311. Disorders of Platelet Number or Function: Thrombotic Thrombocytopenic Purpura and Platelet Dysfunction
Eleni Gavriilaki, Panagiotis G Asteris, Styliani Kokoris, et al.
Authors Conclusion from the Abstract: We have detected for the first time rare and pathogenic TMA-associated variants in patients with severe COVID-19. Our findings of variants in complement-regulatory genes and ADAMTS13 suggest genetic susceptibility and define proof-of-concept for proper selection of patients that would benefit from complement inhibition.
Senthil Sukumar, Max Brodsky, Sarah Hussain, et al
Authors Conclusion from the Abstract: TTP survivors have a two-fold higher mortality rate than expected rates from a reference US population, adjusted for age, sex, and race. Cardiovascular disease is a leading cause of death in patients that survive their first episode of TTP. This may be due to higher rates of cardiovascular risk factors such as hypertension in TTP survivors. Reduced ADAMTS13 activity is a risk factor for all-cause and cardiovascular death in the general population (Sonneveld et al. Arterioscler Thromb Vasc Biol. 2016) and may contribute to cardiovascular death in TTP survivors. Our results highlight the need to screen and aggressively manage cardiovascular risk factors in TTP survivors, and for prospective studies examining the vascular sequelae of TTP.
Jin-Sup Shin, Geraldine Cambridge, Yanping Guo, et al.
Authors Conclusion from the Abstract: At acute iTTP presentation and prior to elective re-treatment with RTX, activated (CD4+CXCR5+PD1+ICOS+) cTfh cells are increased, suggesting a role of T cell help in the development of anti-ADAMTS13 IgG antibodies. Prior to RTX, B cell phenotype is also altered in acute TTP, with decreased frequency of memory subsets and a trend to increased naïve cells and plasmablasts. Persistent changes in B cell subsets were seen in ER patients who had received previous RTX with naive cells predominating and reduced memory cells. Interestingly, no patient relapsed/ required re-treatment related to B cell return, with relapse occurring at least 4 months after detection of B cells. Resumption of the autoimmune response, therefore, appeared limited by the rate of maturation of autoantigen(ADAMTS13)-specific B cells, either by selection/differentiation of ADAMTS13-naive B cells and/or expansion of ADAMTS13-specific memory B cells to Ig producing cells. This process, presumably driven by interaction with Tfh cells, suggests a role of T cell help in the development of anti-ADAMTS13 IgG antibodies. Longitudinal analysis of the evolution of B and cTfh cells may help in predicting relapse in iTTP.
Noor Dhaliwal, Sarah Hussain, Harshvardhan Upreti, et al.
Authors Conclusion from the Abstract: Eculizumab discontinuation with close monitoring is safe in the majority of patients with aHUS (with native kidneys), with low rates of TMA recurrence and nearly complete salvage with eculizumab retreatment in the event of a recurrence. CFH and MCP variants may be associated with a higher risk of relapse, which needs to be evaluated in larger, multicenter studies.
Natthapol Songdej, Fabiola Del carpio-cano, Guangfen Mao, et al.
Authors Conclusion from the Abstract: Overall, these studies provide the first evidence that hematopoietic transcription factor RUNX1 regulates the expression of F13A1 in megakaryocytic cells and that platelet expression of F13A1 is decreased in platelets from patients with RUNX1 haplodeficiency. The decreased expression of F13A1 in RHD may contribute to platelet dysfunction in RHD. These findings are particularly interesting because they reflect the regulation of a coagulation protein (FXIIIA) by hematopoietic transcription factor RUNX1.
Matthew Duvernay, PhD, Breanne HY Gibson, Lydia Joy Mckeithan, et al
Authors Conclusion from the Abstract: Pediatric scoliosis surgery is characterized by persistent fibrinolysis platelet dysfunction, activation of the APR, and coagulopathy despite administration of the anti-fibrinolytic TXA. Future studies will focus on altering the dose of TXA to determine if an optimal dosing can be achieved that effectively inhibits fibrinolysis and answer important questions about the dependence of the APR and platelet hypofunction on the persistent fibrinolysis seen in these patients.