Frequency Of Venous Thromboembolism Research Articles

Patient Weight and Chemoprophylaxis in Abdominoplasty: Does It Result in More Bleeding Events?

Bariatric surgery has gained popularity in recent decades as an effective treatment for obesity. Abdominoplasty is one of the most often performed aesthetic procedures all over the world. In post-bariatric patients undergoing abdominoplasty, the diameter size and number of the abdominal wall perforators increase proportionally with increased body weight. Postoperative complications that may occur are haematoma, and venous thromboembolism (VTE). In plastic surgery procedures VTE prophylaxis grades vary due to the lack of consensus and clear guidelines. The aim of this study was to explore the frequency of postoperative bleeding and VTE in patients undergoing abdominoplasty and to explore the risk factors associated with major bleeding. A retrospective single-centre study of adult patients who were operated on by abdominoplasty between 2011 and 2020. Chemoprophylaxis including low molecular weight heparin (LMHW) was recommended when the operating time exceeded 2h. A total of 102 patients were included. There were no patients with VTE. Eight patients were re-operated for major haematoma. The weight loss (peak weight to weight before the abdominoplasty) was 14.4kg larger in the re-operation group (p = 0.03). Eighty-eight percent in the re-operation group and 67% in the other group were treated with LMWH (p = 0.43). Multivariable logistic regression showed that with each decrease from the peak in BMIkg/m2 the risk of re-operation for major haematoma was increased by 22% (p = 0.02). Abdominoplasty in patients after massive weight loss has a higher risk of postoperative bleeding. Having a clear protocol for chemoprophylaxis should be considered. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Venous thromboembolism in patients with isolated moderate to severe traumatic brain injury

Background. Traumatic brain injury (TBI) remains a big problem of modern neurosurgery, accompanied by high rates of disability and lethality. Venous thromboembolism (VTE) including venous thrombosis and pulmonary embolism (PE) plays a significant role in the structure of mortality in this pathology. Regimens and schemes of pharmacological prevention of VTE in TBI as well as corresponding preventative measures are not yet determined completely.Aim. To identify the frequency of VTE in patients with isolated moderate and severe TBI, and to evaluate the results of prevention and treatment of these complications in patients of this category.Materials and methods. Over a 3‑year period (from 2020 to 2023) 73 patients with isolated moderate and severe TBI (51 men and 22 women, mean age 61.0 ± 13.0 years) were treated in the V. M. Buyanov City Clinical Hospital. Of these, 31 patients received only conservative therapy, and 42 patients underwent surgery (craniotomy with hematoma removal, closed external hematoma drainage, and installation of intracranial pressure sensor). Ultrasound examination of the lower limb veins was performed at patient admission, then every 7 days until discharge from the hospital. Pharmacological prevention of VTE using low molecular weight heparin in non‑surgical patients was started after 1–2 days if computed tomography of the brain 24 h after admission showed no negative hematoma dynamics. Surgical patients were prescribed preventive medications 24 h after surgery if computed tomography confirmed intracranial hemostasis.Results. Venous thrombosis was detected in 22 (30.1 %) of 73 patients. PE complicated the underlying disease in 1 (1.4 %) case and was non‑fatal. There was no fatal PE in the study group. An increase of the initial intracranial hematoma volume occurred in 3 (4.1 %) patients, in 2 (2.8 %) patients the recurrence of hemorrhage occurred before the beginning of heparin administration, and in 1 (1.4 %) case against the background of therapeutic doses of anticoagulants prescribed for venous thrombosis. In the majority of cases (82.0 %; 18 of 22 patients) thromboses were localized in deep veins of the lower leg and were asymptomatic. Intrahospital mortality was 23.3 % (17 patients), all lethal outcomes were due to the course of traumatic brain disease.Conclusion. VTE is a frequent complication of TBI with intracranial hemorrhage. Regular ultrasound diagnostics makes it possible to diagnose asymptomatic distal venous thrombosis in a timely manner and to prescribe therapeutic doses of low molecular weight heparin in time which in turn allows to avoid fatal PE. Currently, there are no clear domestic recommendations for the prevention and, most importantly, for the treatment of these complications in patients with isolated moderate and severe TBI, which requires further active study of this problem.

Venous Thromboembolism in Peritoneal Mesothelioma: Uncovering the Hidden Risk.

Venous thromboembolism (VTE) is a common complication in patients with abdominal malignancies. Despite known associations between pleural mesothelioma and increased VTE risk, the characteristics of VTE in patients with peritoneal mesothelioma (PeM) remain undescribed. Patients treated for PeM were retrospectively identified from our institutional database. The frequency of VTE was assessed and logistic regression modeling was employed to assess VTE risk factors. The association between VTE and overall survival was also ascertained. Recommended thromboprophylaxis for patients who underwent surgery at our institution comprised a single preoperative dose of prophylactic anticoagulation, followed by daily dosing for fourweeks postoperatively. Among 120 PeM patients, 26 (21.7%) experienced VTE, including 19/91 (20.9%) surgical patients, 4/23 (17.4%) patients who received systemic therapy, and 3/6 (50%) patients who underwent observation (p=0.21). Most events were symptomatic (n=16, 62%) and were attributable to pulmonary emboli (n=16, 62%). The 90-day postoperative VTE rate was 4.4% (4/91), including 1 of 60 patients who underwent index surgical intervention at our institution and 3 patients with surgery elsewhere. A low serum albumin concentration was associated with VTE in non-surgical patients (odds ratio 0.12, confidence interval [CI] 0.02-0.72; p=0.03). No significant difference in overall survival was observed between patients with and without VTE (median 46.0 months [CI 24.9-67.0] vs. 55.0 months [CI 27.5-82.5]; hazard ratio 0.98 [CI 0.54-1.81], p=0.98). A high risk of VTE was observed in PeM patients, warranting suspicion throughout the disease trajectory. Postoperative VTE rates were within acceptable limits with 4-week thromboprophylaxis.

