PMID- 27601054 OWN - NLM STAT- MEDLINE DCOM- 20180103 LR - 20230829 IS - 1538-7836 (Electronic) IS - 1538-7836 (Linking) VI - 14 IP - 11 DP - 2016 Nov TI - Mechanical circulatory support is associated with loss of platelet receptors glycoprotein Ibalpha and glycoprotein VI. PG - 2253-2260 LID - 10.1111/jth.13497 [doi] AB - 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) Ibalpha and GPVI may increase bleeding risk. SUMMARY: 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 GPIbalpha 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 GPIbalpha 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. CI - (c) 2016 International Society on Thrombosis and Haemostasis. FAU - Lukito, P AU - Lukito P AD - Haematology Unit, Alfred Hospital, Melbourne, Australia. FAU - Wong, A AU - Wong A AD - Haematology Unit, Alfred Hospital, Melbourne, Australia. FAU - Jing, J AU - Jing J AD - Australian Centre for Blood Diseases, Monash University, Melbourne, Australia. FAU - Arthur, J F AU - Arthur JF AD - Australian Centre for Blood Diseases, Monash University, Melbourne, Australia. FAU - Marasco, S F AU - Marasco SF AD - Cardiothoracic Unit, Alfred Hospital, Melbourne, Australia. FAU - Murphy, D A AU - Murphy DA AD - Intensive Care Unit, Alfred Hospital, Melbourne, Australia. FAU - Bergin, P J AU - Bergin PJ AD - Cardiology Unit, Alfred Hospital, Melbourne, Australia. FAU - Shaw, J A AU - Shaw JA AD - Cardiology Unit, Alfred Hospital, Melbourne, Australia. FAU - Collecutt, M AU - Collecutt M AD - Haematology Laboratory, Alfred Hospital, Melbourne, Australia. FAU - Andrews, R K AU - Andrews RK AD - Australian Centre for Blood Diseases, Monash University, Melbourne, Australia. FAU - Gardiner, E E AU - Gardiner EE AD - Department of Cancer Biology and Therapeutics, The John Curtin School of Medical Research, The Australian National University, Canberra, Australia. FAU - Davis, A K AU - Davis AK AD - Haematology Unit, Alfred Hospital, Melbourne, Australia. LA - eng PT - Journal Article PT - Observational Study PT - Research Support, Non-U.S. Gov't DEP - 20161020 PL - England TA - J Thromb Haemost JT - Journal of thrombosis and haemostasis : JTH JID - 101170508 RN - 0 (Platelet Glycoprotein GPIb-IX Complex) RN - 0 (Platelet Membrane Glycoproteins) RN - 0 (glycocalicin) RN - 0 (platelet membrane glycoprotein VI) RN - 0 (von Willebrand Factor) RN - 5Q7ZVV76EI (Warfarin) RN - 9005-49-6 (Heparin) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Aortic Valve Stenosis/physiopathology MH - Blood Platelets/*cytology/metabolism MH - Cohort Studies MH - *Extracorporeal Membrane Oxygenation MH - Female MH - Heart Failure/complications MH - *Heart-Assist Devices MH - Hemorrhage/complications MH - Heparin/therapeutic use MH - Humans MH - Male MH - Middle Aged MH - Platelet Activation MH - Platelet Glycoprotein GPIb-IX Complex/*chemistry MH - Platelet Membrane Glycoproteins/*chemistry MH - Stress, Mechanical MH - Thrombosis MH - Warfarin/therapeutic use MH - Young Adult MH - von Willebrand Factor/chemistry OTO - NOTNLM OT - extracorporeal membrane oxygenation OT - heart-assist devices OT - platelet glycoprotein Ib OT - platelet glycoprotein VI OT - von Willebrand disease EDAT- 2016/10/21 06:00 MHDA- 2018/01/04 06:00 CRDT- 2016/09/08 06:00 PHST- 2016/06/08 00:00 [received] PHST- 2016/08/22 00:00 [accepted] PHST- 2016/10/21 06:00 [pubmed] PHST- 2018/01/04 06:00 [medline] PHST- 2016/09/08 06:00 [entrez] AID - S1538-7836(22)03394-3 [pii] AID - 10.1111/jth.13497 [doi] PST - ppublish SO - J Thromb Haemost. 2016 Nov;14(11):2253-2260. doi: 10.1111/jth.13497. Epub 2016 Oct 20.