Thromboembolic Episodes Research Articles

Extended anticoagulation for venous thromboembolism: A survey of the American Venous Forum and the European Venous Forum

ObjectiveExtended anticoagulation therapy should always be considered after standard treatment of an unprovoked episode of venous thromboembolism (VTE). It can also be considered for selected patients with provoked VTE. However, the evidence-based protocols suggested by some clinical guidelines and risk assessment tools to guide this practice are limited and ambiguous. The goal of the present survey research was to analyze current practices in applying extended anticoagulation therapy for patients with VTE among members of the American Venous Forum (AVF) and European Venous Forum (EVF). MethodsAn online survey was created by the AVF Research Committee. The survey consisted of 16 questions to identify the country of practice, specialty, experience of the participating physicians, and their clinical practice patterns in applying extended anticoagulation therapy for VTE patients. The survey was distributed via e-mail to the members of the AVF and EVF. ResultsA total of 144 practitioners, 48 AVF members (33%) and 96 EVF members (66%), participated in the survey. Most of the respondents identified themselves as vascular specialists with primary certification in vascular surgery (70%), vascular medicine or angiology (9%), and venous disease or phlebology (3%). Of the 144 respondents, 72% believed that the risk of VTE recurrence will generally overweigh the risk of bleeding for patients with unprovoked VTE. Extended anticoagulation therapy might be used by 97% of providers. Different patterns in real world clinical practice were identified. More than one half of the practitioners estimated the VTE recurrence and bleeding risk subjectively. The antithrombotic drugs most commonly used for secondary prophylaxis were rivaroxaban, apixaban, warfarin, dabigatran, and aspirin, in decreasing order of frequency. Among the reasons selected for not regularly considering extended anticoagulation therapy were the lack of specific clinical practice guidelines (24%), lack of reported evidence (9%), and absence of valid VTE and/or bleeding risk prediction calculators (8%). Twelve participants (8%) stated that extended anticoagulation therapy would not be beneficial for most patients with VTE. Ten participants (7%) indicated that prescribing extended anticoagulation therapy was outside the scope of their specialty. ConclusionsDifferent practice patterns exist regarding extending anticoagulation therapy beyond the standard treatment for patients with VTE. Major gaps in knowledge remain a serious challenge at least partially explaining the inaccuracy and inconsistency in long-term VTE management. Appropriately designed studies are needed to evaluate risk stratification tools when contemporary best medical therapy is used, accurately predict VTE recurrence and its long-term outcomes, and tailor safe and effective secondary prophylaxis.

Science, Medicine, and the Anesthesiologist

Science, Medicine, and the Anesthesiologist

No VTE Recurrence After 1-Year Follow-Up of Hospitalized Patients With COVID-19 and a VTE Event: A Prospective Study

No VTE Recurrence After 1-Year Follow-Up of Hospitalized Patients With COVID-19 and a VTE Event: A Prospective Study

Abstract P4-02-15: Thromboembolic events (TEE) in patients with HER2-negative, hormone receptor-positive metastatic breast cancer treated with Ribociclib combined with Letrozole or Fulvestrant. Real-world data

