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Biomedical subjects

L W Hoyer

Publications and source records attributed to L W Hoyer.

At least 19 recordsLinked to original sources
PubMed1979

Prenatal diagnosis of classic hemophilia.

Prenatal diagnosis of classic hemophilia (hemophilia A) in mid-trimester was achieved by means of immunoradiometric assays for factor VIII on fetal plasma and amniotic-fluid mixtures obtained by fetoscopy. Samples were analyzed from six male fetuses at risk for severe hemophilia and from nine control fetuses for which fetoscopy was carried out to attempt prenatal diagnosis of other genetic disorders. The factor VIII coagulant-antigen values for the control (non-hemophilic) samples were 17 to 94, and the factor VIII related-antigen concentrations were 50 to 155 U per deciliter. Three of the fetuses at risk for hemophilia had factor VIII values in the control range, and these infants were normal at birth. The other three fetuses had low concentrations of factor VIII coagulant antigen but normal concentrations of factor VIII related antigen. These values and the diagnoses of severe hemophilia were confirmed with blood from the abortuses.

Amniotic Fluid↗
PubMed1978

Thrombin activation of factor VIII. II. A comparison of purified factor VIII and the low molecular weight factor VIII procoagulant.

The current experiments examine the reaction between purified human alpha-thrombin and purified human factor VIII and compare this with the reaction between alpha-thrombin and the low molecular weight factor VIII procoagulant activity obtained by high ionic strength dissociation. The reaction patterns of both procoagulants are similar, demonstrating in initial increase in factor VIII activity followed by a decay of procoagulant activity. The extent of activation which is observed in the initial phase decreases with lower temperatures and with lower thrombin concentrations. A pseudo-first order relationship is demonstrated for the activation phase. The labile factor VIII procoagulant activity produced by the initial action of thrombin appears to be intrinsically unstable, since the addition of hirudin or diisopropylfluorophosphate does not prevent the subsequent decay of the procoagulant activity. The similar activation and decay patterns of purified factor VIII and the dissociated low molecular weight factor VIII procoagulant support the concept that the low molecular weight procoagulant itself represents the functional coagulant moiety of the factor VIII complex.

Chemical Phenomena↗
PubMed1978

Immunoradiometric measurement of the factor VIII procoagulant antigen.

A fluid-phase immunoradiometric assay has been developed which identifies an antigen on the Factor VIII (antihemophilic factor) procoagulant protein. This sensitive and quantitative assay is not influenced by levels of Favor VIII-related antigen (von Willebrand factor) or other plasma proteins. There is a close correlation of procoagulant activity and immunologically detectable protein in normal and von Willebrand's disease plasmas. In contrast, several different patterns have been identified in hemophilic plasmas. Neither procoagulant activity nor procoagulant antigen is detectable in plasmas from patients with severe classic hemophilia. Patients with mild and moderate hemophilia have either comparable plasma concentrations of procoagulant activity and procoagulant antigen or relatively greater levels of immunologically detectable protein.

Antigens↗
PubMed1977

A co-operative study for the detection of the carrier state of classic hemophilia.

To determine the specificity and sensitivity of current technics for detecting carriers of classic hemophilia, three investigators simultaneously tested obligate carriers and noncarriers for immunologic and procoagulant factor VIII activity. Overall correct classification ranged from 72 per cent (36 of 50) to 94 per cent (47 of 50). The maximum accuracy obtained with the same linear-discriminant-function method on all data was 90 per cent (26 of 29) in detecting carriers without misclassifying normal persons as carriers (none of 21). Lowest accuracy by the same technic was 66 per cent (19 of 29) carrier detection while misclassifying 19 per cent (four of 21) normal persons. Precision of testing for both factor VII activity and antigen was high (standard deviations from 0.004 to 0.026 on a log scale). Differences between participants seemed related to laboratory technics rather than to statistical methods. The factor VIII activity/antigen measurement is a valid technic for detecting in the carrier state of hemophilia A.

Antigens↗
PubMed1977

von Willebrand's disease and hemorrhagic telangiectasia: association of two complex disorders of hemostasis resulting in life-threatening hemorrhage.

The clinical and laboratory findings in a patient with uncontrolled gastrointestinal bleeding secondary to combined hemostatic defects (von Willebrand's disease and hemorrhagic telangiectasia) are described. Evidence for von Willebrand's disease was found in five family members, but no other affected relative was found to have hemorrhagic telangiectasia. Complete assestivity, factor VIII antigen and von Willebrand factor levels. The patient described also was evaluated for her response to transfusion utilizing these same measurements. Previous reports of the coexistence of hemostatic defects with hereditary hemorrhagic telangiectasia are reviewed. The importance of complete hemostatic evaluation of patients with mucocutaneous bleeding is stressed in light or current knowledge of the diagnostic specificity of available laboratory tests.

Blood Coagulation Tests↗
PubMed1977

Thrombin activation of factor VIII: the effect of inhibitors.

Factor VIII is a large glycoprotein which can be separated into a high molecular weight component which retains factor VIII-related antigens and supports ristocetin-induced platelet agglutination, and a low molecular weight component which has procoagulant activity. It has been suggested that this separation, observed in high ionic strength buffers, might be the consequence of proteolysis by plasma proteins. To consider this possibility, we have examined the interaction of the proteolytic enzyme thrombin with factor VIII. This study, carried out with highly purified materials, has used thrombin-mediated factor VIII proagulant activation as an indicator of this interaction. Several proteolytic inhibitors have been studied to determine their ability to inhibit factor VIII activation by thrombin. Under the current experimental conditions, diisopropylfluorophosphate (DFP) and hirudin inhibited the reaction, while heparin was an effective inhibitor only when plasma proteins were added. Benzamidine inhibited factor VIII activation when used at high concentrations, and phenylmethyl sulphonylfluoride and soybean trypsin inhibitor were found to be ineffective. These results show that DFP and hirudin prevent thrombin alteration of factor VIII and will be useful in purification and characterization studies of the factor VIII molecule.

