Hemoglobin-based oxygen carriers do not alter platelet functions: study of three chemically modified hemoglobin solutions.
OBJECTIVE
Chemically modified hemoglobins are being developed as potential oxygen-carrying blood substitutes (HBOCs). Clinical and preclinical data demonstrate the vasoactive properties of HBOCs by trapping of nitric oxide, which is also known to have platelet inhibitory activities properties. This study evaluated the effects of three structurally different HBOCs (Hb-Dex-BTC, alphaalpha-Hb, and o-raffinose-poly-Hb) on platelet functions in vitro to compare to those elicited by plasma substitutes, such as hydroxyethylstarch.


METHODS
Platelet activation state was assessed using platelet-rich plasma diluted to 20% (v/v) with the different solutions, by main measuring glycoproteins (GPIb, GPIIb/IIIa, and P-selectin) using flow cytometry. Aggregation was assessed by impedance aggregometry on whole blood hemodiluted to 20% (v/v) with the solutions.


METHODS
Biological hematology department of the university hospital of Nancy-Brabois.


METHODS
Ten healthy volunteers consent and informed of the study who denied taking any drugs at the time of the experiment.


RESULTS
None of these solutions induced activation nor modified reactivity of platelets as measured by the surface expression of glycoproteins GPIb, GPIIb/IIIa, and P-selectin. Moreover, none of these solutions induced platelet aggregation when added alone, nor modified the aggregation patterns of platelets induced by collagen (0.5 microg/ml) and thrombin receptor agonist peptide (12.5 microM).


CONCLUSIONS
The three tested structurally different HBOCs, as with hydroxyethylstarch, did not alter platelet functions in vitro.
Toussaint
Marie
M
Université Henri Poincaré Nancy 1, France. marie.toussaint@pharma.uhp-nancy.fr
Latger-Cannard
Véronique
V
Caron
Alexis
A
Lecompte
Thomas
T
Vigneron
Claude
C
Menu
Patrick
P
D001792:Blood Platelets / Q000187:drug effects*; D001802:Blood Substitutes / Q000494:pharmacology*; D003911:Dextrans / Q000494:pharmacology*; D005434:Flow Cytometry; D006454:Hemoglobins / Q000494:pharmacology*; D006801:Humans; D006895:Hydroxyethyl Starch Derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D010952:Plasma Substitutes / Q000494:pharmacology; D015539:Platelet Activation / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects; D010980:Platelet Membrane Glycoproteins / Q000187:drug effects / Q000378:metabolism; D011887:Raffinose / Q000031:analogs & derivatives* / Q000494:pharmacology*
D001802:Blood Substitutes; D003911:Dextrans; D006454:Hemoglobins; D006895:Hydroxyethyl Starch Derivatives; C097124:O-raffinose cross-linked human hemoglobin; D010952:Plasma Substitutes; D010980:Platelet Membrane Glycoproteins; C095659:hemoglobin-dextran 10-benzene-tetracarboxylate; D011887:Raffinose