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Platelet membrane abnormalities in myeloproliferative disorders: decrease in glycoproteins Ib and IIb/IIIa complex is
M Mazzucato1, L De Marco, V De Angelis
1Centro Immunotrasfusionale e Chimica Clinica, C.R.O. Aviano, U.S.L. n. 11, Pordenone, Italy.
Abstract:
The number and functional activity of membrane glycoproteins (GP) Ib and IIb/IIIa were investigated in platelets from 11 patients with myeloproliferative disorders (MPD). Three patients had essential thrombocythaemia, two had chronic myeloid leukaemia and six had polycythaemia vera. The numbers of GPIb and GPIIb/IIIa molecules were detected on the platelet surface using different 125I-labelled monoclonal antibodies. The functional properties of GPIb and GPIIb/IIIa were evaluated using purified 125I-labelled asialo von Willebrand factor (vWF) and purified 125I-labelled fibrinogen, respectively, in a binding assay. Binding of the anti-GPIIb/IIIa antibody was decreased by 40% in almost all patients studied and, when measured, it was accompanied by decreased fibrinogen binding to activated platelets. Binding of anti-GPIb antibodies to platelets was also slightly decreased or virtually the same in eight out of 11 patients. The decrease correlated with decreased binding of asialo vWF. The increased plasma glycocalicin levels, measured in four patients, depended on the high platelet count. Scatchard analysis revealed normal receptor binding affinity for all ligands tested in all but one patient. In this report we demonstrate that abnormalities in the concentrations of GPIIb/IIIa membrane proteins are commonly present in patients with MPD, while a decrease in GPIb concentration is also seen, although in fewer patients. These abnormalities are accompanied by a concurrent decrease in the respective receptor functions. These findings may explain part of the haemorrhagic tendency often encountered in MPD.
Insights
Platelet membrane glycoproteins (GP) Ib and IIb/IIIa are often abnormal in myeloproliferative disorders (MPD). These changes correlate with reduced function and may explain bleeding risks in MPD patients.
Area of Science:
- Hematology
- Oncology
- Biochemistry
Background:
- Myeloproliferative disorders (MPD) are a group of conditions affecting blood cell production.
- Platelets play a crucial role in hemostasis, and their membrane glycoproteins are key to function.
- Abnormalities in platelet glycoproteins have been implicated in bleeding tendencies in MPD.
Purpose of the Study:
- To investigate the number and functional activity of platelet membrane glycoproteins (GP) Ib and IIb/IIIa in patients with MPD.
- To determine if alterations in these glycoproteins correlate with clinical manifestations like bleeding.
Main Methods:
- Quantification of GPIb and GPIIb/IIIa on platelet surfaces using 125I-labelled monoclonal antibodies.
- Assessment of GPIb and IIb/IIIa functional activity via binding assays with labeled asialo von Willebrand factor (vWF) and fibrinogen.
- Scatchard analysis to evaluate receptor binding affinity.
Main Results:
- Decreased binding of anti-GPIIb/IIIa antibody (approx. 40%) and reduced fibrinogen binding to activated platelets in most MPD patients.
- Slightly decreased or unchanged binding of anti-GPIb antibodies in most patients, correlating with reduced asialo vWF binding.
- Normal receptor binding affinity observed in Scatchard analysis for most ligands and patients.
- Increased plasma glycocalicin levels were dependent on high platelet counts.
Conclusions:
- Abnormalities in the concentration and function of GPIIb/IIIa are common in MPD patients.
- Decreased GPIb concentration and function are also observed in a subset of MPD patients.
- These glycoprotein abnormalities may contribute to the hemorrhagic tendency frequently seen in MPD.