Arterial and venous involvement in Behçet's syndrome: a narrative review.

Behçet syndrome (BS) is a unique type of vasculitis that affects veins and arteries of all sizes, leading to recurrent vascular events, mostly venous thrombosis. The prevalence of venous thromboembolism in BS patients ranges between 15 and 40%. Thrombosis is usually an early manifestation leading to diagnosis of BS in up to 40% of patients. BS is per se a model of inflammation-induced thrombosis. The primary autoimmune response activates lymphocytes that in turn produce a cytokine cascade that activates neutrophils, which modify the secondary structure of fibrinogen making it less susceptible to plasmin-induced lysis. This leads to endothelial dysfunction, platelet activation and overexpression of tissue factor leading to inflammatory thrombi, usually attached to the wall. The pathogenesis of thrombosis is especially relevant to direct the specific treatment, that is based on immunosuppression rather than anticoagulation. Superficial vein thrombosis (SVT) and deep vein thrombosis (DVT) are the most common form of thrombosis in BS, but thrombosis in atypical sites (cava vein, suprahepatic veins, intracardiac thrombus) and arterial involvement can also occur. We assessed the latest update of the European League Against Rheumatism recommendations for the management of BS. Vascular Behçet treatment is usually based of immunosuppressants, and the role of anticoagulation remains controversial. The use of interventional and surgical procedures should be carefully evaluated, due to the risk of triggering a vascular pathergy phenomenon.

Inflammatory Biomarkers in the Short-Term Prognosis of Venous Thromboembolism: A Narrative Review.

The relationship between inflammation and venous thrombosis is not well understood. An inflammatory response may be both the cause and consequence of venous thromboembolism (VTE). In fact, several risk factors of VTE modulate thrombosis through inflammatory markers. Acute pulmonary embolism (PE) is burdened by a remarkable mortality rate, up to 34% in severely ill patients presenting with hemodynamic instability. Initial mortality risk stratification is based on hemodynamic instability. Patients with a situation of hemodynamic stability require immediate further risk assessment based on clinical, imaging, and circulating biomarkers, as well as the presence of comorbidities. Some inflammatory biomarkers have shown potential usefulness in the risk stratification of patients with VTE, especially acute PE. C-reactive protein on admission is associated with 30-day mortality and bleeding in VTE patients. P-selectin is associated with right ventricle dysfunction in PE patients and might be associated with VTE recurrences and the extension of thrombosis. Tissue factor microparticles are associated with VTE recurrence in cancer-associated thrombosis. Other inflammatory biomarkers present scarce evidence (inflammatory cytokines, erythrocyte sedimentation rate, fibrinogen, leukocyte count). In this manuscript, we will review the prognostic role of different inflammatory biomarkers available both for clinical practice and research in VTE patients.

Long-term follow-up of patients with venous thromboembolism and COVID-19: Analysis of risk factors for death and major bleeding.

INTRODUCTION: COVID-19 predisposes patients to a higher risk of venous thromboembolism (VTE), although the extent of these implications is unclear and the risk of bleeding has been poorly evaluated. To date, no studies have reported long-term outcomes of patients with COVID-19 and VTE. METHOD: Prospective observational study to evaluate long-term (90 days or more) outcomes of patients diagnosed with VTE (PE, DVT of the extremities, or both) in the setting of COVID-19. The main outcome of the study was a compound of major bleeding and death. RESULTS: The study comprised 100 patients (mean age 65 ± 13.9 years). At the time of VTE diagnosis, 66% patients were hospitalized, 34.8% of them in the ICU. Mean follow-up was 97.9 ± 23.3 days. During the study period, 24% patients died and median time to death was 12 (IQR: 2.25-20.75) days, 11% patients had major bleeding and median time to event was 12 (IQR: 5-16) days. The cause of death was PE in 5% and bleeding in 2% of patients. There were no VTE recurrences. The main study outcome occurred in 29% patients. Risk of death or major bleeding was independently associated with ICU admission (HR 12.2; 95% CI 3.0-48.3), thrombocytopenia (HR 4.5; 95% CI 1.2-16.5), and cancer (HR 21.6; 95% CI 1.8-259). CONCLUSION: In patients with COVID-19 and VTE, mortality and major bleeding were high and almost a third of deaths were VTE-related. The majority of complications occurred in the first 30 days. ICU admission, thrombocytopenia, and cancer are risk factors for poor prognosis.

