Therapy For Venous Thromboembolism Research Articles

Impact of Apixaban Lead-In Therapy Duration After Parenteral Anticoagulation on Bleeding in Patients Treated for Venous Thromboembolism.

Background: Venous thromboembolism (VTE) treatment with apixaban uses a higher 10mg twice daily regimen for 7days (lead-in therapy). But, in patients with initial parenteral anticoagulation treatment or those with higher bleeding risk, clinicians may not always adhere to the full 7-day lead-in duration. Methods: This retrospective cohort study included adult patients admitted to the Veterans Affairs Health care System from January 2011 to April 2022, who received at least 24hours of parenteral anticoagulation followed by lead-in apixaban therapy for VTE. The primary outcome evaluated bleeding among patients treated with shortened lead-in apixaban (study group) compared to the standard 7-day duration (control group). Results: Seventy-eight patients were included in the control and 65 in the study group. Most patients were treated for PE (72%) and received initial treatment with enoxaparin (71%). Duration of parenteral anticoagulation was longer in the study group (3.6days ± 3.2 vs 2.5days ± 1.9; P < .01), and length of apixaban lead-in therapy was decreased (4.1days ± 2.2 vs 7days; P < .01). The primary outcome of bleeding was higher in the study group (18.5% vs 5.1%; P = .02), with no difference in VTE recurrence. P2Y12 and P-gp inhibitor use, and increased creatinine and age were predictors of bleeding. Conclusion and Relevance: Bleeding events were increased in the study group, and patients with bleeding risk factors may not benefit from apixaban 10mg twice daily. Larger studies are needed where apixaban lead-in therapy is omitted following parenteral anticoagulation in patients with bleeding risk factors.

Factor V Leiden mutation in patients with polyarthralgia – case reports and review of literature

Patients with rheumatological diseases might be at increased risk of venous thromboembolism (VTE) because of inflammation, autoimmune disturbances, prolonged immobilization, and corticosteroid (CS) use. Therefore, more efforts are needed to identify additional prothrombotic factors and provide preventive strategies. Herein, we presented two cases of young men with polyarthralgia who have undergone unprovoked VTE. The first patient underwent VTE after several intra-articular CS applications, while the other had no concomitant risk factors. The hereditary thrombophilia testing revealed a heterozygous Factor V Leiden (FVL) state in the first patient and homozygous FVL carrier status in the second patient. Both cases suggest a possible benefit of thrombophilia testing in men under the age of 50 years with polyarthralgia, unprovoked VTE, and impending CS therapy. Estimating the complex thrombotic risk in rheumatological patients before CS use is crucial for preventing thromboses.

Treatment of VTE in the thrombocytopenic cancer patient.

Thrombocytopenia is a frequent complication in patients with cancer, mostly due to the myelosuppressive effects of antineoplastic therapies. The risk of venous thromboembolism (VTE) in patients with cancer is increased despite low platelet counts. The management of cancer-associated VTE in patients with thrombocytopenia is challenging, as the risk of both recurrent VTE and bleeding complications is high. Moreover, the time-dependent nature of thrombocytopenia over the course of antineoplastic therapies further complicates the management of patients in clinical practice. In the absence of evidence from high-quality studies, the management of anticoagulation therapy for VTE must be personalized, balancing the individual risk of VTE progression and recurrence against the risk of hemorrhage. In the present case-based review, we highlight the clinical challenges that arise upon managing cancer-associated VTE in the setting of present or anticipated thrombocytopenia, summarize the available evidence, and provide a comparative overview of available guidelines.

Evaluation of unfractionated heparin therapy for venous thromboembolism using adjusted body weight in elderly or higher weight patients.

