scholarly journals Coexistent antiphospholipid syndrome and myeloproliferative neoplasm

Lupus ◽  
2021 ◽  
pp. 096120332110211
Author(s):  
Zara Sayar ◽  
Susanna Nallamilli ◽  
Maria Efthymiou ◽  
Jonathan Lambert ◽  
Hannah Cohen

Antiphospholipid syndrome (APS) and myeloproliferative neoplasms (MPN) are associated with an increased risk of thrombosis. The optimal management of patients with coexistent APS and MPN has not been defined. A single centre and systematic literature review of patients with coexistent APS and MPN was performed. Cases were divided into two groups based on whether they met international consensus criteria for APS. Of the 12 studies identified, eight were excluded (leaving five of a total 54 patients), as although antiphospholipid antibodies (aPL) were documented, the diagnosis of APS was not conclusively demonstrated. Another ten patients with definite APS were identified at our centre. Fifteen patients (ten females, five males) were therefore included in this analysis (eleven definite APS and four highly likely), median age 44 (range: 13–71) years. Nine had polycythaemia vera and six, essential thrombocythaemia. Thirteen of the 15 patients (86.7%) had thrombotic APS (seven with initial venous events and six arterial) and two (13.3%) had obstetric APS. Nine patients were single-positive, and six double-positive for aPL. None were triple aPL-positive. Four patients at our centre had recurrent thrombotic/obstetric events, including while on anticoagulation/antiplatelet treatment.

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1039.2-1039
Author(s):  
S. Vardanyan ◽  
K. Ginosyan ◽  
V. Vardanyan ◽  
A. Sargsyan ◽  
A. Simonyan

Background:Chronic anticoagulation with vitamin K antagonists (VKA) is the standard treatment to prevent thrombotic events in antiphospholipid syndrome (APS). But in recent years treatment schemes began to include rivaroxaban. Use of direct oral anticoagulants (DOAC) is an attractive and often preferred alternative to VKAs in other medical settings owing to greater ease of use, fewer food and drug interactions, and lower bleeding risks [1].However, according to last guidelines, rivaroxaban should not be used in patients with triple aPL positivity due to the high risk of recurrent events [2].Objectives:1.To determine the risk of recurrent thrombosis in single or double positive APS patients treated with rivaroxaban.2.Find out possible association between presence of particular antiphospholipid antibodies or high level of lupus anticoagulant (LA) and type of vascular events.Methods:33 patients with confirmed APS (25 female (75.8%), 8 male (24.2%), mean age 43.2±11.6 years) were included in the study. 17 (51.5%) of investigated patients had primary APS, in remaining 16 (48.5%) APS was included in the framework of SLE. 18 (54.5%) patients were treated with warfarin 2.5-7.5 mg/daily, 15 (45.5%) patients - with rivaroxaban 20mg/daily for a follow-up period of 12 months. The data is introduced as odds ratios (OR) with 95% confidence interval (CI). The results were considered significant when p <0.05.Results:At baseline 21 (63.6%) patients had history of arterial thrombosis, 10 (30.3%) - venous thrombosis, 17 (51.5%) - pregnancy loss. According to results of serum immunology check, 29 (87.9%) patients were anticardiolipin antibody (ACA) positive, 9 (27.3%) - LA positive, 19 (57.6%) - anti-ß2-glycoprotein antibodies (anti-ß2-gp) positive; 20 (60.6%) patients were double positive (12 (36.4%) of them had positive ACA and anti-ß2-gp, 6 (18.2%) - ACA and LA, and 2 (6.1%) - anti-ß2-gp and LA), 4 (12.1%) patients were triple positive.No association between vascular event and/or pregnancy loss in patients with single positive ACA was found. We have found positive association between arterial thrombosis and single positive anti-ß2-gp (OR /CI 95%/ = 5.0 /2.08 – 23.06/, p< 0.05), positive association between positive LA and venous thrombosis (OR /CI 95%/ = 10 /1.7-57.7/, p< 0.05), strong positive association between positive LA and thromboembolism of pulmonary artery (OR /CI 95%/ = 46.0 /4.0-525.1/, p< 0.001), negative association between positive LA and pregnancy loss (OR /CI 95%/ =0.06 /0.03 – 0.1/, p< 0.01).Risk of thrombosis and/or pregnancy loss was not significantly increased in double positive patients, but triple positive patients had increased risk of venous thrombosis (OR /CI 95%/ =9.4 /3.2 – 105.8/, p<0.04).Recurrent thrombosis was detected in 16 patients: 2 patients (12.5%) were on warfarin, 14 (87.5%) - on rivaroxaban (10 (71.4%) arterial thrombosis, 4 (28.6%) venous thrombosis).No association between warfarin 2.5-7.5 mg/daily and occurrence of recurrent thrombosis was detected. An association between use of warfarin and increased risk of bleeding was found, but the risk was not significant (OR /CI 95%/ = 7.0 /0.7 – 66/, p= 0.09). Rivaroxaban 20 mg/daily was associated with recurrent thrombosis not only for triple positive patients (p< 0.02), but also in double positive patients (OR /CI 95%/ = 21.3 /1.8 – 251/, p< 0.04).Conclusion:Rivaroxaban does not prevent recurrent thrombosis not only in triple positive patients, but also in single and double positive APS patients. Type of antiphospholipid antibodies can be predictive for the type of further vascular event.References:[1]Vittorio Pengo, Gentian Denas, Giacomo Zoppellaro et al.Rivroxaban vs warfarin in high risk patients with antiphospholipid syndrome, Blood. 2018 Sep 27; 132(13); 1357-1358.[2]EULAR recommendations for the management of antiphospholipid syndrome in adults, Annals of the Rheumatic Diseases/ Volume 78: Issue 10:1296-1304.Disclosure of Interests:None declared


Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2202 ◽  
Author(s):  
Sarah Friis Christensen ◽  
Robyn Marie Scherber ◽  
Nana Brochmann ◽  
Martin Goros ◽  
Jonathan Gelfond ◽  
...  

Elevated body mass index (BMI) is a global health problem, leading to enhanced mortality and the increased risk of several cancers including essential thrombocythemia (ET), a subtype of the Philadelphia-chromosome negative myeloproliferative neoplasms (MPN). Furthermore, evidence states that BMI is associated with the severity of symptom burden among cancer patients. MPN patients often suffer from severe symptom burden. The purpose of this study was to examine whether deviations from a normal BMI in an MPN population are associated with higher symptom burden and reduced quality of life (QoL). A combined analysis of two large cross-sectional surveys, the Danish Population-based Study, MPNhealthSurvey (n = 2044), and the international Fatigue Study (n = 1070), was performed. Symptoms and QoL were assessed using the validated Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF). Analysis of covariance was used to estimate the effects of different BMI categories on symptom scores while adjusting for age, sex, and MPN subtype. A U-shaped association between BMI and Total Symptom Burden was observed in both datasets with significantly higher mean scores for underweight and obese patients relative to normal weight (mean difference: underweight 5.51 (25.8%), p = 0.006; obese 5.70 (26.6%) p < 0.001). This is an important finding, as BMI is a potentially modifiable factor in the care of MPN patients.


2021 ◽  
Author(s):  
Daniel H Kwon ◽  
Jose Eduardo Cadena Pico ◽  
Sam Nguyen ◽  
Kwan Ho Ryan Chan ◽  
Brian Soper ◽  
...  

