Synopsis of the 2025 guideline for the diagnosis and management of adult primary immune thrombocytopenia

Primary immune thrombocytopenia (ITP) is an acquired autoimmune disorder causing isolated thrombocytopenia. Driven by the rapid emergence of novel therapies and new clinical evidence, the Thrombosis and Hemostasis Group of the Chinese Society of Hematology has released the 2025 edition of its guideline for adult ITP.[1] This update incorporates major advances, including new roles for thrombopoietin receptor agonists (TPO-RAs) and the introduction of spleen tyrosine kinase (SYK) inhibitors, Bruton’s tyrosine kinase (BTK) inhibitors, and neonatal Fc receptor (FcRn) antagonists. The key recommendations emphasize a shift toward individualized, goal-directed therapy aimed at achieving sustained, treatment-free remission. Diagnostic Evaluation The diagnosis of ITP remains one of exclusion. Key diagnostic criteria include at least two consecutive blood tests showing a platelet count <100 × 109/L, a normal peripheral smear, the absence of splenomegaly, and the exclusion of other secondary causes, with bone marrow cytology typically revealing increased or normal megakaryocytes with maturation disorders. The laboratory workup consists of basic evaluations (e.g., complete blood count, viral screening, and autoantibody tests for secondary causes) and special evaluations for specific scenarios (e.g., platelet-specific autoantibodies and thrombopoietin [TPO] levels). Additionally, assessment of reticulated platelets or the immature platelet fraction is useful for evaluating platelet production, whereas next-generation sequencing is now recommended in refractory or early-onset cases to rule out hereditary or clonal disorders. Bleeding Scoring System To quantify bleeding risk, the guideline uses a 2-domain score. The total score is the sum of an age component (1 point for ≥65 years, 2 points for ≥75 years) and a bleeding-manifestation component. For bleeding, points are assigned based on the single most severe manifestation, with scores escalating based on location and severity [Supplementary Table 1, https://links.lww.com/CM9/C914]. A total score of ≥5 signifies a high risk of life-threatening bleeding and warrants urgent intervention. Management Principles The goal of ITP treatment is to achieve a safe platelet count that prevents bleeding, not necessarily to normalize it. Therapy must be individualized, balancing hemostatic efficacy against treatment toxicity, with a preference for finite-duration strategies aimed at achieving long-term, treatment-free remission. Crucially, the 2025 update emphasizes thrombosis risk assessment. For individualized evaluation, the guideline recommends the use of the risk assessment scales from the “Chinese expert consensus on the diagnosis and management of thromboembolism in ITP (2023)”. The guideline places a parallel emphasis on health-related quality of life (HRQoL), establishing it as a key treatment outcome and advocating for regular monitoring with validated tools such as the disease-specific ITP-patient assessment questionnaire (ITP-PAQ). Therapeutic Algorithms The overall therapeutic algorithm, which integrates the management principles described above, is presented in Figure 1. The levels of evidence and grades of recommendation used in this guideline follow the approach described in the updated international consensus report on ITP [Supplementary Table 2, https://links.lww.com/CM9/C914]. The grading scheme used here is a traditional Levels I–IV/Grades A–C framework.Figure 1: Diagnosis and management algorithm for adult ITP. BTK: Bruton’s tyrosine kinase; CBC: Complete blood count; CsA: Cyclosporine A; FcRn: Neonatal Fc receptor; HD-DXM: High-dose dexamethasone; ITP: Primary immune thrombocytopenia; IVIg: Intravenous immunoglobulin; Methylpred: Methylprednisolone; PDN: Prednisone; PLT: Platelet; rhTPO: Recombinant human thrombopoietin; RTX: Rituximab; SYK: Spleen tyrosine kinase; TPO-RAs: Thrombopoietin receptor agonists.Emergency treatment Emergency treatment is indicated for patients with severe, life-threatening bleeding (score ≥5) or those requiring urgent surgery. The standard regimen involves intravenous immunoglobulin (IVIg) and/or high-dose methylprednisolone. Platelet transfusions are used adjunctively for critical hemostasis. The guideline also notes that recombinant human TPO (rhTPO) or romiplostim/romiplostim N01 can be added to accelerate platelet recovery (evidence level III/IV). Initial treatment Corticosteroids and IVIg are the cornerstones of first-line treatment. The preferred corticosteroid regimen is high-dose dexamethasone (HD-DXM; 40 mg/day for 4 days) due to its rapid onset and short course (evidence level Ia). Prednisone (1 mg∙kg−1∙day−1) is an alternative but should be tapered promptly over 6–8 weeks. IVIg is another key option, particularly for patients requiring a rapid platelet increase, those with contraindications to corticosteroids, or those in the peripartum setting. Initial combination treatment The 2025 guideline refines the specific indication for initial combination strategies. This approach is now specifically recommended for newly diagnosed patients who respond to corticosteroids but experience