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.

Hematological disorders as a complication of COVID-19

Background. Coronavirus disease (COVID-19) can affect the blood and hemostasis systems and lead to complications that require intensive care. The aim is to detect such common complications by studying literary sources and clinical experience. Materials and methods. The search for relevant literature was conducted in PubMed, and in the other databases such as Science Direct, Google Scholar, Scopus and Web of Science. The literature search was done using the keywords “COVID-19”, “SARS-CoV-2” in combination with “coagulation dysfunction”, “coagulopathy”, “hematological manifestations”, “hematological parameters”, “deep vein thrombosis”, “pulmonary embolism”, “arterial thrombosis”, “D-dimer”, “fibrinogen”, “lymphopenia”, “thrombocytopenia”. Results. COVID-19-associated coagulopathy is characterized by high levels of D-dimer and fibrin degradation products in blood plasma, changes in prothrombin time, activated partial thromboplastin time, fibrinogen, and platelet count. Endothelial dysfunction caused by coronavirus leads to an increased risk of thrombotic complications, both in venous and arterial systems, additionally to the existing higher risk of thrombosis in the intensive care unit. The venous thromboembolism frequency among unvaccinated hospitalized patients and during ultrasound screening is significantly higher. Coronavirus disease can lead to arterial thrombosis in areas such as the aorta, kidneys, cerebral and peripheral arteries. COVID-19 can cause enhanced-fibrinolytic-type disseminated intravascular coagulation or limited thrombotic microangiopathy. According to research, patients with severe COVID-19 usually had leukocytosis, lymphopenia, and an elevated neutrophil-to-lymphocyte ratio. Thrombocytopenia is observed not only during the acute coronavirus disease, but also in the post-COVID-19 period. Both thrombosis and bleeding can occur in patients undergoing extracorporeal membrane oxygenation. Conclusions. A high level of D-dimer, a prolongation of prothrombin time, an increase or a quick decrease in fibrinogen level, lymphopenia, neutrophilia, and an increase in the neutrophil-to-lymphocyte ratio are considered prognostic factors for the severity of coronavirus disease. Deep vein thrombosis and pulmonary embolism are the most common thrombotic events in patients with COVID-19. Arterial thrombosis occurs more often in the cerebral arteries and arteries of the extremities.

Role of Fibrin Monomer Complex in Coronavirus Disease 2019 for Venous Thromboembolism and the Prognosis.

Objective Venous thromboembolism (VTE) is a common complication of severe coronavirus disease 2019 (COVID-19) and is associated with its prognosis. The fibrin monomer complex (FMC), a marker of thrombin generation, is reportedly useful in diagnosing acute thrombosis. To date, there has been only one report on FMC in COVID-19, and the usefulness of FMC in COVID-19 is unknown. We therefore evaluated the frequency of VTE in non-intensive-care unit COVID-19 patients in Japan and determine the clinical utility of FMC in COVID-19. Methods This was a single-center retrospective study. Laboratory test results and outcomes (thrombosis and severe progression of COVID-19) were obtained via medical record review. We assessed the relationship between FMC and VTE incidence and evaluated the association between elevated FMC levels and severe progression of COVID-19. Patients/Materials This study included 247 patients with COVID-19 who were hospitalized between December 2020 and September 2021 and had had their levels of D-dimer and FMC measured. Results Of the 247 included patients, 3 (1.2%) developed VTE. All three had elevated FMC levels on admission; however, the D-dimer level was not elevated in one case on admission. The FMC level was significantly higher in the group with severe COVID-19 progression than in the group without severe progression. A multivariate analysis showed that severe progression was associated with elevated FMC levels (odds ratio, 7.40; 95% confidence interval, 2.63-22.98; p<0.001). Conclusion FMC can be useful for diagnosing VTE in the acute phase of COVID-19. Elevated FMC was found to be associated with severity on admission and severe progression.

Clinical case of development of thromboembolism after thyroidectomy with concomitant diseases