Background: Patients with cancer are at risk for poor COVID-19 outcomes. We aimed to identify cancer-related risk factors for poor COVID-19 outcomes. Patients and Methods: We conducted a retrospective cohort study using the University of California Health COVID Research Data Set. This database includes prospectively-collected, electronic health data of patients who underwent testing for SARS-CoV-2 at seventeen California medical centers. We identified adult patients tested for SARS-CoV-2 between February 1, 2020 and December 31, 2020, and selected a cohort of patients with cancer using diagnostic codes. We obtained demographic, comorbidity, laboratory, cancer type, and antineoplastic therapy data. The primary outcome was hospitalization within 30 days after first positive SARS-CoV-2 test. Secondary outcomes were SARS-CoV-2 positivity and composite endpoint for severe COVID-19 (intensive care, mechanical ventilation, or death within 30 days after first positive test). We used multivariable logistic regression to identify cancer-related factors associated with outcomes. Results: We identified 409,462 patients undergoing SARS-CoV-2 testing. Of 49,918 patients with cancer, 1,781 (3.6%) tested positive. Patients with cancer were less likely to test positive (OR 0.69, 95%CI 0.66-0.73, P<0.001). BCR-ABL-negative myeloproliferative neoplasms (polycythemia vera, essential thrombocythemia, and primary myelofibrosis) (OR 2.51, 95%CI 1.29-4.89, P=0.007); venetoclax (OR 3.63, 95%CI 1.02-12.92, P=0.046); methotrexate (OR 3.65, 95%CI 1.17-11.37, P=0.026); Asian race (OR 1.92, 95%CI 1.23-2.98, P=0.004); and Hispanic/Latino ethnicity (OR 1.96, 95%CI 1.41-2.73, P<0.001) were associated with increased hospitalization risk. Among 388 hospitalized patients with cancer and COVID-19, cancer type and therapy type were not associated with severe COVID-19. Conclusions: In this large, diverse cohort of Californians, cancer was not a risk factor for SARS-CoV-2 positivity. Patients with BCR/ABL-negative myeloproliferative neoplasm and patients receiving methotrexate or venetoclax may be at an increased risk of hospitalization following SARS-CoV-2 infection. Further mechanistic and comparative studies are needed to explain and confirm our findings.


2021 ◽  
Vol 28 ◽  
pp. 107327482110468
Author(s):  
Niloofar Allahverdi ◽  
Mohamed Yassin ◽  
Mohamed Ibrahim

Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell disorders characterized by the overproduction of mature myeloid cells and are often associated with an acquired genetic mutation of Janus Kinase2V617F. Various epidemiological studies have indicated associations between environmental factors, lifestyle factors, and host characteristics with developing MPNs. This review aims to collect and summarize the existing information on these risk factors and establish their association with pathogenesis MPNs. Medline, Embase, PubMed, and grey literature were systematically searched using key terms for MPNs, and epidemiological study designs, that is, cross-sectional studies, case-control, and cohort, that investigated the risk factors for MPNs published were identified. Out of the 4621 articles identified, 20 met the selection criteria and were included in this review. Heterogeneity, study reliability, and bias were assessed. A significant association was found between smoking and the development of MPNs. This relationship has been explained by the substantial increase in several proinflammatory mediators and systematic oxidative stress causing hyperstimulation of myeloid compartments leading to the development of MPNs. Obesity was modestly linked with an increased risk of MPNs. The underlying mechanisms have been linked to changes in endocrine, metabolic, and inflammatory systems. No strong association was found between exposure to hazardous substances, that is, benzene and MPNs, but further investigation on the effects of increased levels and duration of exposure on hematopoietic stem cells will be beneficial. Unique individual and host variations have been determined as a modifier of disease pathogenesis and phenotype variations. There is a higher incidence rate of females developing MPNs, specifically ET, than males with higher PV incidence. Therefore, gender contributes to the heterogeneity in myeloproliferative neoplasm. Studies identified as part of this review are very diverse. Thus, further in-depth assessment to explore the role of these etiological factors associated with MPNs is warranted.


Lupus ◽  
2019 ◽  
Vol 29 (1) ◽  
pp. 37-44 ◽  
Author(s):  
K Malec ◽  
E Broniatowska ◽  
A Undas

Objectives Despite controversies, direct oral anticoagulants (DOACs) are increasingly used in antiphospholipid syndrome (APS). We investigated the safety and efficacy of DOACs versus vitamin K antagonists (VKAs) in real-life consecutive APS patients. Patients and methods In a cohort study of 176 APS patients, which included 82 subjects who preferred DOACs or had unstable anticoagulation with VKAs, we recorded venous thromboembolism (VTE), cerebrovascular ischemic events or myocardial infarction, along with major bleeding or clinically relevant non-major bleeding (CRNMB). Results APS patients were followed for a median time of 51 (interquartile range 43–63) months. Patients on DOACs and those on VKAs were similar with regard to baseline characteristics. APS patients treated with DOACs had increased risk of recurrent thromboembolic events and recurrent VTE alone compared with those on VKAs (hazard ratio (HR) = 3.98, 95% confidence interval (CI): 1.54–10.28, p = 0.004 and HR = 3.69, 95% CI: 1.27–10.68, p = 0.016, respectively) with no differences between rivaroxaban and apixaban or single- or double-positive and triple-positive APS. Thromboembolism on DOACs was associated with older age (median 52 versus 42 years, p = 0.008) and higher global APS score (median 13 versus 8.5, p = 0.013). Patients on DOACs had increased risk of major bleeding or CRNMB (HR = 3.63, 95% CI: 1.53–8.63, p = 0.003), but rates of gastrointestinal bleeds (HR = 3.36, 95% CI: 0.70–16.16, p = 0.13) and major bleeds or CRNMB other than heavy menstrual bleeding (HR = 2.45, 95% CI: 0.62–9.69, p = 0.2) were similar in both treatment groups. Conclusion During long-term follow-up of real-life APS patients, DOACs are less effective and less safe as VKAs in the prevention of thromboembolism.


