Background: HELLP (Hemolysis, elevated liver enzymes and low platelets) syndrome is a severe and acute pregnancy-related disorder that occurs in approximately 2.5 per 1000 deliveries and represents a major cause of maternal and perinatal morbidity and mortality. This syndrome has been suggested to be a microangiopathy and delivery is the only effective treatment. Objectives: The aim of this study was to investigate the pathophysiology of HELLP syndrome by simultaneously exploring complement, haemostasis, autoimmunity and inflammation in relation to the clinical outcome. Methods: We investigated 19 HELLP patients at the time of diagnosis and 3 months after delivery, for complement function, haemostasis and inflammation with immunoenzymatic methods. Complement-related gene variants were also analyzed by next generation sequencing and multiplex ligation-dependent probe amplification. Nineteen age-matched healthy pregnant women served as controls. Results: At diagnosis, HELLP patients, compared to controls, showed significantly higher plasma levels of SC5b-9 (median 710 ng/ml [range 216–1499] vs 253 ng/ml [19–371], P < 0.0001) and of C5a (20.8 ng/ml [5.6–27.5] vs 12.7 ng/ml [3.2–24.6]; P = 0.004), which decreased three months after delivery (SC5b9: 190 ng/ml [83–446] vs 160 ng/ml [107–219]; C5a: 9.28 ng/ml [2.3–21.6] vs 10.7 ng/ml [2.5–21.2]). A significantly higher frequency of genetic variants involving complement regulatory genes was also observed (52.6% vs 15.8%; P = 0.016). Moreover, at HELLP diagnosis, patients showed increased coagulation markers (fragment F1 + 2 and D-dimer; P = 0.0001) while both patients and controls had high thrombin-generation potential that decreased after delivery. Conclusions: In the pathophysiology of HELLP syndrome, complement dysregulation, in addition to coagulation activation, is involved and may represent a potential target for treatment with the aim of delaying delivery.

Genetic and molecular evidence for complement dysregulation in patients with HELLP syndrome / M. Bazzan, T. Todros, S. Tedeschi, G. Ardissino, S. Cardaropoli, S. Stella, B. Montaruli, C. Marchese, D. Roccatello, M. Cugno. - In: THROMBOSIS RESEARCH. - ISSN 0049-3848. - 196(2020 Dec), pp. 167-174. [10.1016/j.thromres.2020.08.038]

Genetic and molecular evidence for complement dysregulation in patients with HELLP syndrome

M. Cugno
2020

Abstract

Background: HELLP (Hemolysis, elevated liver enzymes and low platelets) syndrome is a severe and acute pregnancy-related disorder that occurs in approximately 2.5 per 1000 deliveries and represents a major cause of maternal and perinatal morbidity and mortality. This syndrome has been suggested to be a microangiopathy and delivery is the only effective treatment. Objectives: The aim of this study was to investigate the pathophysiology of HELLP syndrome by simultaneously exploring complement, haemostasis, autoimmunity and inflammation in relation to the clinical outcome. Methods: We investigated 19 HELLP patients at the time of diagnosis and 3 months after delivery, for complement function, haemostasis and inflammation with immunoenzymatic methods. Complement-related gene variants were also analyzed by next generation sequencing and multiplex ligation-dependent probe amplification. Nineteen age-matched healthy pregnant women served as controls. Results: At diagnosis, HELLP patients, compared to controls, showed significantly higher plasma levels of SC5b-9 (median 710 ng/ml [range 216–1499] vs 253 ng/ml [19–371], P < 0.0001) and of C5a (20.8 ng/ml [5.6–27.5] vs 12.7 ng/ml [3.2–24.6]; P = 0.004), which decreased three months after delivery (SC5b9: 190 ng/ml [83–446] vs 160 ng/ml [107–219]; C5a: 9.28 ng/ml [2.3–21.6] vs 10.7 ng/ml [2.5–21.2]). A significantly higher frequency of genetic variants involving complement regulatory genes was also observed (52.6% vs 15.8%; P = 0.016). Moreover, at HELLP diagnosis, patients showed increased coagulation markers (fragment F1 + 2 and D-dimer; P = 0.0001) while both patients and controls had high thrombin-generation potential that decreased after delivery. Conclusions: In the pathophysiology of HELLP syndrome, complement dysregulation, in addition to coagulation activation, is involved and may represent a potential target for treatment with the aim of delaying delivery.
Complement system proteins; Genetic variants; Haemostasis; HELLP syndrome; Pregnancy
Settore MED/09 - Medicina Interna
dic-2020
ago-2020
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/783974
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