Low Molecular Weight Heparin Research Articles

A Systematic Review: Safety and Efficacy of Anticoagulation therapy for Atrial fibrillation and venous thromboembolism

For the prevention and treatment of thrombosis, anticoagulants  continue to be the principal approach. Since direct thrombin  inhibitors are usually saved for patients who need intervention or  who have complications, unfractionated heparin, low molecular  weight heparin, and warfarin have all been thoroughly studied and  used.As a result of their improved pharmacodynamic profiles and ease of  use, novel oral anticoagulants are predicted to supplant older ones  once they emerge from clinical development. Of all the side effects  of anticoagulants, bleeding is the most worrying. Anticoagulant  pharmacology, dosage, and toxicity are widely used, so clinicians  must be well-versed in these areas. 
  Traditionally, heparin was given to patients who needed  parenteral anticoagulation, while warfarin was given to patients who  needed oral anticoagulation. There has been a push to create newer,  more potent anticoagulants because of warfarin's limited therapeutic  index and the requirement for regular laboratory monitoring. 

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.

Hemorrhage induced by antithrombotic agents: new insights from a real-world pharmacovigilance study

ABSTRACT Background Hemorrhage represents the most common and serious side effect of antithrombotic agents. Many studies have compared the risk of bleeding between different antithrombotic agents, but analysis of time-to-onset for hemorrhage induced by these drugs is yet sparse. Methods We conducted a retrospective study based on the adverse drug reaction reports on antithrombotic agents collected by the Henan Adverse Drug Reaction Monitoring Center. We assessed the reporting odds ratio to determine the disproportionate reporting signals for bleeding and the Weibull shape parameter was used to evaluate the time-to-onset data. Results In the signal detection, crude low molecular weight heparin-hemorrhage was found as a positive signal. The hemorrhage for most antithrombotic agents was random failure profiles. In particular, the hazard of hemorrhage decreased over time for warfarin and clopidogrel and increased for alteplase, nadroparin, and dipyridamole. Conclusion We found that the risk of bleeding in patients taking Crude low molecular weight heparins was significantly higher compared to other antithrombotic agents, but with a small magnificence, which may be attributed to the severely irrational use of this medication under improper management. Statistics in days, results showed that the risk of bleeding decreased over time for warfarin and clopidogrel and increased for alteplase, nadroparin, and dipyridamole.

The incidence of venous thromboembolism after curative colon cancer surgery within an enhanced recovery after surgery programme

AimBased on three randomised controlled trials performed more than a decade ago, several national guidelines recommend prolonged venous thromboprophylaxis for 28 days following elective surgery for colon cancer. None of these studies were conducted within enhanced recovery after surgery setting. Newer studies indicate that prolonged prophylaxis might not be necessary with enhanced recovery after surgery. We aimed to provide further evidence to this unresolved discussion. MethodRetrospective study of patients undergoing elective surgery for colon cancer stage I-III with enhanced recovery after surgery in the Capital Region of Denmark from 2014 to 2017. Patients were excluded if discharged on postoperative day 28 or later, dying before discharge, undergoing concomitant rectum resection, or discharged with vitamin K antagonists, direct-oral anticoagulants, or low molecular weight heparin treatment. All patients received only low-dose low molecular weight heparin as prophylaxis during their admission.The primary endpoint was symptomatic lower limb deep venous thrombosis or pulmonary embolism diagnosed within 60 days postoperatively. ResultsOut of the included population of 1806 patients, only three experienced a symptomatic venous thromboembolic event; none was fatal. Two had pulmonary embolism associated with pneumonia, while one patient was diagnosed with lower limb deep venous thrombosis at postoperative day 15 after an uncomplicated course with first discharge at postoperative day 2. ConclusionThe risk of symptomatic venous thromboembolism after elective surgery for colon cancer with enhanced recovery after surgery seems negligible even without prolonged prophylaxis. The current guidelines need to be reconsidered.

