. TRIAL REGISTRATION: ISRCTN65203415.

Intestinal obstruction as a result of intra-abdominal hematoma: a complication of low molecular weight heparin in pediatric patients. / Obstrucción intestinal por hematoma intraabdominal: una complicación de la heparina de bajo peso molecular en el paciente pediátrico.

INTRODUCTION: Hematomas are a rare cause of intestinal obstruction. Subcutaneous heparin can bring about direct punctures on small bowel loops, potentially leading to traumatic hematoma and intestinal obstruction. CASE REPORTS: We present three cases of pediatric patients with clinical signs of intestinal obstruction treated with subcutaneous heparin. Two cases had increased acute-phase reactants and radiological signs of intestinal suffering, so surgical treatment was decided upon, with intramural hematoma emerging as an intraoperative finding. The third case was conservatively managed with anticoagulant discontinuation and gut rest, since the patient had an adequate general condition and no findings compatible with ischemia or necrosis were noted in the complementary tests. DISCUSSION: The administration of subcutaneous heparin may cause intestinal wall hematomas due to its anticoagulating effect and to the risk of inadvertent punctures on small bowel loops.

INTRODUCCION: Los hematomas son una causa poco frecuente de obstrucción intestinal. La heparina subcutánea tiene riesgo de producir la punción directa de un asa intestinal, provocando un hematoma traumático que genere una obstrucción intestinal. CASOS CLINICOS: Se describen tres casos de pacientes pediátricos con clínica de obstrucción intestinal en tratamiento con heparina subcutánea. Dos casos presentaron elevación de reactantes de fase aguda y signos radiológicos de sufrimiento intestinal por lo que se optó por tratamiento quirúrgico, con el hallazgo intraoperatorio de hematoma intramural. El tercer caso fue manejado de manera conservadora con supresión de la anticoagulación y reposo intestinal, dado el adecuado estado general y ausencia de hallazgos compatibles con isquemia o necrosis en las pruebas complementarias. COMENTARIOS: La administración de heparina subcutánea puede provocar la aparición de hematomas de pared intestinal, tanto por su efecto anticoagulante, como por el riesgo de punción inadvertida de un asa intestinal.

Obstrucción intestinal por hematoma intraabdominal: una complicación de la heparina de bajo peso molecular en el paciente pediátrico / Intestinal obstruction as a result of intra-abdominal hematoma: a complication of low molecular weight heparin in pediatric patients

Introducción: Los hematomas son una causa poco frecuente deobstrucción intestinal. La heparina subcutánea tiene riesgo de producirla punción directa de un asa intestinal, provocando un hematoma trau-mático que genere una obstrucción intestinal. Casos clínicos: Se describen tres casos de pacientes pediátricos conclínica de obstrucción intestinal en tratamiento con heparina subcutánea.Dos casos presentaron elevación de reactantes de fase aguda y signosradiológicos de sufrimiento intestinal por lo que se optó por tratamientoquirúrgico, con el hallazgo intraoperatorio de hematoma intramural. Eltercer caso fue manejado de manera conservadora con supresión de laanticoagulación y reposo intestinal, dado el adecuado estado generaly ausencia de hallazgos compatibles con isquemia o necrosis en laspruebas complementarias. Comentarios: La administración de heparina subcutánea puedeprovocar la aparición de hematomas de pared intestinal, tanto por suefecto anticoagulante, como por el riesgo de punción inadvertida deun asa intestinal.(AU)

Introduction: Hematomas are a rare cause of intestinal obstruc-tion. Subcutaneous heparin can bring about direct punctures on smallbowel loops, potentially leading to traumatic hematoma and intestinalobstruction. Case reports: We present three cases of pediatric patients withclinical signs of intestinal obstruction treated with subcutaneous heparin. Two cases had increased acute-phase reactants and radiological signsof intestinal suffering, so surgical treatment was decided upon, withintramural hematoma emerging as an intraoperative finding. The thirdcase was conservatively managed with anticoagulant discontinuationand gut rest, since the patient had an adequate general condition andno findings compatible with ischemia or necrosis were noted in thecomplementary tests. Discussion: The administration of subcutaneous heparin may causeintestinal wall hematomas due to its anticoagulating effect and to therisk of inadvertent punctures on small bowel loops.(AU)

Incidence of Symptomatic Venous Thromboembolisms in Stroke Patients.