Abstract Background: Breast cancer is the most common cancer diagnosed among women worldwide. More than 70% of breast cancers are hormone receptor (HR)-positive, for which endocrine therapy (ET) is the preferred initial treatment especially so for those with low burden disease. Majority of patients with HR-positive metastatic breast cancer (mBC) acquire resistance to endocrine therapy. CDK4/6 inhibitors modulate this resistance and are integral treatment for patients with advanced HR-positive, HER2-negative breast cancer. Since their approval, CDK4/6 inhibitors are widely used in clinical practice. Thromboembolic events (TEE) were not a major issue among patients treated on clinical trials. However, conflicting data starts to emerge describing higher than expected rates of both arterial and venous thrombosis in patients treated with CDK4/6 inhibitors. In this study, we use real world data to study TEE rates in patients treated with ribociclib in real-world settings.Methods: The study is a retrospective analysis of individual patients’ data. All consecutive patients with mBC treated with ribociclib combined with aromatase inhibitors or fulvestrant were reviewed. Data were collected from patients’ electronic medical records and from radiology department archives. All episodes of radiology confirmed arterial or venous thrombosis were recorded. TEE was considered ribociclib related if diagnosed while patients on the drug or withing 4 weeks after the last dose.Results: During the study period, a total of 305 patients were enrolled. Median age (range) was 49 (22-87) years. All patients had metastatic disease and 168 (55.1%) were de novo metastasis. Most (n=241, 79.0%) of the patients had visceral metastasis at time of ribociclib therapy; only 64 (20.9%) had bone-only disease. Ribociclib was used in combination with letrozole in first-line setting in 195 (63.9%) and with fulvestrant or letrozole in 110 (35.9%) patients who failed one or more lines of ET or chemotherapy. Median duration (range) of ribociclib therapy was 7 (1-45) months. Episodes of venous thromboembolism were confirmed in only 5 (1.6%) patients; 3 were PE with or without DVT and 2 were lower extremity DVT and all were symptomatic. Another patient had arterial thrombosis (lower limb ischemia). During the chart review, 7 (2.3%) more patients had a confirmed diagnosis of VTE prior to ribociclib and another 4 (1.3%) patients had a confirmed episode after (range: 2-7 months) stopping it. All patients were treated with low-molecular heparin (LMWH) with no complications. Given the small number of patients with TEE, no clinical or pathological predictors could be used to identify subgroups of patients at higher risk for TEE while on ribociclib.Conclusions: In real-world settings, and contrary to recent reports, breast cancer patients treated with ribociclib with AI or fulvestrant are not at higher risk for arterial or venous thromboembolic events. Patients had similar rates prior to initiation, and after stopping ribociclib. Citation Format: Hikmat Abdel-Razeq, Faris Tamimi, Sarah Edaily, Baha' Sharaf, Mahmoud Abunasser, Osama Salama, Rashid Abdel-Razeq, Hazem Abdulelah, Rayan Bater. Thromboembolic events (TEE) in patients with HER2-negative, hormone receptor-positive metastatic breast cancer treated with Ribociclib combined with Letrozole or Fulvestrant. Real-world data [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-02-15.

The Birmingham and Black Country cohort of Venous Thromboembolism (BBC-VTE) registry: Rationale, design and preliminary results

The Birmingham Black Country Venous Thromboembolism registry (BBC-VTE) is a multi-ethnic cohort of patients who suffered a first episode of venous thromboembolism (VTE) and were admitted to various hospital sites across the West Midlands and Black Country regions in the United Kingdom. The BBC-VTE registry is a retrospective, observational cohort study which aims to collect data on outcomes including mortality, bleeding and VTE recurrence in this patient cohort. In addition, the comprehensive, structured data collected will allow us to conduct machine learning analyses for risk prediction in such patients and also to compare to previously derived mortality scores such as the PESI and the simplified PESI (sPESI).Our registry included 2183 patients admitted to hospital between the years 2012–14 and 2016–18 with a first episode of VTE and the mean follow up was 36 months. The cohort was ethnically diverse with 72.5% white Caucasian, 8.2% Asian (including South Asian), 6.7% black, and 11.7% of unknown/other ethnicity. Of those admitted during the collection period 56% had PE, 40% had DVT, with the rest presenting with both PE and DVT. Around 7% of patients went on to develop a bleeding episode and 36% died (all-cause mortality). Of the deaths, 10% of patients died within 30-days of admission (30-day mortality), with 16% dying within 90 days. In summary, this study investigates real-world outcomes of patients after the first index VTE event and attempts to bridge the gap in evidence for contemporary data in this population which will allow to construct more accurate risk prediction tools and management decisions.

