Abstract:
Immunological Thrombocytopenic Purpura or ITP is the most common benign blood disease in pediatrics.
The aim of this work is to analyze the epidemiological, clinical, paraclinical and etiological profile of Primary and secondary immune thrombocytopenia.
It is a retrospective study over a period of four years from September 2017 to September 2021, collecting all cases of immunological thrombocytopenic purpura hospitalized in hematology pediatric unit at the Abderrahim Harouchi Children’s Hospital in Casablanca.
135 patients with ITP were hospitalized in this period including 76 boys (56.3%) and 59 girls (43.7%). The average age was 5.8 years (1 month -14 years). According to Buchanan bleeding score, 3.4% of the patients were grade 0, 9.6%, were grade 1 and 39.2% of the patients were grade 2, 41.5 % of the patients were grade 3, 5% in grade 4 and only 1 case was in grade 5. Etiologically, 86% of primary ITP and 14% of secondary ITP were recorded. The etiological assessment revealed 9 cases of Helicobacter pilori infection, 6 cases of immune deficiency (5 cases of WISKOTT ALDRICH and 1 case of ALPS) and4 probable cases of systemic lupus erythematosus.
Patients were treated with either corticosteroids or intravenous immunoglobulin (IgIV). The trend was towards acute ITP in 85 cases (63%), persistent and chronic ITP in 50 cases (37%).
For a better management of chronic and persistent ITP a complete etiological assessment is essential. This will allow to propose an etiological treatment and therefore an improvement of thrombocytopenia.
Keywords: primary immune thrombocytopenia, secondary immune thrombocytopenia, child, wiskott Aldrich syndrome, helicobacter infection.
INTRODUCTION
Immune thrombocytopenic purpura (ITP) is the most common benign hemopathy in pediatrics, it is defined as an acquired autoimmune bleeding disorder with a low platelet count, usually, less than 100,000 in the presence of a generalized petechial rash, bruising, or bleeding in an otherwise healthy child [1].The incidence of ITP ranges from 1.1 to 6.4 cases per 100,000 children-years with peak in childhood (age 1–5 years) [2,3]. There is a slight predominance in males than females [4].
The classification of ITP depends on the duration of disease based on the following definitions: newly diagnosed (from diagnosis to three months), persistent (3-12 months), and chronic (after 12 months) [3,5]. Chronic ITP is seen in 10 to 25% of these patients with a prevalence estimated as 9.5 to 11.2 per 100,000 persons year [3].
The ITP etiology should be sought in the presence of a recurrent or chronic ITP. Most cases are considered idiopathic and labelled as ‘primary ITP’, whereas approximately 20% of ITP cases are associated with an underlying disorder and are labelled as ‘secondary ITP’[3]. This secondary ITP can be due to infection with a number of agents, including hepatitis C virus (HCV), human immunodeficiency virus (HIV), and Helicobacter pylori. Other causes include underlying autoimmune and lymphoproliferative disorders such as systemic lupus erythematosus, Wiskott-Aldrich syndrome, and common variable immunodeficiency, as well as drugs such as trimethoprim-sulfamethoxazole [3].
The ITP patients are usually treated with steroids or immunoglobulin as a first line treatment. For chronic ITP the traditional therapies are rituximab and splenectomy [3]. Mortality from ITP in children is rare and mainly due to complications from catastrophic bleeding, specifically intracranial hemorrhage [1]. The disease is self-limiting in a large proportion of patients, and 75% to 90% of children will recover spontaneously within 6 to 12 months [2,6].
The aim of this retrospective study is to highlight the frequency of secondary ITP among ITP patients, to precise the specificities of theses patients, and to determine the etiological profile of the ITP in children.
MATERIALS AND MEHODS
In this retrospective study, 135 ITP patients admitted in Hematology-oncology unit in pediatrics 3 Department, A. HAROUCHI University Hospital, Casablanca, Morocco, between September 2017 and September 2021 were included. Patients were included in this study if their age at diagnosis was less than15 years, and their platelet count was low (less than 100 000/mm3). Exclusion criteria included the following: the presence of mild splenomegaly and having received treatment that may cause drug-induced thrombocytopenia. The demographic and clinical characteristics of patients at the initial diagnosis of ITP were abstracted from their medical records. These data included age, gender, initial platelet count, initial presentation of mucocutaneous purpura.The bleeding was assessed using the BUCHANAN score (grade 0, grade 1, grade 2, grade 3, grade 4 and grade 5). Patients were graded based on their medical history or a physical examination completed at the time of the appointment. Grade 1 is few bruises and petechiae. Grade 5 is life threatening hemorrhage. Furthermore, data about the need for treatment of ITP and the response to treatment were collected. The screening for antinuclear antibody (ANA), hepatitis C virus (HCV), hepatitis B virus (HBV), human immunodeficiency virus (HIV), immunoglobulin dosage and lymphocyte phenotype were tested in the patients with chronic ITP. The H. pylori stool antigen test or the urea breath test were used to screen patients for H. pylori were abstracted from the medical records.
RESULTS
A total of 135 children who were diagnosed with ITP at our unit between September 2017 and September 2021 and were included in this study. Their age at diagnosis ranged between 1 month and 14 years, with a mean of 5,8. There were 76 boys (56.3%) and 59 girls (43.7%). According to Buchanan bleeding score, 3.4% of the patients (5 cases) were grade 0, 9.6% (13 cases), were grade 1 and 39.2% of the patients (53 cases) were grade 2, 41.5 % of the patients (56 cases) were grade 3, 5% in grade 4 and only 1 case was in grade 5.
116 patients (86%) were diagnosed as having primary ITP and 19 (14%) were considered to have secondary ITP because the ITP was associated with another underlying disorder or condition. Among the 135 children, 85 patients (62.9%) had an acute ITP and 50 patients (37%) had a chronic ITP. In these chronic ITP, a concurrent immune disease was observed in 19 (38%) patients who were diagnosed with secondary ITP. Of those who were diagnosed with secondary ITP, 6 (31,5%) had primary immune deficiency and 4 (21%) had systemic lupus erythematosus. The 9 remaining patients (47.3%) had a helicobacter infection. All patients were tested for the presence of HCV, HBV, and HIV, and none tested positive. In patients with primary immune deficiency we found 5 cases of Wiskott Aldrich syndrome. All these patients had thrombocytopenia, eczema and recurrent infections.
Table 1 shows the characteristics of patients with primary and secondary ITP. Patients with secondary ITP were slightly younger than patients with primary ITP. The mean age was 6 years for patients with primary ITP and 5.4 years for patients with secondary ITP. Among patients with secondary ITP, the mean age of patients with a primary immune deficiency (mean: 3.7 years) was lower than that for patients with other disorders (mean: 6.5 years). At the time of diagnosis, 74% of patients with secondary ITP and 62% patients with primary ITP had an initial platelet count >30 109 /L. Among patients with secondary ITP, the median initial platelet count for patients with a primary immune deficiency was slightly higher (34 109 /L) than that for patients with other disorders (23 109 /L). At the time of diagnosis, the Buchanan bleeding score was higher than 2 in 48 % of patients with primary ITP and in 37% of patient with secondary ITP. The two groups had poor response to corticosteroid treatment (less than 20% had good response). However, the primary ITP patients had good response to immunoglobulin in 55% of cases versus 14,8% of good response in the secondary ITP patients.
Table 1. Clinical, laboratory characteristics and response of treatment of the whole cohort of 143 patients