Manifestation Of Venous Thromboembolism Research Articles

The Vulnerable Elders Survey-13 scale is superior to the simplified Pulmonary Embolism Score Index in predicting 3-month postdischarge mortality in elderly survivors of acute pulmonary embolism.

Acute pulmonary embolism (APE) is the most serious manifestation of venous thromboembolism. The simplified Pulmonary Embolism Severity Index (sPESI) is employed for prediction of 30-day mortality in APE. The Vulnerable Elders Survey (VES-13) is used to identify participants at a risk of health impairment. We aimed to compare the VES-13 and sPESI scales for prediction of 3-month mortality inelderly patients hospitalized for APE. All patients with APE were managed according to the European Society of Cardiology (ESC) guidelines and followed up for at least 3 months after discharge. Clinical evaluation of all patients involved the Charlson Comorbidity Index (CCI) and biochemical tests. The patients with VES-13 score equal to or above 3 (VES-13≥3) were evaluated with comprehensive geriatric assessment (CGA). A total of 164 patients met the inclusion criteria. There were significantly fewer men in the VES-13≥3 than the VES-13<3 group (34% vs 54.5%; P <0.01). The patients in the VES-13≥3 group had lower median (interquartile range [IQR]) body mass index and higher sPESI score than those in the VES-13<3 group (25.6 [21.8-28.4] kg/m2 vs 28 [25.3-31] kg/m2; P = 0.001 and 2 [1-2] points vs 1 [0-1] point; P <0.001, respectively). There were no differences in APE severity according to the ESC stratification and CCI. Logistic regression analysis identified the VES-13 score as a significant independent risk factor for 3-month mortality. The VES-13 score is a better tool than sPESI for predicting 3-month mortality. Geriatric survivors of APE characterized with VES-13≥3 points should be closely monitored after discharge. The Norton Scale Score in a combination with the VES-13 may be useful in predicting 3-month mortality among numerous tests used in the CGA.

The risk for venous thromboembolism and cardiometabolic disorders in offspring from thrombosis-prone pedigrees

BackgroundMost family studies on venous thromboembolism (VTE) have focused on first-degree relatives. ObjectivesWe took a pedigree-based approach and examined the risk of VTE and cardiometabolic disorders in offspring from extended pedigrees according to the densities of VTE in pedigrees. MethodsFrom the Swedish population, we identified a total of 482 185 pedigrees containing a mean of 14.2 parents, aunts/uncles, grandparents, and cousins of a core full sibship that we termed the pedigree offspring (n = 751 060). We then derived 8 empirical classes of these pedigrees based on the density of cases of VTE. The risk was determined in offspring for VTE and cardiometabolic disorders as a function of VTE density in their pedigrees. Bonferroni correction for multiple comparisons was performed. ResultsVTE was unevenly distributed in the population; the Gini coefficient was 0.59. Higher VTE density in pedigrees was associated in the offspring with a higher risk of different VTE manifestations (deep venous thrombosis, pulmonary embolism, pregnancy-related VTE, unusual thrombosis, and superficial thrombophlebitis), thrombophilia, and lower age of first VTE event. Moreover, VTE density in pedigrees was significantly associated in the offspring with obesity, diabetes, gout, varicose veins, and arterial embolism and thrombosis (excluding brain and heart). No significant associations were observed for retinal vein occlusion, hypercholesterolemia, hypertension, coronary heart disease, myocardial infarction, ischemic stroke, atrial fibrillation, heart failure, primary pulmonary hypertension, cerebral hemorrhage, aortic aneurysm, peripheral artery disease, and overall mortality. ConclusionOffspring of pedigrees with a high density of VTE are disadvantaged regarding VTE manifestations and certain cardiometabolic disorders.

Direct oral anticoagulants for the treatment of splanchnic vein thrombosis: A state of art.

Splanchnic vein thrombosis (SVT) is a manifestation of venous thromboembolism in an unusual site. Portal, mesenteric, and splenic veins are the most common vessels involved in SVT which occurs mainly in patients with liver cirrhosis, although non-cirrhotic patients could be affected as well. Thrombosis of hepatic veins, also known as Budd-Chiari syndrome, is another manifestation of SVT. Prompt diagnosis and intervention are mandatory in order to increase the recalization rate and reduce the risk of thrombus progression and hypertensive complications. Traditional anticoagulation with heparin and vitamin-K antagonists is the treatment of choice in these cases. However, recent studies have shown promising results on the efficacy and safety of direct oral anticoagulants (DOACs) in this setting. Available results are mainly based on retrospective studies with small sample size, but first clinical trials have been published in the last years. This manuscript aims to provide an updated overview of the current evidence regarding the role of DOACs for SVT in both cirrhotic and non-cirrhotic patients.

