Anticoagulation Group Research Articles

Low-dose anticoagulation for peripheral deep vein thrombosis of the lower extremities in cancer patients

Abstract Background Venous thromboembolism (VTE) is a frequent complication in cancer patients and is often detected as asymptomatic peripheral deep vein thrombosis (DVT). However, guidelines for peripheral DVT have not been established in either general cardiology or onco-cardiology. Furthermore, in cancer patients, it is generally considered difficult to administer standard doses of anticoagulants due to the high risk of bleeding caused by thrombocytopenic tendency during chemotherapy, as well as bleeding lesions such as gastrointestinal and gynecological cancers. Treatment of peripheral DVT with direct oral anticoagulants (DOACs) may minimize the worsening of bleeding and prevent the transition to proximal DVT. Objective The purpose of this study was to investigate the optimal treatment for peripheral DVT in cancer patients. Methods 242 consecutive patients with peripheral DVT of the lower extremities (excluding complications of pulmonary thromboembolism or proximal DVT) were examined by venous ultrasound from April 2019 to March 2020. 190 patients could be followed up by ultrasound examination, for up to 2 years. The course of the DVT was retrospectively examined. In cases of anticoagulant therapy, standard and low dosage of DOACs were evaluated. Results 142 patients were treated with anticoagulant (AC) therapy (group AC(+)), 48 patients were without AC therapy (group AC(−)). (4 of the 142 patients were treated with warfarin and the rest with DOACs). DVT worsened in 8 patients (5.6%) in the AC(+) group and 23 patients (47.9%) in the AC(−) group. DVT worsening was significantly less in the AC(+) group (p<0.0001). There were no cases of worsening to proximal type in the AC(+) group and 4 cases (17.4%) in the AC(−) group. Of the 138 patients who used DOACs as AC therapy, 62 used half or less than the standard dose for maintenance (low-dose DOAC group), and 76 used the standard dose as maintenance (standard-dose DOAC group). In the low-dose DOAC group, DVT worsened in 5 cases, remained unchanged in 7 cases, and improved in 50 cases. In the standard-dose DOAC group, there were 4 cases of worsening DVT, 3 cases of no change, and 69 cases of improvement. There was no significant difference in the DVT treatment effect between the two groups. There were no thrombus-related deaths. Conclusion Peripheral DVT worsens in about half of cancer patients without anticoagulation, and 17% of these worsen to proximal VTE. In addition, low-dose DOACs are found to be as effective as standard-dose DOACs in treating peripheral DVT in cancer patients. Peripheral DVT treatment with low-dose DOACs can reduce the risk of bleeding complications and thrombus-related mortality in cancer patients and should be one of the supportive treatments for the completion of cancer management. Funding Acknowledgement Type of funding sources: None.

Optimal thromboprophylaxis and anticoagulant strategies in patients with COVID-19 pneumonia. The PROTHROMCOVID Trial

Abstract Introduction Hospitalized patients with COVID-19 are at increased risk of venous and arterial thrombosis, ARDS, and death. The optimal dosage of thromboprophylaxis in patients is unknown. Objective To evaluate the efficacy and safety of tinzaparin in prophylactic, intermediate and therapeutic doses in non-critical patients admitted for COVID-19 pneumonia. Design, Setting, and Participants: The PROTHROMCOVID multicenter randomized clinical trial enrolled noncritical hospitalized adult patients with COVID-19 pneumonia from February 1, 2021, to September 30, 2021, at 18 centers in Spain. Methods Patients were randomized to prophylactic tinzaparin 4500IU or intermediate dose 100IU/kg or therapeutic tinzaparin 175IU/kg during hospitalization, followed by 7 days of prophylactic tinzaparin at discharge. The patients were stratified at the time of randomization according to age, sex and the presence or absence of hypertension.The primary efficacy outcome was a composite endpoint of symptomatic systemic thrombotic events, need for invasive or non invasive mechanical ventilation or not, including high-flow nasal cannula oxygen, or death within 30 days. The main safety outcome was major bleeding at 30 days. Data were collected and adjudicated locally by non-blinded investigators through imaging, laboratory, and health record data. Results Of 311 patients randomized, 300 were included in the analysis (mean [SD]age, 56.7 [14.6] years; men, 182 [60.7%]; women, 118 [39.3%]). 106 patients (35.33%) were assigned to the prophylaxis group, 91 patients (30.33%) were allocated to the intermediate dose group and 103 patients (34.33%) were randomized to the anticoagulant dose group. The composite endpoint thrombotic event, need for invasive (IMV) or noninvasive mechanical ventilation (NIV) or HFT via nasal cannula or death at 30 days from randomization occurred in 58 patients (19.3%) of the whole population, 19 patients (17.09%) in prophylactic group, 20 (21.98%) in intermediate group and 19 (18.45%) in therapeutic group (P=0.72). No major bleeding were reported in the trial and non-major bleeding occurred in 5 patients (4.71%) in prophilactic, in 3 patients (3.2%) in intermediate arm and in 3 patients (2.9%) in therapeutic, without significant differences in each group (P=0.31). Conclusions In non-critically ill patients with COVID 19, intermediate or full-dose of tinzaparin do not appear to offer benefit over standard prophylactic doses IU in the likelihood of thrombotic event, non-invasive ventilation or high-flow oxygen, or death. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Leo Pharma

