Early Thrombotic Events Research Articles

Thrombosis and anticoagulation after portal vein reconstruction during pancreatic surgery: a systematic review

BackgroundPortal vein (PV) resection and reconstruction, which includes the resection and reconstruction of the PV and superior mesenteric vein, enable surgical removal of borderline resectable and locally advanced pancreatic cancer. Thrombosis of the reconstructed PV represents a major cause of early postoperative and long-term morbidity and mortality. No universally accepted standard for anticoagulation exists. This study aimed to assess early and late thrombosis rates after PV reconstruction with special regard to the type of PV reconstruction and anticoagulation regimen and to comprehensively assess thrombotic events and their clinical effect in patients receiving pancreatic surgery with venous resection and reconstruction. MethodsThe Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Studies reporting on PV resection and reconstruction providing data on thrombosis rates were included. The following parameters were assessed: study type, year of publication, number of patients, type/number of PV reconstruction, follow-up period, postoperative mortality, thrombosis rate of the reconstructed PV axis, intraoperative blood loss, and anticoagulation. ResultsA total of 23 studies with 2751 patients were included in the final analysis. Of note, 670 patients received tangential resection of the PV with venorrhaphy or patch repair, 1505 patients had segmental resection with end-to-end reconstruction, and 576 patients received reconstruction with an interposition graft/conduit. The pooled overall thrombosis rate was 15%. Reconstruction of tangential defects with either venorrhaphy or patch repair and end-to-end repair of segmental defects resulted in a thrombosis rate of 12%. Subgroup analysis according to the type of graft reconstruction revealed the highest occlusion rates of 55% in patients with allogeneic grafts, followed by up to 27% in patients with synthetic PV conduits. Autologous conduits had a thrombosis rate of 10%. Early thrombotic events were detected in 5% of patients after venorrhaphy/patch reconstruction and end-to-end reconstruction. Early events were most common in the allogeneic graft subgroup (22%), followed by synthetic conduits (15%). There were fewer early events in the autologous graft group (7%). Early PV thrombosis was associated with relevant mortality of up to 26%. Anticoagulation regimens varied between studies. ConclusionThe overall thrombosis rate after PV resection is low. However, among the different reconstruction techniques, allogeneic interposition grafts/conduits had the highest thrombosis rates among the different types of reconstruction after PV resection. No specific anticoagulation strategy can be considered beneficial based on the existing literature.

Mass-spectrometry analysis of blood plasma and extracellular vesicles proteome for early thrombotic events prediction in patients with acute myocardial infarction

Mass-spectrometry analysis of blood plasma and extracellular vesicles proteome for early thrombotic events prediction in patients with acute myocardial infarction

The clinical significance of TAT, PIC, TM, and t-PAIC in vascular events of BCR/ABL-negative myeloproliferative neoplasms

Predicting the likelihood vascular events in patients with BCR/ABL1-negative myeloproliferative neoplasms (MPN) is essential for the treatment of the disease. However, effective assessment methods are lacking. Thrombin-antithrombin complex (TAT), plasmin-α2- plasmininhibitor complex (PIC), thrombomodulin (TM), and tissue plasminogen activator-inhibitor complex (t-PAIC) are the new direct indicators for coagulation and fibrinolysis. The aim of this study was to investigate the changes of these four new indicators in thrombotic and hemorrhagic events in BCR/ABL1-negative MPN. The study cohort of 74 patients with BCR/ABL negative myeloproliferative disorders included essential thrombocythemia, polycythemia vera, and primary myelofibrosis (PMF). A panel of 4 biomarkers, including TAT, PIC, TM, and t-PAIC were determined using Sysmex HISCL5000 automated analyzers, whereas fibrin/fibrinogen degradation products (FDP), D-dimer and Antithrombin III (ATIII) were analyzed using Sysmex CS5100 coagulation analyzer. A total of 24 (32.4%) patients experienced thrombotic events and hemorrhagic events occurred in 8 patients (10.8%). Compared to patients without hemorrhagic-thrombotic events, patients with thrombotic events had higher fibrinogen (FIB) level, FDP level and lower ATIII activity, while patients with hemorrhagic events had lower white blood cell count and hemoglobin level, higher FDP level (P < 0.05). Patients with a JAK2V617F mutation were more likely to experience thrombotic events (P < 0.05). In addtion, patients with thrombotic events had higher TAT, PIC, TM, and t-PAIC levels than patients without hemorrhagic-thrombotic events (P < 0.05), whereas patients with hemorrhagic events had a lower median value in TAT and TM (no statistical difference, P > 0.05). Patients with higher TAT, TM and t-PAIC were more likely to experience thrombotic events (P < 0.05), and only TAT was positively correlated with thrombotic events (Spearman r =0.287, P = 0.019). TAT, PIC, TM, and t-PAIC combined with ATIII and FDP have a certain value for predicting thrombosis in patients with BCR/ABL1-negative MPN. These 6 parameters are worth further exploration as predictive factors and prognostic markers for early thrombotic events.

