The Role of Cytomegalovirus in Immune Thrombocytopenia Purpura.
Authors: Di Maggio Dina M. , Bussel James B. 
Published: April 2020

Abstract
Immune thrombocytopenia purpura(ITP) is one of the most common causes of acquired thrombocytopenia. Although ITP is believed to result from autoreactive antibodies that lead to platelet destruction, its exact pathogenesis is not known. Cytomegalovirus(CMV) has been implicated as a possible causative agent of ITP. Based on three case reports described here we believe that CMV may be a cause of refractory ITP in certain patients and that eradication of CMV with antiviral therapy will improve the ITP. A 72-year-old man experienced recurrent epistaxis and was found to be thrombocytopenic. He was diagnosed with ITP, and treated with IVIG and solumedrol, with platelets transiently rising to 45K/ul. He suffered a subdural hematoma and was placed on IVIG and prednisone daily and referred for splenectomy. Rituximab was ineffective. Testing for CMV revealed a positive PCR and ganciclovir IV qd, valganciclovir, and cytogam 2 times per week were initiated. With this regimen, the CMV PCR became undetectable and steroids and his anti-CMV medications were weaned off. He now maintains a normal count on no treatment. A 48-year-old male developed ITP which was refractory to treatment with steroids, IVIG, rituximab, danazol, vincristine, anti-thymocyte globulin, and IV anti-D; his platelet count was &lt;20,000/ul and he had marked skin and oral bleeding. After being diagnosed with CMV, he was started on IV ganciclovir and cytogam for several months and was weaned after his PCR became undetectable. In retrospect, he had had mild transaminitis and atypical lymphocytes reported at presentation at another center. He experienced a reactivation of his CMV while being treated with 1 week of steroids for asthma, requiring a second 4 month course of ganciclovir. Currently he receives IVIG every 2-8 weeks. A 3-year-old female was well until 4 months of age, when she developed fevers, thrombocytopenia, elevated liver enzymes and a positive CMV PCR for which she was started on ganciclovir. She developed pancytopenia; bone marrow biopsy was consistent with ITP. She had poor responses to IVIG, IV anti-D and pulse steroids. She suffered from chronic CMV infection for which she received cytogam BIW and initially ganciclovir daily, until its discontinuation secondary to myelosuppression. Once her CMV PCR was negative and her platelets improved to near normal, cytogam was discontinued. Soon after discontinuation her platelet count dropped below 10,000K/ul. She was restarted on the ganciclovir and cytogam without effect. She experienced an intracranial hemorrhage, RSV bronchiolitis, gram positive bacteremia, and respiratory failure with multiple failed extubations and expired at 3 years of age. Toll like receptors 2, 7, and 9 were normal. Several reports have implicated CMV in the pathogenesis of rare cases of ITP. Our previous study suggested that it was at most rarely involved in ITP (Levy, A., 2002; BJH). We describe three cases of refractory ITP associated with CMV. The presentations include severe symptomatic treatment-refractory ITP, fever of unknown origin, and transaminitis. Treatment with immunosuppressive medication may have worsened the CMV-ITP. All cases showed dramatic improvement in platelet counts within 1-2 weeks when ganciclovir and cytogam were instituted. The relationship between CMV and ITP may be explained by immune-mediated destruction of infected platelets or by direct infection of megakaryoblasts by cytomegalovirus(Xiao,Y., 2006). Based on these case reports we believe that CMV infection needs to be considered in cases of refractory ITP and antiviral therapy instituted when infection is identified.