To Compare the Effectiveness of Low-Molecular-Weight Heparin and Unfractionated Heparin in Reducing Lower Limb Girth in Deep Vein Thrombosis.

INTRODUCTION: Treating deep vein thrombosis (DVT) using a once-daily dose of enoxaparin offers greater convenience and the possibility of home-based care for certain patients, as opposed to a continuous infusion of unfractionated heparin (UFH). The study aimed to determine the most cost-effective thromboprophylaxis between low-molecular-weight heparin (LMWH) and UFH for hospitalized patients. MATERIALS AND METHODS: After obtaining clearance from the institutional ethical committee, the study was conducted in the Department of General Surgery, Sri Devaraj Urs Medical College, over a period of six months. Informed consent was obtained from all 46 patients included in this study. The participants were divided into two groups: group A received LMWH and group B received UFH. RESULTS: The mean age in group A was 59.8 + 10.6 years and in group B was 54.9 + 12.3 years. There was no significant difference in the girth of the lower limb between the groups during the follow-up period (p > 0.05). In group A, there was a highly significant reduction in lower limb girth from day one to day five (p < 0.0001), day five to day 10 (p < 0.0001), and day one to day 10 (p < 0.0001). In group B, there was no significant reduction from day one to day five (p = 0.06), but there was a significant reduction from day five to day 10 (p = 0.001) and day one to day 10 (p = 0.001). CONCLUSION: Treatment with LMWH as an anticoagulant significantly reduced the lower extremity girth and thrombus thickness in cases of DVT when compared to UFH.

Triumph Over Adversity: A Comprehensive Case Series on Successful Pregnancy Outcomes in Antiphospholipid Antibody (APLA)-Positive Patients.

The intricate relationship between antiphospholipid antibody (APLA) syndrome and pregnancy outcomes challenges the prevailing notion of inevitable reproductive complications associated with APLA. The introduction provides a comprehensive overview of APLA, its autoimmune thrombophilic nature, and its common association with adverse pregnancy outcomes, emphasizing the need for a nuanced understanding. Here we discuss five case reports to showcase diverse scenarios, each highlighting successful pregnancies in APLA-positive patients, thereby contributing valuable insights into the management of this complex condition. The cases span various clinical presentations, patient demographics, and therapeutic approaches, emphasizing the heterogeneity of APLA-positive pregnancies and the importance of personalized care. The discussion delves into the broader context of APLA's impact on pregnancy, emphasizing recurrent miscarriage and venous thromboembolism (VTE) as severe complications. It underscores the significance of pre-conceptional counseling, a multidisciplinary approach, and regular antenatal monitoring in managing APLA-positive pregnancies. The identification of commonalities among the cases provides a basis for recognizing mitigating factors that contribute to positive outcomes, offering valuable guidance for healthcare providers. The series acknowledges the existence of catastrophic antiphospholipid syndrome (CAPS) and underscores the importance of early recognition and intervention in high-risk cases. Despite the challenges posed by APLA, the cases in the series offer a ray of hope by showcasing instances of successful pregnancies, attributing positive outcomes to optimized therapeutic interventions and vigilant antenatal care. In conclusion, the case series serves as a valuable resource for healthcare professionals, researchers, and policymakers, providing a nuanced perspective on APLA-positive pregnancies. By synthesizing diverse experiences and outcomes, the series contributes to the ongoing dialogue surrounding optimal management strategies, ultimately aiming to improve the quality of care for individuals facing the unique challenges posed by APLA during their reproductive journey.

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.

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.

Primary Thromboprophylaxis for the Prevention of Venous Thromboembolism in Cancer Patients with Central Venous Catheters: A Literature Review.

