Establishment of a swine model of delayed bleeding after endoscopic procedure.

Objectives: Although delayed bleeding after endoscopic procedures has become a problem, currently, there are no appropriate animal models to validate methods for preventing it. This study aimed to establish an animal model of delayed bleeding after endoscopic procedures of the gastrointestinal tract. Methods: Activated coagulation time (ACT) was measured using blood samples drawn from a catheter inserted into the external jugular vein of swine (n = 7; age, 6 months; mean weight, 13.8 kg) under general anesthesia using the cut-down method. An upper gastrointestinal endoscope was inserted orally, and 12 mucosal defects were created in the stomach by endoscopic mucosal resection using a ligating device. Hemostasis was confirmed at this time point. The heparin group (n = 4) received 50 units/kg of unfractionated heparin via a catheter; after confirming that the ACT was ≥200 s 10 min later, continuous heparin administration (50 units/kg/h) was started. After 24 h, an endoscope was inserted under general anesthesia to evaluate the blood volume in the stomach and the degree of blood adherence at the site of the mucosal defect. Results: Delayed bleeding was observed in three swine (75%) in the heparin-treated group, who had a maximum ACT of >220 s before the start of continuous heparin administration. In the non-treated group (n = 3), no prolonged ACT or delayed bleeding was observed at 24 h. Conclusion: An animal model of delayed bleeding after an endoscopic procedure in the gastrointestinal tract was established using a single dose of heparin and continuous heparin administration after confirming an ACT of 220 s.

Retrospective Study of the Use of Heparins in Pregnant Women and in vitro Testing on the HCT 116 Colorectal Carcinoma Cell Line.

Introduction: Pregnant women manifest an increased risk of developing coagulation disorders. Unfractionated heparin (HEP) and low-molecular-weight heparin (LMWHep) are considered as selective medication in the case of pregnancy which needs anticoagulant treatment. In addition to anticoagulant properties, HEP and its derivatives manifest other properties including anti-cancer potential. According to Globocan's latest data, colorectal cancer (CRC) is the second most encountered form of malignancy in the case of women, manifesting some special particularities, as confusion of symptoms from cancer with symptoms encountered normally in pregnant women (such as constipation or rectal bleeding), delayed diagnosis because of limitations imposed both for the fetus and for the mother, and the need for special treatment. Aim: The aim of the present work is to follow the incidence and safety of consumption of HEP and LMWHep in the case of pregnant women and to analyze their potential on the HCT 116 colorectal carcinoma cells. Results: Analyzing the consumption of heparins in case of pregnant women hospitalized from 01.01.2022 to 31.12.2022 at the Pius Brînzeu" Emergency Clinical Hospital from Timisoara, Obstetrics and Gynecology Clinic I, it was observed that 44,6% of the patients were administered the following medication and no administration risks were observed. When tested on HCT 116 cells, heparins manifested a significant anti-migratory effect (with wound healing rates of 2,6%, when tested with HEP 100 UI concentration and 14.52% wound healing rates in case of fraxiparine 100 UI). In addition, different signs of apoptosis were observed, suggesting the pro-apoptotic potential of the tested substances. Conclusions: Heparins remain the preferred medication to be administered to pregnant women with the potential for coagulation disorders, showing a high safety profile. Testing on the cancerous line of colorectal carcinoma highlights important properties that stimulate future studies, to establish the anti-tumor potential and the exact mechanism of action.

Effect of bivalirudin on myocardial microcirculation and adverse events after interventional therapy in older patients with acute coronary syndrome.

