Application of prognostic score IPSET-thrombosis in patients with essential thrombocythemia of a Brazilian public service

Summary Introduction: In patients with essential thrombocythemia (ET), the vascular complications contribute to morbidity and mortality. To better predict the occurrence of thrombotic events, an International Prognostic Score for Thrombosis in Essential Thrombocythemia (IPSET-thrombosis) has recently been proposed. We present the application of this score and compare its results with the usual classification system. Method: We retrospectively evaluated the characteristics and risk factors for thrombosis of 46 patients with a diagnosis of ET seen in the last 6 years at Faculdade de Medicina do ABC (FMABC). Results: Thrombosis in the arterial territory was more prevalent than in venous sites. We observed that cardiovascular risk factors (hypertension, hypercholesterolemia, diabetes mellitus, and smoking) were also risk factors for thrombosis (p<0.001). Age over 60 years and presence of JAK2 V617F mutation were not associated with the occurrence of thrombotic events. No patient classified by IPSET-thrombosis as low risk had a thrombotic event. Furthermore, using the IPSET-thrombosis scale, we identified two patients who had thrombotic events during follow-up and were otherwise classified in the low-risk group of the traditional classification. Leukocytosis at diagnosis was significantly associated with arterial thrombosis (p=0.02), while splenomegaly was associated with venous thrombotic events (p=0.01). Conclusion: Cardiovascular risk factors and leukocytosis were directly associated with arterial thrombosis. IPSET-thrombosis appears to be better than the traditional classification at identifying lower risk patients who do not need specific therapy.

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Essential Thrombocythemia: Analysis of Risk Factors for Thrombotic Events in a Series of 306 Patients.

Blood ◽

10.1182/blood.v106.11.4937.4937 ◽

2005 ◽

Vol 106 (11) ◽

pp. 4937-4937

Author(s):

Franca Radaelli ◽

Stefania Bramanti ◽

Mariangela Colombi ◽

Alessandra Iurlo ◽

Alberto Zanella

Keyword(s):

Risk Factors ◽

Cardiovascular Risk ◽

Cardiovascular Risk Factors ◽

Essential Thrombocythemia ◽

Thrombotic Event ◽

Previous History ◽

Significant Difference ◽

Platelet Number ◽

History Of

Abstract Essential thrombocythemia (ET) is a chronic myeloproliferative disorder characterized by peripheral thrombocytosis and abnormal proliferation of megakariocytes in the bone marrow. Even thought thrombosis is frequently associated to ET, the risk factors of this clinical complication are still controversial. The aim of this retrospective, single institution study was to investigate clinical and laboratory characteristics associated with the occurrence of thrombotic events, with the purpose of identifying subgroups of patients who could benefit from antiaggregant and/or cytostatic treatment. 306 consecutive ET patients (109 men and 197 females, median age 58 yr) diagnosed between January 1979 and December 2002 were included in the study. At the time of analysis, 196 patients were still alive with a median follow up of 96 months. The following variables were investigated for the association with thrombotic complications: age, platelet count, previous history of thrombotic events, time from diagnosis, treatment with antiaggregant/cytostatic drugs, and cardiovascular risk factors such as arterial hypertension, obesity, hypercolesterolemia, diabetes, cigarette smoking. At the time of last follow up, 46 patients (15%) experienced at least one thrombotic event. The occurrence of thrombotic events was observed in 26/64 (40.6%) patients with previous history of thrombosis and in 20/242 (8.3%) patients with no previous history of thrombosis (p<0.0001 Fisher’s exact test, odd ratio 7.6). A significant difference between the two groups of patients was also confirmed when Kaplan Meier estimates of thrombosis-free survival were compared by log-rank test (p<0.0001). By logistic regression, platelet number at diagnosis did not associate with occurrence of thrombosis in the whole patient population. When patients without previous history of thrombosis were stratified according to the number of cardiovascular risk factors (none vs one vs more than one), a significant correlation with occurrence of thrombotic events was observed (Mantel-Haenszel Chi-square 5.47, p<0.05). This study confirms that history of thrombosis is strongly related with risk of further thrombotic events in patients with ET, whereas platelet number at diagnosis does not seem to represent a prognostic factor. In patients with no previous history of thrombosis, the presence of other cardiovascular risk factors has to be taken into account when establishing the therapeutic approach.