Cancer is a known risk factor for venous thromboembolism (VTE). The wider adoption of immunotherapy and anti-angiogenic drugs in recent years have increased this risk further. Central venous catheters (CVCs) are widely used access devices utilized to deliver infusion therapy, mostly in ambulatory settings. The endothelial injury associated with the use of these catheters adds to the risk of VTE to already high-risk patients. The introduction of direct oral anticoagulants (DOACs), with its proven efficacy and safety in multiple clinical indications, have renewed the attention to VTE prophylaxis in cancer patients with CVC. Several clinical trials and meta-analyses had shown that both apixaban and rivaroxaban are effective in lowering the risk of VTE, without increasing the risk of bleeding. Several risk assessment models (RAM) have utilized patient-related, tumor-related, and treatment-related factors, in addition to widely available biomarkers, like Hemoglobin (Hb) level, white blood cell (WBC) and platelets counts to stratify patients into two or three VTE risk levels. In this manuscript, we review the published clinical trials and meta-analyses that attempted to study the efficacy and safety of anticoagulants, mostly the DOACs, in cancer patients with CVCs. We will also propose a practical risk-directed approach to enhance VTE prophylaxis rate.

The safety and efficacy of NOACs versus LMWH for thromboprophylaxis after THA or TKA: A systemic review and meta-analysis.

The differences in the safety and efficacy of anticoagulation between different types of new oral anticoagulants(NOACs) and low molecular weight heparin(LMWH) are still controversial. The main purposes of this study were to analyze safety and efficacy of NOACs versus LMWH for thromboprophylaxis, and perform subgroup analyses stratified by individual NOACs and different populations after total hip arthroplasty (THA) or total knee arthroplasty (TKA). Literature search was performed in PubMed, EMBASE, Cochrane Library, CNKI and Wanfang databases until June 31, 2022. This systematic review and meta-analysis included 46 randomized controlled trials (RCT) with 39, 924 patients. We evaluated the safety and efficacy of thromboprophylaxis between LMWH and NOACs. NOACs were more effective in reducing deep vein thrombosis (DVT) (RR0.59; 95%CI 0.49-0.71) and adverse events (RR: 0.96; 95%CI: 0.93-0.99) than LMWH. The subgroup analyses for different anticoagulants revealed that rivaroxaban (RR:0.49; 95%CI:0.36-0.66), apixaban (RR: 0.54; 95%CI: 0.36-0.81) and edoxaban (RR:0.49; 95%CI: 0.32-0.75) have the lower risk of DVT than LMWH. Apixaban (RR:0.89; 95%CI: 0.80-1.00) had superior prevention of bleeding to LMWH. Edoxaban exhibited a lower risk of VTE (RR: 0.46; 95%CI: 0.33-0.65), advantage events (RR: 0.87; 95%CI: 0.82-0.93), and drug-related adverse events (DRAEs) (RR: 0.64; 95%CI: 0.53-0.76) than LMWH. East Asian population was superior to western population for preventing DVT, advantage events, and DRAE using NOACs. In conclusion, NOACs are more effective than LMWH at preventing DVT and adverse events after arthroplasty. Apixaban has lower bleeding than LMWH, and East Asian populations may benefit more than western population from NOACs.

Heparin-Induced Thrombocytopenia: A Case Report Four Years After the Initiation of Maintenance Hemodialysis.

Heparin-induced thrombocytopenia type II (HIT) is a rare and serious complication of heparin exposure and is always a potential risk in hemodialysis patients who routinely receive heparin. It is particularly likely to occur during the induction phase of dialysis. However, it is known to be less prevalent in long-term maintenance dialysis. In the present study, we experienced a maintenance dialysis patient who developed HIT four years after starting dialysis. After careful diagnosis with antibodies assay and clinical scores, the patient was treated with immediate heparin interruption, argatroban administration followed by nafamostat, and simple plasma exchange, which resulted in remission. Therefore, even in the maintenance phase of hemodialysis, it is important to consider HIT in the differential diagnosis of thrombocytopenia.

Large variation in anti-factor Xa levels with nadroparin as thromboprophylaxis in COVID-19 and non-COVID-19 critically ill patients.