Venous thromboembolism (VTE) is a common but preventable complication observed in critically ill patients. Deep vein thrombosis (DVT) is the most common type of VTE, with clinical significance based on location and symptoms. There is an increased incidence of DVT and pulmonary embolism (PE) in ischemic stroke patients using unfractionated heparin (UFH) for VTE prophylaxis compared with those using enoxaparin. However, UFH is still used in some patients due to its perceived safety, despite conflicting literature suggesting that enoxaparin may have a protective effect. The current study aimed to determine the incidence of VTEs in patients with acute ischemic strokes on UFH versus enoxaparin for VTE prophylaxis, subclassifying the VTEs depending on their location and symptoms. It also aimed to examine the safety profile of both drugs. A total of 909 patients admitted to the Neuro-ICU with the diagnosis of acute ischemic stroke were identified, and 634 patients were enrolled in the study-170 in the enoxaparin group and 464 in the UFH group-after applying the exclusion criteria. Nineteen patients in the UFH group (4.1%) and 3 patients in the enoxaparin group (1.8%) had a VTE. The incidence of DVT in the UFH group was 12 (2.6%), all of which were symptomatic, compared with 3 (1.8%) in the enoxaparin group, wherein one case was symptomatic. Nine patients (1.9%) in the UFH group developed a PE during the study period, and all of them were symptomatic. No patients in the enoxaparin group developed PE. No statistically significant difference was found between both groups. However, 18 patients in the UFH group (3.9%) experienced intracranial hemorrhage compared with none in the enoxaparin group, and this difference was statistically significant. Enoxaparin was found to be as effective as and potentially safer than UFH when used for VTE prophylaxis in stroke patients.

Real-world Data on Treatment Patterns and Bleeding in Cancer-associated Thrombosis: Data from the TROLL Registry.

Background International guidelines are increasingly recommending direct oral anticoagulants (DOACs) as the first-line treatment for cancer-associated thrombosis (CAT). However, data regarding treatment patterns and adherence to guidelines in patients with CAT are scarce. Objectives This study aimed to explore anticoagulant treatment patterns in patients with CAT and to calculate the incidence rates of bleeding events. Methods Patients ≥18 years with active cancer and a first-time venous thromboembolism between 2005 and 2020 were identified through the Venous T hrombosis R egistry in Østf OL d Hospita L . Outcome measures were patterns of anticoagulant treatment during the study period and bleeding events. We calculated overall incidence rates per 100 person-years and 6- and 12-month cumulative incidence of major and clinically relevant nonmajor bleeding (CRNMB) during anticoagulant treatment. Results Median age of 842 CAT patients at the time of thrombosis was 69 years (interquartile range 61-77), and 443 (52.6%) were men. In total, 526 patients (62.5%) had pulmonary embolism and 255 (30.3%) had deep vein thrombosis. Low molecular weight heparin (LMWH) was prescribed to 713 (85.8%) patients, whereas 64 (7.7%) received DOACs and 54 (6.5%) received vitamin K antagonists as the initial anticoagulant treatment. Prescription of DOACs as initial treatment increased from 3.0% in 2013/2014 to 18.0% in 2019/2020. The incidence rate of major bleeding was 6.9 (95% confidence interval [CI] 5.2-9.2) and 10.1 (95% CI 8.0-12.9) in CRNMB. Conclusion Most patients were treated with LMWH. However, a gradual shift in treatment toward DOACs was observed. Overall, bleeding complications were rare and comparable to those reported in randomized trials.

Anticoagulation in venous thromboembolism for the general physician.

Venous thromboembolism (VTE) is frequently encountered across various specialties. The management of VTE has become more nuanced, requiring consideration of several factors when deciding on the choice and duration of anticoagulation. This evidence-based review article summarises the current practice and evidence behind anticoagulation in VTE, incorporating national and international guidelines. Factors influencing decision-making around the choice and duration of anticoagulation, along with special circumstances such as cancer and antiphospholipid syndrome, are discussed. The clinical utility of thrombophilia screening is also addressed.

Synthesis of bioengineered heparin chemically and biologically similar to porcine-derived products and convertible to low MW heparin.

Heparins have been invaluable therapeutic anticoagulant polysaccharides for over a century, whether used as unfractionated heparin or as low molecular weight heparin (LMWH) derivatives. However, heparin production by extraction from animal tissues presents multiple challenges, including the risk of adulteration, contamination, prion and viral impurities, limited supply, insecure supply chain, and significant batch-to-batch variability. The use of animal-derived heparin also raises ethical and religious concerns, as well as carries the risk of transmitting zoonotic diseases. Chemoenzymatic synthesis of animal-free heparin products would offer several advantages, including reliable and scalable production processes, improved purity and consistency, and the ability to produce heparin polysaccharides with molecular weight, structural, and functional properties equivalent to those of the United States Pharmacopeia (USP) heparin, currently only sourced from porcine intestinal mucosa. We report a scalable process for the production of bioengineered heparin that is biologically and compositionally similar to USP heparin. This process relies on enzymes from the heparin biosynthetic pathway, immobilized on an inert support and requires a tailored N-sulfoheparosan with N-sulfo levels similar to those of porcine heparins. We also report the conversion of our bioengineered heparin into a LMWH that is biologically and compositionally similar to USP enoxaparin. Ultimately, we demonstrate major advances to a process to provide a potential clinical and sustainable alternative to porcine-derived heparin products.

