Decreased platelet reactivity identified by whole blood flow cytometry in Fanconi anaemia patients.
Fanconi anaemia (FA) is a rare inherited chromosome instability disorder characterized by congenital anomalies and a high risk for bone marrow failure and cancer. Bleeding is a frequent complication in FA, leading to substantial morbidity and mortality. Thrombocytopenia is a major factor leading to this complication, but the bleeding tendency of FA patients often exceeds what one might expect based on their platelet counts. We therefore investigated if alterations of platelet function contribute to the bleeding tendency of FA patients. We assessed platelet function in 11 FA patients and 23 controls with whole blood flow cytometry. We analyzed the expression of platelet membrane glycoprotein receptors, reactivity of platelets to physiologic agonists and the proportion of young platelets. In FA patients platelet reactivity was decreased: Expression of P-selectin and binding of PAC-1 after stimulation with thrombin receptor activating peptide (TRAP) and adenosine diphosphate (ADP) were 15-70% lower than in controls. We found no or only minor differences of platelet glycoprotein receptor expression between groups. While the proportion of reticulated platelets was not different, the absolute number of reticulated platelets was markedly lower in FA patients. Our data show that FA is associated with reduced platelet reactivity, which may contribute to the high bleeding tendency in FA patients. Whole blood flow cytometry is a suitable method for analysis of platelet function in FA patients.
University Children's Hospital, University of Wuerzburg, Germany.
Susanne
S
Holzhauer
Ana-Gabriela
AG
Sitaru
Wolfram
W
Ebell
Detlev
D
Schindler
Helmut
H
Hanenberg
Johannes
J
Wirbelauer
Ulrich
U
Walter
Ralf
R
Grossmann
D000244:Adenosine Diphosphate / Q000378:metabolism; D000293:Adolescent; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D005199:Fanconi Anemia / Q000097:blood* / Q000150:complications; D005260:Female; D005434:Flow Cytometry; D006470:Hemorrhage / Q000097:blood / Q000209:etiology*; D006801:Humans; D008297:Male; D019007:P-Selectin / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D015539:Platelet Activation / Q000187:drug effects; D010976:Platelet Count; D010979:Platelet Function Tests / Q000379:methods*; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D018179:Receptors, Thrombin / Q000819:agonists / Q000378:metabolism; D013921:Thrombocytopenia / Q000097:blood / Q000150:complications* / Q000209:etiology
D019007:P-Selectin; D010446:Peptide Fragments; D010980:Platelet Membrane Glycoproteins; D018179:Receptors, Thrombin; D000244:Adenosine Diphosphate