Abstract Number: OC 54.3
Meeting: ISTH 2021 Congress
Theme: Coagulation and Natural Anticoagulants » Contact Pathway
Background: Previously, we have shown that factor (F) XII knockdown attenuates catheter thrombosis in rabbits. Because histidine-rich glycoprotein (HRG) inhibits FXIIa, we hypothesized that HRG knockdown would enhance catheter thrombosis.
Aims: Determine the role of HRG in catheter thrombosis.
Methods: Rabbits (n=8/group) were treated with rabbit-specific antisense oligonucleotides (ASOs) against HRG, FXII, or a control ASO for four weeks. Blood was collected before and after the treatment to examine the effect of HRG or FXII knockdown on the activated partial thromboplastin time (APTT), prothrombin time (PT), and catheter-induced thrombin generation in vitro. Polyurethane catheters were then inserted into the right external jugular vein of the rabbits, and blood was withdrawn and reinjected every 5 min until the catheters occluded as evidenced by pressure over 90 mmHg or an inability to withdraw blood from the catheter.
Results: Treatment with the HRG or FXII ASO reduced hepatic messenger RNA and plasma HRG or FXII antigen levels by over 90% compared with the control. Whereas HRG knockdown shortened the APTT by 2.5-fold compared with control, FXII knockdown prolonged it by 4-fold. Neither treatment affected the prothrombin time. Catheter segments shortened the lag time and increased peak thrombin in plasma from control rabbits; effects that were enhanced in plasma from rabbits treated with the HRG ASO and attenuated in plasma from rabbits treated with the FXII ASO. Whereas the time to catheter occlusion in control rabbits was 62 ± 8 min, the time to occlusion was significantly reduced to 34 ± 9 min with HRG knockdown and significantly prolonged to 128 ± 19 min with FXII knockdown.
Conclusions: By attenuating FXIIa activity, HRG knockdown enhances catheter-induced thrombin generation in vitro and catheter thrombosis in rabbits. These findings add to the evidence that HRG regulates the contact pathway and suggest that supplemental HRG or HRG analogs may attenuate medical device-induced thrombosis.
To cite this abstract in AMA style:
Malik RA, Liao P, Zhou J, Fredenburgh JC, Hussain RH, Revenko A, Weitz JI. Histidine-rich Glycoprotein Attenuates Catheter Thrombosis in Rabbits [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/histidine-rich-glycoprotein-attenuates-catheter-thrombosis-in-rabbits/. Accessed October 2, 2023.« Back to ISTH 2021 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/histidine-rich-glycoprotein-attenuates-catheter-thrombosis-in-rabbits/