2023 ACR/EULAR classification criteria in existing research cohorts: an international study.

OBJECTIVE: To assess the impact of the updated ACR/EULAR APS classification criteria on two large research cohorts. METHODS: Consecutive patients who tested persistently positive for at least one aPL in the last three years were enrolled. The first APS Sydney index event was considered and computed for the comparison between Sydney and 2023 APS criteria. When computing the 2023 APS criteria, additional manifestations were also considered. RESULTS: The cohort comprised 249 patients (185 with APS and 64 aPL carriers according to Sydney criteria). The 185 patients had as first index event venous thrombosis in 55 cases (29.8%), arterial thrombosis in 63 (34%) and pregnancy morbidity in 67 (36.2%). When applying the updated criteria, 90 subjects (48.7%) failed to reach the composite score of the new criteria. The percentage of thrombotic APS per Sydney criteria decreased from 47.3% to 34.9% because of high cardiovascular risk in 23 cases, IgM aPL profile in six cases and in two patients for both reasons. Patients with pregnancy morbidity decreased from 26.9% to 3.2% (39 cases of recurrent early pregnancy loss and 20 of fetal losses). Consequently, the percentage of aPL carriers increased from 26% to 61%. When looking at the disease evolution at follow-up, 32 additional patients out of 90 (35.6%) fulfilled the new APS criteria, after developing additional clinical manifestation following index event. CONCLUSION: When applying the new APS criteria to our research cohorts, not-negligible differences exist in patients' classification. A multidisciplinary approach will be mandatory to assess the impact of the new criteria on research and, ultimately, patients' care.

Intelligent classification of platelet aggregates by agonist type.

Platelets are anucleate cells in blood whose principal function is to stop bleeding by forming aggregates for hemostatic reactions. In addition to their participation in physiological hemostasis, platelet aggregates are also involved in pathological thrombosis and play an important role in inflammation, atherosclerosis, and cancer metastasis. The aggregation of platelets is elicited by various agonists, but these platelet aggregates have long been considered indistinguishable and impossible to classify. Here we present an intelligent method for classifying them by agonist type. It is based on a convolutional neural network trained by high-throughput imaging flow cytometry of blood cells to identify and differentiate subtle yet appreciable morphological features of platelet aggregates activated by different types of agonists. The method is a powerful tool for studying the underlying mechanism of platelet aggregation and is expected to open a window on an entirely new class of clinical diagnostics, pharmacometrics, and therapeutics.

Platelets are small cells in the blood that primarily help stop bleeding after an injury by sticking together with other blood cells to form a clot that seals the broken blood vessel. Blood clots, however, can sometimes cause harm. For example, if a clot blocks the blood flow to the heart or the brain, it can result in a heart attack or stroke, respectively. Blood clots have also been linked to harmful inflammation and the spread of cancer, and there are now preliminary reports of remarkably high rates of clotting in COVID-19 patients in intensive care units. A variety of chemicals can cause platelets to stick together. It has long been assumed that it would be impossible to tell apart the clots formed by different chemicals (which are also known as agonists). This is largely because these aggregates all look very similar under a microscope, making it incredibly time consuming for someone to look at enough microscopy images to reliably identify the subtle differences between them. However, finding a way to distinguish the different types of platelet aggregates could lead to better ways to diagnose or treat blood vessel-clogging diseases. To make this possible, Zhou, Yasumoto et al. have developed a method called the "intelligent platelet aggregate classifier" or iPAC for short. First, numerous clot-causing chemicals were added to separate samples of platelets taken from healthy human blood. The method then involved using high-throughput techniques to take thousands of images of these samples. Then, a sophisticated computer algorithm called a deep learning model analyzed the resulting image dataset and "learned" to distinguish the chemical causes of the platelet aggregates based on subtle differences in their shapes. Finally, Zhou, Yasumoto et al. verified iPAC method's accuracy using a new set of human platelet samples. The iPAC method may help scientists studying the steps that lead to clot formation. It may also help clinicians distinguish which clot-causing chemical led to a patient's heart attack or stroke. This could help them choose whether aspirin or another anti-platelet drug would be the best treatment. But first more studies are needed to confirm whether this method is a useful tool for drug selection or diagnosis.