COVID-19 as a trigger for splenic infarction in a patient with sickle cell trait: A case report.

Sickle cell trait (SCT) is the carrier state for sickle cell disease (SCD) and is usually perceived as a mild condition; however, previous studies have shown that hypoxemia may trigger sickle-cell related complications in these patients, including splenic infarction. Hypoxemia is a common finding in patients with COVID-19 pneumonia. We present the case of a 19-year-old male with a history of epilepsy who presented to the emergency room due to abdominal pain in the left flank that appeared after presenting generalized tonic-clonic seizures and fever. SARS-CoV-2 RT-PCR testing in nasopharyngeal swab was positive and an abdominal computerized tomography (CT) revealed a massive splenic infarction. Hemoglobinopathy study using high-efficiency liquid chromatography demonstrated the presence of 39.7% HbS, thus confirming the diagnosis of SCT. Hypoxemia, endothelial dysfunction and hypercoagulability caused by SARS-CoV-2 infection could lead to complement activation and microangiopathy, triggering the vaso-occlusive crisis that led to splenic infarction.

Long-term anticoagulant treatment in patients with inferior vena cava agenesis and deep vein thrombosis.

INTRODUCTION: Inferior vena cava agenesis (IVCA) is a rare and underdiagnosed congenital anomaly that predisposes to deep vein thrombosis (DVT). Optimal duration of anticoagulant treatment in these patients is not well established. METHOD: Observational retrospective study that included all consecutive patients older than 18 diagnosed with IVCA and DVT. Data including demographics, initial clinical presentation, modality of diagnosis, treatment and outcomes were obtained. RESULTS: In patients with IVCA and DVT (n = 9), mean age was 42 and 66% were males. Five (55,5%) patients had bilateral DVT and the most frequent location was ilio-femoral. Only one patient had concomitant pulmonary embolism (PE). During follow-up (mean of 77.8 months), anticoagulation was withdrawn in 2 patients and both developed recurrence of DVT (22.2%, CI 95% 2.8-60.0). One minor bleeding (11.1%, CI 95% 0.3-48.3), five post-thrombotic syndrome (55.6%, CI 95% 21.2-86.3) and no deaths were registered. CONCLUSION: In patients with DVT and IVCA, post-thrombotic syndrome was developed in approximately half of the patients. No major bleeding events were recorded during long-term anticoagulant therapy and recurrences occurred only in patients who had anticoagulation withdrawn. These data suggest that extended anticoagulant therapy might be considered in these patients.

Differential diagnosis and treatment approach to pulmonary artery sarcoma: a case report and literature review.

Pulmonary artery sarcoma is an aggressive tumour that originates from the intimal layer of the pulmonary trunk and pulmonary arteries. Clinical presentation may resemble a pulmonary embolism. Prompt diagnosis is necessary to improve survival. https://bit.ly/2xZwENm.

Evaluation of the SAMe-TT2R2 score to predict the quality of anticoagulation control in patients with venous thromboembolism treated with vitamin K antagonists: Findings from the RIETE registry.

BACKGROUND: The time in therapeutic range (TTR) of patients with venous thromboembolism (VTE) treated with vitamin K antagonists (VKA) is usually below recommended, leading to higher frequency of vascular events, bleeding and mortality. The SAMe-TT2R2 prediction score discriminates those patients with high or low probability of obtaining poor INR control and its use is recommended in patients with atrial fibrillation. Its usefulness has been evaluated in patients with VTE, with conflicting results. METHOD: We included consecutive patients enrolled in Registro Informatizado Enfermedad TromboEmbolica (RIETE), a prospective multicenter VTE registry, treated with VKA for >90 days and a minimum of 3 INR determinations. We analyzed the relationship between the SAMe-TT2R2 score and TTR, determined by the Rosendaal method and by the percentage of INR determinations (after excluding the first month). A ROC curve was calculated considering a cut-off point of TTR ≥65% for good anticoagulation control. RESULTS: 3893 patients were included and classified in high (1411 patients) or low (2482 patients) probability of obtaining poor INR control according to the total score obtained (0-1 points versus 2 points, respectively). TTR, calculated by direct method and Rosendaal method, was 51.2 (±23.4) and 55.4 (±25.9) in the high probability group; and 54.4 (±23.0) and 58.2 (±25.6) in the low probability group, respectively (p < 0.001 for both comparisons). The outcomes were similar between groups. The predictive capacity of the SAMe-TT2R2 score showed an area under the ROC curve of 0.54 (CI 95% 0.52-0.56) and 0.53 (CI 95% 0.51-0.55). CONCLUSIONS: In patients with VTE treated with VKA, the SAMe-TT2R2 score discriminated those patients with high probability of obtaining poor INR control, but with a low predictive capacity. Further studies are required to assess the usefulness of the score in clinical decision-making.