PURPOSE: Critically ill COVID-19 and non-COVID-19 patients receive thromboprophylaxis with the LMWH nadroparin. Whether a standard dosage is adequate in attaining the target anti-FXa levels (0.20-0.50 IU/ml) in these groups is unknown. METHODS: This study was a prospective, observational study in the ICU of a large general teaching hospital in the Netherlands. COVID-19 and non-COVID-19 patients admitted to the ICU who received LMWH in a prophylactic dosage of 2850 IU, 5700 IU or 11400 IU subcutaneously were eligible for the study. Anti-FXa levels were determined 4 h after administration. Relevant laboratory parameters, prespecified co-variates and clinical data were extracted from the electronic health record system. The primary goal was to evaluate anti-FXa levels in critically ill patients on a prophylactic dosage of nadroparin. The second goal was to investigate whether covariates had an influence on anti-FXa levels. RESULTS: A total of 62 patients were included in the analysis. In the COVID-19 group and non-COVID-19 group, 29 (96%) and 12 patients (38%) reached anti-FXa levels above 0.20 IU/ml, respectively. In the non-COVID-19 group, 63% of the patients had anti-FXA levels below the target range. When adjusted for nadroparin dosage a significant relation was found between body weight and the anti-FXa level (p = 0.013). CONCLUSION: A standard nadroparin dosage of 2850 IU sc in the critically ill patient is not sufficient to attain target anti-FXa levels in the majority of the studied patient group. We suggest a standard higher dosage in combination with body-weight dependent dosing as it leads to better exposure to nadroparin. CLINICAL TRIALS REGISTRATION: Retrospectively registered, ClinicalTrials.gov ID NTC 05926518 g, date of registration 06/01/23, unique ID 2020/1725.

Anticoagulant prescribing patterns in patients with primary central nervous system malignancies and secondary metastases.

To evaluate the safety of direct oral anticoagulants (DOACs) versus low-molecular weight heparin (LMWH) in patients with central nervous system (CNS) malignancies and secondary metastases. All adult patients with CNS malignancies and secondary metastases who were treated with a DOAC or LMWH for any indication from 2018 to 2022 were included. The primary outcome was the incidence of any intracranial hemorrhage (ICH) after anticoagulation initiation. Secondary outcomes included non-ICH bleeding events and thromboembolic events. Tolerability was assessed by any changes in anticoagulant therapy during study period. 153 patients were included; 48 patients received enoxaparin and 105 received DOACs, of which apixaban was used most commonly. The population was predominantly White (74%) and male (59%) with a median age of 65. Data was censored for immortal time bias for outcomes evaluated beyond 3 months. ICH occurred in 7.7% of the population, more frequently in the enoxaparin group (DOACs 4, 4% vs. enoxaparin 7, 16%, p = 0.037). Non-ICH bleeds were predominantly minor and more common in the DOAC group (DOACs 13, 13% vs. enoxaparin 1, 2%, p = 0.037). Thromboembolic events were not different between groups (DOACs 9. 9% vs, enoxaparin 2, 4%, p = 0.503). Anticoagulant switches occurred more in the enoxaparin group (DOACs 12, 12.4% vs. enoxaparin, 37.8%, p < 0.001), primarily due to patient or provider preference. Our data supports DOACs to be preferred over LMWH for the treatment of VTE or for stroke prevention with AF to prevent ICH in patients with brain tumors or metastases.

Monitoring anti-Xa Levels to Optimize Low-Molecular-Weight-Heparin Thromboprophylaxis in High-Risk Hospitalized Patients: A Stratified Meta-Analysis.

