Plasma thromboplastin antecedent (PTA, factor XI): a specific and sensitive radioimmunoassay

Abstract A specific, sensitive, and reproducible radioimmunoassay for human plasma thromboplastin antecedent (PTA, factor XI) has been developed with purified PTA and monospecific rabbit antiserum. Precise measurements of PTA antigen were possible for concentrations as low as 0.3% of that in normal pooled plasma. Normal plasma contained approximately 6 microgram PTA/ml. A good correlation (correlation coefficient 0.68) existed between the PTA procoagulant assays and radioimmunoassays among 50 normal adults (25 males and 25 females). PTA antigen was markedly reduced in plasma of 13 patients with congenital homozygous PTA deficiency (range less than 0.003–0.128 U/ml) and 9 patients with hepatic cirrhosis (0.35+/-0.17 U/ml), but was normal in those of 9 patients under treatment with warfarin, 8 patients with disseminated intravascular coagulation and 16 patients with other congenital clotting factor abnormalities, including prekallikrein deficiency (Fletcher trait) and high molecular weight kininogen deficiency (Fitzgerald trait).

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Plasma thromboplastin antecedent (PTA, factor XI): a specific and sensitive radioimmunoassay

Blood ◽

10.1182/blood.v50.3.377.bloodjournal503377 ◽

1977 ◽

Vol 50 (3) ◽

pp. 377-385

Author(s):

H Saito ◽

GH Jr Goldsmith

Keyword(s):

Molecular Weight ◽

Human Plasma ◽

High Molecular Weight ◽

Disseminated Intravascular Coagulation ◽

Hepatic Cirrhosis ◽

Rabbit Antiserum ◽

Clotting Factor ◽

High Molecular Weight Kininogen ◽

Factor Xi ◽

Normal Adults

A specific, sensitive, and reproducible radioimmunoassay for human plasma thromboplastin antecedent (PTA, factor XI) has been developed with purified PTA and monospecific rabbit antiserum. Precise measurements of PTA antigen were possible for concentrations as low as 0.3% of that in normal pooled plasma. Normal plasma contained approximately 6 microgram PTA/ml. A good correlation (correlation coefficient 0.68) existed between the PTA procoagulant assays and radioimmunoassays among 50 normal adults (25 males and 25 females). PTA antigen was markedly reduced in plasma of 13 patients with congenital homozygous PTA deficiency (range less than 0.003–0.128 U/ml) and 9 patients with hepatic cirrhosis (0.35+/-0.17 U/ml), but was normal in those of 9 patients under treatment with warfarin, 8 patients with disseminated intravascular coagulation and 16 patients with other congenital clotting factor abnormalities, including prekallikrein deficiency (Fletcher trait) and high molecular weight kininogen deficiency (Fitzgerald trait).

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DETECTION AND QUANTITATION OF CLEAVED AND UNCLEAVED HIGH MOLECULAR WEIGHT KININOGEN IN PLASMA BY LIGAND BLOTTING WITH RADIOLABELED PLASMA PREKALLIKREIN OR FACTOR XI

10.1055/s-0038-1642850 ◽

1987 ◽

Author(s):

B Lämmle ◽

B L Zuraw ◽

M J Heeb ◽

H P Schwarz ◽

J G Curd ◽

...

Keyword(s):

Molecular Weight ◽

Human Plasma ◽

High Molecular Weight ◽

Normal Human Plasma ◽

High Molecular Weight Kininogen ◽

Single Chain ◽

Factor Xi ◽

Sds Page ◽

Normal Human

A method for the quantitative assay of native single chain and kallikrein cleaved two-chain high molecular weight kininogen (HMWK) in plasma has been developed. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) of whole plasma is followed by electroblotting of the electropherogram to nitrocellulose membranes and detection of the inmobilized HMWK with its physiologic ligands, plasma prekallikrein or factor XI. Using 1251-prekallikrein or 125I-F.XI overlay nitrocellulose bound HMWK can be visualized by autoradiography.Using unreduced SDS-PAGE cleaved two-chain HMWK (Mr 107,000 and 95,000) is electrophoretically separated from uncleaved single chain HMWK (Mr 150,000). Counting the radioactivity of the nitrocellulose pieces corresponding to cleaved HMWK permits its quantitative measurement by comparison with standards consisting of decreasing amounts of fully dextran sulfate activated normal human plasma. Single chain HMWK is similarly assayed using reduced SDS-PAGE and unactivated normal human plasma standards.This technique is highly specific and sensitive to ˜ 50 ng of either cleaved or uncleaved HMWK. Varying concentrations of cleaved HMWK were found in plasmas from patients suffering from various systemic inflanmatory conditions. Higher levels of in vivo cleaved HMWK were observed during acute attacks of hereditary angioedema due to Cl-inhibitor deficiency.This technique may be useful for the assessment of the degree of in vitro or in vivo activation of the contact system of plasma.