Effects of hierarchical nursing management in patients with acute pulmonary embolism

BackgroundAcute pulmonary embolism (acute PE) is the most serious manifestation of venous thromboembolism. Hierarchical nursing management is an improved option for nursing, but no study that indicated the effects of hierarchical nursing management in patients with acute PE could be found. This study aimed to explore the effects of hierarchical nursing management on the quality of nursing care and the prognosis of patients with acute PE.MethodsFrom January 2020 to January 2022, 92 patients with acute PE were recruited and divided into the study group and the control group. The study group was designated with our hierarchical nursing care and the control group was designated with a conventional nursing care. The data of general characteristics, nursing quality, the improvement of clinical symptoms, the job satisfaction of nursing was collected and compared.ResultsThe door-to-needle time, the thrombectomy time and length of emergency staying the study group were shorter than those in the control group (P < 0.005). The rate of complications in the study group was lower than that in the control group (P = 0.158). The scores of the nursing quality and the nursing satisfaction levels in the study group were remarkably higher than that in the control group.ConclusionFor acute PE patients, the using of hierarchical nursing management can shorten the rescue time, reduce the rate of complications and improve the nursing quality of nursing care.

Venous Thromboembolism After Interventions on the Ovarian Veins in Patients With Pelvic Venous Disorder

Ovarian vein resection (OVR) and ovarian vein embolization (OVE) are effective options for treating patients with pelvic venous disorder (PeVD). However, due to in an abrupt cessation of blood flow in the ovarian veins (OVs), these interventions can be complicated by pelvic vein thrombosis (PVT). The aim of this study was to assess venous thromboembolism (VTE) rates after OVR and OVE in patients with PeVD. This retrospective cohort study included 272 patients with PeVD who underwent OVR (n=122) or OVE with coils (n=150). The rates and clinical manifestations of VTE were assessed in each group on days 1 and 3 after the intervention using duplex ultrasonography. Vein patency, blood flow velocity, and localization of thrombi in the pelvic (parametrial, uterine, and ovarian), iliac, superficial, and deep veins of the lower extremities were examined. PVT was defined as the formation of blood clots in nontarget (i.e. not intended to intervention) veins of the pelvis (parametrial, uterine veins, or tributaries of the internal iliac veins). VTE after OVR and OVE was identified in 52 (19%) out of 272 patients. In the OVR group, PVT and calf deep vein thrombosis were detected in 9% and 1% of patients, accordingly, while in the OVE group their rates were almost three times higher (24% and 3%; both P=0.001). In both groups, the most common VTE was PVT. The odds ratio for developing VTE with coils was 10 times higher (95% confidence interval: 2.35-56.43) after OVE than after OVR. Clinical manifestations of PVT were observed in 2.5% of patients, and the rest patients were asymptomatic. No cases of pulmonary embolism occurred. VTE after interventions of the ovarian vein in patients with PeVD occurs in every fifth patient. OVE is associated with a higher incidence of PVT.

Analysis of characteristics of the location of lower extremity deep vein thrombosis and the site of pulmonary embolism in hospitalized patients