It is uncertain whether monitoring or targeting anti-Xa levels is necessary when using low-molecular-weight-heparin (LMWH) to prevent venous thromboembolism (VTE). This stratified meta-analysis assessed whether monitoring trough or peak anti-Xa levels with LMWH dosing would reduce risk of VTE. Twelve non-randomized studies involving 3604 hospitalized patients met the inclusion criteria and were subject to meta-analysis. Eight studies assessed the association between VTE and peak anti-Xa levels (between .2 and .5 IU/ml) and four studies assessed the benefits of targeting the trough anti-Xa levels (>.1 IU/ml). Achieving an adequate peak or trough anti-Xa level was associated with a reduced risk of VTE (random-effects model odds ratio [OR] .52, 95% confidence interval [CI] .34-.77; P = .001, I2 = 30% and P-value for heterogeneity = .171) compared with using a fixed standard dose of LMWH. Targeting the trough level (OR .40, 95%CI 0.22-.75, P = .004) appeared to be more effective than targeting the peak level (OR .62, 95%CI 0.37-1.03, P = .066), although a formal interaction analysis did not confirm they were statistically different (ratio of ORs = 1.52, 95%CI 0.68-3.40; z score = 1.03, P = .306). Targeting a higher anti-Xa level did not appear to increase the risk of bleeding or transfusion (OR 1.20, 95%CI 0.46-3.17, P = .707).

Venous thromboembolism management in people with cystic fibrosis.

BACKGROUND: Rates of venous thromboembolism (VTE) are increasing in people with cystic fibrosis (PwCF). Providers treating VTE in PwCF have reported low confidence concerning anticoagulant drug selection, dose, duration, and drug-drug interactions. As there are currently no published reports regarding management of VTE in PwCF, our objective was to describe the management of VTE in PwCF. METHODS: PwCF and VTE at the University of Utah Health were identified through electronic medical record searches. Patients were categorized into one of three treatment groups: warfarin, direct oral anticoagulant (DOAC), and low molecular weight heparin (LMWH). The primary outcome was episodes of major bleeding. Secondary outcomes included clinically relevant nonmajor (CRNM) bleeding. RESULTS: Nine PwCF with a total of 12 unique VTE episodes were included in the study, with all but one episode associated with a peripherally inserted central catheter (PICC). Of the 12 VTE cases, 25% were treated with warfarin, 50% with a DOAC, and 25% with LMWH. There were no episodes of major bleeding and only one episode of CRNM bleeding (Hemoptysis) in the LMWH group. All anticoagulant doses and durations generally followed guidelines for persons without CF. DOACs were the most common VTE treatment, at doses and duration consistent with guidelines for persons without CF, with no major or CRNM bleeding. CONCLUSION: VTE treatment in PwCF is generally consistent with guidelines for persons without CF with low rates of bleeding. DOACs are a potential option for treatment of VTE in PwCF, but more research is needed.

Non-Vitamin K Antagonist Oral Anticoagulants versus Low Molecular Weight Heparin for Cancer-Related Venous Thromboembolic Events: Individual Patient Data Meta-Analysis.

Venous thromboembolism (VTE) is a leading cause of morbidity and mortality in cancer patients. Low molecular weight heparin (LMWH) has been the standard of care but new guidelines have approved the use of non-vitamin K antagonist oral anticoagulants (NOAC). By conducting an individual patient data (IPD) meta-analysis of randomised controlled trials (RCTs) comparing the outcomes of NOAC versus LMWH in cancer patients, we aim to determine an ideal strategy for the prophylaxis of VTE and prevention of VTE recurrence. Three databases were searched from inception until 19 October 2022. IPD was reconstructed from Kaplan-Meier curves. Shared frailty, stratified Cox and Royston-Parmar models were fit to compare the outcomes of venous thromboembolism recurrence and major bleeding. For studies without Kaplan-Meier curves, aggregate data meta-analysis was conducted using random-effects models. Eleven RCTs involving 4844 patients were included. Aggregate data meta-analysis showed that administering NOACs led to a significantly lower risk of recurrent VTE (RR = 0.65; 95%CI: 0.50-0.84) and deep vein thrombosis (DVT) (RR = 0.60; 95%CI: 0.40-0.90). In the IPD meta-analysis, NOAC when compared with LMWH has an HR of 0.65 (95%CI: 0.49-0.86) for VTE recurrence. Stratified Cox and Royston-Parmar models demonstrated similar results. In reducing risks of recurrent VTE and DVT among cancer patients, NOACs are superior to LMWHs without increased major bleeding.