Longitudinal Toxicity over Time (ToxT) analysis to evaluate tolerability: a case study of lenalidomide in the CALGB 50401 (Alliance) trial.

Evaluation of tolerability is increasingly relevant for patients with haematological malignancies treated with chronically administered therapies. Adverse events from these agents might affect the ability of patients to tolerate treatment over time. Conventional toxicity tables that include the incidence of high-grade adverse events, defined by the Common Terminology Criteria for Adverse Events, do not provide information on the time profile of these adverse events or reflect the continuous, lower grade symptomatic toxicities that are particularly relevant to treatment tolerability for patients living with indolent disease. Modern approaches to the evaluation and reporting of toxicity that capture the tolerability of treatment to the patient are imperative. In this Viewpoint, we present a focused, pilot, and longitudinal Toxicity over Time analysis of adverse events from lenalidomide and lenalidomide with rituximab in patients with follicular lymphoma treated in the CALGB 50401 (Alliance; NCT00238238) trial to define the trajectory of adverse events and quantify the burden of continuous, low-grade events. Toxicity over Time analyses provided clinically relevant descriptions of neutropenia and fatigue trajectories caused by lenalidomide that were not identified by standard analysis of the maximum grade events defined by the Common Terminology Criteria for Adverse Events. Systematic, rigorous incorporation of patient-reported outcomes in clinical trials will be crucial to our understanding of the tolerability of chronically administered therapies in patients with haematological malignancies.

Clinical Courses of HeartMate II Left Ventricular Assist Device Thrombosis.

We observed different temporal patterns of HeartMate II left ventricular assist device (LVAD) thrombosis regarding clinical manifestations and lactate dehydrogenase (LDH) trends. We propose nomenclature for classification of LVAD thrombosis and compare patient characteristics and outcomes in each pattern of LVAD thrombosis. We reviewed electronic medical records of 362 consecutive HeartMate II devices implanted at Cleveland Clinic from October 2008 to July 2014. We categorized clinical courses of confirmed device thrombosis based on clinical manifestations and LDH patterns. Patients' characteristics, clinical variables, and outcomes were collected for comparison. From a total of 19 confirmed device thromboses, we categorized the patterns of thrombosis into three distinctive types; abrupt thrombosis (Type 1), subacute thrombosis (Type 2), and asymptomatic hemolysis (Type 3). Abrupt thrombosis (Type 1) tended to be the most morbid clinical course with acute-onset thrombosis at 56.5 (interquartile range: 44-71) days, all New York Heart Association functional class III or IV at presentation. Death and need for surgical intervention were not different in each pattern. Asymptomatic hemolysis had unique comorbidities of preexisting cardiac thrombi and preoperative bacteremia. Confirmed LVAD thrombosis has different patterns of clinical presentation and each pattern of thrombosis has unique characteristics and clinical manifestations.

Robotic Radical Nephrectomy and Thrombectomy for Left Renal Cell Carcinoma with Renal Vein Tumor Thrombus: Superior Mesenteric Artery as an Important Strategic Dividing Landmark.

Objective: The aim of this study was to explore a new treatment strategy for left renal vein tumor thrombus directed at the thrombus level and the therapeutic effect of robotic surgery. Materials and Methods: Fifteen patients with left renal cell carcinoma with renal vein tumor thrombus (Mayo level 0) who underwent robotic radical nephrectomy and thrombectomy from July 2013 to July 2017 were included in this series. If the left renal vein thrombus transcended the superior mesenteric artery (SMA), the thrombus was classified as level 0b, the patient was positioned right side up for thrombectomy and repositioned left side up for nephrectomy, and angioembolization of left renal artery was necessary; otherwise, the thrombus was classified as level 0a and the patient was positioned left side up for both nephrectomy and thrombectomy. Baseline, perioperative, and follow-up data were analyzed. Results: Of all 15 patients, 10 had a level 0a tumor thrombus and 5 had a level 0b tumor thrombus. For level 0a patients, median operating time was 130 minutes, median estimated blood loss was 125 mL, with no patient receiving transfusion, and median hospital stay was 3.5 days. For level 0b patients, median operating time was 180 minutes, median estimated blood loss was 250 mL, with one patient receiving transfusion, and median hospital stay was 5 days. No perioperative complications or positive surgical margins occurred. For level 0a patients, one patient with preexisting lumbar vertebral metastasis died during a median follow-up of 39 months. For level 0b patients, all patients were alive at a median follow-up of 16.5 months. Conclusions: Our initial experience shows that the new treatment strategy for left renal vein tumor thrombus with the SMA as a dividing landmark directed at the thrombus level is safe and feasible. A larger cohort of level 0b patients and longer-term follow-up are needed to further assess the strategic advantages.

