Arterial Thrombosis Events Research Articles

Risk of arterial and venous thrombotic events among patients with cancer diagnosed with COVID-19: A real-world data analysis

AimThe risk of venous thromboembolism (VTE) and arterial thrombosis events (ATE) and potential corresponding risk factors were assessed in patients with cancer diagnosed with COVID-19. MethodsAdults with cancer treated in community health systems who were diagnosed with COVID-19 in 2020 were evaluated for absolute risk (risk) of ATE and VTE. Thrombotic events were ascertained in the 90-day window starting with COVID-19 diagnosis (index). ICD codes defined baseline comorbidities, COVID-19, and thrombotic events. Results7591 patients were included with median age of 67, 6% with cardiovascular disease (CVD), 4% with prior VTE, and 24% were hospitalized at index. Risk of ATE and VTE were 2.1% (95%CI: 1.8, 2.5) and 3.2% (95%CI: 2.8, 3.6), respectively. Patients with CVD had increased risk [ATE: 20.1% (95%CI: 16.7, 24.1); VTE: 4.9% (95%CI: 3.3, 7.3)] as did patients with prior VTE [ATE: 3.8% (95%CI: 2.2, 6.6; VTE: 20.5% (95%CI: 16.4, 25.3)] and patients hospitalized with ventilator support [(ATE: 5.7% (95%CI: 2.6, 11.8; VTE: 6.6% (95%CI: 3.2, 13.0)]. Incidence rates for ATE and VTE were 0.094 and 0.141 per person-year, respectively. ConclusionsThis study of cancer patients, conducted in a time period prior to vaccine availability, found patients with CVD, prior VTE, and with higher severity of COVID-19 were at increased risk for ATE and VTE. Identifying patients most at risk can help to target interventions.

Estimating the Burden of Venous and Arterial Thrombotic Events in Hospitalized Adults with COVID-19; A National Multicenter Cohort Study

Background: Patients infected with Coronavirus Disease 2019 (COVID-19) have clinical and laboratory features consistent with a hypercoaguable state, particularly in more severely ill patients that require hospitalization. However, estimates of thrombotic complications in this high risk population vary widely. A geographic representative cohort to explore the rates of thrombotic events in patients hospitalized with COVID-19 in the United States would be useful to better understand the burden of thrombosis in this population. We aimed to assess the rates of venous and arterial thrombosis events during hospitalization in patients with COVID-19 in a national multicenter cohort study. Methods: We conducted a retrospective cohort study of hospitalized patients diagnosed with COVID-19 from January 1 2020 to January 2023. IRB approval was obtained at each site. Inclusion criteria included adults (> 21 years), hospitalized for >1 day and laboratory confirmation of polymerase chain reaction testing of severe acute respiratory syndrome coronavirus 2. Data were extracted by participating centers in a pre-specified instrument from the electronic medical record at each institution and pooled prior to analysis. Data sources included manual extraction by study investigators in 7 sites and electronic extraction based on billing codes at one site (Cleveland Clinic). Primary outcome was venous thrombotic events, including deep vein thrombosis (DVT), pulmonary embolism (PE). Unusual sites including splanchnic vein thrombosis and cerebral venous thrombosis were included if objectively demonstrated on imaging. Arterial thrombotic events including ischemic stroke, acute coronary syndrome were included as secondary outcomes. Data are presented as proportions, with binomial 95% confidence intervals (CI). Results: We included 33,769 patients from eight medical centers across the United States. Participating hospitals included all four census regions from the North East (Beth Israel Deaconess Medical Center, MA (n=1021) Rochester Regional Hospital, NY (n=99)), South (John Hopkins Medical Institute, ML (n=334); Baycare Health System, FL (n=3734), MidWest (Cleveland Clinic Foundation, OH (n=25467); Henry Ford Health System, MI (973); University of Illinois, IL (1192)) and West (University of California, CA (n=613)). (Figure) Of the total 33,433 hospitalized patients with COVID-19 included, 1684 patients developed a venous thrombotic event during the index hospitalization (5.0%, 95% CI 4.8-5.2) and 261 developed an arterial thrombotic event (0.8%, 95% CI, 95% CI 0.7-0.9). Rates of venous events by individual sites ranged from 2.6-8% and arterial events from 0.3-6.6%. Conclusion: In this national multicenter cohort study that included academic and community hospitals from all four US census regions, we estimated the rates of VTE were over five times more frequent than arterial events in hospitalized patients with COVID-19. Accurate estimates of thrombotic rates and trends can help plan targeted interventions related to strategies around thromboprophylaxis interventions and resource allocation for future surges of COVID-19 cases.

