Evaluation of Thrombocytopenia in Patients Receiving Percutaneous Mechanical Circulatory Support With an Impella Device

Houry, Erin; Gengler, Brooke; Alberts, Justin L.; Tuyl, Joseph S. Van

doi:10.1097/cce.0000000000000772

Cited by 3 publications

(2 citation statements)

References 18 publications

(34 reference statements)

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“…The growing body of evidence indicates that shear-mediated quantitative and qualitative platelet dyscrasia is the main driver of MCS bleeding events. Thrombocytopenia defined as platelet count <150,000/μL or 50% less than baseline 5 is observed in up to 86% of MCS patients 7 . Device-related thrombocytopenia has rapid onset, with platelet count declining drastically within 24 hours following device implantation, and persisting until device removal 8 .…”

Section: Introductionmentioning

confidence: 99%

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Shear Stress Promotes Remodeling of Platelet Glycosylation via Upregulation of Platelet Glycosidase Activity: The Ulterior Cause of MCS-Related Thrombocytopenia?

Roka-Moiia,

Lewis,

Cleveland

et al. 2024

Preprint

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Objective: Mechanical circulatory support (MCS) is a mainstay of therapy for advanced and end-stage heart failure. Accompanied by systemic anticoagulation, contemporary MCS has become less thrombogenic, with bleeding complications emerging as a major cause of readmission and 1-year mortality of device-supported patients. Shear-mediated platelet dysfunction (SMPD) and thrombocytopenia of undefined etiology are primary drivers of MCS-related bleeding. Recently, it has been demonstrated that deprivation of platelet surface glycosylation is associated with the decline of hemostatic function, microvesiculation, and premature apoptosis. We tested the hypothesis that shear stress induces remodeling of platelet surface glycosylation via upregulation of glycosidase activity, thus facilitating platelet count decline and microvesiculation. Approach and Results: Human platelets were exposed to continuous shear stress in vitro. Platelets and platelet-derived microparticles were quantified via flow cytometry using size-standard fluorescent nanobeads. Platelet surface glycosylation was evaluated using lectin staining and multicolor flow cytometry; lectin blotting was utilized to verify glycosylation of individual glycoproteins. Platelet glycosidase activities were quantified using 4-methylumbelliferone-based fluorogenic substrates. We demonstrated that shear stress promotes selective remodeling of platelet glycosylation via downregulation of 2,6-sialylation, galactose, and mannose, while 2,3-sialylation remains unchanged. Shear-mediated deglycosylation is partially attenuated by neuraminidase inhibitors DANA and zanamivir, strongly suggesting the involvement of platelet neuraminidase in observed phenomena. Platelets exhibited high basal hexosaminidase and mannosidase activities; basal activities of platelet neuraminidase and galactosidase were rather low and were significantly upregulated by shear stress. Shear stress potentiated a progressive decline of platelet count and immense microvesiculation, both being further exacerbated by neuraminidase. Conclusion: Our data indicate that shear stress accumulation, consistent with supraphysiologic conditions of device-supported circulation, promotes remodeling of platelet glycosylation via selective upregulation of platelet glycosidase activity. Shear-mediated platelet deglycosylation is associated with platelet count drop and increased microvesiculation, thus offering a direct link between deglycosylation and thrombocytopenia observed in device-supported patients.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Shear Stress Promotes Remodeling of Platelet Glycosylation via Upregulation of Platelet Glycosidase Activity: The Ulterior Cause of MCS-Related Thrombocytopenia?

Roka-Moiia,

Lewis,

Cleveland

et al. 2024

Preprint

View full text Add to dashboard Cite

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Shear Stress Promotes Remodeling of Platelet Glycosylation via Upregulation of Platelet Glycosidase Activity: One More Thing

Roka-Moiia,

Lewis,

Cleveland

et al. 2024

Thromb Haemost

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Background: Mechanical circulatory support (MCS) is a mainstay of therapy for advanced heart failure. Shear-mediated platelet dysfunction (SMPD) and thrombocytopenia of undefined etiology are primary drivers of MCS-related bleeding. Recently, it has been demonstrated that deprivation of platelet surface glycosylation is associated with the decline of hemostatic function, microvesiculation, and premature apoptosis. We tested the hypothesis that shear stress induces remodeling of platelet glycosylation via upregulation of glycosidase activity, thus facilitating platelet count decline and microvesiculation. Methods: Human gel-filtered platelets were exposed to shear stress in vitro. Platelets and platelet-derived microparticles were quantified via flow cytometry. Platelet surface glycosylation was evaluated using lectin staining and multicolor flow cytometry; lectin blotting was utilized to verify glycosylation of individual glycoproteins. Neuraminidase, galactosidase, hexosaminidase, and mannosidase activities were quantified using 4-methylumbelliferone-based fluorogenic substrates. Results: Shear stress promotes selective remodeling of platelet glycosylation via downregulation of 2,6-sialylation, terminal galactose. Shear-mediated deglycosylation is partially attenuated by neuraminidase inhibitors, strongly suggesting the involvement of platelet neuraminidase in observed phenomena. Platelets exhibited high basal hexosaminidase and mannosidase activities; basal activities of platelet neuraminidase and galactosidase were rather low and were significantly upregulated by shear stress. Shear stress potentiated an incremental decline of platelet count and increased microvesiculation, both being further exacerbated by neuraminidase and attenuated by neuraminidase inhibition. Conclusions: Shear stress accumulation, consistent with supraphysiologic conditions of device-supported circulation, promotes remodeling of platelet glycosylation via selective upregulation of platelet glycosidase activity. Shear-mediated platelet deglycosylation is associated with platelet count drop and increased microvesiculation.

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Tissue plasminogen activator for axillary Impella 5.0 with heparin-induced thrombocytopenia as a treatment of choice for acute Impella thrombosis: a case report

Merino

Abdelfattah

2023

European Heart Journal - Case Reports

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Background Patients with cardiogenic shock requiring temporary support with percutaneous ventricular assist device (pVAD), such as Impella (Abiomed Inc.), can develop heparin induced thrombocytopenia (HIT) which requires use of alternative purge solution anticoagulation. There are limited recommendations on use of anticoagulation other than standard Unfractionated Heparin in 5% Dextrose solution. Case Summary This case describes 69 year-old female who presented with symptoms of decompensated systolic heart failure and was found to be in cardiogenic shock and despite use of inotropes and vasopressors maintained low systolic blood pressure and low mixed venous oxygen saturation which lead to use of Axillary Impella 5.0 (Abiomed Inc.) who developed HIT. Purge solution anticoagulation was switched to Argatroban, but due to increased motor pressures, tPA was successfully used to maintain proper motor pressures. Ultimately patient was transferred to an outside facility for a transplant evaluation. Discussion This case demonstrates successful and safe use of tPA as an alternative purge solution although more data needed to support this finding.

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Evaluation of Thrombocytopenia in Patients Receiving Percutaneous Mechanical Circulatory Support With an Impella Device

Cited by 3 publications

References 18 publications

Shear Stress Promotes Remodeling of Platelet Glycosylation via Upregulation of Platelet Glycosidase Activity: The Ulterior Cause of MCS-Related Thrombocytopenia?

Shear Stress Promotes Remodeling of Platelet Glycosylation via Upregulation of Platelet Glycosidase Activity: The Ulterior Cause of MCS-Related Thrombocytopenia?

Shear Stress Promotes Remodeling of Platelet Glycosylation via Upregulation of Platelet Glycosidase Activity: One More Thing

Tissue plasminogen activator for axillary Impella 5.0 with heparin-induced thrombocytopenia as a treatment of choice for acute Impella thrombosis: a case report

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