Discussion
Two impressive facts were indicated in this case, namely, splenectomy resolved intractable AIHA in TKS, and chronic macrothrombocytopenia was unexpectedly resolved.
This case suggests that refractory AIHA can be improved by splenectomy. Splenectomy is performed in 15% of the AIHA patients in our country (25%–57% in western countries), and its short-term effectiveness is 60%. The first-line therapy for warm type AIHA is prednisolone. For patients who are resistant or require high-dose prednisolone treatments, rituximab is selected as a second-line therapy.9Splenectomy is positioned as another option for second-line therapy, and is thought to be the most effective conventional treatment for AIHA to be proposed for patients unresponsive to prednisolone.10 In this case, the patient was resistant to prednisolone and rituximab, and the uncontrollable AIHA pathology exacerbated hypersplenism. Increased splenic sequestration of platelets and red cells led to severe anaemia and thrombocytopenia, and therefore, splenectomy was performed as the next second-line therapy. After splenectomy, intractable anaemia improved, never requiring red blood cell transfusion until the present time.
Chronic macrothrombocytopenia also was improved by splenectomy. Generally, inherited thrombocytopenia is caused by the impaired production of platelets from megakaryocytes.11 Giant platelets in TKS suggest disturbance of platelet production,11 but pathophysiology of macrothrombocytopenia in TKS still remains insufficiently elucidated. Previous studies revealed a possible relationship between Wiskott-Aldrich syndrome (WAS) and TKS, as CDC42 directly interacts with the WAS protein.5,7,12 Thrombocytopenia in WAS is caused by an increased clearance of platelets by the reticuloendothelial system and a premature, ectopic release of platelets in the bone marrow8; TKS may be suggested to have a common pathology, but to clarify the mechanisms of macrothrombocytopenia in TKS, further studies are required. Splenectomy has been believed to be contraindicated for treating inherited thrombocytopenia, but the recovery of platelet counts after splenectomy in our patient suggests that an increase in platelet destruction in the spleen contributed to thrombocytopenia. The observations in our patient may provide a novel option for the treatment of TKS. Furthermore, our results might propose a revision of treatment options for inherited thrombocytopenia.
Our case report concludes that splenectomy resolved both refractory AIHA and chronic macrothrombocytopenia. Splenectomy can be suggested as a treatment option for not only refractory AIHA, but also for macrothrombocytopenia in TKS. As this is still the first case, further studies are required to conclude the efficacy, safety, and effects of splenectomy in these cases.