Platelet glycoprotein Ibα ectodomain shedding and non-surgical bleeding in heart failure patients supported by continuous-flow left ventricular assist devices.
BACKGROUND
Non-surgical bleeding (NSB) is a major complication among heart failure (HF) patients supported by continuous-flow left ventricular assist devices (CF-LVADs). Understanding the hemostatic defects contributing to NSB after CF-LVAD implantation is crucial for prevention of this adverse event. The aim of this study was to examine the link between platelet glycoprotein Ibα (GPIbα) ectodomain shedding and NSB in CF-LVAD recipients and to identify a potential biomarker of NSB.


METHODS
Serial blood samples were collected from 35 HF patients supported with CF-LVADs. Platelet function was evaluated by a platelet function analysis device and thromboelastography (TEG). Platelet GPIbα shedding, von Willebrand factor (vWF) antigen and vWF collagen binding capacity were determined using enzyme-linked immunosorbent assays (ELISAs). The structural analysis of vWF was performed by gel electrophoresis. These platelet function measures with vWF parameters of the patients who had NSB between 4 and 32 days after CF-LVAD implantation (bleeder) were analyzed against those without NSB (non-bleeder). Blood samples from 7 healthy individuals were collected to obtain healthy reference values for the laboratory assays.


RESULTS
Elevated GPIbα shedding was found to be a pre-existing condition in all HF patients prior to CF-LVAD implantation. Post-operative level of GPIbα shedding increased and remained elevated in the bleeder group, whereas a consistent decrease was found in the non-bleeder group. A receiver operating characteristic (ROC) analysis indicated that the level of GPIbα shedding had a predictive power of NSB in patients on CF-LVAD support.


CONCLUSIONS
Platelet GPIbα ectodomain shedding which attenuates platelet reactivity is associated with NSB. Plasma GPIbα level may potentially be used to refine bleeding risk stratification in CF-LVAD patients.
Artificial Organs Laboratory, Department of Surgery, University of Maryland, School of Medicine, Baltimore, Maryland.
Jingping
J
Hu
Artificial Organs Laboratory, Department of Surgery, University of Maryland, School of Medicine, Baltimore, Maryland.
Nandan K
NK
Mondal
Department of Clinical Engineering, University of Maryland, Medical Center, Baltimore, Maryland.
Erik N
EN
Sorensen
Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, Maryland.
Ling
L
Cai
Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, Maryland.
Hong-Bin
HB
Fang
Artificial Organs Laboratory, Department of Surgery, University of Maryland, School of Medicine, Baltimore, Maryland.
Bartley P
BP
Griffith
Artificial Organs Laboratory, Department of Surgery, University of Maryland, School of Medicine, Baltimore, Maryland. Electronic address: zwu@smail.umaryland.edu.
Zhongjun J
ZJ
Wu
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D001696:Biomechanical Phenomena / Q000502:physiology; D001792:Blood Platelets / Q000473:pathology* / Q000502:physiology; D016022:Case-Control Studies; D005260:Female; D006333:Heart Failure / Q000628:therapy*; D006353:Heart-Assist Devices / Q000009:adverse effects*; D006470:Hemorrhage / Q000453:epidemiology*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D015539:Platelet Activation / Q000502:physiology; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000378:metabolism*; D012189:Retrospective Studies; D012307:Risk Factors; D013314:Stress, Mechanical; D018487:Ventricular Dysfunction, Left / Q000628:therapy*; D014841:von Willebrand Factor / Q000378:metabolism
D015415:Biomarkers; D019038:Platelet Glycoprotein GPIb-IX Complex; C094990:adhesion receptor; D014841:von Willebrand Factor
continuos flow; heart failure; left ventricular assist device; mechanical circulatory support; non-surgical bleeding; platelet GPIbα shedding