Abstract
Study objectives
We aim to evaluate disease characteristics and treatment practices of pediatric pts. with Immune thrombocytopenia (ITP) in Russia.
Materials and methods
The ITP Registry was a multicenter, prospective, observational cohort study. Inclusion criteria: diagnosis of primary ITP, informed consent of the patient/guardians. Exclusion criteria: secondary or congenital thrombocytopenia. Data from medical records were registered in the e-CRF in average every 3 months. Descriptive statistics were used. Patients were registered since June 2011 till June 2014.
Results
Ninety-three pediatric pts, 46 male (49.5%) and 47 female (50.5%) with a median age 8.4 yrs (range 0.5-17.8) from 5 centers in various regions of Russia were included. The mean observation period reached 17.1 ± 6.5 mo (range1.4 to 28.6 months). Seventy (75.3%) pts had acute and 24.7% pts had insidious disease onset. The presence of trigger factors for ITP development was found in more than half of the cases (in 61.3% of patients), they are listed in Table 1.
Triggers
| . | N . | % . |
|---|---|---|
| No triggers | 36 | 38.7% |
| Infection | 46 | 49.5% |
| Vaccination | 8 | 8.6% |
| Other | 3 | 3.2% |
| Total | 93 | 100% |
| . | N . | % . |
|---|---|---|
| No triggers | 36 | 38.7% |
| Infection | 46 | 49.5% |
| Vaccination | 8 | 8.6% |
| Other | 3 | 3.2% |
| Total | 93 | 100% |
Median disease duration at enrollment was 1.07 years (range 0 to 16.7 yrs). ITP duration shorter than 5 years at the enrollment was reported in 89.2% pts, up to 1 year - in 43 (46.2%), 1- 5 years - in 40 (43%), 5-10 years - in 8 (8.6%), >10 years - in 2 (2.2%) pts. Newly diagnosed ITP was reported in 35 (37.6 %) pts, persistent ITP - in 12 (12.9 %), chronic ITP - in 46 (49.5 %) pts.Median platelets count was 12,0 x 109/L (range 0.0 - 72.0 109/L).
Ninety-two (98%) pts experienced hemorrhagic manifestations during the course of ITP: skin hemorrhages - in 98.9%, oral bleeding - in 15.1%, epistaxis - in 36.6%, gastrointestinal bleeding - in 1.1%, intracranial bleeding - in 1.1%, hematuria - in 1.1%, and other hemorrhages - in 9.7% of pts.
Relationship between hemorrhagic syndrome and platelet count at the enrollment is provided in table 2.
Relationship between hemorrhagic syndrome and platelet count (at enrollment)
| Hemorrhage highest grade according to WHO . | Platelet count (visit 1) . | Total pts / % . | ||
|---|---|---|---|---|
| < 30,000 | 30,000 -50,000 | >50,000 | ||
| 0 | 3 5.5% | 3 5.5% | 49 89.1% | 55 100% |
| 1 | 11 40.7% | 5 18.5% | 11 40.7% | 27 100% |
| 2 | 5 62.5% | 0 0% | 3 37.5% | 8 100% |
| 3 | 2 66.7% | 1 33.3% | 0 0% | 3 100% |
| Total | 21 22,6% | 9 9.7% | 63 67.7% | 93 100% |
| Hemorrhage highest grade according to WHO . | Platelet count (visit 1) . | Total pts / % . | ||
|---|---|---|---|---|
| < 30,000 | 30,000 -50,000 | >50,000 | ||
| 0 | 3 5.5% | 3 5.5% | 49 89.1% | 55 100% |
| 1 | 11 40.7% | 5 18.5% | 11 40.7% | 27 100% |
| 2 | 5 62.5% | 0 0% | 3 37.5% | 8 100% |
| 3 | 2 66.7% | 1 33.3% | 0 0% | 3 100% |
| Total | 21 22,6% | 9 9.7% | 63 67.7% | 93 100% |
Severe course of ITP after enrollment was observed in 12 (13%) pts (of whose 6 (6.5%) had clinically significant hemorrhage at the disease onset and 6 (6.5%) had new clinically significant hemorrhages during follow-up period.
Refractory ITP at enrollment was reported in 9 (9.7%) pts and was associated with the resistance to the first-, second- and subsequent lines of therapy. At enrollment 42 (45.2%) pts received specific treatment for ITP. Before enrollment, splenectomy was reported in only 1 (1.1%) 14-years old patient who had a complete response. During the study, splenectomy was performed in 6 (6.6%) pts with chronic ITP; the duration of the disease at the time of splenectomy varied from 2 to 10 years, with average duration of 4.69 years (median - 4.5 years). Complete response to splenectomy was observed in 3 (50%) pts, a partial response - in 2 (33.3%), no response - in 1 (16.7%) patient. Loss of response to splenectomy was not reported. During the study, severe ITP was reported in 8 (8.7%) pts, 41 (44.6%) pt had various hemorrhagic manifestations of ITP at least at 1 visit, grade IV hemorrhagic syndrome was not reported.
Thirty-eight (41%) pts received 1-st line treatment: glucocorticosteroids (GCS) - 23 (60.5%) pts, IVIG - 5 (13.2%), alfa-interferons -16 pts (42.1%). Twenty-three pts (24.7%) received second-line therapy: GCS - 1 (4.3%), IVIG -1 (4.3%), immunosupression - 1 (4.3%), rituximab - 2 (8.7%), romiplostim - 11 (47.8%), eltrombopag - 14 (60.9%).
Conclusion
For the first time new information on the features of the disease and patterns of management of pediatric pts with primary ITP in Russia was obtained in a prospective study. Interestingly, the preferred therapy for the 2nd or subsequent lines are TPO receptor agonists used outside the approved indications in research institutions, based on published clinical trial data. Splenectomy rate before and during the study was only 7.5% (7 pts) with chronic ITP; in 1 child (14.3%) splenectomy was ineffective. Low acceptance of splenectomy suggests TPO-mimetics as potential second-line therapy. In total, good disease control is achievable in the majority of pediatric pts with ITP.
Off Label Use: use of TPO-mimetics in children.
Author notes
Asterisk with author names denotes non-ASH members.