2019 ◽  
Vol 2019 ◽  
pp. 1-4 ◽  
Author(s):  
Andréanne Durivage ◽  
Geneviève Le Templier ◽  
Annabelle Cumyn ◽  
Nadine Sauvé

Extra-hepatic portal vein thrombosis (EHPVO) represents the obstruction of the portal vein outside the liver and is not related to chronic liver disease or neoplasia. In chronic EHPVO, collateral veins and portal hypertension develop, resulting in splenomegaly and variceal formation. Myeloproliferative neoplasms (MPN) are the most frequent acquired etiology of EHPVO. These conditions put pregnant women at increased risk of vascular complications, including venous thrombosis, occlusion of the placental circulation, and variceal bleeding. In this report, we present a 36-year-old pregnant woman with chronic, anticoagulated EHPVO secondary to latent MPN who developed severe intrauterine growth restriction and had cesarean section at 32+1 weeks for increased umbilical doppler resistance and breech presentation. The article will emphasize outcome and management of pregnancies complicated by chronic EHPVO, portal hypertension, and MPN.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e19533-e19533
Author(s):  
Dilhan Weeraratne ◽  
Hu Huang ◽  
David Brotman ◽  
Shang Xue ◽  
Young Kyung Lee ◽  
...  

e19533 Background: Therapeutic, prognostic, and diagnostic insights gained from next generation sequencing (NGS) are a key premise of genomics-informed cancer care in hematological diseases. Particularly in BCR-ABL negative myeloproliferative neoplasms (MPN), insights gained from NGS is integral for risk stratification and prognostication. In this study, MPN patients of South Korean descent were sequenced, interpreted, and compared with a published validation cohort to identify variations in mutational profiles specific to demographics. Methods: 31 South Korean MPN patients including 12 essential thrombocythemia, 6 polycythemia vera, 6 primary myelofibrosis, and 7 chronic myelogenous leukemia were sequenced in 2018 and 2019 using the 54 gene Illumina TruSight Myeloid Panel at Hallym University College of Medicine. Orthogonal testing for CALR mutations was done by Sanger sequencing. Watson for Genomics (WfG), an artificial intelligence offering was used for variant interpretation and annotation. A cohort of 151 MPN patients previously published in the New England Journal of Medicine (NEJM) was used for comparison (PMID:24325359). Results: The table shows identified actionable mutations. Conclusions: Two novel pathogenic mutations in CALR (c.1162delG and c.1100_1145del)) were identified in Korean MPN patients. NOTCH1 pathogenic mutations were exclusive while TP53 mutations were significantly enriched in the Korean cohort suggesting that these pathways may play a role in MPN. TP53 mutations in MPN are clinically significant as they have been associated with increased risk for leukemic transformation. Of note, MPL mutations were not detected in the Korean cohort. In conclusion, race and ethnicity may contribute to some mutational signatures in cancer. [Table: see text]


2015 ◽  
Vol 113 (01) ◽  
pp. 13-19 ◽  
Author(s):  
Samuel J. Machin ◽  
Ian J. Mackie ◽  
Hannah Cohen ◽  
Deepa R. Jayakody Arachchillage

