The Epidemiology of Immune Thrombocytopenia in Taiwan: A Retrospective Analysis of Data from the National Health Database


Tzeon-Jye Chiou*

Citation: The Epidemiology of Immune Thrombocytopenia in Taiwan: A Retrospective Analysis of Data from the National Health Database. American Research Journal of Hematology; 3(1): 1-15.

Copyright This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Abstract:

Objectives: This study aimed to investigate the prevalence and current treatment status of immune thrombocytopenia (ITP) in Taiwan. Methods: This was a retrospective study conducted using claim data collected from the Bureau of National Health Insurance (BNHI) of Taiwan from 2003 to 2007. ITP patients were identified using the ICD-9 code, 287.3 (primary thrombocytopenia), with two diagnoses separated by at least 14 days for diagnostic specificity. In addition, sensitivity analysis was based on 28 (ITP-28) and 84 (ITP-84) days. Results: ITP prevalence ranged from 10.35 to 11.02 (per 100,000 individuals) with an annual number of 2,300 to 2,500 patients, and sensitivity analyses using ITP-28 and ITP-84 criteria showed that the prevalence were “9.52 to 10.35” and “6.87 to 8.14” in 5,445 ITP patients, respectively. The median age of ITP-14 patients was 46.5 years. In children, the female-to-male ratio was nearly equal (0.93), whereas in adults, it was 1.91. About 3.9% received splenectomy, of which 64.3% were responsive to splenectomy. Further, 92.6% were responsive to steroids. The average costs per visit were US$ 36 and US$ 1,700 for outpatients and inpatients, respectively. For steroid-responsive patients, the mean costs for clinic visits and hospitalization were US$ 35 and US$ 1,415, respectively. In contrast, the medical expense for steroid-refractory patients was approximately one and a half times the costs for responsive patients (inpatient: US$ 54; outpatient: US$ 2,349). For splenectomy-responsive inpatients, the average expenses prior to, at, and after splenectomy were US$ 1,877, 5,476, and 2,061, respectively. For splenectomy-refractory inpatients, the costs were comparable to those of responsive patients (P> 0.05). On the contrary, there were significant differences between the expenditure for splenectomy-responsive and -refractory outpatients. Among ITP patients in Taiwan, 7.4% and 6.4% had hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, respectively, and 1.5% had both HBV and HCV infections. Patients with HBV were significantly high in the splenectomy group (splenectomy vs. non-splenectomy 11.7% vs. 7.2%, P = 0.01), and those who were more responsive to splenectomy had a low HCV infection rate, i.e., 14.5% had HCV infection in splenectomy-refractory group vs. 4.38% in splenectomy-responsive group (P = 0.02).

Conclusions:The epidemiology of ITP in Taiwan, including the age and sex, was comparable with that in western countries, except with lower incidence of splenectomy in our patients. The status of HBV and HCV infection in splenectomized patients should be closely monitored. The medical expenditure in Taiwan was much lower than that in western countries. We suggest that novel agents or more aggressive treatment strategies should be further explored or considered in Taiwan.

Keywords: Immune thrombocytopenia (ITP), prevalence rate, medical expenditure, ITP treatment efficacy, claim database


Description:

INTRODUCTION

 Immune thrombocytopenic purpura (ITP) is a common autoimmune hematological disorder characterized by abnormally low levels of platelets due to thrombocytopenia, caused by premature platelet destruction, and can affect children and adults. The prevalence rate of ITP in other countries was reported to be 9.5 to 11.2/100,000 patients (1,2); however, values over 20/100,000 patients (1) have also been reported. The incidence rate was approximately 1.6 to 3.8/100,000 patients in adults (1-8) and up to 4.8/100,000 in children<15 years (9). The female-to-male ratio was 1.9 to 1 (1).

Currently, the epidemiology data of ITP is unavailable in Taiwan. To provide epidemiology data and evaluate the current status of the treatment of ITP in this region, we conducted a retrospective analysis of the prevalence rate, age distribution, sex ratio of ITP patients, current trends in ITP treatment, treatment efficacy, and average medical expenditure for ITP treatment using data from the National Health Insurance Research Database (NHIRD) of Taiwan from 2003 to 2007.

MATERIALS AND METHODS

Data Collection

Claim data were collected from Bureau of National Health Insurance (BNHI), including outpatient and inpatient records from January 1, 2003 to December 31, 2007, with an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code of 287.3. The main data evaluated in our study included ambulatory care expenditure by visits, details of ambulatory care orders, inpatient expenditure by admissions, and details of inpatient orders.

Study Design and Eligibility

The ICD-9-CM code used to screen ITP patients was 287.3 (primary thrombocytopenia). The screened ITP patients were excluded if they were diagnosed with human immunodeficiency virus (HIV); malignancies or secondary malignancies of the lymph nodes or Hodgkin’s disease; myeloma or aplastic anemia; lymphoid, myeloid, or monocytic leukemia; other specified and unspecified leukemias; or systemic lupus erythematosus in the claimed database. Patients <1 year at the first diagnosis of ITP since 2003 were also excluded due to the possibility congenital or hereditary thrombocytopenia. In addition, each ITP patient was required to have two diagnoses of ITP, separated by at least 14 days, to improve the specificity of the ITP code. To identify ITP patients, sensitivity analyses were varied by adjusting the visit interval from 14 days to 28 and 84 days. 