Clinical analysis of twenty-one cases of acute ischemic stroke related to Trousseau syndrome.

Trousseau syndrome (TS) is relatively rare and easily overlooked by clinicians, causing misdiagnosis and affecting subsequent treatment. In this study, clinical features, laboratory examination, imaging features, treatment, and prognosis of patients with TS were discussed. From February 2018 to April 2022, cases of 21 patients with malignant tumors complicated by acute ischemic stroke (AIS) were admitted to the Neurology Department of the hospital, and were retrospectively analyzed and discussed based on the literature. Twenty-one cases were included in the study. Of these, 95.23% (20/21) developed AIS 6-21months after the onset of malignant tumors, 9.52% (2/21) had ischemic stroke as the first symptom, 4.76% (1/21) had recurrent ischemic stroke, and 14.29% (3/21) subsequently experienced venous and arterial thrombosis events; 80.95% (17/21) were pathologically confirmed to have adenocarcinoma; and 90.47% (19/21) of infarction cases involved multiple blood vessel feeding sites. MRI showed multiregional, multifocal patchy infarcts. D-dimer concentration was higher than normal in all patients. In addition, 61.90% (13/21) of the patients had poor outcomes according to mRS. TS is a rare clinical type. It is often associated with adenocarcinoma, and the treatment is different from that of conventional cerebral infarction and the prognosis is very poor. In clinical practice, for AIS of unknown cause, if MRI shows multiple small lesions accompanied by a significant increase in D-dimer, routine screening for latent malignant tumors is recommended.

Angiotensin-II for vasoplegia following cardiac surgery.

The objective of this study was to describe the implementation and outcomes of a protocol outlining angiotensin-II utilization for vasoplegia following cardiac surgery. This was a retrospective chart review at a single-center university hospital. Included patients received angiotensin-II for vasoplegia refractory to standard interventions, including norepinephrine 20mcg/min and vasopressin 0.04 units/min, following cardiac surgery between April 2021 and April 2022. 30 patients received angiotensin-II for refractory vasoplegia. Adjunctive agents at angiotensin-II initiation included corticosteroids (26 patients; 87%), epinephrine (26 patients; 87%), dobutamine (17 patients; 57%), dopamine (9 patients; 30%), milrinone (2 patients; 7%), and hydroxocobalamin (4 patients; 13%). At 3hours, the median mean arterial pressure increased from baseline (70 vs 61.5mmHg, p = .0006). Median norepinephrine doses at angiotensin-II initiation, 1hour, 3hours, and angiotensin-II discontinuation were 0.22, 0.16 (p = .0023), 0.10 (p < .0001), and 0.07 (p < .0001) mcg/kg/min. Median dobutamine doses decreased throughout angiotensin-II infusion from eight to six mcg/kg/min (p = .0313). Other vasoactive medication doses were unchanged. Three patients (10%) subsequently received hydroxocobalamin. Thirteen (43.3%) and five (16.7%) patients experienced mortality by day 28 and venous or arterial thrombosis events, respectively. The administration of angiotensin-II to vasoplegic patients following cardiac surgery was associated with increased mean arterial pressure, reduced norepinephrine dosages, and reduced dobutamine dosages.