Safety of Continuing Aspirin Use in Patients With Coronary Heart Disease Who Undergo Thyroid Surgery During the Perioperative Period.

Objective: To investigate the safety of continuing aspirin use in patients with coronary heart disease undergoing thyroid surgery during the perioperative period. Methods: Forty-four patients with coronary heart disease who underwent thyroid surgery in our department from July 2019 to June 2023 were selected as the observation group, and the observation group continued to use aspirin during the perioperative period. Forty-four patients who underwent the same surgery during the same period without coronary heart disease and without anticoagulant or antiplatelet therapy were selected as control group 1. Another 44 patients with coronary heart disease who underwent the same surgery from August 2015 to June 2019 and used low molecular weight heparin bridging during the perioperative period were selected as control group 2. Clinical data from the 3 groups of patients were collected for retrospective analysis. Results: The age and proportion of male patients in the observation group and control group 2 were higher than those in control group 1, and the total hospital stay in control group 2 was longer than in the observation group and control group 1, with statistically significant differences (all P < .05). There were no statistically significant differences in surgical time, intraoperative blood loss, postoperative drainage volume, duration of drainage tube retention, postoperative hospital stay, and perioperative hemoglobin, platelet, and international normalized ratio between the 3 groups of patients (all P > .05). All patients in the 3 groups successfully completed surgery without serious complications or death during the perioperative period. Conclusion: Continuing to use aspirin in patients with coronary heart disease who undergo thyroid surgery during the perioperative period can safely complete surgery without increasing the risk of intraoperative and postoperative bleeding.

Is early bilateral compression ultrasonography and D-dimer monitoring appropriately for prophylaxis and diagnosis of deep venous thrombosis after cesarean section women: a single-center observation study of Chinese Han population

BackgroundVenous thromboembolism (VTE) is most prevalent among parturients following a cesarean section (CS). The objective of this study was to assess the practical utility of bilateral compression ultrasonography (CUS) of the lower limbs, coupled with D-dimer monitoring, in the early diagnosis of VTE within the Han Chinese population.MethodsOur prospective observational study included 742 women who underwent CUS and D-dimer testing on the first day post-CS. Subsequently, telephone or outpatient follow-ups were conducted until 42 days postpartum. States of hypercoagulation and thrombosis, as indicated by CUS, were classified as CUS abnormal. A D-dimer level ≥ 3 mg/l was considered the D-dimer warning value. Early ambulation and mechanical prophylaxis were universally recommended for all parturients post-CS. A sequential diagnostic strategy, based on the 2015 RCOG VTE risk-assessment tool, was employed. Therapeutic doses of low-molecular-weight heparin (LMWH) were administered for the treatment of thromboembolic disease. Prophylactic doses of LMWH were given for VTE prophylaxis in parturients with hypercoagulative status accompanied by D-dimer levels ≥ 3 mg/l. All high-risk women (RCOG score ≥ 4 points) were additionally treated with preventive LMWH. Statistical analyses were conducted using the R statistical software, with a two-sided P value < 0.05 considered statistically significant.ResultsFifteen cases of VTE and 727 instances without VTE were observed. The overall VTE rate post-CS was 2.02% (15/742), with 66.7% (10/15) being asymptomatic. Eleven patients received a VTE diagnosis on the first postpartum day. Among the 41 parturients exhibiting hypercoagulation ultrasound findings and D-dimer levels ≥ 3 mg/l, despite receiving pharmacological VTE prophylaxis with LMWH, 4.88% (2/41) in the high-risk group were eventually diagnosed with VTE. A total of 30.86% (229/742) exhibited normal ultrasound findings and D-dimer levels < 3 mg/l on the first day post-CS, with no VTE occurrences in the postpartum follow-up. According to RCOG’s recommendation, 78.03% (579/742) of cesarean delivery women should receive prophylactic anticoagulation, while only 20.62% (153/742) met our criterion for prophylactic anticoagulation.ConclusionThe strategy of timely routine bilateral CUS and D-dimer monitoring is conducive to the early diagnosis and treatment of VTE, significantly reducing the use of LMWH in the Chinese Han population.