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Observation versus antiplatelet therapy as primary prophylaxis for thrombosis in low-risk essential thrombocythemia

Blood ◽

10.1182/blood-2010-01-263319 ◽

2010 ◽

Vol 116 (8) ◽

pp. 1205-1210 ◽

Cited By ~ 137

Author(s):

Alberto Alvarez-Larrán ◽

Francisco Cervantes ◽

Arturo Pereira ◽

Eduardo Arellano-Rodrigo ◽

Virginia Pérez-Andreu ◽

...

Keyword(s):

Risk Factors ◽

Cardiovascular Risk ◽

Venous Thrombosis ◽

Antiplatelet Therapy ◽

Essential Thrombocythemia ◽

Arterial Thrombosis ◽

Primary Prophylaxis ◽

Low Risk ◽

Increased Risk ◽

Risk Patients

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.

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CARDIOVASCULAR RISK IN ESSENTIAL THROMBOCYTHEMIA AND POLYCYTHEMIA VERA: THROMBOTIC RISK AND SURVIVAL

Mediterranean Journal of Hematology and Infectious Diseases ◽

10.4084/mjhid.2020.008 ◽

2020 ◽

Vol 12 (1) ◽

pp. e2020008

Author(s):

Vincenzo Accurso ◽

Marco Santoro ◽

Salvatrice Mancuso ◽

Angelo Davide Contrino ◽

Paolo Casimio ◽

...

Keyword(s):

Risk Factors ◽

Cardiovascular Risk ◽

Cigarette Smoking ◽

Cardiovascular Risk Factors ◽

Polycythemia Vera ◽

Essential Thrombocythemia ◽

Thrombotic Event ◽

Bleeding Events ◽

Thrombotic Risk ◽

The Impact

Abstract Thromboembolic and bleeding events pose a severe risk for patients with Polycythemia Vera (PV) and Essential Thrombocythemia (ET). Many factors can contribute to determine the thrombotic event, including the interaction between platelets, leukocytes and endothelium alterations. Moreover, a very important role can be played by cardiovascular risk factors (CV.R) such as cigarette smoking habits, hypertension, diabetes, obesity and dyslipidemia. In this study we evaluated the impact that CV.R plays on thrombotic risk and survival in patients with PV and ET.

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Cardiovascular Risk Factors and Diabetes in Medical Students: Observational Study, Experience in Colombia

International Journal of Medical Students ◽

10.5195/ijms.2018.24 ◽

2018 ◽

Vol 6 (2) ◽

pp. 61-65 ◽

Cited By ~ 1

Author(s):

Diego Mauricio Bados Enriquez ◽

Karoll Vanessa Ladino Oyola ◽

Juan Esteban Yucuma Ruiz

Keyword(s):

Diabetes Mellitus ◽

Risk Factors ◽

Cardiovascular Disease ◽

Cardiovascular Risk ◽

Medical Students ◽

Cardiovascular Risk Factors ◽

Risk Score ◽

Low Risk ◽

Early Interventions ◽

Moderate Risk

Background: Cardiovascular Disease is a leading cause of preventable death. Cardiovascular risk factors’ identification is the cornerstone for effective and early interventions decreasing the frequency of acute health-threatening events. Since adolescence and youth are very vulnerable stages to develop risky habits, we decided to run this study in the Multidisciplinary Universitary Camp for Research and Service. Methods: A descriptive cross-sectional study was performed in the Multidisciplinary Universitary Camp for Research and Service in which 450 medical students from Colombia were assessed. After a probabilistic random simple sampling (n=50), we applied the World Health Organization test and Finnish Risk Score to calculate Cardiovascular and Diabetes Mellitus risk, respectively. We characterized the population by sociodemographic variables and anthropometric measurements. Results: The study shows that from 18 participating universities (n=50), the mean age of the participants was 21.14 years (SD 7.3) of whom 40% were male and 60% were female. Overall, 92% have a low risk of cardiovascular disease, 6% are at moderate risk and 2% are at high risk. 92% have low risk of diabetes mellitus and 8% are at moderate risk of having diabetes mellitus in the long term. Conclusion: The early identification of and intervention on risk factors could decrease significantly the onset of acute health-threatening cardiovascular pathologies. As medical students, adolescents and young adults are at risk of developing unhealthy habits which increase the incidence of cardiovascular disorders. The use of anthropometric measures and validated risk score scales is an appropriate way to get evidence for starting early interventions.

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Thrombocytosis and leukocytosis interaction in vascular complications of essential thrombocythemia

Blood ◽

10.1182/blood-2008-04-153783 ◽

2008 ◽

Vol 112 (8) ◽

pp. 3135-3137 ◽

Cited By ~ 74

Author(s):

Alessandra Carobbio ◽

Guido Finazzi ◽

Elisabetta Antonioli ◽

Paola Guglielmelli ◽

Alessandro M. Vannucchi ◽

...