To investigate the characteristics and relationship between the location of lower extremity deep vein thrombosis (DVT) and the site of pulmonary embolism in hospitalized patients. The data of patients with lower extremity DVT diagnosed by ultrasound examination and pulmonary embolism diagnosed by CT pulmonary angiography from December 2017 to December 2021 were analyzed retrospectively. According to the location of lower extremity DVT, the patients were divided into mixed DVT, proximal DVT, and distal DVT which was further divided into anterior/posterior tibial vein or peroneal vein thrombosis and calf muscular venous thrombosis. Mixed DVT was referred to the presence of both proximal and distal DVT. According to the involved site of pulmonary artery, pulmonary embolism was divided into three types: main pulmonary artery, left or right pulmonary artery trunk embolism, lobar pulmonary artery embolism and segmental pulmonary artery embolism. The location of lower extremity DVT, the site of pulmonary embolism, the clinical manifestation (shortness of breath, chest tightness, chest pain, hemoptysis, cough, lower limb swelling, lower limb pain, syncope, fever) and risk factors (fracture/trauma, tumor, diabetes, hypertension, atrial fibrillation, infection, surgery, autoimmune diseases, paralysis, pregnancy) of venous thromboembolism (VTE), and the level of D-dimer were analyzed. A total of 209 patients were enrolled finally, including 127 patients with left lower extremity DVT (60.8%) and 82 with right lower extremity DVT (39.2%). Mixed DVT accounted for 39.2%, proximal DVT accounted for 17.3%, and distal DVT accounted for 43.5% (anterior/posterior tibial vein and peroneal vein thrombosis accounted for 14.8%, calf muscular venous thrombosis accounted for 28.7%). The incidences of main pulmonary artery embolism, left or right pulmonary artery trunk embolism in the mixed DVT and proximal DVT were significantly higher than those in the anterior/posterior tibial vein or peroneal vein thrombosis and calf muscular venous thrombosis [41.5% (34/82), 38.8% (14/36) vs. 16.2% (5/31), 10.0% (6/60)], with statistically significant differences (all P < 0.05). The incidences of pulmonary segmental artery embolism in the anterior/posterior tibial vein or peroneal vein thrombosis were higher than those in the mixed DVT and proximal DVT [41.9% (13/31) vs. 26.8% (22/82), 30.6% (11/36)], but the difference was not statistically significant (both P > 0.05). The incidences of pulmonary segmental artery embolism in the calf muscular venous thrombosis were significantly higher than those in the mixed DVT and the proximal DVT [66.7% (40/60) vs. 26.8% (22/82), 30.6% (11/36)], and the difference was statistically significant (both P < 0.05). The levels of D-dimer in patients with calf muscular venous thrombosis combined with main pulmonary artery embolism, left or right pulmonary artery trunk embolism were significantly higher than those in patients with calf muscular venous thrombosis combined pulmonary segmental artery embolism (mg/L: 6.08±3.12 vs. 3.66±2.66, P < 0.05). There were no significant differences in D-dimer levels in other patients with DVT combined with pulmonary embolism in different sites. In terms of the clinical manifestations of VTE, the incidences of lower limb swelling in the mixed DVT and proximal DVT were significantly higher than those in the anterior/posterior tibial vein or peroneal vein thrombosis and calf muscular venous thrombosis [54.9% (45/82), vs. 29.0% (9/31), 15.0% (9/60), both P < 0.05], the incidences of lower limb swelling in the proximal DVT were significantly higher than those in the calf muscular venous thrombosis [41.7% (15/63) vs. 15.0% (9/60), P < 0.05], there were no significant difference in the other clinical manifestations among the DVT groups. There was no significant difference in the incidence of VTE risk factors among the groups. The DVT of inpatients mostly occurred in the left lower limb, and the incidence of distal DVT was higher than that of proximal DVT. Mixed DVT and proximal DVT combined with pulmonary embolism mostly occurred in the main pulmonary artery, left or right pulmonary artery trunk, while distal DVT combined with pulmonary embolism mostly occurred in the pulmonary segmental artery. The levels of D-dimer in patients with lower extremity DVT combined with main pulmonary artery or left and right pulmonary artery trunk embolism were higher than those in patients with pulmonary lobe and segmental artery embolism. The incidence of lower extremity swelling in patients with mixed DVT and proximal DVT was higher than that in patients with distal DVT.

Differences in duration of anticoagulation after pulmonary embolism and deep vein thrombosis: Findings from the SWIss Venous ThromboEmbolism Registry (SWIVTER)

BackgroundAlthough the two manifestations of venous thromboembolism (VTE), deep vein thrombosis (DVT) and pulmonary embolism (PE), vary considerably, the consensus guidelines recommend similar algorithms for therapeutic anticoagulation in both conditions. Real-world data assessing contemporary management strategies in PE and DVT alone may help tailoring future recommendations towards more individualized patient care. MethodsIn the present analysis, we compared demographics, comorbidities, treatment patterns, and clinical outcomes of PE versus DVT only among 2062 consecutive patients with confirmed VTE enrolled by 11 acute care hospitals between November 2012 and February 2015 in the SWIss Venous ThromboEmbolism Registry (SWIVTER). ResultsOverall, 1246 (60 %) patients were diagnosed with PE. In comparison to DVT alone, PE patients were older (66 vs. 59 years; p < 0.001), more frequently had acute and chronic comorbidities, less frequently had prior VTE and hormone replacement, and were less often pregnant. VTE was considered similarly often provoked in patients with PE and DVT alone (33.8 % vs. 33.5 %; p = 0.88). Anticoagulation for an indefinite duration was more often prescribed to patients with PE than those with DVT alone (45.7 vs. 19.6 %; p < 0.001), and PE diagnosis was the strongest independent predictor of indefinite anticoagulation (OR 3.21; 95 % CI 2.55–4.06; p < 0.001). Diagnosis of PE was associated with both increased risk of 90-day mortality (HR 2.31, 95 % CI 1.44–3.71; p = 0.001) and major bleeding (HR 3.88, 95 % CI 1.63–9.22; p = 0.002). ConclusionsOur analysis affirms differences in demographics, risk factors, and clinical outcomes of PE versus DVT alone. In routine clinical practice, duration of anticoagulation is being managed differently between the two manifestations of VTE, in contrast to recommendations of the current consensus guidelines.