Effect of therapeutic versus prophylactic anticoagulation therapy on clinical outcomes in COVID-19 patients: a systematic review with an updated meta-analysis

BackgroundPrevious studies demonstrate a reduced risk of thrombosis and mortality with anticoagulant treatment in patients with COVID-19 than in those without anticoagulation treatment. However, an open question regarding the efficacy and safety of therapeutic anticoagulation (T-AC) versus a lower dose, prophylaxis anticoagulation (P-AC) in COVID-19 patients is still controversial.MethodsWe systematically reviewed currently available randomized clinical trials (RCTs) and observational studies (OBs) from January 8, 2019, to January 8, 2022, and compared prophylactic and therapeutic anticoagulant treatment in COVID-19 patients. The primary outcomes were risk of mortality, major bleeding, and the secondary outcomes included venous and arterial thromboembolism. Subgroup analysis was also performed between critically ill and non-critically ill patients with COVID-19 and between patients with higher and lower levels of D-dimer. Sensitivity analysis was performed to decrease the bias and the impact of population heterogeneity.ResultsWe identified 11 RCTs and 17 OBs fulfilling our inclusion criteria. In the RCTs analyses, there was no statistically significant difference in the relative risk of mortality between COVID-19 patients with T-AC treatment and those treated with P-AC (RR 0.95, 95% CI, 0.78–1.15, P = 0.60). Similar results were also found in the OBs analyses (RR 1.21, 95% CI, 0.98–1.49, P = 0.08). The pooling meta-analysis using a random-effects model combined with effect sizes showed that in the RCTs and OBs analyses, patients with COVID-19 who received T-AC treatment had a significantly higher relative risk of the major bleeding event than those with P-AC treatment in COVID-19 patients (RCTs: RR 1.76, 95% CI, 1.19–2.62, P = 0.005; OBs: RR 2.39, 95% CI, 1.56–3.68, P < 0.0001). Compared with P-AC treatment in COVID-19 patients, patients with T-AC treatment significantly reduced the incidence of venous thromboembolism (RR 0.51, 95% CI, 0.39–0.67, P<0.00001), but it is not associated with arterial thrombosis events (RR 0.97, 95% CI, 0.66–1.42, P = 0.87). The subgroup analysis of OBs shows that the mortality risk significantly reduces in critically ill COVID-19 patients treated with T-AC compared with those with P-AC treatment (RR 0.58, 95% CI, 0.39–0.86, P = 0.007), while the mortality risk significantly increases in non-critically ill COVID-19 patients treated with T-AC (RR 1.56, 95% CI, 1.34–1.80, P < 0.00001). In addition, T-AC treatment does not reduce the risk of mortality in COVID-19 patients with high d-dimer levels in RCTs. Finally, the overall sensitivity analysis after excluding two RCTs studies remains consistent with the previous results.ConclusionsIn our integrated analysis of included RCTs and OBs, there is no significant difference between the mortality of T-AC and P-AC treatment in unselected patients with COVID-19. T-AC treatment in COVID-19 patients significantly reduced the incidence of venous thromboembolism but showed a higher risk of bleeding than those with P-AC treatment. In addition, P-AC treatment was superior to T-AC treatment in non-critically ill COVID-19 patients, the evidence supporting the necessity for T-AC treatment in critically ill COVID-19 patients came only from OBs.Trial registrationProtocol registration: The protocol was registered at PROSPERO (CRD42021293294).Graphical abstract

Venous and Arterial Thrombosis in Ambulatory and Discharged COVID-19 Patients: A Systematic Review and Meta-analysis.

Introduction Venous and arterial thromboses are frequently observed complications in patients with severe novel coronavirus disease 2019 (COVID-19) infection who require hospital admission. In this study, we evaluate the epidemiology of venous and arterial thrombosis events in ambulatory and postdischarge patients with COVID-19 infection. Materials and Method EMBASE and MEDLINE were searched up to July 21, 2021, in addition to other sources. We included studies that assessed the epidemiology of venous and arterial thrombosis events in ambulatory and postdischarge COVID-19 patients. Results A total of 16 studies (102,779 patients) were identified. The overall proportion of venous thromboembolic events in all patients, that is, ambulatory and postdischarge, was 0.80% (95% confidence interval [CI]: 0.44–1.28), 0.28% (95% CI: 0.07–0.64), and 1.16% (95% CI: 0.69–1.74), respectively. Arterial events occurred in 0.75% (95% CI: 0.27–1.47) of all patients, 1.45% (95% CI: 1.10–1.86) of postdischarge patients, and 0.23% (95% CI: 0.019–0.66) of ambulatory patients. The pooled incidence rate estimates per 1,000 patient-days for VTE events were 0.06 (95% CI: 0.03–0.08) and 0.12 (95% CI: 0.07–0.19) for outpatients and postdischarge, respectively, whereas for arterial events were 0.10 (95% CI: 0–0.30) and 0.26 (95% CI: 0.16–0.37). Conclusion This study found a low risk of venous and arterial thrombi in ambulatory and postdischarge COVID-19 patients, with a higher risk in postdischarge patients compared with ambulatory patients. This suggests that regular universal thromboprophylaxis in these patient populations is probably not necessary.

