Factor V anticoagulants: clinical, biochemical, and immunological observations

Feinstein, Donald I.; Rapaport, Samuel I.; McGehee, William; Patch, Mary Jane

doi:10.1172/jci106375

Cited by 64 publications

(25 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Feinstein et al. were also unable to detect cross-reacting material in plasma from the same patient (K. H. in their study) with a different homologous anti-Factor V antibody (10).…”

Section: Resultsmentioning

confidence: 75%

Patients with Congenital Factor V Deficiency have Decreased Factor Xa Binding Sites on their Platelets

Miletich¹,

Majerus²,

Majerus³

1978

J. Clin. Invest.

143

View full text Add to dashboard Cite

A B S T R A C T Human platelets have binding sites for plasma coagulation Factor Xa that are available only after the platelet release reaction. Platelets from 15 normal donors bound 216±52 (SD) molecules of Factor Xa per platelet. The association of Factor Xa with its platelet surface receptor results in a 300,000-fold increase in the catalytic activity of Factor Xa in forming thrombin from prothrombin. The turnover number for platelet-bound Factor Xa was 1,850+460 mol thrombin/ ml per min per mol Factor Xa in experiments with platelets from 15 normal donors. Platelets from five patients with varying degrees of Factor V deficiency were investigated to determine whether or not coagulation Factor V participates in either aspect of the Factor X.-platelet interaction. The binding of Factor Xa to platelets and the accompanying increase in rate of thrombin formation were either reduced in parallel or absent in each case with values ranging from 0 to 45% of control values. The apparent affinity of Factor Xa from Factor V-deficient patients was normal when platelet binding was detected. The supernate from thrombin-treated control platelets, which contains Factor V activity, corrected the Factor Xa binding deficiency of the platelets from three patients tested. Immunoreactive Factor V determined with an homologous antibody corresponded to the functional Factor V activity of platelets from one patient with Factor V deficiency, suggesting that the patient's platelets have a decreased amount of normal Factor V.The ability of platelets from the patients to bind Factor Xa and increase the rate of thrombin formation correlated with the severity of each patient's bleeding disorder better than the plasma level of Factor V. The results indicate that Factor V is required for the Factor X.-platelet interaction and that thrombin formation at the platelet surface is important in normal hemostasis.

show abstract

“…Feinstein et al. were also unable to detect cross-reacting material in plasma from the same patient (K. H. in their study) with a different homologous anti-Factor V antibody (10).…”

Section: Resultsmentioning

confidence: 75%

Patients with Congenital Factor V Deficiency have Decreased Factor Xa Binding Sites on their Platelets

Miletich¹,

Majerus²,

Majerus³

1978

J. Clin. Invest.

143

View full text Add to dashboard Cite

show abstract

“…However, the inability of previous investigators using human antibodies to Factor V to detect human mutants with abnormal Factor V protein (19,20) may have been due to the similarity of these antibodies to the human antibody used in this study.…”

Section: Discussionmentioning

confidence: 84%

Heterogeneity of human factor V deficiency. Evidence for the existence of antigen-positive variants