Incidence and Risk Factors of Pulmonary Hypertension After Venous Thromboembolism: An Analysis of a Large Health Care Database.

Background Pulmonary hypertension (PH) is a devastating potential complication of pulmonary embolism, a manifestation of venous thromboembolism (VTE). The incidence of and risk factors for PH in those with prior VTE are poorly characterized. Methods and Results International Classification of Diseases (ICD) codes from inpatient and outpatient medical claims from MarketScan administrative databases for years 2011 to 2018 were used to identify cases of VTE, comorbidities before the VTE event, and PH occurring subsequent to the VTE event. Cumulative incidence and hazard ratios (HR), and their 95% CI, were calculated. The 170021 VTE cases included in the analysis were on average (±SD) 57.5±15.8years old and 50.5% were female. A total of 5943 PH cases accrued over an average follow-up of 1.94years. Two years after incident VTE, the cumulative incidence (95% CI) of PH was 3.5% (3.4%-3.7%) overall. It was higher among older individuals, among women (3.9% [3.8%-4.1%]) than men (3.2% [3.0%-3.3%]), and among patients presenting with pulmonary embolism (6.2% [6.0%-6.5%]) than those presenting with deep vein thrombosis only (1.1% [1.0%-1.2%]). Adjusting for age and sex, risk of PH was higher among patients with VTE with underlying comorbidities. Using the Charlson comorbidity index, there was a dose-response relationship, whereby greater scores were associated with increased PH risk (score ≥5 versus 0: HR, (2.50 [2.30-2.71])). When evaluating individual comorbidities, the strongest associations were observed with concomitant heart failure (HR, 2.17 [2.04-2.31]), chronic pulmonary disease (2.01 [1.90-2.14]), and alcohol abuse (1.66 [1.29-2.13]). Conclusions In this large, real-world population of insured people with VTE, 3.5% developed PH in the 2years following their initial VTE event. Risk was higher among women, with increasing age, and in those with additional comorbidities at the time of the VTE event. These data provide insights into the burden of PH and risk factors for PH among patients with VTE.

Thromboembolic Events among Multiple Trauma Victims with Pelvic Fractures with Injury Severity Score Greater Than 16 with and without Deep Vein Thrombosis Prophylactic Doses of Enoxaparin

Introduction: Venous thromboembolism (VTE) is a common life-threatening complication in patients affected by severe trauma. The clinical manifestations of VTE are deep venous thrombosis (DVT) and pulmonary embolism (PE). Various prophylactic pharmacological strategies are used. We studied the efficacy of enoxaparin in preventing VTE in our level 1 trauma center. Materials and Methods: This cross-sectional study included patients with polytrauma with an Injury Severity Score (ISS) of greater than 16 units and a pelvis fracture diagnosis. Clinical features, laboratory data, and images were reviewed from medical documents. Moreover, the prophylactic medication regimens were recorded. Development of VTE was identified in patients, and a p-value <0.05 was considered statistically significant. Results: A total of 327 patients were examined, of which 18 had developed VTE (5.5%). The frequency was relatively higher in males, cases with fractures, and cases with a history of VTE. Patients with two or more pelvic fracture sites and those with a history of VTE manifested are statistically more likely to develop VTE than those with fewer than two pelvic fracture sites and no history of VTE (p-value = 0.02 and 0.006, respectively). Moreover, the administration of prophylactic doses of enoxaparin n had no statistically significant effect on VTE prevention (p-value = 0.08). Conclusion: In conclusion, we found no significant correlation between the prophylactic doses of enoxaparin and VTE probability. Furthermore, a history of VTE and more fracture sites would increase the probability of VTE.

Correlation between serum factor VIII:C levels and deep vein thrombosis following gynecological surgery

ABSTRACT Deep vein thrombosis (DVT) is common in patients following gynecological surgery. Coagulation factor VIII (FVIII) is an important part of the human coagulation system, and FVIII:C is a component of FVIII with anticoagulant activity. 800 patients who underwent gynecological surgery were enrolled. General clinical data were harvested, and pre – and postoperative serum FVIII levels were determined. Lower-extremity ultrasound examination and/or postoperative pulmonary angiography were performed. Related data were analyzed statistically. DVT was the first manifestation of venous thromboembolism in all cases. There were a total of 46 cases, and the incidence of DVT was 5.8%. Progression to pulmonary embolism was confirmed in 16 cases, with an incidence of 2.0%. The independent risk factors for DVT after gynecological surgery were postoperative FVIII:C levels (odds ratio [OR] = 1.01), age (OR = 6.57), and operation time ≥3 hours (OR = 2.90) (P < 0.05). When the FVIII:C level was greater than the 75th centile (≥150 IU/dL), the risk of DVT was 2.99 times higher than that below the 25th centile (<100 IU/dL) (P < 0.05). When combined with the risk factor of operation time ≥3 hours, the risk increased to 3.17 times (P = 0.10). When combined with age ≥60 years, the risk was significantly increased, reaching 12.0 times (P < 0.05). Serum FVIII:C levels are an independent risk factor for DVT after gynecological surgery. Higher levels increase the risk of DVT after gynecological surgery, and they may have a dose-dependent relationship. A synergistic effect exists in combination with other risk factors, which further increases the risk.

