Faculty of Medicine

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Failure rate of the pulmonary embolism rule-out criteria rule for adults 35 years or younger: Findings from the RIETE Registry
(Wiley (United States), 2025)
Jossein T,
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Mazzolai L,
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Lorenzo Hernández A,
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Rivas Guerrero A,
Background The use of a computed tomography pulmonary angiogram to diagnose pulmonary embolism (PE) has increased, leading not only to higher PE diagnoses but also to overdiagnosis and unnecessary radiation exposure, even in young patients despite a lower PE incidence. The aim of this study was to assess the failure rate of the pulmonary embolism rule-out criteria 35 (PERC-35) rule developed to reduce unnecessary testing in individuals aged ≤35 years among patients included in the Registro Informatizado de la Enfermedad TromboEmbolica Venosa (RIETE) Registry. Methods This retrospective cohort study used data from the RIETE Registry, an ongoing, international prospective registry of patients with objectively confirmed venous thromboembolism. The primary outcome was the missed PE rate using PERC-35 criteria. Secondary outcomes included the comparison of demographic and clinical characteristics, PE localization, treatment strategies, and outcomes between PERC-negative (PERC-35N) versus PERC-positive (PERC-35P) patients. Results Of 58,918 adult patients with acute PE, the PERC-35 rule demonstrated a low missed PE rate of 0.35% (n = 204), with an upper 95% confidence interval [CI] of 0.40%. The missed rate was 7.0% (95% CI 6.0%–7.9%) in the 18- to 35-year subgroup. Compared to PERC-35P patients, PERC-35N patients were younger (mean age 28.4 years), with a lower body mass index, and included a higher proportion of pregnant/postpartum women. PERC-35N patients had a significantly lower rate of chronic diseases and presented less frequently with dyspnea or syncope but more often with chest pain. They showed lower rates of positive D-dimer and troponin levels. PERC-35N patients experienced fewer major bleeding episodes, similar recurrence rates of PE/deep vein thrombosis, and no deaths during anticoagulation. Conclusions The PERC-35 rule demonstrated a low failure rate to exclude PE in patients aged 18–35 years and could reduce imaging and radiation exposure in young patients with a low PE pretest probability if confirmed prospectively.
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Special Conditions in Venous Thrombembolism - Case Series
(Macedonian Academy of Sciences and Arts/Walter de Gruyter GmbH, 2019-10-01)
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Klincheva, Milka
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Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is a preventable cause of in-hospital death, and one of the most prevalent vascular diseases. There is a lack of knowledge with regards to contemporary presentation, management, and outcomes of patients with VTE. Many clinically important subgroups (including the elderly, those with recent bleeding, renal insufficiency, disseminated malignancy or pregnant patients) have been under-represented in randomized clinical trials. We still need information from real life data (as example RIETE). The paper presents case series with VTE in special conditions, including cancer associated thrombosis, malignant homeopathies, as well in high risk population.
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Special Conditions in Venous Thrombembolism – Case Series
(Macedonian Academy of Sciences and Arts, 2019-10-01)
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Klincheva, Milka
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Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is a preventable cause of in-hospital death, and one of the most prevalent vascular diseases. There is a lack of knowledge with regards to contemporary presentation, management, and outcomes of patients with VTE. Many clinically important subgroups (including the elderly, those with recent bleeding, renal insufficiency, disseminated malignancy or pregnant patients) have been under-represented in randomized clinical trials. We still need information from real life data (as example RIETE). The paper presents case series with VTE in special conditions, including cancer associated thrombosis, malignant homeopathies, as well in high risk population.
