Inna Tzoran

Silent pulmonary embolism in patients with proximal deep vein thrombosis in the lower limbs.

Summary.  Background:  One in every three patients with deep vein thrombosis (DVT) in the lower limbs may have silent pulmonary embolism (PE), but its clinical relevance has not been thoroughly studied.

VTE Registry: What Can Be Learned from RIETE?

The Registro Informatizado de Enfermedad TromboEmbólica (RIETE Registry) is an ongoing, international, prospective registry of consecutive patients with acute venous thromboembolism (VTE) designed to gather and analyze data on treatment patterns and outcomes in patients with acute VTE. It started in Spain in 2001, and 6 years later the database was translated into English with the aim to expand the Registry to other countries. In contrast to randomized controlled trials, there is no imposed experimental intervention: the management is determined solely by physicians. Thus, it provides data on patients with VTE in a real-world situation with an unselected patient population. Data from RIETE are hypothesis-generating and provide feedback from real-world clinical situations. So far, we learned about the natural history of VTE in patients with relative or absolute contraindications to anticoagulant therapy. We also learned interesting aspects on the natural history of VTE, and we built a number of prognostic scores to identify VTE patients at low, moderate, or high risk for adverse outcome.

Clinical outcome in patients with venous thromboembolism receiving concomitant anticoagulant and antiplatelet therapy.

INTRODUCTION Patients with arterial disease receiving antiplatelet agents may develop venous thromboembolism (VTE) and need anticoagulant therapy, although concomitant use of these drugs may increase bleeding risk. We analyzed RIETE data and compared clinical outcomes depending on decision to discontinue or maintain antiplatelet therapy at VTE diagnosis. METHODS Consecutive patients with acute VTE were enrolled in RIETE. Only patients receiving antiplatelet therapy at baseline were included in this analysis. Primary outcomes were: rate of subsequent ischemic events, major bleeding or death during anticoagulation course. RESULTS 1178 patients who received antiplatelet drugs at VTE diagnosis were included. Antiplatelet therapy was discontinued in 62% of patients. During anticoagulation course, patients also receiving antiplatelet therapy had higher rates of lower limb amputations (2.28 vs. 0.21 events per 100 patients-years; p<0.01), any ischemic events (5.7 vs. 2.28 events per 100 patients-years; p<0.05) or death (23.6 vs. 13.9 deaths per 100 patients-years; p<0.01). No differences in the rate of major bleeding or recurrent VTE were revealed. In matched analysis, patients on antiplatelet therapy were found to have a significantly higher rate of limb amputations (odds ratio: 15.3; 95% CI: 1.02-229) and an increased number of composite outcomes including all-cause deaths, arterial and VTE events (odds ratio: 1.46; CI: 1.03-2.06), with no differences in major bleeding rate. CONCLUSION Concomitant anticoagulant and antiplatelet therapy in patients with VTE and arterial disease is not associated with increased risk for bleeding, recurrent VTE or death. The worse outcome observed in patients who continued antiplatelet therapy requires further investigations.

Recurrence of venous thromboembolism in patients with recent gestational deep vein thrombosis or pulmonary embolism: Findings from the RIETE Registry

INTRODUCTION The aim of this study was to investigate the recurrence rate of venous thromboembolism (VTE) and the prevalence of major bleeding or death in patients with previous VTE in pregnancy and puerperium. Risk factors for VTE recurrence were also assessed. MATERIALS AND METHODS We evaluated a cohort of patients enrolled in the international, multicenter, prospective Registro Informatizado de la Enfermedad Trombo-Embólica (RIETE) registry with objectively confirmed VTE. RESULTS In the registry, 607 women were presenting with VTE that occurred during pregnancy or puerperium. The 2-year VTE recurrence rate was 3.3% (CI: 95 1.5-5.0%) and the recurrent VTE incidence rate was 2.28events/100 patients-year. Among the 16 cases of VTE recurrence 11 cases appeared during drug treatment while only five cases were diagnosed after therapy discontinuation. No significant difference was found in treatment duration among these two subgroups of VTE recurrence cases and women without recurrence. Furthermore, the use of thrombolytics and inferior vena cava filter in initial treatment was associated to an increased risk of VTE recurrence. CONCLUSIONS The current study provides new insights on VTE recurrence rate in patients with deep vein thrombosis (DVT) or pulmonary embolism (PE) that occurred in pregnancy or postpartum period. These findings can contribute to risk assessment of thrombotic burden, thereby allowing for better decision making regarding antithrombotic management in this clinical setting.