Heritable Thrombophilia in Venous Thromboembolism in Northern Pakistan: A Cross-Sectional Study.

Background Venous thromboembolism (VTE) is referred to as formation of clots in a deep vein or lodging of thrombus towards the lungs which could be fatal yet preventable. The risk of developing VTE can be increased by various factors. Where there are innumerable acquired causes, the possibility of inherited thrombophilia cannot be ignored. In view of this, we have evaluated all patients with venous thromboembolism for inherited thrombophilia. Objective To evaluate the frequencies of antithrombin (AT) deficiency, protein C and S deficiencies, Factor V Leiden, and prothrombin gene mutations in patients harboring venous thromboembolism. Materials and Methods A study comprising of 880 patients who were presented with manifestations of venous thromboembolism was conducted from July 2016 to June 2017. A blood sample collected from patients was screened for thrombophilia defects encompassing AT, protein C and S deficiencies, Factor V Leiden, and prothrombin gene mutations. All acquired causes of thrombosis were excluded. Results Of 880 patients who underwent screening for thrombophilia, 182 patients demonstrated VTE history. Their age ranged from 1 to 58 years. Males constituted a predominant group. About 45 (24.7%) patients had evidence of heritable thrombophilia. Of these, 20 (10.9%) had AT deficiency, 9 (4.9%) had Factor V Leiden mutation, 6 (3.2%) had protein C deficiency, whereas protein S deficiency and prothrombin gene mutation both were found in 5 (2.7%) patients. Conclusion Our study illustrated the highest frequency of antithrombin deficiency among other investigated thrombophilia defects.

Genetic association study of fatal pulmonary embolism

Pulmonary embolism (PE) is a complex multi-factorial disease and represents one manifestation of venous thromboembolism (VTE). Most commonly PE constitutes a complication of VTE’s other clinical presentation deep vein thrombosis (DVT). The majority of studies concerning risk factors do not distinguish between PE and DVT. The risk factors are often estimated to be alike, but the prevalence and the risk associated with the major genetic factor Factor V Leiden differ between the two disease states. We have investigated the association of 22 SNPs with PE in 185 PE case and 375 healthy control subjects. At p = 0.05, eight SNPs presented with nominally significant evidence of association (EOA), although no significantly different genotype distributions remained between cases and controls after Bonferroni correction. Three of these variants (rs1800790, rs3813948, rs6025) showed EOA in the main analysis, and five variants (rs169713, rs1801131, rs4524, rs5985 and rs8176592) demonstrated EOAs in subgroups. Genomic variation modulating Factor V, Factor XIII, Beta fibrinogen (FGB), TFPI or HIVEP1 should be worth to be followed in subsequent studies. The findings of this study support the view that PE represents a complex disease with many factors contributing relatively small effects. Larger sample sizes will be required to reliably detect these small effects.

Short-term effects of particulate matter concentrations on Pulmonary Embolism and Deep Vein Thrombosis at national level in Italy

Background: Several studies reported a link between increases of particulate matter (PM) air pollution and cardiovascular diseases. However, only few reported consistent associations with Venous Thromboembolism (VTE), i.e., Pulmonary Embolism (PE) and Deep Vein Thrombosis (DVT), the third most frequent cardiovascular disease. Our aim was to estimate the association between hospital admissions for these clinical manifestation of VTE and PM concentrations at the national level in Italy.Methods: We collected all hospital discharges during 2006-2015 from the Italian Ministry of Health. Daily counts of VTE, PE and DVT admissions in all the 8,094 municipalities were merged with daily and concentrations estimated by a satellite-based spatiotemporal model. First, we applied multivariate Poisson regression models at province level; then, we aggregated results by random-effects meta-analysis and obtained the overall effect at national level. We analyzed each outcome at different temporal latencies (lags), in the warm period (defined as April to September) and in the main urban areas.Results: Analysis were conducted on 432,245 VTE hospitalizations (PE= 219,952; DVT= 275,506). National daily mean (standard deviation) concentrations of and were 23 (14) and 17 (12) , respectively. Meta-analytical results showed weak associations between PM concentrations and the study outcomes in the full year analysis. During the warm season and in the main urban areas, the daily relative increase of VTE admissions per 10 increment in same day was 3.4% (95% Confidence Intervals [CI]: -0.01; 6.93). Corresponding estimate for PE and DVT were 3.9% (95% CI: -0.51; 8.68) and 1.4% (95% CI: -2.61; 5.50).Conclusions: This is the first study conducted in Europe to investigate the association between air pollutants and PE-DVT at national level. We found an immediate effect of on VTE only during the warm months and in the main urban areas.

