BACKGROUND: Recent studies suggest that low-molecular-weight heparin (LMWH) may play a role in mitigating the severity of acute pancreatitis (AP). This systematic review and meta-analysis aims to synthesise existing evidence on the effectiveness and safety of LMWH in the treatment of moderately-severe and severe AP.
METHODS: This systematic review and meta-analysis was conducted in accordance with the 2020 update of the PRISMA guidelines and the Cochrane Handbook for Systematic Reviews of Interventions. The systematic search was conducted in MEDLINE, the Cochrane Central Register of Controlled Trials, Scopus, and EMBASE, covering studies published up to February 2024. Randomised controlled trials (RCTs) and observational studies (n-RCTs) that reported the differences in the outcomes of AP for patients receiving LMWH in addition to the standard treatment (Intervention), compared to patients managed by standard treatment without LMWH (Control) were eligible. A random-effects model was used to calculate the pooled relative risk (RR) and mean differences (MD) with the corresponding 95% CI.
RESULTS: Thirteen studies were included in the meta-analysis, all published between 2004 and 2022. Eight studies were RCTs, and five were n-RCTs. Data from 13,709 patients (6.971 Interventions and 6.738 Controls) were analysed. The comparison of Intervention and Control groups showed the superiority of LMWH to standard treatments in terms of overall mortality (RR = 0.44, 95% CI = 0.31; 0.64, P < 0.0001, I2 = 51%), acute necrotic collections (RR = 0.24, 95% CI = 0.09; 0.62, P = 0.003, I2 = 0%), and organ failure (RR = 0.67, 95% CI = 0.48; 0.93, P = 0.02, I2 = 78%). The Intervention group showed superior outcomes compared with the Control group for gastrointestinal bleeding (RR = 0.64, 95% CI = 0.44; 0.94, P = 0.02, I2 = 0%), length of hospital stay (MD= - 6.08, 95% CI = - 10.08; - 2.07, P = 0.003, I2 = 98%), need for operative interventions (RR = 0.50, 95% CI = 0.29; 0.87, P = 0.01, I2 = 61%), and vascular thrombosis (RR = 0.43, 95% CI = 0.31; 0.61, P < 0.00001, I2 = 0%).
CONCLUSIONS: Moderate to high-quality evidence suggests that early intervention with LMWH could improve the prognosis of non-mild AP in terms of mortality, organ failure, and decreased incidence of vascular thrombosis. In light of our findings, integrating LMWH into the treatment regimen for moderate-severe to severe AP is advocated.

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.

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.

OBJECTIVE: To systematically evaluate the efficacy of low molecular weight heparin (LMWH) to prevent preeclampsia in high risk pregnant women without thrombophilia.
METHODS: PubMed, Embase and the Cochrane library were searched for articles published before 1st August 2022 using the combination keywords \"preeclampsia\", \"Low Molecular Weight Heparin\", \"LMWH\", \"Heparin, Low Molecular Weight\", \"Dalteparin\", \"Nadroparin\", and \"Tinzaparin\".
METHODS: Randomized controlled trials evaluating the use of LMWH in pregnant women at high risk of preeclampsia without thrombophilia.
METHODS: Ten studies were included in the meta-analysis (1758 patients in total). Outcomes were expressed as relative risk (RR) with 95% confidence intervals (CI).
RESULTS: LMWH reduced the incidence of PE (RR = 0.67; 95% CI = 0.50-0.90; P = 0.009) in high risk pregnant women without thrombophilia. Subgroup analysis found that the prophylactic effect of LMWH was only significant in studies using low-dose aspirin (LDA) as the primary intervention. The combination of LMWH and LDA was also effective for the prevention of preterm birth and fetal growth restriction, but had no effect on the incidence of placenta abruption.
CONCLUSIONS: For women at high risk of developing preeclampsia without thrombophilia, the combination of LMWH and low-dose aspirin is effective for the prevention of preeclampsia, preterm birth and fetal growth restriction and is superior to LDA alone.

Adrenal hemorrhage is a rare, but important, diagnosis to recognize, in particular when there is involvement of both adrenal glands. Bilateral adrenal hemorrhage can in fact lead to adrenal insufficiency, with dramatic consequences if not promptly recognized and treated. It is normally caused by systemic conditions that lead to the vasoconstriction and thrombosis of the adrenal vein. Oftentimes, the clinical diagnosis of this condition can be very challenging, as its signs and symptoms are generalized and nonspecific (abdominal pain, nausea, and fatigue). Here, we present the cases of two patients admitted to the Emergency Department in 2016 and 2022 with acute abdominal pain, having recently undergone surgery and subsequently prescribed low-molecular-weight heparin. In both cases, laboratory results revealed neutrophilic leukocytosis and an unexplained anemia. Due to the persistence of abdominal pain despite medication, a CT scan was performed, showing an enlargement of both adrenal glands suggestive of bilateral adrenal hemorrhage. Adrenal function was tested that correlated with a diagnosis of adrenal insufficiency, and both patients were promptly treated with parenteral hydrocortisone as a result. On 5 years\' follow-up from the acute event, the second patient\'s adrenal function had returned to normal, and he has not needed further adrenal replacement therapy; the first patient however demonstrated persistence of adrenal failure requiring replacement therapy. In this paper, through our experience and a literature analysis, we will aim to outline some clues to identify patients at potential risk of bilateral adrenal hemorrhage.

