Campbell W. McMillan

Use of Recombinant Antihemophilic Factor in the Treatment of Two Patients with Classic Hemophilia

COMMERCIAL concentrates of human antihemophilic factor (factor VIII) have been available for nearly 20 years and have resulted in dramatic changes in the treatment of classic hemophilia. Home thera...

Inheritance Pattern and Clinical Response to Splenectomy as a Reflection of Erythrocyte Spectrin Deficiency in Hereditary Spherocytosis

To determine how various inheritance patterns and responses to splenectomy relate to erythrocyte spectrin deficiencies in hereditary spherocytosis, we measured the spectrin content of erythrocytes by radioimmunoassay in 33 patients with this disease. Patients with the dominant form of hereditary spherocytosis generally had mild anemia, with spectrin at 63 to 81 percent of normal levels. Patients with the nondominant form of the disease had anemia ranging from severe to mild, with corresponding spectrin levels of 30 to 74 percent; their siblings were affected similarly. Distantly related homozygotes had different clinical severities with correspondingly different spectrin levels. The parents and offspring of patients with the nondominant form were clinically normal but consistently had subtle erythrocyte abnormalities. Spectrin levels in all patients were inversely related to osmotic fragility (P less than 0.0001), and they were also correlated with the clinical response to splenectomy: patients with spectrin levels above 70 percent achieved normal blood counts, those with levels of 40 to 70 percent had compensated hemolysis, and those with levels below 40 percent improved but remained anemic (P less than 0.0001). We conclude that the inheritance pattern and response to splenectomy in hereditary spherocytosis reflect erythrocyte spectrin deficiencies as determined by radioimmunoassay.

Neuropsychologic and academic functioning of children with sickle cell anemia

This study compared neuropsychologic test results and academic functioning among 28 school-age children with sickle cell anemia (SCA), and 28 healthy, age-, sex-, and socioeconomically matched black peers followed at a tertiary care center. Children with SCA scored significantly lower on reading and spelling achievement scores than healthy matched peers. Also, older children with SCA performed significantly less well on tests of visual-motor and attention skills than younger children with SCA. These results were unrelated to most measures of physical illness severity. The data suggest that sickle cell anemia may be associated with subtle neuropsychological and learning deficits that can contribute to decreased school performance. J Dev Behav Pediatr 9:213–220, 1988. Index terms: neuropsychologic, academic function, sickle cell anemia.

Continuous Intravenous Infusion of Factor VIII in Classic Haemophilia

The effects of continous intravenous infusion of factor VIII were studied under varied conditions in five children with classic haemophilia. Factor‐VIII activity was stable at room temperature (73–76°F) up to 12 hr in cryoprecipitates from fresh plasma and up to 27 hr in glycine‐precipitated fractions (Fraction AA and Method 4, Hyland). Constant infusion (17 ml/hr) of different concentrations of these fractions produced levels of plasma factor‐VIII activity which were proportional to the dose‐rate and became relatively steady after 12‐18 hr. In separate studies of two of the subjects, dental extraction and laminectomies were uneventfully supported by an initial dose of factor VIII followed by continuous infusions. It is suggested that continuous intravenous infusion of factor VIII is useful for studying the regulation of factor‐VIII levels in plasma and for maintaining steady plasma factor‐VIII activity during replacement therapy.

Congenital Combined Deficiency of Coagulation Factors II, VII, IX and X: Report of a Case

PLASMA activities of coagulation factors II (prothrombin), VII (proconvertin), IX (Christmas factor) and X (Stuart factor) have in common 3 generally recognized characteristics: these activities ar...