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

BackgroundPediatric 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.MethodsAfter 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.ResultsThe 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).ConclusionThis 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 numberRegistry: clinicaltrials.gov PRS NCT06166914 date of initial release 4/12/2023. Unique Protocol ID: 9,163,209 date 21/10/2021. Retrospectively registered

Enzymatic construction of a library of even- and odd-numbered heparosan oligosaccharides and their N-sulfonated derivatives

Low-molecular-weight heparins (LMWHs), especially the specific-sized heparin oligosaccharides, are attractive for the therapeutic applications, while their synthesis remains challenging. In the present study, unsaturated even-numbered heparosan oligosaccharides were firstly prepared by cleaving high-molecular-weight heparosan using recombinant heparinase III (HepIII). The conversion rates of the unsaturated disaccharides, tetrasaccharides, hexasaccharides, octasaccharides, and decasaccharides were 33.9 %, 47.9 %, 78.7 %, 71.8 %, and 53.4 %, respectively. After processing the aforementioned heparosan oligosaccharides with the Δ4,5 unsaturated glycuronidase, saturated odd-numbered heparosan trisaccharides, pentasaccharides, heptasaccharides, and nonasaccharides were produced. It was observed that among them, the pentasaccharides were the smallest units of saturated odd-numbered oligosaccharides recognized by HepIII. These oligosaccharides were further catalyzed with bifunctional heparan sulfate N-deacetylase/N-sulfotransferase (NDST) under optimized reaction conditions. It was found that the tetrasaccharide was defined as the smallest recognition unit for NDST, obtaining the N-sulfonated heparosan tetrasaccharides, pentasaccharides, and hexasaccharides with a single sulfonate group, as well as N-sulfonated heparosan heptasaccharides, octasaccharides, and nonasaccharides with multiple sulfonate groups. These results provide an easy pathway for constructing a library of specific-sized N-sulfonated heparosan oligosaccharides that can be used as the substrates for the enzymatic synthesis of LMWHs and heparin oligosaccharides, shedding new light on the substrate preference of NDST.

Effectiveness of Taohong Siwu decoction in the prevention of deep vein thrombosis in hip surgery patients: A systematic review and meta-analysis of randomized controlled trials.

This systematic review and meta-analysis aimed to evaluate the effects of Taohong Siwu Decoction (THSWD) combined with low molecular weight heparin (LMWH), as well as THSWD alone, on the incidence of Deep vein thrombosis (DVT), D-dimer levels, prothrombin time (PT), activated partial thromboplastin time (APTT), visual analogue scale (VAS) pain score, and calf swelling in patients undergoing hip fracture or replacement surgery, compared to LMWH. According to the predefined inclusion criteria, we conducted a comprehensive search for randomized controlled trials (RCTs) examining the efficacy of THSWD combined with LMWH or THSWD compared to LMWH in patients with hip fractures or undergoing replacement surgery. The search was performed across multiple databases including China National Knowledge Internet, WanFang, Sinomed, Duxiu, PubMed, Embase, Google Scholar, Cochrane, and Web of Science from their inception until December 2023. Additionally, relevant literature references were retrieved and hand searching of pertinent journals was conducted. The methodological quality assessment of the included trials was carried out following the guidelines outlined in the Cochrane Handbook. Review Manager 5.4 was applied in analyzing and synthesizing. A total of 18 RCTs with 1353 patients were included. The results of meta-analysis showed that compared with the control group, the combined group had a better effect on the incidence of DVT [RR = 0.32, 95% CI(0.17, 0.58; P = .0002], D-dimer [SMD = -5.88, 95% CI(-7.66, -4.11); P < .00001], VAS [MD = -1.16, 95% CI(-1.81, -0.50); P = .0005], Calf circumference difference [MD = -0.56, 95% CI(-1.05, -0.08); P = .02]. There was no significant difference in PT and APTT between the combined group and the control group. Meta-analysis results show that the D-dimer, incidence of DVT, PT, and APTT did not significantly differ between the THSWD and the LMWH groups. This meta-analysis shows that compared with LMWH, THSWD combined with LMWH has a better efficacy in the treatment of DVT after hip surgery, without a significant increase in the incidence of adverse events. Additionally, the combined therapy can also reduce D-dimer, VAS, and swelling. However, due to the limitations of the included studies (such as small sample size and low-quality evidence), the results need to be further verified in more rigorous multicenter clinical trials with a large sample size.

