scholarly journals Antithrombotic Management in Ischemic Stroke with Essential Thrombocythemia: Current Evidence and Dilemmas

Author(s):  
Shubhabrata Das ◽  
Anasua Deb

Thrombotic diseases like ischemic stroke are common complications of essential thrombocythemia (ET) due to abnormal megakaryopoiesis and platelet dysfunction. Ischemic stroke in ET can occur as a result of both cerebral arterial and venous thrombosis. Management of ET is aimed at preventing vascular complications including thrombosis. Acute management of ischemic stroke in ET is the same as that in the general population without myeloproliferative disorder. However, an ET patient with ischemic stroke is at high risk for re-thrombosis and therefore additionally managed with cytoreductive therapy and antithrombotic agents. Given abnormal platelet production in ET, there is suboptimal suppression of platelets with the usual recommended dose of Aspirin for cardiovascular (CV) prevention. Hence, for optimal CV protection in ET, low dose Aspirin is recommended twice daily in an arterial thrombotic disease like atherothrombotic ischemic stroke in presence of the following risk factors: age > 60 years, Janus kinase2V617F gene mutation, presence of CV risk factors. In presence of the same risk factors, concurrent antiplatelet and anticoagulant therapy is suggested for venous thrombosis. However, increased risk of bleeding with dual anti-thrombotic agents poses a significant challenge in their use in cerebral venous thromboembolism or, atrial fibrillation in presence of the above-mentioned risk factors. We discuss these dilemmas about antithrombotic management in ischemic stroke in ET in this cased based review of literature in the light of current evidence.

Blood ◽  
2010 ◽  
Vol 116 (8) ◽  
pp. 1205-1210 ◽  
Author(s):  
Alberto Alvarez-Larrán ◽  
Francisco Cervantes ◽  
Arturo Pereira ◽  
Eduardo Arellano-Rodrigo ◽  
Virginia Pérez-Andreu ◽  
...  

Abstract The effectiveness of antiplatelet therapy as primary prophylaxis for thrombosis in low-risk essential thrombocythemia (ET) is not proven. In this study, the incidence rates of arterial and venous thrombosis were retrospectively analyzed in 300 low-risk patients with ET treated with antiplatelet drugs as monotherapy (n = 198) or followed with careful observation (n = 102). Follow-up was 802 and 848 person-years for antiplatelet therapy and observation, respectively. Rates of thrombotic events were 21.2 and 17.7 per 1000 person-years for antiplatelet therapy and observation, respectively (P = .6). JAK2 V617F–positive patients not receiving antiplatelet medication showed an increased risk of venous thrombosis (incidence rate ratio [IRR]: 4.0; 95% CI: 1.2-12.9; P = .02). Patients with cardiovascular risk factors had increased rates of arterial thrombosis while on observation (IRR: 2.5; 95% CI: 1.02-6.1; P = .047). An increased risk of major bleeding was observed in patients with platelet count greater than 1000 × 109/L under antiplatelet therapy (IRR: 5.4; 95% CI: 1.7-17.2; P = .004). In conclusion, antiplatelet therapy reduces the incidence of venous thrombosis in patients with JAK2-positive ET and the rate of arterial thrombosis in patients with associated cardiovascular risk factors. In the remaining low-risk patients, this therapy is not effective as primary prophylaxis of thrombosis, and observation may be an adequate option.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3906-3906
Author(s):  
Alberto Alvarez-Larrán ◽  
Francisco Cervantes ◽  
Eduardo Arellano-Rodrigo ◽  
Virginia Pérez-Andreu ◽  
Juan-Carlos Hernández-Boluda ◽  
...  