Safety of Bariatric Surgery in Obese Patients With Hypertrophic Cardiomyopathy

Obesity is an independent risk factor for heart failure in patients with hypertrophic cardiomyopathy (HC). In this study, we examined national trends and early outcomes of bariatric surgery for obesity in patients with HC. Using the weighted discharge data from the National Inpatient Sample, we identified adult patients with HC who underwent elective bariatric surgery for obesity between 2011 and 2017. A total of 443 obese patients with HC were identified, and 42% (n=185) had obstructive HC. The annual number of patients increased from 18 in 2011 to 130 in 2017. Overall, the median (interquartile range) age was 50 (43 to 57) years, and 85 patients (19%) were 60 years or older. Approximately 20% (n=90) of the patients had heart failure at the time of operation. Atrial fibrillation was present in 83 patients (19%), and 22% (n=95) of the cohort had a pacemaker or automatic cardiac defibrillator implanted before the operation. Laparoscopic sleeve gastrectomy (72%, n=318) and laparoscopic Roux-en-Y gastric bypass (25%, n=110) were the most commonly performed bariatric procedures. Overall, patients stayed in the hospital for a median (interquartile range) of 2 (1 to 2) days. During the hospital stay, there were no deaths, myocardial infarctions, or documented episodes of thromboembolism. In conclusion, bariatric surgery in patients with HC is performed more frequently in recent years and is safe and associated with few perioperative complications. Because of the impact of obesity on long-term survival, clinicians should strongly consider bariatric surgery for obese HC patients who do not respond to conservative weight loss measures.

Bleeding Complications in Relation to the International Normalized Ratio for Dental Extractions in Patients under Chronic Anticoagulant Therapy - An Evaluative Study.

Recent simple dental extraction protocols suggest that therapeutic levels of the anticoagulant drug should be maintained because bleeding complications could be managed with local haemostasis manoeuvres. The aim of the present study was to evaluate the association between bleeding complications and the international normalized ratio (INR) values in patients after dental extractions completed with a plug of bismuth subgallate, without interrupting anticoagulant administration. Patients undergoing oral Vitamin K antagonist chronic anticoagulant therapy requiring simple dental extractions were included in the study. INRs were recorded on the day of the surgery, and dental extractions were performed applying bismuth subgallate as a haemostatic agent. Patients took their anticoagulation drug normally. Bleeding complications were recorded. The study included 694 patients, of whom 11 (1.58%) presented mediate post-operative bleeding that was effectively controlled through local manoeuvres. No episode of thromboembolism or infectious endocarditis was observed. The incidence of bleeding complications was not related to the INR values (P > 0.05). INR values were not related to bleeding complications when simple dental extractions were performed applying bismuth subgallate as a haemostatic agent.

Острый тромбоз бедренно-подколенного сегмента, осложнившийся ТЭЛА. Описание клинического случая

Deep vein thrombosis (DVT) and PE are classified as venous thromboembolic complications (VTEO), they remain an important problem in clinical medicine and affect the professional sphere of doctors of all specialties, since their pathogenesis is based on hypercoagulation caused by various causes, in particular, genetic defects of blood clotting factors, diseases of the cardiovascular system, severe injuries and subsequent immobilization, iatrogenic lesions, etc. The article describes a clinical case of treatment, observation and treatment of a patient diagnosed with Subacute phlebothrombosis of the left lower limb. Popliteal-femoral segment. VN II. Non-massive bilateral pulmonary embolism. DN 0-1. Arterial hypertension 2 stages, 2 degrees, risk 3.CHF 1. The study was conducted on the basis of the Regional Clinical Hospital No. 2 in Tyumen. Aim. Description of the identified case, subcute thrombosis of the femoral-popliteal segment, complicated by PE, for a more complete understanding of the problem due to the high prevalence of this pathology in the structure of vascular diseases; analysis of the possibility of early diagnosis and treatment on the example of a specific case. Material and methods. A retrospective analysis of the patient’s medical history was carried out and an example from the practice of the admission department of the Regional Clinical Hospital No. 2 in Tyumen of clinical observation of a patient diagnosed with subacute thrombosis of the femoral-popliteal segment, complicated by PE. Anamnesis of life and disease, clinical, laboratory and instrumental data were evaluated. Conclusion. The most realistic prevention of threatening PE is the effective treatment of acute venous thrombosis. It is very important to timely and adequately assess the risk of thrombosis in each individual case. The consequences of the lack of prevention of thrombosis lead to an increased risk of repeated episodes of venous thromboembolism, the development of post-thrombotic disease, and can also lead to death from PE. It should be noted that it is necessary to monitor CT scans – angiopulmonography – to control the development of pulmonary embolism as a complication against the background of newly formed thrombosis of the femoral-popliteal segment. Sanitary and educational work, active tactics, timely treatment and hospitalization of patients with acute deep vein thrombosis BPS will contribute to improving the quality of life of this category of patients, reducing the percentage of PE and deaths.

