Immune Thrombocytopenia in Very Elderly Patients: Particularities in Presentation and Management. Results from the Multicenter Prospective Carmen-France Registry
Authors: Sokal Aurélien , de Nadaï Thomas , Comont Thibault , Limal Nicolas , Michel Marc , Beyne-Rauzy Odile , Godeau Bertrand , Adoue Daniel , Mahévas Matthieu , Moulis Guillaume , investigators Group Carmen 
Published: November 2019

Introduction: The incidence of immune thrombocytopenia (ITP) is high in the elderly. Observational studies demonstrated that age above 65 years impacts ITP presentation and management. However, data are lacking in very elderly patients (VEP) with ITP. The aim of this study was to describe the presentation and the management of primary ITP that occurs in VEP (≥80 year-old) in comparison with elderly patients (EP; ≥65-79 year-old).
Methods: Data source was the CARMEN-France registry. The CARMEN (Cytopénies Auto-immunes : Registre Midi-PyréneEN) registry is aimed at the prospective follow-up of all incident ITP adult patients in the French Midi-Pyrénées region (South-West of France, 3 million inhabitants) since June 2013. Each investigator follows all adult patients (aged ≥18 years) newly diagnosed for ITP in routine visit or hospital stay and detailed information on patients' characteristics and management of ITP are prospectively recorded. This registry has been implemented in the French referral center for ITP (Créteil) since October 2015, taking the name of CARMEN-France. Inclusion criteria in the present study were: inclusion in the CARMEN-France registry between June 2013 and December 2018; age ≥65 years at ITP onset; primary ITP defined by international criteria (platelets count <100 x 109/L and exclusion of other causes of thrombocytopenia) and with normal bone marrow examination. Patients were then categorized by age groups (VEP vs EP). We compared patients' characteristics, ITP presentation including bleeding by platelet counts, exposure to first and second-line treatments. We also assessed the factors associated to any and severe (hematuria, gastro-intestinal tract or intracranial) bleeding at ITP onset in the VEP group using logistic regression models.
Results: Out of 541 patients included in the CARMEN-France registry, 184 fulfilled inclusion criteria: 87 in the VEP group and 97 in the EP group. Mean age was 85.7 years in the VEP group versus 71.8 in the EP group. Male:female sex-ratio was similar (63.2% vs. 60.8%). Patients in the VEP group had more frequently comorbidities of the Charlson's Index (67.4% versus 47.9%) and polypharmacy (≥4 drugs; 63.3% versus 45.4%); they were more frequently exposed to antiplatelet drugs (37.9% versus 23.7%) and to anticoagulant (18.4% versus 10.3%). Median platelet counts at ITP onset were similar (22.0 versus 18.0 x 109/L). The frequencies of any bleeding were similar (58.6% versus 54.6%) as well as mucosal bleeding (25.3% versus 26.8%), but severe bleeding was more frequent in the VEP group (10.3% versus 4.1%). The frequencies of any bleeding and mucosal bleeding were higher in case of platelet count <20 x 109/L in both groups. Severe bleeding occurred with platelet count <20 x 109/L in all EP cases (n=4) while they occurred at any platelet count in the VEP group. In the VEP group, 85.1% of the patients were treated for ITP, versus 80.4% in the EP group. Among treated patients, 36.5% in the VEP group had steroids alone and 60.3% steroids plus intravenous immunoglobulin (IVIg), in comparison with 50.0% and 48.7% in the EP group, respectively. Second-line treatment was prescribed in 39.1% of VEP versus 37.5% of EP: thrombopoietin receptor agonists (13.8% versus 13.4%), dapsone (8.1% versus 8.2%), rituximab (6.9% versus 6.2%), and danazol (6.9% versus 4.1%). In univariate analysis, the factors associated with any bleeding in the VEP group were: female sex (odds ratio - OR: 1.97; 95% confidence interval - CI: 0.79-4.93), polypharmacy (OR: 2.64; 95% CI: 1.08-6.48); infection within the six weeks before ITP onset (OR: 2.60; 95% CI: 0.66-10.4) and platelet count < 20 x 109/L (OR: 10.0; 95% CI: 3.49-28.63). In univariate analysis, the main factors associated with severe bleeding were exposure to anticoagulant (OR: 7.61; 95% CI: 1.77-32.83), polypharmacy (OR: 5.28; 95% CI: 0.63-44.30), a Charlson's Comorbidity Index score ≥1 (OR: 4.32; 95% CI: 0.51-36.38); the OR for a platelet count <20 x 109/L was 1.54 (95% CI: 0.38-6.16).
