Prevalence of human parvovirus B19 and TT virus in a group of young haemophiliacs in South Africa.

A well recognized hazard of transfusion with blood or blood products is the acquisition of a viral infection. Parvovirus B19 and transfusion transmitted virus (TTV) are two of several non-enveloped viruses that may on rare occasions be present in coagulation factor concentrates. The prevalence of these viruses in the South African Haemophilia population has not previously been studied. Thirty-nine Haemophiliac children were investigated for evidence of parvovirus and TTV infection. 26 boys with Haemophilia A had been treated with cryoprecipitate or intermediate purity factor VIII, and 13 boys with Haemophilia B had received prothrombin complex concentrates. All the plasma products were prepared from South African donors and were virally inactivated by heat or solvent/detergent since 1992. A control group of 32 children who had not been transfused were also studied. IgG antibodies to B19 were present in 29 of the 39 patients (74%), 18/26 (69%) with Haemophilia A and 12 of the 13 (85%) with Haemophilia B. None of the patients was IgM antibody positive but two children were PCR positive for B19 DNA. Of the control children, 47% had IgG antibodies to B19, but none were IgM antibody or B19 DNA positive. TTV viral DNA was found in 10.2% of patients and in 9% of the control group. The results indicate that our locally produced plasma products are not a significant source of TTV transmitted infection but may contribute to infection by B19 parvovirus.

Von Willebrand's disease in the Western Cape.

OBJECTIVE: To establish the prevalence of the various subtypes of Von Willebrand's disease (VWD) among patients with bleeding disorders in the Western Cape and to review appropriate treatment strategies. DESIGN: A systematic clinical and laboratory study. SETTING: Haemophilia clinics at two tertiary referral hospitals (Groote Schuur Hospital and Red Cross War Memorial Children's Hospital) in the Western Cape. PATIENTS: Twenty-two patients (14 females, 8 males; ages 3 - 55 years) were studied. Those studied were selected for reasons of convenience, as they were compliant and regular attenders at the clinics. MAIN OUTCOME MEASURES: History of a bleeding tendency; bleeding time measurements; factor VIII assays, von Willebrand factor (VWF) antigen assays; ristocetin co-factor assays and VWF multimer analysis. RESULTS: Fourteen patients had typical type I VWD; 2 had type II and 5 had type III variants, and there was 1 unclassifiable variant. Analysis of local factor VIII concentrates showed the presence of high-molecular-weight VWF multimers. CONCLUSION: The results are similar to patterns reported elsewhere in the world. Locally produced factor VIII concentrates, unlike a number of commercially produced concentrates, contain sufficient multimers for use as appropriate replacement therapy.

Chemotherapy and combined modality advances in children.

The sustained improvements in pediatric cancer therapy are partially due to the large randomized and nonrandomized studies being conducted by multidisciplinary cooperative groups. Theoretic concepts of chemotherapy are better knowledge of the pharmacokinetics, pharmacodynamics, and drug resistance of current and new drugs are enabling a more rational approach to multiagent therapy. Biologic modifiers are adding to our current multimodal therapeutic approach.

Epidemiology of acute leukaemia in the Cape Province of South Africa.

Of 535 consecutive cases of acute leukaemia diagnosed in the Cape Province between 1978 and 1985, demographic data are incomplete in 75 black patients and they have had to be excluded from the spatial analysis. Of the remaining 460 cases, 223 (48.5%) occurred in white patients and 237 (51.5%) in those of mixed ancestry, classified as coloureds according to the Population Registration Act No. 30 of 1950. The average incidence was 2.12, 1.37 and 0.58/100,000 for whites, coloureds and blacks respectively. There was no temporal trend in the incidence of acute leukaemia between the three race groups. The median age for whites was 30 years and for the coloureds was 15 years, which is comparable to the 16 years for the black patients. The two-peak age distribution for leukaemia was seen in the white group, but was absent in the other two groups. This is accounted for by a different distribution in non-lymphoblastic as opposed to lymphoblastic subtypes. Furthermore, there was a disproportionately high frequency of acute progranulocytic leukaemia in the black patients, whereas the white and coloured groups were similar. There was a single, clearly defined macro-scale cluster restricted to white patients in Statistical Region 17 (SR-17). This exploratory study provides the first epidemiologic data for acute leukaemia in the Cape Province. It needs to be extended in order to verify these observations under more controlled circumstances and to seek evidence for some environmental factors that may account for the geographical cluster.