Adult Wilms Tumor: Effect of Combined Therapy on Survival

Thirty-one adults with Wilms tumor were reported to the National Wilms Tumor Study from 1968 to 1979. Treatment and survival data for these patients were analyzed and compared to similar information derived from children enrolled in the first National Wilms Tumor Study. The ages of the 31 adults ranged from 17 to 63 years (mean 29 years). All but 3 patients had surgical resection or excision of tumor, 7 did not receive postoperative irradiation and all but 1 had chemotherapy. Actinomycin D and vincristine were the drugs used most commonly, 26 of the 31 patients receiving both agents. Advanced disease at diagnosis (6 stage III and 9 stage IV versus 9 stage I and 5 stage II--in 2 cases stage was not known) was found more often than in children in whom stages III and IV disease made up 27 per cent of the first National Wilms Tumor Study population. The 3-year actuarial survival rate for the 31 adults was 24 per cent: 48 per cent for stages I and II disease and 11 per cent for Stage IV disease. Comparable data for children in the first National Wilms Tumor Study, adjusted for stage, were 74, 87 and 53 per cent, respectively. It is concluded that adults with Wilms tumor treated as were these have a worse prognosis than children managed according to the first National Wilms Tumor Study regimen. However, those adults in this series who were treated aggressively, that is surgical excision, postoperative irradiation and multi-agent chemotherapy, appeared to have fared better than adults treated in the pre-chemotherapy era. It is concluded that aggressive therapy should be given to all adults with Wilms tumor irrespective of stage.

Severe factor VIII and factor IX deficiency in females

Abstract A survey of 11 hemophilia centers produced data concerning 28 females with extremely low levels of factor VIII or IX coagulant activity. Ten of the 28 have hemophilia A, six have hemophilia B, and 12 have severe von Willebrands disease. The 16 females who have severe factor VIII or factor IX deficiency as an isolated defect exemplify several of the possible genetic explanations for the occurrence of hemophilia in females. All 16 bruise excessively, and several have had recurrent hemarthroses. Three of these girls, ages five, 10 and 23 years, have evidence of chronic hemophilic arthropathy. The 12 females with severe von Willebrands disease are either homozygous for von Willebrands disease or severely affected heterozygotes. All 12 have mucous membrane bleeding. In addition, five of the 12 have recurrent hemarthroses and three have evidence of chronic joint disease. However, the major problem in the adult females with von Willebrands disease has been extreme menorrhagia. One of the seven adults underwent irradiation sterilization and another had a hysterectomy because of menorrhagia. The others have been managed with anovulatory drugs or plasma infusions and EACA. Despite menorrhagia, five pregnancies and deliveries have been uneventful in three of these women.

Treatment of Classic Hemophilia: The Use of Fibrinogen Rich in Factor VIII for Hemorrhage and for Surgery

CLASSIC hemophilia, comprising about 80 per cent of the heritable coagulation disorders, is characterized by a hemostatic defect largely attributed to deficiency of a clot-promoting principle in th...

Low risk of viral infection after administration of vapor-heated factor VIII concentrate

A multicenter prospective study was carried out to evaluate whether a vapor‐heated factor VIII concentrate transmitted blood‐borne viral infections over a surveillance period of 15 months. Thirty‐five patients with hemophilia and von Willebrand disease who had never received any blood components were treated. Twenty‐eight were analyzed and found not to have non‐A,non‐B hepatitis. Sera from 20 of these 28 patients were also tested for the antibody to the hepatitis C virus. None had sero‐converted during the follow‐up period. None of the patients analyzed developed markers of the hepatitis B virus (n = 17) or the human immunodeficiency virus (n = 31). This vapor‐heated factor VIII concentrate carries a low risk of transmitting hepatitis and human immunodeficiency virus infection.

Neuropsychologic functioning of human immunodeficiency virus-infected children with hemophilia.

Efforts to detect subtle but objective neuropsychologic deficits could clarify the early involvement of the central nervous system and the progression of human immunodeficiency virus (HIV) infection in older children and young adolescents. Baseline examinations of 63 children and adolescents with hemophilia were conducted by examiners unaware of HIV status or staging or of our studys major hypotheses. They measured six domains of neuropsychologic functioning (motor, language, memory, attention, visual processing, and problem solving), and no differences between groups of similar age, race, and socioeconomic status defined by HIV seropositivity (n = 25) and HIV seronegativity (n = 38) were revealed. A high incidence of subtle neuropsychologic deficits relative to (1) age norms and (2) individual cognitive potential was found on measures of motor performance, attention, and speeded visual processing within both infected and uninfected groups. On the basis of these baseline data, it seems premature to attribute early, subtle neuropsychologic deficits in seropositive children with hemophilia to the central nervous system effects of HIV infection.