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FREQUENCY OF GENETIC VARIANTS ASSOCIATED WITH CORONARY ARTERY DISEASE AND VENOUS THROMBOEMBOLISM IN YOUNG PATIENTS IN REPUBLIC OF N. MACEDONIA
(Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, 2022)
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Clinical Characteristics and Outcomes of Patients with Lung Cancer and Venous Thromboembolism
(2018)
Ruiz-Artacho P,
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Trujillo-Santos J,
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López-Jiménez L,
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Font C,
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Díaz-Pedroche MDC,
Background The natural history of patients with lung cancer and venous thromboembolism (VTE) has not been consistently evaluated. Methods We used the RIETE (Registro Informatizado Enfermedad TromboEmbólica) database to assess the clinical characteristics, time course, and outcomes during anticoagulation of lung cancer patients with acute, symptomatic VTE. Results As of May 2017, a total of 1,725 patients were recruited: 1,208 (70%) presented with pulmonary embolism (PE) and 517 with deep vein thrombosis (DVT). Overall, 865 patients (50%) were diagnosed with cancer <3 months before, 1,270 (74%) had metastases, and 1,250 (72%) had no additional risk factors for VTE. During anticoagulation (median, 93 days), 166 patients had symptomatic VTE recurrences (recurrent DVT: 86, PE: 80), 63 had major bleeding (intracranial 11), and 870 died. The recurrence rate was twofold higher than the major bleeding rate during the first month, and over threefold higher beyond the first month. Fifty-seven patients died of PE and 15 died of bleeding. Most fatal PEs (84%) and most fatal bleeds (67%) occurred within the first month of therapy. Nine patients with fatal PE (16%) died within the first 24 hours. Of 72 patients dying of PE or bleeding, 15 (21%) had no metastases and 29 (40%) had the VTE shortly after surgery or immobility. Conclusion Active surveillance on early signs and/or symptoms of VTE in patients with recently diagnosed lung cancer and prescription of prophylaxis in those undergoing surgery or during periods of immobilization might likely help prevent VTE better, detect it earlier, and treat it more efficiently.
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Sex Differences in Patients With Occult Cancer After Venous Thromboembolism.
(2018)
Jara-Palomares L,
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Otero R,
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Jiménez D,
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Praena-Fernández JM,
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Rivas A,
In patients with venous thromboembolism (VTE), male sex has been associated with an increased risk of occult cancer. The influence of sex on clinical characteristics, treatment, cancer sites, and outcome has not been thoroughly investigated yet. We used the Registro Informatizado Enfermedad TromboEmbólica registry to compare the clinical characteristics, treatment strategies, cancer sites, and clinical outcomes in patients with VTE having occult cancer, according to sex. As of June 2014, 5864 patients were recruited, of whom 444 (7.6%; 95% confidence interval: 6.8-8.2) had occult cancer. Of these, 246 (55%) were men. Median time elapsed from VTE to occult cancer was 4 months (interquartile range: 2-8.4), with no sex differences. Women were older, weighed less, and were less likely to have chronic lung disease than men. The most common cancer sites were the lung (n = 63), prostate (n = 42), and colorectal (n = 29) in men and colorectal (n = 38), breast (n = 23), uterine (n = 18), hematologic (n = 17), or pancreas (n = 15) in women. Men were more likely to have lung cancer than women (2.18% vs 0.30%; P < .01) and less likely to have pancreatic cancer (0.17% vs 0.5%; P = .03). Interestingly, breast cancer was more likely found in women aged ≥50 years than in those aged <50 years (0.97% vs 0.14%; P = .03). This study highlights the existence of sex differences in patients with VTE having occult cancer. One in every 2 men had lung, prostate, or colorectal cancer. In women, there is a heterogeneity of cancer sites, increasing risk of breast cancer in those aged >50 years.
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Development of a Risk Prediction Score for Occult Cancer in Patients With VTE
(Elsevier, 2016)
Jara-Palomares L,
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Otero R,
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Jimenez D,
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Carrier M,
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Tzoran I,
Background: The benefits of a diagnostic workup for occult cancer in patients with VTE are controversial. Our aim was to provide and validate a risk score for occult cancer in patients with VTE. Methods: We designed a nested case-control study in a cohort of patients with VTE included in the RIETE (Registro Informatizado Enfermedad TromboEmbólica) registry from 2001 to 2014. Cases included cancer detected beyond the first 30 days and up to 24 months after VTE. Control subjects were defined as patients with VTE with no cancer in the same period. Results: Of 5,863 eligible patients, 444 (7.6%; 95% CI, 6.8%-8.2%) were diagnosed with occult cancer. On multivariable analysis, variables selected were male sex, age > 70 years, chronic lung disease, anemia, elevated platelet count, prior VTE, and recent surgery. We built a risk score assigning points to each variable. Internal validity was confirmed using bootstrap analysis. The proportion of patients with cancer who scored ≤ 2 points was 5.8% (241 of 4,150) and that proportion in those who scored ≥ 3 points was 12% (203 of 1,713). We also identified scores divided by sex and age subgroups. Conclusions: This is the first risk score that has identified patients with VTE who are at increased risk for occult cancer. Our score needs to be externally validated.