The use of weight-based unfractionated heparin (UFH) infusions is the standard of care in hospital management of venous thromboembolism (VTE). Initial dosing strategies for UFH in older adults and higher body weight patients remain uncertain given differences in pharmacokinetics and concerns for over-anticoagulation. Methods: This was a single-center, retrospective, pre-post study involving older adults aged ≥ 65years and patients weighing ≥ 100kg with suspected or confirmed VTE to determine if the use of adjusted body weight (AdjBW)-based UFH regimens improves time to therapeutic anti-Xa levels compared to total body weight (TBW)-based regimens Patients received weight-based UFH infusions, dosed according to either TBW or AdjBW, to target a therapeutic anti-Xa level. Each cohort consisted of 40 patients, stratified by whether they met age or weight criteria to ensure equal representation of elderly and higher body weight patients between cohorts. The median time to therapeutic anti-Xa levels was shorter in the AdjBW group compared to the TBW group (13.6h versus 20.9h; point estimate 5.3h (95% CI 0.2 to 9.9)). This finding was driven by those aged ≥ 65years and those who received a bolus dose at the start of the infusion. Among older adults and higher weight adults with suspected or confirmed VTE, the use of AdjBW to guide heparin infusion initiation was associated with shorter time to therapeutic anti-Xa levels. This finding driven by the older adult sample and the subgroup analyses did not find a statistically significant difference in time to therapeutic anti-Xa levels in higher body weight patients aged less than 65years.

Edoxaban and Cancer-Associated Venous Thromboembolism: A Meta-analysis of Clinical Trials

Introduction Cancer patients face a venous thromboembolism (VTE) risk that is up to 50 times higher compared to individuals without cancer. In 2010, direct oral anticoagulants (DOACs) such as apixaban, rivaroxaban, and edoxaban were introduced, consequently becoming the controversial oral anticoagulants for VTE therapy. This study is a meta-analysis of randomized clinical trials (RCTs) evaluating the use of edoxaban for treating VTE in cancer patients over different treatment durations. Methods Using Google Scholar, a systematic search for RCTs on edoxaban for cancer-associated VTE was performed. The data extracted covered patient numbers, age, gender, BMI, cancer type, edoxaban dosage, treatment duration, comorbidities, major bleeding, recurrent VTE incidence, and deaths. Statistical significance was set at 0.05. Results Out of 52 studies, nine with 3,190 cases met the inclusion criteria. The mean age was 66.68 years, with 1,604 females (50.28%). Major bleeding occurred in 192 patients (7.66%) in the 6- or 12-month group and 57 (8.35%) in the 3-month group (p=0.573). Recurrent VTE was observed in 145 patients (5.78%) in the 6- or 12-month group and 95 (13.91%) in the 3-month group (p&lt;0.001). Deaths from any cause totaled 548 (21.86%) in the 6- or 12-month group and 165 (24.16%) in the 3-month group (p=0.110). Conclusion Cancer patients receiving edoxaban for six or 12 months experience a lower recurrence rate of VTE compared to those on a 3-month treatment. The incidence of major bleeding appears to be similar between the two treatment durations.

Thrombolytic Therapy for Venous Thromboembolism in the Pediatric Population: A Systematic Review and Meta-Analysis

Thrombolytic Therapy for Venous Thromboembolism in the Pediatric Population: A Systematic Review and Meta-Analysis

Anticoagulation Therapy for Venous Thromboembolism in the Pediatric Population: A Systematic Review and Meta-Analysis

Anticoagulation Therapy for Venous Thromboembolism in the Pediatric Population: A Systematic Review and Meta-Analysis

The initial high-dose versus maintenance-dose anticoagulation therapy with direct oral anticoagulants for cancer-associated venous thromboembolism: from the COMMAND VTE Registry-2