Cumulative Incidence of Thromboembolism and Prognostic Impact of Stroke in BRAF V600E-mutant Non-small-cell Lung Cancer.

Cancer and ischemic stroke are closely associated. Thromboembolism susceptibility in lung cancer may differ depending on oncogenic alterations. However, the clinical characteristics of thromboembolism in patients with BRAF-mutant non-small-cell lung cancer remain unknown. Thus, this study aimed to evaluate the cumulative incidence of thromboembolism in this population and describe such cases in detail. We retrospectively investigated consecutive patients with BRAF V600E-mutant non-small-cell lung cancer. Cumulative incidence was calculated using a competing risk analysis. Of 10 patients with BRAF-V600E mutant lung cancer, five developed a total of seven thromboembolic events, showing a 1-year cumulative incidence of 43% (95% confidence interval=11-72%). These events consisted of four cancer-related stroke (CRS) events and three venous events including deep vein thrombosis or pulmonary embolism. Of note, most of the early thrombotic events were CRS. Two patients with CRS had multiple brain infarctions during anticancer drug therapy, characterized by high D-dimer levels, resulting in short-term mortality (13 and 22 days after stroke onset). A substantial proportion of patients with BRAF V600E-mutant lung cancer experienced thromboembolism during their disease course. CRS of undetermined source may predict a worse prognosis in this population.

Predictors of Early Thrombotic Events in Adult Patients with Acute Myeloid Leukemia: A Real-World Experience.

Information regarding the incidence and the prognostic impact of thrombotic events (TE) in non-promyelocytic acute myeloid leukemia (AML) is sparse. Although several risk factors associated with an increased risk of TE development have been recognized, we still lack universally approved guidelines for identification and management of these complications. We retrospectively analyzed 300 consecutive patients with newly diagnosed AML. Reporting the incidence of venous TE (VTE) and arterial TE (ATE) was the primary endpoint. Secondarily, we evaluated baseline patient- and disease-related characteristics with a possible influence of VTE-occurrence probability. Finally, we evaluated the impact of TE on survival. Overall, the VTE incidence was 12.3% and ATE incidence was 2.3%. We identified three independent predictors associated with early-VTE: comorbidities (p = 0.006), platelets count &gt;50 × 109/L (p = 0.006), and a previous history of VTE (p = 0.003). Assigning 1 point to each variable, we observed an overall cumulative incidence of VTE of 18.4% in the high-risk group (≥2 points) versus 6.4% in the low-risk group (0-1 point), log-rank = 0.002. Overall, ATE, but not VTE, was associated with poor prognosis (p &lt; 0.001). In conclusion, TE incidence in AML patients is not negligible. We proposed an early-VTE risk score that could be useful for a proper management of VTE prophylaxis.

On-admission versus in-hospital thromboembolism due to COVID-19 infection. What is the particular characteristic of those with early thrombotic events?

Increasing evidence has declared a hypercoagulable state in the coronavirus 2019 infection (COVID-19), while the etiology has remained a question. For the first time, the current study has aimed to compare the contributors of thromboembolism among those whose primary manifestations of COVID-19 were thrombosis vs the patients with a thrombotic event during the period of hospitalization. This case-control study has been conducted on 267 COVID-19 patients, including 59, 48, and 160 ones with an on-admission, in-hospital, and without a thrombotic event, respectively. The events were defined as deep vein thrombosis (DVT), ischemic cerebrovascular accidents (CVA), pulmonary thromboembolism (PTE), or acute myocardial infarction (AMI). The demographic, physical examination, clinical and laboratory assessments of the groups were compared. The DVT (OR: 5.18; 95% CI: 1.01-26.7), AMI (OR: 11.1; 95% CI: 2.36-52.3), and arterial thrombosis (OR: 5.93; 95% CI: 0.63-55.8) were significantly associated with an on-admission thrombosis compared to those who presented in-hospital events. Lower levels of oxygen saturation were the only significant predictor index inversely associated with on-admission thrombosis compared to those with an event during the hospital admission period. PTE development was the most common in-hospital thrombotic event, whereas other thromboembolism types were remarkably more often among cases with on-admission events. Oxygen saturation was the only predictor of premature thrombosis that was inversely associated with outpatient events.