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

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

Strategies to reduce rates of severe endothermal heat-induced thrombosis following radiofrequency ablation

ObjectiveEndothermal heat-induced thrombosis (EHIT) is a potential complication of radiofrequency ablation (RFA). Data on effective prophylaxis of EHIT are limited. In 2018, a high-volume, single institution implemented strategies to decrease the incidence of EHIT, including a single periprocedural prophylactic dose of low-molecular-weight heparin to patients with a great saphenous vein (GSV) diameter of ≥8 mm or saphenofemoral junction (SFJ) diameter of ≥10 mm and limiting treatment to one vein per procedure. The size threshold was derived from existing literature. The study objective was to evaluate the effects of these institutional changes on thrombotic complication rates after RFA. MethodsA retrospective cohort control study was conducted using the Vascular Quality Initiative database. Data were collected for patients who underwent RFA with a GSV diameter of ≥8 mm or SFJ diameter of ≥10 mm from January 2015 to July 2022. The clinical end points were thrombotic complications (ie, thrombophlebitis, EHIT, deep vein thrombosis) and bleeding complications. Patient demographic and procedural variables were included in the analysis, and significant variables after univariable logistic regression were included in a multivariable logistic regression. ResultsAfter the policy change, the overall vein center EHIT rate decreased from 2.6% to 1.5%, with a trend toward significance (P = .096). The inclusion criterion of a GSV diameter of ≥8 mm or an SFJ diameter of ≥10 mm yielded 845 patients, of whom 298 were treated before the policy change and 547 after. There was a significant reduction in the rate of EHIT classified as class ≥III (2.34 vs 0.366; P = .020) after the institutional changes. Treatment of two or more veins and an increased vein diameter were associated with an increased risk of EHIT (P = .049 and P < .001, respectively). No significant association was found between periprocedural anticoagulation and all-cause thrombotic complications or EHIT (P = .563 and P = .885, respectively). ConclusionsThe institutional policy changes have led to lower rates of EHIT, with a reduction in severe EHIT rates in patients with an ≥8-mm diameter GSV or a ≥10-mm diameter SFJ treated with RFA. Of the changes implemented, restricting treatment to one vein was associated with a reduction in severe EHIT. No association was found with periprocedural low-molecular-weight heparin, although a type 2 error might have occurred. Alternative strategies to prevent thrombotic complications should be explored, such as increasing the dosage and duration of periprocedural anticoagulation, antiplatelet use, and nonpharmacologic strategies.

Ressenti des femmes après traitement prophylactique par héparine de bas poids moléculaire après une césarienne

ObjectiveTo assess women's experiences with skin-related side effects following subcutaneous low molecular weight heparin (LMWH) injections after a cesarean section, and to analyze their impact on treatment adherence. MethodA questionnaire was developed in collaboration with Cesarine, a patients’ association, to explore various aspects of LMWH administration, including prevention methods, cutaneous side effects, treatment compliance, perceived constraints, apprehension, and understanding of treatment benefits. Additionally, women's opinions on an alternative oral administration approach were solicited, taking into consideration breastfeeding contraindication. The questionnaire was on the Facebook® page and blog of the association. ResultsOne hundred and sixty-four women participated in the survey. Among them, 139 women (84.8%) reported bruising, while 117 (71.3%) reported pruritus, erythema, or nodules at the injection site. Treatment discontinuation was observed in 36 cases (22%), decided mostly by the women themselves (77.8%). The main reasons cited for discontinuation were discomfort during injection (71.4%), skin reactions (31.4%), and a perceived lack of effectiveness (54.3%). Furthermore, 88 women (53.7%) wanted to quit the treatment prematurely, citing similar reasons. Thirty-three women (20.1%) reported oversights. For most women, the treatment was perceived as burdensome and caused apprehension. An alternative oral administration method was of interest to 131 women (79.9%). However, only 28 (17.8%) would have accepted if the medication was incompatible with breastfeeding. ConclusionCutaneous side effects of LMWH injections, as well as injection process itself, have a negative impact on adherence in the postpartum period following a c-section. These findings highlight the need to explore alternative to improve women's compliance and comfort.