BACKGROUND: Bivalirudin, a direct thrombin inhibitor, is used in anticoagulation therapies as a substitute for heparin, especially during cardiovascular procedures such as percutaneous coronary intervention. AIM: To explore the effect of bivalirudin on myocardial microcirculation following an intervention and its influence on adverse cardiac events in elderly patients with acute coronary syndrome (ACS). METHODS: In total, 165 patients diagnosed with acute myocardial at our hospital between June 2020 and June 2022 were enrolled in this study. From June 2020 to June 2022, elderly patients with ACS with complete data were selected and treated with interventional therapy. The study cohort was randomly divided into a study group (n = 80, administered bivalirudin) and a control group (n = 85, administered unfractionated heparin). Over a 6-mo follow-up period, differences in emergency processing times, including coronary intervention, cardiac function indicators, occurrence of cardiovascular events, and recurrence rates, were analyzed. RESULTS: Significant differences were observed between the study cohorts, with the observation group showing shorter emergency process times across all stages: Emergency classification; diagnostic testing; implementation of coronary intervention; and conclusion of emergency treatment (P < 0.05). Furthermore, the left ventricular ejection fraction in the observation group was significantly higher (P < 0.05), and the creatine kinase-MB and New York Heart Association scores were notably lower than those in the control group (P < 0.05). CONCLUSION: In elderly patients receiving interventional therapy for ACS, bivalirudin administration led to increased activated clotting time achievement rates, enhanced myocardial reperfusion, and reduced incidence of bleeding complications and adverse cardiac events.

Apixaban versus low molecular weight heparin in patients with cancer-associated venous thromboembolism: a systematic review and meta-analysis.

Background: The optimal treatment regimen for patients with cancer-associated venous thromboembolism (CA-VTE) remains unclear. Therefore, the authors sought to compare the outcomes of (VKAs) versus direct apixaban and low molecular weight heparin (LMWH) in patients with CA-VTE. Methods: MEDLINE, Embase, and Cochrane Central databases were searched for randomized controlled trials (RCTs) and observational studies comparing the efficacy and safety of apixaban and LMWH in patients with CA-VTE. Major bleeding, clinically relevant non-major bleeding (CRNMB), recurrence of pulmonary embolism (PE), deep venous thrombosis (DVT) and bleeding-related mortality were among outcomes of interest. Mantel-Haenszel weighted random-effects model was used to calculate relative risks (RRs) with 95% CIs. Results: The analysis included 12 011 patients from 3 RCTs and 2 observational studies. Compared to LMWH, apixaban significantly decreased the risk of major bleeding [RR 0.67 (95% CI 0.54, 0.83); P=0.0003, I2=0%] without significantly changing the risk of clinically relevant non-major bleeding [RR 0.96 (95% CI 0.64, 0.1.45); P=0.85, I2=57%]. Patients on apixaban had a noticeably reduced the risk of recurrence of PE than those taking LMWH, according to a meta-analysis [RR 0.56 (95% CI 0.32, 0.99); P=0.05, I2=0%]. There was no discernible difference between apixaban and LMWH in bleeding-related mortality events [RR 0.20 (95% CI 0.01, 4.18); P=0.30, I2=NA%], and recurrence of DVT [RR 0.60 (95% CI 0.22, 1.59); P=0.23, I2=32%]. Conclusion: Due to its lower risk of severe bleeding and reduced PE recurrence, apixaban may be a preferable treatment option for CA-VTE, but additional research is required to validate these conclusions and evaluate its long-term efficacy and safety.

Treatment of Superficial Vein Thrombosis: Recent Advances, Unmet Needs and Future Directions.

Once considered relatively benign, superficial vein thrombosis (SVT) of the lower limbs is linked to deep vein thrombosis (DVT) or pulmonary embolism (PE) in up to one fourth of cases. Treatment goals include alleviating local symptoms and preventing SVT from recurring or extending into DVT or PE. Fondaparinux 2.5 mg once daily for 45 days is the treatment of choice for most patients with SVT. Potential alternatives include intermediate-dose low-molecular-weight heparin or the direct oral factor Xa inhibitor rivaroxaban, however, these require further evidence. Despite these treatment options, significant gaps remain, including the role of systemic or topical anti-inflammatory agents alone or combined with anticoagulants, and the optimal duration of anticoagulation for patients at varying risk levels. Additionally, the efficacy and safety of factor Xa inhibitors other than rivaroxaban, management of upper extremity SVT, and optimal treatment for SVT near the sapheno-femoral or sapheno-popliteal junctions are not well understood. This narrative review aims to summarize current evidence on anticoagulant treatment for SVT, highlight key unmet needs in current approaches, and discuss how ongoing studies may address these gaps.

Butyrate Increases Heparin Synthesis and Storage in Human Mast Cells.