Incidence, Risk Factors, Progression, and Treatment of Endovenous Heat-Induced Thrombosis Class 2 or Greater After Endovenous Radiofrequency Ablation.

BACKGROUND: Endovenous heat-induced thrombosis (EHIT) is a thrombus that extends from an ablated saphenous vein into the common femoral vein after endovenous radiofrequency ablation (RFA). OBJECTIVE: To investigate the incidence, progression, treatment, and risk factors associated with EHIT-2 or greater after RFA. MATERIALS AND METHODS: This retrospective study included patients diagnosed with symptomatic superficial venous incompetence that were treated by RFA of the great saphenous vein or anterior accessory saphenous vein during the July 2012 to December 2016 study period. Duplex ultrasound scanning was performed at 1 week, 1 month, 3 months, and every year after RFA to detect EHIT. RESULTS: A total of 317 legs from 274 patients were included. The incidence of EHIT-2 or greater was 7.0%, including 5.4% EHIT-2, 1.3% EHIT-3, and 0.3% EHIT-4. No symptomatic pulmonary embolism was found. The independent risk factors for EHIT-2 or greater were vein diameter (p = .027) and concomitant sclerotherapy (p = .037). CONCLUSION: The risk factors found to be independently associated with EHIT-2 or greater were large vein size and concomitant sclerotherapy. Screening for EHIT should be performed in patients with one or both of these risk factors within 1 week after RFA and in patients with postoperative symptoms suggestive of venous thromboembolism.

Analysis of Patient Characteristics and Risk Factors for Thrombosis After Surgery for Congenital Heart Disease.

OBJECTIVES: Thrombosis is a cause of morbidity in 4-15% of children who undergo pediatric cardiac surgery. Data on how to prevent this complication are sorely needed. We aimed to identify risk factors for thrombosis following pediatric cardiac surgery and determine if use of low molecular weight heparin prophylaxis is associated with a reduction in thrombosis risk. DESIGN: Retrospective cohort study. SETTING: Tertiary pediatric cardiovascular ICU. PATIENTS: Patients who underwent cardiac surgery between June 2014 and December 2015. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data from patients with venous or arterial thrombosis confirmed by radiologic studies were matched two-to-one to controls based on age, Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery mortality category, and gender. Thrombosis was detected in 33 patients (6.2%): 25 patients (76%) had venous thromboses, five patients (15%) had arterial thromboses, and three patients (9%) had both. Median time to thrombosis detection was 13 days (25-75%; 7-31 d). On multivariate analysis, which included adjustment for postoperative disease severity, fresh frozen plasma exposure was independently associated with thrombosis (odds ratio, 3.7; 95% CI, 1.4-9.4). Twenty-eight patients (85%) had central venous catheter-related thromboses. Low molecular weight heparin prophylaxis use in this subset of patients was not statistically different from controls (50% vs 45%, respectively; p = 0.47). On multivariable analysis, fresh frozen plasma exposure was also independently associated with central venous catheter-related thrombosis (odds ratio, 3.6; 95% CI, 1.2-10.6). CONCLUSIONS: The occurrence of thrombosis after pediatric cardiac surgery at our institution was 6.2%, similar to what has been reported in other studies, despite frequent use of low molecular weight heparin. Further study is needed to determine the role of low molecular weight heparin for thromboprophylaxis and the relationship between fresh frozen plasma and thrombosis risk in children who undergo cardiac surgery.