Fine-needle cytology of solid tumors: method, diagnostic accuracy, and role in management.

Fine-needle cytology was obtained from 14 solid tumors in 12 children. Both aspiration and nonaspiration techniques were used and several staining methods were applied. May Grünwald Giemsa and Papanicolaou stains were preferred. The nonaspiration method yielded a superior quality cytology smear with less blood contamination. There were no complications recorded. Confirmation of the diagnosis with cytology allowed for planned management with preoperative cytotoxic chemotherapy and/or radiotherapy in 10 children, immediate surgery in one, and radiotherapy to a vertebral recurrence in one. Fine-needle cytology is considered a useful technique in the management of a selected group of children with solid tumors.

Presentation and outcome of 25 cases of Fanconi's anemia.

Twenty-five children with Fanconi's anemia (FA) who attended the Paediatric Haematology Clinic of Red Cross Children's Hospital over the past 20 years were retrospectively reviewed. There was a female predominance with 17 girls and 8 boys in the group. The clinical features and laboratory data are enumerated. An unusually high prevalence of gastrointestinal anomalies (20%) was found. Seventeen children received an adequate trial of androgen therapy and in 12 the initial hemoglobin concentration increased by more than 2 g/dl or return to normal. Most patients subsequently required intermittent courses of androgens but three were able to stop treatment and maintain a normal hemoglobin concentration for from 3.5 to 20 years. Ten patients remain alive, of whom five had less severe hematological problems and did not require any treatment. The mean period of follow-up of the survivors is 8.7 years. Thirteen patients have died, with a mean time of 5.5 years from diagnosis to death. Of the deaths, two were due to malignant disease and one resulted from cerebral hemorrhage. The other 10 children died of confirmed or suspected infections. Treatment options of FA are discussed.

Transient dyserythropoiesis occurring during the involutionary phase of stage IV-S neuroblastoma.

An acutely ill 6-month-old female infant presented with massive hepatomegaly, accompanied by severe anemia with peripheral normoblastemia and thrombocytopenia. Bone marrow examination revealed erythroid hyperplasia with gross erythroid dysplasia, reduced granulocytic precursors, and virtually absent megakaryocytes. The bone marrow also contained completely necrotic cells occurring in clumps as well as singly. The appearances suggested bone marrow involvement by neuroblastoma. Accordingly, combination chemotherapy was instituted and laparotomy was performed as soon as her clinical condition had improved. Left adrenalectomy was carried out, because a small adrenal nodule of ganglioneuroma was present. Liver biopsy showed expansion of portal tracts by loose fibrous connective tissue containing hemosiderin deposits and some degenerate cellular debris, consistent with areas of involuted metastatic neuroblastoma. Complete recovery followed, and subsequent bone marrow examination was entirely normal. It is thought that the dyserythropoiesis probably resulted from the release of toxic metabolites from regressing neuroblastoma.

Reduction of neonatal blood eliminates the error induced by oxygen saturation in the spectrophotometric measurement of carboxyhaemoglobin.

Blood carboxyhaemoglobin (COHb) is a sensitive index of haemolysis and has been used in assessing the cause of different types of neonatal jaundice. Although the introduction of automated spectrophotometry provides rapid and accurate measurement in adult blood, in neonates oxygenated foetal haemoglobin (HbF) is thought to interfere with COHb measurement. In an attempt to eliminate this problem, the haemoglobin in neonatal blood was reduced with sodium dithionite. Cord blood from 50 infants was measured before and after reduction using an IL-282 co-oximeter; COHb levels fell after reduction. A significant positive correlation was found between apparent COHb% and oxygenation of cord blood. In contrast, no significant correlation was found between these parameters in adult blood where COHb values remained the same or rose slightly after reduction. In 20 healthy non-icteric neonates the mean reduced blood COHb value was not significantly different from the mean COHb value of 23 healthy non-smoking adults. We suggest that COHb in neonatal blood can be simply and accurately measured by the IL-282 co-oximeter provided that the blood is fully reduced.