Early Thrombotic Events Following Splenectomy for Myelofibrosis: Incidence, Risk Factors and Effect of Pre-Emptive Anticoagulant Therapy

Background:Current drug therapy in myelofibrosis (MF) is mostly palliative. Other treatment modalities with palliative value in MF include red cell transfusion support, involved field radiotherapy, and splenectomy. Indications for splenectomy in MF include drug-refractory symptomatic splenomegaly, frequent transfusion need, refractory thrombocytopenia and complications from portal hypertension. The salutary effects of splenectomy include symptomatic relief and improvement in anemia and thrombocytopenia. Complications following splenectomy include perioperative bleeding, infections and thrombosis. The current study addresses the latter, in terms of prevalence, vascular distribution, risk factors and the effect of preventive anticoagulant therapy.Methods:Study patients were selected from institutional databases. Diagnosis of MF, including primary (PMF) and post-essential thrombocythemia (post-ET) and post-polycythemia vera (post-PV), was according to World Health Organization (WHO) (Blood 2016;127:2391) or international working group for MPN research and treatment (IWG-MRT) (Leukemia 2008;22:437) criteria. All surgical procedures were performed at our institution. Statistical analyses considered clinical and laboratory data collected at time of splenectomy. Early thrombotic events constituted those occurring in the first two months of splenectomy. Pre-emptive anticoagulant therapy was acknowledged if documented in the first two weeks of splenectomy, prior to an event.Results:Between 2001 and 2016, therapeutic splenectomies were performed on 123 consecutive patients with chronic phase MF; amongst these patients, 120 were evaluable for the occurrence of post-operative thrombotic events. Median time between initial diagnosis and date of splenectomy was 3.2 years. •Clinical and laboratory features at time of splenectomyMedian age was 66 years (range 43-84) and 58% were males. MF variants were PMF 76%, post-PV MF 18% and post-ET MF 6%. Risk distribution, according to the dynamic international prognostic scoring system (DIPSS) (Blood . 2010;115:1703) was 21% high, 55% intermediate-2, 21% intermediate-1 and 3% low. 60% of the patients had constitutional symptoms, 61% were red cell transfusion-dependent and median platelet and leukocyte counts were 106 x 10(9)/L (range 1-699) and 13.5 x 10(9)/L (range 0.5-113), respectively. Driver mutational status was known in 89 patients and included JAK2 75%, CALR 15%, MPL 4% and triple-negative 6%. Karyotype was abnormal in 60%. History of thrombosis prior to splenectomy was documented in 22% (arterial 15% and venous 7%). •Early post-splenectomy thrombosis and its risk factorsMedian follow-up from the time of splenectomy was 1.3 years (range 0.02-8.5). 34 (28%) patients experienced post-splenectomy thrombosis in the first 2 months of surgery (median 7 days; range 1-60); these constituted venous events in 91% of the cases and involved portal and/or splenic veins in 20 and 13 episodes, respectively. During a comprehensive analysis of clinical and laboratory variables, post-splenectomy thrombosis was significantly associated with pre-splenectomy history of venous thrombosis (p=0.02) and higher platelet count at time of splenectomy (p=0.03); there were no associations with driver mutational status, leukocyte count, karyotype, age or gender. •Pre-emptive anticoagulant therapy within two weeks of surgery and its effect on post-splenectomy thrombosisPre-emptive anticoagulant therapy within two weeks of surgery and a minimum treatment duration of 3 consecutive days was instituted in 77 (62%) patients and included heparin therapy in full therapeutic (n=17; 14%) or prophylactic (n=58; 48%) dose and continued warfarin therapy for a history of pre-splenectomy thrombosis (n=2; 2%). Post-splenectomy thrombosis occurred in none (0%) of the patients receiving full therapeutic dose heparin, 26% of those on prophylactic heparin therapy, both (100%) patients on warfarin therapy and 40% of those on no anticoagulant therapy (p=0.002).Conclusions:More than a quarter of MF patients undergoing therapeutic splenectomy might experience mostly venous post-splenectomy thrombosis, in the first two months of surgery; pre-emptive full dose heparin therapy might be protective in this regard and risk factors include history of venous thrombosis and higher platelet count at time of splenectomy. DisclosuresNo relevant conflicts of interest to declare.

