Demographic, Clinical and Laboratory Features, Management and Outcome of Immune Thrombocytopenia (ITP) in Greece: The National ITP Registry of the Hellenic Society of Hematology

Immune thrombocytopenia (ITP) is a heterogeneous autoimmune disorder mediated by platelet antibodies thought to accelerate platelet destruction while inhibiting also their production. ITP may be primary (with no apparent underling etiology) or secondary to another disorder.

ITP features in the general Greek population have not been properly investigated. The purpose of the study is to access systematically, for the first time, the demographic, clinical, laboratory, treatment-related characteristics and outcome of ITP in Greece, based on the national database (ITP registry) operated under the auspices of the Hellenic Society of Hematology, managed by the Hematology Department of the University of Crete (UoC) and supported by the Center of Information and Communications Technologies of the UoC.

From 2013 to June 2017 718 adult patients from 16 different hospitals throughout Greece were registered. The median age at diagnosis was 53 years (range, 18-97 years). Two peaks were observed at 19-30 and 71-80 years of age. The female to male ratio was 1.9:1. The median platelet (PLT) count at diagnosis was 15x10³/ml. 56.6% of patients presented with bleeding manifestations, including cutaneous bleeding (90.1%), oral cavity bleeding (29.1%), epistaxis (12.6%), menorrhagia (11.3%) and gastrointestinal bleeding (8%). 454 patients (63.2%) had primary ITP and 264 (36.8%) secondary ITP. Among the latter cases, 22.34% were related to infectious agents, 29.54% to drugs, 7.95% to collagen vascular diseases and 16.28% to cancer. Patients with positive ANA antibodies with no evidence of any underlying diseases were included in the primary ITP group. The main patient comorbidities were hypertension (19.95%), thyroid disease (11.32%) and cardiovascular disease (9.1%). Bleeding manifestations were significantly more frequent in the secondary ITP group as compared to the primary ITP group (P<0.0001), although there was no difference in PLT count on diagnosis. Treatment was administered in 657 patients on diagnosis. Specifically, 91.78% of patients were treated with corticosteroids (CS), 47.48% with i.v. IgG, 44.29% with both and 21.91% received other treatments, including rituximab (4.8%), anti-D immunoglobulin (4.14%) and thrombopoietin receptor agonists (2.81%). 91.62% of patients responded to the initial treatment.

At 1 year after ITP diagnosis data from 156 patients was available. Among these patients 44% had persistent ITP, while the rest achieved PLT count 100,000/μl (recovery) either spontaneously (27%) or with a disease modifying treatment (29%). There was no difference in median age, median PLT count, frequency and severity of bleeding manifestations nor in ANA antibody positivity on diagnosis between patients with persistent ITP and those with spontaneous recovery. All patients in the latter group were female, as compared to 53% in the former group (P<0.0001).

59 patients (36 women and 23 men) with a median age of 47 years (range, 23-94) have been splenectomized. The median time from diagnosis to splenectomy was 11 months (range, 1.5-258) and the median pre-operative PLT count was 32,500/μl (range, 5-200,000/μl). The outcome after splenectomy was assessed in 19/59 patients, for whom evaluable data were provided. 74% of patients responded to splenectomy. Responders did not differ from non-responders in female to male ratio, nor in the median pre-preoperative PLT count nor in the median PLT number on diagnosis. A significant higher proportion of responders to splenectomy had responded to first-line treatment as compared to non-responders (P=0.0374). Furthermore, responders had received significantly fewer number of therapies before splenectomy (P=0.0361).

In conclusion, primary ITP is more frequent than secondary ITP in Greece. ITP displays a bimodal distribution, with peaks at 19-30 and 71-80 years of age, it has a female predominance and presents with bleeding manifestations in half of patients. Treatment is mainly based on CS and/or i.v IgG. Splenectomy is effective in about 2/3 of patients. At one year of diagnosis 27% of patients achieved spontaneous recovery. Registration and follow-up of a larger number of patients and evaluation of response to various treatments are anticipated to extend our knowledge on the pathophysiology and natural history of ITP and identify predictive factors of the disease course, possibly associated with peculiarities of the Greek population.