Superior sagittal sinus thrombosis in the course of mixed phenotype acute leukaemia treated with acute lymphoblastic leukaemia-like therapy-a case report.

Mixed phenotype acute leukaemia (MPAL) is associated with worse overall survival, compared with other acute leukaemias in adults. Lack of clear treatment guidelines makes the therapy challenging. ALL-like induction and consolidation treatment followed by allo-HSCT is the preferred first-line treatment. We present a case of a 36-year-old woman diagnosed with MPAL (EGIL Myelo/B) with KMT2A rearrangement, treated with the PALG-ALL-7 (including PEG-asparaginase) protocol. On day 25 after the induction therapy initiation, numbness of limbs and dizziness were observed. Therefore, the imaging studies (CT and MRI) were performed and a diagnosis of thrombosis of superior sagittal sinus of the brain was established. Routinely performed blood coagulation tests showed prolonged APTT and PT, decreased antithrombin III activity and decreased free protein S concentration. LMWH treatment and substitutional therapy with antithrombin III were started, which resulted in a significant reduction in the thrombosis associated symptoms and improvement of the neurological status after 3 days. After induction and consolidation therapy, the patient obtained complete haematological remission and negative measurable residual disease. Six months after the diagnosis, allo-HSCT was successfully performed. During the 4 months follow-up, the patient remained MRD negative and thrombotic symptoms free. To the best of our knowledge, our communication has been the first report of such complication in an MPAL patient treated with PEG-asparaginase containing protocol in adults. We recommend increased vigilance in patients manifesting any mild neurological symptoms and early decision about the MRI study performance.

The Antineoplastic Effect of Heparin on Colorectal Cancer: A Review of the Literature.

Heparin and derivatives are commonly used for thrombophylaxis in surgical colorectal cancer (CRC) patients. Recent studies have suggested that, besides its protective effect on the incidence of venous thromboembolism, heparin has an anti-cancer effect. The aim of this review was to explore the literature and report the antineoplastic effect of heparin and derivatives on CRC. MEDLINE and EMBASE databases were searched for relevant articles. Nineteen studies were included (n = 19). Fifteen were lab studies conducted in vivo or in vitro on CRC cell lines and/or mice (n = 15). Four were in vivo clinical studies (n = 4). CRC tumor growth was reduced by 78% in one study, (p < 0.01), while tumorigenesis was suppressed in heparin-treated mice in seven studies. A high dose of low molecular weight heparin for extended duration significantly reduced post-operative VEGF, suggesting that such a regime may inhibit tumor angiogenesis and distant metastasis. A randomized trial demonstrated the antineoplastic effect of nadroparin as the 6 month survival in palliative patients increased. Another study has reported that disease-free survival of CRC patients was not affected by a similar tinzaparin regime. The anti-cancer properties of heparin and derivatives are promising, especially in lab studies. Further clinical trials are needed to investigate the anti-cancer benefit of heparin on CRC.

Does the choice of chemoprophylaxis affect the prevention of deep vein thrombosis in lumbar fusion surgery? A systematic review of the literature.

Introduction: To date, the available guidance on venous thromboembolism (VTE) prevention in elective lumbar fusion surgery is largely open to surgeon interpretation and preference without any specific suggested chemoprophylactic regimen. Research question: This study aimed to comparatively analyze the incidence of deep vein thrombosis (DVT) and pulmonary embolism (PE) with the use of commonly employed chemoprophylactic agents such as unfractionated heparin (UH) and low molecular weight heparin (LMWH) in lumbar fusion surgery. Material and methods: An independent systematic review of four scientific databases (PubMed, Scopus, clinicaltrials.gov, Web of Science) was performed to identify relevant articles as per the preferred reporting in systematic reviews and meta-analysis (PRISMA) guidelines. Studies reporting on DVT/PE outcomes of lumbar fusion surgery in adult patients with UH or LMWH chemoprophylaxis were included for analysis. Analysis was performed using the Stata software. Results: Twelve studies with 8495 patients were included in the analysis. A single-arm meta-analysis of the included studies found a DVT incidence of 14% (95%CI [8%-20%]) and 1% (95%CI [-6% - 8%]) with LMWH and UH respectively. Both the chemoprophylaxis agents prevented PE with a noted incidence of 0% (95%CI [0%-0.1%]) and 0% (95%CI [0%-1%]) with LMWH and UH respectively. The risk of bleeding-related complications with the usage of LMWH and UH was 0% (95% CI [0.0%-0.30%]) and 3% (95% CI [0.3%-5%]) respectively. Discussion and conclusion: Both LMWH and UH reduces the overall incidence of DVT/PE, but there is a paucity of evidence analyzing the comparative effectiveness of the chemoprophylaxis regimens in lumbar fusion procedures. The heterogeneity in data prevents any conclusions, as there remains an evidence gap. We recommend future high-quality randomized controlled trials to investigate in this regard to help develop recommendations on thromboprophylaxis usage.