Objective. To study a clinical case after a planned thyroidectomy. Venous thromboembolism in the form of deep vein thrombosis or LE is the third most common in the world, being the second only to myocardial infarction and stroke. In epidemiological studies, the annual incidence of pulmonary embolism ranges from 39 to 115 persons per 100 000 of the population; for deep vein thrombosis, the incidence rates range from 53 to 162 per 100 000 of the population. The cross-sectional analysis data show that the frequency of venous thromboembolism is almost 8 times higher in persons over 80 years of age than in the fifth decade of life. Pulmonary embolism is a stop of blood flow in the branch of the pulmonary artery due to obstruction by a clot. The most frequent places of blood clots are the deep veins of the lower extremities. Risk factors for thromboembolism may be surgical operations, varicose veins, age, overweight. This is one of the most common and severe complications of the postoperative period. Our article considers a clinical example of the development of thromboembolism after thyroidectomy, presents the results of pathomorphological studies, autopsy, histological studies.&#x0D; Materials and methods. The work consisted in the study of a clinical case of pulmonary embolism after a planned surgical intervention for nodular goiter. Histological sections of organs such as the heart, kidneys, gallbladder, thyroid gland, liver were studied.&#x0D; Results. The results of our study showed that thyroidectomy refers to operations of a high complexity and high risk of multiple complications as well as the occurrence of a fatal outcome. Therefore, a thorough examination of all organs and systems in patients is necessary, especially those who belong to the elderly and severe comorbid pathology groups. This is due to the fact that the risk of death without a proper preparation for surgery with available concomitant diseases (nodular colloidal goiter, empyema of the gallbladder, Gilbert's disease, persistent hepatitis, type 2 diabetes mellitus, hypertension, chronic coronary heart disease) was very high for this patient.&#x0D; Conclusions. Diffuse nodular toxic goiter is a complex surgical pathology involving many organs and systems. Patients with such a diagnosis require a thorough history collection, carrying out clinical, instrumental and laboratory research methods, including successful surgical intervention.

Impact of Institutional Prophylaxis Guidelines on Rates of Pediatric Venous Thromboembolism Following Trauma - a Multicenter Study from the Pediatric Trauma Society Research Committee.

A paucity of data exists with regard to the incidence, management, and outcomes of venous thromboembolism (VTE) in injured children. We sought to determine the impact of institutional chemoprophylaxis guidelines on VTE rates in a pediatric trauma population. A retrospective review of injured children (<15 years) admitted between 2009-2018 at ten pediatric trauma centers was performed. Data was gathered from institutional trauma registries and dedicated chart review. The institutions were surveyed as to whether they had chemoprophylaxis guidelines in place for high risk pediatric trauma patients, and outcomes were compared based on the presence of guidelines using chi-square analysis (p < 0.05). 45,202 patients were evaluated during the study period. Three institutions (28,359 patients, 63%) had established chemoprophylaxis policies during the study period ("Guidelines"); the other seven centers (16,843 patients, 37%) had no such guidelines ("Standard"). There were significantly lower rates of VTE in the Guidelines group, but these patients also had significantly fewer risk factors. Amongst critically injured children with similar clinical presentations, there was no difference in VTE rate. Specifically within the Guidelines group, 30 children developed VTE. The majority (17/30) were actually not indicated for chemoprophylaxis based on institutional guidelines. Still, despite protocols only one VTE patient in the Guidelines group who was indicated for intervention ended up receiving chemoprophylaxis prior to diagnosis. No consistent ultrasound screening protocol was in place at any institution during the study. The presence of an institutional policy to guide chemoprophylaxis for injured children is associated with a decreased overall frequency of VTE, but this disappears when controlling for patient factors. However, the overall efficacy is impacted by a combination of deficits in guideline compliance and structure. Further prospective data is needed to help determine the ideal role for chemoprophylaxis and protocols in pediatric trauma.Level IV, therapeutic/care management.

VENOUS THROMBOEMBOLISM WITH THE USE OF ASPIRIN VERSUS ENOXAPARIN AS PROPHYLACTIC AGENTS AFTER HIP ARTHROPLASTY

Objective: To assess how often venous thromboembolism (VTE) occurs in patients on low dosage aspirin versus enoxaparin for VTE prevention after hip arthroplasty. Methodology: This quasi-randomized controlled trial was conducted at the Department of Trauma &amp; Orthopedics, Lady Reading Hospital, Peshawar. The study was conducted over a period of 6 months. Lottery method was used to collect data and the patients were divided into two groups. The chi-square test was used to compare the frequency of VTE between groups. Effect modifiers such as age, gender, and BMI were managed through stratification. The post-stratification chi-square test was used to determine whether there is a relationship between these impact modifiers and study results. P-value 0.05 was used to define a significant difference. Results: A total of 74 patients undergoing total/partial hip arthroplasty in orthopedics surgery were observed, which were divided in two equal groups. Patients in Group A were managed by aspirin (75mg/day) and Group B patients received enoxaparin (0.5mg/kg). Group A had 2(5.4%) patients with VTE in follow-up and 35(94.6%) patients had observed no VTE. Group B had VTE in 4(10.8%) patients and no VTE in 33(89.2%) patients which shows that VTE was high in group B as compared to group A. The difference was insignificant with p-value=0 .337. Incidence of VTE was seen to be higher in patients aged more than 50 years. Conclusion: The difference in incidence of VTE after hip arthroplasty with use of either Aspirin or Enoxaparin as prophylactic agents was statistically insignificant.

Clotting Propensity in Trauma Patients According to Marijuana Use: A Descriptive Analysis.

Marijuana use has been reported to promote hypercoagulable states among trauma patients, particularly respecting venous thromboembolism (VTE), a major contributor to morbidity and mortality in patients sustaining traumatic injury. We sought to investigate this further through a retrospective, single institutional study performed from January 2018 through June 2021, utilizing data from patients presenting to a Level 1 Trauma Center as a trauma activation. We observed less frequent VTE development in the marijuana-positive group compared to the marijuana-negative group, with patient thromboelastography revealing a longer mean R-time in the marijuana-positive group. Overall occurrence of VTE was too low for definitive conclusions, but a trend toward reduction in VTE frequency among marijuana users compared to nonusers was noted. More studies with larger populations and more VTE occurrences are needed to confirm a potential correlation between marijuana use and VTE development.