Comparative Analysis of Direct Oral Anticoagulants and Vitamin K Antagonists in Antiphospholipid Syndrome Patients

IntroductionAntiphospholipid syndrome (APS) is a major acquired thrombophilia in which vascular thrombosis (venous or arterial) and/or pregnancy losses occur. Despite the use of vitamin K antagonists (VKAs), the annual risk for recurrent thrombosis among APS patients ranges between 2-5% (Crowther et al. NEJM 2003). The evidence for direct oral anticoagulants (DOAC) use in APS patients is still lacking. Therefore, we conducted a retrospective cohort study to explore the efficacy and safety of DOACs vs. VKAs in this patient population.MethodsThe electronic medical records at Emory University Hospitals were queried for patients ≥18 years old with APS diagnosis, according to the Sydney international census criteria (Miyakis et al. JTH 2006). Included patients must have experienced acute thrombosis between 01/01/2012 and 12/31/2018 and started anticoagulation therapy with DOACs or VKAs. We reviewed patient charts from the index thrombosis date till the end of the study period (12/31/2019). Clinical endpoints were: recurrent vascular thrombosis, clinically relevant bleeding (CRB), which included major and non-major bleeding events as defined by the ISTH society, and composite outcome of thrombosis and bleeding (Kaatz et al. JTH 2015). Patients presenting with pregnancy complications only during the identification period were excluded.ResultsA total of 153 patients with confirmed APS diagnosis were included in the study. Mean age was 51 (range, 18-79 y.o.). 94 patients (61.4%) were females and 80 patients (52.3%) were white. The most common sites of index thrombosis were pulmonary embolism (N=62, 40.5%), proximal lower extremity deep venous thrombosis (N=49, 32%), and stroke/TIA (N=29, 19%). The majority of patients had a single positive antiphospholipid antibody (aPL) (N=83, 54.2%). 35 (22.9%) had double positive and 24 (15.7%) had triple positive disease.Following index thrombosis, 75 patients started DOAC, whereas 72 started warfarin. Six patients started subcutaneous heparin for a short duration before starting an oral form of anticoagulation. Of those on DOAC, 50 started rivaroxaban while 22 started apixaban. After a mean of 19.8 months (range, 0.68 - 69.8) from the index thrombosis, 62 patients (40.5%) switched to a different class of anticoagulation. The most common reasons for switching therapy were recurrent thrombosis (N=16, 25.8%), followed by patient preference (N=13, 20.9%), side effects including bleeding (N=9, 14.5%), and other reasons, such as confirmed APS diagnosis or renal insufficiency (N=12, 19.3%).We found no statistically significant differences in risk of recurrent thrombosis or CRB events among patients who were started on DOAC vs. VKAs (Figure). The number of arterial thrombosis events was minimal and similar in both treatment groups: N=3 in DOAC group vs. N=5 in the VKA group. Patients treated with rivaroxaban had a similar risk of recurrent thrombosis (log rank, p-value=0.629) and CRB events (log rank, p-value=0.631) compared to those treated with apixaban. The risk of recurrent thrombosis was not affected by degree of aPL positivity or previous history of arterial thrombosis in multivariate models (HR 0.791, 95% CI 0.357 - 1.751) (Table).Discussion and ConclusionOur experience suggests that DOACs -particularly rivaroxaban / apixaban- could be an effective and safe alternative to warfarin in APS patients. We realize that patients with triple aPL positivity constitute a special population with a substantial risk of arterial and venous thrombosis. Given the retrospective nature of our data and that triple aPL positive patients compromised only 15% of our patient population, we conclude that the use of DOACs in these high risk patients remains uncertain. Prospective and large-scale multicenter studies are highly encouraged to explore DOAC use in APS patients with various background profiles. We build on our current experience by starting a multicenter collaboration that will facilitate meaningful subgroup comparisons in APS patients. [Display omitted] DisclosuresGaddh: Agios: Consultancy, Other: Advisory board.