Clinical therapeutics for proliferative vitreoretinopathy in retinal detachment.

Proliferative vitreoretinopathy (PVR) is an abnormal and prolonged healing response to retinal injury (retinal detachment, post retinal detachment surgery) characterised by: pre/subretinal membrane formation; retinal gliosis and retinal shortening, retinal pigment epithelium cell proliferation; and increased glial (mainly Mu¨ller cells), fibroblast and inflammatory cell (macrophage, lymphocyte) activity, leading to tractional retinal holes/breaks and multiple costly eye operations suffered by patients. PVR can cause retinal re-detachment following primary surgical intervention for rhegmatogenous retinal detachment. Vitrectomy and scleral buckling surgery are the main approaches for treating PVR complications of retinal detachment. Patients require many operations to remove the scar tissue but vision results are suboptimal, and do not meet patient expectations. Over the past 40 years, this has been one of the greatest challenges for vitreoretinal surgeons and patients. Despite previous large clinical trials of multiple candidate drug therapeutics, no proven adjunctive treatment currently exists to either prevent, reduce, or treat PVR formation in retinal detachment. Both cellular proliferation and the intraocular inflammatory response are realistic targets for adjunctive treatments in PVR. The cellular components of PVR periretinal membranes (retinal pigment epithelial, glial, inflammatory and fibroblastic cells) proliferate and are thus targets for antiproliferative agents. In recent years, several new therapeutics have been tested, and we present an updated review of the clinical therapeutics for PVR in retinal detachment.

Efficacy of 5-fluorouracil (5-FU) and low molecular weight heparin (LMWH) in high-risk pediatric retinal detachment; randomized clinical trial.

BACKGROUND: Pediatric rhegmatogenous retinal detachments (PRRDs) are complex, rare occurrences and are often related to trauma or congenital abnormalities. Children often do not recognize or report symptoms of retinal detachment. Thus at presentation, PRRD is typically advanced often with macular involvement, proliferative vitreoretinopathy (PVR), chronic duration, and poor visual acuity. Because 5-FU and LMWH are effective in different aspects in the PVR process, it was believed that a syngergistic approach to the prevention of PVR would be advantageous. METHODS: After informed consent, children under 14 years of age with high-risk PRRD underwent pars plana vitrectomy and silicone oil injection with scleral buckle divided into 2 groups in prospective randomized trial. Group A received intraoperative infusion of 5-FU (200 µg/ml) and LMWH (5 IU/ml), group B received infusion of normal saline. Primary outcome was occurrence of recurrent PRRD within 12 weeks, secondary outcomes were occurrence of PVR, best corrected visual acuity (BCVA), number and timing of secondary procedures within 12 weeks. RESULTS: The study included 42 eyes of 41 patients, 21 in group A and 21 in group B, the duration of PRRD ranged from 0.5 to 7 months in group A and 0.25-5 months in group B.The rate of recurrent PRRD was higher in group B 33% compared to 19% in group A (p = 0.292). The mean timing of occurrence of recurrent PRRD was 9.5 ± 5 weeks in group A compared to 2.86 ± 2.41 weeks in group B (p = 0.042), more patients in group B ended up with more advanced PVR (p = 0.038), BCVA was hand movement (HM) only in all cases preoperatively and improved to HM-0.3 Snellen in group A compared to light perception (PL)-0.1Snellen in group B (p = 0.035), there was no difference in any of secondary procedures but with later timing in group A 9.71 ± 3.73 weeks than in group B 4.0 ± 2.83 weeks (p = 0.042). CONCLUSION: This study concluded that the use of the 5-FU and LMWH combination in high risk PRRD resulted in lower rate of postoperative PVR, later recurrence of PRRD and better final BCVA. TRIAL REGISTRATION NUMBER: Registry: clinicaltrials.gov PRS NCT06166914 date of initial release 4/12/2023. Unique Protocol ID: 9,163,209 date 21/10/2021. Retrospectively registered.

A systematic review of therapeutic enoxaparin dosing in obesity.

