Patient-specific severity of von Willebrand factor degradation identifies patients with a left ventricular assist device at high risk for bleeding

Hennessy-Strahs, Samson; Kang, Jooeun; Krause, Eric; Dowling, Robert D.; Rame, J. Eduardo; Bartoli, Carlo

doi:10.1016/j.jtcvs.2022.03.018

Cited by 4 publications

(3 citation statements)

References 24 publications

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“…Shortly after LVAD implantation, nearly all patients develop the acquired von Willebrand syndrome (AVWS), indicated by the loss of large multimers of the vWF and reduced adhesive activity of blood platelets. The AVWS may influence bleeding episodes in LVAD patients, but not all patients develop post-implant bleeding complications [ 35 , 36 ]. In this study, the reported differences in GPIbα expression occurred within the first 3 months post-implantation but not in patients with NSB in the later follow-up.…”

Section: Discussionmentioning

confidence: 99%

The Glycoprotein (GP)Ib-IX-V Complex on Platelets: GPIbα Protein Expression Is Reduced in HeartMate 3 Patients with Bleeding Complications within the First 3 Months

Klaeske

Brade

Eifert

et al. 2023

IJMS

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Non-surgical bleeding (NSB) remains the most critical complication in patients under left ventricular assist device (LVAD) support. It is well known that blood exposed to high shear stress results in platelet dysfunction. Compared to patients without NSB, decreased surface expression of platelet receptor GPIbα was observed in LVAD patients with NSB. In this study, we aimed to compare the expression level of glycoprotein (GP)Ib-IX-V platelet receptor complex in HeartMate 3 (HM 3) patients with and without bleeding complications to investigate the alterations of the platelet transcriptomic profile on platelet damage and increased bleeding risk. Blood samples were obtained from HM 3 patients with NSB (bleeder group, n = 27) and without NSB (non-bleeder group, n = 55). The bleeder group was further divided into patients with early NSB (bleeder ≤ 3 mo, n = 19) and patients with late NSB (bleeder > 3 mo, n = 8). The mRNA and protein expression of GPIbα, GPIX and GPV were quantified for each patient. Non-bleeder, bleeder ≤ 3 mo and bleeder > 3 mo were comparable regarding the mRNA expression of GPIbα, GPIX and GPV (p > 0.05). The protein analysis revealed a significantly reduced expression level of the main receptor subunit GPIbα in bleeders ≤ 3 mo (p = 0.04). We suggest that the observed reduction of platelet receptor GPIbα protein expression in patients who experienced their first bleeding event within 3 months after LVAD implantation may influence platelet physiology. The alterations of functional GPIbα potentially reduce the platelet adhesion capacities, which may lead to an impaired hemostatic process and the elevated propensity of bleeding in HM 3 patients.

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Section: Discussionmentioning

confidence: 99%

The Glycoprotein (GP)Ib-IX-V Complex on Platelets: GPIbα Protein Expression Is Reduced in HeartMate 3 Patients with Bleeding Complications within the First 3 Months

Klaeske

Brade

Eifert

et al. 2023

IJMS

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“…In LVAD patients, the permanent exposure of blood components to device-induced non-physiological shear stress disrupts the hemostasis [ 4 ]. The documented changes in blood components during LVAD support are the activation of platelets, changes in platelet receptors [ 6 ] and the reduction in large multimers of the von Willebrand factor (vWF) leading to the development of the acquired von Willebrand syndrome (aVWS), which is associated with bleeding [ 7 , 8 ]. Because aVWS occurs in practically all LVAD patients, but not all LVAD patients develop bleeding complications, changes in platelets seem to be relevant to developing NSB [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Decreased Platelet Specific Receptor Expression of P-Selectin and GPIIb/IIIa Predict Future Non-Surgical Bleeding in Patients after Left Ventricular Assist Device Implantation

