Decreased generation of procoagulant platelets detected by flow cytometric analysis in patients with bleeding diathesis

Daskalakis, Michael; Colucci, Giuseppe; Keller, Peter; Rochat, Sophie; Silzle, Tobias; Demarmels Biasiutti, Franziska; Barizzi, Gabriela; Alberio, Lorenzo (2014). Decreased generation of procoagulant platelets detected by flow cytometric analysis in patients with bleeding diathesis. Cytometry. Part B, Clinical cytometry, n/a-n/a. Wiley 10.1002/cytob.21157

[img]
Preview
Text
10.1002cytob.21157.pdf - Accepted Version
Available under License Publisher holds Copyright.

Download (825kB) | Preview

Background: A clinically relevant bleeding diathesis is a frequent diagnostic challenge, which sometimes remains unexplained despite extensive investigations. The aim of our work was to evaluate the diagnostic utility of functional platelet testing by flow cytometry in this context. Methods: In case of negative results after standard laboratory work-up, flow cytometric analysis (FCA) of platelet function was done. We performed analysis of surface glycoproteins (GP) Ibα, IIb, IIIa; P-selectin expression and PAC-1 binding after graded doses of ADP, collagen and thrombin; content/secretion of dense granules; ability to generate procoagulant platelets. Results: Out of 437 patients investigated with standard tests between January 2007 and December 2011, we identified 67 (15.3%) with high bleeding scores and non-diagnostic standard laboratory work-up including platelet aggregation studies. Among these patients FCA revealed some potentially causative platelet defects: decreased dense-granule content/secretion (n=13); decreased alpha-granule secretion induced by ADP (n=10), convulxin (n=4) or thrombin (n=3); decreased fibrinogen-receptor activation induced by ADP (n=11), convulxin (n=11) or thrombin (n=8); decreased generation of COAT-platelets, i.e. highly procoagulant platelets induced by simultaneous activation with collagen and thrombin (n=16). Conclusion: Our work confirms that storage pool defects are frequent in patients with a bleeding diathesis and normal coagulation and platelet aggregations studies. Additionally, flow cytometric analysis is able to identify discrete platelet activation defects. In particular, we show for the first time that a relevant proportion of these patients has an isolated impaired ability to generate COAT-platelets - a conceptually new defect in platelet procoagulant activity, that is missed by conventional laboratory work-up. © 2014 Clinical Cytometry Society.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Haematology and Central Haematological Laboratory
04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Nephrology and Hypertension

UniBE Contributor:

Daskalakis, Michael; Colucci, Giuseppe; Keller, Peter; Rochat, Sophie; Demarmels Biasiutti, Franziska and Alberio, Lorenzo

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1552-4949

Publisher:

Wiley

Language:

English

Submitter:

Verena Zwahlen

Date Deposited:

06 Oct 2014 16:27

Last Modified:

18 Feb 2015 12:41

Publisher DOI:

10.1002/cytob.21157

PubMed ID:

24458871

Additional Information:

Accepted, unedited article published online and citable. The final edited and typeset version of record will appear in future

Uncontrolled Keywords:

COAT platelets, platelet aggregation, flow cytometry, bleeding diathesis, bleeding scoring system

BORIS DOI:

10.7892/boris.48149

URI:

https://boris.unibe.ch/id/eprint/48149

Actions (login required)

Edit item Edit item
Provide Feedback