ABCL-104 Direct Oral Anticoagulants for the Treatment of Venous Thromboembolism in Patients With Hematological Malignancies

Data is needed on direct oral anticoagulants (DOACs) for the treatment of venous thromboembolism (VTE) in hematological malignancies (HM). Retrospective studies to date have lacked a control group and included patients with atrial fibrillation and/or VTE, but not VTE alone. Assess the incidence of VTE recurrence and bleeding in HM patients treated with low molecular weight heparin (LMWH) or DOACs for acute VTE. Retrospective cohort study. The study included subjects with active HM and newly diagnosed VTE treated as inpatients or outpatients in the hemato-oncology department at Rabin or Meir Medical Centers (1/2015-7/2021). Patients were indexed on the first day of anticoagulation for VTE and followed for 12 months. Type of anticoagulation at study index, classified as LMWH or DOAC. Composite of recurrent VTE, clot progression, major bleeding, or clinically relevant non-major bleeding (CRNMB). Cumulative incidence (95% confidence interval [CI]) was calculated for each anticoagulation group (LMWH, DOAC) and hazard ratios (HRs) were calculated using the Cox proportional-hazards model with death as a competing risk. A total of 143 HM patients treated with LMWH (96) or DOACs (47) for acute VTE were included. HM was lymphoma in 83 (58%). DOAC-treated patients were older and had more pulmonary embolisms and less splanchnic vein thrombosis. The 12-month cumulative incidence of the primary outcome was 24.2% (95% CI 15.9%-33.5%; n=22) in the LMWH group and 18.5% (8.5%-31.5%; n=8) in the DOAC group (HR 1.51 [0.695-3.297]). Two recurrent VTEs occurred (both in the DOAC group while off-treatment). Nine (9.4%) LMWH-treated patients and 1 (2.1%) DOAC-treated patient (HR 4.85 [0.64-36.56]) had major bleeding. There were 13 (13.5%) CRNMB cases in the LMWH group and 5 (10.6%) in the DOAC group (HR 1.44 [0.52-3.98]). This study generates the hypothesis that DOACs may be a safe and effective alternative to LMWH for VTE in patients with lymphoma or plasma cell dyscrasia. Larger prospective studies are needed to confirm these findings.

Effect of Chronic Antiplatelet and Anticoagulant Medication in Neck Hematoma and Perioperative Outcomes after Carotid Endarterectomy

A retrospective analysis of neck hematoma, stroke, and mortality after symptomatic and asymptomatic carotid endarterectomy (CEA) was conducted, to determine the most appropriate perioperative medication for these patients. Thirty-day outcomes of moderate and severe neck bleeding were also investigated. Patients undergoing CEA in a Vascular Surgery department were analyzed (2015-2019). Preprocedure antithrombotic medication (from the 5 days prior to surgery) was identified. End point predictors were identified by univariate and multivariable analyses and adjusted for confounders. A total of 304 CEA were included. Almost half of the included patients (49.67%) were under low-dose aspirin, 17.55% other single antiplatelet agent, 12.59% dual antiplatelet therapy, 8.61% anticoagulation, and 10.92% no antithrombotic therapy. There was a 8.22% rate of important hematoma, including 4.93% severe (requiring surgical exploration) hematomas and a 30-day all-stroke incidence of 2.94% in symptomatic and 1.79% asymptomatic patients (P=0.51). When compared to aspirin, severe hematoma was more prevalent with single clopidogrel or triflusal (relative risk [RR] 4.25, P=0.11), dual antiplatelet group (RR 11.84, P=0.002), and anticoagulation (RR 8.604, P=0.02). Dual antiaggregation and anticoagulation did not confer postoperative stroke protection compared to single aspirin in either symptomatic or asymptomatic patients. Nonsignificant higher intrahospital mortality was noted in no medication, dual antiplatelet, and anticoagulation groups in contrast to aspirin. Severe neck bleeding was associated with increased congestive heart failure (9.26-fold, P=0.03) and longer hospital stay (11.20±24.69days vs. 3.18±4.79 with no bleeding, P<0.001), with a tendency for higher hospital readmission at 30 days (4.66-fold, P=0.13). Mortality and stroke rates were similar. Double antiaggregation and anticoagulation did not confer better perioperative outcomes after elective CEA in our study. These regimens were associated with an increased risk of neck hematoma, especially severe bleeding, with similar rates of neurologic events in both symptomatic and asymptomatic patients and no mortality benefit. Monotherapy with aspirin appears to be the safest perioperative antithrombotic regimen for elective CEA.

