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, 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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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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PLUCNA EMBOLIJA U BOLESNIKA S LEIDENOVOM TROMBOFILIJOM FAKTORA V I PSORIJAZOL: PRIKAZ SLUCAJ.
(Association of pulmologists from Republika Srpska, 2023-05)
Baloski Marjan
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Bushev Jane
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Brishkoska-Boshkovski Vesna
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Hasan Taner
Cilj: Genetski faktori rizika pove!avaju rizik venske tromboembolije. Poremecaji u sintezi ili aktivnosti faktora koagulacije. Faktor V Leiden, protrombin (20210-A), antitrombinski deficit, deficit proteina C i proteina S i hiperhomocisteinemija najcesce su mutacije gena povezanih sa venskim tromboembolijom . Uvod : Psorijaza i prisutvo mutacije trombofilnih gena povecava rizik venske tromboembolije. Prethodna venska tromboembolija je jedan od najjacih faktora rizika, cak i kod pacijenata koji su aktivno leceni antikoagulansom. Psorijaza je kompleksna imuno posredovana bolest, povezana sa kardiovaskularnim rizikom, markerima hiperkoagulabilnosti i povisenim homocisteinom. Mnogo izvjestaja o opservacijama sugerira povecanu ucestalost venskih trombembolickih dogadaja kod pacijenata sa psorijazom. Nalazi: Prikazujemo bolesnika s nasljednom trombofilijom i kronicnom difuznom psorijazom kompliciranom plu!nom embolijom. Analiza DNK ukazuje na prisutnost homozigoze za mutaciju faktora V Leidena. Dermatoloska anamneza je pozitivna na psorijazu. Zaklju!ak: Prikaz ovog slucaja ukazuje na povezanost venske tromboembolije i psorijaze. Pacijenti sa naslednom trombofilijom, psorijazom I plucnim tromboembolizmom, imaju visoki rizik od razvoj venske tromboembolije.
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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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Successful treatment of massive pulmonary embolism with rescue fibrinolysis in young patient with homocystinemia – case report
(Faculty of Medical Sciences, University of Kragujevac, 2020-10-01)
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Lazarova, Emilija
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Pulmonary embolism (PE) is the most frequently missed diag- nosis in the urgent clinical department with serious consequences. Patients with unprovoked PE have increased risk of recurrent PE. Approximately 5 to 8% of PE patients have inherited thrombo- philias. A solated homocystinemia is a rare cause of unprovoked acute pulmonary embolism. Timely diagnosis and proper treat- ment can prevent complications, costs and mortality and provide patient better quality of life. We are presenting a 42-year-old woman was admitted to our emergency department with the first episode of severe dyspnea and chest pain. She had no history of previous cardiovascular or respiratory disease and no history of previous pulmonary embolism (PE) or deep vein thrombosis (DVT). Urgent echocardiography showed indirect signs of pul- monary embolism which was confirmed by the pulmonary artery CT angiography performed one day after the patient’s admission. After two days of heparin infusion, she developed a hemodynamic instability with cardiogenic shock and was treated successfully with fibrinolysis. After the clinical stabilization, she was put on the rivaroxaban therapy, which was recommended for additional six months. The thrombophilia profile was done two weeks after stop- ping the therapy with rivaroxaban. The thrombophilia panel came back positive for high levels of homocysteine (67 μmol/L), with other thrombophilia results within normal limits. The patient was stable during the follow-up period. Pulmonary embolism should be always suspected in younger patients with acute severe dysp- nea even without provocable risk factors. High suspicion level and fast diagnosis are lifesaving. In younger patients presented with unprovoked pulmonary embolism, clinicians should consider inherited prothrombotic factors and homocystinemia as a poten- tial cause. Rescue fibrinolysis is a lifesaving therapy in hemody- namic worsening in intermediate high-risk PE patients. A longer anticoagulation therapy should be considered in these cases with novel oral anticoagulants that are recommended as safer and su- perior therapy.
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Pulmonary Embolism (PE) in patients with Chronic Obstructive Pulmonary Disease (COPD)
(Slovenian Respiratory Society, 2020-12)
Introduction: Many studies have shown that COPD is a moderate and independent factor for PE. Patients with COPD are at a high risk for PE because of systemic inflammation, limited mobility and co-existing comorbidities: cardiovascular disease, anemia, polycythemia, malnutrition, muscle disorder, osteoporosis, metabolic syndrome, diabetes, gastroesophageal reflux, anxiety, depression, hormonal imbalance, infections, lung cancer, thrombosis. Methods: Prospective, observational study of 50 hospitalized patients with COPD, diagnosed according to GOLD criteria (stages I-IV), 40-75 years (mean age 65.4±12.3 divided in subgroups (PE-diagnosed/non-PE and with known/undetermined exacerbation etiology). Investigations: clinical risk assessment, laboratory, spirometry, gas-analysis, electrocardiogram, D-dimer (DD), chest X-ray, chest ultrasound. Dopplerultrasonography of deep-veins of lower-extremities. Patients with high DD and deep vein thrombosis (DVT) or high DD and abnormal chest ultrasound underwent computed-tomography pulmonary-angiography. Results: PE was diagnosed in 13(26%) of 50 hospitalized COPD patients. Frequencies of PE in PE-diagnosed group according to GOLD-stages I-IV, were 0(0.0%), 1(7.7%), 4(30.8%), 8(61.5%) respectively with positive correlation between airflow limitation and PE. Patients with pleuritic chest-pain, chest ultrasound abnormality, DVT and high DD were more likely to develop PE. DD was significantly higher among patients with PE than those without (2.14±1.4μg/ml vs. 1.5±0.4μg/ml, P<0.0001). There was positive correlation between the presence of PE and elevated DD>2.0μg/ml (P<0.05). There was no statistically significant difference between patients with PE and without, according to age, gender and comorbidities (P>0.05). Immobility and obesity were significantly higher among PE patients, P<0.05 and P<0,0001 respectively. Conclusion: Clinical manifestations of PE like pleuritic chest pain, dyspnoea are nonspecific, and easily could be underestimated in COPD patients, which leads to disease worsening, delay of anticoagulant therapy and higher mortality rate.

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