Primary immune thrombocytopenia (ITP), a common hemorrhagic disease causing a tremendous burden to the social economy, is characterized by the bleeding of mucosa, skin, brain, and/or other important organs.[1] Serious hemorrhage can even lead to death. Despite its seriousness, the golden criteria for ITP diagnosis and treatment are lacking. Consequently, much hinges upon physician experience as well as the willingness of patients and their families. In fact, standards for diagnosis and treatment of patients with ITP only appeared when the American Society of Hematology published a landmark guideline in 1996. It is important to find out hematologists’ routine strategies for managing ITP and the extent they have complied with or deviated from ITP guidelines. However, such research is few and far between. We published such a study in 2009.[2] After that, the context for China-based hematologists diagnosing and treating ITP has undergone fundamental changes, including the publication of the Chinese Society of Hematology (CSH) guideline in 2011 and its update in 2016.[3]
To better understand how Chinese hematologists are informed by the guidelines in diagnosing and treating ITP nowadays, we conducted another survey among Chinese hematologists in 2018, using the same questionnaire for the 2009 survey. About 534 questionnaires were issued in 2009, 246 (46.1%) were recovered and 241 were available for analysis. In 2018, 150 questionnaires were issued with 70 (46.6%) being recovered and used for analysis. Data were processed by SPSS 18.0 (SPSS Inc., Chicago, IL, USA) for statistical analysis. The ratio between the two surveys was compared using the Chi-squared test or Fisher exact test. P < 0.05 was considered significant.
Three questions about ITP diagnosis were asked, with the first one being whether the respondents would prescribe peripheral blood smears if a patient was suspected of ITP. A similar percentage of the doctors in the two surveys answered: “yes” (72.2% in 2009 and 77.6% in 2018, P > 0.05). The second question about diagnosis invited the respondents to choose laboratory tests they would prescribe for patients suspected of ITP. In general, doctors in 2018 reported prescribing more tests than those surveyed in 2009, with 14 of the listed tests being preferred by over half of the doctors in 2018 in contrast to only seven by a similar percentage of those in 2009 [Figure 1].
Figure 1.
The proportion of hematologists who choose these laboratory examinations to diagnose ITP in 2019 and 2018. ∗P < 0.05, compared with the year of 2009. ANA: Anti-nuclear antibodies; APL: Anti-phospholipid antibody; BMB: Bone marrow biopsy; BMP: Bone marrow puncture; dsDNA: Double-stranded deoxyribonucleic acid; ENA: Extractable nuclear antigen; HBV: Hepatitis B virus; HCV: Hepatitis C virus; HIV: Human immunodeficiency virus; Hp: Helicobacter pylori; Ig: Immunoglobulin quantification; ITP: Primary immune thrombocytopenia; MAIPA: Monoclonal antibody-specific immobilization of platelet antigen; PAIg: Platelet-associated immunoglobulin; PBS: Peripheral blood smears; Ret: Reticulocyte; TA: Thyroid antibody; TPO: Thrombopoietin.
Noticeably, a surprisingly high rate of doctors would prescribe bone marrow puncture across 10 years, as 95.8% of respondents in 2009 and 97.1% in 2018 reported using it. This trend contradicts the international guidelines which suggest that bone marrow puncture be prescribed only under certain conditions (eg, in patients aged over 60 years or those considering splenectomy) to avoid unnecessary pain and to save medical resources.[4] Nevertheless, bone marrow puncture can be necessary in China for two reasons. Firstly, it can prevent potential conflicts between doctors and patients. Secondly, it helps to rule out many more diseases in Asian patients than in non-Asian ones.
In addition, most respondents dismissed ineffective splenectomy as a key criterion for diagnosing refractory ITP (76.8% in 2009 vs. 73.0% in 2018, P = 0.536). This practice deviated from the recommendations in all major guidelines including CSH ones. We speculate that this may be related to the fact that patients with ITP in China would reject splenectomy more frequently than those in western countries. Therefore, CSH may need to address this issue in its update of the 2016 guideline.
In terms of treatment, the most important goal was to control the bleeding degree as 40.2% of the hematologists in 2009 and 68.3% in 2018 selected it (χ2 = 15.326, P < 0.001). Moreover, the respondents in 2018 held more stringent criteria for starting treatment and hospitalization (P < 0.05). This trend tends to align better with the international literature about ITP treatment.
Most doctors would choose glucocorticoid, usually in a small dose for a long period, as the primary therapy. This choice differs from the CSH 2016 guideline which recommends that a high dose of dexamethasone (HD-DXM) at 40 mg/day for 4 days being used instead of a small dose of prednisone for a long course for initial treatment.[3]
In this study, we surveyed Chinese hematologists’ strategies in diagnosing and treating ITP in 2018 and then compared the results with those obtained from our 2009 survey. There are similarities and differences between Chinese hematologists’ ITP management strategies in 2009 and 2018. For diagnosis, while the practices had changed a decade later due to the increased use of laboratory tests in 2018 in comparison to 2009, Chinese hematologists persisted in using bone marrow puncture and dismissing ineffective splenectomy as a major criterion of diagnosing refractory ITP. For treatment, Chinese hematologists adopted more stringent criteria for starting treatment and hospitalization in 2018 than in 2009. However, they kept on using a small dose of glucocorticoid for a long period as their primary therapy despite the recommendation of the CSH 2016 guideline to use a high dose of HD-DXM for a short course. There are limitations to this study. For instance, the sample size in 2018 was limited, and the recovery rate of the questionnaires was low. Therefore, further studies with larger samples are desirable.
Acknowledgements
The authors thank Dr. Luo Na at the Chinese University of Hong Kong and Mr. Qi-Yuan Zhou at the University of California, Davis for editing the language of this manuscript.
Funding
This work was supported in part by grants from the Training Plan of Yunnan Medical leaders (No. L-2017005) and Kunming Medical University Medical Innovation Team (No. CXTD201615).
Conflicts of interest
None.
Footnotes
How to cite this article: Wang HH, Bi H, Zhang L, Li HY, Xue F, Zhou ZP, Yang RC. Strategy changes in Chinese hematologists’ diagnosis and treatment of primary immune thrombocytopenia across 10 years (2009–2018). Chin Med J 2019;00:00–00. doi: 10.1097/CM9.0000000000000511
Hong-Hui Wang and Hui Bi contributed equally to the work.
References
- 1.Cooper N, Ghanima W. Immune thrombocytopenia. N Engl J Med 2019; 381:945–955. doi: 10.1056/NEJMcp1810479. [DOI] [PubMed] [Google Scholar]
- 2.Zhou Z, Yang R. Investigation on the strategy of the diagnosis and treatment of primary immune thrombocytopenia in hematological doctor in our country. Chin J Hematol 2011; 32:201–203. doi: 10.3760/cma.j.issn.0253-2727.2011.03.015. [PubMed] [Google Scholar]
- 3.Thrombosis and Hemostasis Group, Hematology Society, Chinese Medical Association. Consensus of Chinese experts on diagnosis and treatment of adult primary immune thrombocytopenia (version 2016) [in Chinese]. Chin J Hematol 2016; 37:89–93. doi: 10.3760/cma.j.issn.0253-2727.2016.02.001. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Neunert C, Lim W, Crowther M, et al. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood 2011; 117:4190–4207. doi: 10.1182/blood-2010-08-302984. [DOI] [PubMed] [Google Scholar]