Hospitalized patients with isolated distal deep vein thrombosis: anticoagulation therapy or not?

BackgroundIsolated distal deep vein thrombosis (IDDVT), a disease frequently detected in hospitalized patients, can progress to proximal deep vein thrombosis (PDVT) and pulmonary embolism (PE). Here, we evaluated the effects of anticoagulation in hospitalized IDDVT patients.MethodsWe conducted a retrospective study in our hospital and enrolled hospitalized IDDVT patients diagnosed by compression ultrasonography (CUS) from January to December 2020. Participants were divided into anticoagulation (AC) and non-anticoagulation (non-AC) groups. After propensity score matching (PSM), multivariate Cox regression analyses were performed to assess whether anticoagulation was associated with PDVT/PE, and all-cause mortality.ResultsA total of 426 IDDVT inpatients with CUS follow-up were screened from 1502 distal DVT patients and finally enrolled. The median age was 67 years with 51.4% males and 15.5% cancer patients. The median follow-up was 11.6 months. There were 288 and 138 patients treated with or without anticoagulants, respectively. Patients in the non-AC group had less body mass index and more comorbidities. Patients in the AC group were treated with rivaroxaban or dabigatran (52.1%), low molecular weight heparin (42.7%), and warfarin (5.2%). The PSM generated 111 pairs of well-matched IDDVT patients with or without anticoagulation. The Kaplan–Meier analysis demonstrated that neither the incidence of PDVT/PE (5.4% vs. 2.7%, log-rank p = 0.313) nor all-cause mortality (27.9% vs. 18.9%, log-rank p = 0.098) was significant different between groups. Anticoagulation was not associated with PDVT/PE and all-cause mortality in the multivariable Cox regression analyses using the matched cohorts. The main risk factors for all-cause mortality were age, malignancy history, BMI, sepsis, heart failure, and white blood cell (WBC) count.ConclusionsIn hospitalized IDDVT patients, the thrombosis extension rate to PDVT/PE was low. Anticoagulation did not reduce the incidence of thrombosis extension of IDDVT and was not associated with all-cause mortality.

Efficacy and Safety of Anticoagulants for COVID-19 Patients in the Intensive Care Unit: A Systematic Review and Meta-Analysis.

This study aims to analyze the efficacy and safety of anticoagulants for COVID-19 patients in the intensive care unit. A comprehensive search was conducted using databases such as MEDLINE, PubMed, EuropePMC, Science Direct, Google Scholar, Clinicaltrial.gov, The Cochrane Central Register of Controlled Trial (CENTRAL, Cochrane Library) and several other published articles from the systematic review up to March 31, 2021. The Newcastle-Ottawa Scale (NOS) was used for the studies' qualitative assessment. The primary outcome examined was mortality rate, while the secondary included the length of stay (LOS) in thei care unit; hospital length of stay (HOS), coagulation markers including D-dimer, Platelet count, aPTT, PT and fibrinogen; markers of inflammation specifically C-reactive protein; and other adverse events ranging from hemorrhage to thrombosis. Additionally, the quantitative synthesis was conducted using fixed and random effects model in "The Revman 5.4", while heterogeneity was tested using the I-squared (I2) measure. A total of 1,062 articles were found during the initial search step and eventually 12 were chosen to be analyzed quantitatively in a meta-analysis. Comparison of the results related to anticoagulant group with no anticoagulant or standard care treatment showed that anticoagulant group significantly reduced mortality rate with RR= 0.53; 95 % CI, 0.30-0.95; P= 0.03, with I2 = 88% and venous thromboembolism (VTE) RR = 0.53; 95% CI, 0.37-0.76; P = .0007 with I2 = 35%. Based on the results, anticoagulants can mitigate mortality rate and VTE in COVID-19 patients.

Long term follow up of direct oral anticoagulants and warfarin therapy on stroke, with all-cause mortality as a competing risk, in people with atrial fibrillation: Sentinel network database study.