Haemoglobin Köln in Cape Town. A case report.

A 7-year-old patient presented with an acute haemolytic episode. Investigation showed the presence of an unstable haemoglobin (Hb), identified as Hb Köln. No other members of the family were affected. This disorder has occasionally been seen as a spontaneous mutation. This is the first report of Hb Köln in a South African family, although other unstable Hb variants have been described.

The relationship between prognosis and scintigraphic evidence of bone metastases in neuroblastoma.

The clinical records, scintigrams, radiographic skeletal surveys, and bone marrow aspiration and trephine results of 30 children with neuroblastoma were reviewed to determine the relationship between the result of the scintigram and the clinical outcome of the patient. The nine patients with normal radiographic skeletal surveys and no evidence of bone metastases on scintigraphy are alive and well having been off treatment for between 14 and 83 months. Eleven of the 13 children who had bone metastases on scintigraphy and radiography have died, as have seven of the eight patients who had positive scintigrams and normal radiographs. Scintigraphic evidence of bone metastases is associated with a very poor prognosis irrespective of the results of other investigations.

Immunological studies in haemophilic children.

A majority of haemophiliacs who have received large-pool plasma products within the past 5 years have been exposed to the putative agent of the acquired immunodeficiency syndrome (AIDS)--HIV. It is not known what the risk of infection is among patients in South Africa. A study was made of 39 children with congenital coagulation disorders attending the Red Cross War Memorial Children's Hospital Haemophilia Clinic. All but 3 had been treated exclusively with small-pool lyophilised cryoprecipitate or a factor IX concentrate prepared by local blood transfusion services. Three patients had also received imported non-heat-treated commercial products FEIBA (Immuno), Autoplex, Proplex (Hyland) or Factorate (Armour). Absolute lymphocyte counts were normal in all patients but the OKT4/OKT8 ratio was reduced below 1.0 in 9 children including 2 of the 3 who had received commercial plasma concentrates. A high titre of HIV antibody was present in 2 of the 38 patients tested. Both of these children had received imported plasma concentrates and 1 shows some features of the AIDS-related complex. These results suggest that haemophiliacs who receive non-heat-treated commercial concentrates may be at greater risk of HIV infection than patients treated with locally produced plasma products.

Inherited haemoglobin variants in a South African population.

We present the findings of a survey to determine the prevalence of inherited haemoglobin disorders in the Coloured (mixed ethnic origin) population of South Africa. A variety of haemoglobins was found. Of the structural variants, Hb E and Hb S were the most common, the former probably originating from South-East Asia and the latter from East Africa and possibly Madagascar. The alpha+ (-alpha) thalassaemia haplotype is particularly common with an observed frequency of 0.023. Beta thalassaemia was rather less common, while hereditary persistence of fetal haemoglobin was found for the first time in this population group, occurring in two subjects.

Acute promyelocytic leukemia. A childhood cluster.

Nine children with acute promyelocytic leukemia (APL) are presented. This series of children represents 7% of all acute leukemias and 21% of acute myelogenous leukemias seen during the same period at the Red Cross War Memorial Children's Hospital. These figures are much higher than the incidence quoted in other series of childhood leukemia. In addition, most of those children came from a confined geographic area. Two of the patients were younger than 2 years of age. The youngest patient with APL previously reported in the literature was 24 months.

Fanconi's anemia. A family study with 20-year follow-up including associated breast pathology.

A brother and sister with Fanconi's anemia, having typical skeletal deformity and characteristic chromosomal breaks in their lymphocytes and who followed the typical clinical course, with progressive bone marrow insufficiency beginning late in the first decade, are described. The natural history of the disease before chemotherapy was available is contrasted with the response to intermittent courses of anabolic steroids during a continuous 20-year follow-up. The female patient developed a carcinoma of the breast at the age of 26, from which she died 5 years later. This neoplasm may reflect increased susceptibility of cells with proven chromosomal abnormality to the influence of carcinogens. Her brother required repeated surgery for painful, but benign, breast masses. The explanation for the latter lesion is unknown but may be related to endocrine disturbances occurring in patients with Fanconi's anemia.