Low Rate of Thrombosis in Mexican Patients with COVID-19 Infection. a Benefit of Higher Doses Anticoagulants or a Sub Diagnosis?

Background: Patients with COVID-19 have an increased risk of thromboembolic disease, this has been partly attributed to an excessive inflammatory response that is associated with hypercoagulability; patients develop thrombotic complications with rates of 6.4% in non-critically ill and 15 to 31 % in critically ill patients. With this data some clinicians have incorporated thromboprophylaxis with higher dose heparin into the management of this patients, to date there´s no information of the effect of this intervention.Methods: We conducted a prospective cohort, including consecutive critical and non-critical adults admitted to a referral center in Mexico City, between March 18 and May 19, all with a positive RT-PCR for SARS-CoV 2. Conventional coagulation test results were collected on admission and during hospitalization; use of anticoagulation, and patient outcomes were recorded, all patients had been discharged at the time of the final analysis. Thromboprophylaxis was administered according to institutional recommendations and individual medical criteria, we defined anticoagulant dose according to each medication. We compared the basal characteristics and outcomes in critical and non-critical patients. We evaluated the factors associated with thrombosis, bleeding, and mortality using the Cox Regression Model.Results: We evaluated 447 consecutive hospitalized patients with COVID-19, median age was 50 years (range,18-91), 62.6 % were male, 111 (24.8%) were critical. At admission 156 patients (34.9%) had D-dimer values above 3000 ng/mL, median fibrinogen was 651 mg/dL (range 130-1095), APTT was prolonged (> 3 seconds) in 179 patients (40%), and INR >1.2 in 26 patients (5.8%), median platelet value 215 X103/uL (range 33-666). Thromboprophylaxis’ dosages were prophylactic in 267 (59.7%), intermediate in 75 (16.8%) and therapeutic in 91 (20.4%), 14 patients (3.1%) did not receive any medical thromboprophylaxis and 26 patients (5.8%) received aspirin during hospitalization. According to the International Society on Thrombosis and Hemostasis’ criteria (ISTH criteria) 40 patients (8.9%) had overt-DIC, sepsis induced coagulopathy (SIC) was present in 28 patients (6.3%), and high risk for bleeding by IMPROVE score ≥7 points was found in 5 patients (1.1%). Overall thrombotic event (TE) was confirmed in five patients (1.1%), arterial thrombosis events in 0.4%, one stroke and one acute myocardial infarction; radiographically confirmed venous thrombosis in 0.67%, two with pulmonary embolism (PE) and one with deep venous thrombosis (DVT). The TE were more common in critical than in non-critical patients (3.6% vs 0.3%). The number of CT pulmonary angiogram or duplex ultrasounds performed when PE/DVT was suspected was eighteen (4%), eight (47%) non-critically ill and ten (53%) in the ICU; the rate of radiographically positive results was 22.2%. The overall major bleeding rate was 2.5%, of these 91% were in the ICU. Mortality was 23.5% in the cohort. Table 1.No factors were found to be associated with thrombosis. The factors associated with bleeding were an INR >1.2 (HR 9.0, 95% CI 1.2-67.3, p 0.03), IMPROVE score ≥7 (HR 81.3, 95% CI 11.9-555.6, p < 0.01), and mechanical ventilation (HR 33.1, 95% CI 4.1-262.2, p 0.01). Factors associated with mortality were: age >70 (HR 2.5, 95% CI 1.5-4.2, p <0.01), D-Dimer >3000 ng/mL (HR 2.0,95% CI 1.2-3.4, p <0.01), and mechanical ventilation (HR 1.7, 95% CI 1.01-2.8, p = 0.02). The presence of more than 450x109/L platelets was associated with reduced mortality (HR 0.31 95% CI 0.19-0.50). Figure 1Discussion: The late outbreak of COVID-19 in Latin America had led to an empiric use of aggressive thromboprophylaxis. Our data shows a low TE rate as compared with other groups, nevertheless we cannot prove a direct impact of the aggressive thromboprophylaxis, firstly because of the low rate or events, and secondly, due to the limitations of an observational study. On the other hand, the incidence of PE/DVT is conditioned by the number of studies performed, yet radiological confirmation has proven difficult due to concerns about virus exposure. Regarding the security of the intervention, major bleeding rates were slightly higher to what has been otherwise reported, but with no bleeding related deaths. The benefit of higher anticoagulant doses most be shown in clinical trials before we can recommend their generalized use in COVID-19 patients.DisclosuresNo relevant conflicts of interest to declare.