Positive predictive values of peripheral arterial and venous thrombosis codes in French hospital database.

French hospital database, called Programme de Médicalisation des Systèmes d'Information (PMSI), covers all hospital stays in France (>66 million inhabitants). The aim of this study was to estimate the positive predictive values (PPVs) of primary diagnosis codes of peripheral arterial and venous thrombosis codes in the PMSI, encoded with the International Classification of Diseases, 10th revision. Data were extracted from the PMSI database of Toulouse University Hospital, south of France. We identified all the hospital stays in 2015 with a code of peripheral arterial or venous thrombosis as primary diagnosis. We randomly selected 100 stays for each category of thrombosis and reviewed the corresponding medical charts. The PPV of peripheral arterial thrombosis codes was 83.0%, 95% confidence interval (CI): 73.9-89.1, and the PPV of correct location of thrombosis was 81.0%, 95% CI: 72.2-87.5. The PPV of pulmonary embolism was 99.0%, 95% CI: 93.8-99.9. The PPV of peripheral venous thrombosis was 95.0%, 95% CI: 88.2-98.1, and the PPV of correct location of thrombosis was 85.0%, 95% CI: 76.7-90.7. Primary diagnoses of peripheral arterial and venous thrombosis demonstrated good PPVs in the PMSI.

Assessment of aortic wall thrombus predicts outcomes of endovascular repair of complex aortic aneurysms using fenestrated and branched endografts.

OBJECTIVE: The goal of this study was to investigate the correlation between atherothrombotic aortic wall thrombus (AWT) and clinical outcomes in patients treated by fenestrated-branched endovascular aortic repair (F-BEVAR) and present a new classification system for assessment of AWT burden. METHODS: The clinical data of 301 patients treated for pararenal and thoracoabdominal aortic aneurysms (TAAAs) by F-BEVAR was reviewed. The study excluded 89 patients with extent I to III TAAA because of extensive laminated thrombus within the aneurysm sac. Computed tomography angiograms were analyzed in all patients to determine the location, extent, and severity of atherothrombotic AWT. The aorta was divided into three segments: ascending and arch (A), thoracic (B) and renal-mesenteric (C). Volumetric measurements (cm3) of AWT were performed using TeraRecon software (TeraRecon Inc, Foster City, Calif). These volumes were used to create an AWT index by dividing the AWT volume from the total aortic volume. A classification system was proposed using objective assessment of the number of affected segments, thrombus type, thickness, area, and circumference. Clinical outcomes included 30-day mortality, neurologic and gastrointestinal complications, renal events (Risk, Injury, Failure, Loss of kidney function, End-stage renal disease [RIFLE]), and solid organ infarction. RESULTS: The study included 212 patients, 169 men (80%) and 43 women (20%), with a mean age of 76 ± 7 years. A total of 700 renal-mesenteric arteries were incorporated (3.1 ± 1 vessels/patient). AWT was classified as mild in 98 patients (46%) and was considered moderate or severe in 114 (54%). There was one death (0.5%) at 30 days. Solid organ infarction was present in 50 patients (24%), and acute kidney injury occurred in 45 patients (21%) by RIFLE criteria. An association with higher AWT indices was found for time to resume enteral diet (P = .0004) and decline in renal function (P = .0003). Patients with acute kidney injury 2 by RIFLE criterion had significantly higher (P = .002) AWT index scores in segment B. Spinal cord injury occurred in three patients (1.4%) and stroke in four (1.9%), but were not associated with the AWT index. Severity of AWT using the new proposed classification system correlated with the AWT index in all three segments (P < .001). Any of the end points occurred in 35% of the patients with mild and in 53% of those with moderate or severe AWT (P = .016). CONCLUSIONS: AWT predicts solid organ infarction, renal function deterioration, and longer time to resume enteral diet after F-BEVAR of pararenal and type IV TAAAs. Evaluation of AWT should be part of preoperative planning and decision making for selection of the ideal method of treatment in these patients.