We investigated differences in risk of stroke, with all-cause mortality as a competing risk, in people newly diagnosed with atrial fibrillation (AF) who were commenced on either direct oral anticoagulants (DOACs) or warfarin treatment. We conducted a retrospective cohort study of the Oxford Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) database (a network of 500 English general practices). We compared long term exposure to DOAC (n = 5,168) and warfarin (n = 7,451) in new cases of AF not previously treated with oral anticoagulants. Analyses included: survival analysis, estimating cause specific hazard ratios (CSHR), Fine-Gray analysis for factors affecting cumulative incidence of events occurring over time and a cumulative risk regression with time varying effects.We found no difference in CSHR between stroke 1.08 (0.72-1.63, p = 0.69) and all-cause mortality 0.93 (0.81-1.08, p = 0.37), or between the anticoagulant groups. Fine-Gray analysis produced similar results 1.07 (0.71-1.6 p = 0.75) for stroke and 0.93 (0.8-1.07, p = 0.3) mortality. The cumulative risk of mortality with DOAC was significantly elevated in early follow-up (67 days), with cumulative risk decreasing until 1,537 days and all-cause mortality risk significantly decreased coefficient estimate:: -0.23 (-0.38-0.01, p = 0.001); which persisted over seven years of follow-up. In this large, contemporary, real world primary care study with longer follow-up, we found no overall difference in the hazard of stroke between warfarin and DOAC treatment for AF. However, there was a significant time-varying effect between anti-coagulant regimen on all-cause mortality, with DOACs showing better survival. This is a key methodological observation for future follow-up studies, and reassuring for patients and health care professionals for longer duration of therapy.

Outcomes by Class of Anticoagulant Use for Nonvalvular Atrial Fibrillation in Patients With Active Cancer

BackgroundThe choice of anticoagulant agent for patients with nonvalvular atrial fibrillation (NVAF) in the setting of active cancer has not been well studied. ObjectivesThe aim of this study was to compare the rates of cerebrovascular accident (CVA), gastrointestinal bleeding (GIB), and intracranial hemorrhage (ICH) in patients treated with direct oral anticoagulant agents (DOACs) compared with warfarin for NVAF in patients with active cancer. MethodsThis was a retrospective electronic medical record review of eligible patients treated at a cancer hospital. The outcome events were CVA; GIB; ICH; the composite of GIB, CVA, or ICH; and overall mortality. Propensity score matching (1:1) was conducted to select comparable patients receiving warfarin vs DOACs. Fine-Gray models were fitted for each outcome event. ResultsThe study cohort included 1,133 patients (mean age 72 ± 8.8 years, 42% women), of whom 74% received DOACs (57% received apixaban). After propensity score matching, 195 patients were included in each anticoagulant agent group. When comparing warfarin with DOACs, there were similar risks for CVA (subdistribution HR: 0.738; 95% CI: 0.334-1.629); ICH (subdistribution HR: 0.295; 95% CI: 0.032-2.709); GIB (subdistribution HR: 1.819; 95% CI: 0.774-4.277); and the composite of GIB, CVA, or ICH (subdistribution HR: 1.151; 95% CI: 0.645-2.054). ConclusionsPatients with active cancer had similar risks for CVA, ICH, and GIB when treated with DOACs compared with warfarin for NVAF.

Can Routine Blood Tests Be Used To Predict The Prognosis of COVID-19 Patients Using Antithrombotic Drugs

Background: COVID-19 may predispose to thromboembolism due to excessive inflammation, hypoxia, and immobilization. We investigated whether these antithrombotic drugs are useful or harmful to tackle COVID-19 and which laboratory parameters are more usable for this purpose. Materials and methods: In our study, patients diagnosed with COVID-19 while using antithrombotic drugs and COVID-19 patients who did not use antithrombotic drugs were compared. Demographic data, laboratory values, clinical results, duration of hospital stay, and mortality were noted and compared. Results: The study was conducted on 236 patients admitted to the emergency department. The mean value of creatine, LDH, PT, NLR, troponin, and ferritin were higher in the drug-using group. Home quarantine and hospitalization rate was 68.8% (n = 33) in antiplatelet users, and 46.2% (n = 6) in the anticoagulant group. Conclusion: The difference between the groups may have been caused by the number of chronic diseases and polypharmacy. The interaction of drugs used for the treatment of COVID-19 with antithrombotic agents is unknown. In addition, as the correlation between COVID-19 and thrombosis is not exactly known, adding antithrombotic drugs to the treatment of the disease is controversial. In our study, the biomarkers used to predict prognosis were worse in COVID-19 patients who continued antithrombotic therapy at the therapeutic dose. In the case of antithrombotic agents, the risks that may arise should always be considered. We recommend monitoring routine blood parameters, especially NLR, LDH, PT, APTT, troponin, and ferritin levels, for the prognosis monitoring of COVID-19 patients who will continue their current antithrombotic therapy