Frailty is associated with vascular thrombosis events in chronic hemodialysis patients

Abstract Background Frailty is common in chronic hemodialysis patients and is associated with increased risk of mortality. In hemodialysis patients, cardiovascular disease is the most cause of mortality but the impact of frailty on cardiovascular disease remained unknown. Purpose To access if there was an association between frailty and vascular thrombotic events among chronic hemodialysis patients. Methods This is a multi-center cohort study of chronic hemodialysis patients conducted since Jan, 2018 (last follow-up in December, 2020). Baseline data were collected from medical records and hemodialysis records. Frailty was defined by the Fried's criteria, a composite construct that incorporated poor physical functioning, exhaustion/fatigue, low physical activity, and undernutrition using a self-reported questionnaire. The primary outcome was vascular thrombosis events, defined as myocardial infarction, ischemic stroke, acute or critical limb ischemia, and dialysis vascular access thrombosis. The outcomes were assessed from a prospectively-collected nationwide registration system which was updated every 3 months and verified after review of medical records or discussion with caring physicians. Results During the study period, 571 chronic hemodialysis patients were enrolled. The mean age of study participants was 66 years old (SD, 13) and 55% of them were male. A total of 247 patients (43%) were categorized as frail. At baseline, logistic regression analysis revealed that older age, female sex, diabetes, low albumin and history of stroke were independently associated with frailty. During the follow-up period (median, 18 months), 57 patients (10%) died and 182 patients (31.9%) had vascular thrombosis events, including 101 arterial thrombosis (17.7%) and 105 dialysis access thrombosis (18.4%). In the primary outcome analysis, Cox proportional hazards modeling indicated that frailty was independently associated with vascular thrombosis events (Hazard ratio [HR] 1.71, 95% confidence interval [CI] 1.132–2.597). In the secondary analysis, frailty was associated death (HR 2.25, CI 1.16–4.37), arterial thrombosis events (HR 1.92, CI 1.16–3.18), and dialysis vascular access thrombosis events (HR 1.90, CI 1.24–2.91). Conclusion Frailty phenotype is extremely common in hemodialysis patients. It is associated with mortality and vascular thrombosis events among chronic hemodialysis patients. Given its prevalence and consequence, research focus on interventions aimed to prevent or attenuate frailty in hemodialysis patients should be warranted. Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): Grants from National Taiwan University Hospital, Hsinchu Branch.

Arterial Thrombosis in Cancer: Spotlight on the Neglected Vessels.

Cancer patients are at risk for both venous and arterial thrombotic events. Accumulating evidence suggests a link between cancer and arterial thrombosis events. The pathophysiology of arterial thrombosis in cancer is complex and multifactorial. The risk of arterial thrombosis in cancer patients relies on individual risk factors, on cancer-related hypercoagulability, on anticancer drugs and radiotherapy often via a common underlying mechanism of endothelial dysfunction. This review describes the mechanisms involved in the development of arterial thrombotic events and their clinical manifestations. Furthermore, it provides an overview on therapeutic agents associated with arterial thrombosis.