Management and Outcomes of Patients with Occlusive Thrombosis after Pediatric Cardiac Surgery.

OBJECTIVES: To evaluate management and outcomes of thrombosis after pediatric cardiac surgery and stratify thrombi according to risk of short- and long-term complications to better guide therapeutic choices. STUDY DESIGN: Retrospective review was performed of 513 thrombi (400 occlusive) diagnosed after 213 pediatric cardiac operations. Long-term outcomes over time were assessed with the use of parametric hazard regression models. RESULTS: Serious complications and/or high-intensity treatment occurred with 17%-24% of thrombi depending on location, most commonly in thrombi affecting the cardiac and cerebral circulation. Bleeding complications affected 13% of patients; associated factors included thrombolytics (OR 8.7, P < .001), greater daily dose of unfractionated heparin (OR 1.25 per 5 U/kg/day, P = .03), and extracorporeal support (OR 4.5, P = .007). Radiologic thrombus persistence was identified in 30% ± 3% at 12 months; associated factors included extracorporeal support (hazard ratio [HR] 1.9, P = .003), venous (HR 1.7, P = .003), and occlusive thrombi at presentation (HR 1.8, P = .001); greater oxygen saturation before surgery (HR 1.13/10%, P = .05) and thrombi in femoral veins (HR 1.9, P = .001) were associated with increased hazard of resolution. Freedom from postthrombotic syndrome was 83% ± 4% at 6 years, greater number of persistent vessel segment occlusions (HR 1.8/vessel, P = .001) and greater fibrinogen at diagnosis (HR 1.1 per g/L, P = .02) were associated with increased hazard. CONCLUSIONS: Thrombosis outcomes after pediatric cardiac surgery remain suboptimal. Given that more intensive treatment would likely increase the risk of bleeding, the focus should be on both thrombosis-prevention strategies, as well as in tailoring therapy according to a thrombosis outcome risk stratification approach.

Antiphospholipid-mediated thrombosis: interplay between type of antibodies and localisation of lung, and cardiovascular incidences in primary antiphospholipid syndrome.

OBJECTIVES: The aim of this study was to analyse prevalence and type of pulmonary manifestations in patients with primary antiphospholipid syndrome (PAPS), their association to antiphospholipid antibody (aPL) type and localisation of peripheral vascular thrombosis, and possible relationship to existing cardiac manifestations. METHODS: Our cross-sectional study comprised 318 PAPS patients, enrolled in the study as the Serbian APS Registry. aPL analysis included detection of aCL (IgG/IgM), ß2GPI (IgG/IgM) and LA, served to evaluate associations with cardiac and pulmonary manifestations. RESULTS: In patients with pulmonary embolism and infarction, we observed significant prevalence of myocardial infarction (p=0.044), unstable angina pectoris (p=0.001), venous thrombosis (p=0.007) arterial thrombosis (p=0.0001), deep venous thrombosis of the low extremities (p=0.008), and superficial thrombophlebitis of the low extremities (p=0.023). Patients with primary pulmonary hypertension were more prone to unstable angina pectoris (p=0.009), while patients with secondary pulmonary hypertension were more prone to venous thrombosis (p=0.04) and deep venous thrombosis of the inferior extremities (p=0.04). Patients with pulmonary microthrombosis were more prone to unstable angina pectoris (p=0.026), arterial thrombosis (p=0.002), venous thrombosis (p=0.001), deep venous thrombosis of the inferior extremities (p=0.001), and superficial thrombophlebitis of the inferior extremities (p=0.001). The presence of LA was significantly higher in patients with pulmonary embolism and infarction (p=0.001), secondary pulmonary hypertension (p=0.032), and pulmonary microthrombosis (p=0.001). CONCLUSIONS: Presence of LA was associated with distinct pulmonary manifestations in the Serbian APS cohort. There is a strong link between some cardiovascular and pulmonary manifestations in PAPS patients, suggesting complexity and evolutionary nature of PAPS.

