Diagnosis of Bernard-Soulier syndrome and Glanzmann's thrombasthenia with a monoclonal assay on whole blood.

Montgomery, Robert R.; Kunicki, Thomas J.; Taves, Cynthia J.; Pidard, Dominique; Corcoran, M.

doi:10.1172/jci110780

Cited by 180 publications

(53 citation statements)

References 13 publications

(13 reference statements)

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“…1) which is similar with other CD9 clusters such as PMA IgG (46OOO/platelet) [6] and AG-1 Fab (65 OOO/platelet) [7]. The high copy numbers of binding sites were also reported with major platelet membrane glycoproteins such as GPIb (25000-34000) [27,28] or GPIIb/IIIa (40000-50000) [29-311. There are a few reports that no change in molecular weight of p24 was found on reduction, implying that there are no disulphide bonds [1,14]. However, our data show that there is an apparent difference in molecular mass of both purified CD9 antigen and immunoprecipitated antigen (Fig.…”

Section: Discussionsupporting

confidence: 72%

Purification and partial characterization of CD9 antigen of human platelets

et al. 1990

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CD9 antigen (p24) was purified from human platelets and partially characterized. The yield was 75 μg from 10 units of platelet concentrates. p24 (38 000 copies/platelet) has intramolecular disulfide bond(s) and, in SDS‐PAGE, consists of major 24‐kDa molecule and minor 26‐ to 31‐kDa molecules. The N‐terminal sequence of p24, PVKGOTKXIKYLLFGFNFIF, indicates that the protein has not previously been characterized and amino terminus (position 12–20) is hydrophobic.

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Section: Discussionsupporting

confidence: 72%

Purification and partial characterization of CD9 antigen of human platelets

et al. 1990

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“…3). The same proteins reacted with AP2, a well-characterized anti-GPIIb/IIIa monoclonal antibody (19,37).…”

Section: Resultsmentioning

confidence: 99%

Independent modulation of von Willebrand factor and fibrinogen binding to the platelet membrane glycoprotein IIb/IIIa complex as demonstrated by monoclonal antibody.

Lombardo¹,

Hodson²,

Roberts³

et al. 1985

J. Clin. Invest.

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104

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In this study we have used two new monoclonal antibodies, designated LIP5 and LJP9, as well as a previously described one, AP2, all specific for the platelet membrane glycoprotein (GP)IIb/ IIIa complex. None of them reacted with dissociated GPIIb or GPIIIa. The monovalent Fab fragment of both LJP5 and LJP9 bound to unstimulated platelets in a saturable manner, but binding was markedly decreased after platelets had been incubated at 370C in the absence of added extracellular calcium. The binding of LJP9 was not affected by AP2, but was blocked by excess UP5. On the contrary, the binding of LJP5 was blocked in the presence of both AP2 and LJP9. Thus, these antibodies bound to distinct epitopes of GPIIb/IIIa. At saturation, the binding to unstimulated platelets was between 2.41 and 10.9 X 104 molecules/platelet for LJP5 and between 3.47 and 9.1 X 104 molecules/platelet for LJP9 (range of 11 and 10 experiments, respectively). Binding increased up to 50% after thrombin stimulation. The estimated association constant, K., was 2.7 X 107 M-1 for LJP5 and 3.85 X 107 M-1 for LJP9. Both UP5 and 1JP9 partially inhibited the association of 45Ca2W with the surface of unstimulated platelets. Moreover, both antibodies blocked the binding of von Willebrand factor (vWF) to stimulated platelets, whereas only UJP9, but not UP5, blocked fibrinogen binding. LJP9 was also a potent inhibitor of platelet aggregation, whereas UP5 was without effect in this regard. The results of the present study demonstrate that independent modulation of vWF and fibrinogen binding to stimulated platelets can be attained with monoclonal antibodies directed against distinct epitopes of GPIIb/IIIa.

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“…A major problem in detecting acquired disorders may be the susceptibility of platelets to membrane alterations during isolation procedures used for previous methods of analysis (22) that could obscure minor glycoprotein abnormalities or cause the loss ofan abnormal platelet subpopulation. The measurement of platelet surface glycoproteins directly in immediately fixed whole blood samples with '251-labeled monoclonal antibodies (23) overcomes the risks from these in vitro artefacts. We have adapted this method to define the pattern of platelet membrane changes caused by in vitro thrombin-induced secretion, and the microparticle changes caused by whole blood coagulation.…”

Section: Introductionmentioning

confidence: 99%

Platelet surface glycoproteins. Studies on resting and activated platelets and platelet membrane microparticles in normal subjects, and observations in patients during adult respiratory distress syndrome and cardiac surgery.

George¹,

Pickett²,

Saucerman³

et al. 1986

J. Clin. Invest.

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451

164

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The accurate definition of surface glycoprotein abnormalities in circulating platelets may provide better understanding of bleeding and thrombotic disorders. Platelet surface glycoproteins were measured on intact platelets in whole blood and platelet membrane microparticles were assayed in cell-free plasma using 125I-monoclonal antibodies. The glycoproteins (GP) studied were: GP lb and GP Ilb-Illa, two of the major intrinsic plasma membrane glycoproteins; GMP-140, an a-granule membrane glycoprotein that becomes exposed on the platelet surface following secretion; and thrombospondin (TSP), an a-granule secreted glycoprotein that rebinds to the platelet surface. Thrombin-induced secretion in normal platelets caused the appearance of GMP-140 and TSP on the platelet surface, increased exposure of GP Ilb-Illa, and decreased antibody binding to GP lb. Patients with adult respiratory distress syndrome had an increased concentration of GMP-140 and TSP on the surface of their platelets, demonstrating in vivo platelet secretion, but had no increase of platelet microparticles in their plasma. In contrast, patients after cardiac surgery with cardiopulmonary bypass demonstrated changes consistent with membrane fragmentation without secretion: a decreased platelet surface concentration of GP lb and GP 1Ib with no increase of GMP-140 and TSP, and an increased plasma concentration of platelet membrane microparticles. These methods will help to define acquired abnormalities of platelet surface glycoproteins.

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Diagnosis of Bernard-Soulier syndrome and Glanzmann's thrombasthenia with a monoclonal assay on whole blood.

Cited by 180 publications

References 13 publications

Purification and partial characterization of CD9 antigen of human platelets

Purification and partial characterization of CD9 antigen of human platelets

Independent modulation of von Willebrand factor and fibrinogen binding to the platelet membrane glycoprotein IIb/IIIa complex as demonstrated by monoclonal antibody.

Platelet surface glycoproteins. Studies on resting and activated platelets and platelet membrane microparticles in normal subjects, and observations in patients during adult respiratory distress syndrome and cardiac surgery.

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