Anticoagulation in Italian patients with venous thromboembolism and thrombophilic alterations: findings from START2 register study.

Randomised control trials have assessed the efficacy and safety of direct oral anticoagulants in the prophylaxis and treatment of venous thromboembolism (VTE). Positive but limited results have been reported in patients with inherited thrombophilia. Using an Italian, multicentre, prospective registry of consecutive patients presenting with symptomatic, acute VTE, we aimed to assess which factors are involved in making the choice of the drug that best fits the patient's risk profile in a large real-world setting of VTE patients. We investigated 4,866 VTE patients who took oral anticoagulants in the period between 2012 and April 2018 to prevent a new thromboembolic episode. The large majority of patients who underwent thrombophilic screening, regardless of the results obtained, were prescribed direct oral anticoagulants rather than conventional anticoagulant therapy (p<0.001). During anticoagulation, bleeding events occurred more frequently in patients on conventional anticoagulant therapy (4.2%) than in those receiving direct oral anticoagulants (1.8%) and an increase in bleeding events was observed in patients who tested positive at the thrombophilic screening. Overall, a higher number of recurrent VTE was observed in patients not screened for thrombophilia (n=36; 1.7%) than in those screened (n=20; 0.7%; adjusted odds ratio: 2.2; 95% confidence interval: 1.2-4.1). The present data confirm previous findings from other post-marketing registries and suggest that the choice of oral anticoagulation is strongly driven by patients' characteristics and VTE manifestations. Factors leading to the prescription of thrombophilic screening may identify a patient with a lower risk of VTE recurrence during anticoagulation.

Cerebral and Splanchnic Vein Thrombosis: Advances, Challenges, and Unanswered Questions.

Cerebral vein thrombosis (CVT) and splanchnic vein thrombosis (SVT) are two manifestations of venous thromboembolism (VTE) at unusual sites. They have an incidence at least 25–50 times lower than usual site VTE, but represent true clinical challenges. Recent evidence on the epidemiology, risk factors, prognosis, and treatment of CVT and SVT has been published in the last two decades, thus contributing to a better understanding of these diseases. The improvement in imaging techniques and a higher degree of clinical suspicion may have led to the observed increased frequency, whereas a better knowledge of provoking mechanisms could have contributed to reducing the proportion of events classified as unprovoked or idiopathic (13–21% of CVT, 15–27% of SVT). Few small randomized clinical trials and a number of observational studies, although hampered by heterogeneous therapeutic approaches, shed light on the safety and effectiveness of anticoagulant therapy in these populations. However, there are still some grey areas that warrant future research. In this narrative review, we discuss recent advances and therapeutic challenges in CVT and SVT.

Positive Association of Mutations in VKORC1 and CYP2C9 Genes with Venous Thrombo-Embolism (VTE) in Indian Population: A Case Control Study

Background: Venous thrombo-embolism (VTE) refers to a blood clot that starts in vein. It is the third most common vascular disease in the world, after myocardial infarction (MI) and stroke, affecting millions of individuals every year. Two main clinical manifestations of VTE include deep vein thrombosis (DVT) and pulmonary embolism (PE), the later one being potentially fatal. Objective: The aim of this study is to investigate whether mutations in two genes VKORC1 and CYP2C9 and subsequent changes in their plasma levels can be used to predict the risk for venous thromboembolism (VTE). Method: A total of five polymorphisms in two genes VKORC1 and CYP2C9 were genotyped in approximately 145 VTE patients and 229 control subjects. The genotyping was done through PCR-RFLP method. Plasma concentrations of VKORC1 and CYP2C9 were estimated using ELISA technique. Results: Genotypic analysis of common polymorphisms in VKORC1 gene showed significantly higher percentage of GG genotype of -1639G&gt;A, CC genotype of 1173 C&gt;T and TT genotype of -497T&gt;G polymorphism in control subjects compared to VTE patients. Also, significantly higher percentage of CC genotype in 416C&gt;T and AA genotype in 1061 A&gt;C polymorphism of CYP2C9*2 and CYP2C9*3 genes respectively was observed in VTE patients in comparison to healthy controls. In addition to genotypic significance, plasma concentrations of both VKORC1 and CYP2C9 were significantly higher in patients group. Conclusion: All the three polymorphisms in VKORC1 gene; -1639G&gt;A, 1173 C&gt;T and -497T&gt;G and two polymorphism 416C&gt;T and 1061A&gt;C of CYP2C9 gene showed significant association with VTE pathophysiology

Venous Thrombosis could be Gender Specific, Women Beware!