Different Timing of Cholangiocyte and Hepatocyte Damage in Liver Preservation: Time to Implement Donor Interventions and New Preservation Techniques to Prevent Ischemic-type Biliary Lesions.

We read with interest the article by Gilbo et al1 assessing the impact of donor hepatectomy and implantation time on the incidence of early allograft dysfunction (EAD) and nonanastomotic strictures (NASs) in liver transplantation (LT). Donor hepatectomy and implantation time seem to have a linear negative impact on the incidence of NAS and EAD, respectively. A 10-min increase in either of these times is roughly as detrimental as a 1-h increase of cold ischemia time. This article expands our understanding of the importance of warm ischemia in LT, confirming findings from previous studies.2 We would like to provide further data and share our comments on this inspiring article. In 2016–1017, we collected data about times and graft temperatures in 160 first adult LTs with grafts from brain-dead donors. Liver temperature was measured at different time points using an infrared thermometer. In our experience, we were unable to show a significant impact of donor hepatectomy and implantation time on LT outcome, likely because of limited sample size and different practices that led to very little variability of these parameters. Median (interquartile range) time of donor hepatectomy and portal vein anastomosis was 47 (40–55) and 24 (21–28) min, respectively, and correlated poorly with graft temperature at the end of donor hepatectomy (R = 0.03, P = 0.61) and before graft reperfusion into recipient (R = 0.11, P = 0.16). However, our data (Figure 1) clearly show that liver grafts do suffer from a period of warm ischemia during retrieval and implantation.FIGURE 1.: Boxplot showing liver graft temperature at different time points during retrieval, back table preparation, and implantation. IQR, interquartile range.Analysis of EAD predictors in the study by Gilbo et al was somewhat hampered by the lack of inclusion of potentially important confounders, like macrosteatosis and severity of liver disease. Moreover, blood transfusions and early thrombotic events are also main determinants of EAD, as demonstrated by their incorporation in the recently developed early allograft failure simplified estimation score.3 Nonetheless, this study interestingly suggests that donor and recipient warm ischemia may impact differently on cholangiocytes and hepatocytes. Indeed, donor hepatectomy time had no effect on EAD (which is mainly determined by hepatocytes function), whereas implantation time was irrelevant with regard to NAS, which reflects cholangiocytes damage. Thus, cholangiocyte injury seems to happen at an earlier timing during graft retrieval and preservation, a finding in keeping with observations that histological damage to biliary epithelium and peribiliary glands is already apparent before graft reperfusion. As a logical implication, interventions focused on the earlier phase of organ preservation are likely needed to tackle NAS, especially in donors after circulatory death, a setting in which normothermic regional perfusion and hypothermic oxygenated machine perfusion have been associated with a significant NAS reduction.4,5 Besides underscoring once more the importance of proper training and technique in LT, this study confirms the role of ischemia-reperfusion injury in determining NAS and highlights the need to implement donor and preservation strategies to reduce their incidence. Future studies will have to assess whether the detrimental role of donor hepatectomy and implantation time persists also when alternative retrieval or preservation modalities are used.

Clinical utility of C-peptide measurement after pancreas transplantation with especial focus on early graft thrombosis.

Since the beginning of our pancreas transplant programme, plasma C-peptide was routinely measured daily during the postoperative period. We aimed to evaluate the clinical interest of the C-peptide in the follow-up of pancreas transplantation with a particular look on early graft failure. From 2000 to 2016, 384 pancreas transplantations were evaluated. We collected and compared C-peptide, glycaemia and adjusted C-peptide (aCP; calculated based on C-peptide, glycaemia and creatininaemia) in patients with and without pancreas failure within 30days after surgery. Variations of glycaemia, C-peptide and aCP between the day before and the day of failure were also recorded. The difference of aCP was significant during the first week after transplantation between patients with thrombosis and those with functional allograft: 63.2 vs. 26.7 on day 1, P=0.0003; 61.4 vs. 26.7 on day 3, P<0.0001; 64.8 vs. 5.7 on day 7, P<0.0001, respectively. Glycaemia had a median increase of 8% on the day of failure, whereas C-peptide and aCP had, respectively, a median decrease of 88% and 83%. C-peptide monitoring after pancreas transplantation may help to identify graft function and early failure. This sensitive biomarker could allow pre-emptive diagnosis of an early thrombotic event allowing the possibility of rescue interventions.

