The goal of this clinical trial is to learn if hydroxychloroquine (HCQ) plus thrombopoietin receptor agonists (TPO-RA) works to treat primary immune thrombocytopenia with positive anti-nuclear antibodies in adults. It will also learn about the safety of HCQ plus TPO-RA. The main questions it aims to answer are:

Does HCQ plus TPO-RA raise the response rate in participants, compared to TPO-RA alone? Does HCQ plus TPO-RA prolong the response duration in participants, compared to Pred alone? Does HCQ plus TPO-RA decrease the dose of TPO-RA to maintain response in participants, compared to TPO-RA alone? What medical problems do participants have when taking HCQ plus TPO-RA? Researchers will compare HCQ plus TPO-RA with TPO-RA alone to see if HCQ plus TPO-RA works better to treat primary immune thrombocytopenia with positive anti-nuclear antibodies.

Participants will:

Take TPO-RA every day for no more than 24 weeks, adjust the dose of TPO-RA according to the platelet level, with or without HCQ twice a day for 1 year; Visit the clinic once every 1 weeks for the first 8 weeks, and once every 2-4 weeks in the following 10 months for checkups and tests; Keep a diary of their symptoms

Primary immune thrombocytopenia (Primary immune thrombocytopenia, ITP) is an acquired autoimmune hemorrhagic disease characterized by a decreased peripheral platelet count and an increased risk of bleeding. It has been reported that 33.3% -39.2% of ITP patients have positive antinuclear antibodies (ANA) in the course of the disease.In the meantime, they do not meet the diagnostic criteria for rheumatic diseases such as lupus erythematosus(SLE). ITP patients with positive ANA are prone to relapse and chronicity. Therefore, it is necessary to explore new clinical treatments to attain long-term remission in these patients.

Hydroxychloroquine (HCQ) has immune modulating role on a variety of immune cells.A clinical trial enrolled immune thrombocytopenia secondary to SLE, and ITP with positive anti-nuclear antibodiy (ANA) were treated with HCQ combined with glucocorticoids. The results showed an overall response rate of 60% (24 / 40), including 18 continuous complete response (CR) and 6 continuous response (R), and some patients had continued elevated platelet counts 3 months after treatment initiation. The above studies illustrate that HCQ contributes to the treatment of chronic ITP, especially as a long-term therapeutic agent with low economic burden and good tolerance. In patients who do not response to HCQ plus corticosteroids, TPO-RA, a second line treatment, will be recommended. By now, no study has assess the efficacy and safety of HCQ plus TPO-RA in these patients. In the current study, the question will be answered.

Inclusion Criteria:

1. Age is above 15 years old.
2. Before randomization, the clinical diagnosis is primary immune thrombocytopenia. The platelet count is less than 30×10^9 / L within 1 week before enrollment, or platelet count is less than 50×10^9 / L with bleeding symptoms within 1 week before enrollment.
3. The antinuclear antibody is positive.
4. Other autoantibodies (mainly including dsDNA antibodies, SSA, SSB, RNP, β 2-GP, ACA, ANCA) are negative.
5. Participants who had received at least two HD-DXM 40 mg/d ×4 d, failed or relapsed, or received standard dose prednisone (1-2 mg/kg/d) for 4 weeks, the platelet count remained <30×10 9 / L, or the platelet count normalized but decreased with prednisone tappering off, or prednisone 30mg to maintain the platelet number.
6. Prothrombin time does not exceed ± 3s of the normal value ranget, activated partial thrombin time is not outside normal range ± 10s; no history of coagulopathy except ITP.

(6)Understand the study procedures and sign the written informed consent form.

Exclusion Criteria:

1. Secondary thrombocytopenia caused by myelodysplastic syndrome, immune diseases such as systemic lupus erythematosus, early aplastic anemia, atypical reanemia, antiphospholipid syndrome, thrombotic thrombocytopenic purpura and various other causes.
2. The participant has experienced any arterial or venous thrombosis (stroke, transient ischemic attack, myocardial infarction, deep vein thrombosis or pulmonary embolism), or clinical symptoms and medical history indicate thrombophilia.
3. Congestive heart disease, including New York Heart Association (NHYA) Grade III / IV, occurred within 3 months prior to screening, arrhythmia requiring medication or myocardial infarction, or arrhythmia known to increase the risk of thrombotic events (such as atrial fibrillation), or corrected QT interval (QTc) is longer than 450 ms, or QTc> 480 ms in paricipants with bundle branch block.
4. A medical history of parenchymal organ transplantation or allogeneic bone marrow transplantation.
5. Having received any medication affecting platelet function ( Including but not limited to aspirin, aspirin-containing complexes, clopidogrel, salicylates, and / or non-steroidal anti-inflammatory drugs NSAIDs ) or anticoagulant therapy for over consecutive 3 days within 2 weeks before screening.
6. With Glucose-6-phosphate dehydrogenase deficiency.
7. With retinal or visual field changes caused by 4-aminoquinoline compounds.
8. Being allergic to 4-aminoquinoline compounds.
9. Having evidence of Human Immunodeficiency Virus (HIV)/ hepatitis C virus(HCV)/ hepatitis B virus(HBV) infection (HIV antibody or HCV antibody is positive, HBV surface antigen is positive, or HBV surface antigen is negative but HBV-DNA indicating viral replication.
10. Glutamate transaminotransferase (ALT) or glutamate transaminase (AST) is higher than 1.5 times the upper limit of normal value (ULN), or total bilirubin or blood creatinine is higher than 1.2 times the ULN.
11. With liver cirrhosis or portal hypertension.
12. With evidence of malignant tumor activity, or receiving anti-tumor treatment within 5 years prior to the screening.
13. Participants being pregnant or lactating, or with potential fertility, reluctance to use effective contraception within the entire trial cycle and within 28 days after the end of the trial (or within 28 days after premature withdraw).

IPD information will become available starting 6 months after publication, for 1 year.