Sulphated glycosaminoglycans (GAGs) such as heparin are a major component of mast cell granules and form the matrix within which biogenic mediators are stored. Since GAGs released from mast cells also play an important role in helminth expulsion, understanding GAG storage can offer new insights into mast cell function. Sodium butyrate (NaBu), a short-chain fatty acid, causes ultrastructural changes within the granules of human mast cells (HMC-1) and increases their histamine content. Therefore, we hypothesized that NaBu treatment would also modify the storage of polysaccharides such as GAGs. NaBu (1 mM) significantly increased GAG content and granularity in a time- and concentration-dependent manner without affecting cell viability and metabolic activity. NaBu increased the expression of enzymes associated with heparin biosynthesis (GLCE, NDST1, NDST2, HS6ST1, and GALT1) in a time-dependent manner. A cholesteryl butyrate emulsion (CholButE) increased heparin content after 24 and 48 h and modestly altered the expression of genes involved in heparin biosynthesis. Similar to NaBu, CholButE reduced cell proliferation without significantly altering viability or metabolic activity. These data show that butyrate increases the synthesis and storage of heparin in human mast cells, perhaps by altering their metabolic pathways.

Intravenous injection of nattokinase-heparin electrostatic complex improves the therapeutic effect of advanced tumors by dissolving cancer-related thrombosis.

AIMS: Cancer-related thrombosis (CAT) is a common complication in cancer patients, significantly impacting their quality of life and survival prospects. Nattokinase (NK) has potent thrombolytic properties, however, its efficacy is limited by low oral bioavailability and the risk of severe allergic reactions with intravenous use. Heparin (HP) is a widely used anticoagulant in clinical settings. This study aimed to overcome the intravenous toxicity of NK and explore its effect on CAT in advanced tumors. MAIN METHODS: In this study, NK-HP electrostatic complexes were constructed, and their safety and thrombolytic efficacy were verified through guinea pig allergy tests, mouse tail vein tests, and both in vivo and in vitro thrombolysis experiments. Additionally, an S180 advanced tumor model was developed and combined with sialic acid-modified doxorubicin liposomes (DOX-SAL) to investigate the impact of NK-HP on CAT and its antitumor effects in advanced tumors. KEY FINDINGS: We observed that NK-HP can eliminate the intravenous injection toxicity of NK, has strong thrombolytic performance, and can prevent thrombosis formation. Intravenous injection of NK-HP can enhance the antitumor effect of DOX-SAL by reducing the fibrin content in advanced tumors and increasing the levels of the cross-linked protein degradation product D-dimer. SIGNIFICANCE: This study developed a method to eliminate the intravenous injection toxicity of NK, proposing a promising therapeutic strategy for CAT treatment, particularly for CAT in advanced tumors, and improving the efficacy of nano-formulations in anti-tumor therapy.

Relation between antithrombin-III activity and activated clotting time for cardiopulmonary bypass.

Heparin resistance (HR) is observed before cardiopulmonary bypass (CPB), despite with normal antithrombin III (AT-III) levels. The relationships between preoperative AT-III activity and activated clotting time (ACT) after the first heparin dose should be clarified. We retrospectively analyzed the data of 818 patients who underwent CPB surgery, with the initial heparin of 300, 400, and 500 IU/kg, between 2017 and 2021. We defined HR as the failure to achieve ACT after the initial heparin dose (Post ACT) of > 480 s.There were no significant correlations between the AT-III activity and Post ACT in all patients, including 143 patients with AT-III activity < 80% and 675 patients with AT-III activity of ≥ 80%. Also, there were no significant correlations between the AT-III activity and Post ACT in 74 patients who received heparin of 300 IU/kg, in 186 patients with 400 IU/kg, and in 339 patients with 500 IU/kg. After identifying smoking, HR, activated partial thromboplastin time, fibrinogen degradation products (FDP), and ACT as influencing factors, multiple comparisons using the Steel-Dwass test showed significant difference in FDP and HR among the patients who received heparin of 300 IU/kg, 400 IU/kg, and 500 IU/kg. There is no association between preoperative AT-III activity and ACT after the first heparin administration for CPB, even in different dose of heparin. Rather, the higher the initial UFH dose is, the higher ACT may be, regardless of the AT-III activity.

Pre-hospital heparin is not associated with infarct vessel patency and mortality in ST-segment elevation myocardial infarction patients with out-of-hospital cardiac arrest.

