Before starting treatment of ITP, special attention to thrombocytopenia associated with H. pylori infection is needed in the regions of its high prevalence. Since a high prevalence of H. pylori and a high platelet response rate to its eradication are well demonstrated in Japan [36], a recent Japanese reference guide for management of adult chronic ITP recommends to screening and eradication of H. pylori when ITP is suspected, irrespective of platelet counts (Fig. 1) [37]. However, the value of the screening and eradication of H. pylori is uncertain in the regions of its low prevalence and a low platelet response to its eradication, like the United States [36, 38].

After exclusion of H. pylori-associated ITP, treatment of ITP should be initiated to maintain safe platelet counts as a goal. Although the safe platelet count may depend on age, comorbidities, and lifestyle of each patient, several observational studies have suggested that bleeding risk is increased with platelets below 20–30 × 10³/μL [6, 15]. Therefore, many guidelines recommend treating patients with platelets below 20–30 × 10³/μL and/or severe bleeding ([37, 39–42]). First-line treatment is corticosteroids, usually prednisolone. Seventy to eighty percent of patients will respond to prednisolone initially; however, sustained response would be achieved to a limited portion of patients, and 10-year disease-free survival is estimated as 13–15% [42]. Some studies demonstrated better sustained response of high-dose dexamethasone (HD-DEX) [43, 44]. A recent prospective randomized study performed in China showed that one or two courses of HD-DEX provided better initial response and less toxicity compared with conventional prednisolone therapy with the same sustained response rate [45]. Splenectomy has been recommended for corticosteroid-resistant patients as a second-line treatment. Splenectomy has a 60-year record of success for achieving durable remissions in approximately two-thirds of patients [46]. However, splenectomy increases lifelong risk of severe infection and thrombosis [29]. In elder patients, splenectomy may often be contraindicated because of comorbidity, and a favorable response may be less common in elder patients than in young patients [47]. For refractory ITP patients in whom splenectomy has failed or is avoided by patients’ and/or doctors’ decision, many drugs have been recommended as third-line treatments, although consistent better outcomes to refractory patients by randomized studies have been shown only in TPO-RAs. Two TPO-RAs, romiplostim and eltrombopag, are currently approved for use in adult ITP in Japan [48]. Randomized studies demonstrate that both drugs are highly effective in both splenectomized and non-splenectomized patients with minimal complications [49, 50]. Extended studies show sustained response and no increase of additional side effects in patients treated with TPO-RAs for up to 5 years [51, 52]. Off-label use of the anti-CD20 antibody rituximab to refractory ITP patients has been widely performed [53], and rituximab provides initial response rates of around 60% and sustained response rates of 20–30% [54]. Other third-line treatments may be also effective in some refractory cases [42, 55] (Table 2); however, the chances of administration of these drugs are very limited in these days because of considerable toxicity of these drugs and availability of TPO-RAs in addition to no approval for usage in ITP.

In case of a requirement of rapid platelet increase because of bleeding emergency, surgical procedure, or delivery, IVIG is recommended [37, 39–42]. Administration of 5 days of 0.4 g/kg/day or 1–2 days of 1 g/kg/day IVIG leads to transient increase of platelet with peak on about 1 week after treatment in ~80% patients [42]. High-dose methylprednisolone may also be effective for rapid increase of platelet [56]. Platelet transfusion may be also effective for bleeding emergency, although higher dose of platelet concentrates may be required because of rapid turnover of infused platelets [57]. Platelet transfusion combined with IVIG may work better for rapid restoration of adequate platelet counts [58].