Low COAT platelets are frequent in patients with bleeding disorders of unknown cause (BDUC) and can be enhanced by DDAVP

Segot, Amandine; Adler, Marcel; Aliotta, Alessandro; Matthey‐Guirao, Elena; Nagler, Michael; Calderara, Debora Bertaggia; Grandoni, Francesco; Gómez, Francisco; Alberio, Lorenzo

doi:10.1111/jth.15687

Cited by 7 publications

(4 citation statements)

References 39 publications

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“…Clinical interest in procoagulant platelets is growing as studies are conducted to better understand their in vivo importance [ 19 , 20 ]. The potential to form procoagulant platelets is on average about 30% in healthy donors and remains stable over time [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

Discriminating young platelets on human leukocyte antigen-I expression highlights their extremely high reactivity potential

Angénieux¹,

Couvidou²,

Brouard³

et al. 2023

Research and Practice in Thrombosis and Haemostasis

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Section: Discussionmentioning

confidence: 99%

Discriminating young platelets on human leukocyte antigen-I expression highlights their extremely high reactivity potential

Angénieux¹,

Couvidou²,

Brouard³

et al. 2023

Research and Practice in Thrombosis and Haemostasis

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“…Another limitation is that currently we do not measure COAT platelets in our patients. 68 Furthermore, potentially pathological findings in LTA are of unknown clinical significance. Nevertheless, LTA is the gold standard for analyzing patients with MBD for potential PFD and should be offered by every center.…”

Section: Platelet Function Defectsmentioning

confidence: 99%

Bleeding Disorder of Unknown Cause: A Diagnosis of Exclusion

Mehic,

Gebhart,

Pabinger

2024

Hamostaseologie

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Patients with an unexplained mild to moderate bleeding tendency are diagnosed with bleeding disorder of unknown cause (BDUC), a classification reached after ruling out other mild to moderate bleeding disorders (MBD) including von Willebrand disease (VWD), platelet function defects (PFDs), coagulation factor deficiencies (CFDs), and non-hemostatic causes for bleeding. This review outlines our diagnostic approach to BDUC, a diagnosis of exclusion, drawing on current guidelines and insights from the Vienna Bleeding Biobank (VIBB). According to guidelines, we diagnose VWD based on VWF antigen and/or activity levels ≤50 IU/dL, with repeated VWF testing if VWF levels are <80 IU/dL. This has been introduced in our clinical routine after our findings of diagnostically relevant fluctuations of VWF levels in a high proportion of MBD patients. PFDs are identified through repeated abnormalities in light transmission aggregometry (LTA), flow cytometric mepacrine fluorescence, and glycoprotein expression analysis. Nevertheless, we experience diagnostic challenges with regard to reproducibility and unspecific alterations of LTA. For factor (F) VIII and FIX deficiency, a cutoff of 50% is utilized to ensure detection of mild hemophilia A or B. We apply established cutoffs for other rare CFD being aware that these do not clearly reflect the causal role of the bleeding tendency. Investigations into very rare bleeding disorders due to hyperfibrinolysis or increase in natural anticoagulants are limited to cases with a notable family history or distinct bleeding phenotypes considering cost-effectiveness. While the pathogenesis of BDUC remains unknown, further explorations of this intriguing area may reveal new mechanisms and therapeutic targets.

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“…These platelets are generated after combined activation by collagen plus thrombin, are coated with alpha‐granule proteins retained on their surface by a serotonin‐transglutaminase‐dependent mechanism and are highly efficient in maintaining thrombin generation. In a recent study investigating three cohorts of BDUC patients, Segot et al reported a reduced ability to form COAT platelets in 36 of 157 patients with BDUC (23%) 46 …”

Section: Introductionmentioning

confidence: 99%

“…Besides VWD and CFD patients, thrombin generation has also been the most widely investigated global assay in BDUC patients, as comprehensively reviewed by Thomas et al45 As a mechanism of impaired thrombin generation, defective generation of procoagulant, collagen and thrombin activated (COAT), coated platelets has been explored as a potential cause of bleeding tendency in BDUC patients.These platelets are generated after combined activation by collagen plus thrombin, are coated with alpha-granule proteins retained on their surface by a serotonin-transglutaminase-dependent mechanism and are highly efficient in maintaining thrombin generation. In a recent study investigating three cohorts of BDUC patients, Segot et al reported a reduced ability to form COAT platelets in 36 of 157 patients with BDUC (23%) 46. Turbidimetric assays of plasma clot formation and lysis have been examined in bleeding patients to assess possible anomalies in fibrin clot formation and structure 47.…”

mentioning

confidence: 99%

How to investigate mild to moderate bleeding disorders and bleeding disorder of unknown cause

Casini,

Gebhart

2024

Int J Lab Hematology

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A bleeding tendency is one of the most common complaints observed by hematologists. It is challenging to differentiate a clinically insignificant bleeding from a bleeding phenotype that requires hemostatic evaluation and medical intervention. A thorough review of personal and familial history, objective assessment of bleeding severity using a bleeding assessment tool, and a focused physical examination are critical to correctly identifying suspected patients with mild to moderate bleeding disorders (MBDs). A basic laboratory work‐up should be performed in all patients referred for a bleeding tendency. If a hemostatic abnormality is found such as evidence of von Willebrand disease, a platelet function disorder, or a coagulation factor deficiency, more extensive testing should be performed to further characterize the bleeding disorder. Conversely, if all results are normal the patient is considered to have bleeding disorder of unknown cause (BDUC). For patients with BDUC, further evaluation may include non‐routine testing to look for rare bleeding disorders not detected by routine hemostasis tests, such as thrombomodulin‐associated coagulopathy, tissue factor pathway inhibitor‐related bleeding disorder, hyperfibrinolytic‐bleeding disorders or impaired tissue factor production. In this review, we summarize the stepwise diagnostic procedure in MBDs and provide some insights into the biological features of BDUC.

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Low COAT platelets are frequent in patients with bleeding disorders of unknown cause (BDUC) and can be enhanced by DDAVP

Cited by 7 publications

References 39 publications

Discriminating young platelets on human leukocyte antigen-I expression highlights their extremely high reactivity potential

Discriminating young platelets on human leukocyte antigen-I expression highlights their extremely high reactivity potential

Bleeding Disorder of Unknown Cause: A Diagnosis of Exclusion

How to investigate mild to moderate bleeding disorders and bleeding disorder of unknown cause

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