Fatal Mesenteric Ischemia in a Severely Ill COVID-19 Patient: a Case Report

Background: Emerging data suggest a complex role for immuno-thrombosis in the thrombotic complications in COVID-19. We report the case of a fatal mesenteric ischemia to illustrate the mechanisms of endothelial dysfunction in the gut, and the resulting hypercoagulability. Case Report: A 58-year-old woman was admitted in Intensive Care Unit, with initial severe acute respiratory distress syndrome due to SARS-CoV-2 pneumonia. Her respiratory status worsened, with a septic shock thirteen days after symptoms onset. The blood culture was positive with Pseudomonas aeruginosa and Candida. A rapid consecutive deterioration leading to multiorgan failure revealed colic perforation complicated with secondary peritonitis. Histopathological findings revealed small vein occlusions. Surprisingly, no SARS-CoV-2 viral particles could be detected in the bowel. We found intense endothelial dysfunction, contrasting with only mild neutrophil activation. A major increase in von Willebrand factor and resistance to fibrinolysis were the main hemostatic abnormalities. Discussion: This case highlights that COVID-19-associated hypercoagulability can lead to early primitive thrombotic events in small vessels, and adds new evidence concerning a potential role for immuno-thrombosis. Close monitoring of endothelial dysfunction, and further consideration of new targets to prevent thrombosis by adjunctive therapies may thus appear fundamental.

Pulmonary Arterial Thrombosis in a Murine Model of Blunt Thoracic Trauma.

Pulmonary thromboembolic events cause significant morbidity and mortality after severe trauma. Clinically, these lesions are believed to be emboli arising secondary to deep venous thrombosis (DVT) in the lower extremities. Recently, this notion has been challenged by clinical studies, showing that pulmonary clots arise after trauma in the absence of DVT. This suggests that pulmonary blood clots arise in situ via de novo thrombosis. In the present study, we characterize a murine weight-drop model of lateral blunt thoracic trauma. Our model demonstrates severe unilateral lung contusion injury with low (10%) mortality in the absence of extrapulmonary injury, after impact with a 50-g weight dropped from 45 cm height (657 J/m). At 24 h after injury, immunofluorescence and histological evidence revealed early pulmonary arterial thrombosis in the form of eccentric accumulation of fibrin and CD41 positive eosinophilic proteinaceous material, on both coup and contrecoup lung lobes of injured mice, indicating early thrombotic events both within and outside of the area of primary lung injury. Our model is ideal in that lateral impact enables greater impact energy to be applied to achieve significant lung contusion without significant mortality or extrapulmonary injury, and the model has additional translational value in creating thrombosis analogous to pulmonary embolism observed clinically after blunt thoracic trauma. To our knowledge, this is the first demonstration of de novo pulmonary thrombosis in a clinically translational model of blunt thoracic trauma, and supports challenges to current assumptions about the origin of pulmonary blood clots in the wake of severe traumatic injury.