Venous thrombosis (VT) is the third major cause of mortality in the world after heart attack and stroke. Its two major clinical manifestations are deep vein thrombosis (DVT) and pulmonary embolism (PE) which are serious medical conditions but often remain under-diagnosed. Although rate of occurrence of venous thrombosis in men is slightly higher, a number of studies have pointed out that woman poses higher risk of venous thromboembolism (VTE) compared to men at various stages of life. Risk of VTE increases in women’s life particularly with use of oral contraceptives, during pregnancy and with exogenous administration of hormones like in post-menopausal hormone therapy. Various reports show that these factors increase risk of DVT and PE by several folds. DVT is considered as an important cause of maternal death in western countries. It is often asymptomatic and its signs and symptoms are similar to those of normal pregnancy. The hormonal changes at various stages of life and less physical activity increase the risk of VTE by blood flow stasis. It is extremely important for women to know the stages of life when they are prone to develop VTE, about its prevention and treatment. Detailed studies on differences in clinical manifestations of VTE between men and women are lacking. This review focusses on assessing the increased risk of VTE and its prognosis in women based on available literature.

PB2426 CLINICAL MANIFESTATION OF HEREDITARY THROMBOPHILIA IN CHILDREN

Background:Venous thromboembolism (VTE) in children is becoming a more frequent problem. The pathogenesis of thrombosis is complex: thrombophilia, background disease, trigger factor. Special attention should be deserved to hereditary thrombophilia (HT), which from childhood can be accompanied by persistent disorders in the hemostasis system and significantly increase the risk of thrombosis.Aims:To assess the influence of HT on the development of venous thromboembolic complications in children.Methods:We have examined 24 patients aged from 1 day to 18 years, who had various types of thrombotic manifestations (n = 20) or the threat thereof taking into account the family history (n = 4). The average age of children was 5.6 years, the ratio of girls to boys was 1.4 / 1.0. All patients underwent a full laboratory examination aimed at the diagnosis of HT and antiphospholipid syndrome (APS): levels of antithrombin III (ATIII), protein C and S, antibodies to β2‐glycoprotein and cardiolipin, lupus anticoagulant, homocysteine level. Molecular genetic testing included thrombogenic mutations and polymorphisms.Results:In half of the cases of VTE, the lower extremity deep vein thrombosis of was diagnosed. Venous sinus thrombosis ‐ in 20% of the examined (n = 4); pulmonary artery thromboembolism in one case; thrombosis in the pool of the portal and superior vena cava ‐ in 35%. VTE recurrences were observed in 20% of cases. The diagnosis of HT is verified in 62.5% of all examined children and in 55% of children with thrombosis. The HT variants were distributed in the following way: 33.3% ‐ mutation in the FV Leiden (het) gene; 20% ‐ in the prothrombin G20210A (het) gene; AT III deficiency was diagnosed in three patients (20%); combined mutations in MTHFRC‐677T (T/T) and PAI‐1 (4G/4G) genes‐ 26.7%. MTHFRC‐677T (T/T) mutations in two cases were accompanied by moderate hyperhomocysteinemia. Trigger factors for VTE not associated with HT were background diseases and its associated complications: acute lymphoblastic leukemia (n = 4); parenteral nutrition (n = 1); operative interventions (n = 2); autoimmune diseases (n = 2) and APS (n = 1). Clinical manifestation of HT in 63.3% of cases was observed in patients over 10 years old. In 72.7% of cases, VTE occurred spontaneously. The earliest spontaneous VTE was detected in a child at the age of 1 day (portal vein thrombosis). In 75% of cases of recurrent VTE, HT has occurred.Summary/Conclusion:Hereditary thrombophilia is a sign of the potential risk of thrombosis in children. Clinical manifestation of VTE occurs at any location, at any age, but significantly more often in children older than 10 years. The presence of HT is a high risk factor for recurrent and spontaneous VTE. Diagnosis of HT is reasonable to carry out in all cases of VTE in children, which is important not only for assessment of the risk of repeated thrombotic episodes, but also for selecting the antithrombotic therapy regimen and optimizing preventive measures.