BACKGROUND: Pre-hospital heparin administration has been reported to improve prognosis in patients with out-of-hospital cardiac arrest (OHCA). This beneficial effect may be limited to the subgroup of ST-segment elevation myocardial infarction (STEMI) patients. METHODS: To assess the impact of pre-hospital heparin loading on TIMI (Thrombolysis in Myocardial Infarction) flow grade and mortality in STEMI patients with OHCA, we analyzed data from 2,566 consecutive patients from two hospitals participating in the prospective Feedback Intervention and Treatment Times in ST-segment Elevation Myocardial Infarction (FITT-STEMI) trial. RESULTS: In 394 participants with OHCA, 272 (69%) received heparin from the emergency medical service (EMS). Collapse witnessed by EMS (odds ratio (OR) = 3.53, 95%-confidence interval (CI) = 1.54-8.09; p = 0.003) and pre-hospital ECG recording (OR = 3.32, 95% CI = 1.06-10.35; p = 0.039) were identified as parameters significantly associated with pre-hospital heparin use. In univariate analysis, in-hospital mortality was lower in the group receiving heparin in the pre-hospital setting (26.8% vs. 42.6%, p = 0.002). However, in a regression model, pre-hospital heparin use was no longer a significant predictor of mortality (OR = 0.992; p = 0.981). Patency of the infarct artery prior to coronary revascularization, as measured by TIMI flow grade, was not associated with pre-hospital administration of heparin in OHCA patients (OR = 0.840; p = 0.724). CONCLUSIONS: In STEMI patients with OHCA, pre-hospital use of heparin is neither associated with improved early patency of the infarct artery nor with a better prognosis. Our results do not support the assumption of a positive effect of heparin administration in the pre-hospital treatment phase in STEMI patients with OHCA. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00794001.

Heparin Induced Thrombocytopenia Testing.

This article provides a comprehensive overview of Heparin-Induced Thrombocytopenia (HIT) with an emphasis on laboratory testing and advantages of automation. HIT is a critical condition arising from heparin exposure, leading to a contradictory combination of thrombocytopenia with an increased thrombosis risk. The article discusses HIT's history, clinical presentation, laboratory diagnosis, and management strategies. It highlights the importance of interdisciplinary collaboration for effective diagnosis and treatment, underscoring advancements in technology and targeted therapies that are shaping future approaches to HIT management.

Pre-hospital admission of heparin in patients with suspected non-ST segment elevation acute coronary syndrome.

BACKGROUND: Evidence supporting pre-hospital heparin administration in patients with suspected non-ST segment elevation acute coronary syndrome (NSTE-ACS) is lacking. We aim to evaluate if pre-hospital heparin administration by emergency medical service improves clinical outcome in patients with suspected NSTE-ACS. METHODS: Patients with suspected myocardial infarction (MI) presenting to the emergency department were prospectively enrolled from 2013 to 2021, excluding those with ST segment elevation MI. Patients with and without prehospital heparin administration were compared using propensity score matching. To assess the association between pre-hospital heparin loading, 30-day and 1-year mortality, Kaplan-Meier estimations and Cox regression models were used. RESULTS: Among 1,234 patients, median age was 69 years, 755 (61.2%) were male, 867 (70.5%) with known hypertension, 177 (14.4%) had diabetes, 280 (23.1%) were current smokers, and 444 (36.0%) had a history of CAD. Compared to patients without pre-hospital heparin administration, heparin pre-treated patients were more often active smokers (26.5% vs. 20.8%). After propensity matching, 475 patients with vs. without pre-hospital heparin administration were compared, with no significant difference in 30-day mortality (no-heparin 1.3% vs. heparin 0.4%) and 1-year mortality (no-heparin 7.2% vs. heparin 5.5%, adjusted HR 0.98, CI 0.95-1.01, p = 0.22). Bleeding events occurred at a low frequency (< 2%) and did not differ between groups. CONCLUSIONS: In this study, pre-hospital heparin administration was not associated with improved clinical outcome in patients with suspected NSTE-ACS. These findings question pre-hospital heparin therapy in this patient population and might potentially warrant a more restricted utilization pending in-hospital risk assessment.

Alpha-Gal Syndrome and Cardiac Surgery.

