Impact of risk factors on the occurrence of arterial thrombosis and venous thromboembolism in adults with primary immune thrombocytopenia – Results from two nationwide cohorts

Ekstrand, Charlotta; Linder, Marie; Baricault, Bérangère; Lafaurie, Margaux; Sailler, L.; Lapeyre‐Mestre, Maryse; Kieler, Helle; Moulis, Guillaume; Bahmanyar, Shahram

doi:10.1016/j.thromres.2019.04.016

Cited by 24 publications

(28 citation statements)

References 47 publications

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“…Limited data suggest that these mechanisms resulting in an increased risk of VE in cancer may persist even after the cancer is in remission 28 . In line with that, in ITP patients, a past history of malignancy increases the risk of venous thromboembolism with an HR of of 1.8 29 . However, in our study the risk of VE in ITP patients with a history of previous neoplasia while on TPO-RA was disproportional (more than 40-fold increased risk in elderly patients), suggesting a novel association of these variables with VE in elderly ITP patients under TPO-RA therapy.…”

Section: Discussionsupporting

confidence: 76%

Deciphering predictive factors for choice of thrombopoietin receptor agonist, treatment free responses, and thrombotic events in immune thrombocytopenia

Lozano

Mingot‐Castellano

Perera

et al. 2019

Sci Rep

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Very few data exist on when a particular thrombopoietin-receptor agonist (TPO-RA) is favored in clinical practice for the treatment of patients with immune thrombocytopenia (ITP), about novel risk factors for vascular events (VE) with these drugs, nor about predictive factors for therapy free responses (TFR). We conducted an observational, retrospective, long-term follow-up multicenter study from November 2016 to January 2018 of 121 adult ITP patients initiating TPO-RA between January 2012 to December 2014. Data reflected that a platelet count ≤25 × 109/l at the time when the TPO-RA was initiated was associated with a 2.8 higher probability of receiving romiplostim vs. eltrombopag (P = 0.010). VE on TPO-RA was related to previous neoplasia in patients over 65 years (50% vs. 2.2%, P < 0.001), and to previous splenectomy in younger patients (100% vs. 33%, P = 0.001). Receiving romiplostim as first TPO-RA with no subsequent TPO-RA switching was associated with a 50% likelihood of TFR after 2.9 years of therapy (3.3 years in chronic ITP patients). These real-world data help deciphering some areas of uncertainty, and offer insight into some of the most relevant challenges of ITP which may help clinicians make appropriate treatment decisions in the management of adult ITP patients with TPO-RA.

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Section: Discussionsupporting

confidence: 76%

Deciphering predictive factors for choice of thrombopoietin receptor agonist, treatment free responses, and thrombotic events in immune thrombocytopenia

Lozano

Mingot‐Castellano

Perera

et al. 2019

Sci Rep

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“…Later clinical studies revealed low annualized rates for 100 patient‐years with 1.14 (95% confidence interval [CI], 0.84‐1.54), 0.39 (95% CI, 0.23‐0.65), and 0.71 (95% CI, 0.49‐1.04) for total, venous, and arterial thrombosis, 13 respectively. Other risk factors such as increasing age or male sex may contribute more strongly to the thrombosis risk in ITP 14 than a potential platelet associated risk. Treatment with eltrombopag increases platelet counts and MPV in responding chronic ITP patients but does not induce additional platelet activation or hyper‐reactivity 15 .…”

Section: How Does Platelet Size Change In Disease?mentioning

confidence: 99%

Large and small platelets—(When) do they differ?

Handtke

Thiele

2020

Journal of Thrombosis and Haemostasis

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Platelets are most important in providing cellular hemostasis but also take part in inflammation and immune processes. Increased platelet size has been regarded as a feature describing a young and more reactive subpopulation until studies were published which questioned this concept. Moreover, changes of platelet size given by the mean platelet volume (MPV) were described for immune thrombocytopenia, cardiovascular disease, atherosclerosis, venous thromboembolism, chronic lung disease, sepsis, cancer‐associated thrombosis, autoimmune disorders, and others. This review summarizes the literature on what is known about platelets with different size and describes controversies of studies with large and small platelets putting a focus on their thrombogenicity, age, and on the association of MPV with the mentioned diseases.

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“…Paradoxically, patients with ITP have a small increased risk of both venous and arterial thromboembolic events (TEEs) compared with the general population. 1 – 3 The risk of TEE appears to be further increased in ITP patients who are over 60 years of age, male, and/or obese (BMI ⩾ 30), as well as in those with prothrombotic comorbid conditions such as cancer, hyperlipidemia, diabetes, hypertension, coronary artery disease, and chronic kidney disease. In other words, the same risk factors are operative in patients with ITP as in patients who do not have ITP.…”

Section: Introductionmentioning

confidence: 99%

Assessment of thrombotic risk during long-term treatment of immune thrombocytopenia with fostamatinib

Cooper

Altomare

Thomas

et al. 2021

Therapeutic Advances in Hematology

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Background: Patients with immune thrombocytopenia (ITP) are at risk of bleeding and, paradoxically, thromboembolic events (TEEs), irrespective of thrombocytopenia. The risk of thrombosis is increased by advanced age, obesity, and prothrombotic comorbidities: cancer, hyperlipidemia, diabetes, hypertension, coronary artery disease, and chronic kidney disease, among others. Certain ITP treatments further increase the risk of TEE, especially splenectomy and thrombopoietin receptor agonists. Spleen tyrosine kinase (SYK) is a key signaling molecule common to thromboembolic and hemostatic (in addition to inflammatory) pathways. Fostamatinib is an orally administered SYK inhibitor approved in the USA and Europe for treatment of chronic ITP in adults. Methods: The phase III and extension studies included heavily pretreated patients with long-standing ITP, many of whom had risk factors for thrombosis prior to initiating fostamatinib. This report describes long-term safety and efficacy of fostamatinib in 146 patients with up to 5 years of treatment, a total of 229 patient-years, and assesses the incidence of thromboembolic events (by standardized MedDRA query). Results: Platelet counts ⩾50,000/µL were achieved in 54% of patients and the safety profile was as described in the phase III clinical studies with no new toxicities observed over the 5 years of follow-up. The only TEE occurred in one patient (0.7%, or 0.44/100 patient-years), who experienced a mild transient ischemic attack. This is a much lower rate than might be expected in ITP patients. Conclusion: This report demonstrates durable efficacy and a very low incidence of TEE in patients receiving long-term treatment of ITP with the SYK inhibitor fostamatinib. identifiers: NCT02076399, NCT02076412, and NCT02077192.

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Impact of risk factors on the occurrence of arterial thrombosis and venous thromboembolism in adults with primary immune thrombocytopenia – Results from two nationwide cohorts

Cited by 24 publications

References 47 publications

Deciphering predictive factors for choice of thrombopoietin receptor agonist, treatment free responses, and thrombotic events in immune thrombocytopenia

Deciphering predictive factors for choice of thrombopoietin receptor agonist, treatment free responses, and thrombotic events in immune thrombocytopenia

Large and small platelets—(When) do they differ?

Assessment of thrombotic risk during long-term treatment of immune thrombocytopenia with fostamatinib

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