Enoxaparin is a hydrophilic drug with obesity having little effect on its apparent volume of distribution, therefore patients with obesity receiving standard 1 mg/kg dosing may be at a higher risk of supratherapeutic dosing. Conversely, dose reducing patients with obesity could place already at risk patients at higher risk of a thrombotic event. Data and recommendations are variable for the most appropriate weight-based dose of therapeutic enoxaparin in obese patients, particularly those a weight > 100 kg or a body mass index (BMI) ≥ 40 kg/m2. The purpose of this systematic review was to globally evaluate these data to surmise optimal dosing recommendations for patients with obesity. A systematic review of English language studies was conducted and identified articles via Pubmed, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) searches. Studies were included if they reported therapeutic enoxaparin use in adult patients with a BMI ≥ 40 kg/m2 or body weight > 100 kg and the percentage of patients achieving a therapeutic anti-Xa based on a weight-based dose or the weight-based dose required to produce a therapeutic anti-Xa level. Therapeutic attainment of anti-Xa levels were assessed across enoxaparin weight-based dosing categories including a very low dose group: < 0.75 mg/kg, low dose group: 0.75-0.85 mg/kg, and standard dose group: ≥ 0.95 mg/kg. Rates of bleeding and thrombosis were also evaluated. A total of eight studies were included. For anti-Xa level assessment, 682 patients were included. A total of 62% of anti-Xa levels were therapeutic in the very low dose group, 66% in the low dose group, and 42% in the standard dose group. Overall rates of total bleeding and thrombosis were assessed in 798 patients. A total of 29 bleedings (3.6%) occurred, and 27 reported a relationship to dose. Most bleedings, 85.2% (n = 23/27), occurred with doses in the standard dose group (≥ 0.95 mg/kg). Thrombosis occurred in 5 patients (0.6%). Utilization of a reduced weight-based dosing strategy for therapeutic enoxaparin in obese patients may increase the percentage of patients with a therapeutic anti-Xa level.

Is a minimum duration of 5 days of unfractionated heparin infusion necessary before transition to oral anticoagulation in cerebral venous thrombosis? a retrospective chart review.

In managing cerebral venous sinus thrombosis (CVT), the standard approach has been administering parenteral anticoagulation for at least five days, despite limited supporting evidence. This study aimed to determine the optimal duration of parenteral anticoagulation for CVT patients and its potential impact on their functional outcomes upon discharge. This retrospective observational cohort study was conducted across multiple healthcare centers and included adult CVT patients who received varying durations of parenteral anticoagulation: less than 5 days (n = 25) or 5 days or more (n = 16). The primary focus was on the duration of acute anticoagulation treatment, with secondary endpoints including hospital stay length and functional outcomes. The study found that a shorter duration of anticoagulation treatment (< 5 days) was linked to more favorable outcomes, as measured by the modified Rankin Scale (mRS) (68% vs. 25%, RR = 0.37, CI 0.15-0.90, p = 0.007). However, regression analysis showed non statistically significant associations for all variables except gender. Female patients were significantly more likely to receive a shorter duration of anticoagulation (Odds Ratio: 2.6, 95% CI: 2.2-3.1, P-Value: <0.001). These findings suggest a potential connection between shorter anticoagulation duration (< 5 days) and improved CVT patient outcomes, as indicated by their mRS scores at discharge. The observed relationship between female gender and shorter anticoagulation duration warrants further exploration. Nevertheless, caution is necessary when interpreting these findings due to the small sample size and specific patient characteristics. Further research in a larger and more diverse cohort is essential to validate these results and understand their implications fully.

Smaller nadroparin dose reductions required for patients with renal impairment: A multicenter cohort study.

BACKGROUND: Guidelines advise 50 % and 25 % dose reduction of the therapeutic nadroparin dose (86 IU/kg) in patients with eGFR 15-29 and 30-60 ml/min respectively. For monitoring, peak anti-Xa levels are suggested. Data lack whether this results in therapeutic anti-Xa levels or in anti-Xa levels that are comparable to those of patients without renal impairment. AIMS: To determine dose ranges in patients with renal impairment that result in therapeutic anti-Xa levels and to determine the percentage of the 86 IU/kg dose that results in anti-Xa levels normally occurring in patients without renal impairment. METHODS: A retrospective cohort study was conducted in five hospitals. Patients ≥18 years of age, with an eGFR ≥ 15 ml/min were included. The first correctly sampled peak (i.e. 3-5 h after ≥ third administration, regardless of dose per patient) was included. Simulated prediction models were developed using multiple linear regression. RESULTS: 770 patients were included. eGFR and hospital affected the association between dose and anti-Xa level. The doses for peak anti-Xa levels of 0.75 IU/ml differed substantially between hospitals and ranged from 55 to 91, 65-359 and 68-168 IU/kg in eGFR 15-29, 30-60 and > 60 ml/min/1.73m2, respectively. In eGFR 15-29 and 30-60 ml/min/1.73m2, doses of 75 % and 91 % of 86 IU/kg respectively, were needed for anti-Xa levels normally occurring in patients with eGFR > 60 ml/min. CONCLUSION: We advise against anti-Xa based dose-adjustments as long as anti-Xa assays between laboratories are not harmonized and an anti-Xa target range is not validated. A better approach might be to target levels similar to eGFR > 60 ml/min/1.73m2, which are achieved by smaller dose reductions.