Direct Oral Anticoagulants for the Treatment of Acute Venous Thromboembolism Associated with Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: International guidelines have endorsed the use of edoxaban or rivaroxaban as an alternative to low-molecular-weight heparin (LMWH) for the treatment of acute venous thromboembolism (VTE) in cancer patients. Recently, a large randomized controlled trial of apixaban versus dalteparin in patients with cancer was completed. We performed an updated meta-analysis to assess the efficacy and safety of direct oral anticoagulants (DOACs) versus LMWH in patients with cancer-associated VTE. METHODS: MEDLINE, EMBASE, and CENTRAL (Cochrane Controlled Trials Registry) were systematically searched up to March 30, 2020 for randomized controlled trials comparing DOACs versus LMWH for the treatment of VTE in patients with cancer. The two coprimary outcomes were recurrent VTE and major bleeding at 6 months. Data were pooled by the Mantel-Haenszel method and compared by relative risk ratios (RRs) and 95% confidence intervals (CIs). RESULTS: Four randomized controlled studies (2,894 patients) comparing apixaban, edoxaban, or rivaroxaban with dalteparin were included in the meta-analysis. Recurrent VTE occurred in 75 of 1,446 patients (5.2%) treated with oral factor Xa inhibitors and in 119 of 1,448 patients (8.2%) treated with LMWH (RR 0.62; 95% CI 0.43-0.91; I 2, 30%). Major bleeding occurred in 62 (4.3%) and 48 (3.3%) patients receiving oral factor Xa inhibitors or LMWH, respectively (RR 1.31; 95% CI 0.83-2.08; I 2, 23%). CONCLUSION: In patients with cancer-associated VTE, oral factor Xa inhibitors reduced the risk of recurrent VTE without a significantly higher likelihood of major bleeding at 6 months compared with LMWH.

Chronic Budd-Chiari syndrome in Behçet's disease successfully managed with transjugular intrahepatic portosystemic shunt: a case report and literature review.

Budd-Chiari syndrome (BCS) is characterized by an obstruction of hepatic venous outflow from small hepatic veins to inferior vena cava, caused by acute thrombosis or its fibrous sequellae. An underlying myeloproliferative neoplasm is present in 50% of cases. Clinical manifestations are widely variable, from asymptomatic to fulminant episodes. Long-term complications range from cirrhosis to hepatocellular carcinoma. Behçet's disease (BD) is a rare recurrent inflammatory multisystemic disorder characterized by recurrent skin-mucosa lesions and systemic involvement. Vascular involvement is observed in up to 40% of the patients with BD, and it is one of the major causes of mortality and morbidity. BCS is a rare complication of BD with a frequency of < 5% among patients with vascular involvement. Immunosuppressive treatment is the cornerstone for the management of vascular involvement in BD, while anticoagulant therapy has been an issue of debate. Transjugular intrahepatic portosystemic shunt (TIPS) in severe cases of BCS-of all causes- improves survival. However, there is scarce evidence about the role of TIPS in the setting of BCS in BD. We present a case of a vascular Behçet's disease associated with chronic Budd-Chiari syndrome with progression of thrombosis despite adequate anticoagulant and immunosuppressive treatment, successfully managed with TIPS.

Letter by Garcia A, et al. regarding article: Coronary artery disease risk reclassification by a new acoustic-based score.

The best cost-effective non-invasive test for the diagnosis of coronary artery disease (CAD) in patients with intermediate pre-test probability (PTP) is unknown. Nevertheless one of the most common non invasive test used is the exercise treadmill testing (ETT) that is the less expensive non-invasive test but with the lowest sensitivity for the diagnosis of CAD, therefore many patients with intermediate PTP will required another non-invasive test with a higher cost and some of them require exposure to radiation. Despite all these measures, an estimated $108.9 billion is spent annually on CAD treatment. Some studies had showed that diastolic dysfunction is associated to CAD. A novel signal-processed surface ECG (MyoVista hsECG) can detection the abnormal myocardial relaxation and therefore identified CAD. The non-invasive acoustic device CADScore V3 algorithm had lower cost compared with any noninvasive test, with a high negative predictive value but not good enough specificity to diagnose CAD, hence should be the first approach in patients with a low and intermediate probability of CAD, and if to this evaluation will added the Myovista hs ECG to detection of CAD, therefore some patients with intermediate PTP could be reclassified into high risk and a better cost-effective decisions could be taken as referring directly to coronary angiography.