Outcome Measures

The primary objective of this study was to estimate the prevalence rates of ITP in Taiwan from 2003 to 2007. This was defined as patients who sought medical services for ITP in a single year from ITP patients who fulfilled the inclusion and exclusion criteria divided by the total population of Taiwan for the corresponding year. The total population of Taiwan as the denominator was obtained from the Department of Household Registration Affairs, Ministry of the Interior, Taiwan. 

The secondary endpoints included the following: 1.) the characteristics of ITP in Taiwan (including sex and age distribution), 2.) Current clinical treatment efficacy (analysis subgroup: non-splenectomy steroid responsive, non-splenectomy steroid refractory, splenectomy-responsive as well as splenectomy-refractory), 3.) Percentage of ITP patients with hepatitis B virus and/or hepatitis C virus infection, and 4.) The medical expenditure covered by BHNI for ITP patients in Taiwan.

Statistical Analysis

To evaluate the epidemiology in different age groups, we further subdivided our study group by age into prevalence in children (<18 years) and in adults (≥18 years).

Patients’ characteristics, including age, sex, medical expenditure, frequency of visiting the outpatient clinics (OPD), splenectomy, and hepatitis B/C infection were examined. Age was calculated as the date of first diagnosis of ITP from the available data. The mean, standard deviation, median, and minimum and maximum values of age are used in this study. The expenditure and visit frequency were viewed individually for outpatients and inpatients. In addition, the length of hospitalization was analyzed for inpatient cares. Characteristics of sex, splenectomy, and hepatitis B/C infection are presented by the number of subjects and the corresponding percentage in the contingency tables. 

Comparisons among patients grouped by sex, age, splenectomy, and ITP treatment were adopted. The age, medical expense, and visit frequency for ITP patients between groups were examined using the t-test. The chi-squared test was conducted to determine statistically significant differences in sex, splenectomy frequency, and hepatitis B/C infection occurrence rate between groups.

RESULTS

 Prevalence and Characteristics

The data pool obtained from NHIRD between January 1, 2003 and December 31, 2007 revealed that 14,022 unique patients were diagnosed with ITP in Taiwan. Patients with a concurrent disease that made ITP as the unlikely diagnosis, included 25 patients with HIV infection. A total of 391 children<1 year of age were excluded from this study. In addition, 2,237 patients diagnosed with alternative diseases (including malignancies or secondary malignancies of the lymph nodes or Hodgkin’s disease; myeloma or aplastic anemia; lymphoid, myeloid, or monocytic leukemia; other specified and unspecified leukemias; or systemic lupus erythematosus) were excluded from this study. The remaining 11,369 patients who fulfilled all of the cohort definitions were enrolled in our study.

The enrollment criteria that there be two ITP diagnoses separated by at least 14 days further reduced the number of eligible patients to 5,445. To further improve sensitivity analysis, the number of patients with ITP diagnoses separated by 28 or 84 days was reduced to 4,659 and 3,042, respectively (Figure 1).


The prevalence rate of ITP in this study was 6.87 to 11.02/100,000 patients (based on different diagnosis criteria, e.g., ITP-14, ITP-28, and ITP-84) (Table 1). ITP prevalence rate in adults and children (according to ITP-14) was conspicuously higher in adults (up to 12.09/100,000 patients) than in children (up to 8.37/100,000 patients) (Table 1).

ITP-14, patients with any two diagnoses separated by at least 14 days
ITP-28, patients with any two diagnoses separated by at least 28 days
ITP-84, patients with any two diagnoses separated by at least 84 days
Sex distribution with female-to-male ratio was 1.67 and the median age of patients was46.5 years (Table 2). The age distribution of ITP-14 patients by sex is presented in Figure 2. Of 961 children <18 years, the sex ratio was comparable (male-to-female: 499 : 462) in contrast to the ratio of female-to-male of 1.91 among 4,484 adults.

Current Treatment Efficacy
Of 5,445 ITP-14 patients, 3.9% underwent splenectomy. Splenectomy was only performed in 1.7% children, but this value was conspicuously higher in adults (4.4%, 197/4,484 patients, P<0.0001). Of 213 ITP patients who received splenectomy, 64.3% (137/213) responded to the surgery. The median age of patients receiving splenectomy with response was 41.3 years, and that of refractory to splenectomy patients was45.4 years (Table 3). 
Majority of ITP patients who did not receive splenectomy were responsive to corticosteroids (92.6%, 4,844/5,232 patients), and were first diagnosed with ITP at a young age (steroid-refractory vs. steroid-responsive = 49.0 vs. 44.3, P = 0.0003) (Table 3).