Factor VIII↗
PubMed1977

Stabilization of factor VIII in plasma by the von Willebrand factor. Studies on posttransfusion and dissociated factor VIII and in patients with von Willebrand's disease.

In normal plasma, the ratio of the procoagulant activity of factor VIII (VIII(AHF)) to that of the von Willebrand factor activity (ristocetin cofactor, VIII(VWF)) or factor VIII antigen (VIII(AGN)) is approximately 1, but ratios > 1 (e.g., VIII(AHF) > VIII(VWF) or VIII(AGN)) may be observed in some patients with von Willebrand's disease and in the "late" posttransfusion plasmas of patients with this disorder. The lability of VIII(AHF) was studied by incubating plasma, diluted 1:10 in imidazole buffer pH 7.1, for 6 h at 37 degrees C. With normal plasmas, 77+/-12% (SD) of the original VIII(AHF) activity remained after incubation. VIII(AHF) was labile (e.g., 35-55% residual activity) in the "late" posttransfusion plasmas (VIII(AHF) >> VIII(VWF)) of a patient with von Willebrand's disease, but not in the "early" posttransfusion plasmas (VIII(AHF) approximately VIII(VWF)). VIII(AHF) was also labile in the (base-line) plasmas of three patients with von Willebrand's disease in whom the ratios of VIII(AHF) to VIII(VWF) were 4.4 to 8.1, but not in the plasmas of four other patients in whom the ratio was approximately 1. The electrophoretic mobility of factor VIII antigen was increased in two of the three patients with labile VIII(AHF). In both of these patients, and in the late posttransfusion plasmas, labile VIII(AHF) activity could be stabilized by the addition of purified von Willebrand factor (lacking VIII(AHF) activity) or by hemophilic plasma, but not by plasmas of patients with severe von Willebrand's disease. Thus, VIII(VWF) may serve to stabilize VIII(AHF) and this might explain the posttransfusion findings in von Willebrand's disease.

Blood Coagulation Factors↗
PubMed1977

The properties of immune complexes formed by human antibodies to factor VIII.

Although human antibodies to Factor VIII inactivate its procoagulant activity, they do not form immunoprecipitates when tested with this antigen. To understand this observation, we have examined the interaction of normal human Factor VIII with four high-titer human anti-Factor VIII, two from transfused hemophiliacs and two "spontaneous" antibodies from nonhemophilic individuals. An estimate of the size of complexes formed by these antibodies has been obtained by agarose gel filtration of mixtures of anti-Factor VIII with cryoprecipitate. Complexed anti-Factor VIII was detected by the method of Allain and Frommel: acid dissociation of complexes at pH 3.5. Complexed anti-Factor VIII was detected in column fractions eluting between the void volume and those which correspond to the elution volume of human IgG. In contrast, Factor VIII procoagulant activity was restricted to void volume fractions when separations were carried out in antigen excess, and free anti-Factor VIII was limited to late-eluting fractions when separations were carried out in antibody excess. A small proportion of the complexed anti-Factor VIII was present in void volume fractions; the quantity was directly related to the ratio of antibody to antigen.Thus, although some complexed anti-Factor VIII is detected in void volume fractions, as would be expected for complexes formed with a very large plasma protein, most immune complexes elute in fractions that indicate interaction with a smaller antigen. These findings suggest that human anti-Factor VIII inactivates procoagulant activity by forming a complex with a small, apparently univalent, component of Factor VIII. This property may prevent immunoprecipitate formation.

Antibodies↗
PubMed1977

Rabbit factor VIII: identification of size heterogeneity.

Two forms of rabbit factor VIII procoagulant activity, distinguishable by size on gel filtration and ultracentrifugation, have been identified in normal rabbit plasma. These studies have been carried out with citrate-anticoagulated rabbit plasma obtained by cardiac puncture. Two peaks of factor VIII activity were obtained on agarose gel chromatography, using physiologic ionic strength buffers: a high molecular weight peak eluting at the void volume and a second peak eluting with smaller plasma proteins. The presence of high and low molecular weight factor VIII activities was confirmed by sucrose density gradient centrifugation. The two peaks of factor VIII activity remained distinct when proteolytic inhibitors were added to the plasma and eluting buffers. Both the high and low molecular weight factor VIII procoagulant activities were inhibited by antibodies to human and rabbit factor VIII, and both were activated by thrombin. The identification of size heterogeneity of factor VIII in normal rabbit plasma, in the absence of any modification by ionic strength, may permit more satisfactory study of the relationship of factor VIII size to function.

Animals↗
PubMed1976

The effects of epinephrine infusion in patients with von Willebrand's disease.

Epinephrine infusion causes variable increases in the components of the Factor VIII (antihemophilic factor) complex in patients with von Willebrand's disease. The increase in antihemophilic factor procoagulant activity was greater than that of Factor VIII-related antigen and von Willebrand factor activity in two patients with von Willebrand's disease. Similar increases in the three individual factors were demonstrated in two other patients. A 4-10-fold increase in Factor VIII-related properties was identified in each of these individuals after infusion. One patient has been studied with very severe von Willebrand's disease; none of the Factor VIII-related properties increased despite two infusions of epinephrine. Bleeding times were normalized or remained normal in the two patients whose von Willebrand factor activity was greater than 25 U/100 ml. It remained prolonged in those three patients whose von Willebrand factor activity levels remained below that concentration. The increase in procoagulant activity was transient in all patients and t 1/2 values were estimated to be between 0.8 and 3.4 h.

Adult↗