Safety of anticoagulation use for treatment of portal vein thrombosis in liver cirrhosis and its effect on hospital-based outcomes: an insight from a US nationwide database

Background and aimAnticoagulation use for portal vein thrombosis (PVT) in patients with advanced liver disease is controversial. We investigated the effect of anticoagulation on outcomes in patients with PVT with...

Review: Drug Discovery and Development of Warfarin

Background: The history of the discovery of Warfarin started from the plains of North America in Canada in 1920. Livestock in that area died from bleeding. Warfarin was first used in 1948 as a rodenticide, and in 1954 the US Food and Drug Administration (FDA) approved it for medical use as an anticoagulant.&#x0D; Purpose: This review article aims to discuss the history of the discovery of warfarin starting from the presence of blood clotting disorders to the point that researchers worked to find drugs that can inhibit blood clotting, namely the anticoagulant group.&#x0D; Research Methods: The method used is the study of relevant literature which is accessed through online sites such as Google Scholar, Research Gate, Science Direct, Springer Link, and NCBI.&#x0D; Conclusion: In its development, several trials such as in silico, preclinical, and clinical trials have shown significant results but are always associated with bleeding.&#x0D;

Pulmonary vein stump thrombosis after lung resection for lung cancer: clinical features and outcome.

Pulmonary vein stump thrombosis (PVST) is uncommonly encountered postoperative in-situ thrombosis in the stump of pulmonary veins after lung resection. Data regarding the incidence and clinical behaviour of PVST are scarce. Thus, this study aims to investigate the incidence, clinical characteristics and outcome of PVST after lung resection in patients with lung cancer. Follow-up enhanced chest computed tomography (CT) scans acquired after the surgery were retrospectively reviewed to determine PVST presence for patients with lung cancer who underwent lung resection in two tertiary referral centres. Out of the 1885 patients with lung cancer who underwent lobectomy or more extensive lung resection, PVST was observed in 37 patients (2.0%) on their follow-up chest CT. Most stump thrombi were observed in the left superior pulmonary vein [35 (94.6%)] and in patients who underwent left upper lobectomy [34 (91.9%)]. At the last CT follow-up of each patient, 33 (89.2%) exhibited complete resolution, three partial resolution and one stabilization. Eleven (29.7%) patients received anticoagulant therapy after the diagnosis. The rate of complete PVST resolution did not differ significantly between the anticoagulation and nonanticoagulation groups. None of the PVST patients experienced systemic embolic events, regardless of anticoagulation. The PVST incidence diagnosed at routine chest CT follow-up following lung cancer surgery was 2%. PVST was characterized by a benign clinical course without progression and systemic embolization, regardless of anticoagulation. However, further studies are required to determine individualized therapeutic strategies, including anticoagulation.

Clinical study of heparin anticoagulation scheme during plasma adsorption therapy for liver failure