Klaeske

Meyer

Saeed

et al. 2022

IJMS

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Non-surgical bleeding (NSB) is one of the major clinical complications in patients under continuous-flow left ventricular assist device (LVAD) support. The increased shear stress leads to an altered platelet receptor composition. Whether these changes increase the risk for NSB is unclear. Thus, we compared the platelet receptor composition of patients with (bleeder group, n = 18) and without NSB (non-bleeder group, n = 18) prior to LVAD implantation. Blood samples were obtained prior to LVAD implantation and after bleeding complications in the post-implant period. Platelet receptor expression of GPIbα, GPIIb/IIIa, P-selectin and CD63 as well as intra-platelet oxidative stress levels were quantified by flow cytometry. Bleeders and non-bleeders were comparable regarding clinical characteristics, von Willebrand factor diagnostics and the aggregation capacity before and after LVAD implantation (p > 0.05). LVAD patients in the bleeder group suffered from gastrointestinal bleeding (33%; n = 6), epistaxis (22%; n = 4), hematuria or hematoma (17%; n = 3, respectively) and cerebral bleeding (11%; n = 2). Prior to LVAD implantation, a restricted surface expression of the platelet receptors P-selectin and GPIIb/IIIa was observed in the bleeder group (P-selectin: 7.2 ± 2.6%; GPIIb/IIIa: 26,900 ± 13,608 U) compared to non-bleeders (P-selectin: 12.4 ± 8.1%, p = 0.02; GPIIb/IIIa: 36,259 ± 9914 U; p = 0.02). We hypothesized that the reduced platelet receptor expression of P-selectin and GPIIb/IIIa prior to LVAD implantation may be linked to LVAD-related NSB.

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“…HRAEs are the result of a progressive change in the coagulation profile of the patients toward a pro-thrombotic/pro-hemorrhagic state driven by different synergic contributory mechanisms (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). Nevertheless, the lack of association between HRAEs and standard coagulation parameters highlights a critical gap in their diagnostic and therapeutic pathway.…”

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confidence: 99%

Left ventricular assist devices promote changes in the expression levels of platelet microRNAs

Lombardi

Bonora

Baldetti

et al. 2023

Front. Cardiovasc. Med.

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IntroductionMicroRNAs (miRs) emerged as promising diagnostic and therapeutic biomarkers in cardiovascular diseases. The potential clinical utility of platelet miRs in the setting of left ventricular assist device (LVAD) support is unexplored.MethodsWe prospectively measured the expression levels of 12 platelet miRs involved in platelet activation, coagulation, and cardiovascular diseases in LVAD patients by quantitative real-time polymerase chain reaction. Data were longitudinally measured before LVAD implant and after 1, 6, and 12 months of LVAD support, and compared with those measured in healthy volunteers (controls). In silico analysis was also performed to identify pathways targeted by differentially expressed miRs.ResultsData from 15 consecutive patients and 5 controls were analyzed. Pre-implant expression levels of platelet miR-126, miR-374b, miR-223, and miR-320a were significantly different in patients vs. controls. The expression levels of platelet miR-25, miR-144, miR-320, and miR-451a changed significantly over the course of LVAD support; in silico analysis revealed that these miRs are implicated in both cardiac- and coagulation-associated pathways. Furthermore, the patients who suffered from bleeding (n = 5, 33%) had significantly higher pre-implant expression levels of platelet miR-151a and miR-454 with respect to the patients who did not. The same miRs were also differentially expressed in bleeders following LVAD implantation early before the clinical manifestation of the events.DiscussionThis study provides a proof-of-concept evidence of significant modulation of platelet miRs expression driven by LVADs. The possible existence of a platelet miRs signature predictive of the development of bleeding events warrants further validation studies.

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Patient-specific severity of von Willebrand factor degradation identifies patients with a left ventricular assist device at high risk for bleeding

Cited by 4 publications

References 24 publications

The Glycoprotein (GP)Ib-IX-V Complex on Platelets: GPIbα Protein Expression Is Reduced in HeartMate 3 Patients with Bleeding Complications within the First 3 Months

The Glycoprotein (GP)Ib-IX-V Complex on Platelets: GPIbα Protein Expression Is Reduced in HeartMate 3 Patients with Bleeding Complications within the First 3 Months

Decreased Platelet Specific Receptor Expression of P-Selectin and GPIIb/IIIa Predict Future Non-Surgical Bleeding in Patients after Left Ventricular Assist Device Implantation

Left ventricular assist devices promote changes in the expression levels of platelet microRNAs

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