Abstract Background/Introduction Initial high-dose anticoagulation therapy with rivaroxaban and apixaban has been a standard treatment for venous thromboembolism (VTE), although there could be concerns of an increased risk of bleeding events especially among high bleeding-risk patients including those with active cancer. Purpose The present study aimed to evaluate the clinical outcome of initial high-dose anticoagulation therapy comparing to maintenance-dose anticoagulation therapy in patients with cancer-associated VTE using propensity score-matching analysis. Methods The COMMAND VTE Registry-2 is a multicenter registry enrolling 5197 consecutive acute symptomatic VTE patients among 31 centers in Japan between January 2015 and August 2020. Among 1507 patients with cancer-associated VTE, we evaluated 180-day clinical outcomes before discontinuation of anticoagulation therapy using a 1:1 propensity score-matching model with 21 risk-adjusting variables Results After the propensity score-matching, we enrolled 324 patients with initial high-dose anticoagulation therapy and 324 patients with initial maintenance dose anticoagulation therapy. Of patients with initial high-dose anticoagulation therapy, rivaroxaban and apixaban were administered in 198 and 126 patients, respectively. Of those with initial maintenance-dose anticoagulation therapy, rivaroxaban, apixaban, and edoxaban were administered in 34, 46 and 244 patients, respectively. The median durations of initial high-dose anticoagulation therapy were 18 [IQR: 15-21] days for rivaroxaban and 7 [IQR: 7-7] days for apixaban. In the current study population, the mean age was 67±12 years, 346 were women, and the mean body weight was 58±12 kg. There was no significant difference in the distribution of gastrointestinal cancer such as stomach and colorectal cancer between the 2 groups (4.6% vs. 4.9%, P=1.0, 8.3% vs. 11.4%, P=0.22). The cumulative 180-day incidence of discontinuation of anticoagulation was not significantly different between the 2 groups (27.8% vs. 30.5%, P=0.50). There were no significant differences in the cumulative 180-day incidences of recurrent VTE (3.1% vs. 1.0%, P=0.08), nor major bleeding (8.1% vs. 7.0%, P=0.66), nor all-cause death (25.1% vs. 21.6%, P=0.33) between the 2 groups. There were also no significant differences in the cumulative 180-day incidences of all clinically relevant bleeding (14.9% vs. 13.3%, P=0.72), gastrointestinal bleeding (8.4% vs. 5.4%, P=0.15), nor major gastrointestinal bleeding (5.4% vs. 2.7%, P=0.10). Conclusions There was no signal of an increased risk of recurrent VTE in the initial maintenance-dose anticoagulation therapy. Considering a numerically slightly higher incidence of gastrointestinal bleeding in the initial high-dose anticoagulation therapy for cancer-associated VTE, the initial maintenance-dose anticoagulation therapy could be a potential treatment option for selected patients including patients at a high risk of gastrointestinal bleeding.Study flow chartResults

Application of DOAC Score for the risk-stratification of major bleeding in patients with venous thromboembolism on direct oral anticoagulants: insight from the COMMAND VTE Registry-2

Abstract Background/Introduction Bleeding complications are still a major concern in anticoagulation therapy for venous thromboembolism (VTE), even in the direct oral anticoagulant (DOAC) era. Thus, the risk stratification of bleeding during anticoagulation therapy is essential, although most of currently available bleeding risk scores have been developed from patients receiving vitamin K antagonists, which could have limited validity in those receiving DOACs. Very recently, the DOAC Score has been developed to predict major bleeding in patients with atrial fibrillation on DOACs; however, the score has not yet been validated in patients with VTE. Purpose The present study aimed to evaluate the usefulness of the DOAC Score in patients with VTE, using a large-scale multicenter observational database of patients with VTE. Methods The COMMAND VTE Registry-2 is a multicenter registry enrolling 5197 consecutive acute symptomatic VTE patients among 31 centers in Japan between January 2015 and August 2020. The present study population was consisted of 3539 patients with VTE who received DOACs and had a calculated DOAC Score. The eligible patients were classified into 5 risk categories: very low (score 0–3), low (score 4–5), moderate (6–7), high (score 8–9), and very high (score ≥10). We used the Kaplan-Meier method to estimate the cumulative incidence and assessed the discriminatory ability of the DOAC Score for major bleeding at 1 year by calculating the area under the receiver operating characteristic curve. We also assessed the discriminatory ability of the VTE-BLEED and RIETE scores. Results In the present study population, the very low-risk group accounted for 1437 patients (41%), low-risk group for 828 (23%), moderate-risk group for 812 (23%), high-risk group for 326 (9.2%), and very high-risk group for 136 (3.8%). The proportion of anemia was highest in the very high-risk group (71%) and lowest in the very low-risk group (47%). The prevalence of active cancer was highest in the low-risk group (36%) and lowest in the very high-risk group (18%). During the first year of anticoagulation therapy, major bleeding occurred in 180 patients. The cumulative 1-year incidence of major bleeding seemed to be different according to the 5 groups, but the risks could not be well-stratified (Figure 1). The discriminating power of the DOAC Score was relatively low with a C-statistic of 0.52 (95% CI, 0.48–0.57) (Figure 2), while those of VTE-BLEED and RIETE scores were modest with C-statistics of 0.66 (95% CI, 0.60–0.73) and 0.67 (95% CI, 0.64–0.71), respectively. Conclusions The risk of 1-year major bleeding on DOACs in patients with VTE was not well-stratified according to the risk categories by the DOAC Score, which might suggest that patients with VTE have different risk factors for bleeding on DOACs as compared to those with atrial fibrillation. A new bleeding risk score for DOAC specifically in patients with VTE would be warranted in the future.Figure 1Figure 2