Keyword(s):

Risk Factors ◽

Platelet Count ◽

Essential Thrombocythemia ◽

Cardiovascular Events ◽

Multivariable Analysis ◽

Vascular Complications ◽

Low Risk ◽

Risk Category ◽

Mutational Status ◽

Thrombosis Risk

Abstract To elucidate the role of thrombocytosis, alone or in combination with standard (age, previous cardiovascular events) and novel (leukocytosis, JAK2V617F mutational status) risk factors, in the cardiovascular events of essential thrombocythemia (ET), we analyzed a cohort of 1063 patients. We found that a platelet count at diagnosis greater than 1000 × 109/L was associated with significantly lower rate of thrombosis in multivariable analysis and, if combined with leukocytes less than 11 × 109/L, pointed to a “low-risk” category with a rate of thrombosis of 1.59% of patients/year. On the contrary, the highest risk category (thrombosis rate, 2.95% of patients/year) was constituted of patients with leukocytosis, lower platelet count, and a JAK2V617F mutated genotype in most cases (77% vs 26% in the low-risk group), independently from standard risk factors. These data challenge the theory that elevated platelet count increases thrombosis risk in ET and suggest prospective clinical trials to support this hypothesis.

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Risk Factors for Thrombosis Vary According to Age in Patients with Essential Thrombocythemia: a Retrospective Analysis of 1090 Patients from the “Gruppo Laziale SMPC Ph Negative “,

Blood ◽

10.1182/blood.v118.21.3854.3854 ◽

2011 ◽

Vol 118 (21) ◽

pp. 3854-3854

Author(s):

Marco Montanaro ◽

Roberto Latagliata ◽

Michele Cedrone ◽

Nicoletta Villivà ◽

Raffaele Porrini ◽

...

Keyword(s):

Risk Factors ◽

Cardiovascular Risk ◽

Cardiovascular Risk Factors ◽

Thrombotic Event ◽

Age Groups ◽

Thrombotic Risk ◽

Mutational Status ◽

Group A ◽

Group B

Abstract Abstract 3854 Increasing age is a well-recognised risk factor for thrombotic events in patients with Essential Thrombocythemia (ET): however, few data exist on the role of other clinical and biological features in different age groups. To address this issue, we analysed retrospectively 1090 ET patients (M/F 403/687, median age 63 years, IR 17 – 96) diagnosed at 11 Hematological Institutions in the Lazio region from 1980 to 2010 and with a median period of follow-up of 84 months (IR 1 – 371). Based on the commonly adopted age threshold, 480 patients (44 %) were < 60 years (Group A) and 610 (56 %) were ≥ 60 years (Group B). Clinical and biological features as well as cardiovascular risk factors analyzed for the impact on the thrombotic risk in the two age groups are reported in the Table.Group A < 60 yearsGroup B ≥ 60 yearsPutative risk factorsRisk ratio (95% CI)P valueRisk ratio (95% CI)P valueM/F167/3132.68 (1.03–6.94)0.0029236/3741.12 (0.17–2.59)0.73WBC median (range) x 109/l8.9 (4.29–22.35)0.387 (0.149–1,004)0.06458.9 (1.2–57.7)0.79 (0.41–1.47)0.445PLTS median (range) x 109/l837 (451–3582)0.37 (0.258–1.70)0.66802 (450–3104)0.52 (0.28–0.99)0.0052Hb median, g/dL (range)14.1 (6.0–18.4)0.86 (0.33–2.24)0.76914.0 (7.0–17.8)0.87 (0.45–1.67)0.674*JAK-2 mutational status: wild type/mutated (%)53.2/46.81.57 (0.50–4.87)0.4434.1/65.90.498 (0.17–1.48)0.209Previous thrombotic events: n° (%)· All events72 (15)2.18 (0.59–7.96)0.12149 (24.4)3.01 (1.38–6.57)0.0004· within 24 months from diagnosis48 (10)1.43 (0.19–10.4)0.7464 (10.5)0.506 (0.18–1.39)0.189· within 60 months from diagnosis60 (12.5)NA0.5191 (14.9)0.323 (0.11–0.95)0.023Cardiovascular risk factors: Y/N %○ Arterial hypertension41.7/58.31.68(0.64–4.36)0.2880.7/19.30.96 (0.36–2.57)0.935○ Diabetes10.2/89.81.11 (0.23–5.15)0.8925.0/75.01.09 (0.38–3.11)0.86○ Smoking attitude45.6/54.42.78 (1.01–7.65)0.06758.3/41.71.04 (0.35–3.09)0.94○ Hyperlipidemia31.0/69.03.11(0.917–10.592)0.03951.6/48.42.31 (0.70–7.55)0.203 In Group A, 39 patients (8.1%) had at least one thrombotic event during follow-up; there were 20 (51.3%) arterial thrombosis and 19 (48.7%) venous thrombosis. In Group B, 63 patients (10.3%) had at least one thrombotic event during follow-up; there were 38 (69.4%) arterial thromboses and 25 (39.6%) venous thromboses. In group A univariate analysis for thrombosis-free survival performed by Kaplan-Meier method, disclosed a significant impact of male gender (p=0.0029, CI 1.03–6.94, HR 2.68), > 2 cardiovascular risk factors (p=0.0002, CI 1.87 – 190, HR 18.94) and isolated hyperlipidemia (p=0.039, CI 0.917 – 10.59, HR 3.11), while previous thrombotic events had no significant impact (p=0.27). By contrast, the presence of a previous thrombotic event was the only feature with a significant impact on thrombotic risk in Group B (p=0.0004, CI 1.38 – 6.55, HR 3.01). WBC and PLTS values at different cut-off levels as well as JAK-2 mutational status did not have any impact on thrombosis in either age groups. However, in group B, we observed a trend (p=0.052, CI 0.28–0.99, HR 0.52) towards a protective effect of higher PLTS values (> 800 × 109/l). In conclusion, our data seem to reinforce the need of a different thrombotic risk assessment in distinct age groups: in particular, younger patients could benefit from early recognition and treatment of well-known cardiovascular risk factors. Disclosures: No relevant conflicts of interest to declare.