Venous Thromboembolism Associated with Assisted Reproductive Technology: A Systematic Review and Meta-analysis.

Hormonal exposure leads to an increased risk of venous thromboembolism (VTE) but the risk of VTE associated with assisted reproductive technology (ART) is not clearly determined. We searched in PubMed, EMBASE, Web of Science, and the Cochrane Library databases and identified all relevant articles published up to February 1, 2021. The primary objective was to determine the frequency of VTE associated with ART. Secondary objectives were to determine (1) the risk of VTE associated with ART as compared to pregnancy without ART; (2) the risk of VTE associated with ovarian hyperstimulation syndrome (OHSS); and (3) to determine potential risk factors of VTE related to ART. Fourteen studies were included. The overall frequency of VTE associated with ART was 0.23% (95% confidence interval [CI]: 0.07-0.46). Women undergoing ART had a two- to threefold increased risk of VTE as compared to spontaneous pregnancy (relative risk [RR]: 2.66; 95% CI: 1.60-4.43). The overall frequency of VTE specifically related to OHSS was <0.001%. The risk of VTE after ART complicated by OHSS, as compared to ART without OHSS, was higher but not statistically significant (RR: 14.83; 95% CI: 0.86-255.62). Risk factors of VTE associated with ART were in vitro fertilization procedure (RR, odds ratio [OR], and hazard ratio varying from 1.77, 95% CI: 1.41-2.23 to 4.99, 95% CI: 1.24-20.05), hyperhomocysteinemia (OR: 15.2; 95% CI: 2.0-115.0), polycystic ovarian syndrome (PCOS) (RR: 4.8; 95% CI: 1.7-13.4), successful ART leading to pregnancy (OR: 13.94; 95% CI: 1.41-137.45). Further large prospective studies on risk factors of VTE in women undergoing ART are needed in order to optimize thromboprophylaxis in this context.

Frequency and Risk Factors for Venous Thromboembolism Among Patients with Multiple Myeloma or Aggressive Lymphoma: A 6-Year Single Center Retrospective Analysis

Background and Aims: Patients with hematologic malignancies are characterized by presence of altered hemostatic system, which translates into a high risk of venous thromboembolism (VTE) with an estimated annual incidence of VTE higher when compared with the general population (0.5% vs 0.1%). Moreover, VTE contributes to morbidity and mortality in these patients and is a frequent complication of anticancer therapy. Even VTE is clearly associated with decreased survival, the development of validated scores delineate the risk of VTE by hematological disorders subtype still lacking. In the current study, the frequency and the risk factors associated with VTE were examined among a cohort of patients with aggressive lymphoma and multiple myeloma. Methods: We retrospective analyzed clinical data of 231 patients with multiple myeloma and 227 patients diagnosed with aggressive lymphoma, followed in our institute from January 2015-December 2020. Among patients affected by myeloma, extramedullary disease was observed in 18% of patients. Among the lymphoma cohort, the most common type was diffuse large B-cell lymphoma (84%), followed by mantle cell lymphoma (8%), peripheral T cell lymphoma (4%), Burkitt lymphoma (2%), and primary mediastinal large B-cell lymphoma (2%). Results: Fourty-six (19.9%) patients with diagnosis of multiple myeloma experienced a VTE, in a median follow-up of 23.09 month (range, 1.01-135.95). Half of patients (50%) had TVP, followed by EP in 28% and TVS in 22% of patients. VTE occurred in older age (pV=0.027), bone disease (pV=0.002), and the presence of central venous catheter (pV<0.001). Instead, no clinical and laboratory features at diagnosis affect the occurrence of thrombosis in patients with myeloma. Interesting, Lenalidomide-based therapy, monoclonal antibody-based therapy, and Carfizomib-based therapy increase the risk of VTE (HR 2.55 (1.31-4.95), pV=0.005; HR 2.36 (1.07-5.19), pV=0.037; HR 6.1 (2.8-13.6), pV<0.001; respectively). Even in patients with aggressive lymphoma the frequency of VTE was 19.8% (n=45) in a median follow up of months 28.87 (range, 0.23-177.18), despite 55.5% underwent thromboprophylaxis treatment. Older patients (pV= 0.029), with concomitant HIV infection (pV=0.031), and with spleen involvement (pV=0.022) were risk factors of development of VTE. Moreover, higher level of LDH (pV=0.042), leukocytosis (pV=0.004) and higher neutrophil-to-lymphocyte ratio (NLR) (pV=0.022) were significantly associated with increased risk of thrombosis. In our analysis, VTE did not significantly affect the overall survival of patients with myeloma and aggressive lymphoma. Conclusions: VTE is a frequent complication in patients with multiple myeloma or aggressive lymphoma, and about 20% of these patients presented VTE during therapy. In our cohort of multiple myeloma, the therapeutic approach seems play a crucial role in development of thrombosis, although clinical presentation had less impact on VTE. In patients affected by aggressive lymphoma, NLR, a new inflammatory status marker, turns out to be an independent risk factor for VTE. This study showed new clinical and therapeutic risk factors for VTE, but the development of a predictive model for identifying patients with myeloma and lymphoma at high risk for developing thrombosis is an unmet need in clinical management.