The epidemiology and clinical characteristics of myeloproliferative neoplasms in Malaysia

BackgroundThe evolution of molecular studies in myeloproliferative neoplasms (MPN) has enlightened us the understanding of this complex disease consisting of polycythaemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). The epidemiology is well described in the western world but not in Asian countries like Malaysia.Materials and methodsThis retrospective national registry of MPN was conducted from year 2009 to 2015 in Malaysia.ResultsA total of 1010 patients were registered over a period of 5 years. The mean age was 54 years with male predominance. The ethnic distribution revealed that Chinese had a relatively high weighted incidence proportion (43.2%), followed by Indian (23.8%), Malay (15.8%) and other ethnic groups (17.2%). The types of MPN reported were 40.4% of ET (n = 408), 38.1% of PV (n = 385), 9.2% of PMF (n = 93), 3.1% of hypereosinophilic syndrome (HES) (n = 31) and 7.9% of unclassifiable MPN (MPN-U) (n = 80). Splenomegaly was only palpable clinically in 32.2% of patients. The positive JAK2 V617F mutation was present in 644 patients with 46.6% in PV, 36.0% in ET, 9.0% in PMF, and 7.4% in MPN-U, and had significantly lower haemoglobin (p < 0.001), haematocrit (p < 0.001) and white blood cells (WBC) (p < 0.001) than those with negative mutation. Significant differences in platelet and WBC count were detected in ethnic groups and MPN sub-types. There were more arterial thrombosis events seen in those with JAK2 V617F mutation as compared to venous thrombosis events (23.1% vs 4.4%). The bleeding rate was only 6.6%. Among the risk factors, previous thrombosis, old age (≥ 60 years) and hypertension were significantly correlated to positive JAK2 V617F mutation. The arterial thrombosis event is associated with higher presenting HB, HCT and PLT while the bleeding event is associated with lower presenting HB, HCT but higher PLT. The presence of JAK2 V617F mutation is associated with higher risk of arterial thrombosis.ConclusionChinese ethnicity is associated with higher rates of MPN. The history of thrombosis, age ≥ 60 years and hypertension are risk factors that can be correlated to JAK2 V617F mutation. This study is instrumental for policy makers to ensure preventive strategies can be implemented in future.

Risk of thrombosis with anti-phospholipid syndrome in systemic lupus erythematosus treated with thrombopoietin-receptor agonists.

The use of thrombopoietin-receptor agonists (TPO-RAs) has increased as a second-line therapy in ITP, but the efficacy and safety of such drugs has not been evaluated in SLE-associated ITP. This was a multicentre retrospective cohort study from 2009 to 2016. Participating centres (n = 11) were secondary- or tertiary-care hospitals belonging to the French national network for adult ITP. We included 18 patients with SLE-ITP treated with TPO-RAs; 10 (55%) had aPL, 5 (27%) showing definite APS. Except for one patient, all (94%) achieved response with TPO-RAs overall. After a median follow-up of 14.7 months with TPO-RAs, four arterial thrombosis events (including one catastrophic APS) occurred in four patients. Two venous thrombosis events occurred in a patient without APS or aPLs. Our results suggest that aPLs should be systematically screened before TPO-RA initiation in patients with SLE. With aPL positivity, alternative therapy should be discussed (if possible), especially in patients with definite APS or suboptimal adherence to anti-coagulation therapy.

Diagnostic value of anti-annexin A5 antibodies in seropositive versus seronegative antiphospholipid syndrome patients

Background: Current laboratory criteria for antiphospholipid syndrome (APS) classification recommend testing positive for antiphospholipid (aPL) antibodies. However, there appears to be a subset of patients with classical APS manifestations who test negative. Aim of the work: To analyze the potential clinical usefulness of testing for anti-annexin A5 antibodies in patients with APS and to study the effectiveness of testing for non-criteria aPLs in an attempt to increase the diagnostic yield, particularly in seronegative APS. Patients and methods: 60 APS patients were divided into two groups; 30 seropositive (SP-APS) (group I) and 30 age and sex matched seronegative (sN-APS) testing negative for aPL antibodies. Serum assay for detection of isotypes of anti-annexin A5 antibodies (IgG and IgM) were conducted. Results: The mean age of the patients was 32.9±5.8years, female:male 57:3 and disease duration in SP-APS versus sN-APS (10.17±4.9years versus 9.6±5.5years) respectively. Secondary APS was present in 16(53.3%) patients in group I compared to 3(10%) in group II (p<0.0001). The mean anti-AnxA5 IgG level was 10.7±5.6U/ml and IgM was 11.2±7.1U/ml and were comparable between the 2groups. The obstetric and thrombotic morbidity had no significant differences between SP and sN-APS. The IgG and IgM levels significantly correlated with the pregnancy morbidity, venous and arterial thrombosis events and showed reasonable sensitivities in their prediction (IgG:71.2%,72.8% and 75.8%; IgM: 68%,67.8% and 71.4% respectively) and specificities (IgG:75.9%,77.8% and 81.5%; IgM: 70.9%,73.1% and 73.7% respectively). Conclusion: anti-annexinA5 antibodies are promising for detecting obstetric and thrombotic morbidity in both SP- and sN-APS patients.

