Factor-VIII-related antigen in platelets

Howard, Margaret A.; Montgomery, Danielle C.; Hardisty, R. M.

doi:10.1016/0049-3848(74)90218-7

Cited by 107 publications

(40 citation statements)

References 7 publications

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“…The high molecular weight nature of Factor VIII is probably a serious impediment for passage to the extravascular space. Although it was found that Factor VIII may be bound by platelets to some extent (40)(41)(42),7 no Factor VIII was taken up by the platelets of transfused, severe von Willebrand's disease patients (43)(44)(45). Similarly, no Factor VIII was detected in the endothelium after transfusion of such patients (46).…”

Section: Discussionmentioning

confidence: 99%

Survival of 125iodine-labeled Factor VIII in normals and patients with classic hemophilia. Observations on the heterogeneity of human Factor VIII.

Over¹,

Sixma²,

Bruïne³

et al. 1978

J. Clin. Invest.

100

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Section: Discussionmentioning

confidence: 99%

Survival of 125iodine-labeled Factor VIII in normals and patients with classic hemophilia. Observations on the heterogeneity of human Factor VIII.

Over¹,

Sixma²,

Bruïne³

et al. 1978

J. Clin. Invest.

100

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“…Proteins such as VIII:AGN probably do not cross cell membranes and therefore it is unlikely that intracellular granule VIII:AGN is derived from plasma. Platelets and megakaryocytes in patients with severe von Willebrand's disease do not contain intracellular VIII:AGN (7)(8)(9)(10)(11)(12) and do not acquire the protein after transfusion (7,10,11). These observations suggest that exogenous plasma VIII:AGN does not gain access to the platelet's interior and suggests that megakaryocytes and (or) platelets synthesize the VIII:AGN and VIII:VWF present in the granule pool.…”

Section: Introductionmentioning

confidence: 96%

“…Studies from several laboratories clearly indicate that exogenous plasma VIII:AGN does not gain access to the platelet intracellular VIII:AGN pool (7,10,11). It thus seems logical to assume that the intracellular platelet VIII:AGN is derived from megakaryocyte synthesis.…”

mentioning

confidence: 99%

Synthesis of Factor VIII Antigen by Cultured Guinea Pig Megakaryocytes

Nachman¹,

Levine²,

Jaffe³

1977

J. Clin. Invest.

369

134

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A B S T R A C T Immunoprecipitates containing guinea pig Factor VIII antigen were prepared from guinea pig plasma with a cross-reacting rabbit anti-human Factor VIII. Monospecific antisera to guinea pig Factor VIII antigen were produced in rabbits by using these washed immunoprecipitates as immunogens. The resulting antisera to guinea pig Factor VIII antigen detected Factor VIII antigen in guinea pig plasma and inhibited the von Willebrand factor activity in guinea pig plasma. This antibody also detected Factor VIII antigen in a solubilized protein mixture prepared from isolated cultured guinea pig megakaryocytes. Cultured guinea pig megakaryocytes were labeled with radioactive leucine. By radioautography, 96.2% of the radioactivity was present in megakaryocytes. The radioactive Factor VIII antigen present in the solubilized cell protein mixture was isolated by immunoprecipitation and characterized by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The results demonstrate that cultured guinea pig megakaryocytes synthesize Factor VIII antigen which contains the same polypeptide subunit (mol wt 200,000) present in guinea pig plasma Factor VIII antigen.

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“…Besides circulating in plasma, significant amounts of VWF are also stored within the a-granules of platelets. 1,2 This platelet-VWF is synthesized during megakaryocytopoiesis and accounts for 10% to 20% of the total VWF present in normal platelet-rich plasma. [2][3][4] Importantly, the platelet-VWF pool is distinct from plasma-VWF and is enriched in hemostatically active high molecular weight multimers (HMWM).…”

Section: Introductionmentioning

confidence: 99%