One-Year Incidences of Venous Thromboembolism, Bleeding, and Death in Patients With Lung Cancer (Cancer-VTE Subanalysis)

IntroductionThis subanalysis aimed to provide real-world data on venous thromboembolism (VTE) from patients with lung cancer in the Cancer-VTE Registry. MethodsThe primary outcome was the number of baseline VTE events in patients with lung cancer. The 1-year cumulative incidences of symptomatic VTE; composite VTE (symptomatic and incidental VTE requiring treatment); bleeding; cerebral infarction, transient ischemic attack, and systemic embolic events; and all-cause death were calculated. Clinical trial registration: UMIN000024942. ResultsThe study enrolled a total of 2377 patients with lung cancer; of these, 119 (5.0%) had VTE (six [0.3%], symptomatic, and 113 [4.8%], asymptomatic) and 14 (0.6%) had pulmonary embolism at baseline. During the follow-up period (mean, 337.7 d), the incidence was 0.6% for symptomatic VTE, 1.8% for composite VTE, 1.5% for bleeding events, 1.3% for cerebral infarction, transient ischemic attack, and systemic embolism, and 19.1% for all-cause death. Composite VTE frequency did not vary by anticancer drug type. Patients with (versus without) VTE at baseline had higher hazard ratios (HRs) for composite VTE (unadjusted HR: 5.29; Gray test p < 0.001) and symptomatic VTE (unadjusted HR: 4.89; Gray test p = 0.007). Patients with VTE at baseline had higher HRs for bleeding events (unadjusted HR: 3.27; Gray test p = 0.010) and all-cause death (unadjusted HR: 2.73; log-rank test p < 0.001) than patients without. In multivariable analysis, patients with baseline VTE prevalence and Eastern Cooperative Oncology Group Performance Status of 2 had increased composite VTE risk during cancer therapy. There were no other risk factors for composite VTE. ConclusionsOur findings emphasize the importance of VTE screening at cancer diagnosis.

Risk of venous thromboembolism in patients with pancreatic cancer

Venous thromboembolism (VTE) is often diagnosed in patients with pancreatic cancer, resulting in increased morbidity and mortality. Objective: to study the relationship between clinical characteristics and hemostatic disorders in patients with pancreatic cancer and determine their role in predicting VTE. Material and Methods. The study included 246 patients with pancreatic cancer. Pancreatic ductal adenocarcinoma was diagnosed in 91.9 % of patients. In most patients (68.3 %), the tumor was localized in the head of the pancreas; 45.9 % of patients had stage IV disease at diagnosis (T1–4N0–2M1); 31.7 % of patients manifested jaundice at diagnosis. A small proportion of patients (17.5 %) received chemotherapy, and 28 % of patients underwent surgery. Within the 12-month follow-up period, the frequency of VTE was 15.4 %. Clinical characteristics and hemostasis parameters were retrospectively compared in patients with VTE and without VTE diagnosed during the follow-up period. Results. The risk of developing VTE in cancer patients was higher with a larger tumor size and the presence of distant metastases. The initial high level of D-dimers increased the risk of VTE during the frst 12 months of diagnosis. In a multivariate analysis, the elevated level of D-dimers was a signifcant risk factor for VTE. Conclusions. The tumor size, advanced tumor stage (stage IV), and elevated levels of D-dimer in patients with pancreatic cancer are of prognostic signifcance for VTE. The study of hemostasis parameters (D-dimer) can help identify patients at risk of developing VTE, who are advised to take anticoagulant therapy with low hemorrhagic risk.

The Impact of Degree of Anticoagulation on Thrombotic and Other Complications in Hospitalized COVID-19 Patients

