Positivity Rates of Tests Used at Immune Thrombocytopenia Diagnosis to Detect Associated Diseases. a Prospective Multicenter Cohort Study of 218 Patients

Introduction:The frequency ofimmune thrombocytopenia (ITP)-associated diseases detected at ITP onset is not well known. The positivity rates of tests performed at ITP onset in order to detect these diseases are discussed or unknown, leading to discrepancies among recommendations. The aim of this study was to compare the positivity rates of tests used at ITP diagnosis to detect ITP-associated diseases in the overall ITP population, in the presence of signs evocative of these diseases and in the absence of these signs.

Methods:We studied all patients included between June 2013 and May 2016 in the CARMEN (CytopéniesAuto-immunes : Registre Midi-PyréneEN) registry. This multicenter registry is aimed at the prospective follow-up of all incident ITP adults in the French Midi-Pyrénées region (South of France, 3 million inhabitants). Each investigator prospectively follows every patient newly diagnosed for ITP in routine visit or hospital stay. ITP is defined in accordance with French guidelines: platelet count <150 x 10⁹/L and exclusion of other causes of thrombocytopenia. Investigations performed at ITP diagnosis are recorded with their results. We assessed their positivity rates in the entire cohort and depending on the clinical and biological context. Patients with a cause of secondary ITP already known at ITP diagnosis were excluded for these calculations.

Results:We included 218patients. Median age was 66 years (range: 18-96), 47.3% were female, 34 (15.8%) had a secondary ITP, 104 (48.2%) had bleeding signs, median platelet count was 18 x10⁹/L (range: 1-135) and 144 (66.1%) were treated for ITP within the month following the diagnosis.

Bone marrow examination was performed in 167patients. Fivemyelodysplastic syndromes (MDS) were found (3 refractory cytopenia with unilineage dysplasia and 2 with multilineage dysplasia). These 5 ITP patients had platelet count <15x 10⁹/L and responded to corticosteroids. The positivity rate among patients with anemia or neutropenia was 6.6% (4/61 patients) and 0.9% in case of isolated thrombocytopenia (1/106). Among patients aged >60 years, these rates were 8.3% and 1.5%, respectively.

Antinuclear antibodies (ANAs) were tested in 170 patients without known connective tissue disease and were positive (titer³1/160) in 73 (42.9%). The positivity rates were 40.0% incase of clinical signs of connective tissue disease and 41.8% otherwise.

Antiphospholipid antibodies were positive in 7 patients (73 tested). The positivity rates were 11.1%in case of history of thrombosis or fetal loss and 9.4% in the absence of evocative context.

The positivity rates ofdirectantiglobulintest (tested in 64 patients) were 30.4% in case of anemia or lowhaptoglobinlevel, and 7.3% otherwise.

Serum protein electrophoresis was performed in 158 patients. None had a history of repeated or severe infections.Hypogammaglobulinemia(<5g/L) was detected in 1 patient over 76 with lymphopenia and in1 patient without lymphopenia.

HCV, HBV and HIV were tested in respectively 143, 140 and 159 patients. No new infection was detected.

Nine patients were tested for Helicobacter pylori infection and 3 were positive. One patient had symptoms evocative of gastritis and was positive for Helicobacter. Among the 7 patients without symptoms of gastritis, 2 were positive (28.6%).

Thyroid stimulating hormone (TSH) was tested in 112 patients without history of thyroid dysfunction. The positivity rates were 50.0% in case of symptoms evocative of thyroid dysfunction and 7.3% otherwise.

Conclusions: Except for ANAs (whose presence may lead to hydroxychloroquine prescription) andhypogammaglobulinemia, the positivity rates were at least three-fold higher in case of evocative context, discussing the systematic use of these tests. HIV, HCV and HBV infections revealed by ITP seem very rare in France.