Abstract Abstract 3906 Poster Board III-842 Essential thrombocythemia (ET) patients under the age of 60 years without history of thrombosis are not considered candidates for cytoreductive therapy. In these patients, risk factors for thrombosis as well as the benefit of platelet antiaggregants are not well established. The aim of the present study was to determine the risk factors for thrombosis in ET patients without indication of cytoreductive therapy and to assess the effect of platelet antiaggregation in thrombosis prevention. For such purpose 300 patients (101 M, 199F) diagnosed with ET at a median age of 39 years (range 5-59) were included in a multicenter retrospective study. Initial treatment consisted of platelet antiaggregants (n=196) or observation (n=104). During a median follow up of 8.6 years (range: 0.2-25), 137 patients initiated cytoreductive therapy being the indication for cytoreduction age > 60 years (n=18), thrombosis (n=25), bleeding (n=13), microvascular symptoms not responding to platelet antiaggregants (n=37), extreme thrombocytosis (n=37) and other (n=7). Median time free of cytoreductive therapy was 4.4 years (Range: 0.1-25). Thrombosis-free survival restricted to the time of cytoreductive therapy abstention was calculated using the Kaplan-Meier method. Variables attaining a significant level at the univariate analysis were included in a Cox proportional hazard model. A total of 32 thromboses (arterial thrombosis: n=21, vein thrombosis: n= 11) were registered during the period of cytoreduction abstention. The probability of survival free of arterial thrombosis was 94% at five years. Elevated serum LDH levels at ET diagnosis and smoking were associated with an increased risk of arterial thrombosis, hazard ratio: 3.1 (CI95%: 1.1-8.3) and 2.9 (CI95%: 1.1-7.9) for LDH and smoking respectively. Age, gender, hypertension, diabetes mellitus, hypercholesterolemia, leukocytosis, thrombocytosis and JAK2 mutational status were not associated with an increased risk of arterial thrombosis. Platelet antiaggregant therapy did not reduce the incidence of arterial thrombosis. The probability of survival free of venous thrombosis was 96% at five years. Patients with JAK2V617F mutation showed and increased risk of venous thrombosis: HR 4.6 (IC95%: 1.1-18.3) whereas platelet antiaggregant therapy resulted in a low risk of venous thrombosis: HR 0.12 (CI95%: 0.03-0.5). When analysis was restricted to patients with the JAK2V617F mutation, the probability of venous thrombosis at 5 years was 96% in those patients receiving platelet antiaggregants and 58% in those patients managed with observation alone (p=0.0006). Platelet antiaggregant therapy was not associated with an increased risk of severe/major bleeding. In conclusion, JAK2V617F-positive ET patients without indication of cytoreductive therapy have an increased risk of venous thrombosis that could be reverted with platelet antiaggregant therapy. Disclosures: No relevant conflicts of interest to declare.


2020 ◽  
Vol 18 (5) ◽  
pp. 431-446 ◽  
Author(s):  
George E. Fragoulis ◽  
Ismini Panayotidis ◽  
Elena Nikiphorou

Rheumatoid arthritis (RA) is an autoimmune inflammatory arthritis. Inflammation, however, can spread beyond the joints to involve other organs. During the past few years, it has been well recognized that RA associates with increased risk for cardiovascular (CV) disease (CVD) compared with the general population. This seems to be due not only to the increased occurrence in RA of classical CVD risk factors and comorbidities like smoking, obesity, hypertension, diabetes, metabolic syndrome, and others but also to the inflammatory burden that RA itself carries. This is not unexpected given the strong links between inflammation and atherosclerosis and CVD. It has been shown that inflammatory cytokines which are present in abundance in RA play a significant role in every step of plaque formation and rupture. Most of the therapeutic regimes used in RA treatment seem to offer significant benefits to that end. However, more studies are needed to clarify the effect of these drugs on various parameters, including the lipid profile. Of note, although pharmacological intervention significantly helps reduce the inflammatory burden and therefore the CVD risk, control of the so-called classical risk factors is equally important. Herein, we review the current evidence for the underlying pathogenic mechanisms linking inflammation with CVD in the context of RA and reflect on the possible impact of treatments used in RA.


Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Ava L Liberman ◽  
Alexander E Merkler ◽  
Gino Gialdini ◽  
Michael P Lerario ◽  
Steven R Messe ◽  
...  