PB2432 POSSIBLE GENETIC RISK FACTORS OF PULMONARY EMBOLISM IN YOUNG PATIENTS FROM THE NORTH‐WESTERN REGION OF RUSSIA

Background:Pulmonary embolism (PE) and deep‐vein thrombosis (DVT) are the most common clinical manifestations of venous thromboembolism (VTE) which associated with high rates of morbidity and mortality in population. To date, little is known about the factors which could predict PE development in VTE patients. Several studies have shown that fibrin clot structure as well as the rate of clot lysis could influence the risk of PE development. Moreover, nucleotide variations in genes coding for components involved in processes of thrombus formation or its lysis are well‐described. Nevertheless, association between patient's genotype and features of clinical VTE manifestation, in particular, risk of PE development, remains debatable.Aims:To reveal possible association between the alpha‐fibrinogen (FI‐A), factor XIII A‐subunit (FXIII‐A), tissue plasminogen activator (TPA) and plasminogen activator inhibitor type I (PAI‐1) gene polymorphisms and the features of clinical VTE manifestation in patients with early‐onset disease from the North‐Western region of Russia.Methods:We analyzed 243 young patients under 45 years old (119 men and 124 women, mean age – 37.4 years) with at least one confirmed episode of acute VTE. Isolated DVT (“DVT only”) was diagnosed in 154 (63.4%), DVT complicated by PE (“DVT + PE”) – in 53 (21.8%), and isolated PE (“PE only”) – in 36 (14.8%) patients. Genotyping for the FI‐A Thr312Ala, FXIII‐A Val34Leu, PAI‐1 ‐675 4G/5G and TPA 311 bp Ins/Del variations was performed by PCR‐RFLP. To assess intergroup differences in genotype frequencies, the odds ratios (OR), their 95% confidence intervals (CI) and p‐values were calculated by Fisher's exact method.Results:Distributions of the FI‐A, FXIII‐A, PAI‐1 and TPA genotypes in patients with different clinical manifestations of VTE have shown several differences. Frequency of the TPA Del/Del genotype was significantly increased in VTE patients with the signs of PE when compared to those with isolated DVT (31.5% vs. 18.8%, respectively, OR = 2.0; 95% CI: 1.1‐3.6; p = 0.029). Homozygosity for the TPA Del allele was most prevalent in patients with isolated PE (38.9% vs. 18.8% in the group “DVT only”, OR = 2.7; 95% CI: 1.3‐6.0; p = 0.014). In this group, the frequency of the FI‐A 312 Ala/Ala variant was 2‐fold increased when compared to patients with isolated DVT (22.2% vs. 11.0%, respectively, OR = 2.3; 95% CI: 0.9‐5.9; p = 0.098). In patients with the signs of PE, homozygosity for the FXIII‐A 34Leu variant was observed more frequently than in the “DVT only” group (11.2% vs. 6.5%, respectively, OR = 1.8; 95% CI: 0.7‐4.6; p = 0.23). At the same time, the frequency of heterozygous FXIII‐A genotype was significantly increased in patients with isolated DVT when compared to “DVT + PE” group (48.7% vs. 30.2%, respectively, OR = 2.2; 95% CI: 1.1‐4.3; p = 0.024).Summary/Conclusion:TPA Del/Del genotype is associated with the risk of PE development in young VTE patients from the North‐Western region of Russia, whereas heterozygous FXIII‐A variant (34 Val/Leu) could protect from PE in patients with DVT. Role of the FI‐A 312 Ala/Ala and FXIII‐A 34 Leu/Leu variants as possible determinants of different clinical course of VTE needs further clarification.

Venous Thromboembolism as an Adverse Effect During Treatment With Olanzapine: A Case Series.

Objective: Venous thromboembolism (VTE) is a serious multifactorial disorder. Patients with severe mental illness have a higher risk of developing the condition compared to the general population. Methods: We observed 10 cases of VTE in patients with mental illness who were treated with the antipsychotic drug olanzapine. The diagnosis of VTE was made at the University Hospital Hradec Kralove (UH HK) from 2004 to 2013. VTE was objectively determined by imaging techniques (duplex ultrasonography, CT angiography) and laboratory tests (D-dimer). The average age was 46 years. The clinical manifestation of VTE was deep vein thrombosis in nine cases, including one case of simultaneous pulmonary embolism and one case of a concurrent ischemic cerebrovascular accident (iCVA). None of our patients had a history of malignant disease, trauma, or surgery. Results: Apart from antipsychotic medication, all the patients had clinical or laboratory risk factors for VTE. The most frequent clinical risk factors were obesity (n = 7) and smoking (n = 6). The most frequent laboratory risk factors were increased levels of FVIII (n = 4), mild hyperhomocysteinemia (n = 3), and factor V Leiden mutation (n = 2). VTE developed within 3 months after antipsychotic drug initiation in three patients and within 6 months in three patients. Conclusion: Olanzapine can be considered a precipitating factor for VTE formation. When olanzapine is administered, we need to monitor for clinical signs and symptoms of VTE, especially when other risk factors are present.