Overview of Venous Thromboembolism and Emerging Therapeutic Technologies Based on Nanocarriers-Mediated Drug Delivery Systems

Venous thromboembolism (VTE) is a serious health condition and represents an important cause of morbidity and, in some cases, mortality due to the lack of effective treatment options. According to the Centers for Disease Control and Prevention, 3 out of 10 people with VTE will have recurrence of a clotting event within ten years, presenting a significant unmet medical need. For some VTE patients, symptoms can last longer and have a higher than average risk of serious complications; in contrast, others may experience complications arising from insufficient therapies. People with VTE are initially treated with anticoagulants to prevent conditions such as stroke and to reduce the recurrence of VTE. However, thrombolytic therapy is used for people with pulmonary embolism (PE) experiencing low blood pressure or in severe cases of DVT. New drugs are under development, with the aim to ensure they are safe and effective, and may provide an additional option for the treatment of VTE. In this review, we summarize all ongoing trials evaluating anticoagulant interventions in VTE listed in clinicaltrials.gov, clarifying their underlying mechanisms and evaluating whether they prevent the progression of DVT to PE and recurrence of thrombosis. Moreover, this review summarizes the available evidence that supports the use of antiplatelet therapy for VTE. Since thrombolytic agents would cause off-target effects, targeted drug delivery platforms are used to develop various therapeutics for thrombotic diseases. We discuss the recent advances achieved with thrombus-targeting nanocarriers as well as the major challenges associated with the use of nanoparticle-based therapeutics.

Safety and efficacy of direct oral anticoagulants in chronic kidney disease: a meta-analysis

BackgroundDirect oral anticoagulants (DOACs) have emerged as the first-line therapy for venous thromboembolism and stroke prophylaxis in atrial fibrillation. As DOACs are partially excreted renally, their safety in patients with chronic kidney disease (CKD) is unclear. ObjectivesTo synthesize primary evidence on the safety profile of DOACs in patients with CKD. MethodsWe searched MEDLINE and Embase from inception to June 2023 for randomized and nonrandomized cohort studies comparing DOACs with vitamin K antagonists (VKAs) in CKD patients. Screening and data collection were conducted in duplicate. The primary safety outcome was major bleeding, defined by International Society on Thrombosis and Haemostasis criteria, stratified by CKD severity. Meta-analysis was done using the Mantel–Haenszel random-effects model, presented as odds ratios (ORs) with corresponding 95% CIs. ResultsOf the 2355 articles captured in the literature search, 25 nonrandomized studies (n = 6832) and 6 randomized studies (n = 66,898) were included. DOACs reduced major bleeding compared with VKAs in all subgroups (stage 4: OR, 0.73; 95% CI, 0.58, 0.93; stage 5/renal replacement therapy: OR, 0.70; 95% CI, 0.50, 0.98; stage unspecified: OR, 0.72; 95% CI, 0.63, 0.83). Apixaban and rivaroxaban both reduced major bleeding in stage 5/renal replacement therapy patients (apixaban: OR, 0.66; 95% CI, 0.52, 0.85; rivaroxaban: OR, 0.58; 95% CI, 0.35, 0.94). ConclusionIn this meta-analysis, DOACs reduced major bleeding compared with VKAs in stage 4, stage 5/renal replacement therapy, and CKD stage unspecified patients. Future analysis should evaluate the impact of specific DOACs and dosage on safety and efficacy in this population.

Inferior Vena Cava Filter in Cancer-Associated Thrombosis: A Vade Mecum for the Treating Physicians: A Narrative Review.