Predictors of recurrence of venous thromboembolic disease after discontinuing of anticoagulation: a prospective cohort study.

We aim to evaluate factors associated with the recurrence of thromboembolic episodes among patients with a first episode of venous thromboembolic disease during anticoagulation treatment and at least one year after treatment suspension. A prospective cohort of patients with a first episode of deep vein thrombosis confirmed by Doppler ultrasound and initiated anticoagulation treatment. Participants were registered in the Institutional Registry of Thromboembolic Disease between June 2015 and March 2019. Patients with cancer, with permanent inferior vena cava filter implant, and those who refused to participate or did not provide informed consent were excluded. All patients were evaluated within treatment at 30 days and at least one year after the suspension of anticoagulation with a D-dimer study and an ultrasound. All patients were evaluated for recurrence, bleeding (major and minor), and death. A total of 304 patients were recruited during the study period. Seventy-three percent were female, and the median age was 80 years. The rate of recurrence rate during anticoagulation treatment was 5% (N = 16/303; 95% confidence interval: 3 to 8), and 5% during post-suspension follow-up (N = 11/202; 95%CI: 3 to 9). The overall bleeding rate was 13% (N = 39; 95%CI: 9 to 17), and 5% for major bleeding. Patients who recurred had higher basal D-dimer mean, higher neutrophils and monocytes, and a higher prevalence of age-adjusted D-dimer ratio greater than 0.5 before discontinuation. In addition, they more frequently had complete leg involvement by ultrasound and received a shorter treatment. Although some baseline and pre-suspension parameters had a higher recurrence incidence, statistical significance was not reached, probably due to small statistical power and a short-term follow-up.

DIAGNOSTIC DILEMMA IN RENAL TRANSPLANT COVID-19 POSITIVE PATIENT - A CASE REPORT

INTRODUCTION: Covid 19 infection is caused by SARS-COVID virus and responsible for pandemic in 2020. Most common signs and symptoms include fever, cough, lower respiratory tract infection etc. CASE REPORT: A 51 year old male patient, a known case of diabetes, hypertension and chronic renal disease with renal transplant 3 years back and on immunosuppressive drugs was complaining of high degree fever, myalgia, fatigue, abdominal pain, more over the left upper abdomen. USG shows Hypoechoic collection in the inferior pole of spleen measuring 5x6cm with mild perisplenic collection, suggestive of splenic abscess. The patient had undergone emergency laparotomy of splenectomy. On histopathology, refractile, aseptate, broad angle fungal hyphae suggestive of Mucormycosis. PAS stain was Positive. DISCUSSION: Spleen is a rare site for fungal infection. With superadded COVID 19 infection and bilateral basal consolidation in the lungs, the underlying splenic lesion will be confused as part of thromboembolic episodes rather than fungal infection. Hence, delay in treatment of antifungal drugs will lead to mortality in such cases. CONCLUSION: In COVID 19 infections, the rare manifestation of fungal infection to be considered while treating the immunosuppressive patients.

Pulmonary Embolism in Patients with COVID-19: Comparison between Different Care Settings.

The clinical characteristics and outcomes of patients with coronavirus disease 2019 (COVID-19) who develop pulmonary embolism (PE) in the full spectrum of patient care settings need to be elucidated. The aim of this study was to compare the clinical characteristics, treatment, and 90-day outcomes in patients diagnosed with PE while recovering from COVID-19 in the outpatient setting versus those who were diagnosed with PE while being hospitalized with COVID-19. Data from the international Registro Informatizado de Enfermedad TromboEmbólica (RIETE) registry were used. The major study outcomes were all-cause death, major bleeding, and venous thromboembolism (VTE) recurrences during the first 90 days after PE. From March 2020 to March 2021, 737 patients with COVID-19 experienced acute PE. Of these, 340 (46%) were recovering from COVID-19 as outpatients (267 patients who had been treated at home for COVID-19 and 73 discharged after being hospitalized with COVID-19). Compared with inpatients with COVID-19, those recovering in the outpatient setting upon PE were less likely to be men (odds ratio [OR]: 0.54; 95% confidence interval [CI]: 0.40-0.72) and less likely to have hypertension (OR: 0.55; 95% CI: 0.41-0.74) or diabetes (OR: 0.51; 95% CI: 0.33-0.76). At 90-day follow-up, eight patients (none recovering from COVID-19 as outpatient vs. 2.4% of inpatients with COVID-19) developed recurrent VTE, 34 (1.9 vs. 7.9%) had major bleeding, and 128 (10 vs. 24%) died. On multivariable analysis, inpatients with COVID-19 were at a higher risk of major bleeding (adjusted hazard ratio [HR]: 6.80; 95% CI: 1.52-30.4) or death (adjusted HR: 2.24; 95% CI: 1.40-3.58). In conclusion, using a large multinational registry of patients with COVID-19 who experienced PE, thromboembolic episodes occurring in those recovering from COVID-19 as outpatients were associated with less ominous outcomes than inpatients with COVID-19.