Safety and Efficacy of Enoxaparin During Low-Risk Elective Percutaneous Coronary Intervention

Intravenous unfractionated heparin (UFH) is the most frequently used anticoagulant for percutaneous coronary intervention (PCI). Intravenous enoxaparin, a low-molecular weight heparin, has superior pharmacokinetic and pharmacodynamic properties compared with UFH. Multiple trials have shown enoxaparin to be safe and effective in PCI. However, there has not been a contemporary study evaluating its safety and efficacy. To assess its efficacy and safety, intravenous enoxaparin during PCI via radial artery access was evaluated in PCI patients from Jan 2015 to Dec 2019. Outcomes included procedural success, all-cause mortality, ischemic complications, and bleeding complications from the time of the procedure until hospital discharge. 1,019 consecutive eligible patients were identified. Median age was 63 years, and 70% were males. The indication for PCI was stable and unstable angina in two thirds of cases (77%). Few patients had myocardial infarction (MI) (2.2%) as the indication for intervention. The procedure was successful in 98.2% of cases. There were no deaths. Procedural MI occurred in 0.3% of patients. Acute stent thrombosis occurred in 0.4%. Urgent revascularization and stroke occurred in 0.1% each. Small wrist hematomas occurred in 0.3% and all were managed conservatively. There was one radial artery pseudoaneurysm. There were no cases of major bleeding. In conclusion, this single-center study showed that intravenous enoxaparin is a reasonable alternative anticoagulant for use in low-risk and elective non-myocardial infarction percutaneous coronary intervention via radial artery access.

Fetal Warfarin Syndrome - A Case Report

Fetal warfarin syndrome (FWS) or warfarin embryopathy also known as “Di Sala syndrome” is a rare fetal anomaly which occurs as a result of fetal exposure to warfarin during the early stages of pregnancy. FWS is characterised by nasal hypoplasia and skeletal abnormalities, including short limbs and digits and stippled epiphyses. Here we present a case of foetal embryopathy due to warfarin use in a female with an unplanned pregnancy while taking warfarin for cerebral venous thrombosis. The case was reported in Adverse Drug Reaction (ADR) Monitoring centre in August 2023. The purpose of this case report is to caution all the clinicians particularly obstetricians regarding the fetal abnormalities of warfarin. If the mother had history of warfarin usage, paediatricians should also be vigilant regarding the possibility of congenital warfarin syndrome in the newborn.&#x0D; Warfarin is an oral anticoagulant drug that decreases the production of clotting factors (II, VII, IX, X) which are vitamin K-dependent. Warfarin is used in the treatment of patients with thromboembolic disorders and in patients who are predisposed to the development of thrombus. Especially those people with prosthetic heart valves, those who have had ischemic stroke and atrial fibrillation. Warfarin is a teratogen which can cross the placental barrier and cause harm to the developing foetus.[1] Warfarin causes inhibition of clotting factors leading to internal bleeding of the fetus, while inhibition of osteocalcin retards bone growth. In addition to birth defects, warfarin can induce spontaneous abortion, premature delivery, neonatal death and even congenital anomalies known as fetal warfarin syndrome.[2] The risk of teratogenicity is not predictable with any dose of warfarin. The first case of embryopathy due to warfarin was reported by Di Sala in 1966 hence, it is also known as Di Sala syndrome.[3,4] Warfarin leads to embryopathy which is characterized by the abnormalities of cartilages and bones known as chondrodysplasia punctata.[5] Almost 6% of babies born to mothers treated with warfarin during the first trimester have a pattern of congenital anomalies like nasal hypoplasia and stippling of vertebrae or bony epiphyses.[6] So, warfarin is contraindicated during pregnancy.&#x0D; Here we present a case of foetal embryopathy due to warfarin use in a female with an unplanned pregnancy while taking warfarin for cerebral venous thrombosis. This form of stroke is relatively rare and underdiagnosed which accounts for 0.5%-1% of all strokes mostly occurring in young adults, especially in women. Pregnancy, use of oral contraceptive pills (OCPs), puerperium, malignancies and other conditions with hypercoagulable states have been recognised as predisposing risk factors.[7] The conventional therapy for venous thromboembolism includes treatment with parenteral low-molecular-weight heparin (LMWH) and the vitamin K antagonist warfarin.[7]

