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Several studies have shown a relation between hyperhomocysteinaemia and arterial vascular disease. We looked at the association between hyperhomocysteinaemia and venous thrombosis which could be clinically important as hyperhomocysteinaemia is easily corrected by vitamin supplementation. We studied 185 patients with a history of recurrent venous thrombosis and 220 controls from the general population. Homocysteine concentrations were measured before and 6 h after oral methionine loading. We defined hyperhomocysteinaemia as the homocysteine concentration above the fasting or the postmethionine value found for the 90th percentile of the controls. Of the 185 patients with recurrent thrombosis, 46 (25%) had fasting homocysteine concentrations above the 90th percentile or the controls (odds ratio is 3·1 [1·8-5·5]). After adjustment for age, sex, and menopausal status the odds ratio was 2·0 (1·5-2·7). Similar results were found for the post-methionine value (unadjusted odds ratio 3·1 [1·7-5·5], adjusted 2·6 [1·9-3·5]). Hyperhomocysteinaemia is a common risk factor for recurrent venous thrombosis and can lead to a two-fold or three-fold increase in risk.

Abstract —Hyperhomocysteinemia is a risk factor for atherosclerosis and thrombosis and is inversely related to plasma folate and vitamin B12 levels. We assessed the effects of vitamin supplementation on plasma homocysteine levels in 89 patients with a history of recurrent venous thrombosis and 227 healthy volunteers. Patients and hyperhomocysteinemic (homocysteine level >16 μmol/L) volunteers were randomized to placebo or high-dose multivitamin supplements containing 5 mg folic acid, 0.4 mg hydroxycobalamin, and 50 mg pyridoxine. A subgroup of volunteers without hyperhomocysteinemia was also randomized into three additional regimens of 5 mg folic acid, 0.5 mg folic acid, or 0.4 mg hydroxycobalamin. Before and after the intervention period, blood samples were taken for measurements of homocysteine, folate, cobalamin, and pyridoxal-5′-phosphate levels. Supplementation with high-dose multivitamin preparations normalized plasma homocysteine levels (≤16 μmol/L) in 26 of 30 individuals compared with 7 of 30 in the placebo group. Also in normohomocysteinemic subjects, multivitamin supplementation strongly reduced homocysteine levels (median reduction, 30%; range, −22% to 55%). In this subgroup the effect of folic acid alone was similar to that of multivitamin: median reduction, 26%; range, −2% to 52% for 5 mg folic acid and 25%; range, −54% to 40% for 0.5 mg folic acid. Cobalamin supplementation had only a slight effect on homocysteine lowering (median reduction, 10%; range, −21% to 41%). Our study shows that combined vitamin supplementation reduces homocysteine levels effectively in patients with venous thrombosis and in healthy volunteers, either with or without hyperhomocysteinemia. Even supplementation with 0.5 mg of folic acid led to a substantial reduction of blood homocysteine levels.

This case report describes a patient with localized hyaline-vascular (H-V) type Castleman's disease with concomitant malignant B-cell lymphoma. Malignant lymphoma has been described in association with multicentric type Castleman's disease, but not in association with the localized H-V type. Evidence for a relation between the two lesions in this patient by means of histologic, flow-cytometric, cytogenetic and gene rearrangement studies was not found.

The effect of conservative treatment of aplastic anaemia was evaluated retrospectively in 40 patients. No significant beneficial effect was provided by long-term high-dose oxymethalone in 20 patients or by metenolone, adrenstonolone, or testosterone in 14 patients. Splenectomy gave no improvement in the majority of cases, although in some it decreased the transfusion requirement. Immunosuppressive treatment was successful in 1 patient with a positive LE phenomenon. Until a specific treatment becomes available, the possibility offered by alternative treatment, e.g. bone marrow transplantation, in cases with poor prognostic parameters should be considered.

A case report is presented of a 39-year-old woman suffering from a myelodysplastic syndrome, who developed a moderately severe stable diffuse intravascular coagulation (DIC) during an uneventful pregnancy. Intravenous administration of antithrombin III concentrate was attempted to combat the DIC. Improved survival of platelet transfusions, facilitating supportive care, suggested some therapeutic benefit. In contrast, only minimal effects on the results of the coagulation tests were observed.

The effect of conservative treatment of aplastic anaemia was evaluated retrospectively in 40 patients. No significant beneficial effect was provided by long-term high-dose oxymethalone in 20 patients

Together with Dr. E. Gluckman (Hopital St. Louis, Paris) and Dr. B. Speck (Kanton Hospital, Basel) we have recently published a study, in which the effect of ATG on the clinical course of severe aplastic anemia was assessed [13]. Our conclusions were that: a) about half of the patients suffering from severe aplastic anemia improved significantly after 4 daily doses of ATG; b) it was unlikely that this apparent beneficial effect of ATG was due to patient selection in the sense that we had selected patients which without ATG treatment would have survived anyhow; c) it was possible that the ATG removed from the bone marrow T cells which interfered with the differentiation of the stem cells. A possibility which is strongly supported by in vitro studies by one of us [8] and others [1].

The factor VIII ratio was measured in 102 pregnant women (43 uncomplicated pregnancies, 19 with pre-eclampsia without fetal growth retardation, 8 pre-eclampsia complicated by fetal growth retardation, 12 with only fetal growth retardation and 20 with gestational diabetes). The pathological pregnancies showed a statistically significant elevation of the factor VIII ratio compared to the normal pregnancies. The group of pre-eclampsia complicated by fetal growth retardation showed the most marked increase of the factor VIII ratio. The results are discussed in relation to the hypothesis that the elevated factor VIII ratio is mainly due to the release of factor VIII antigen by various forms of vascular stress.