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Biomedical subjects

C F Abildgaard

Publications and source records attributed to C F Abildgaard.

At least 19 recordsLinked to original sources
PubMed1990

Human recombinant DNA-derived antihemophilic factor (factor VIII) in the treatment of hemophilia A. recombinant Factor VIII Study Group.

BACKGROUND: Current treatment of hemophilia A, a hereditary disorder affecting approximately 1 in 10,000 males, relies on plasma-derived factor VIII concentrates. We tested the safety and efficacy of a recombinant factor VIII preparation for the treatment of this disorder. METHODS: We conducted the investigation in three stages: comparing the pharmacokinetics of plasma-derived and recombinant factor VIII, assessing the efficacy of recombinant factor VIII for home therapy, and assessing its efficacy for major surgical procedures and hemorrhage. A total of 107 subjects with hemophilia, 20 of whom had not been treated previously, enrolled in the investigation. RESULTS: The in vivo recovery and elimination half-lives of recombinant factor VIII equaled or exceeded those of plasma-derived factor VIII. Seventy-six subjects participated in a home-treatment program, using recombinant factor VIII for 69 to 807 days (median, 618); home diaries of 56 subjects treated for 5 months were analyzed. Of 540 bleeding episodes, 399 (73.9 percent) required only one treatment with recombinant factor VIII. The projected annual consumption of recombinant factor VIII was similar to that of plasma-derived factor VIII concentrate. Twenty-six subjects received recombinant factor VIII for 22 surgical procedures and 10 serious hemorrhages; hemostasis was excellent in all cases. De novo formation of inhibitors occurred in only 1 of 85 previously treated subjects. Inhibitor antibodies also developed in 6 of 21 children, 20 of whom had not previously been treated; 5 had low levels (less than or equal to 7.5 Bethesda units) despite continued treatment with recombinant factor VIII. There was no evidence of new formation of antibody to foreign proteins, and recombinant factor VIII was well tolerated. CONCLUSIONS: Recombinant factor VIII has biologic activity comparable to that of plasma factor VIII and is safe and efficacious for the treatment of hemophilia A.

Adult↗
PubMed1990

Age and human immunodeficiency virus infection in persons with hemophilia in California.

Thirteen hemophilia centers provide comprehensive care to approximately 90 percent of persons with hemophilia in California. For 1987, these centers reported patient human immunodeficiency virus (HIV) antibody status, age group, level of clotting factor deficiency, and hemophilia type on 1,438 persons with hemophilia A and B; HIV serologic status was known for 860 persons (59.8 percent) of whom 537 (62.4 percent) were HIV-antibody-positive. The HIV positivity rate increased with age after taking into account hemophilia type, clotting factor level and treatment center type. The three-year cumulative incidence of reported AIDS (acquired immunodeficiency syndrome) cases based on the number of HIV positive patients, was 11.6 percent. The cumulative incidence rate was 14.6 percent (54 of 370) for those patients over 20 years of age and 4.8 percent (8 of 167) for those under 21 years of age. Although a comparable distribution of the date of diagnoses of AIDS was seen by age group, there appeared to be a bimodal distribution in the rate of AIDS among the age groups, with the 6-12-year-olds and the 21 and older age groups showing higher incidence rates.

Acquired Immunodeficiency Syndrome↗
PubMed1989

von Willebrand factor multimer analysis using a sensitive peroxidase staining method.

A peroxidase staining method for von Willebrand factor (vWF) multimer analysis was modified for comparison with an autoradiographic method. This method consists of SDS-agarose electrophoresis followed by blotting to a nitrocellulose membrane and a sensitive peroxidase staining method. The resolution of vWF multimers on the nitrocellulose membrane is comparable to that on the conventional autoradiography. Results can be obtained in 3 days. This nonradioisotopic method will be useful for the determination of the type of von Willebrand's disease in clinical laboratories.

Autoradiography↗
PubMed1989

Acquired von Willebrand's syndrome with lupus-like serology.