Galactose-alpha-1,3-galactose (alpha-gal) is a carbohydrate expressed by all mammals except for humans and certain old-world primates. It can be found in a plethora of products derived from mammals, including milk, organs, skeletal muscle and gelatin, in addition to products prepared with mammalian cells or constituents. In the late 2000s, an association between tick bites and the development of immunoglobulin E antibodies to the alpha-gal carbohydrate was discovered. The term "alpha-gal syndrome" (AGS) was then coined to describe allergic reactions to mammalian meat or other alpha-gal-containing products derived from mammals. Symptoms are often delayed several hours from consumption and can be urticarial and/or gastrointestinal. Medications and bioprosthetic inserts derived from mammals were also noted to cause allergic reactions in affected patients. Cardiac surgery, in particular, is considered high risk, given that unfractionated heparin has a bovine or porcine origin and is administered in large doses for cardiopulmonary bypass. Bioprosthetic valves have similar origins and risks. Awareness of AGS in cardiac surgery patients can lead to decreased risk preoperatively and inform management perioperatively and postoperatively. In this narrative review, we have reviewed the published literature relevant to AGS in patients undergoing cardiac surgery and shared our treatment approach.

Oleanolic acid derivative self-assembled aggregates based on heparin and chitosan for breast cancer therapy.

Oleanolic acid is an active ingredient from natural products with anti-breast cancer activity. However, the poor solubility in water and low bioavailability have limited its effectiveness in clinic. To improve the anticancer activity of oleanolic acid, we synthesized a novel oleanolic quaternary ammonium (QDT), which, driven by electrostatic interactions, was introduced into heparin and coated with chitosan to obtain a QDT/heparin/chitosan nanoaggregate (QDT/HEP/CS NAs). QDT/HEP/CS NAs showed the negative zeta potential (-35.01 ± 4.38 mV), suitable mean particle size (150.45 ± 0.68 nm) with strip shape, and high drug loading (36 %). The coated chitosan had strong anti-leakage characteristics toward QDT under physiological conditions. More importantly, upon sustained release in tumor cells, QDT could significantly decrease the mitochondrial membrane potential and induce apoptosis of breast cancer cells. Further in vivo antitumor study on 4 T1 tumor-bearing mice confirmed the enhanced anticancer efficacy of QDT/HEP/CS NAs via upregulation of caspase-3, caspase-9 and cytochrome C, which was attributed to the high accumulation in tumor via the enhanced permeability and retention effect. Moreover, QDT/HEP/CS NAs significantly enhanced the biosafety and biocompatibility of QDT in vitro and in vivo. Collectively, the development of QDT/HEP/CS NAs with high antitumor activity, favorable biodistribution and good biocompatibility provided a safe, facile and promising strategy to improve the anti-cancer effect of traditional Chinese medicine ingredients.

An endothelium membrane mimetic antithrombotic coating enables safer and longer extracorporeal membrane oxygenation application.

Thrombosis and plasma leakage are two of the most frequent dysfunctions of polypropylene (PP) hollow fiber membrane (PPM) used in extracorporeal membrane oxygenation (ECMO) therapy. In this study, a superhydrophilic endothelial membrane mimetic coating (SEMMC) was constructed on polydopamine-polyethyleneimine pre-coated surfaces of the PPM oxygenator and its ECMO circuit to explore safer and more sustainable ECMO strategy. The SEMMC is fabricated by multi-point anchoring of a phosphorylcholine and carboxyl side chained copolymer (PMPCC) and grafting of heparin (Hep) to form PMPCC-Hep interface, which endows the membrane superior hemocompatibility and anticoagulation performances. Furthermore, the modified PPM reduces protein adsorption amount to less than 30 ng/cm2. More significantly, the PMPCC-Hep coated ECMO system extends the anti-leakage and non-clotting oxygenation period to more than 15 h in anticoagulant-free animal extracorporeal circulation, much better than the bare and conventional Hep coated ECMO systems with severe clots and plasma leakage in 4 h and 8 h, respectively. This SEMMC strategy of grafting bioactive heparin onto bioinert zwitterionic copolymer interface has great potential in developing safer and longer anticoagulant-free ECMO systems. STATEMENT OF SIGNIFICANCE: A superhydrophilic endothelial membrane mimetic coating was constructed on surfaces of polypropylene hollow fiber membrane (PPM) oxygenator and its ECMO circuit by multi-point anchoring of a phosphorylcholine and carboxyl side chain copolymer (PMPCC) and grafting of heparin (Hep). The strong antifouling nature of the PMPCC-Hep coating resists the adsorption of plasma bio-molecules, resulting in enhanced hemocompatibility and anti-leakage ability. The grafted heparin on the zwitterionic PMPCC interface exhibits superior anticoagulation property. More significantly, the PMPCC-Hep coating achieves an extracorporeal circulation in a pig model for at least 15 h without any systemic anticoagulant. This endothelial membrane mimetic anticoagulation strategy shows great potential for the development of safer and longer anticoagulant-free ECMO systems.

