Prospective evaluation of ADAMTS-13 and von Willebrand factor multimers in cardiac surgery

Abstract

Acquired thrombotic-thrombocytopenic purpura, one of the main representatives of thrombotic microangiopathies (TMAs), is caused by the accumulation of antibodies against ADAMTS-13. Several cases of postoperative TMAs have been observed during the past few years, but the pathogenesis remains unknown. In addition to this, it is unclear whether the use of extracorporeal circulation (ECC) during cardiac surgery has an influence on the occurrence of cardiac surgery-associated TMA. In this study, we investigated the relationship between ADAMTS-13 (a disintegrin and metalloprotease with thrombospondin type 1 motifs 13), ADAMTS-13 inhibitor, von Willebrand factor (VWF) and large VWF multimers in cardiac surgery with and without the use of ECC. Blood samples were taken preoperatively, intraoperatively and up to 6 days postoperatively. A total of 47 patients (median age 70 years, 18 women, 29 men) undergoing cardiac surgery were included; cardiac surgery with the use of ECC (cardiopulmonary bypass) was used in 39 patients, and the off-pump coronary artery bypass technique was used in eight patients. TMA was not diagnosed in any of the patients. Cardiac surgery led to a significantly reduced ADAMTS-13 activity (from 67 to 51%, P < 0.001 in the cardiopulmonary bypass group, from 64 to 48%, P = 0.02 in the off-pump coronary artery bypass group) and higher amounts of large VWF multimers. Development of ADAMTS-13 antibodies was not induced by cardiac surgery. Cardiac surgery led to a slight but significant decrease of ADAMTS-13, but this decrease was not associated with TMA.

Acquired von Willebrand syndrome in congenital heart disease surgery: results from an observational case‐series

“…already described a markedly increased biologic activity of von Willebrand factor after CPB in children , but multimer analysis was not performed in their cohort. In accordance with the findings in adults undergoing cardiac surgery under CPB , the neonates and infants also showed an increase in the absolute values of VWF:Ag, VWF:CB, VWF:RCo and FVIII:C after discontinuation of CPB compared with their preoperative values. This increase is probably a result of VWF release from activated platelets and endothelial cells under CPB conditions, but it does not necessarily reflect the multimer function.…”

“…extracorporeal circulation support (ECLS) and ventricular assist devices) trigger the development of aVWS . By contrast, recent data in adults showed that CPB does not induce aVWS .…”

Prospective Evaluation of the Pre-, Intra-, and Postoperative Kinetics of ADAMTS-13, von Willebrand Factor, and Interleukin-6 in Vascular Surgery

“…14 Recent investigations could not detect any appearance of new inhibitory ADAMTS-13 antibodies after cardiac surgery. 6 In contrast to these findings, Sridharan et al 24 identified 2 of the patients in their institutional review with immunemediated pTTP. In both reviews, cardiovascular and vascular surgery were identified as the most common procedures leading to pTTP.…”

“…Multimers of higher molecular weight are thereby more hemostatically active than smaller multimers. [4][5][6] ADAMTS-13 (a disintegrin and metalloprotease with thrombospondin type 1 motifs, member 13) is the metalloproteinase specifically cleaving VWF into smaller subunits in the circulation by hydrolysis. [7][8][9][10] High shear stress as occurring in the microcirculation seems to be needed to make the cleavage site of the VWF subunit accessible to ADAMTS-13.…”

“…We included vascular surgery patients undergoing procedures of different extent because we hypothesized that major vascular surgery would lead to higher vascular/endothelial damage, with presumed higher VWF stimulation 6 than the previously performed investigations mainly including coronary artery bypass grafting (CABG) patients.…”