OP.8A.01] NEWLY DIAGNOSED DIABETES MELLITUS IS ASSOCIATED WITH INCREASED LEVELS OF ERYTHROCYTE MICROPARTICLES

Objective: Patients with Diabetes Mellitus (DM) carry a high burden of cardiovascular damage and high risk of early thrombotic events. It is currently unknown how early this damage occurs and if it preexists in naive newly diagnosed DM patients. Design and method: We sought to determine the thrombotic tendency of patients with known cardiovascular risk factors. To this end we used sophisticated, novel markers of atherosclerotic and thrombotic damage: platelet (PLTs) and erythrocyte (RBCs) microparticles. Consecutive patients of the Micro- and Macro-vascular disease Clinic of Third Department of Internal Medicine at Papageorgiou General Hospital of Thessaloniki were included in the study. A thorough medical history was taken and a blood sample was drawn. A 24-hour urine collection was performed to assess the presence of microalbuminuria. Furthermore, PLTs and RBCs were determined using flow cytometry according to specific protocol. Cardiovascular risk factors were evaluated with emphasis on hypertension, newly diagnosed DM, dyslipidemia, smoking and body mass index. Results: Our study sample consisted of 45 patients aged 52.5 ± 11.9 years, 19 men: 26 women, with mean systolic / diastolic blood pressure: 132.7 ± 16.8 / 83.3 ± 13.7 mmHg. Newly-diagnosed DM was found in 19 patients, while untreated hypertension in 16. Multiple linear regression analysis showed that DM makes the strongest contribution to high RBCs values (beta: 0,673, p = 0,021) after the effect of cardiovascular risk factors is controlled for. No significant predictor of PLTs could be identified. Conclusions: In our study, RBCs strongly correlated with the presence of DM at the very early stages of the disease, despite the small sample size. Current knowledge suggests that RBCs consist a robust indicator of thrombotic tendency. The fact that PLTs did not correlate with the presence of DM in our study may, at least in part, reflect the multifactorial role of platelets not only in the thrombotic but also in the inflammatory process of atherosclerosis. Larger studies are needed to determine the value of PLTs and RBCs in patients with cardiovascular risk factors.

Are BVS suitable for ACS patients? Support from a large single center real live registry

ObjectivesTo investigate one-year outcomes after implantation of a bioresorbable vascular scaffold (BVS) in patients presenting with acute coronary syndrome (ACS) compared to stable angina patients. BackgroundRobust data on the outcome of BVS in the setting of ACS is still scarce. MethodsTwo investigator initiated, single-center, single-arm BVS registries have been pooled for the purpose of this study, namely the BVS Expand and BVS STEMI registries. ResultsFrom September 2012–October 2014, 351 patients with a total of 428 lesions were enrolled. 255 (72.6%) were ACS patients and 99 (27.4%) presented with stable angina/silent ischemia. Mean number of scaffold/patient was 1.55±0.91 in ACS group versus 1.91±1.11 in non-ACS group (P=0.11). Pre- and post-dilatation were performed less frequent in ACS patients, 75.7% and 41.3% versus 89.0% and 62.0% respectively (P=0.05 and P=0.001). Interestingly, post-procedural acute lumen gain and percentage diameter stenosis were superior in ACS patients, 1.62±0.65mm (versus 1.22±0.49mm, P<0.001) and 15.51±8.47% (versus 18.46±9.54%, P=0.04). Major adverse cardiac events (MACE) rate at 12months was 5.5% in the ACS group (versus 5.3% in stable group, P=0.90). One-year definite scaffold thrombosis rate was comparable: 2.0% for ACS population versus 2.1% for stable population (P=0.94), however, early scaffold thromboses occurred only in ACS patients. ConclusionsOne-year clinical outcomes in ACS patients treated with BVS were similar to non-ACS patients. Acute angiographic outcomes were better in ACS than in non-ACS, yet the early thrombotic events require attention and further research.

RUNX1 Amplification Increases the Risk for Thrombosis in Children With B-cell Acute Lymphoblastic Leukemia.

RUNX1 (AML1) amplification in patients with B-cell acute lymphoblastic leukemia (B-ALL) has been associated with poor survival for unclear reasons. Our anecdotal experience suggests that children with B-ALL and RUNX1 amplification might be predisposed to thrombosis. We performed a retrospective cohort study of children with B-ALL treated from 2008 to 2014 at the North Carolina Children's Hospital. Patient demographics, cytogenetics, and diagnosis of thrombosis were extracted by blinded chart review. Analysis was performed examining the relationship between RUNX1 amplification and thrombosis. We identified 119 patients with B-ALL and a median age of 4.9 years (interquartile range, 2.9 to 8.6 y) at diagnosis. Four patients (3%) had RUNX1 amplification. The average number of RUNX1 copies among those with amplification was 5 (SD 0.81 [range, 4 to 6]). Eighteen thromboses were diagnosed within 6 months of starting treatment. These events were more likely among patients with RUNX1 amplification than in patients without amplification (75% vs. 13%; RR 5.75, 95% confidence interval, 2.75-12.01). RUNX1 amplification may predispose to early thrombotic events in children with B-ALL which could, in part, contribute to their poorer outcomes. Treatment implications, including possible prophylactic anticoagulation of patients with of RUNX1 amplification, justify larger studies to confirm these findings.

