Radioimmunoassay of factor V in human plasma and platelets

Tracy, PB; Eide, LL; Bowie, E. J. W.; Mann, KG

doi:10.1182/blood.v60.1.59.59

Cited by 228 publications

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“…1b) or thrombin-activated releasate (Fig. 2b) is approximately 60% of the normal control, indicating that her platelets should contain from 2700 to 9000 molecules of FV/platelet [4]. Therefore, under the conditions of the study shown in Fig.…”

Section: Discussionmentioning

confidence: 81%

Megakaryocytes endocytose and subsequently modify human factor V in vivo to form the entire pool of a unique platelet-derived cofactor

Gould

Simioni

Silveira

et al. 2005

Journal of Thrombosis and Haemostasis

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To cite this article: Gould WR, Simioni P, Silveira JR, Tormene D, Kalafatis M, Tracy PB. Megakaryocytes endocytose and subsequently modify human factor V in vivo to form the entire pool of a unique platelet-derived cofactor. J Thromb Haemost 2005; 3: 450-6.See also Hoffman M. One more way that mice and men are different. This issue, pp 448-9.Summary. Factor Va (FVa), derived from plasma or released from stimulated platelets, is the essential cofactor in thrombin production catalyzed by the prothrombinase complex. Plasma-derived factor V (FV) is synthesized in the liver. The source(s) of the platelet-derived cofactor remains in question. We identified a patient homozygous for the FV Leiden mutation, who received a liver transplant from a homozygous wildtype FV donor. Eighteen days post-transplant, phenotypic analysis of the patient's platelet-derived FV indicated that the platelets were acquiring wild-type FV, consistent with the temporal differentiation of megakaryocytes and subsequent platelet production. Nine months post-transplant, the plateletderived FV pool consisted entirely of wild-type FV. Consequently, megakaryocyte endocytosis of plasma-derived FV must account for the entire platelet-derived pool, because blood-borne platelets cannot bind or endocytose FV. Subsequent to this endocytic process, the patient's platelet-derived FV was cleaved to a partially active cofactor, and rendered resistant to phosphorylation catalyzed by a platelet-associated kinase, and hence less susceptible to activated protein C-catalyzed inactivation. These data provide the first in vivo demonstration of an endocytosed plasma protein undergoing intracellular modifications that alter its function. This process results in the sequestration of active FVa within the platelet compartment, poised for immediate action subsequent to release from platelets at a site of injury.

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Section: Discussionmentioning

confidence: 81%

Megakaryocytes endocytose and subsequently modify human factor V in vivo to form the entire pool of a unique platelet-derived cofactor

Gould

Simioni

Silveira

et al. 2005

Journal of Thrombosis and Haemostasis

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“…*P < .01; † P < .001; ‡ P < 0.0001 approximately 5-to 10-fold, which is consistent with previous studies. 45,46 In platelets, an even larger concentration range was observed, at approximately 10-fold for TFPI, and approximately 20-fold for fV and PS. This suggests that the effect of race on the concentration of these proteins is minor relative to random variation.…”

Section: Discussionmentioning

confidence: 98%

Correlates of plasma and platelet tissue factor pathway inhibitor, factor V, and Protein S

Ellery

Hilden

Sejling

et al. 2018

Research and Practice in Thrombosis and Haemostasis

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SummaryBackgroundPlasma Tissue Factor Pathway Inhibitor (TFPI) circulates bound to factor V (fV) and Protein S (PS). Estrogen therapy decreases plasma TFPI and PS. TFPI, fV, and PS circulate within platelets, and are released upon activation to modulate thrombus formation.ObjectiveIdentify factors affecting the concentrations of plasma and platelet TFPI, fV, and PS.MethodsBlood samples were obtained from 435 healthy individuals. Plasma total TFPI, TFPIɑ, fV, and PS, and platelet TFPI, fV, and PS were quantified. Correlations between these protein concentrations and age, gender, race, and estrogen use were established.ResultsIn males, only plasma fV increased with age, while in females, all plasma analytes increased with age. Males had higher plasma total TFPI, TFPIα, and PS than females. The platelet proteins in either sex remained relatively stable with increasing age. Platelet TFPI and PS were comparable in both sexes, while platelet fV was higher in females. Estrogen use was associated with decreased plasma total TFPI and TFPIα, and platelet PS, but not with platelet TFPI concentration. Racial differences in plasma and platelet proteins were observed, some of which were larger than inter-individual differences observed within racial groups. TFPI, fV and PS concentrations correlated in plasma, while only fV and PS correlated in platelets.ConclusionsPlasma and platelet TFPI, fV and PS differ in their: (i) in vivo association; (ii) demographic correlates; and (iii) alteration by estrogen therapies. Therefore, the plasma and platelet pools of these proteins may modulate hemostasis and thrombosis via different biochemical pathways.

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“…About 18%-25% of FV is also stored in platelet alpha-granules so platelet transfusions can effectively treat bleeds in FV deficiency, as they were given in the acute treatment of our patient's initial intracranial hemorrhage. 2,9 Platelet transfusions may actually be superior to FFP because platelets localize at the site of vascular injury and release FV from alpha-granules, which persists in circulation well after FV from FFP becomes undetectable. 10 In fact, the reason bleeding tendency in FV deficiency does not correlate well with actual factor levels may be because of compensation by platelet FV.…”

Section: Discussionmentioning

confidence: 99%

Management of intracranial hemorrhage in severe factor V deficiency and definitive treatment with liver transplantation

DesPain

Kshetrapal

Kousa

et al. 2017

Pediatric Transplantation

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FV is primarily produced in the liver, and congenital FV deficiency is a disorder with an incidence of one in 1 million. Standard care is to treat severe bleeding phenotypes with FFP as there is no recombinant or plasma-derived FV concentrate. We present a case of a neonate with known severe FV deficiency diagnosed after prolonged bleeding after circumcision who represented at age 2 months with a large left intraparenchymal hemorrhage. His bleed was treated with FFP, platelet transfusion, recombinant VIIa, and emergent evacuation. He was maintained on plasma infusions but was unable to space his infusions beyond 48 hours. Liver transplantation was considered as a definitive treatment for this condition. While awaiting a suitable liver, his FV trough levels occasionally dropped below 5%, and he suffered from a second acute intracranial bleed. He received an orthotopic liver transplant at age 5 months, resulting in correction of his FV levels. He has not required any plasma infusions post-transplantation and has had no further bleeding episodes. Liver transplantation should be considered as definitive treatment early in the course for patients with severe FV deficiency and first time life-threatening bleed.

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Radioimmunoassay of factor V in human plasma and platelets

Cited by 228 publications

References 0 publications

Megakaryocytes endocytose and subsequently modify human factor V in vivo to form the entire pool of a unique platelet-derived cofactor

Megakaryocytes endocytose and subsequently modify human factor V in vivo to form the entire pool of a unique platelet-derived cofactor

Correlates of plasma and platelet tissue factor pathway inhibitor, factor V, and Protein S

Management of intracranial hemorrhage in severe factor V deficiency and definitive treatment with liver transplantation

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