Antiphospholipid Syndrome Nephropathy Occurs in Pregnancy: A Case Report.

OBJECTIVE: This paper presents an analysis of the pregnancy trajectory and therapeutic regimen documentation of a primigravida with APSN. It aims at communicating the therapeutic approach and preventive measures for APSN in pregnancy. CASE PRESENTATION: This paper reports the trajectory and therapeutic regimen documentation of a primigravida with APSN. The APSN was discovered in a primigravida woman aged 26 years at 11 weeks of gestation. The initial therapy regimen consists of daily administration of prednisone 10 mg, hydroxychloroquine 200 mg, dapparin 5000 IU, and aspirin 50 mg. At a gestational age of 20 + 3 weeks, the dosage of dapparin was modified to 5000 IU/other day, along with a significant rise in urinary protein level seen at 30 + 3 weeks of gestational age. The initial dosage of dapanin sodium was renewed. The patient delivered at 38 + 3 weeks of gestation without other complications. CONCLUSION: It is imperative to acknowledge that altering the dosage and administration of medication should not be done haphazardly during pregnancy.

Identification of small molecule antagonists of sonic hedgehog/heparin binding with activity in hedgehog functional assays.

Sonic hedgehog (Shh) is a morphogen with important roles in embryonic development and in the development of a number of cancers. Its activity is modulated by interactions with binding partners and co-receptors including heparin and heparin sulfate proteoglycans (HSPG). To identify antagonists of Shh/heparin binding, a diverse collection of 34,560 chemicals was screened in single point 384-well format. We identified and confirmed twenty six novel small molecule antagonists with diverse structures including four scaffolds that gave rise to multiple hits. Nineteen of the confirmed hits blocked binding of the N-terminal fragment of Shh (ShhN) to heparin with IC50 values <50 µM. In the Shh-responsive C3H10T1/2 cell model, four of the compounds demonstrated the ability to block ShhN-induced alkaline phosphatase activity. To demonstrate a direct and selective effect on ShhN ligand mediated activity, two of the compounds were able to block induction of Gli1 mRNA, a primary downstream marker for Shh signaling activity, in Shh-mediated but not Smoothened agonist (SAG)-mediated C3H10T1/2 cells. Direct binding of the two compounds to ShhN was confirmed by thermal shift assay and molecular docking simulations, with both compounds docking with the N-terminal heparin binding domain of Shh. Overall, our findings indicate that small molecule compounds that block ShhN binding to heparin and act to inhibit Shh mediated activity in vitro can be identified. We propose that the interaction between Shh and HSPGs provides a novel target for identifying small molecules that bind Shh, potentially leading to novel tool compounds to probe Shh ligand function.

Therapeutic Enoxaparin Dosing in Obesity.