Застарелое повреждение мышц надплечья и вращательной манжеты плеча: клинический кейс миофасциальной транспозиции

Introduction A case of a successful surgical treatment of a neglected injury of the upper arm muscles and rotator cuff in a working-age man with a history of an episode of thromboembolism of small branches of the pulmonary artery is presented. The aim of this study was to demonstrate one of the approaches to surgical treatment of this pathology that resulted in the improvement of upper limb function and the quality of life of the patient. Material and methods A comprehensive study of the patient's outpatient and inpatient records, results of clinical, instrumental and laboratory methods, the types of intervention and rehabilitation along with medical prevention of thrombosis are described in detail. Results Eight months after the surgery, there was an improvement in the function of the right shoulder joint. The range of active motion significantly increased; the DASH score decreased from 136 to 52 points; pain decreased from 46 to 31 points according to VAS; the level of self-service significantly improved. Discussion Сombined techniques of preserved muscle transposition to replace the lost function of the damaged ones was a condition and a guarantee of the achieving significant progress in the anatomical and functional status of the patient. Nevertheless, a further search for more rational technologies for restorative reconstruction in the disorders under consideration seems appropriate. Conclusion A correctly chosen and based on clinical and instrumental data transposition of the tendons of the active muscles of the shoulder joint area to replace the lost shoulder antagonists provides improvement of the upper arm function and patients’ quality of life while the justified tactics of thromboprophylaxis allows control of hemostasis and absence of vascular failures.

Atypical Presentations of Appendicitis

Appendicitis has its acute, subacute, recurrent and chronic forms. Appendicitis is commonly predisposed to and precipitated by a single or a combination of multiple discrete factors like obstruction of lumen, ischemia from thromboembolic episodes, infection or idiopathic etc. Typically, it starts as umbilical or peri-umbilical or midline abdominal dull aching pain that soon gets localized in the right iliac region. Movements worsen the pain. Other typical features include nausea, vomiting, anorexia, pyrexia, preference to lie down with or without curling up, chills, constipation, diarrhea, fever, shaking etc. The atypical symptoms of appendicitis include a dull or sharp pain anywhere in the abdomen, back, rectum, painful urination, bloating, flatulence, generalized abdominal tenderness, distension simulating acute intestinal obstruction, enlarging abdominal mass with or without overlying skin erythema, normal bowel movements, normal vital signs and even with no pain, no nausea, no vomiting no pyrexia or no weight loss. These atypical symptoms very often misguide the primary care physicians and the surgeons resulting in failure of diagnosis putting the patients to the risks of life-endangering complications. Diagnosis of appendicitis in absence of typical features are to be made from pre-occupied knowledge and clinical suspicion with or without the help of biochemical and/or imaging studies. Early and timely diagnosis and appropriate treatment are essential to save the life and to reduce the morbidity as well. Appendicitis should be thought in all cases of abdominal pain irrespective of its type and location, as must meningitis be thought in all cases of headaches. KYAMC Journal.2021;12(02): 101-106

British Society for Haematology guidelines for the management of adult myelodysplastic syndromes.

British Society for Haematology guidelines for the management of adult myelodysplastic syndromes.

