Clinical Implications of Elevated Antiphospholipid Antibodies in Adult Patients with Primary Immune Thrombocytopenia

Yang, Young-Joon; Yun, Gak-Won; Song, Ik‐Chan; Baek, Seung‐Woo; Lee, Kyu-Seop; Ryu, Ho‐Sung; Lee, Myung-Won; Yun, Hwan‐Jung; Kim, Samyong; Jo, Deog‐Yeon

doi:10.3904/kjim.2011.26.4.449

Cited by 31 publications

(19 citation statements)

References 16 publications

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“…Following ITP diagnosis, the pooled ‘annualised’ cumulative risk for TE was 2.97%/yr (Fig. ) and the pooled ‘annualised’ cumulative incidence for TE was 1.29%/yr (Figure S2, Supporting information). Among studies which followed patients from their splenectomy procedures, the pooled ‘annualised’ cumulative risk for TE was 0.99%/yr (Fig.…”

Section: Resultsmentioning

confidence: 99%

Thromboembolism in adults with primary immune thrombocytopenia: a systematic literature review and meta‐analysis

Doobaree

Nandigam

Bennett

et al. 2016

European J of Haematology

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Adults with primary immune thrombocytopenia (ITP) may be susceptible to thromboembolism (TE). The objective of this systematic review was to evaluate studies that reported the prevalence and risk of developing TE in the ITP population from ITP diagnosis and splenectomy. We searched several bibliographic databases and included 29 studies. Using meta-analytical techniques, the pooled prevalence of TE before ITP diagnosis was 7.84% (arterial 6.25%; venous 1.95%). The pooled 'annualised' cumulative incidence (without prior TE) and cumulative risk (irrespective of prior TE) were 1.29%/yr and 3.00%/yr, respectively. Splenectomised patients had pooled cumulative risk of arterial TE (ATE) and venous TE (VTE) of 0.19%/yr and 1.10%/yr, respectively. In cohorts, regardless of a history of TE, the pooled relative risk (RR) of any TE was 1.60 (1.34, 1.86) for ITP vs. ITP-free individuals [arterial: 1.52 (1.25, 1.80); venous: 1.70 (0.96, 2.43)]. Splenectomised patients were at higher risk of venous events, pooled RR 2.39 (1.61, 3.17). To conclude, we found an increased risk of TE (mainly ATE) among ITP individuals and a higher risk of VTEs after splenectomy. How intrinsic (ITP pathophysiology, age, gender) and extrinsic factors (treatment) contribute to this risk could not be investigated here but is a task for future studies. Primary immune thrombocytopenia (ITP) in adults is a rare heterogeneous blood disorder which is characterised by a reduced peripheral blood platelet count below 100 9 10 9 /L (1). Its underlying mechanisms are increasingly explained within an 'autoimmune' paradigm in which platelets are destroyed through antibody-mediated destruction and thrombocytopoiesis is reduced through immune-mediated megakaryocytic downregulation (2).Although bleeding is a prominent feature of the disease, patients often present with other comorbid conditions at ITP diagnosis or throughout the course of the disease (3, 4). Notably, there are studies that showed that the risk of thromboembolic events (TE) could be elevated among patients with ITP (4, 5) and also among patients who had ITP-related splenectomies (6). How such a paradoxical 'prothrombotic and thrombocytopenic' state coexists is not completely understood. One likely explanation for this heightened risk for TE is that the ITP pathophysiology promotes a prothrombotic state but the evidence is unclear and weak (7-9). On the other hand, the distribution and influence of typical prothrombotic risk factors, including obesity, smoking, family history of TE, and the impact of ITP-related treatments, such as long-term corticosteroid use or splenectomy, on the risk of TE in ITP have been not completely described and explained. Before engaging into investigative studies on the contributory factors of TE in ITP, it is important to review the published evidence to date to establish whether there is a heightened risk of TE in the ITP population.

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Section: Resultsmentioning

confidence: 99%

Thromboembolism in adults with primary immune thrombocytopenia: a systematic literature review and meta‐analysis

Doobaree

Nandigam

Bennett

et al. 2016

European J of Haematology

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“…Presumably these events are driven by the presence of large and immature platelets, thrombosis risk factors, and increased levels of antiphospholipid antibodies . However, research on risks of thrombosis in ITP patients has been conducted in small selected cohorts, and prior to the availability of rituximab and thrombopoietin receptor‐agonists as ITP treatments . Earlier research also did not assess events in patients by ITP phase, and risk of thromboembolic events could vary by duration of disease .…”

Section: Introductionmentioning

confidence: 99%

Cardiovascular and bleeding outcomes in a population‐based cohort of patients with chronic immune thrombocytopenia

