Histamine H2-receptor antagonists are widely used in the treatment of gastrointestinal diseases related to gastric acid hypersecretion. Cimetidine was introduced into medical practice in 1976 and ranitidine, famotidine and nizatidine in 1981, 1985 and 1987, respectively. Haematological adverse effects are relatively uncommon and most have been reported in cases of cimetidine administration. These adverse effects are reviewed under 4 main headings: (a) blood cytopenias and leucocytosis; (b) coagulation disorders related to drug interactions with oral anticoagulants; (c) reduction of dietary iron absorption; and (d) reduction of dietary cobalamin absorption. 85 reported cases of blood cytopenias attributed to these drugs are reviewed, of which 75 (88%) were associated with cimetidine therapy. In postmarketing surveillance studies, the incidence of cimetidine-associated blood cytopenia has been evaluated at about 2.3 per 100,000 patients. Neutropenia and agranulocytosis are by far the most frequently encountered. Whatever the drug or the type of cytopenia, this adverse effect is almost always rapidly reversible when treatment is stopped. Moreover, in several cases other factors such as underlying diseases or additional drugs could have been responsible, at least partly, for the cytopenia. The pathophysiological basis of these adverse effects remains poorly explained. Various mechanisms have been proposed, which in some cases are probably associated: (a) direct toxicity for haemopoietic stem cells; (b) drug-induced immune reactions leading to blood or bone marrow cell damage, and (c) drug interactions, with increased and prolonged action of potentially haematotoxic drugs. Mechanisms (a) and (c) appear to be of particular clinical importance in cases of impaired renal elimination of H2-receptor antagonists. Cimetidine and probably to a lesser extent ranitidine potentiate the action of oral anticoagulants of both coumarin and indanedione structure. This may result in haemorrhagic complications. Such action is a consequence of the reduced hepatic metabolism of oral anticoagulants through a dose-dependent, reversible inhibition of cytochrome P450. Malabsorption of dietary iron and cobalamin appears to result from inhibition of gastric secretion by the H2-receptor antagonists. This is of no clinical importance in short term treatment, but long term use of H2-receptor antagonists may theoretically contribute to the occurrence of iron or cobalamin deficiency anaemia.

Thirty-nine members of one family, covering three generations, were HLA-typed. Twenty-five suffered from primary diffuse articular chondrocalcinosis, and all had the same dominantly transmitted autosomally controlled disease. This was characterized by acute articular attacks, which always started before the age of 35, and radiologically by typical cartilaginous and fibrocartilaginous deposits associated with para-articular calcifications. The lesions were both peripherally and axially generalized. None of the 28 HLA antigens tested seemed related to the disease, nor did the disease segregate with an HLA haplotype.

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SummaryA new family with congenital dysfibrinogenemia without bleeding tendency has been discovered in Nancy. Identical laboratory abnormalities were found in the mother and son plasma: prolongation of thrombin and reptilase clotting time.The abnormal fibrinogen affects, only a little, the normal plasma fibrinoformation.The functional characterization of the defect is localized in fibrin monomer aggregation. The release of fibrinopeptides is normal.The abnormal fibrinogen showsa) an alteration in glucidic moiety of the molecule with a high level of sialic acid,b) an disturbance of chromatography on D. E. A. E. cellulose andc) of the electrophoretic mobility.

We prospectively studied the incidence of post-transfusion non-A, non-B hepatitis in 64 cardiac surgery patients: 4 (6.25%) developed non-A, non-B hepatitis after an incubation period of 4-10 weeks. Units of blood products from donors seropositive for antibody to hepatitis B core antigen (anti-HBc) were not associated with a greater risk of non-A, non-B hepatitis in recipients than units from seronegative donors. Our data indicate that donor blood anti-HBc testing is of no value as a screening method to reduce the incidence of post-transfusion non-A, non-B hepatitis.

In a nonrelated white family, the Fletcher factor level in the father was 0.41 U/ml and in the mother, 0.30 U/ml (controls, 0.75-1.25 U/ml). One sibling with recurrent epistaxis had a level of 0.012 U/ml, whereas the other without tendency to spontaneous bleeding had levels between 0.75 and 0.32 U/ml. This suggests autosomal recessive transmission with clinical symptoms when the defect is homozygous. HLA antigens were studied to determine whether characters of the histocompatibility system and this defect are linked: we determined that the gene(s) of the disease is (are) not shared on the HLA complex.

SUMMARY One hundred and forty-one patients with rheumatoid arthritis treated with aurothiopropanol sulphonate or D-penicillamine, or both were examined for HLA antigens to investigate the genetic influence on the occurrence of different adverse reactions during therapy. All 13 patients possessing HLA-DR3 had toxic reactions. The relative risk for DR3 positives of developing skin eruptions or proteinuria was calculated to be 10*5 times and seven times respectively that of DR3 negatives. The incidence of DR7 antigen in 94 patients with toxic reactions was significantly decreased (11% compared with 28% in controls) suggesting a protective role for this antigen.

We report a case of amodiaquine-induced agranulocytosis in a 60-year-old woman. Four months after the agranulocytosis episode we investigated the effect of the drug using in vitro agar culture techniques. Amodiaquine at increasing concentrations (0.005, 0.05 and 0.5 μg/ml) displayed an inhibitory effect, probably dose-dependent, on the growth of the patient’s bone marrow GM-CFU colonies in the absence of autologous serum. In contrast, no effect was found on the colony and cluster growth of bone marrow samples from 13 healthy controls. Though it has been shown in several cases that amodiaquine-induced agranulocytosis occurs via immune-mediated mechanisms, our data are in support of a direct toxic effect of the drug on abnormally sensitive myeloid progenitor cells.