Chiu¹,

Whitaker²,

Colman³

1983

J. Clin. Invest.

View full text Add to dashboard Cite

A B S T R A C T Functional human Factor V has been purified using a rapid immunoaffinity method. Following barium citrate adsorption of plasma, Factor V was precipitated with polyethylene glycol at a concentration between 5 and 14%. The resulting preparation was applied to a column containing an immobilized immunoadsorbent consisting of an IgG fraction containing a naturally occurring human monoclonal (IgG4 X) antibody with inhibitory activity against human Factor V. The solid phase immunoglobulin quantitatively bound Factor V from human plasma. The bound Factor V was effectively eluted with a Tris buffer pH 7.2 containing 1.2 M NaCl and 1 M a-methyl-D-mannoside. The isolated native Factor V with high specific activity (92 U/mg) showed a single band (Mr, 350,000) on both reduced and nonreduced sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Factor V was purified 5,100-fold over plasma with an overall yield of 77%. The purified Factor V when subjected to thrombin activation exhibited an 18-fold increase in coagulant activity.The isolated Factor V neutralized the inhibitory activities of the monoclonal antibody that was used to purify it, as well as the rabbit antibodies produced by immunizing the animals with the purified Factor V. Immunoelectrophoresis of purified Factor V against the polyclonal rabbit antiserum resulted in a single precipitin arc of identical mobility to the Factor V in normal human plasma. Analysis by double immunodiffusion showed a line of identity between plasma and purified Factor V and crossed immunoelectrophoresis showed a single species in normal plasma.A competitive enzyme-linked immunosorbent assay using the rabbit antibody against Factor V was applied to quantify Factor V antigen level in human plasma. Reconstitution of congenitally deficient or immunodepleted plasma with normal plasma or purified Factor V gave parallel dose-response curves. In 14 normal plasma the coagulant activity was 0.98±0.02 U/ml (mean±SEM) and antigen concentration was 11.1±0.4 ,lg/ml. A pool of 14 patients with congenital Factor V deficiency were studied. 10 patients had Factor V antigen ranging from 1.0 to 2.4 jg/ml with corresponding coagulant activities (0-0.17 U/ml) indicating a low concentration of normal Factor V, presumnably due to decreased synthesis or increased degradation. When these patient plasmas and the normal plasmas were analyzed together an excellent correlation (r = 0.97, P < 0.01) was obtained. However, four patients with coagulant activity (0-0.08 U/ml) had Factor V antigen concentrations ranging from 4.4 to 6.1 ,ug/ml, indicating the presence of a reduced concentration of abnormal Factor V protein. The presence of patients with antigen similar in concentration to coagulant activity and antigen in excess of Factor V activity indicates the heterogeneity of congenital Factor V deficiency.

show abstract

“…PTs and PTTs were performed as previously de scribed [3]. Fibrinogen titers were done using a tube dilution method; the highest dilution of plasma pro ducing a visible clot upon addition of thrombin was recorded.…”

Section: Coagulation Testsmentioning

confidence: 99%

Clinical Significance of Accelerated Fibrinolysis in Liver Disease

Francis¹,

Feinstein²

1984

Pathophysiol Haemos Thromb

Self Cite

View full text Add to dashboard Cite

We compared site and severity of bleeding in 46 patients with cirrhosis of the liver and accelerated fibrinolysis (defined as a dilute whole-blood clot lysis time < 2 h) to 44 patients with cirrhosis of the liver and normal fibrinolysis (dilute whole-blood clot lysis time > 4 h). Patients with accelerated fibrinolysis had a significantly higher incidence of severe soft-tissue bleeding after trauma and a trend toward increased intracranial bleeding. Mucosal, postoperative, and gastrointestinal bleeding were equally frequent in the two groups. The median partial thromboplastin time was significantly longer, and the median bilirubin and fibrin/fibrinogen degradation product levels were significantly higher in the group with accelerated fibrinolysis, but median prothrombin time, platelet count, and levels of fibrinogen and serum albumin were comparable. The fibrinolytic inhibitor ε-aminocaproic acid successfully controlled bleeding in 4 of 6 cases used. Accelerated fibrinolysis may predispose patients with cirrhosis to soft-tissue and intracranial bleeding.

show abstract

Factor V anticoagulants: clinical, biochemical, and immunological observations

Cited by 64 publications

References 31 publications

Patients with Congenital Factor V Deficiency have Decreased Factor Xa Binding Sites on their Platelets

Patients with Congenital Factor V Deficiency have Decreased Factor Xa Binding Sites on their Platelets

Heterogeneity of human factor V deficiency. Evidence for the existence of antigen-positive variants

Clinical Significance of Accelerated Fibrinolysis in Liver Disease

Contact Info

Product

Resources

About