Summary
Recent reports have suggested a variation in the density and affinity of fibrinogen
binding sites in platelets from patients with myeloproliferative disorders (MPD) which
may reflect platelet functional abnormalities in these subjects. We have investigated
the binding of 125I-fibrinogen (125I-Fb) to gel-filtered platelets from a large relatively homogeneous group of patients
with MPD compared to normal age matched controls. Twenty-two of the patients investigated
had polycythaemia vera and four essential thrombocythaemia.
The maximal density and affinity (Kd) of 125I-Fb binding was assessed by saturation analysis in gel-filtered platelets (GFP) stimulated
with either 10 εM ADP or 150 mU thrombin. In addition the functional significance
of the binding sites was studied by evaluating the response of GFP from the two experimental
groups by assessing the effects of increasing concentrations of added fibrinogen on
the response to 10 εM ADP using standard light transmission aggregometry.
In both groups the density of fibrinogen binding sites expressed in response to thrombin
stimulation was significantly higher (approximately 2-3 fold) than that found in response
to ADP. However, fewer binding sites were detected in the MPD group as compared with
the control group in response to both ADP and thrombin. The Kd for 125I-Fb was similar for both agonists in normal controls and was significantly lower
than that found in the MPD subjects.
Although the 125I-Fb binding study results indicate a significant reduction in both the number and
affinity of fibrinogen binding sites in patients with myeloproliferative disorders,
the clinical and functional significance of these findings remain uncertain.