We describe a 12-year-old boy with acquired von Willebrand's syndrome, who also had various autoantibodies. He presented with recent hemorrhagic symptoms and a prolonged bleeding time. Hemostatic studies revealed severely reduced levels of factor VIII procoagulant activity (VIII:C), von Willebrand's factor (vWF) antigen (vWF:Ag), and ristocetin cofactor activity (RCoF). An inhibitor that could be detected in the patient's plasma moderately decreased the levels of vWF:Ag in normal plasma, but did not interfere with the measurement of VIII:C or RCoF. Following the infusion of cryoprecipitate, half-lives of VIII:C, vWF:Ag, and RCoF were markedly reduced. 1-Deamino-8-D-arginine vasopressin infusion induced normalization of the prolonged bleeding time and caused a marked increase in VIII:C, vWF:Ag, and RCoF. Prior to treatment, there was a uniform reduction of all the multimers of plasma vWF in sodium dodecyl sulfate agarose gel electrophoresis. Following prednisone therapy, clinical and hemostatic findings were improved, and the multimeric patterns of vWF were normalized. These findings suggest that the low levels of all three parameters of factor VIII and all the multimers of plasma vWF in the patient are caused by rapid elimination of factor VIII complex from the circulation.

Child↗
PubMed1989

Response to desmopressin in type IID von Willebrand's disease.

Dominant transmission of a variant of von Willebrand's disease (vWD) with aberrant polymerization of von Willebrand factor (vWF) has been identified in a Scottish family. Multimer analysis of plasma vWF from the propositus and her father revealed an identical pattern to that previously reported in families designated as type IID vWD. There is loss of the larger multimers and presence of an intermediate subsidiary band not seen in normal subjects or other vWD variants. Platelet/vWF interaction induced by ristocetin is not enhanced in these cases and the platelet vWF shows the same aberrant multimer pattern as plasma vWF. DDAVP infusion in two affected members of the Scottish family and in one of the index cases produced a rise in plasma vWF antigen and factor VIII. Higher molecular weight vWF multimers appeared transiently after infusion of desmopressin (1-deamino-8-D-arginine vasopressin, abbreviated DDAVP) coincident with shortening of the bleeding time. The platelet counts did not change after the DDAVP infusions. DDAVP should be considered for management of bleeding in this variant of von Willebrand's disease.

Adult↗
PubMed1987

Involvement of von Willebrand factor in thrombosis following asparaginase-prednisone-vincristine therapy for leukemia.

To determine if factor VIII-von Willebrand factor (vWF) complex is involved in the thrombosis associated with asparaginase-prednisone-vincristine induction therapy for acute lymphoblastic leukemia, plasma vWF was analyzed by sodium dodecyl sulfate-agarose gel electrophoresis and crossed immunoelectrophoresis. Five patients with cerebral thrombosis were studied; all had a decreased platelet count following the complication. Sequential studies of three patients disclosed changes in plasma vWF multimer pattern. One patient who was studied serially from 2 days before to 1 day after the event, had an increase in unusually large plasma vWF multimers that disappeared after the complication. The other two patients who were studied at presentation subsequently showed a decrease in plasma large vWF multimers, especially remarkable in the patient having the sharpest decrease in platelet count. No appreciable difference in vWF multimer pattern, when compared to normal pooled plasma, was found in the remaining two patients who were only studied at presentation, or in the seven controls who received the same treatment but did not develop thrombosis. Crossed immunoelectrophoretic analyses of two patients tested disclosed a right shift of immunoprecipitin line in one and a left shift in the other. Our findings suggest that the thrombotic complications resulted from platelet agglutination by plasma vWF.

Acute Disease↗
PubMed1985

Multicenter comparison of von Willebrand factor multimer sizing techniques. Report of the Factor VIII and von Willebrand Factor Subcommittee.

A multicenter study of various types of von Willebrand's disease (vWD) was conducted in order to compare the different electrophoretic techniques used to evaluate von Willebrand factor multimers in plasma. Seven laboratories participated in the blind study of eight plasma samples from two healthy subjects and six vWD types and subtypes (Ia, Ib, IIA, IIB, IIC and IID). From the results of the multimeric analysis of these samples, it appears that the differential diagnosis of vWD types and subtypes should be first approached by using a low-resolution electrophoretic technique, where each vWF multimer appears as a single band. Low-resolution techniques differentiate type I from type II, subtype Ia from Ib and also subtype IIA from other type II subtypes. When type II subtypes other than IIA are identified with these techniques, samples should be rerun using high resolution techniques that resolve each of the fastest migrating multimers in at least three subbands, and permit the differentiation of subtypes IIB, IIC and IID.

Electrophoresis, Agar Gel↗
PubMed1979

The factor VIII abnormality in severe von Willebrand's disease.