Conclusion: VEP had more frequently severe bleeding at ITP onset. They were more frequently exposed to IVIg but did not require more frequently a second-line treatment. The pattern of second-line treatment was similar between VEP and EP. Platelet count <20 x 109/L was a major risk factor for any bleeding in VEP. In contrast, exposure to anticoagulant, and not platelet count <20 x 109/L, was highly associated with severe bleeding in VEP. Introduction: The incidence of immune thrombocytopenia (ITP) is high in the elderly. Observational studies demonstrated that age above 65 years impacts ITP presentation and management. However, data are lacking in very elderly patients (VEP) with ITP. The aim of this study was to describe the presentation and the management of primary ITP that occurs in VEP (≥80 year-old) in comparison with elderly patients (EP; ≥65-79 year-old).
Methods: Data source was the CARMEN-France registry. The CARMEN (Cytopénies Auto-immunes : Registre Midi-PyréneEN) registry is aimed at the prospective follow-up of all incident ITP adult patients in the French Midi-Pyrénées region (South-West of France, 3 million inhabitants) since June 2013. Each investigator follows all adult patients (aged ³18 years) newly diagnosed for ITP in routine visit or hospital stay and detailed information on patients' characteristics and management of ITP are prospectively recorded. This registry has been implemented in the French referral center for ITP (Créteil) since October 2015, taking the name of CARMEN-France. Inclusion criteria in the present study were: inclusion in the CARMEN-France registry between June 2013 and December 2018; age ≥65 years at ITP onset; primary ITP defined by international criteria (platelets count <100 x 109/L and exclusion of other causes of thrombocytopenia) and with normal bone marrow examination. Patients were then categorized by age groups (VEP vs EP). We compared patients' characteristics, ITP presentation including bleeding by platelet counts, exposure to first and second-line treatments. We also assessed the factors associated to any and severe (hematuria, gastro-intestinal tract or intracranial) bleeding at ITP onset in the VEP group using logistic regression models.
Results: Out of 541 patients included in the CARMEN-France registry, 184 fulfilled inclusion criteria: 87 in the VEP group and 97 in the EP group. Mean age was 85.7 years in the VEP group versus 71.8 in the EP group. Male:female sex-ratio was similar (63.2% vs. 60.8%). Patients in the VEP group had more frequently comorbidities of the Charlson's Index (67.4% versus 47.9%) and polypharmacy (³4 drugs; 63.3% versus 45.4%); they were more frequently exposed to antiplatelet drugs (37.9% versus 23.7%) and to anticoagulant (18.4% versus 10.3%). Median platelet counts at ITP onset were similar (22.0 versus 18.0 x 109/L). The frequencies of any bleeding were similar (58.6% versus 54.6%) as well as mucosal bleeding (25.3% versus 26.8%), but severe bleeding was more frequent in the VEP group (10.3% versus 4.1%). The frequencies of any bleeding and mucosal bleeding were higher in case of platelet count <20 x 109/L in both groups. Severe bleeding occurred with platelet count <20 x 109/L in all EP cases (n=4) while they occurred at any platelet count in the VEP group. In the VEP group, 85.1% of the patients were treated for ITP, versus 80.4% in the EP group. Among treated patients, 36.5% in the VEP group had steroids alone and 60.3% steroids plus intravenous immunoglobulin (IVIg), in comparison with 50.0% and 48.7% in the EP group, respectively. Second-line treatment was prescribed in 39.1% of VEP versus 37.5% of EP: thrombopoietin receptor agonists (13.8% versus 13.4%), dapsone (8.1% versus 8.2%), rituximab (6.9% versus 6.2%), and danazol (6.9% versus 4.1%). In univariate analysis, the factors associated with any bleeding in the VEP group were: female sex (odds ratio - OR: 1.97; 95% confidence interval - CI: 0.79-4.93), polypharmacy (OR: 2.64; 95% CI: 1.08-6.48); infection within the six weeks before ITP onset (OR: 2.60; 95% CI: 0.66-10.4) and platelet count < 20 x 109/L (OR: 10.0; 95% CI: 3.49-28.63). In univariate analysis, the main factors associated with severe bleeding were exposure to anticoagulant (OR: 7.61; 95% CI: 1.77-32.83), polypharmacy (OR: 5.28; 95% CI: 0.63-44.30), a Charlson's Comorbidity Index score ³1 (OR: 4.32; 95% CI: 0.51-36.38); the OR for a platelet count <20 x 109/L was 1.54 (95% CI: 0.38-6.16).
Conclusion: VEP had more frequently severe bleeding at ITP onset. They were more frequently exposed to IVIg but did not require more frequently a second-line treatment. The pattern of second-line treatment was similar between VEP and EP. Platelet count <20 x 109/L was a major risk factor for any bleeding in VEP. In contrast, exposure to anticoagulant, and not platelet count <20 x 109/L, was highly associated with severe bleeding in VEP.

Disclosures
Comont: BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees. Michel:Rigel: Consultancy; Amgen: Consultancy; Novartis: Consultancy. Beyne-Rauzy:Cellgene: Research Funding; Novartis: Research Funding. Godeau:Amgen: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau. Moulis:Amgen pharma: Research Funding, Speakers Bureau; Novartis pharma: Research Funding, Speakers Bureau; CSL Behring: Research Funding.