Introduction:In hospitalized patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the frequency of venous thromboembolism (VTE) is increased. Retrospective studies suggested that an elevated D-dimer level is associated with increased mortality and predictive of thrombosis in these patients. In the spring of 2020, our institution developed a risk protocol for stratification of hospitalized COVID-19 patients into high, intermediate, or low risk groups, based upon history of thrombosis and D-dimer level. These patients were treated with full-dose anticoagulation, high- or standard-dose prophylaxis, respectively. The goal of this project was to determine the impact of this protocol on VTE frequency, need for intensive care unit (ICU) admission, organ failure and in-hospital mortality while assessing the frequency of hemorrhagic complications when compared to standard prophylactic anticoagulation.Methods:We performed a retrospective chart review of adults hospitalized between March 1 - June 1, 2020 who tested positive for SARS-CoV-2 by nasopharyngeal polymerase chain reaction (PCR). Patients were excluded if they were initially admitted to the ICU. VTE was defined as either a deep vein thrombosis (DVT) on Duplex ultrasound and/or pulmonary embolism (PE) on computed tomography (CT) angiogram. We collected demographic data, medical histories, laboratory and radiologic data on all subjects. Data were analyzed using the Chi Square test and Fisher's Exact Test to establish significant association with clinical outcomes between 3 anticoagulation regimens. Statistical significance was assessed at the p<0.05 level.Results:Data were analyzed from 910 patients; 496 (54.6%) were male and the mean age was 57.8 ± 16.9 years. 419 (46%) subjects were Black, 151 (16.6%) Caucasian, 133 (14.6%) Latinx. Diabetes mellitus (35.3%) and hypertension (59.8%) were common in our cohort as were tobacco (12.6%) and alcohol (20.4%) use. Only 69 (7.6%) were treated with chronic anticoagulation and 216 (23.7%) were on antiplatelet agents. 123 (13.5%) required an ICU transfer and the overall mortality was 5.3%. Most patients, 809 (88.9%), received standard prophylactic anti-coagulation initially (Group A); 32 (3.5%) received high dose prophylaxis (Group B) and 69 (7.6%) received therapeutic dose anticoagulation (Group C). In the entire cohort, 46 (5.1%) developed VTE; 29 (3.6%) in Group A, 2 (6.3%) in Group B, and 15 (22%) in Group C (p<0.0001). ICU admission was required for 102 (12.6%) in Group A, 7 (21.9%) in Group B, and 14 (20.3%) in Group C (p=0.075). 73 ICU patients (8%) required vasopressors, including 57 (7%) in Group A, 6 (18.8%) in Group B and 10 (14.5%) in Group C (p=0.175). 81 ICU patients (8.9%) required mechanical ventilation, including 66 (8.2%) in Group A, 6 (18.8%) in Group B, and 9 (13%) in Group C (p=0.513). One patient in Group B developed an intracerebral hemorrhage. Gastrointestinal hemorrhage occurred in 11 (1.2%) of the cohort; similar rates were observed across treatment arms. The overall in-hospital mortality was 5.3% in this cohort (4.7% in Group A, 12.5% in Group B, and 8.6% in Group C, p=0.064).Conclusion:The rate of VTE in COVID-19 patients receiving any form of anti-coagulation was low. There was an increased rate of VTE, but not rates of ICU admission, mortality, mechanical ventilation nor vasopressor use in those receiving either high dose prophylaxis or therapeutic anticoagulation, suggesting an increased propensity for thrombosis either related to prior thrombotic events or reflected by increased D-dimer levels. These findings need to be confirmed in prospective studies. DisclosuresDiLorenzo: Abbott: Current holder of individual stocks in a privately-held company; Merck & Co: Current holder of individual stocks in a privately-held company; Glaxo Smith Kline: Current holder of individual stocks in a privately-held company. Sloan: Pharmacosmos: Membership on an entity's Board of Directors or advisory committees; Astra Zeneca: Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria; Stemline: Honoraria. Weinberg: Janssen Pharmaceuticals: Other: Serve on data safety monitoring boards; Merck & Co: Current holder of individual stocks in a privately-held company. Klings: CSL Behring: Other: Consultant; Omeros: Other: Consultant; Bluebird Bio: Other: Consultant; Bayer: Research Funding; Novartis: Research Funding; FORM therapeutics: Research Funding.

Risk of Recurrent Venous Thromboembolism and Hemorrhage Following Interruption of Anticoagulation at Delivery

Background: Current guidelines for regional anesthesia advise for the discontinuation of prophylactic and therapeutic low molecular weight heparin (LMWH) 12 hours and 24 hours, respectively prior to the use of neuraxial anesthesia (NA) for obstetric patients. Re initiating a prophylactic dose 12 hours following epidural catheter insertion/spinal anesthesia (SA) and at least 4 hours following epidural catheter removal is also recommended. There are limited data on the recurrent risk of venous thromboembolism (VTE) and bleeding using these standards. We conducted a retrospective single center study to assess the risk of VTE and/or bleeding in pregnant women using these criteria.Methods: Consecutive patients from 2013 to 2018 at Mount Sinai Hospital, a university affiliated tertiary care center in Toronto, Canada who were prescribed therapeutic or prophylactic LMWH antenatally and postpartum and who had NA were included. Hospital records were reviewed to determine the indication and dosage of LMWH, presence of thrombophilia, time of first LMWH injection postpartum, the mode of neuraxial anesthesia and delivery, the time of epidural catheter/spinal anesthesia, the time of epidural catheter removal, laboratory parameters and comorbid illnesses. Patients requiring therapeutic or prophylactic LMWH were assessed in the Hematology clinic and were advised to discontinue anticoagulation according to current recommendations. The primary outcomes were frequency of VTE, spinal hematoma and volume of postpartum blood loss. Statistical Analysis: Continuous variables were summarized as medians and interquartile ranges. Categorical variables were summarized as percentages. Characteristics associated with VTE and hemorrhage were analyzed using regression analysis.Results: Of 169 pregnancies, 158 fulfilled criteria, and 110 had complete data for the time of epidural catheter removal and initiation of LMWH. Median age was 34 (IQR 5) years and median weight 90 (IQR 70) kgs. Diagnoses included antiphospholipid syndrome, Budd Chiari, provoked and unprovoked VTE. Median platelet count at delivery was 185 (IQR 76) x 10(9)/L. Thirty-three percent were using concomitant ASA antenatally. Forty-four percent (n=48) had a vaginal delivery (VD). Sixty five (59%) had epidural anesthesia, 43 (39%) had SA and, two had combined spinal/epidural anesthesia. Median time to restarting LMWH was 7.8 (IQR 4.7) hours from epidural catheter removal/spinal insertion and 9 (IQR 3.9) hours from SA. There were no spinal hematomas. Median blood loss was 500 (IQR 400) ml. One patient, who received prophylactic dose LMWH antepartum, had a Caesarean delivery, spinal anesthesia and a prophylactic dose re-started 13.7 hours after SA, developed a delayed postpartum hemorrhage. One patient developed a VTE (1%). She developed a distal and superficial thrombus immediately after delivery. She was using antenatal prophylactic LMWH as she had an unprovoked VTE predating pregnancy, was heterozygous for the prothrombin gene mutation, had epidural anesthesia and VD. She received prophylactic LMWH three hours after catheter removal which was also 10 hours after catheter insertion.Limitations: Time of discontinuation of LMWH prior to induction could not be confirmed definitively as this was a retrospective review.Conclusion: Prospective studies are required to confirm these findings and to determine the safety of current recommendations of interrupting anticoagulation prior to regional anesthesia and delivery and to identify risk factors for hemorrhage and recurrent VTE to optimize anticoagulation regimens for these patients. DisclosuresMalinowski: Alexion: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy.