Safety and efficacy of apixaban vs. enoxaparin in thromboprophylaxis after spinal stenosis and degenerative spine surgery

IntroductionDegenerative spine surgeries often require postoperative immobilization or reduced mobility, predisposing patients to the formation of thrombosis and higher risk of thromboembolic complications. Despite the significance of this issue, there remains a lack of consensus on the optimal anticoagulant agent for postoperative thromboprophylaxis in spinal stenosis and degenerative spine surgeries. Low molecular weight heparins and direct Xa inhibitors represent two anticoagulant groups with high chemoprophylactic potential. MethodsThis study included a prospective cohort of patients undergoing posterior decompressive surgery with or without instrumentation for degenerative spine disease and/or spinal stenosis. Patients receiving postoperative prophylactic Enoxaparin and Apixaban were selected to evaluate the rate of complications, as assessed by Clavien-Dindo classification, thromboembolic events, and 30-day mortality, readmission, and reoperation rate between the two anticoagulants. Results130 patients were included in the analysis. 65 patients received Apixaban and Enoxaparin in each group. Mean age of the participants was 57.6±11.0. 83.1% underwent laminectomy and posterior spinal fusion, while 22 patients underwent decompressive surgery only. The incidence of venous thromboembolism (P-value=0.403), deep vein thrombosis (p-value=0.999), hematoma formation (p-value=0.403), surgical site infection (p-value=0.901), readmission (p-value=0.545), reoperation (p=0.510), mortality (p=0.648), and complications rate (p-value=0.232) were not statistically different between Enoxaparin and Apixaban. DiscussionBoth Apixaban and Enoxaparin may be viable options for postoperative thromboprophylaxis in spine surgeries with comparable efficacy and safety profile. Future research endeavors should investigate the efficacy of these agents in comparison to placebo in a randomized setting.

Аналіз перинатальних наслідків у жінок із загрозою невиношування вагітності в першому триместрі залежно від факту утворення ретрохоріальної гематоми

