Mechanical circulatory support is associated with loss of platelet receptors glycoprotein Ibα and glycoprotein VI.
Essentials Relationship of acquired von Willebrand disease (VWD) and platelet dysfunction is explored. Patients with ventricular assist devices and on extracorporeal membrane oxygenation are investigated. Acquired VWD and platelet receptor shedding is demonstrated in the majority of patients. Loss of platelet adhesion receptors glycoprotein (GP) Ibα and GPVI may increase bleeding risk.



Background Ventricular assist devices (VADs) and extracorporeal membrane oxygenation (ECMO) are associated with bleeding that is not fully explained by anticoagulant or antiplatelet use. Exposure of platelets to elevated shear in vitro leads to increased shedding. Objectives To investigate whether loss of platelet receptors occurs in vivo, and the relationship with acquired von Willebrand syndrome (AVWS). Methods Platelet counts, coagulation tests and von Willebrand factor (VWF) analyses were performed on samples from 21 continuous flow VAD (CF-VAD), 20 ECMO, 12 heart failure and seven aortic stenosis patients. Levels of platelet receptors were measured by flow cytometry or ELISA. Results The loss of high molecular weight VWF multimers was observed in 18 of 19 CF-VAD and 14 of 20 ECMO patients, consistent with AVWS. Platelet receptor shedding was demonstrated by elevated soluble glycoprotein (GP) VI levels in plasma and significantly reduced surface GPIbα and GPVI levels in CF-VAD and ECMO patients as compared with healthy donors. Platelet receptor levels were also significantly reduced in heart failure patients. Conclusions These data link AVWS and increased platelet receptor shedding in patients with CF-VADs or ECMO for the first time. Loss of the platelet surface receptors GPIbα and GPVI in heart failure, CF-VAD and ECMO patients may contribute to ablated platelet adhesion/activation, and limit thrombus formation under high/pathologic shear conditions.
Haematology Unit, Alfred Hospital, Melbourne, Australia.
P
P
Lukito
Haematology Unit, Alfred Hospital, Melbourne, Australia.
A
A
Wong
Australian Centre for Blood Diseases, Monash University, Melbourne, Australia.
J
J
Jing
Australian Centre for Blood Diseases, Monash University, Melbourne, Australia.
J F
JF
Arthur
Cardiothoracic Unit, Alfred Hospital, Melbourne, Australia.
S F
SF
Marasco
Intensive Care Unit, Alfred Hospital, Melbourne, Australia.
D A
DA
Murphy
Cardiology Unit, Alfred Hospital, Melbourne, Australia.
P J
PJ
Bergin
Cardiology Unit, Alfred Hospital, Melbourne, Australia.
J A
JA
Shaw
Haematology Laboratory, Alfred Hospital, Melbourne, Australia.
M
M
Collecutt
Australian Centre for Blood Diseases, Monash University, Melbourne, Australia.
R K
RK
Andrews
Department of Cancer Biology and Therapeutics, The John Curtin School of Medical Research, The Australian National University, Canberra, Australia.
E E
EE
Gardiner
Haematology Unit, Alfred Hospital, Melbourne, Australia.
A K
AK
Davis
D000293:Adolescent; D000328:Adult; D000368:Aged; D001024:Aortic Valve Stenosis / Q000503:physiopathology; D001792:Blood Platelets / Q000166:cytology* / Q000378:metabolism; D015331:Cohort Studies; D015199:Extracorporeal Membrane Oxygenation; D005260:Female; D006333:Heart Failure / Q000150:complications; D006353:Heart-Assist Devices; D006470:Hemorrhage / Q000150:complications; D006493:Heparin / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D015539:Platelet Activation; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000737:chemistry*; D010980:Platelet Membrane Glycoproteins / Q000737:chemistry*; D013314:Stress, Mechanical; D013927:Thrombosis; D014859:Warfarin / Q000627:therapeutic use; D055815:Young Adult; D014841:von Willebrand Factor / Q000737:chemistry
D019038:Platelet Glycoprotein GPIb-IX Complex; D010980:Platelet Membrane Glycoproteins; C023592:glycocalicin; C098341:platelet membrane glycoprotein VI; D014841:von Willebrand Factor; D014859:Warfarin; D006493:Heparin
extracorporeal membrane oxygenation; heart-assist devices; platelet glycoprotein Ib; platelet glycoprotein VI; von Willebrand disease