Heparin-induced hyperkalemia, can LMWH cause hyperkalemia? A systematic review.

Hyperkalemia, an elevated blood potassium concentration exceeding 5.0 mEq/L, is associated with adverse outcomes and is frequently observed in hospitalized patients. Drug-induced hyperkalemia accounts for a significant proportion of cases, with heparin, commonly used for venous thrombosis prevention, suspected to contribute, though less recognized than other heparin-related side effects. Both unfractionated heparin (UFH) and low molecular weight heparin (LMWH) have been implicated in inducing hyperkalemia, primarily through the suppression of aldosterone levels and modulation of angiotensin II receptors. This systematic review examines the relationship between heparin, particularly LMWH, and hyperkalemia. Thirteen studies involving 1407 patients were analyzed. Findings indicated a lack of highquality evidence, with no significant increase in potassium levels associated with LMWH use. LMWH did not exhibit a dose-response relationship with hyperkalemia incidence. Additionally, mechanisms underlying the hypothetical LMWHinduced hyperkalemia remained inconclusive. While this suggests that LMWH is unlikely to be a primary cause of hyperkalemia, caution is warranted, especially in patients with elevated baseline potassium levels.

A Case of Non-cirrhotic Portal Hypertension in a Patient With Primary Myelofibrosis Disease.

Idiopathic non-cirrhotic portal hypertension can emerge due to a varied spectrum of underlying and contributory factors, presenting in the form of abdominal distention as the initial symptom encountered. Often, a patient remains asymptomatic to the underlying cause and seeks medical care for their abdominal enlargement. As the portal hypertension continues to progress, ascites begins to develop due to a history of portal vein thrombosis being sufficient to increase splanchnic blood flow in a portal hypertensive pattern. We present a rare case of ascites in a non-cirrhotic patient due to portal vein thrombus with underlying myeloproliferative disease of primary myelofibrosis.

Thrombin Generation Decrease After LMWH Administration in an Antithrombin-Deficient Pregnant Woman With a Homozygous HBS II Mutation.

The cases of antithrombin (AT)-deficient pregnant women with a homozygous HBS II mutation are relatively rare and are accompanied by an increased thrombophilic risk, which is manifested by increased thrombin generation (TG). It is very difficult to ensure their prophylactic treatment during pregnancy. We aimed to determine the utility of the thrombin generation assay (TGA) and anti-factor Xa (anti-FXa) test to monitor the effects of a prophylactic dose of low-molecular-weight heparin (LMWH) in a 28-year-old woman with homozygous AT deficiency caused by mutation c.391C > T#, (p.Leu131Phe†) in the SERPINC1 gene and to compare the findings with those from a group of pregnant and non-pregnant women also treated with LMWH. TG monitoring was chosen due to severe AT deficiency that was manifested by low levels of anti-FXa activity when monitoring the efficacy of LMWH treatment. A significant decrease in TG was detected in all monitored groups (P < .05). There were no thrombotic complications during the whole pregnancy of the woman with AT deficiency. Consistent monitoring of TG with LMWH anticoagulant therapy administration during pregnancy together with AT administration before and after delivery may improve the overall condition of pregnant women and the quality of their care.