Purpose - to evaluate the effectiveness of the developed personalized approach to the management of patients with a threat of miscarriage in the first trimester depending on the fact of the formation of a retrochorial hematoma (RCH) in order to prevent the occurrence of preeclampsia (PE) in them. Materials and methods. A prospective analysis of the course of pregnancy and childbirth was conducted in 137 women with a threat of pregnancy aged from 20 to 47 years (the Group I - 60 patients with RCH, the Group II - 77 patients with a threat of termination of pregnancy without hematoma). Bibliosemantic analysis was used in the study; estimated anthropometric data; an enzyme-linked immunosorbent assay was performed to study hormone levels; polymerase chain reaction was used to determine polymorphisms of thrombophilia and angiogenesis genes; instrumental - to assess the condition of the fetus (ultrasound diagnosis of the fetus with Doppler blood flow of the umbilical artery, uterine arteries, middle cerebral arteries, non-stress test). Results. The average age of women of the Group I was 31.2±0.6 (95% CI: 30.0-32.4) years, of the Group II - 32.2±0.6 (95% CI: 31.0-33.3) of the year (p=0.243 according to the t-criterion). According to the Alberta Perinatal Health Program (APHP) adapted perinatal risk scale, 21 (35.0%) and 36 (46.7%) patients were assigned to the low perinatal risk group, respectively, and 30 (50.0%) medium risk) and 32 (41.5%) women, and to the high-risk group - 9 (15.0%) and 9 (11.7%) at p&gt;0.05. During the treatment and observation of women with a threat of miscarriage in the first trimester, the developed treatment algorithm was followed: stabilization of the hematoma, reduction of myometrial tone, hormonal support of pregnancy with further determination of the need for the use, dose and duration of low-molecular-weight heparin (LMWH) in combination with aspirin. Differences between the Groups I and II revealed by means of a comparative analysis made it possible to outline the clinical and anamnestic factors that can serve as predictors of the development of PE in women with RCH. Conclusions. The occurrence of RCH at the stage of early placentation increases the risks of developing placental dysfunction and obstetric complications related to it. The early appointment of aspirin (up to 12 weeks) in women with a high risk of developing PE allows to reduce the synthesis of platelets and thromboxane while preserving the synthesis of prostacyclin in the vascular wall in the initial stages of placentation. The combination of aspirin with the use of LMWH in women with the presence of genetic polymorphisms of candidate genes for thrombophilia and angiogenesis prevents the delay in the onset of uteroplacental circulation and promotes full placentation. A personalised approach to the management of pregnancy in women with a threat of termination due to the formation of RCH in the first trimester of pregnancy has made it possible to improve perinatal outcomes in the management of this category of pregnant women. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

Comparative Analysis of Antithrombotic Therapy Outcomes in Mild Traumatic Brain-Injury Patients: A Focus on Bleeding Risk and Hospital-Stay Duration.

Traumatic brain injury (TBI) in the elderly is a noteworthy pathology due to the exponential increase in population age, and the effects of antiplatelet and anticoagulation on patients' outcomes are still a matter of dispute. The aim of the present study was to evaluate the impact of various antithrombotic agents on patients with mild TBI, focusing on the risk of intracranial bleeding (ICH) and length of hospitalization (LOS). A retrospective analysis was conducted, including patients with a diagnosis of TBI admitted to the Emergency Department between 2021 and 2022. Patients were classified according to the concurrent antithrombotic therapy as aspirin (ASA), antiplatelets, direct oral anticoagulants (DOACs), and low-molecular-weight heparin (LMWH). The primary outcome was the ICH occurrence, while the secondary outcome was the LOS. The statistical analysis was performed via logistic regression models in R and STATA 13.1 software. Fisher's exact test was used for the statistical significance. 267 patients with mild TBI were included; 148 were not on antithrombotic agents, 43 were on aspirin, 33 on DOACs, 5 on LMWH, 22 on antiplatelets, and 16 on VKA. Out of the total, 9 patients experienced ICH, none of which were on DOACs, LMWH, or VKA, but 4-out of 65-were on antiplatelets, and 5-out of 148-were not on antithrombotic therapies. Patients not on antithrombotic therapy had the shortest LOS at 0.46 days, while those on VKA had the longest LOS at 1.19 days; similar trends were observed for patients on DOAC and LMWH. The results reveal that TBI patients on anticoagulants/antiplatelets had longer hospital stays compared with those on aspirin alone. Notably, VKA was the strongest predictor for an extended LOS. Regarding ICH, patients taking only aspirin were twice as likely to experience bleeding compared with those on anticoagulants/antiplatelets. However, to achieve statistically significant evidence, further research with a larger cohort of patients is needed.

[Venous thromboembolism - was is new in the revised AWMF guideline?]