暂无摘要。

In recent years, many important advances have been seen in anticoagulation therapy. However, bleeding risk is still a major concern. Factor XI (FXI) inhibition has emerged as a potential advantageous target to minimize this risk.
We conducted a systematic review and meta-analysis of current evidence on FXI inhibitors for thromboprophylaxis in major orthopedic surgery.
We performed a systematic search of electronic databases (PubMed, CENTRAL, and Scopus) until May of 2022. Studies were considered eligible if they were randomized controlled trials (RCTs) evaluating FXI inhibitors in thromboprophylaxis versus low molecular weight heparin (LMWH). For analysis purposes, we considered efficacy (venous thromboembolism [VTE], symptomatic VTE) and safety (major and clinically relevant non-major [CRNM] bleeding events, major bleeding events, blood transfusion necessities, adverse events, major adverse events) outcomes.
Overall, four RCTs were included, with a total of 2269 patients, 372 VTE events, and 50 major or CRNM bleeding events. Regarding efficacy outcomes, FXI inhibitors were associated with a significant reduction in the incidence of VTE events (odds ratio [OR] 0.50; 95% confidence interval [CI: 0.36, 0.69]). Concerning safety outcomes, FXI inhibitors significantly reduced major or CRNM bleeding events (OR 0.41; 95% CI [0.22, 0.75]). It was also associated with a lower percentage of patients needing a blood transfusion, despite not meeting statistical significance (OR 0.69; 95% CI [0.32, 1.48]). Incidence of adverse events and major adverse events were similar between groups.
Factor XI inhibitors showed a significant reduction in the incidence of VTE and bleeding events among patients submitted to major orthopedic surgery.

Direct oral anticoagulants (DOACs) could effectively prevent the occurrence of cancer-associated venous thromboembolism (CAVTE), which incidence rate was estimated to be 4-20%. But the efficacy and safety remain controversial between DOACs and low molecular weight heparin (LMWH).
PubMed, Cochrane Library, Embase, ClinicalTrials.gov databases for randomized controlled trials (RCTs) were systematically searched from inception to March 15, 2022. A random-effects model was used to report the odds ratio (OR) and 95% confidence interval (CI) for both direct and network meta-analyses.
Seven studies were included totaling 3242 patients. A lower rate of recurrence VTE was noted in the DOACs compared with LMWH (OR 0.62, 95% CI 0.47-0.82, I2=0.0%). The aspect of major bleeding (MB) was similar (OR 1.30, 95% CI 0.77-2.18, I2=34.9%). When assessing clinically relevant nonmajor bleeding (CRNMB) (OR 1.61, 95% CI 1.17-2.22, I2=20.7%) and clinically relevant bleeding (CRB) (OR 1.39, 95% CI 1.11-1.74, I2=0.0%), a higher risk of events was observed in DOACs. In subgroup analyses, the MB of gastrointestinal and genitourinary malignancies had a higher rate in the DOACs. For ranking, apixaban ranked the first in prevention of VTE and reducing MB events. Edoxaban had the highest risk drug in MB. In terms of CRNMB and CRB, LMWH showed the lowest risk.
Compared with LMWH, DOACs seemed to have a decreased risk of recurrence VTE while increasing CRNMB and CRB. DOACs and LMWH were equivalent to the aspect of MB, but DOACs had a higher MB risk in patients with gastrointestinal and genitourinary malignancies. Apixaban may be the lowest risk compared to the other DOACs in precaution of VTE and reducing bleeding events.

The identification of effective pharmacotherapies for traumatic brain injury (TBI) remains a major challenge. Treatment with heparin and its derivatives is associated with neuroprotective effects after experimental TBI; however, the optimal dosage and method of administration, modes of action, and effects on hemorrhage remain unclear. Therefore, this review aimed to systematically evaluate, analyze, and summarize the available literature on the use of heparin and low molecular weight heparins (LMWHs) as treatment options for experimental TBI. We searched two online databases (PubMed and ISI Web of Science) to identify relevant studies. Data pertaining to TBI paradigm, animal subjects, drug administration, and all pathological and behavior outcomes were extracted. Eleven studies met our pre-specified inclusion criteria, and for outcomes with sufficient numbers, data from seven publications were analyzed in a weighted mean difference meta-analysis using a random-effects model. Study quality and risk of bias were also determined. Meta-analysis revealed that heparin and its derivatives decreased brain edema, leukocyte rolling, and vascular permeability, and improved neurological function. Further, treatment did not aggravate hemorrhage. These findings must be interpreted with caution, however, because they were determined from a limited number of studies with substantial heterogeneity. Also, overall study quality was low based on absences of data reporting, and potential publication bias was identified. Importantly, we found that there are insufficient data to evaluate the variables we had hoped to investigate. The beneficial effects of heparin and LMWHs, however, suggest that further pre-clinical studies are warranted.

OBJECTIVE: Low molecular weight heparins (LMWHs) are a group of heterogenous moieties, long used in the prevention and treatment of thrombosis. They derive from heparin and since they are prepared by different methods of depolymerization, they differ in pharmacokinetic properties and anticoagulant profiles, and thus are not clinically interchangeable.
METHODS: In this review we provide an overview of tinzaparin\'s main characteristics and uses.
RESULTS: Tinzaparin which is produced by the enzymatic depolymerization of unfractionated heparin (UFH) can be used for the treatment and prevention of deep venous thrombosis (DVT) and pulmonary embolism (PE); it has been also used in special populations such as elders, obese, pregnant women, and patients with renal impairment and/or cancer with favorable outcomes in both safety and efficacy, with a once daily dose regimen. Furthermore, LMWHs are extensively used in clinical practice for both thromboprophylaxis and thrombosis treatment of COVID-19 patients.
CONCLUSIONS: Tinzaparin features support the hypothesis for having a role in immunothrombosis treatment (i.e. in the context of cancer ,COVID-19), interfering not only with coagulation cascade but also exhibiting anti-inflammatory potency.