Antithrombin Dublin (p.Val30Glu): a relatively common variant with moderate thrombosis risk of causing transient antithrombin deficiency.

The key haemostatic role of antithrombin and the risk of thrombosis associated with its deficiency support that the low incidence of antithrombin deficiency among patients with thrombosis might be explained by underestimation of this disorder. It was our aim to identify mutations in SERPINC1 causing transient antithrombin deficiency. SERPINC1 was sequenced in 214 cases with a positive test for antithrombin deficiency, including 67 with no deficiency in the sample delivered to our laboratory. The p.Val30Glu mutation (Antithrombin Dublin) was identified in five out of these 67 cases, as well as in three out of 127 cases with other SERPINC1 mutations. Genotyping in 1593 patients with venous thrombosis and 2592 controls from two populations, revealed a low prevalent polymorphism (0.3 %) that moderately increased the risk of venous thrombosis (OR: 2.9; 95 % CI: 1.07-8.09; p= 0.03) and identified one homozygous patient with an early thrombotic event. Carriers had normal anti-FXa activity, and plasma antithrombin was not sensitive to heat stress or proteolytic cleavage. Analysis of one sample with transient deficit revealed a type I deficiency, without aberrant or increased latent forms. The recombinant variant, which lacked the two amino-terminal residues, had reduced secretion from HEK-EBNA cells, formed hyperstable disulphide-linked polymers, and had negligible activity. In conclusion, p.Val30Glu by affecting the cleavage of antithrombin's signal peptide, results in a mature protein lacking the N-terminal dipeptide with no functional consequences in normal conditions, but that increases the sensitivity to be folded intracellularly into polymers, facilitating transient antithrombin deficiency and the subsequent risk of thrombosis.

Targeting aspirin in acute disabling ischemic stroke: an individual patient data meta-analysis of three large randomized trials.

BackgroundAspirin is of moderate overall benefit for patients with acute disabling ischemic stroke. It is unclear whether functional outcome could be improved after stroke by targeting aspirin to patients with a high risk of recurrent thrombosis or a low risk of haemorrhage.AimsWe aimed to determine whether patients at higher risk of thrombotic events or poor functional outcome, or lower risk of major haemorrhage had a greater absolute risk reduction of poor functional outcome with aspirin than the average patient.MethodsWe used data on individual ischemic stroke patients from three large trials of aspirin vs. placebo in acute ischemic stroke: the first International Stroke Trial (n = 18 372), the Chinese Acute Stroke Trial (n = 20 172) and the Multicentre Acute Stroke Trial (n = 622). We developed and evaluated clinical prediction models for the following: early thrombotic events (myocardial infarction, ischemic stroke, deep vein thrombosis and pulmonary embolism); early haemorrhagic events (significant intracranial haemorrhage, major extracranial haemorrhage, or haemorrhagic transformation of an infarct); and late poor functional outcome. We calculated the absolute risk reduction of poor functional outcome (death or dependence) at final follow‐up in: quartiles of early thrombotic risk; quartiles of early haemorrhagic risk; and deciles of poor functional outcome risk.ResultsIschemic stroke patients who were older, had lower blood pressure, computerized tomography evidence of infarct or more severe deficits due to stroke had increased risk of thrombotic and haemorrhagic events and poor functional outcome. Prediction models built with all baseline variables (including onset to treatment time) discriminated weakly between patients with and without recurrent thrombotic events (area under the receiver operating characteristic curve 0·56, 95% CI:0·53–0·59) and haemorrhagic events (0·57, 0·52–0·64), though well between patients with and without poor functional outcome (0·77, 0·76–0·78) in the International Stroke Trial. We found no evidence that the net benefit of aspirin increased with increasing risk of thrombosis, haemorrhage or poor functional outcome in all three trials.ConclusionsUsing simple clinical variables to target aspirin to patients after acute disabling stroke by risk of thrombosis, haemorrhage or poor functional outcome does not lead to greater net clinical benefit. We suggest future risk stratification schemes include new risk factors for thrombosis and intracranial haemorrhage.

Individualising dual antiplatelet therapy after percutaneous coronary intervention: the IDEAL-PCI registry

ObjectiveTo evaluate the clinical utility of individualising dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) in an all-comers population, including ST-elevation myocardial infarction (STEMI) patients.SettingTertiary care single centre registry.Participants1008...