For the diagnosis of a lower-extremity deep vein thrombosis (LEDVT), venous duplex ultrasound is the method of first choice. If a qualified ultrasonography is not timely available, D-dimer testing, and limited ultrasound protocols (point-of-care ultrasound, POCUS) can contribute to therapeutic decision-making when clinical probability is low. A DOAC-based treatment regimen is preferable to a vitamin K antagonist for both acute therapy and secondary prophylaxis of venous thromboembolism (VTE). Treatment with DOACs is unproblematic up to a body weight (BW) of 120 kg or a body mass index (BMI) of 40 kg/m². Weight restrictions are no longer recommended for apixaban and rivaroxaban, but determination of DOAC trough and peak levels is recommended in the extremely obese and patients after bariatric surgery. In cancer-associated VTE, the direct factor Xa inhibitors are a good and safe alternative to low-molecular weight heparins (LMWH) for many patients; the adherence to oral therapy is also higher. Meaningful initial documentation and structured follow-up after LEDVT and pulmonary embolism (PE) are important in order to make an individualized risk-benefit assessment at the end of the therapy phase with regard to continued pharmacological secondary prophylaxis and to reassess patients' symptoms indicating post-thrombotic syndrome (PTS) or chronic thromboembolic pulmonary hypertension (CTEPH).

Efficacy and safety of direct oral anticoagulants versus low-molecular-weight heparin for thromboprophylaxis after cancer surgery: a systematic review and meta-analysis.

Direct oral anticoagulants (DOACs) used as an alternative to low-molecular-weight heparin (LMWH) for thromboprophylaxis after cancer surgery for venous thromboembolic events (VTE) remains unclear. This study aimed to investigate the efficacy and safety of DOACs versus LMWH in these patients. A search of EMBASE, MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science was carried out and included all randomized controlled trials (RCTs) and observational studies that directly compared DOACs with LMWH for thromboprophylaxis in patients after cancer surgery through July 25, 2023. The primary efficacy and safety outcomes were VTE, major bleeding, and clinically relevant non-major bleeding (CRNMB) within 30days of surgery. The risk of bias was assessed using the Cochrane Risk of Bias 2 (RoB2) tool for RCTs and ROBINS-I tool for non-randomized studies. This study was registered in PROSPERO (CRD42023445386). We retrieved 5149articles, selected 27 for eligibility, and included 10 studies (three RCTs and seven observational studies) encompassing 3054 patients who underwent postoperative thromboprophylaxis with DOACs (41%) or LMWH (59%). Compared to LMWH thromboprophylaxis, DOACs had a comparable risk of VTE (RR:0.69[95% CI:0.46-1.02], I2 = 0%), major bleeding (RR:1.55 [95% CI:0.82-2.93], I2 = 2%), and CRNMB (RR, 0.89 [95% CI, 0.4-1.98], I2 = 31%) during the 30-day postoperative period. Subgroup analysis of VTE and major bleeding suggested no differences according to study type, extended thromboprophylaxis, tumor types, or different types of DOAC. DOACs are potentially effective alternatives to LMWH for thromboprophylaxis in patients undergoing cancer surgery, without increasing the risk of major bleeding events.

Caltrop-like Small-Molecule Antidotes That Neutralize Unfractionated Heparin and Low-Molecular-Weight Heparin In Vivo.

Unfractionated heparin (UFH) and low-molecular-weight heparins (LMWHs) are widely applied for surgical procedures and extracorporeal therapies, which, however, suffer bleeding risk. Protamine, the only clinically approved antidote, can completely neutralize UFH, but only partially neutralizes LMWHs, and also has a number of safety drawbacks. Here, we show that caltrop-like multicationic small molecules can completely neutralize both UFH and LMWHs. In vitro and ex vivo assays with plasma and whole blood and in vivo assays with mice and rats support that the lead compound is not only superior to protamine by displaying higher neutralization activity and broader therapeutic windows but also biocompatible. The effective neutralization dose and the maximum tolerated dose of the lead compound are determined to be 0.4 and 25 mg/kg in mice, respectively, suggesting good promise for further preclinical studies.