We attempted to characterize the small amounts of factor VIII-related antigen detectable in the severe recessive form of von Willebrand's disease with newly developed radioimmunoprecipitin techniques and radiocrossed immunoelectrophoresis. Previous studies have failed to demonstrate factor VIII-related antigen in most patients tested even with the highly sensitive immunoradiometric assays. Using the newer techniques, we found antigen in the plasma of six of eight patients with severe von Willebrand's disease from different kindreds. Qualitative abnormalities of the trace quantities of factor VIII-related antigen were demonstrated in five of the patients, with absence or relative decrease of the larger, less anodal forms. In addition, five distinct patterns were observed, each suggesting a different molecular abnormality. Heterozygous parents had normal to moderately decreased factor VIII-related antigen, with normal crossed immunoelectrophoretic patterns. This study suggests that severe von Willebrand's disease is a heterogeneous syndrome with various underlying molecular defects.

Antigens↗
PubMed1979

Ontogeny of bovine hemostasis.

Ontogeny of selected hemostatic system components was studied in 120 bovine fetuses which had been divided into eight monthly gestational age groups. Fetal blood was subjected to the following tests: platelet count, partial thromboplastin time, prothrombin time, thrombin time, fibrinogen quantitation, and assays for prothrombin and factors V and VIII. Platelet numbers corresponding to adult numbers were in fetal blood at least as early as gestation day 60, and their numbers varied only slightly thereafter. Bovine blood was incapable of in vitro coagulation at gestation day 90, with all samples coagulating by gestation day 150. Fetal coagulation screening test times (partial thromboplastin time, prothrombin time, and thrombin time) shortened during gestation and were near times of adults at birth. Of the four individual coagulation factors tested, only factor VIII reached adult values in the fetus in utero. Amounts of fibrinogen, prothrombin, and factors V and VIII in the neonate exceeded that of normal adult cattle.

Animals↗
PubMed1977

Multiple hepatic tumors and peliosis hepatis in Fanconi's anemia treated with androgens.

We report the case of a 13-year-old boy who was known to have Fanconi's anemia for five years. For treatment of this condition he was given androgens and corticosteroids. Two months before his death, severe varicella developed complicated by pneumonia, jaundice, and prolonged fever; all of which resolved during a five-week hospitalization. Three weeks later he died of Clostridium septicum sepsis caused by necrotizing enterocolitis. At autopsy he was found to have multiple hepatocellular neoplasms. A striking feature of the neoplasms was cholestasis. The liver also showed peliosis hepatis. The association of the use of certain androgenic steroids with hepatic neoplasms histologically resembling hepatocarcinomas, but characterized by lack of metastases and apparent reversibility, suggests the desirability of a new nomenclature for these hepatocellular lesions.

Adolescent↗
PubMed1976

Prothrombin complex concentrate (Konyne) in the treatment of hemophilic patients with factor VIII inhibitors.

Two prothrombin complex concentrates, Auto-Factor IX and Proplex, have been reported to be effective in controlling bleeding in hemophilic patients with factor VIII inhibitors. A third PCC, Konyne, was used to treat 64 bleeding episodes (130 infusions) in five hemophilic patients with factor VIII inhibitors. Prompt control of bleeding was observed in each instance with doses of 15 to 100 units of factor IX/kg; no complications were encountered. Konyne resulted in in vivo and in vitro shortening of the partial thromboplastin time of patients with factor VIII inhibitors, but the mechanism of action is unknown. If further studies confirm the efficacy and safety of PCC in the treatment of such patients, its use for this purpose could lead to significant saving of factor VIII concentrates.

Adolescent↗
PubMed1976

Treatment of idiopathic autoimmune hemolytic anemia in children. Review and report of two fatal cases in infancy.

Report of two cases of severe idiopathic autoimmune hemolytic anemia (AIHA) in infants who underwent splenectomy and received corticosteroids and cyclophosphamide without benefit. One infant, additionally, was treated with thymectomy and azathioprine without influencing his disease. Experience of therapy for childhood AIHA is reviewed. Four children with AIHA have been thymectomized. Two of these failed to benefit from surgery. There have been fifteen previous trials with immunosuppressive agents in childhood AIHA. About 60% of the children so treated (9 of 15) have shown improvement. Additional clinical trials with this agent are warranted.

Adrenal Cortex Hormones↗