Tissue Factor Expression As a Prognostic Marker in Patients with B-Cell Malignant Lymphoma

Background. Studies in tumor cell lines have shown an increased expression of TF. Expression of TF in adenocarcinoma of the pancreas is associated with tumor progression. It has been described that between 5% and 10% of patients with malignant lymphoma (ML) may develop VTD. The mechanisms of ML-associated thrombosis are unknown, however, expression of functional TF may increase as much as 75-fold in peripheral blood monocytes, particularly during relapse. As expected, thrombosis was found in patients with the highest TF levels. The role of TF in the biology of ML has not yet been determined. Considering indirect evidence, it seems that, besides its procoagulant effects, TF may have a role in tumor progression.Objective. The purpose of the present study was to elucidate whether the interaction of tissue factor and TF/VIIa could induce relapsed in non Hodgkin Lymphoma patients.Patients and Methods. We therefore performed a prospective study (cohort) to evaluate the risk of TF in non Hodgkin Lymphoma patients without a previous episode of venous thromboembolism. 59 patients 30 women and 29 men were enrolled in this study. The median age was 43.3 ± 14.5 (range 20 to 59). The TF and FT/VIIa activity was performed on fresh plasma (American Diagnostics, USA), and other tests (PC, PS, AT and activated protein C resistance) (STAGO, Asnieres, Francia).Results.59 patients with B-cell ML, 30 women and 29 men with a mean age of 43.3 years (ranges 20 to 59). According to the Ann Arbor Staging system, 44% percent of patients (n=26) had a stage IV and only 14% at stage I. ML was mostly limited to lymph nodes (74%).Results of hemostatic markers were between the normal ranges. However, concentrations of factors involved in the initiation phase of fluid phase of blood coagulation (TF, FT/VIIa complex, and FVII) had an abnormal distribution. None case with APCR was found.Comparison between complete remission and relapsing patients. Thirty-one patients (52.5%) achieved complete remission at the end of follow-up and 28 (47.5%) relapsed. Mean follow up for patients with complete remission was 48 months vs. 18 months for relapsing patients (p <0.001). After comparing TF concentrations between the groups, relapsing patients had higher levels of TF (p=0.005). TF/FVIIa complex levels were also significantly higher in patients with relapsing disease (p=0.019). As expected LDH levels were significantly lower in patients with complete remission (p=0.0001).TF levels and response to treatment. Twenty-nine patients had normal TF levels. Relapses were more frequently found in patients with elevated TF concentrations (n=19) as compared with patients with normal TF levels (n=9) (p=0.013). Elevated TF/FVIIa complexes levels were also more frequently seen among patients with relapsing ML (n=32) as compared with patients with complete remission (n=27) (p=0.046).As expected, other factors associated with a poor prognosis were DHL levels (p=0.001) and IPI (p=0.001).Discussion. TF and TF/FVIIIa concentrations were significantly different in patients who achieved complete remission as compared with those with relapse after treatment. As expected for the staging of patients included LDH serum levels as well as IPI score were also significantly different between these two groups of patients. Moreover, estimation of the relative risks associated with relapsing disease showed that also these four variables were associated with relapsing disease. However, linear regression analysis showed that TF, LDH, and IPI but not TF/FVIIa complexes remained as a risk factor for relapse in patients with ML. To our knowledge, we have demonstrated for the first time that high TF concentration is a prognosis factor for relapse in patients with B-cell ML.Our results seem consistent with previous reports regarding an association between the increased TF expression and advanced staging of the malignant disease. It has been demonstrated the presence of high plasma levels of TF and FVIII in patients with solid tumors suggesting that it may be an important mechanism to activate blood coagulation system in cancer patients. Tumor cells may also induce TF expression on the cell surface of peripheral blood monocytes and macrophages. DisclosuresNo relevant conflicts of interest to declare.

Prevalence of Thromboembolic Complications in COVID-19 Infection: A Systematic Review and Meta-Analysis