diminishing efficacy during the tapering phase. To prevent relapse and facilitate successful steroid discontinuation, the guideline advises adding a second agent to the ongoing corticosteroid regimen. Recommended combination partners include rhTPO, rituximab, oseltamivir, all-trans retinoic acid, caffeic acid, or mycophenolate mofetil (evidence level Ib). This strategy aims to sustain the initial remission and minimize prolonged steroid exposure. Subsequent treatment For patients who are corticosteroid-dependent or unresponsive, subsequent therapies include: Thrombopoietin receptor agonists This class includes rhTPO, eltrombopag, hetrombopag, avatrombopag, and romiplostim (or the biosimilar romiplostim N01). They stimulate platelet production and demonstrate high overall response rates (ORRs >60%; evidence level Ib, Grade A recommendation). The choice of agent depends on administration preference (oral vs. subcutaneous) and dietary restrictions. Switching between different TPO-RAs is recommended if the first choice is ineffective. Rituximab B-cell depletion therapy with rituximab is an established second-line option. Both the standard dose (375 mg/m2 × 4 weeks) and low dose (100 mg/week × 4 weeks or 375 mg/m2 once) are effective (evidence level IIa/IIb, Grade B recommendation). It is particularly suitable for patients seeking long-term drug-free remission, though the onset of action is slower than TPO-RAs. SYK inhibitors The 2025 guideline now includes SYK inhibitors, which inhibit SYK‑mediated signaling downstream of Fcγ receptors and B‑cell receptors, thereby reducing antibody‑mediated platelet destruction and potentially limiting autoantibody production. Fostamatinib shows an ORR of 43–73% with a time to response (TTR) of approximately 2 weeks (evidence level Ib). In a phase III trial, sovleplenib, an agent developed in China, demonstrated an ORR of 80%, a median TTR of 8 days, and a 6-month sustained response rate (SRR) of 48% (evidence level Ib), providing a potent oral option for refractory patients. BTK inhibitors BTK inhibitors suppress key pathogenic pathways in ITP, including B-cell activation and macrophage phagocytosis. Rilzabrutinib demonstrated an ORR of 64% with a median TTR of 15 days and a 24-week SRR of 23% (evidence level Ib). A Chinese phase II trial of orelabrutinib showed an ORR of 40% and a median TTR of 9 days (evidence level III), with improved efficacy observed in patients who had previously responded to initial therapy. FcRn antagonists Efgartigimod is a FcRn antagonist that selectively targets and promotes the degradation of immunoglobulin G antibodies. This leads to a rapid reduction in the levels of pathogenic immunoglobulins G. Efgartigimod has demonstrated an ORR of 46% with a median TTR of 7 days (evidence level Ib). It is generally well tolerated, with common adverse events including headache and hematuria. Decitabine Low-dose decitabine is an option for refractory ITP (evidence level IIa, Grade B recommendation). Its mechanism is thought to involve both restoring normal megakaryocyte apoptosis and modulating immune responses. The therapy has shown efficacy and a favorable safety profile in patients unresponsive to other treatments. Subsequent combination therapies The guideline explicitly recommends combining agents with different mechanisms for refractory patients to achieve synergistic effects and improve sustained response. Key evidence-based combinations include rituximab plus rhTPO, rituximab plus all-trans retinoic acid (ATRA), eltrombopag plus diacerein, tacrolimus plus danazol, and ATRA plus danazol (evidence level Ib). Clinical trials Enrollment in phase II/III clinical trials investigating novel agents, repurposed drugs, and combination therapies is recommended for eligible patients. This provides access to novel investigational agents and contributes to advancing the treatment of ITP. Splenectomy Splenectomy remains a curative option but is generally deferred until medical therapies have failed and the disease duration exceeds 12 months (Grade C recommendation). It is less commonly performed due to the availability of effective pharmacological alternatives but remains valuable for patients desiring a permanent drug-free solution. Other agents For patients failing the above treatments, other immunosuppressive or immunomodulatory agents such as cyclosporine A, danazol, azathioprine, and vincristine are also options, but are typically reserved for refractory cases due to limited evidence and side effect profiles. In conclusion, the 2025 Chinese guideline marks a paradigm shift in ITP management, moving beyond platelet count normalization to focus on preventing bleeding and improving quality of life. The introduction of novel agents—including SYK, BTK, and FcRn inhibitors—alongside refined combination strategies has significantly expanded the therapeutic toolkit. By standardizing diagnosis and stratifying treatment, this guideline aims to optimize outcomes for adults with ITP in China. Future research should prioritize identifying biomarkers to further personalized therapy. This should be coupled with a greater emphasis on patient-reported outcomes, ensuring that improvements in HRQoL are a fundamental goal of treatment.