Objective: To investigate the reasonable dosage of heparin anticoagulation scheme during plasma adsorption (PA) therapy for liver failure. Methods: Patients with liver failure treated with PA therapy were retrospectively collected and divided according to the anticoagulation scheme into the first-dose heparin anticoagulation group and the first-dose plus maintenance heparin anticoagulation group. Clinical data and laboratory test results were compared before and after treatment between the two groups. Paired t-tests were used for comparison within the normally distributed groups. An independent two-sample t-test was used for inter group comparison. Wilcoxon rank-sum test was used for measurement data that did not conform to a normal distribution. Fisher's exact test was used to compare the count data between groups. Results: There were 138 cases with liver failure treated with PA therapy from October 2017 to September 2020. Among them, 83 and 55 cases were in the first-dose heparin anticoagulation and first-dose plus maintenance heparin anticoagulation group, respectively. Age, gender, and laboratory data before treatment were comparable between the two groups. PA treatment was successfully completed in both groups of patient, and there was no statistically significant difference in the determination of coagulation level with plasma separators (Z=-0.15, P=0.216). There were different degrees of bleeding complications in both groups. In the first-dose heparin anticoagulation group, there were two cases (2.4%) of central venous catheter bleeding and one case (1.2%) of epistaxis. In the first-dose plus maintenance heparin anticoagulation group, there were five cases (9.1%) of central venous catheter bleeding, two cases (3.6%) of skin bleeding, one case (1.8%) of epistaxis, and one case (1.8%) of upper gastrointestinal bleeding. The incidence of bleeding complications was lower in the first-dose of heparin anticoagulation than first-dose plus maintenance heparin anticoagulation group, and the difference was statistically significant (P<0.001). The activated partial thromboplastin time of the two groups was prolonged after therapy withdrawal than with therapy, and the difference was statistically significant (first-dose heparin anticoagulation group: t=3.850, P=0.022; first-dose plus maintenance heparin anticoagulation group: t=6.733, P=0.007). The activated partial thromboplastin time was prolonged in patients with first-dose plus maintenance heparin anticoagulation than first-dose heparin anticoagulation group, and the difference was statistically significant (P=0.025). The total bilirubin of the two groups before and after PA was significantly changed (the first-dose heparin anticoagulation group: Z=-2.455, P=0.017; the first-dose plus maintenance heparin anticoagulation group: Z=-2.307, P=0.024), and there was no statistically significant difference between the two groups (P=0.412). There was no statistically significant difference in platelet changes before and after PA therapy between the two groups (the first dose of heparin anticoagulation group: Z=-0.529, P=0.480; the first-dose plus maintenance heparin anticoagulation group: Z=-0.276, P=0.362). Conclusion: Anticoagulation scheme without maintenance medication is feasible with prothrombin activity before ≤20-40%, activated partial thromboplastin time of ≤87 s (2 times the upper normal value), platelet count before treatment (excluding contraindications to heparin) ≥50×109/L, and the first dose of heparin administration of 0.2 mg/kg during PA therapy in patients with liver failure.

Comparison of transjugular intrahepatic portosystemic with endoscopic treatment plus anticoagulation for esophageal variceal bleeding and portal vein thrombosis in liver cirrhosis

Background and aim The optimal management of esophageal variceal bleeding (EVB) and portal vein thrombosis (PVT) in liver cirrhosis has not been well-established. The aim of the present study was to compare the efficacy and safety of transjugular intrahepatic portosystemic shunt (TIPS) and endoscopic treatment (ET) plus anticoagulation in cirrhotic patients with EVB and PVT. Patients and methods A total of 66 cirrhotic patients with PVT and EVB (31 in the TIPS group and 35 in the ET plus anticoagulation group) were evaluated retrospectively between January 2016 and January 2022. Results During the follow-up period, 85.5% of patients in the TIPS group achieved complete recanalization of the portal vein, as compared with 19.6% in the ET plus anticoagulation group (p < .001). The cumulative 5-year rate of variceal rebleeding in the TIPS group was significantly lower than that in the ET plus anticoagulation group (31.0 vs. 50.1%; p = .017). The TIPS group exhibited a significantly higher incidence of overt hepatic encephalopathy (HE) than the ET plus anticoagulation group (25.8 vs. 5.7%; p = .037). No difference in the 5-year survival rate (74.1 vs. 85.7%; p = .692) and probability of other complications was observed between the two groups. Conclusion TIPS was superior to ET plus anticoagulation in preventing variceal rebleeding and achieving recanalization of PVT but increased the incidence of overt HE without improving the survival rate.

Fascia Iliaca Block in Hip and Femur Fractures to Reduce Opioid Use

BackgroundFascia iliaca compartment block (FICB) has become a keystone technique for acute pain management in patients with hip and proximal femur fractures. ObjectivesTo demonstrate that administering FICB preoperatively to patients with hip or proximal femur fractures in the emergency department (ED) is likely to reduce opioid use and related complications, and to decrease hospital length of stay (LOS). MethodsAn unblinded study of adult patients with hip and proximal femur fractures who consented to receive an FICB with 30 cc of bupivacaine with epinephrine administered in the ED. We compared this group with a contemporaneous group of controls who only received systemic opioids. Over the course of approximately 6 months, main outcome measured between the two groups was amount of morphine equivalents given from block administration until 8 h after. We also compared complications such as delirium, constipation, and bleeding rates (oozing from injection site or hematoma formation). ResultsA total of 166 patients with hip and proximal femur fractures from August 12, 2018 to April 25, 2021; 81 received FICB plus systemic opioids, and 85 received only systemic opioids. Among the FICB group, morphine equivalents were reduced by 0.6 mg/h with no significant difference in LOS. A statistically significant difference in opioid-related adverse outcomes was found between the anticoagulated group vs. the no anticoagulation group. ConclusionsFICB is a safe and effective preoperative technique for initial pain management in patients with hip and proximal femur fractures, as it can also be used with additional systemic opioids. FICB administration may reduce systemic opioid use preoperatively, thus reducing opioid-related adverse effects with no significant impact on hospital LOS.

