Cutaneous necrosis of the breast: a complication of oral anticoagulant treatment

Cutaneous necrosis of the breast is a rare complication of oral antivitamin K drugs. It occurs shortly after instituting therapy with well-limited, irreversible skin necrosis developing rapidly. The scar is superficial and only involves the subcutaneous tissue; early and extensive surgery does not therefore seem to be justified. Normal scarring is the eventual spontaneous outcome but this is always a long process. Several arguments are advanced in favour of a toxic effect of the drug itself on the vascular walls of the vessels in the dermis.     

Omeprazole produces parietal cell hypertrophy and hyperplasia in humans

While there is evidence that omeprazole may induce changes in parietal cells, the effect of acid suppression on parietal cells in humans is poorly documented. This study was undertaken to evaluate the effects of omeprazole in human parietal cells over time. The light microscopic morphology of parietal cells in gastric biopsies from 17 patients on omeprazole were compared with those from 13 patients on ranitidine and 20 patients on no acid-lowering medication. Light microscopic and ultrastructural morphology of parietal cells was also evaluated in an additional 14 patients before and after omeprazole administration. Objective measurements of parietal cell height, mass and number were analyzed using analyses of variance. Electron microscopy was used to evaluate parietal cell enlargement. Twenty-five of 31 biopsies from patients on omeprazole, 1 of 13 from patients on ranitidine, and 0 of 20 from patients on neither drug showed parietal cell enlargement. Parietal cell height, mass, and number were increased in omeprazole-treated patients compared with ranitidine-treated patients and those on neither drug, and with the group also evaluated prior to beginning omeprazole treatment. Parietal cell height and mass were increased in patients on omeprazole longer than 12 months compared with biopsies from patients on the drug for less than 12 months. Resin-embedded sections and electron microscopy showed enlarged parietal cells with prominence of cytoplasmic tubulovesicles with sparse secretory canaliculi. Parietal cell hypertrophy and hyperplasia develops in patients on chronic omeprazole therapy; this can be recognized on routine examination of histologic sections. These morphologic changes increase with duration of therapy.     

Resistance to vitamin K antagonists. 6 cases

Haemorrhage is the most frequent complication of oral anticoagulant therapy (OAT) and a resistance to these drugs is rarely reported. The following classification of OAT resistance is proposed: primary or secondary resistance according to the delay of onset (at the initiation of therapy or later); selective or generalized according to the number of drugs involved (only one or several); absolute or relative as judged by the prolongation of the prothrombin time (absent or moderate). Six cases are reported and the mechanisms of resistance are discussed: no intake, variations in the vitamin K availability (diet, intestinal absorption and synthesis of vitamin K), variations in the pharmacokinetics of oral anticoagulants (drug interactions, abnormal hepatic metabolism) and variations in the receptor affinity (hereditary resistance). Resistance is often overcome by progressive increase of the doses of oral coagulant, or by changing drugs, to warfarin or coumadin (long acting drugs).     

Updates in the perioperative and emergency management of non-vitamin K antagonist oral anticoagulants

Perioperative management of patients treated with the non-vitamin K antagonist oral anticoagulants is an ongoing challenge. Due to the lack of good clinical studies involving adequate monitoring and reversal therapies, management requires knowledge and understanding of pharmacokinetics, renal function, drug interactions, and evaluation of the surgical bleeding risk. Consideration of the benefit of reversal of anticoagulation is important and, for some low risk bleeding procedures, it may be in the patient’s interest to continue anticoagulation. In case of major intra-operative bleeding in patients likely to have therapeutic or supra-therapeutic levels of anticoagulation, specific reversal agents/antidotes would be of value but are currently lacking. As a consequence, a multimodal approach should be taken which includes the administration of 25 to 50 U/kg 4-factor prothrombin complex concentrates or 30 to 50 U/kg activated prothrombin complex concentrate (FEIBA®) in some life-threatening situations. Finally, further studies are needed to clarify the ideal therapeutic intervention.     

Immediate food hypersensitivity reactions on the first known exposure to the food

We report 8 infants with immediate hypersensitivity reactions to foods (milk, egg, or peanut), occurring at the first-known exposure. Each developed symptoms within the first hour, but these generally settled within 2 hours. Sensitisation to the food concerned was demonstrated by positive immediate allergen skin prick tests in every case. Symptoms experienced included irritability, erythematous rash, urticaria, angio-oedema, vomiting, rhinorrhoea, and cough. Five infants were being followed prospectively and 4 were clinically tolerant of the food by age 16 months. The most likely route of sensitisation was via breast milk. None of the infants experienced similar reactions while being breast fed, suggesting that the reaction was dose dependent. As 5 out of a group of 80 infants being followed prospectively developed an immediate reaction at their first known exposure to a food, this appeared to be a not uncommon presentation of food hypersensitivity in infancy.