New insights into the glycobiology of immune thrombocytopenia

Tiemeyer, Katherine H.; Kuter, David J.; Cairo, Christopher W.; Hollenhorst, Marie A.

doi:10.1097/moh.0000000000000781

Cited by 5 publications

(1 citation statement)

References 52 publications

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“…In addition, antibody‐triggered platelet desialylation may result in Ashwell‐Morell receptor‐mediated removal by hepatocytes or clearance by hepatic Kupffer cells. 7 , 8 , 9 , 10 Complement‐mediated platelet destruction also may contribute in some cases. 11 Cytotoxic T cell‐mediated platelet destruction may occur in the absence of detectable platelet autoantibodies.…”

Section: Introductionmentioning

confidence: 99%

ACVIM consensus statement on the diagnosis of immune thrombocytopenia in dogs and cats

LeVine,

Kidd,

Garden

et al. 2024

Veterinary Internal Medicne

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Immune thrombocytopenia (ITP) is the most common acquired primary hemostatic disorder in dogs. Immune thrombocytopenia less commonly affects cats but is an important cause of mortality and treatment‐associated morbidity in both species. Immune thrombocytopenia remains a diagnosis of exclusion for which diagnostic guidelines are lacking. Primary, or non‐associative, ITP refers to autoimmune platelet destruction. Secondary, or associative, ITP arises in response to an underlying disease trigger. However, evidence for which comorbidities serve as ITP triggers has not been systematically evaluated. To identify key diagnostic steps for ITP and important comorbidities associated with secondary ITP, we developed 12 Population Evaluation/Exposure Comparison Outcome (PECO) format questions. These questions were addressed by evidence evaluators utilizing a literature pool of 287 articles identified by the panelists using a structured search strategy. Evidence evaluators, using panel‐designed templates and data extraction tools, summarized evidence and created guideline recommendations that then were integrated by diagnosis and comorbidity domain chairs. The revised PECO responses underwent a Delphi survey process to reach consensus on final guidelines. A combination of panel expertise and PECO responses were employed to develop algorithms for diagnosis of ITP in dogs and cats, which also underwent 4 iterations of Delphi review. Comorbidity evidence evaluators employed an integrated measure of evidence (IME) tool to determine evidence quality for each comorbidity; IME values combined with evidence summaries for each comorbidity were integrated to develop ITP screening recommendations, which also were subjected to Delphi review. Commentary was solicited from multiple relevant professional organizations before finalizing the consensus. The final consensus statement provides clinical guidelines for the diagnosis of, and underlying disease screening for, ITP in dogs and cats. The systematic consensus process identified numerous knowledge gaps that should guide future studies. This statement is a companion manuscript to the ACVIM Consensus Statement on the Treatment of Immune Thrombocytopenia.

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Section: Introductionmentioning

confidence: 99%

ACVIM consensus statement on the diagnosis of immune thrombocytopenia in dogs and cats

LeVine,

Kidd,

Garden

et al. 2024

Veterinary Internal Medicne

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ABO blood groups and galectins: Implications in transfusion medicine and innate immunity

Arthur,

Hollenhorst,

et al. 2024

Seminars in Immunology

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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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New insights into the glycobiology of immune thrombocytopenia

Cited by 5 publications

References 52 publications

ACVIM consensus statement on the diagnosis of immune thrombocytopenia in dogs and cats

ACVIM consensus statement on the diagnosis of immune thrombocytopenia in dogs and cats

ABO blood groups and galectins: Implications in transfusion medicine and innate immunity

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

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