Introduction: The coronavirus disease (COVID-19) infection is proved to be involved in the onset of thromboembolism episodes. This study aims to evaluate the prevalence of thromboembolic complications in patients with COVID-19 from March until May 2020. Methods: A literature review was conducted in MEDLINE (via PubMed), Scopus, Embase, Cochrane, and CINHAL without any language and date of publication restriction (Prospero registration number CRD42020186925). The inclusion criteria were as following: 1) patients with diagnosis of COVID-19; 2) occurrence of thromboembolic event, and 3) patients older than 18 years of age. A multi-variable random effects model was computed accounting for correlations among outcomes by considering a heterogeneous compound symmetry covariance matrix. Results: Observational studies included 2,442 participants from 268 to 7,999 participants per study, 1,014 (41.52%) were male and 825 (33.78%) were female. The multi-variable pooled event rate of acute myocardial infarction was rare, estimated to be 0.03 (95% confidence interval [CI]: 0.00–0.07; p=0.23); this is also true for the meta-analytical estimate of disseminated intravascular disease which was 0.04 (95% CI: 0.00–0.08; p=0.03). Conversely, other events were found to be more frequent. Indeed, the pooled proportion of pulmonary embolism was 0.14 (95% CI: 0.08–0.20; p&lt;0.001), while the venous thromboembolic event rate is 0.15 (95% CI: 0.09-0.30; p=0.04). The pooled intrahospital mortality rate was equal to 0.12 (95% CI: 0.08–0.16; p&lt;0.001). Conclusions: Thromboembolic events, particularly venous thromboembolic event rate and pulmonary embolism, are a frequent complication in patients hospitalised with COVID-19. These findings suggest that the threshold for clinical suspicion should be low to trigger prompt diagnostic testing and that evaluation of therapeutic treatment should be considered in patients in intensive care units with COVID-19.

Prescription of Direct Oral Anticoagulants to Patients With Moderate-to-Advanced CKD: Too Little or Just Right?

Chronic kidney disease (CKD) is associated with an increased risk of cardiovascular disease in general and a broad spectrum of cardiac rhythm disorders (including atrial fibrillation [AF]) in particular. Although there are treatment options for many of these disorders, management is often more complex and more restricted in a CKD setting than in a non-CKD setting.1 The risk-benefit ratio for oral anticoagulants is particularly difficult to judge in CKD patients, because of increased risks of both thromboembolic episodes and bleeding events.

MO496PRESCRIPTION OF DIRECT ORAL ANTICOAGULANTS TO PATIENTS WITH MODERATE TO ADVANCED CKD : TOO LITTLE OR JUST RIGHT?

Abstract Background and Aims Prescription of anticoagulants in patients with chronic kidney disease (CKD) is challenging, since these patients are at high risk of thromboembolic episodes, but are also prone to bleeding events. Based on a number of pivotal trials, four direct oral anticoagulants (DOACs) have been approved for use in non-valvular atrial fibrillation (AF) since 2010. These DOACs have now supplanted vitamin K antagonists (VKAs) as first-line treatment in non-CKD patients. Following post-hoc analyses of randomized clinical trials of DOACs in CKD patients performed between 2011 and 2016, a 2018 Kidney Disease Improving Global Outcomes Controversies Conference stated that although there is not enough evidence to recommend DOACs in patients with advanced CKD, these medications are safer than VKAs and not inferior for stroke preventing in patients with AF and an estimated glomerular filtration rate (eGFR) between 30 and 50 ml/min/1.73 m2. Here, in a study of stage 3 to 5 CKD patients, we sought to describe multinational prescription patterns for oral anticoagulants in general and for VKAs vs. DOACs in particular. Method We analyzed data from the international CKD Outcomes and Practice Patterns Study (CKDopps) of non-dialysis CKD patients ≥ 18 years of age with an eGFR &amp;lt;60 mL/min/1.73 m² at study enrollment. Participants were selected from national samples of nephrologist-run CKD clinics in Brazil, France, Germany, and the USA between January 2013 and April 2019. The CKDopps is ongoing, and at least 3 years (for the USA, Germany, and Brazil) or 5 years (for France) of prospective follow-up are planned. We assessed prescription patterns for oral anticoagulants regardless of indication at baseline and during follow-up. Results Of the 8154 patients enrolled, 7092 had drug prescriptions data available at baseline, and 1080 (15%) of these had at least one prescription of an oral anticoagulant. At baseline, VKAs were the most frequently prescribed oral anticoagulants (n=984, 91%), and only 97 of the 1080 patients (9%) were on DOACs (91 on a direct factor Xa inhibitor and 6 on a direct thrombin inhibitor). This low DOAC prescription rate was observed in France, the USA, Brazil and Germany. There was an upward trend in DOAC prescription (relative to VKAs) over the course of the study. Over a median [interquartile range] follow-up period of 3 years [1.5-4.5], 287 incident oral anticoagulant prescriptions were reported, 177 started on VKAs and 110 started on DOACs. Among the patients receiving a VKA at baseline, only 44 switched to a DOAC. Conclusion In an international sample of non-dialysis CKD patients (eGFR &amp;lt;60 mL/min/1.73 m²), we observed low prescription of direct oral anticoagulants (9%) at baseline, relative to vitamin K antagonists (91%) across countries included in the analysis. However, there was an upward trend in DOAC prescriptions (relative to VKAs) over the course of the study. In view of the risk of significant adverse events associated with VKAs, the prescription of DOACs should be encouraged - particularly for CKD stage 3 patients and future studies of risk/benefit comparing VKAs and DOACs are necessary in CKD patients.