Rational classification of portal vein thrombosis and its clinical significance.

Portal vein thrombosis (PVT) is commonly classified into acute (symptom duration <60 days and absence of portal carvernoma and portal hypertension) and chronic types. However, the rationality of this classification has received little attention. In this study, 60 patients (40 men and 20 women) with PVT were examined using contrast-enhanced computed tomography (CT). The percentage of vein occlusion, including portal vein (PV) and superior mesenteric vein (SMV), was measured on CT image. Of 60 patients, 17 (28.3%) met the criterion of acute PVT. Symptoms occurred more frequently in patients with superior mesenteric vein thrombosis (SMVT) compared to those without SMVT (p<0.001). However, there was no significant difference in PV occlusion between patients with and without symptoms. The frequency of cavernous transformation was significantly higher in patients with complete PVT than those with partial PVT (p<0.001). Complications of portal hypertension were significantly associated with cirrhosis (p<0.001) rather than with the severity of PVT and presence of cavernoma. These results suggest that the severity of PVT is only associated with the formation of portal cavernoma but unrelated to the onset of symptoms and the development of portal hypertension. We classified PVT into complete and partial types, and each was subclassified into with and without portal cavernoma. In conclusion, neither symptom duration nor cavernous transformation can clearly distinguish between acute and chronic PVT. The new classification system can determine the pathological alterations of PVT, patency of portal vein and outcome of treatment in a longitudinal study.

[Pathophysiology and classification of thrombosis].

Hemostasis is one of the most important process of physiology for human to live, in which hemostatic factors such as platelets and coagulation factors play an important role. On the other hand, thrombosis is often defined as a critical pathophysiology represented by myocardial infarction, cerebral infarction and pulmonary embolism, in which hemostatic factors also play a key part. Thus, these hemostatic factors have role in both good and bad aspects. Thrombosis is marked by sudden onset, irreversible dysfunction and recurrence, and classified to arterial and venous thromboses. The former is characterized by thrombus formation under fast blood flow, platelet activation, thrombus consisting most platelet and effectively treated by antiplatelet agents. The latter is characterized by thrombus formation under slow blood flow, coagulation activation, thrombus consisting most fibrin and effectively treated by anticoagulant agents. The classification of thrombosis is useful to choose appropriate therapy.

Magnetic resonance direct thrombus imaging differentiates acute recurrent ipsilateral deep vein thrombosis from residual thrombosis.

Accurate diagnostic assessment of suspected ipsilateral recurrent deep vein thrombosis (DVT) is a major clinical challenge because differentiating between acute recurrent thrombosis and residual thrombosis is difficult with compression ultrasonography (CUS). We evaluated noninvasive magnetic resonance direct thrombus imaging (MRDTI) in a prospective study of 39 patients with symptomatic recurrent ipsilateral DVT (incompressibility of a different proximal venous segment than at the prior DVT) and 42 asymptomatic patients with at least 6-month-old chronic residual thrombi and normal D-dimer levels. All patients were subjected to MRDTI. MRDTI images were judged by 2 independent radiologists blinded for the presence of acute DVT and a third in case of disagreement. The sensitivity, specificity, and interobserver reliability of MRDTI were determined. MRDTI demonstrated acute recurrent ipsilateral DVT in 37 of 39 patients and was normal in all 42 patients without symptomatic recurrent disease for a sensitivity of 95% (95% CI, 83% to 99%) and a specificity of 100% (95% CI, 92% to 100%). Interobserver agreement was excellent (κ = 0.98). MRDTI images were adequate for interpretation in 95% of the cases. MRDTI is a sensitive and reproducible method for distinguishing acute ipsilateral recurrent DVT from 6-month-old chronic residual thrombi in the leg veins.

Diagnosis and classification of the antiphospholipid syndrome.