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Association of factor XI and high molecular weight kininogen in human plasma.

Journal of Clinical Investigation ◽

10.1172/jci108898 ◽

1977 ◽

Vol 60 (6) ◽

pp. 1376-1380 ◽

Cited By ~ 195

Author(s):

R E Thompson ◽

R Mandle ◽

A P Kaplan

Keyword(s):

Molecular Weight ◽

Human Plasma ◽

High Molecular Weight ◽

High Molecular Weight Kininogen ◽

Factor Xi

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Fitzgerald factor (high molecular weight kininogen) clotting activity in human plasma in health and disease in various animal plasmas

Blood ◽

10.1182/blood.v48.6.941.941 ◽

1976 ◽

Vol 48 (6) ◽

pp. 941-947 ◽

Cited By ~ 27

Author(s):

H Saito ◽

G Goldsmith ◽

R Waldmann

Keyword(s):

Molecular Weight ◽

Human Plasma ◽

High Molecular Weight ◽

Lupus Erythematosus ◽

Mammalian Species ◽

Clotting Factor ◽

Factor Activity ◽

High Molecular Weight Kininogen ◽

Amphibian Species

Abstract Fitzgerald factor (high molecular weight kininogen) is an agent in normal human plasma that corrects the impaired in vitro surface- mediated plasma reactions of blood coagulation, fibrinolysis, and kinin generation observed in Fitzgerald trait plasma. To assess the possible pathophysiologic role of Fitzgerald factor, its titer was measured by a functional clot-promoting assay. Mean +/- SD in 42 normal adults was 0.99+/-0.25 units/ml, one unit being the activity in 1 ml of normal pooled plasma. No difference in titer was noted between normal men and women, during pregnancy, or after physical exercise. Fitzgerald factor activity was significantly reduced in the plasmas of eight patients with advanced hepatic cirrhosis (0.40+/-0.09 units/ml) and of ten patients with disseminated intravascular coagulation (0.60+/-0.30 units/ml), but was normal in plasmas of patients with other congenital clotting factor deficiencies, nephrotic syndrome, rheumatoid arthritis, systemic lupus erythematosus, or sarcoidosis, or under treatment with warfarin. The plasmas of 21 mammalian species tested appeared to contain Fitzgerald factor activity, but those of two avian, two repitilian, and one amphibian species did not correct the coagulant defect in Fitzgerald trait plasmas.

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Fitzgerald factor (high molecular weight kininogen) clotting activity in human plasma in health and disease in various animal plasmas

Blood ◽

10.1182/blood.v48.6.941.bloodjournal486941 ◽

1976 ◽

Vol 48 (6) ◽

pp. 941-947 ◽

Cited By ~ 1

Author(s):

H Saito ◽

G Goldsmith ◽

R Waldmann

Keyword(s):

Molecular Weight ◽

Human Plasma ◽

High Molecular Weight ◽

Lupus Erythematosus ◽

Mammalian Species ◽

Clotting Factor ◽

Factor Activity ◽

High Molecular Weight Kininogen ◽

Amphibian Species

Fitzgerald factor (high molecular weight kininogen) is an agent in normal human plasma that corrects the impaired in vitro surface- mediated plasma reactions of blood coagulation, fibrinolysis, and kinin generation observed in Fitzgerald trait plasma. To assess the possible pathophysiologic role of Fitzgerald factor, its titer was measured by a functional clot-promoting assay. Mean +/- SD in 42 normal adults was 0.99+/-0.25 units/ml, one unit being the activity in 1 ml of normal pooled plasma. No difference in titer was noted between normal men and women, during pregnancy, or after physical exercise. Fitzgerald factor activity was significantly reduced in the plasmas of eight patients with advanced hepatic cirrhosis (0.40+/-0.09 units/ml) and of ten patients with disseminated intravascular coagulation (0.60+/-0.30 units/ml), but was normal in plasmas of patients with other congenital clotting factor deficiencies, nephrotic syndrome, rheumatoid arthritis, systemic lupus erythematosus, or sarcoidosis, or under treatment with warfarin. The plasmas of 21 mammalian species tested appeared to contain Fitzgerald factor activity, but those of two avian, two repitilian, and one amphibian species did not correct the coagulant defect in Fitzgerald trait plasmas.

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