The effect of renal impairment and obesity on anti-Xa peak and trough levels in patients receiving therapeutic doses of nadroparin: a comparison with control patients.

PURPOSE: Anti-Xa peak level monitoring is recommended during LMWH treatment in renal impairment or obesity. The trough level has been proposed as marker for bleeding. We studied the influence of renal impairment and obesity on anti-Xa levels. METHODS: Peak and trough levels were collected during therapeutic nadroparin treatment in patients with renal impairment, obese patients, and controls. 27 patients (n = 68 samples) were evaluated and combined with published data (n = 319 samples from 35 patients) using population pharmacokinetic (popPK) modelling. RESULTS: Median peak level was 0.44 and 0.95 IU/mL in renal impairment with and without dose reduction and 0.60 and 0.43 IU/mL in obesity and controls, respectively. Trough levels were < 0.5 IU/mL in all patients with renal impairment with dose reduction and in 5/6 control patients. In the popPK model, total body weight and eGFR were covariates for clearance and lean body weight for distribution volume. Model-based evaluations demonstrated peak levels below the therapeutic window in controls and increased levels in renal impairment. Dose reductions resulted in a different effect on peak and trough levels. Obese patients (BMI up to 32 kg/m2) had similar levels upon weight-based dosing. CONCLUSION: In renal impairment, anti-Xa peak levels after dose reduction are comparable to those in controls. Weight-based dosing is suitable for obese patients. Aiming for peak levels between 0.6 and 1.0 IU/mL in these patients would result in overexposure compared to controls. Considering the association of trough levels and bleeding risk and our findings, trough monitoring seems to be a suitable parameter to identify nadroparin accumulation.

Comparative Efficacy of Oral Apixaban and Subcutaneous Low Molecular Weight Heparins in the Treatment of Cancer-Associated Thromboembolism: A Meta-Analysis.

Cancer patients' risk of developing venous thromboembolism (VTE) is four to seven times higher than the general population. Cancer-associated VTE (CA-VTE), is a leading cause of morbidity and mortality in cancer patients. Low Molecular Weight Heparin (LMWH) has historically been the mainstay treatment of CA-VTE; however, complications such as bleeding and recurrent VTE make it challenging to manage these patients. Recent randomized controlled trials (RCTs) have proven that direct oral anticoagulants (DOACs) are as efficacious as LMWHs in treating CA-VTE. We conducted a systematic review and meta-analysis to ascertain the efficacy and safety of LMWH and Apixaban for the treatment of CA-VTE. A systematic review was conducted using Medline, Embase, and Scopus, databases for all cohort studies, case-control studies, and RCTs in English comparing cancer patients undergoing treatment with Apixaban or LMWH to treat CA-VTE from inception-May 2023. The Review Manager program, version 5.4.1, was used for statistical analysis and the Mantel-Haenszel fixed-effects models to calculate the risk ratio (RR) and 95% confidence intervals (CIs) and the inverse variance approach to get the weighted mean difference for the continuous outcomes. Q-test for heterogeneity was used to examine statistical heterogeneity and an I2 statistics value >50% was defined as significant heterogeneity. A total of four studies were included, and the total number of patients was 1,632 across all studies. The Apixaban group was associated with a statistically significant increase in minor bleeding (RR 1.57; 95% CI (1.12, 2.21); p=0.009; I2=0%), but not for major and total bleeding. The Apixaban group showed a statistically significant lower risk of recurrent VTE when compared to the LMWH group (RR: 0.61; 95% CI (0.41, 0.92); p=0.02; I2 = 7%), and there was no statistically significant difference in terms of mortality between the two groups (RR: 0.89; 95% CI (0.73, 1.09); I2=0). Our findings suggest that Apixaban may be a favorable anticoagulant option for managing cancer-associated thromboembolism, as it demonstrated a lower risk of recurrent VTE. The risk of bleeding with DOAC in gastrointestinal cancers warrants further investigation.