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Prevalence of the Antiphospholipid Antibodies in Young Adults with Ischemic Stroke

Blood ◽

10.1182/blood-2019-123727 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 4952-4952

Author(s):

Antonella Vaccarino ◽

Maria Pagliaro ◽

Clara Rollone ◽

Fabio Melis ◽

Federica De Marco ◽

...

Keyword(s):

Risk Factors ◽

Young Adults ◽

Ischemic Stroke ◽

Cardiovascular Risk ◽

Ct Scan ◽

Cardiovascular Risk Factors ◽

Antiphospholipid Antibodies ◽

Thrombotic Event ◽

Ischemic Lesion ◽

Number Of Patients

Background: Ischemic stroke is rare in young adults, with an incidence of about 10-15% of all the ischemic strokes. In about one third of these patients a cause is missing. Among patients with antiphospholipid antibodies syndrome (APS), stroke is the first thrombotic event in about 13% of cases. Aims of our project were: to evaluate the prevalence of antiphosfolipid antibodies (aPL),to investigate on the prevalence of conventional risk factors and to define the radiological characteristics of the ischemic lesion. Materials and methods: this is a no profit, observational multicenter prospective study. Inclusion criteria were: age older than 18 and younger than 55 years, informed written consent, a clinical and radiological diagnosis of stroke. Patient's data were collected at diagnosis and after 30 days from stroke. If any aPL positivity was found the patient was referred to our service to further/eventually confirm the diagnosis of APS. For each patient these data were collected: age, sex, body mass index, personal and familial history, concomitant co morbidities and therapies, cardiovascular risk factors, drug abuse. CT scan or angioCT or MRI was always performed at diagnosis, aPL profile was determined at diagnosis and eventually confirmed after 12 weeks according to the Sapporo criteria. None of the patients had a previous diagnosis of APS. Results: enrolled patients from January 2017 to December2018 were 46 out of 425 ischemic stroke (10.8%). We found 11/46 aPL positivity patients. Among these patients, 7 were confirmed at 12 weeks (15%). Baselines characteristics of the study population are detailed in table 1. We found a high prevalence of associated conventional cardiovascular risk factors: hypertension (56%), dyslipidemia ( 50%), obesity (55%), smoke ( 52%). We didn't find any correlation between APS and a clear radiological pattern on MRI and CT scan. Conclusions: Prevalence of APS was 15% in our cohort of young patients with stroke, 85% of which had an high risk aPL profile. The detection frequency is similar to the recent APS-ACTION and literature findings. In our cohort stroke was a relapse of a previous ischemic event in 24% of the patients, while in 15% there was a stroke's relapse. Even if these data should be confirmed with a wider number of patients, it seems to be useful to evaluate the presence of aPL in a young patient with ischemic stroke . Disclosures No relevant conflicts of interest to declare.

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