SummaryAccurate diagnosis of obstetric antiphospholipid syndrome (APS) is a prerequisite for optimal clinical management. The international consensus (revised Sapporo) criteria for obstetric APS do not include low positive anticardiolipin (aCL) and anti β2 glycoprotein I (aβ2GPI) antibodies (> 99th centile) and/or certain clinical criteria such as two unexplained miscarriages, three non-consecutive miscarriages, late preeclampsia, placental abruption, late premature birth, or two or more unexplained in vitro fertilisation failures. In this review we examine the available evidence to address the question of whether patients who exhibit non-criteria clinical and/or laboratory manifestations should be included within the spectrum of obstetric APS. Prospective and retrospective cohort studies of women with pregnancy morbidity, particularly recurrent pregnancy loss, suggest that elimination of aCL and/or IgM aβ2GPI, or low positive positive aCL or aβ2GPI from APS laboratory diagnostic criteria may result in missing the diagnosis in a sizeable number of women who could be regarded to have obstetric APS. Such prospective and retrospective studies also suggest that women with non-criteria obstetric APS may benefit from standard treatment for obstetric APS with low-molecular-weight heparin plus low-dose aspirin, with good pregnancy outcomes. Thus, non-criteria manifestations of obstetric APS may be clinically relevant, and merit investigation of therapeutic approaches. Women with obstetric APS appear to be at a higher risk than other women of pre-eclampsia, placenta- mediated complications and neonatal mortality, and also at increased long-term risk of thrombotic events. The applicability of these observations to outcomes in women with non-criteria obstetric APS remains to be determined.


Blood ◽  
2009 ◽  
Vol 113 (22) ◽  
pp. 5617-5623 ◽  
Author(s):  
Francesco Dentali ◽  
Alessandro Squizzato ◽  
Lorenza Brivio ◽  
Lorena Appio ◽  
Leonardo Campiotti ◽  
...  

Recent studies suggested that JAK2V617F mutation is frequent in patients with splanchnic vein thrombosis (SVT) but not in patients with other venous thromboembolic events (VTE). However, whether screening for the JAK2V617F mutation in VTE patients is justified remains unclear. Therefore, we performed a systematic review to assess the frequency of JAK2 mutation in VTE patients and the role of JAK2V617F mutation in the diagnosis of myeloproliferative neoplasms. MEDLINE and EMBASE databases were searched. Two reviewers independently performed study selection and extracted study characteristics. Pooled odds ratios of case-control studies and weighted mean proportion of the prevalence of JAK2V617F mutation of uncontrolled series were calculated. Twenty-four studies involving 3123 patients were included. Mean prevalence of JAK2 mutation was 32.7% (95% confidence interval, 25.5%-35.9%) in SVT patients. JAK2 mutation was associated with increased risk of SVT (odds ratio, 53.98; 95% confidence interval, 13.10-222.45). Mean prevalence of JAK2 mutation in other VTE patients was low (range, 0.88%-2.57%). Presence of JAK2V617F mutation in SVT patients was associated with a subsequent diagnosis of myeloproliferative neoplasm in many patients. JAK2 mutation is strongly associated with SVT, and routine screening of JAK2 mutation appears to be indicated in these patients.


2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Ahmet Burak Toros ◽  
Serkan Gokcay ◽  
Guven Cetin ◽  
Muhlis Cem Ar ◽  
Yesim Karagoz ◽  
...  

Background/Objectives. Patients with myeloproliferative neoplasms have a well-established increased risk of thrombosis. Many trials report identification of an underlying myeloproliferative neoplasm by investigation of the patients developing portal hypertensive esophagus and/or fundus variceal hemorrhage in the absence of any known etiology. This trial was designed to investigate the association between myeloproliferative neoplasms and portal hypertension and to detect the frequency of portal hypertension development in this subset of patients. Methodology. Twenty-nine patients previously diagnosed with polycythemia vera, essential thrombocytopenia, and primary myelofibrosis, who were under followup at the hematology outpatient clinic of our hospital, were included in the trial. Results. In our trial, we detected portal hypertension in 13.8% of the patients (n=4), as a finding that was similar to those obtained in other studies performed to date. Conclusions. Considering the fact that diagnosis of myeloproliferative neoplasms usually takes a long time, treatment should be started (while, on the other hand, assessing the investigational and therapeutical choices for the complications) right after the bone marrow biopsy or cytogenetic studies required for establishing the final diagnosis have been performed.


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