Time Course of Inflammation, Myocardial Injury, and Prothrombotic Response After Radiofrequency Catheter Ablation for Atrial Fibrillation

Inflammation has been linked to the genesis of stroke in atrial fibrillation (AF) and is implicated in early recurrent arrhythmia after AF ablation. We aimed to define the time course of inflammation, myocardial injury, and prothrombotic markers after radiofrequency ablation for AF and its relation to AF recurrence. Ninety consecutive AF patients (53% paroxysmal) undergoing radiofrequency ablation were recruited. High-sensitivity C-reactive protein (hs-CRP), Troponin-T, creatine kinase-MB, fibrinogen, and D-Dimer concentrations were measured at baseline, at 1, 2, 3, 7 days, and at 1 month after ablation. AF recurrence was documented at 3 days and at 1, 3, and 6 months follow-up. Troponin-T and creatine kinase-MB peaked at day 1 after procedure (both P<0.05). Hs-CRP peaked at day 3 after procedure (P<0.05). Fibrinogen (P<0.05) and D-Dimer (P<0.05) concentrations were significantly elevated at 1 week after procedure. Ln hs-CRP elevation correlated with Ln Troponin-T and fibrinogen elevation. The extent of Ln hs-CRP, Ln Troponin-T, and fibrinogen elevation predicted early AF recurrence within 3 days after procedure (P<0.05, respectively), but not at 3 and 6 months. Patients undergoing radiofrequency ablation for AF exhibit an inflammatory response within 3 days. The extent of inflammatory response predicts early AF recurrence but not late recurrence. Prothrombotic markers are elevated at 1 week after ablation and may contribute to increased risk of early thrombotic events after AF ablation.

Capillary measurement of lactate and glucose for free flap monitoring

It is reported that the salvage rate of free flaps is inversely related to the time interval between the onset of pedicle impairments and their clinical recognition. Monitoring of free flaps is therefore of major importance and clinical monitoring remains the most used technique because of lack of low-cost and non-invasive techniques. The authors suggested an efficient, simple and cheap technique to detect early thrombotic events in monitoring free flaps with skin paddle. In this multicentre prospective study, measurements of capillary glucose and lactate in the flaps were done. These parameters were compared to standardized clinical monitoring during the first five days. Two sets of data (eventful versus uneventful postoperative period) were analyzed to define the thresholds of lactate and glucose values for diagnosis of pedicle complications, and to establish parameters for this screening test. Over a period of 19 months, 37 patients were included. With 5 pedicle impairments, complication thresholds were defined as lactate ≥ 6.4 mmol L(-1) and glucose ≤ 3.85 mmol L(-1), in order to obtain a sensitivity of 98.5% and a specificity of 99.5% for the test. Modifications of capillary glucose and lactate measurements appeared in average 5.7 hours earlier than clinical symptoms in pedicle impairments. The mean cost of a five-day monitoring was about 90 USD. This simple and cheap technique could be used as a routine technique in monitoring free flaps to improve safety of this reconstructive technique.

Effect of combined aerobic and resistance exercise training on platelet adhesiveness under shear flow in sedentary men

Aerobic or resistance exercise may modulate the risk of vascular thrombotic events. This study investigated how combined aerobic and resistance exercise training influenced platelet adhesiveness under various shear flows. Twelve healthy sedentary males were trained on a bicycle ergometer (60% VO2max for 30 minutes) for 3 days per week and an isokinetic dynamometer (alternating 60°–180°/s for 6 to 10 sessions) for 2 days per week for 6 weeks. A novel microfluidic chamber combined with fluorescence instrument, which provided shear stress values covering the entire physiological range of human circulation, was used to assess platelet adhesiveness in whole blood. The experimental results demonstrated that a higher degree of platelets adhered to fibronectin‐coated surface revealed at 5 dyne/cm2 compared to 1 dyne/cm2 of shear stress. Strenuous, acute exercise significantly increased the platelet adhesiveness under 1 and 5 dyne/cm2 of shear stresses. However, combined aerobic and resistance exercise training suppressed the extents of shear‐mediated platelet adhesiveness at rest and immediately strenuous exercise. Hence, these findings may provide an effective strategy for developing a suitable exercise regimen that prevents early thrombotic events, further retarding the progression of cardiovascular disease.