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Real-life treatment of venous thromboembolism with direct oral anticoagulants: The influence of recommended dosing and regimens
(Thieme Medical Publishers, 2017)
Trujillo-Santos J
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Di Micco P
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Dentali F
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Douketis J
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Díaz-Peromingo JA
In patients with venous thromboembolism (VTE), the influence on outcome of using direct oral anticoagulants (DOACs) at non-recommended doses or regimens (once vs twice daily) has not been investigated yet. We used the RIETE (Registro Informatizado Enfermedad TromboEmbólica) registry to compare the outcomes in patients with VTE receiving DOACs according to the recommendations of the product label versus in those receiving non-recommended doses and/or regimens. The major outcomes were the rate of VTE recurrences, major bleeding and death during the course of therapy. As of March 2016, 1635 VTE patients had received DOACs for initial therapy and 1725 for long-term therapy. For initial therapy, 287 of 1591 patients (18 %) on rivaroxaban and 22 of 44 (50 %) on apixaban did not receive the recommended therapy. For long-term therapy, 217 of 1611 patients (14 %) on rivaroxaban, 29 of 81 (36 %) on apixaban and 15 of 33 (46 %) on dabigatran did not receive the recommended therapy. During the course of therapy with DOACs, eight patients developed VTE recurrences, 14 had major bleeding and 13 died. Patients receiving DOACs at non-recommended doses and/or regimens experienced a higher rate of VTE recurrences (adjusted HR: 10.5; 95 %CI: 1.28-85.9) and a similar rate of major bleeding (adjusted HR: 1.04; 95 %CI: 0.36-3.03) or death (adjusted HR: 1.41; 95 %CI: 0.46-4.29) than those receiving the recommended doses and regimens. In our cohort, a non-negligible proportion of VTE patients received non-recommended doses and/or regimens of DOACs. This use may be associated with worse outcomes.
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Complications associated with acute pulmonary embolism – data from the registry of patients with venous thrombembolism
(Македонско лекарско друштво = Macedonian Medical Association, 2022)
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Dejan Todevski
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Suzana Arbutina
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Correct estimation of the severity, mortality, and complication risk are crucial for effective treatment of pulmonary embolism (PE). A total of 162 patients hospitalized with acute PE, treated either with standard treatment with heparin and vitamin K antagonists (VKA) or heparins, followed by direct oral anticoagulants (DOAC) were followed for a 90-days period. Demography, clinical and radiologic presentation, smoking status and concomitant comorbidities were analyzed. The mortality risk was estimated by calculating PESI and sPESI score. The results showed uneven utilization of both treatment modalities (93.8% treated with VKA versus 6.17% with DOAC). Smoking as an independent factor was detected in 55.56% of patients, and is greater than the overall smoking prevalence in Macedonia. Central propagation of PE was found in 57.79% of cases and together with the presence of pleural effusion was associated with a greater risk for complications. Estimation of 30-day mortality risk with PESI and sPESI showed their high predictive value, with an advantage of sPESI, in terms of better accuracy and simplicity of performance. Correct estimation of risk for complications and mortality is important for improving the overall safety of patients with PE and has a positive „cost-benefit“ effect for organization of the treatment.