Cancer is a remarkable prothrombotic disease, and cancer-associated thrombosis acts as a dreadful omen for poor prognosis. The cornerstone of venous thromboembolism therapy is anticoagulation; however, in patients with venous thromboembolism who are not suitable for anticoagulation (contraindication, failure, or complication), the inferior vena cava filter appears a valuable option in the therapeutic arsenal. The recently heightened trend of steady rise in filter placement mirrors the spread of retrievable devices, together with improvements in physicians' insertion ability, medico-legal issue, and novel and fewer thrombogenic materials. Nevertheless, the exact role of the inferior vena cava filter in cancer has yet to be endorsed due to a dearth of robust evidence. Indeed, data that support the inferior vena cava filter are weak and even controversial, resulting in discrepancies in the interpretation and application of guidelines in daily practice. In this narrative review, we aim at clarifying the state of the art on inferior vena cava filter use in malignancies. Furthermore, we provide a feasible, conclusive 4-step algorithm for the treating physicians in order to offer a practical strategy to successfully employ the inferior vena cava filter as a priceless device in the current armamentarium against cancer.

Anticoagulant therapy in venous thromboembolism and bleeding risk: focus on the use of predictive scores.

The standard treatment for venous thromboembolism (Vte) is anticoagulation. Drug selection and treatment duration will depend on the clinical presentation, the existence of provoking factors, bleeding risk, and the patient's preferences. Anticoagulation therapy is indicated for 3-6 months in all patients with acute Vte but may be extended, even indefinitely in some cases. The most severe side effect of anticoagulation is bleeding, with the highest risk occurring during the 1st months of therapy. Balancing the risk of bleeding and the risk of recurrence in patients with Vte remain a major issue. There are, currently, no simple and validated predictive scores to estimate the long-term bleeding risk in patients undergoing anticoagulant treatment and to safely select those patients with higher bleeding risk. In this review we will examine some of these scores, including the RIETE scores, the HAS-BLED SCORE, the VTE-BLEED score, the VTE- PREDICT and the ACCP guidelines and the timing for their application in the patient's population treated for Vte as well as the initial and long-term management and evaluation of thromboembolic disease.

Poor patients' knowledge about venous thromboembolism and its therapy is associated with increased risk of major bleeding and discontinuation of anticoagulation: A cohort study.

It has been shown that patients' knowledge about venous thromboembolism (VTE) and its therapy is suboptimal, which might reduce compliance and worsen prognosis. We investigated whether low VTE patients' knowledge affects their clinical outcomes during long-term follow-up. We evaluated 151 consecutive patients (51.8 ± 15.7 years) after unprovoked VTE, who were recruited from the outpatient clinic (Krakow, Poland). All patients received anticoagulant treatment, mostly with direct oral anticoagulants (n = 113, 74.8%). The modified Jessa Atrial fibrillation Knowledge Questionnaire (JAKQ-VTE; 16 questions) was used to assess the knowledge of VTE and anticoagulant therapy. During a median follow-up of 58.0 months, VTE recurrence, major bleeding, and anticoagulation withdrawal were recorded. The median percentage of correct responses was 62.5% (12.5-100%) and was inversely correlated with age (P < .01). Diabetic patients and those with positive family history of VTE had lower overall scoring compared to the remainder (both P < .05). Major bleeding (n = 10, 6.6%) and anticoagulation withdrawal (n = 28, 18.5%), but not VTE recurrence (n = 12, 7.9%), were associated with lower overall scoring compared to the remainder (48.8% ± 12.5% vs 63.8% ± 16.3%, P = .003 and 55.3% ± 14.7% vs 64.4% ± 16.3%, P = .040, respectively). Major bleeding was independently associated with the female sex (hazard ratio [HR] 6.18; 95% confidence interval [CI] 1.15-33.19, P = .034), younger age (HR per 10 years 0.55; 95% CI 0.34-0.90, P = .016), OAC therapy discontinuation (HR 6.69; 95% CI 1.62-27.70), and lower overall scoring of JAKQ-VTE (HR 0.60 per 10 percentage points; 95% CI 0.40-0.92, P = .019). Insufficient knowledge about VTE and anticoagulant treatment predisposes to a higher risk of major bleeding and therapy discontinuation, but not VTE recurrence in unprovoked VTE patients during long-term follow-up.