Introduction: Cerebral vein thrombosis (CVT) is associated with an increased risk of subsequent venous thromboembolism. It is unknown whether the risk of pulmonary embolism (PE) after CVT is similar to that of PE after deep venous thrombosis (DVT). Methods: We performed a retrospective cohort study using administrative claims data from all emergency department visits and hospitalizations in California from 2005-2011, New York from 2006-2013, and Florida from 2005-2013. We identified patients with CVT or DVT as well as the primary outcome of PE using previously validated International Classification of Diseases, Ninth Revision, Clinical Modification ( ICD-9-CM ) codes. In order to minimize misclassification error, patients with both CVT and DVT during the same index hospitalization were excluded and patients with CVT were censored at the time of development of DVT and vice versa. Kaplan-Meier survival statistics and Cox proportional hazards models were used to compare the risk of PE after CVT versus after DVT while adjusting for demographics, vascular risk factors, and the Elixhauser comorbidity index. Results: We identified 4,450 patients with CVT and 217,589 patients with DVT. During a mean follow-up of 2.0 (±1.7) years, 124 patients with DVT developed a PE and 18,698 patients with DVT developed a PE. Patients with CVT were younger (mean age 45 vs 63), more often female (71% vs 52%), more often pregnant, and had fewer vascular risk factors than patients with DVT. During the index hospitalization, the rate of PE was 1.5% (95% confidence interval [CI], 1.1-1.8%) in patients with CVT and 6.2% (95% CI, 6.1-6.3%, p<0.001) in patients with DVT. By 5 years, the cumulative rate of PE after CVT was 3.7% (95% CI, 3.0-4.4%) compared to 10.5% (95% CI, 10.3-10.6%, p<0.001) after DVT. After adjustment for demographics and comorbidities, CVT was associated with a significantly lower hazard of PE when compared to DVT (hazard ratio, 0.31; 95% CI, 0.26-0.38). Conclusion: In a large, heterogeneous population, we found that the risk of PE after CVT was significantly lower than that of PE after DVT. Among patients with CVT, the greatest risk for PE was apparent during the index hospitalization.


2021 ◽  
Vol 10 (4) ◽  
Author(s):  
Pietro Enea Lazzerini ◽  
Gabriele Cevenini ◽  
Yongxia Sarah Qu ◽  
Frank Fabris ◽  
Nabil El‐Sherif ◽  
...  

Background Anti‐Sjögren's syndrome‐related antigen A‐antibodies (anti‐Ro/SSA‐antibodies) are responsible for a novel form of acquired long‐QT syndrome, owing to autoimmune‐mediated inhibition of cardiac human ether‐a‐go‐go‐related gene‐potassium channels. However, current evidence derives only from basic mechanistic studies and relatively small sample‐size clinical investigations. Hence, the aim of our study is to estimate the risk of QTc prolongation associated with the presence of anti‐Ro/SSA‐antibodies in a large population of unselected subjects. Methods and Results This is a retrospective observational cohort study using the Veterans Affairs Informatics and Computing Infrastructure. Participants were veterans who were tested for anti‐Ro/SSA status and had an ECG. Descriptive statistics and univariate and multivariate logistic regression analyses were performed to identify risk factors for heart rate‐corrected QT interval (QTc) prolongation. The study population consisted of 7339 subjects (61.4±12.2 years), 612 of whom were anti‐Ro/SSA‐positive (8.3%). Subjects who were anti‐Ro/SSA‐positive showed an increased prevalence of QTc prolongation, in the presence of other concomitant risk factors (crude odds ratios [OR], 1.67 [1.26–2.21] for QTc >470/480 ms; 2.32 [1.54–3.49] for QTc >490 ms; 2.77 [1.66–4.60] for QTc >500 ms), independent of a connective tissue disease history. Adjustments for age, sex, electrolytes, cardiovascular risk factors/diseases, and medications gradually attenuated QTc prolongation estimates, particularly when QT‐prolonging drugs were added to the model. Nevertheless, stepwise‐fully adjusted OR for the higher cutoffs remained significantly increased in anti‐Ro/SSA‐positive subjects, particularly for QTc >500 ms (2.27 [1.34–3.87]). Conclusions Anti‐Ro/SSA‐antibody positivity was independently associated with an increased risk of marked QTc prolongation in a large cohort of US veterans. Our data suggest that within the general population individuals who are anti‐Ro/SSA‐positive may represent a subgroup of patients particularly predisposed to ventricular arrhythmias/sudden cardiac death.


2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi148-vi148
Author(s):  
Alexander Ou ◽  
Heather Lin ◽  
Ying Yuan ◽  
Charles Bornstein ◽  
Kristin Alfaro-Munoz ◽  
...  