OBJECTIVE: This review aims to systematically summarize the available data on efficacy and safety of therapeutic enoxaparin in obese patients and to identify gaps to guide future research. DATA SOURCES: Medline and Embase were systematically searched for eligible studies (last searched December 20, 2023). Studies were included if they reported on therapeutic dosing regimens, adverse bleeding, thrombotic outcomes, or antifactor Xa (AFXa) monitoring in obese adult patients. STUDY SELECTION AND DATA EXTRACTION: The systematic review management tool Covidence was used to manage the study selection and data extraction process. The reference list from eligible studies was screened to determine any additional eligible studies. DATA SYNTHESIS: Sixteen studies were included in the analysis. Studies used a variety of doses, indications, and study designs making comparison difficult. Twelve studies reported the incidence of thrombotic events (median = 1.3% [interquartile range [IQR] = 0.3%-2.3%]) and all studies reported the incidence of bleeding events (median = 5.7% [IQR = 2.4%-14.5%]). Two of the 8 studies analyzing the influence of weight/body mass index (BMI) or dose per kg on AFXa levels reported statistically significant results. One study concluded that BMI did not affect achievement of target AFXa levels. However, the second study found that dosing using actual body weight was an independent predictor of supratherapeutic AFXa levels in the obese population. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: This is the first comprehensive review with a focus on therapeutic dosing of enoxaparin in obesity and has been conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement. Seven of the included studies were published since 2018 indicating that new evidence on this topic is emerging. CONCLUSION: There was inadequate evidence to support an optimal dosing strategy in obese patients due to the heterogeneity of the studies. The AFXa monitoring may be appropriate to guide dosing in this population. Further research is required to determine a suitable dosing regimen.

Treating cancer-associated venous thromboembolism: A practical approach.

Venous thromboembolism (VTE) is a common and potentially life-threatening complication in patients with cancer. Both cancer and its treatments increase the risk of developing VTE. Specific cancer types and individual patient comorbidities increase the risk of developing cancer-associated VTE, and the risk of bleeding is increased with anticoagulation therapies. The aims of this article are to summarize the latest evidence for treating cancer-associated VTE, discuss the practical considerations involved, and share best practices for VTE treatment in patients with cancer. The article pays particular attention to challenging contexts including patients with brain, lung, gastrointestinal, and genitourinary tumors and those with hematological malignancies. Furthermore, the article summarizes specific clinical scenarios that require additional treatment considerations, including extremes of body weight, nausea and gastrointestinal disturbances, compromised renal function, and anemia, and touches upon the relevance of drug-drug interactions. Historically, vitamin K antagonists and low-molecular-weight heparins (LMWHs) have been used as therapy for cancer-associated VTE. The development of direct oral anticoagulants has provided additional treatment options, which, in certain instances, offer advantages over LMWHs. There are numerous factors that need to be considered when treating cancer-associated VTE, and although various treatment guidelines are helpful, they do not reflect each unique scenario that may arise in clinical practice. This article provides a summary of the latest evidence and a practical approach for treating cancer-associated VTE.

Tinzaparin, an alternative to subcutaneous unfractionated heparin, in patients with severe and end-stage renal impairment: a retrospective observational single-center study.

BACKGROUND: Tinzaparin could be easier to manage than unfractionated heparin in patients with severe renal impairment. However, clinical and pharmacologic data regarding its use in such patients are lacking. OBJECTIVES: The aims of this study were to determine, in patients with estimated glomerular filtration rate (eGFR) of <30 mL.min⁻1, tinzaparin pharmacokinetics (PK) parameters using a population PK approach and bleeding and thrombotic complications. METHODS: We performed a retrospective observational single-center study, including in-patients with eGFR of <30 mL.min⁻1 receiving prophylactic (4500 IU.d⁻1) or therapeutic (175 IU.kg⁻1.d⁻1) tinzaparin. Measured anti-Xa levels were analyzed using a nonlinear mixed-effects modeling approach. Individual predicted tinzaparin exposure markers at steady state were calculated for each patient and dosing regimen. The PK was also evaluated through Monte Carlo simulations based on the final covariate model parameter estimates. RESULTS: Over a 22-month period, 802 tinzaparin treatment periods in 623 patients were analyzed: two-thirds received a prophylactic dose, 66% had an eGFR of <20 mL.min⁻1, and 25% were on renal replacement therapy. In patients for whom anti-Xa measurements were performed (n = 199; 746 values), PK parameters, profiles, and maximum plasma concentrations were comparable with those in patients without renal impairment or in healthy volunteers. In the whole population, major bleeding occurred in 2.4% and 3.5% of patients receiving prophylactic and therapeutic doses over a median 9- and 7-day treatment period, respectively. No patients had thrombotic complications. CONCLUSION: Tinzaparin PK parameters and profiles were not affected by renal impairment. This suggests that tinzaparin, at therapeutic or prophylactic dose, could be an alternative to unfractionated heparin in hospitalized patients with severe renal impairment.