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Pulmonary embolism and COVID-19
(2020-10-03)
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Elena Grueva Nastevska
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Bushljetikj Oliver
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Since December 2019, the severe acute respiratory syndrome coronavirus (SARS-CoV-2) outbreak has reached pandemic proportion and has become a public health crisis of unprecedented magnitude. Although coronavirus disease-2019(COVID-19) primarily targets the respiratory system, the cardiovascular system can also be affected in a significant percentage among the patients. Cardiac injuries appear to be a prominent feature of the COVID-19 infection as they occur in 20-30% of the hospitalized patients and are often responsible for deadly outcome. Pulmonary vascular complications such as pulmonary embolism are frequently present, with higher prevalence in COVID-19 than usually encountered in critically ill patients who do not suffer from infection. Moreover, there is a rising evidence that traditional risk factors for PE are not commonly encountered among the patients with COVID-19 infection but rather independent biological and clinical findings, with the inflammation as a main contributor of thromboembolism. The endothelial dysfunction, abnormal hemostasis, severe lung inflammation and disseminated intravascular coagulation play a central role in the predisposition to venous thromboembolic events. Integrated approach of heart and lung multimodality imaging has a crucial role in different clinical scenarios and is of great importance in the diagnosis, management, risk stratification and prognosis of patients with COVID-19, providing a base for further clinical decision making. Routine history, physical examination, laboratory testing, electrocardiography, and plain x-ray imaging may offer the required information in some of the cases but the overlap between COVID-19 and typical cardiovascular diagnoses such as acute myocardial infarction, heart failure and acute pulmonary embolism, mandate advanced imaging techniques to assist in differential diagnosis and treatment. Baseline CT is the most used tool to confirm diagnosis and to give information about the disease extent and severity, but it is also a reference for subsequent imaging follow-up. According to some studies, the sensitivity of chest CT for COVID-19 was 97%. In the clinical scenario of a patient with COVID-19, who has just undergone CT of the lungs but the findings cannot explain the severity of respiratory failure, CT pulmonary angiography should be considered to exclude/confirm pulmonary embolism. We hereby report a case of 72y/old patient who was admitted at our clinic ( which is not a Covid-center) with severe chest pain and signs of hemodynamic instability. His ECG revealed a heart rate of 125/min , right axis deviation and S1Q3T3 pattern. Bedside echo showed severely dilated RV with reduced systolic function and features of pulmonary hypertension. His laboratory findings were consistent with leukocytosis with lymphopenia, elevated CRP, extremely elevated D-dimers and high troponin. Anticoagulation was immediately initiated by using UFH. The patient was referred to CT angiography and it revealed bilateral filling defects in the main pulmonary arteries. Bilateral peripheral ground-glass opacities and small areas of consolidation were also present which raised the suspicion of COVID-19 infection. The swab for SAS-COV-2 was positive. The patient underwent systemic fibrinolysis with full-dose alteplase, with rapid hemodynamic and respiratory success. His further treatment included therapeutic dose of LMWH, parenteral antibiotic and gastroprotective treatment. The repeated echocardiographic exam showed a clear improvement of the hemodynamics of the RV, a reduction of RV dilatation and of pulmonary pressures and reduction of vena cava diameter. The patient was transferred for further treatment at the COVID department and was discharged 2 weeks later after his full recovery and was advised to continue with oral anticoagulant therapy and to use Rivaroxaban 15mg twice daily for 3 weeks and afterwards 20mg once daily. Conclusion: PTE is frequently observed among COVID-19 patients and this complication can happen in the absence of major predisposing factors. COVID-19 pneumonia seems to confirm the impact of severe respiratory infection as a precipitant factor for acute venous thrombo-embolism and the causal relationship. Multimodality imaging in COVID-19 patients with suspected cardiac involvement by using POCUS, chest CT and pulmonary angiography is of crucial importance for rapid differential diagnosis and treatment especially in patients with hemodynamic instability. The use of systemic thrombolysis in haemodynamically unstable patients is the first and more appropriate therapeutic strategy, considering the current guidelines recommendations for management of acute PE. However, thrombocytopenia occurs in a non-neglectable proportion of patients with COVID-19 infection and is an independent predictor of increased mortality in these patients. The reperfusion strategy of COVID-19 patients must be tailored according to the severity of thrombocytopenia where catheter directed treatment might be potential first line therapeutic approach.

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