Analysis of the Coagulation Profile in Children with HIV Infection-Effect of Disease and Anti Retroviral Therapy.

The pathogenesis of hypercoagulability in HIV infection is multifactorial and usually more than one factor is responsible for a thromboembolic episode. The present study was conducted to evaluate the effect of HIV infection and antiretroviral therapy on various coagulation parameters in paediatric patients. Forty two newly diagnosed paediatric patients with HIV infection who were enrolled at the Anti-Retro viral Therapy (ART) centre of Kalawati Saran Children's Hospital were included in the study. The patients were grouped into 4 clinical stages according to the WHO clinical staging of HIV disease. Coagulation tests [PT, aPTT, fibrinogen, D-Dimer and coagulation inhibitors i.e. Protein C (PC), Protein S (PS) and antithrombin III (AT III), Lupus anticoagulant (LA) and Anti phospholipid antibody (APLA)] were performed in all the patients at the time of diagnosis and repeated after 6months. All the patients were started on antiretroviral therapy within 2months of their diagnosis. At the time of diagnosis, prolonged PT and aPTT were observed in 30.9% and 23% of the cases respectively. Hyperfibinogenemia was seen in 11.9% of patients. D-Dimer was raised in 83.3% of patients. PS, PC & AT activities were reduced in 90.4%, 42.8% & 11.9% of cases respectively. A reduction in the PC and AT activity was seen from clinical stage 1 to 4, but the change was not statistically significant. On follow up after 6months, a statistically significant reduction in the level of fibrinogen and D-Dimer was seen. Even though there was improvement in the activity of all the coagulation inhibitor after 6months, statistically significant improvement was seen only for PS. The current study shows that HIV produces a hypercoagulable state in children. Raised d-dimer level and deficiency of natural anticoagulants contribute to the thrombophilic state.

Deciphering Genetic Variants of Warfarin Metabolism in Children With Ventricular Assist Devices.

Warfarin is prescribed in patients with ventricular assist devices (VADs). Dosage depends on several factors including the underlying genotype. These include polymorphisms of genes encoding cytochrome P450 enzymes, the main ones being CYP2C9, VKORC1, and CYP4F2. The objectives of this study were to evaluate the prevalence of CY2CP9 1*2*3*, VKORC1, and CYP4F2 in children with VADs and the time to reach the target international normalized ratio. We performed a retrospective/prospective study in children with VADs. We recorded polymorphisms, disease, type of VAD, ethnicity, age, gender, height, weight, INR values, bleeding, and thromboembolic episodes. Informed consent was obtained. We enrolled 34 children (19 male, 15 female), with a median age of 2years (range 0.3-17years) and median weight of 6.9Kg. The Berlin Heart was the most commonly implanted VAD (22/34; 64%), and the most common diagnosis was dilated cardiomyopathy. Statistical analysis confirmed a significant partial correlation with VKORC1 CC (p = 0.019). The CYP2C9*2 CT genotype showed a late rise in target INR values (p = 0.06), while the CYP2C9*2 CC showed a tendency toward an early INR rise (p = 0.024). We provide new information on the contribution of the warfarin polymorphisms in children with VAD implantation. Pharmacogenomic dosing for children using warfarin has the potential to improve clinical care in VAD patients. Patients with the CYP2C9*2 CT genotype may need more time or higher doses to reach target INR, while clinicians may need to be aware of the potential for a rapid rise in INR in patients with the CYP2C9*2 CC genotype.