Clinical features and management of venous thromboembolism in patients with Behçet's syndrome: a single-center case-control study.

Almost one third of patients with Behçet's syndrome (BS) display vascular involvement. However, data regarding the prevalence and management of venous thromboembolism (VTE) in BS are scanty. We assessed the differential characteristics between patients with and without VTE and the factors associated with VTE incidence. A case-control study in a cohort of patients with BS was performed. 57 patients were included (56.1% women) with a mean follow-up of 10.56 (± 10.7) years. Mean age at diagnosis of BS and diagnosis of the first VTE episode was 34.7 (± 12.1) and 31.2 (± 8.9) years, respectively. Erythema nodosum (OR 4.6, CI 95% 1.2-18.1) and fever (OR 8.2, CI 95% 1.6-42.1) were associated with a higher risk of VTE. 26 episodes of VTE were registered in 12/57 (21%) patients. 83.3% of patients were not diagnosed with BS when the first episode of VTE occurred and, among them, the episode of VTE led to the diagnosis of BS in 40% of cases. Half of patients had at least one VTE recurrence. The absence of immunosuppressive treatment was associated with a higher risk of developing a first episode of VTE (OR 20 CI 95% 19.2-166.6). All patients were treated with anticoagulation and 75% were treated with immunosuppressants after the first VTE event. The diagnosis of VTE usually precedes that of BS, with a high frequency of VTE recurrence. Erythema nodosum and fever were associated with a higher risk of VTE, while the immunosuppressants showed a protective role for the development of VTE.

Venous thromboembolism and gastrointestinal stromal tumour: A rare association.

Gastrointestinal stromal tumours (GISTs) comprise 0.1-3% of all gastrointestinal malignancies and represent the majority of gastrointestinal mesenchymal neoplasms. The major cause of GIST is an abnormal form of tyrosine kinase protein. GISTs may arise anywhere in the gastrointestinal tract, but are more commonly encountered in the stomach and small intestine. Gastrointestinal bleeding and abdominal pain are the most frequent symptoms associated with gastric GISTs. However, venous thromboembolism (VTE) is an uncommon presentation of these tumours. To the best of our knowledge, only 4 cases highlighting the association between these rare tumours and VTE have been reported in the literature to date. We herein report a case of a gastric GIST presenting with pulmonary embolism. Current guidelines recommend anticoagulation with low-molecular-weight heparin as first-line treatment for the acute phase of cancer-associated thrombosis. Prolonged anticoagulation should be considered for an indefinite time period, or until curative treatment. In the present case, tumour resection enabled a reduction in the duration of the anticoagulation treatment, thereby reducing the risk of long-term bleeding complications.

C-reactive protein level predicts 30-day mortality and bleeding in patients with venous thromboembolism: A prospective single-center study.

AIMS: The association of on-admission CRP and early adverse outcomes in acute venous thromboembolism (VTE) has not been investigated. We hypothesized that increased on-admission CRP levels would correlate with adverse outcomes in patients with acute VTE. METHOD: In this prospective observational study, consecutive patients with acute VTE were enrolled and CRP levels were measured within the first 24h after diagnosis. Mortality, bleeding and recurrence were recorded during a 30-day follow-up. RESULTS: 586 patients were included. Higher CRP levels were found in patients with mortality (7.5 vs 4.0mg/dL; p=0.01) and bleeding (7.8 vs 3.9mg/dL; p=0.03). Multivariable logistic regression showed that CRP levels >5mg/dL were associated with higher mortality (OR 6.25; 95% CI, 2.1-18.6) and bleeding (OR 2.7; CI 95% 1.3-5.7). These results were independent to ESC risk score and simplified PESI score for mortality prediction. The predictive capacity of CRP showed an area under the ROC curve - AUC - of .7 (CI 95% .56-.85) for mortality and .65 (CI 95% .54-.75) for bleeding. The prognostic capacity of the ESC risk score and simplified PESI score was improved after adding the CRP cutoff of 5mg/dL (AUC of .87 CI 95% .79-.95). CONCLUSION: Our findings suggest that on-admission CRP level may be a simple, widely available and valuable biomarker to identify high-risk VTE patients for early mortality and bleeding. CRP ≥5mg/dL was independently associated with 30-day VTE related death and bleeding.