Hemostasis and Thrombosis in the Oldest Old

Abstract There is a growing proportion of the elderly population in the Western world, and these individuals require special considerations regarding a broad variety of aspects, including treatment approaches to illnesses that affect all age groups. The hemostatic system in individuals changes considerably with aging. Specifically, changes in levels of procoagulant and natural anticoagulant factors along with thrombopathy simultaneously create a hypercoagulable state and hemostatic difficulties. Underlying morbidities, such as congestive heart failure, chronic obstructive pulmonary disease, diabetes mellitus, and cancer, increase the risk for venous and arterial thrombosis. This population is also increasingly affected by acquired bleeding disorders, including acquired hemophilia and acquired von Willebrand syndrome, as well as mild congenital bleeding disorders. Real‐life data demonstrate that recurrent and fatal venous thromboembolism is the major hemostatic concern in the elderly. The fact that treatment of thrombotic complications increases the bleeding risk also has to be taken into consideration, particularly in the older age group. This remains true in the era of direct oral anticoagulants. In conclusion, maintaining a delicate balance between thrombosis and bleeding risks is the key issue in providing qualified treatment to elderly patients.

Pre-Admission Characteristics Predicting an Adverse Outcome in Asthma Exacerbation

Background: Pre-admission clinical parameters predicting an adverse outcome in subjects presenting to the emergency department (ED) with acute asthma exacerbation, as well as their cutoff levels, are not well defined. This study aims to identify these parameters. In asthma patients, clinical parameters associated with adverse events are well known. However when these patients present with an acute asthma attack, the pre-admission clinical findings associated with an impending inhospital respiratory failure, as well as their cutoff levels, are still lacking. Our study suggests that O2 saturation of 94 percent and lower, PaCO2 levels above 51.5 mmHg and a history of previous hospitalizations due to asthma exacerbations are independent predictors of in-hospital adverse outcome of the index event. Methods: Records of subjects with an ED diagnosis code for asthma were retrospectively reviewed for 32 clinical parameters, including: demographics, symptoms, asthma-related history, current treatment, risk factors, clinical, laboratory and radiographic findings. These parameters were analyzed for their association with an adverse outcome defined as intensive care unit admission, intubation or death. Results: Files of 266 subjects presented to the Rambam ED with acute asthma attack between 01/01/2012 and 12/31/2015 were analyzed. Adverse outcome was recorded in 22. Parameters associated with adverse outcome in a univariate analysis included: routine use of short-acting beta agonists, recent corticosteroids prescription, and prior asthma related admissions, previous mechanical ventilation, low O2 saturation, leukocytosis, respiratory acidosis and abnormal chest X-ray. In a multivariate analysis, the significant independent predictors for in-hospital adverse outcome were: elevated PaCO2 (95% CI 1.002-1.075; p=0.038), low O2 saturation (95% CI 0.662-0.845; p=0.034) and previous hospital admissions (95% CI 1.108-13.440; p <0.001). Cutoff values were 94% for O2 saturation and 51.5 mmHg for PaCO2 levels. Conclusions: The current study suggests that O2 saturation below 94 percent, PaCO2 levels above 51.5 mmHg and prior asthma related admissions are independent predictors of in-hospital adverse outcome. These subjects should be managed in a more intensive manner in the ED.

Gender-related differences in the outcome of patients with venous thromboembolism and thrombophilia

BACKGROUND In patients with venous thromboembolism (VTE) and factor V Leiden (FVL) or prothrombin 20210G-A mutation (PTM), the influence of gender on outcome has not been consistently studied. METHODS We used the RIETE (Registro Informatizado Enfermedad TromboEmbolica) database to assess the existence of gender differences in the rate of VTE recurrences (deep vein thrombosis [DVT] or pulmonary embolism [PE]) or major bleeding during the course of anticoagulation and after its discontinuation in FVL and PTM carriers. RESULTS From March 2001 to September 2016, 11,224 VTE patients underwent thrombophilia testing. Of these, 1,563 were FVL carriers (863 men and 700 women) and 1,231 were PTM carriers (659 men and 572 women). During the course of anticoagulant therapy, men with FVL had a 6-fold higher rate of VTE recurrences than major bleeds (31 vs. 5 events). In women with FVL, the rate of VTE recurrences was 2-fold higher (16 vs. 8), as was in men (17 vs. 8) or women (17 vs. 9) with PTM. After discontinuing anticoagulation, men with FVL had a 3-fold higher rate of DVT recurrences than women (hazard ratio [HR]: 3.13; 95% CI: 1.79-5.67), with no differences in PE recurrences. Among patients with PTM, there were no gender differences in the rate of DVT (HR: 1.89; 95% CI: 1.00-3.65) or PE recurrences (HR: 1.82; 95% CI: 0.83-4.12). CONCLUSIONS During the anticoagulation course, men with FVL are at a much higher risk for VTE recurrences than bleeding. After discontinuing anticoagulation, men with FVL are at an increased risk for DVT recurrences.