High Rate of Recurrent Venous Thromboembolism Is Children with Sickle Cell Disease and History of VTE: Analysis of the Trinetx Research Network Database

Background: Sickle Cell Disease (SCD) is associated with a chronic prothrombotic state that increases the risk of venous thromboembolism (VTE). The rate of VTE in hospitalized children with SCD is nearly 2%, substantively higher than the 0.2-0.6% rate seen in the general pediatric population. 1-3 The frequency and risk factors associated with the development of recurrent VTE in this population are vastly unknown. This knowledge gap hinders the development of disease-specific guidelines for the management and secondary prevention of VTE in pediatric SCD.Aim: To investigate the frequency of recurrent VTE in children birth to 21 years of age (inclusive) with SCD and history of prior VTE.Methods: We analyzed patient-level data from the TriNetX Research Network Database, a global federated network of electronic medical record (EMR) data from 42 health care organizations. Children ≤21 years of age with a diagnosis of SCD and history of VTE between January 1 2008 to March 31 2021 were included in the analysis. Index VTE was defined as the first diagnosis of VTE in the patient's EMR. Recurrent VTE was defined as an acute VTE diagnosis that occurred 90 days after the index VTE discharge date in a different anatomic location from the index VTE. Patient demographic and clinical characteristics were summarized using counts and percentages. Missing values were not imputed. Overall, one year and five-year recurrence VTE are reported with the corresponding 95% confidence intervals (CI).Results: A total of 119 children with SCD and VTE were included. Table 1 shows the patients baseline characteristics. Mean age at the time of index VTE diagnosis was 16.7 years (standard deviation 5.5 years). The majority of patients were Black (87%) and female (61%). The most frequent index VTE diagnosis was pulmonary embolism (42%) followed by lower (23%) and upper (22%) extremity VTE. Of the 119 patients,10 (8.4%, 95%CI=4-15%) developed recurrent VTE within 1-year and 25 (21.0%, 95%CI=14-29%) developed recurrent VTE within 5-years from index VTE. Compared to patients without recurrent VTE, patients with recurrent VTE were more frequently female (50% vs. 68%, respectively), and slightly older (mean age 16.6 years vs. 17.2 years, respectively). The most frequent anatomic location for VTE recurrence was the upper extremity (32%)Conclusions: This retrospective database analysis identified, for the first time, high rates of recurrent VTE of 8.4% and 21% at 1- and 5-years post-VTE in children with SCD. These rates stand in contrast with the 3% VTE recurrence at 1-year reported for the general pediatric VTE population. 4 Further analyses of the database are ongoing to identify risk factors for recurrent VTE in this population. These initial findings highlight the need for cooperative multicenter prospective studies to reliably establish rates of- and prognostic factors associated with recurrent VTE in children with SCD, in order to generate evidence for disease-specific treatment guidelines, and to inform future prognostically-stratified interventional trials designed to optimize VTE outcomes in pediatric SCD.1.Kumar R, Stanek J, Creary S, et al. Prevalence and risk factors for venous thromboembolism in children with sickle cell disease: an administrative database study. Blood Adv 2018;2:285-291.2. Raffini L, Huang YS, Witmer C, Feudtner C. Dramatic increase in venous thromboembolism in children's hospitals in the United States from 2001to 2007. Pediatrics 2009;124:1001-8.3. Setty BA, O'Brien SH, Kerlin BA. Pediatric venous thromboembolism in the United States: a tertiary care complication of chronic diseases. Pediatr Blood Cancer 2012;59:258-64.4. Goldenberg NA, Schulman S, Kittelson JM, et al, Kids-DOTT Trial Investigators and the ATLAS Group. A Six-week versus Three-month Duration of Anticoagulation for Acute Provoked Venous Thromboembolism in Patients < 21 Years Old: Results of the Multinational Kids-DOTT Randomized Controlled Trial. [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 1). [Display omitted] DisclosuresHankins: Global Blood Therapeutics: Consultancy; Vindico Medical Education: Consultancy; UpToDate: Consultancy; Bluebird Bio: Consultancy. Goldenberg: Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Daiici: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Anthos: Membership on an entity's Board of Directors or advisory committees.