Extended Anticoagulation After Pulmonary Embolism: A Multicenter Observational Cohort Analysis.

BackgroundPulmonary embolism (PE) has a long‐term risk of adverse events, which can be prevented by extended anticoagulation. We compared clinical characteristics and outcomes between patients treated with 2‐year extended anticoagulation and those who were not, in a population who had completed an initial phase of 3 to 6 months of anticoagulant therapy after acute PE.Methods and ResultsObservational cohort analysis of patients with PE who survived an initial phase of 3 to 6 months anticoagulation. Primary efficacy outcome was all‐cause death or recurrent venous thromboembolism. Primary safety outcome was major bleeding. In total, 858 (71.5%) patients were treated with and 341 (28.5%) were treated without extended anticoagulant therapy during the active study period. Age <65 years, intermediate‐high or high‐risk index PE, normal platelet count, and the absence of concomitant antiplatelet treatment were independently associated with the prescription of extended anticoagulation. The mean duration of the active phase was 2.1±0.3 years. The adjusted rate of the primary efficacy outcome was 2.1% in the extended group and 7.7% in the nonextended group (P<0.001) for patients treated with extended anticoagulant therapy. Rate of bleeding were similar between the extended anticoagulant group and the nonextended group.ConclusionsExtended oral anticoagulation over 2 and a half years after index PE seems to provide a net clinical benefit compared with no anticoagulation in patients with PE selected to receive extended anticoagulation. Randomized clinical trials are warranted to explore the potential benefit of extended anticoagulation in patients with PE, especially those with transient provoking factors but residual risk.

Effects of Anticoagulants and Immune Agents on Pregnancy Outcomes and Offspring Safety in Frozen-Thawed Embryo Transfer Cycles-A Retrospective Cohort Study.

The application of anticoagulants and immune agents in assisted reproduction technology has been in a chaotic state, and no clear conclusion has been reached regarding the effectiveness and safety of this treatment. We aimed to explore the potential association between adjuvant medication and pregnancy outcomes and offspring safety in a retrospective cohort study including 8,873 frozen-thawed embryo transfer cycles. The included cycles were divided into three groups according to the drugs used, namely, the routine treatment group (without anticoagulant agents and immune agents), the anticoagulant agent group, and the immunotherapy group. Among normal ovulatory patients, those who used immune agents had a 1.4-fold increased risk of miscarriage (≤13 weeks), but a 0.8-fold decreased chance of birth (≥28 weeks) compared with the routine treatment group. Among patients with more than 1 embryo transferred, those who used anticoagulant agents showed a 1.2-fold higher risk of multiple birth than those undergoing routine treatment. Among patients without pregnancy complications, anticoagulant treatment was associated with a 2.1-fold increased risk of congenital anomalies. Among young patients (<26 years) with a singleton pregnancy, the neonatal birth weight of the immunotherapy group and the anticoagulant treatment group was 305.4 g and 175.9 g heavier than the routine treatment group, respectively. In conclusion, adjuvant anticoagulants or immune agent treatment in assisted reproductive technology should be used under strict supervision, and the principle of individualized treatment should be followed.

Exploratory Use of Glycoprotein IIb/IIIa Inhibition in Prevention of Blalock-Taussig Shunt Thrombosis.

Morbidity and mortality related to modified Blalock-Taussig shunt (mBTTS) thrombosis remain a significant risk. Platelet inhibition following mBTTS may reduce this risk. However, oral antiplatelet agents have variable absorption following surgery. We determine risk factors for mBTTS thrombosis and hypothesize that IV glycoprotein IIb/IIIa inhibitor (tirofiban) as a bridge to oral aspirin reduces the rate of shunt thrombosis in the immediate postoperative period. End points within the 14-day follow-up period include mBTTS thrombosis, overall thrombosis, bleeding, length of stay, and mortality. Retrospective, Institutional Review Board-approved cohort study. Single-center cardiac ICU. Patients under the age of 18 who had an mBTTS placed within the study period of January 2008 to December 2018 were included. Patients were divided into two groups: standard of care (SOC) anticoagulation alone and SOC with tirofiban as a bridge to oral aspirin. Freedom from mBTTS thrombosis was estimated using the Kaplan-Meier method. A multivariable predictive model using the four most significant risk factors was developed using logistic regression. A total of 272 patients were included: 36 subjects in the SOC/tirofiban group and 236 in the SOC group. Shunt thrombosis occurred in 26 (11%) SOC group with zero in SOC/tirofiban group ( p = 0.03). The median time to thrombosis was 0 days (range, 0-12 d). The area under the curve for the predictive model (anticoagulation group, history of coagulopathy, intraoperative shunt clipping, and shunt size/weight ratio) is 0.790 ( p < 0.001). Prevalence of bleeding and mortality was not significantly different between the groups. Highest risk for shunt thrombosis following mBTTS occurs within the first few days after surgical procedure. Tirofiban is a safe addition to SOC and may be an effective strategy to prevent early mBTTS thrombosis.