Laboratory findings of postoperative venous thromboembolism (VTE) in Dr. Sardjito General Hospital, Yogyakarta

Venous thromboembolism (VTE) is a significant risk, especially for older individuals. Indonesian studies found 37.1% VTE incidence in bedridden patients over 40 and 2.1% in major surgeries. Surgery, like hip fractures, raises the risk temporarily. Diagnosis relies on tests like ultrasound with Doppler, Wells score, and neutrophil-to-lymphocyte ratio (NLR). This study aimed to evaluate the laboratory findings of postoperative VTE. A retrospective analysis was conducted in Dr. Sardjito General Hospital, Yogyakarta using medical record data of VTE patients who underwent major surgery. The laboratory data, including complete blood count characteristics for every month for three months after postsurgery and DVT presentation when it occurred on the diagnostic day were collected. In total of 27 patients involved in this study, VTE cases were more common in digestive (41.2%) and obstetric gynecology surgeries (29.4%) for females, and nervous (44.4%) and cardiovascular surgeries (22.2%) for males. Females had a higher prevalence of Well Score ≥3 (82.4% vs 40%; p=0.058) and longer VTE therapy durations (65.50 ± 46.51 vs 39.60 ± 41.04 d; p=0.172). Males had more unilateral VTE occurrences (90.9 vs 56.3%; p=0.070) and a higher proportion of total occlusion cases (60 vs 37.5%; p=0.422). NLR exhibited a significant decrease from the 1st to the 2nd month (10.52 vs 3.64; p=0.009), followed by an insignificant increase in the 3rd month (3.64 vs 3.98; p=0.878). Notably, NLR trended downward in the 2nd month examination. In conclusion, VTE occurs in 0.21% of postoperative patients, with the highest incidence observed in post-gynecological surgery patients. The NLR can serve as a diagnostic tool for VTE in extremities, as an elevated NLR indicates the presence of a more proximal thrombus.

Efficacy and safety of DOACs versus LMWH for elderly patients with active cancer: A meta-analysis.

e13776 Background: Anticoagulant treatment in patients with cancer aims to reduce the high risk of thromboembolism. Direct oral anticoagulants (DOACs) and low-molecular-weight heparin (LMWH) are currently approved for the treatment of cancer-related thrombosis. However, there is limited data comparing the efficacy and safety of these two antithrombotic therapies among elderly patients with cancer. Methods: PubMed, Embase, and Cochrane Central Register of Controlled Trials databases were systematically searched for studies comparing DOACs with LMWH in cancer patients with newly diagnosed venous thromboembolism (VTE) or pulmonary embolism (PE). Both solid tumors and hematologic malignancies were included. Outcomes of interest were recurrent VTE and major bleeding. Odds ratio (OR) with 95% confidence intervals (CI) were pooled with a random-effects model. Statistical analysis was performed with Review Manager 5.4.1. Heterogeneity was assessed using the I2 statistic and chi-squared test. Results: Four studies, three randomized controlled trials (RCTs) and one observational, were included. A total of 3,266 patients older than 65 years who underwent anticoagulation with DOACs (35%) or LMWH (65%) were incorporated in the analysis. There was no statistically significant difference between anticoagulation therapies for recurrent VTE (OR, 0.68; 95% CI, 0.41-1.11; p = 0.13; I² = 56%; Table) or major bleeding (OR, 1.18; 95% CI, 0.61-2.25; p = 0.08; I² = 60%; Table). Conclusions: Our findings suggest no statistically significant differences in recurrent VTE or major bleeding between DOACs and LMWH in elderly oncologic patients with newly diagnosed VTE or PE. Given the practical challenges of using LMWH, DOACs may be considered an alternative anticoagulation strategy for these patients. [Table: see text]

Bleeding Outcomes of Direct Oral Anticoagulants and Vitamin K Antagonists for Acute Venous Thromboembolism: A Cross-Sectional Study.