Adelborg

Kristensen

Nørgaard

et al. 2019

Journal of Thrombosis and Haemostasis

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Background: Among patients with chronic immune thrombocytopenia (cITP), little is known regarding risk factors for cardiovascular and bleeding outcomes and how these events influence mortality. Objectives:We examined the rate of cardiovascular events and bleeding requiring a hospital contact according to platelet count levels, as well as the prognostic impact of these events on all-cause mortality in adult patients with cITP. Methods: We identified all cITP patients registered in the Nordic Country PatientRegistry for Romiplostim during 1996 to 2015. Absolute risks and hazard ratios across platelet count levels based on Cox regression analysis were computed, adjusting for age, sex, prevalent/incident cITP, smoking, and comorbidities. We also compared all-cause mortality rates in cITP patients with and without cardiovascular and bleeding events.Results: Among 3 584 cITP patients, 1-year risks were 1.9% for arterial cardiovascular events, 1.2% for venous thromboembolism, and 7.5% for bleeding. Rates of cardiovascular events were similar across platelet counts. Patients with platelet counts <50 × 10 9 /L had >2-fold higher rates of bleeding than patients with normal platelet counts. These associations were unchanged in time-varying analyses that considered changes in platelet counts during follow-up. Occurrences of cardiovascular and bleeding events were associated with 4-fold to 5-fold increases in 1-year mortality. Conclusions:Among patients with cITP, the 1-year risks of cardiovascular events were 1% to 2%, while nearly 8% experienced a bleeding event within 1 year.Cardiovascular events occurred across all platelet levels, while low platelet counts were associated with increased hazards of bleeding. Cardiovascular and bleeding events were strong prognostic factors for mortality. K E Y W O R D Sbleeding, chronic ITP, epidemiology, mortality, stroke, myocardial infarction, venous thromboembolism | 913 ADELBORG Et AL.

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“…Após cinco anos de acompanhamento, a sobrevida acumulada livre de trombose nos pacientes com PTI AAF positivo e AAF negativo foram 39 e 97,7%, respectivamente (valor p < 0,01, teste de Log--rank). No estudo de Yang 18 , a prevalência de AAF em pacientes com PTI foi de 20 entre 70 (28,5%) e houve dois eventos trombóticos entre os pacientes AAF positivo (10%). Nenhum evento trombótico foi detectado em pacientes AAF negativo.…”

Section: Resultsunclassified

“…20 O estudo atual teve média de acompanhamento de 34 meses, similar à de outros estudos com 20 a 32 meses de acompanhamento. 14,16,18 Como não foram detectados eventos trombóticos no estudo atual, análises de sobrevivência como Kaplan-Meier e Cox não puderam ser aplicadas. 17,21 A idade, tempo de acompanhamento e grau de trombocitopenia ao diagnóstico, possíveis fatores de confundimento entre AAF e PTI de adultos e entre AAF e TV em PTI não influenciaram os resultados do estudo atual.…”

Section: Resultsunclassified

“…A prevalência de AAF em PTI varia entre 25 e 40% e a prevalência de TV em pacientes com PTI AAF positivo de 0 a 23%. 2,[14][15][16][18][19] A proporção de pacientes AAF positivo no estudo atual é consistente com o estudo de Despujol (2008), que observou prevalência de 26% (55/215, IC 95% 20,7%-30,9%). 16 Moules (2011) também estimou a positividade de AAF em PTI em 25% 19 .…”

Section: Discussionunclassified

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Assessment of antiphospholipid antibodies in adult patients with immune thrombocytopenic purpura

Bastos¹,

Paiva²,

Reis³

et al. 2014

Revista Médica De Minas Gerais

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Introdução: a púrpura trombocitopênica imune (PTI) é doença autoimune adquirida, caracterizada por trombocitopenia. A PTI em adultos usualmente apresenta evolução crônica e o diagnóstico é sugerido pela exclusão de outras causas de trombocitopenia. Anticorpos antifosfolípides (AAF) com perda fetal ou trombose vascular definem a síndrome antifosfolípide (SAF). AAFs também podem ser identificados em portadores adultos de PTI. O objetivo deste estudo foi avaliar as associações entre AAF e PTI e entre PTI AAF positivo e TV. Método: trata-se de estudo de coorte incluindo pacientes com PTI atendidos em um ambulatório de um hospital público em Belo Horizonte, entre 1981 e 2006. Os dados relativos ao diagnóstico e ao acompanhamento foram extraídos de prontuários médicos, de laudos laboratoriais e por pesquisa telefônica. Resultados: foram diagnosticados 65 adultos com PTI, dos quais 28 (43,1%) foram avaliados para AAF. Cinco pacientes foram AAF positivo (18% dos pacientes avaliados, intervalo de confiança de 95%-7,3% a 33,9%). Não houve diferença entre os grupos AAF positivo e AAF negativo em relação à idade e evolução clínica. Houve tendência ao predomínio de pacientes masculinos no grupo AAF positivo (valor p 0,08, teste qui-quadrado). Nenhum evento trombótico foi observado em 956 meses acumulados de observação. Conclusão: observou-se AAF em 18% dos pacientes com PTI de adultos, mas não se constatou evento trombótico em pacientes com PTI.

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Clinical Implications of Elevated Antiphospholipid Antibodies in Adult Patients with Primary Immune Thrombocytopenia

Cited by 31 publications

References 16 publications

Thromboembolism in adults with primary immune thrombocytopenia: a systematic literature review and meta‐analysis

Thromboembolism in adults with primary immune thrombocytopenia: a systematic literature review and meta‐analysis

Cardiovascular and bleeding outcomes in a population‐based cohort of patients with chronic immune thrombocytopenia

Assessment of antiphospholipid antibodies in adult patients with immune thrombocytopenic purpura

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