Complication Rates in Patients Using Intracavernosal Injection Therapy for Erectile Dysfunction With or Without Concurrent Anticoagulant Use-A Single-Center, Retrospective Pilot Study.

BackgroundIntracavernosal injection therapy (ICI) is an effective intervention used to treat erectile dysfunction (ED). It has been proposed that caution should be exercised when prescribing ICI to patients currently taking anticoagulants (AC) due to the theoretical increased risk of bleeding, however, there is limited literature describing complication rates of actively anticoagulated patients utilizing ICI.AimWe sought to determine whether there was a difference in bleeding and other complications in a cohort of patients using ICI therapy with or without concurrent AC use.MethodsWe reviewed our institutional electronic health record and identified 168 patients who were seen in our clinic from January to August 2020 who had either currently or previously utilized ICI therapy for ED treatment. These patients were surveyed regarding their ICI therapy as well as given the erectile dysfunction inventory for treatment satisfaction questionnaire. Data from 85 patients was obtained; 43 concurrently using AC during ICI therapy and 42 with no AC use. Fisher's exact test for categorical variables and a 2-tailed t-test were used with P < .05 considered to be significant.OutcomeDocumented bleeding events (eg, bruising, hematoma), complications, and mean erectile dysfunction inventory for treatment satisfaction scores were compared between the 2 groups.ResultsThere were more absolute bleeding complications in the AC group vs the no AC group, with 3 of 43 AC patients (7%, 95% confidence interval: 2.4–18.6) and 0/42 no AC patients (0%, 95% confidence interval: 0–8.4) experiencing some type of bleeding complication on ICI. However, there was no statistically significant difference found in overall or stratified documented bleeding events and complications between the 2 groups.Clinical ImplicationsPatients with concurrent AC usage on ICI therapy reported a higher rate of absolute bleeding complications than our non-AC group.Strengths and LimitationsThe strength of this study is addressing question of safety of ICI therapy in patients with concurrent AC usage. Limitations include single-center retrospective study design and underpowered sample size limiting confidence with which conclusions from data should guide future patient counseling regarding ICI risks.ConclusionFindings from a single-center cohort of patients suggest that ICI therapy may be a safe and effective treatment modality for ED in patients with concurrent anticoagulant usage, however, given the higher rate of absolute bleeding events in our AC cohort, future assessment in a higher-powered study is warranted in determining a more accurate estimation of risk or propensity for bleeding complications in patients on AC using ICI therapy.Blum KA, Mehr JP, Green T, et al. Complication Rates in Patients Using Intracavernosal Injection Therapy for Erectile Dysfunction With or Without Concurrent Anticoagulant Use—A Single-Center, Retrospective Pilot Study. Sex Med 2022;10:100535.

Age-related differences in the survival benefit of the administration of antithrombin, recombinant human thrombomodulin, or their combination in sepsis

Disseminated intravascular coagulation (DIC) is one of the major organ dysfunctions associated with sepsis. This retrospective secondary analysis comprised data from a prospective multicenter study to investigate the age-related differences in the survival benefit of anticoagulant therapy in sepsis according to the DIC diagnostic criteria. Adult patients with severe sepsis based on the Sepsis-2 criteria were enrolled and divided into the following groups: (1) anticoagulant group (patients who received anticoagulant therapy) and (2) non-anticoagulant group (patients who did not receive anticoagulant therapy). Patients in the former group were administered antithrombin, recombinant human thrombomodulin, or their combination. The increases in the risk of hospital mortality were suppressed in the high-DIC-score patients aged 60–70 years receiving anticoagulant therapy. No favorable association of anti-coagulant therapy with hospital mortality was observed in patients aged 50 years and 80 years. Furthermore, anticoagulant therapy in the lower-DIC-score range increased the risk of hospital mortality in patients aged 50–60 years. In conclusion, anticoagulant therapy was associated with decreased hospital mortality according to a higher DIC score in septic patients aged 60–70 years. Anticoagulant therapy, however, was not associated with a better outcome in relatively younger and older patients with sepsis.