Venous thromboembolism (VTE) is a widespread and significant cause of morbidity and mortality on a global scale. The primary objective of this cross-sectional study is to examine the impact of anticoagulant therapy on major organ hemorrhage events in patients diagnosed with acute venous thromboembolism (VTE). Specifically, this research compares the effects of vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs). This retrospective observational study examined the medical records of 46 patients who had been diagnosed with VTE and were receiving treatment with DOACs or VKAs. The documentation of patient characteristics encompassed demographic information, comorbidities, and treatment particulars. Within 30 days of hospital admission, the incidence of significant organ bleeding events, with an emphasis on gastrointestinal and intracranial hemorrhage, was the primary outcome evaluated. Overall, 46 patients with VTE who were treated with oral anticoagulation therapy participated in the study. Twenty-four and 22 patients were administered VKAs and DOACs, respectively. The similarity in baseline characteristics between the DOAC and VKA groups ensured that the analyses were well-matched. The examination of bleeding sites unveiled subtle variations, as the DOAC group exhibited a progressive increase in the incidence of intracranial bleeding (12, 55.5%), while the VKA group demonstrated a surge in upper gastrointestinal bleeding (12, 50%) as well. While lacking statistical significance, these observed patterns are consistent with prior research that indicates that DOACs may have a lower risk of catastrophic hemorrhage in comparison to VKAs. The overall in-hospital mortality rate for patients treated with VKA was 33.3% (n=8), while that treated with DOAC was 18.2% (n=4). These differences did not reach statistical significance (P>0.05). In a similar vein, the evaluation of mortality associated with hemorrhage revealed six (25%) in the group receiving VKA and three (13.6%) in the group receiving DOAC; the P value was not statistically significant (P>0.05). This study contributes valuable insights into bleeding outcomes associated with anticoagulant therapy for acute VTE. The nuanced differences in bleeding patterns highlight the complexity of anticoagulant selection, emphasizing the importance of considering bleeding site considerations. The comparable mortality rates support existing evidence regarding the favorable safety profile of DOACs.

Evaluation of Apixaban Use in Patients With Advanced Kidney Disease.

Background: Current guidelines and literature suggest apixaban may be used in patients with severe kidney disease and atrial fibrillation (AF) for stroke and systemic embolism risk reduction (SSE) or patients with acute venous thromboembolism (VTE). Limited data is available for long-term safety and efficacy outcomes in this patient population. Objective: Evaluate the use of apixaban for AF or VTE in patients with advanced kidney disease. Methods: This single-center, retrospective, Investigational Review Board approved study evaluated patients ≥18 years of age with severe kidney disease on apixaban therapy for VTE or AF from March 1, 2018, to December 31, 2020. The primary outcome was major bleeding from apixaban initiation/continuation until 12 months after discharge. The secondary outcomes included a composite bleed (major bleeding, clinically relevant non-major bleeding, and minor bleeding), the occurrence of VTE or SSE, and death during hospitalization from any cause other than bleeding. Results: Overall, 156 patients met inclusion criteria. Six patients experienced major bleeding (3.8%). Composite bleeding occurred in 16 patients (10.3%); no patients had SSE or VTE, and 4 patients died from causes other than bleeding (2.6%). Limitations included the small sample size and retrospective nature of the study. Conclusion: This study demonstrated that patients with advanced chronic kidney disease on apixaban for AF or VTE had low major bleeding and similar overall bleeding rates compared with previously published literature. When considering the use of apixaban in this population, risks and benefits should be weighed in addition to the consideration of FDA-label dosing guidance.

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]

Early Time Courses of Recurrent Venous Thromboembolism and Bleeding during Apixaban or Dalteparin Therapy for Patients with Cancer.

In patients with acute venous thromboembolism (VTE), the rates of recurrence and major bleeding are highest during the first weeks of anticoagulation. The CARAVAGGIO trial demonstrated noninferiority of apixaban to dalteparin for treatment of cancer-associated VTE without an increased risk of major bleeding. We compared the early time course of VTE recurrence and major bleeding events of apixaban compared with dalteparin at 7, 30, and 90 days of treatment in patients with cancer-associated VTE. The study design of the CARAVAGGIO trial has been described. Eligible patients were randomly assigned to receive monotherapy with either apixaban or dalteparin for 6 months. The primary efficacy outcome was the incidence of objectively confirmed recurrent VTE. The primary safety outcome was major bleeding. In 1,155 patients, recurrent VTE after 7, 30, and 90 days occurred in 6 (1%), 15 (2.6%), and 27 (4.7%) patients in the apixaban arm versus 5 (0.9%), 20 (3.5%), and 36 (6.2%) patients respectively in the dalteparin arm. By day 7, 30, and 90, major bleeding events had occurred in 3 (0.5%), 9 (1.6%), and 16 (2.8%) patients in the apixaban group versus 5 (0.9%), 11 (1.9%), and 17 (2.9%) patients in the dalteparin group. The frequencies of recurrent VTE and major bleeding events at 7, 30, and 90 days of apixaban compared with dalteparin were similar in patients with cancer-associated VTE. This supports the use of apixaban for the initiation and early phase of anticoagulant therapy in cancer-associated VTE.