Bevacizumab combined with chemotherapy for ovarian cancer: an updated systematic review and meta-analysis of randomized controlled trials.

BackgroundThis meta-analysis was updated with results from a new trial and final data to reassess the efficacy and safety of bevacizumab combined with chemotherapy in ovarian cancer (OC).MethodsRandomized controlled trials (RCTs) were searched in PubMed, EMBASE, Cochrane clinical trials, Web of Science and clinicaltrial.gov databases. Outcomes included the progression-free survival (PFS), overall survival (OS), objective response rate (ORR) and common adverse events. The hazard ratio (HR), risk ratio (RR) and odds ratio (OR) were pooled when the meta-analysis was performed.ResultsFive RCTs with 4994 patients were included. In overall newly diagnosed OC, bevacizumab combined with chemotherapy did not significantly improve PFS (HR 0.85, 95%CI 0.70-1.02) or OS (HR 0.94, 95%CI 0.84-1.05). In the high-risk progression subgroup, the addition of bevacizumab significantly improved PFS (HR 0.76, 95%CI 0.68-0.84) and OS (HR 0.85, 95%CI 0.74-0.96). In recurrent OC, the addition of bevacizumab to chemotherapy significantly extended PFS (HR 0.53, 95%CI 0.45-0.63) and OS (HR 0.87, 95%CI 0.77-0.99). The ORR was improved (OR 2.37, 95%CI 1.99-2.82) in the overall population. Bevacizumab increased the incidence of hypertension (RR 21.27, 95%CI 9.42-48.02), proteinuria (RR 4.77, 95%CI 2.15-10.61), bleeding (RR 3.16, 95%CI 1.59-6.30), GI perforations (RR 2.76, 95%CI 1.51-5.03), arterial thrombosis events (RR 2.39, 95%CI 1.39-4.10) and venous thrombosis events (RR 1.43, 95%CI 1.04-1.96).ConclusionsBevacizumab combined with chemotherapy significantly improved PFS and OS in both patients with high-risk of progression and patients with recurrent OC, with an increased incidence of common adverse events. However, no statistically significant survival benefit was identified in the front-line settings.

Conservative perioperative anticoagulation management in patients with chronic venous thromboembolic disease: a cohort study

Guidelines for perioperative warfarin management in patients with venous thromboembolic disease (VTE) are largely based on expert opinion. To assess the effectiveness and safety of a conservative perioperative anticoagulation strategy in patients with VTE on chronic warfarin therapy. Our center uses a conservative bridging approach for chronic VTE patients consisting of withholding warfarin for 5 days preoperatively, with prophylactic low-molecular-weight heparin (LMWH) post-procedure only if patients are admitted to hospital. We performed a single-center retrospective cohort study. During the study period (1997-2011) there were 634 procedures in 416 patients that were reviewed for postoperative outcomes at 30 and 90 days. Of the 634 procedures, 156 procedures (24.6%) were completed as inpatients. Pre- and post-procedure LMWH bridging was used in 15 (2.4%) and 152 (24.0%) of all procedures, respectively. The 30-day VTE incidence was 0.32% (95% confidence interval [CI] 0.087-1.14), all non-fatal DVTs. The 30-day incidence of major and total bleeding events was 1.26% (95% CI 0.64-2.47) and 3.00% (95% CI 1.93-4.63), respectively. The all-cause mortality rate was 0.32% (95% CI 0.087-1.14) at 30 days; two patients died from arterial thrombosis events. A randomized controlled trial is needed to provide definitive conclusions but a conservative bridging approach appears promising.