Abstract BACKGROUND Patients with high-grade gliomas (HGG) often receive anti-angiogenic therapy with bevacizumab to slow disease progression and/or palliate neurological symptoms. Bevacizumab has been associated with an increased risk of two major vascular complications: venous thromboembolism (VTE) and intracranial hemorrhage (ICH). We sought to identify clinical, pathologic, and radiographic variables correlated with risk of either event occurring in patients with HGG receiving bevacizumab. METHODS We retrospectively identified 94 patients with HGG who received bevacizumab at our center from 2015-2021. Variables included demographics, performance status, IDH, MGMT, vascular risk factors, baseline anti-coagulant/anti-platelet use, concurrent chemotherapy, and presence of macrobleeds on MRI (&gt;1 cm3 susceptibility) at the time of bevacizumab initiation. We conducted competing risk analysis using subdistribution hazard models with death as competing risk for ICH or VTE. The effects of covariates on the incidence of hemorrhage or VTE were evaluated in univariate and multivariate settings. RESULTS Of 94 patients, 36 (38.3%) and 27 (28.7%) developed VTE and ICH, respectively. 31 (33%) did not develop either. ICH and VTE events occurred after a mean of 4.46 and 5.94 cycles of bevacizumab, respectively. 20 had baseline anti-platelet/anticoagulant use, and 16 had prior VTEs. Patients with macrobleeds on MRI had a larger HR of developing acute hemorrhage [HR=2.368 (1.112, 5.043), p=0.0254]. Patients older than 50 trended toward larger HR of developing VTE in univariate analysis that approached significance [HR=1.799 (0.889, 3.637), p=0.1023]. Sex, performance status, IDH, MGMT, vascular risk factors, baseline anticoagulant/anti-platelet use and concurrent chemotherapy were not significantly associated with occurrence of VTE. CONCLUSIONS The presence of macrobleeds on MRI is associated with increased risk of developing acute ICH while on bevacizumab. Older age at diagnosis of HGG may be associated with an increased risk of VTE in patients receiving bevacizumab. Larger studies are needed to confirm these findings.


Rheumatology ◽  
2019 ◽  
Vol 58 (Supplement_4) ◽  
Author(s):  
Kishore Warrier1 ◽  
Catherine Salvesani ◽  
Samundeeswari Deepak

Abstract Background Rituximab is a chimeric monoclonal antibody that depletes the B cell population by targeting cells bearing the CD20 surface marker and is used widely in the management of paediatric rheumatological conditions like juvenile systemic lupus erythematosus (JSLE), juvenile dermatomyositis (JDM), mixed connective tissue disease (MCTD) and juvenile idiopathic arthritis (JIA). Pneumocystis jirovecii pneumonia (PCP) is a potentially fatal opportunistic infection associated with congenital and acquired defects in T cell–mediated immunity. Our guideline did not recommend prophylaxis against PCP for patients on rituximab, unlike patients on cyclophosphamide, who are on cotrimoxazole until three months after cessation of the treatment. Cyclophosphamide is an alkylating agent which affects both B and T lymphocytes. Following the death of 16 year-old girl with JSLE due to PCP, the team reviewed the possible contributing factors, undertook a review of literature and discussed this at multi-disciplinary meetings involving the microbiology and immunology teams. This patient was found to have other risk factors for PCP – low CD4 T cells, concomitant use of corticosteroids and hypogammaglobulinaemia (IgG 3.0g/L). Although there is limited evidence that rituximab on its own increases the risk of PCP, there is emerging data that B cells may have a role in the protection against pneumocystis. Following the review, it was concluded that children on rituximab and an additional immunosuppressant (including corticosteroids) should receive prophylactic cotrimoxazole to cover PCP. Methods Retrospective audit carried out by the team to look at adherence to the new guideline regarding the use of cotrimoxazole for PCP prophylaxis in patients who have had rituximab between August 2017 and May 2019. Results P54 Table 1 Total number of patients who had rituximab 10 Number of patients who had other immunosuppressants concomitantly / recently (within previous 3 months) 7 Number of patients on rituximab monotherapy 2 Number of patients who are 6 months post-treatment 1 Number of patients with other risk factors for PCP 1 (hypogammaglobulinaemia) Number of patients who are eligible for prophylaxis, as per the guideline 8 (7 for concomitant immunosuppression and 1 for hypogammaglobulinaemia) Number of patients on cotrimoxazole 7 (87.5%) - one of the patients is on methotrexate, which is advised not to combine with cotrimoxazole We achieved 87.5% compliance in prescribing cotrimoxazole for PCP prophylaxis to all rheumatology patients receiving rituximab alongside another immunosuppressant agent; the one patient who this was not adhered to was due to potential adverse drug pharmacodynamic interaction between cotrimoxazole and methotrexate. Conclusion Although the current evidence points to increased risk of PCP in patients with inherited and iatrogenic defect of T cell function, there is emerging evidence that B cells may have a role too. Hence more work is required to determine the risk of PCP in patients on B cell targeted therapy (BCTT) and the need for prophylaxis. Conflicts of Interest The authors declare no conflicts of interest.