Bilateral Deep Vein Thrombosis, Vena Cava Agenesis, and Renal Abnormalities: KILT Syndrome-A Case Report and Literature Review.

KILT (kidney and IVC abnormalities with leg thrombosis) syndrome is a very rare condition that associates inferior vena cava abnormalities, renal defects, and venous thrombosis. These vascular disorders appear in 0.6-2% of patients with cardiovascular events and condition a venous stasis that contributes to the formation of thrombus in the lower limbs. Only a few cases of KILT syndrome have been published in the literature and the genesis, epidemiology, and natural history of the disease are yet unknown. We present a case of a 39-year-old man with no medical background who developed thrombosis of the inferior vena cava in its infrarrenal portion to both common iliac veins, all associated with agenesis of the rest of the vascular structure and an atrophic right kidney. The patient was treated with full anticoagulation, without the development of renal failure, postthrombotic syndrome, nor other complications. Thrombophilia study was normal, including mutations of prothrombin gene, factor V Leiden, and antiphospholipid antibodies. We hypothesize the benefit of an early diagnosis to improve the management of this condition. KILT syndrome must be taken into account in cases of proximal venous thrombosis, especially in young patients without risk factors for the development of thrombosis.

Idiopathic versus Provoked Renal Infarction: Characteristics and Long-Term Follow-Up of a Cohort of Patients in a Tertiary Hospital.

BACKGROUND: There is limited evidence on the etiology and outcomes of renal infarction. A provoking factor is identified only in one- to two-thirds of patients. METHODS: This is a retrospective observational study. The clinical characteristics and outcomes of patients with acute renal infarction were studied; the sample was divided into two groups according to the presence of at least one provoking factor at the time of diagnosis (atrial fibrillation, flutter, major thrombophilia, or renal artery malformations). RESULTS: The study comprised 59 patients with a mean age of 63 (±16.7) years and a follow-up period of 3.1 (±2.8) years. An identifiable provoking factor was found for 59.3% of the renal infarctions at the time of diagnosis, and atrial fibrillation was the most frequent one (in 49.2% of all patients). Renal impairment was found in 49.2% of the patients at diagnosis and in 50.8% of the patients 6 months after the event (p = 0.525). When compared with the idiopathic group, the patients with provoked infarction were older (69.8 vs. 57.9 years, p = 0.014) and had a higher rate of recurrence of arterial thrombosis during follow-up (18.8 vs. 0%, p = 0.028), but there were no differences in the rest of the baseline characteristics or in mortality rates. Six patients (10.2%) in the idiopathic group were diagnosed with atrial fibrillation during follow-up. CONCLUSIONS: Atrial fibrillation, both at diagnosis and at follow-up, is the most common identifiable cause of renal infarction; however, a significant number of patients are idiopathic, and these are younger, but they have a similar burden of cardiovascular disease and a lower risk of arterial recurrence.

Torcular herophili and lateral sinus thrombosis: An atypical presentation of Lemièrre's syndrome.

Lemièrre's syndrome (LS) is an uncommon disease characterized by septic thrombophlebitis of the jugular vein in the context of otorhinolaryngologic infections. These patients are often young and the pharyngotonsillar infection is the most frequent primary focus, but other foci like acute otitis media or otomastoiditis have been described. Although the internal jugular vein is the most commonly affected site, a few case reports have been published with thrombosis of other veins, such as the facial vein or transverse sinus. We report the case of a 93-year-old woman with an atypical presentation of LS presenting with thrombophlebitis of the internal jugular vein, transverse sinuses and Herophili torcula after an acute otitis media complicated with acute otomastoiditis. Infectious cerebral venous thrombosis (CVT) is rare and accounts for 6-12% of the total in large adult series and is usually associated to otorhinolaryngologic infections. CVT is an atypical presentation of LS that can be potentially lethal, especially during the acute phase. For this reason, clinical suspicion and early treatment are vital to improve the prognosis of these patients. Although surgical treatment is recommended in cases of LS complicated with CVT, conservative management with antibiotics and anticoagulation lead to ad integrum restitutio without neurological sequelae in our case, suggesting that surgical treatment may not be necessary in all cases of LS complicated with CVT.