Role of splenectomy in inherited thrombocytopenias

I read with interest Drachman's recent review entitled Inherited thrombocytopenia: when low platelet count does not mean ITP.¹  One of the aims of this paper is to assist clinicians in distinguishing between genetic and acquired thrombocytopenia (especially immune thrombocytopenic purpura [ITP]) in order to avoid unnecessary and potentially harmful treatment. It is therefore surprising that at the end of this paper the author suggests that “splenectomy should be reserved for those individuals with severe inherited thrombocytopenia and no option for stem cell transplantation.” There is no doubt that transplantation is the treatment of choice in young children whenever the bleeding tendency is life threatening and an HLA-matched donor is available, since this procedure normalized platelet count in more than 200 patients with Wiskott-Aldrich syndrome (WAS), congenital amegakaryocytic thrombocytopenia, Bernard-Soulier syndrome (BSS), or amegakaryocytic thrombocytopenia with radioulnar synostosis. In contrast, in the field of inherited thrombocytopenias there is a definite indication for splenectomy only for WAS, in that, in a series of 39 patients, surgery normalized platelet count and morphology in almost all cases, and the median survival of splenectomized subjects was 25 years, compared with less than 5 years in unsplenectomized ones.²  To the best of my knowledge, only anecdotal improvements of bleeding tendency have been observed in other inherited thrombocytopenias.³  Moreover, Najean and Lecompte reported that surgery did not modify platelet count in 10 of 10 patients who underwent splenectomy because of a wrong diagnosis of ITP,⁴  and several other reports indicated that splenectomy did not reduce bleeding diathesis in BSS,³  gray platelet syndrome (GPS),⁵  thrombocytopenia 2 (a new entity due to mutation of the THC2 gene),⁶  and MYH9-related disease (MYH9-RD, a new category that includes syndromic and nonsyndromic thrombocytopenias deriving from MYH9 mutations),⁷  although it increased platelet count in a small percentage of patients. My colleagues and I too have observed subjects with inherited thrombocytopenias who were splenectomized because the genetic origin of their disorder was not recognized: 3 were affected by MYH9-RD,⁸  3 by homozygous BSS⁹  (one unpublished [C.L.B., February 11, 2004]), and 1 by heterozygous BSS (C.L.B., unpublished observation, October 14, 2002). Platelet count increased steadily in only one patient with homozygous BSS, but the bleeding tendency did not improve.⁹ 

The different efficacy of splenectomy in WAS and other genetic thrombocytopenias is not surprising, since increased peripheral destruction of platelets is the cause of thrombocytopenia in the former, while a defect of megakaryocytic differentiation, maturation, or platelet production is the main mechanism of thrombocytopenia in most of the latter disorders.¹⁰  Moreover, the functional platelet defect of BSS, MYH9-RD, and GPS persists after splenectomy and hampers clinical improvement also in the rare cases in whom thrombocytopenia is reduced. In conclusion, I suggest that, excluding WAS, splenectomy is not indicated in inherited thrombocytopenias because it does not reduce bleeding tendency in nearly all cases and it predisposes patients to severe infections.