Author(s):  
Naser A. Alsharairi

Asthma is a chronic respiratory disease which is associated with higher levels of systemic inflammation. The causes of asthma remain poorly understood. Unhealthy diet and food allergy are potential risk factors for developing asthma. The prevalence of asthma in the Arabian Gulf region (AGR), and Kuwait, Saudi Arabia and Qatar in particular, is higher than in other Eastern Mediterranean countries. In the AGR, diets tend to be of low nutritional value due to high levels of total energy, cholesterol, sodium, added sugars and saturated fat, and low levels of fiber, fruit and vegetables. A few studies that include children and adults in the AGR have suggested a potential link between unhealthy diets/specific food allergens and increased risk of asthma, however, the association of food allergy with asthma is still a controversial issue. The aim of this commentary is to consider the evidence from the AGR regarding the effects of diet/food allergy on asthma risk that may be used to make recommendations for future research.


2019 ◽  
Vol 26 (2_suppl) ◽  
pp. 47-54 ◽  
Author(s):  
JWJ Beulens ◽  
F Rutters ◽  
L Rydén ◽  
O Schnell ◽  
L Mellbin ◽  
...  

Type 2 diabetes mellitus (T2DM) is associated with a two- to four-fold increased risk of developing cardiovascular disease (CVD) and microvascular complications, which may already be present before diagnosis. It is, therefore, important to detect people with an increased risk of T2DM at an early stage. In order to identify individuals with so-called ‘pre-diabetes’, comprising impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), current guidelines have developed definitions based on fasting plasma glucose, two-hour glucose concentrations and haemoglobin A1c. Subjects with pre-diabetes are at an increased risk of developing T2DM and CVD. This elevated risk seems similar according to the different criteria used to define pre-diabetes. The risk of progression to T2DM or CVD does, however, depend on other risk factors such as sex, body mass index and ethnicity. Based on the risk factors to develop T2DM, many risk assessment models have been developed to identify those at highest risk. These models perform well to identify those at risk and could be used to initiate preventive interventions. Many studies have shown that lifestyle modification and metformin are effective in preventing the development of T2DM, although lifestyle modification seems to have a more sustainable effect. In addition, lifestyle modification seems more effective in those with IGT than those with IFG. In this review, we will describe the different definitions used to define pre-diabetes, progression from pre-diabetes to T2DM or other vascular complications, risk factors associated with progressions and the management of progression to T2DM, ending with clinical recommendations.


2020 ◽  
Vol 49 (3) ◽  
pp. 341-344 ◽  
Author(s):  
Carlo Emanuele Saggese ◽  
Chiara Del Bianco ◽  
Maria Rita Di Ruzza ◽  
Maria Magarelli ◽  
Roberto Gandini ◽  
...  

Background: The COVID-19 outbreak is currently the major public health concern worldwide. This infection, caused by the novel coronavirus Sars Cov2, primarily affects respiratory system, but there is increasing evidence of neurologic involvement and cerebrovascular accidents. Case Report: We present a case of stroke in a 62-year-old COVID-19-positive patient, with multiple vascular risk factors. The patient arrived 1 h after onset of symptoms, was treated with recombinant tissue plasminogen activator (rtPA) with improvement of neurologic deficits, and later developed right foot arterial ischemia (recanalized by balloon catheter angioplasty) and left arm superficial venous thrombosis. A control computed tomography (CT) scan 7 days after onset showed hemorrhagic transformation of ischemic lesion without mass effect. However, respiratory and neurologic conditions improved so that the patient was discharged to rehabilitation. Discussion: Until now, few cases of stroke in COVID-19 have been described, mainly in severe forms. This patient had ischemic injuries in different sites as well as venous thrombosis; hence, we speculate that Sars Cov2 could have a direct role in promoting vascular accidents since its receptor ACE2 is a surface protein also expressed by endothelial cells. This case suggests that COVID-19 can favor strokes and in general vascular complications, even in milder cases, and the presence of preexisting risk factors could play a determinant role.


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