Low Dose Apixaban As Secondary Prophylaxis for Venous Thromboembolism in Cancer Patients, 30 Months Follow-up

Background: Apixaban is a treatment option for venous thromboembolism (VTE) in cancer patients. There are no data on the effect of low dose apixaban after 6 months treatment. We wanted to assess the efficacy and safety of apixaban 2.5 mg twice daily as prophylaxis for recurrent VTE after 6 months initial treatment with full-dose apixaban.Patients and methods: We included 298 patients with cancer and any type of VTE. All patients were treated with full dose apixaban for the first 6 months. After 6 months, all patients with active cancer continued with apixaban 2.5 mg twice daily and were followed for the next 30 months. The primary endpoint of efficacy was recurrent VTE, the primary safety endpoint was major bleedings. Clinically relevant non-major bleedings was a secondary endpoint. The endpoints are reported as incidence rates or fractions with 95% confidence intervals, and as Kaplan-Meier plots.Results: During the first 6 months of full-dose anticoagulation 12 of 298 patients had recurrent VTE (4.0%, 95% confidence interval 2.1-6.9), 16 experienced major bleeding (5.4%, 95% CI 2.8-7.9%), and 26 patients experienced one or more episodes of CRNMB (8.9%, 95% CI 5.5-12) as previously reported. 1 Of the 298 patients included, 196 continued with apixaban 2.5 mg twice daily after 6 months. During treatment from 6 to 36 months with low-dose apixaban 15 of 196 (7.6%, 95% CI: 4.4-12) patients had recurrent VTE, 7 (3.6%, CI: 1.5-7.2) patients experienced major bleeding and 16 (8.2%, 95% CI: 4.7-13) patients experienced CRNMB. The highest incidence rate of both recurrent VTE and major bleedings were seen during the first month of full-dose apixaban (Table 1). After the dose reduction of apixaban, the incidence rate of recurrent VTE increased slightly during 6 to 12 months while the incidence rate of major bleeding decreased during the same time-period. After 12 months the incidence rate of both recurrent VTE and major bleeding was low and remained low during the entire 30 months follow-up (Table 1 and Figure 1). The Kaplan-Meier plot of the composite endpoint of recurrent VTE or major bleeding did not change after dose-reduction. After about 9 months treatment (i.e. 3 months on low dose apixaban) the Kaplan-Meier curve of the composite endpoint flattened out.Conclusion: Dose reduction of apixaban to 2.5 mg twice daily after 6 months of full dose anticoagulation resulted in a small increase in recurrent VTE, but a marked decrease in major bleedings during the 6-12 months period. After approximately 9 months the frequency of recurrent VTE and major bleedings remained low compared with the first 6 months of full-dose treatment. Reducing the dose of apixaban to 2.5 mg twice daily after 6 months of full-dose treatment appears safe and effective.

Mortality and bleeding complications of COVID-19 critically ill patients with venous thromboembolism.

Venous thromboembolism (VTE) disease in COVID-19 patients is a remarkable issue, especially its relationship with bleeding events and mortality. The objective of this study was to describe the outcomes of critically ill patients with COVID-19, hospitalized in the Intensive Care Unit (ICU), in relationship with VTE during their stay. This is a prospective cohort study of critically ill COVID-19 patients in two hospitals that underwent a venous ultrasound at the beginning of follow-up of both lower limbs in April 2020. In case of clinical suspicion of new VTE during the 30-day follow-up, additional ultrasound or thoracic CT were performed. Global VTE frequency, major bleeding events and survival were collected, and their predictors were studied. We included 230 patients. After 30 days of follow-up, there were 95 VTE events in 86 patients (37.4%). Thirteen patients (5.7%) developed major bleeding complications and 42 patients (18.3%) died. None of the comorbidities or previous treatments were related with bleeding events. D-Dimer at admission was significantly related with VTE development and mortality. Independent predictors of mortality in the regression model were older age (>66 years), D-Dimer at admission (>1.500 ng/mL) and low lymphocyte count (<0.45×109/L) with an AUC in the ROC curve of 0.81 (95% CI: 0.73-0.89). Patients presenting these three conditions presented a mortality of 100% in the predictive model. VTE frequency in ICU COVID-19 patients is high and risk of major bleeding is low. Comorbidities and laboratory parameters of admission in these patients can be a useful tool to predict mortality.

Genetic Variants in the Protein S ( PROS1 ) Gene and Protein S Deficiency in a Danish Population.

Protein S (PS) deficiency is a risk factor for venous thromboembolism (VTE) and can be caused by variants of the gene encoding PS ( PROS1 ). This study aimed to evaluate the clinical value of molecular analysis of the PROS1 gene in PS-deficient participants. We performed Sanger sequencing of the coding region of the PROS1 gene and multiplex ligation-dependent probe amplification to exclude large structural rearrangements. Free PS was measured by a particle-enhanced immunoassay, while PS activity was assessed by a clotting method. A total of 87 PS-deficient participants and family members were included. In 22 index participants, we identified 13 PROS1 coding variants. Five variants were novel. In 21 index participants, no coding sequence variants or structural rearrangements were identified. The free PS level was lower in index participants carrying a PROS1 variant compared with index participants with no variant (0.51 [0.32–0.61] vs. 0.62 [0.57–0.73] × 10 3 IU/L; p < 0.05). The p.(Thr78Met) variant was associated with only slightly decreased free PS levels (0.59 [0.53–0.66] × 10 3 IU/L) compared with the p.(Glu390Lys) variant (0.27 [0.24–0.37] × 10 3 IU/L, p < 0.01). The frequency of VTE in participants with a coding PROS1 variant was 43 and 17% in the group with normal PROS1 gene ( p = 0.05). In conclusion, we report 13 PROS1 coding variants including five novel variants. PS levels differ by PROS1 variant and the frequency of VTE was higher when a coding PROS1 variant was present. Hence, molecular analysis of the PROS1 gene may add clinical value in the diagnostic work-up of PS deficiency.