A role for clonal haematopoiesis in idiopathic splanchnic vein thrombosis

Abstract Background SVT is a dangerous condition affecting the splanchnic veins causing an impairment in their normal blood flow. The pathogenesis of SVT is extremely complex and depends on many different possible underlying conditions. It is indeed known that most SVT patients present with cirrhosis, abdominal cancers and infections or myeloproliferative neoplasm. Notwithstanding what has just been said, a significant portion of SVTs is defined as primary meaning that in these cases the condition appears without the identification of a direct causative agent. It is evident that these conditions are difficult to follow from a clinical perspective and their management is particularly challenging. Objective The study is aimed at assessing the causes of idiopathic-SVT by searching among possible concurrent factors to its onset, channelling the focus onto specific changes in blood examinations and the clonal haematopoiesis of indeterminate potential (CHIP). Method All the patients presenting with SVT at the Division of Internal Medicine-Haematology, unit have been enrolled in the study forming a pool of 41 patients. During the process of care, each one of these patients has been carefully evaluated to gather information regarding different aspects of their disease. In this way a total of 200 variables per patient have been harvested to form a database used to make the due statistical analysis by means of the program Jamovi. Results and Conclusions After the due statistical analysis that we have carried out in this study, these are the results: About 25% (10 out of 41) of patients affected by SVT suffer from primary SVT. By means of a t-test it has been calculated that there is no real difference between the age of the patients affected by primary thrombosis and the age of the patients affected by secondary thrombosis, (p value 0.976). Using the X2 test, a relationship between the pre-existing presence of CHIP and the onset of primary SVT rather than secondary SVT has been noticed (p value <.001). Likewise, fluctuations of the concentration of eosinophils, basophils, lymphocytes and monocytes also seems to be related with the onset of primary SVT. Indeed, the average concentration of eosinophils, basophils and lymphocytes seems to be higher in people affected by primary SVT than secondary SVT (p values of 0.008, 0.001 and 0.047 respectively) While higher frequencies of CHIP have been observed in patients affected by primary SVT compared with the ones affected by secondary SVT, no single specific mutation in the genes ASXL1, CBL, CEBPA, CSF3R, DNMT3A, EZH2, KIT, RUNX1, SETBP, SF3B1, TET2, TP53, ZRSR2 have been found to be able, by itself, to influence the development of primary rather than secondary SVT. On the contrary, the mutation of JAK2, thanks to a X2 test, has been found relatable to the onset of secondary SVT (p value 0.011). Concerning the resolution of primary SVT, the possible relationship with the presence of CHIP as well as fluctuations in the values of eosinophils, lymphocytes and basophils has been investigated indicating an absence of relationship between these factors. On the contrary the resolution of the SVT appears related to the fluctuations in the values of cholesterol, of the MCV and of the ESR in a directly proportionate fashion and to fluctuations of RBCs and total bilirubin levels in an indirectly proportional fashion. In conclusion we have associated CHIP as a potential novel risk factor for idiopathic SVT.