The antiphospholipid syndrome (APS) is defined by the occurrence of venous and arterial thromboses, often multiple, and recurrent fetal losses, frequently accompanied by a moderate thrombocytopenia, in the presence of antiphospholipid antibodies (aPL). Some estimates indicate that the incidence of the APS is around 5 new cases per 100,000 persons per year and the prevalence around 40-50 cases per 100,000 persons. The aPL are positive in approximately 13% of patients with stroke, 11% with myocardial infarction, 9.5% of patients with deep vein thrombosis and 6% of patients with pregnancy morbidity. The original classification criteria for the APS were formulated at a workshop in Sapporo, Japan, in 1998, during the 8th International Congress on aPL. The Sapporo criteria, as they are often called, were revised at another workshop in Sydney, Australia, in 2004, during the 11th International Congress on aPL. At least one clinical (vascular thrombosis or pregnancy morbidity) and one laboratory (anticardiolipin antibodies, lupus anticoagulant or anti-ß2-glycoprotein I antibodies) criterion had to be met for the classification of APS.

Diagnosis of acute aortic syndromes : imaging and beyond.

Acute aortic syndromes are fatal medical conditions including classic acute aortic dissection, intramural hematoma, and penetrating atherosclerotic ulcer. Given the nonspecific symptoms and signs, a high clinical index of suspicion followed by an imaging study, namely transesophageal echocardiography, computed tomography, and magnetic resonance imaging (sensitivity 98-100% and specificity 95-100%), is a conditio sine qua non for prompt diagnosis of acute aortic syndromes. This article provides an overview of established and emerging approaches for the assessment of acute aortic syndromes, with focus on imaging and biomarkers. In this regard, D-dimer levels (cut-off: 500 ng/ml) may be useful to rule out aortic dissection, if used within the first 24 h after symptom onset.

How to manage thrombosis in myeloproliferative neoplasms.

PURPOSE OF REVIEW: In this article, an updated overview of risk factors and management of vascular complications in myeloproliferative neoplasms (MPN) is presented. RECENT FINDINGS: The rate of thrombosis in patients with polycythemia vera, essential thrombocythemia, and primary myelofibrosis is elevated and a risk-oriented therapeutic approach is recommended to avoid inappropriate exposure to cytotoxic drugs on one side or suboptimal treatment on the other. Established thrombosis risk factors are age and previous vascular events but novel disease-related determinants such as leukocytosis and JAK2V617F mutational status and/or mutational burden are now under active investigation. The theory that elevated platelet count increases thrombosis risk in these diseases is now challenged. SUMMARY: Recent recommendations by the European Leukemia Net suggest that MPN patients should be stratified and treated according to conventional risk factors (age and previous events) and that baseline leukocytosis and JAK2V617F mutation should be considered once more information is available and when they have been eventually validated in prospective studies.

Autopsy validation study of the academic research consortium stent thrombosis definition.

OBJECTIVES: This study sought to validate the sensitivity and specificity of the Academic Research Consortium's (ARC) classification of stent thrombosis. BACKGROUND: Classification of stent thrombosis according to ARC criteria has become widely accepted. The criteria have not been validated against an autopsy standard. METHODS: An autopsy registry of 139 subjects with prior coronary stenting underwent detailed histopathological analysis to assess for stent thrombosis. Based on clinical data only, cases were adjudicated according to ARC stent thrombosis criteria, including a proposed modification of the possible classification to include death beyond 30 days due only to sudden death or acute ischemia. RESULTS: Autopsy results confirmed 51 cases as positive and 88 as negative for stent thrombosis. Clinical adjudication classified 105 cases as definite (10), probable (31), or possible (64) ARC stent thrombosis. Specificity was high for definite (99%) and definite plus probable (83%) criteria, but sensitivity was poor at 18% and 51%, respectively. Including the possible cases improved sensitivity to 92% but reduced specificity to 34% (58 false positives). The modified possible criteria eliminated 13 false positive cases (specificity = 49%) and was the best approximation of a hypothetical gold standard in a sensitivity analysis if late death represented at least 20% of all stent thrombosis cases. CONCLUSIONS: In a selected autopsy sample, restricting ARC stent thrombosis to definite or definite plus probable criteria results in substantial under-reporting of confirmed cases. Inclusion of a modified possible classification may provide the best estimate of late and very late stent thrombosis rates.