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Interaction between hypoxia and coagulation is important given the increased risk of thrombotic diseases in chronically hypoxic patients who reside at sea level and in residents at high altitude. Hypoxia alters the proteome of platelets favouring a prothrombotic phenotype, but studies of activation and consumption of specific coagulation factors in hypoxic humans have yielded conflicting results. We tested blood from 63 healthy lowland volunteers acclimatizing to high altitude (5,200 m) using thromboelastometry and assays of platelet function to examine the effects of hypoxia on haemostasis. Using data from two separate cohorts of patients following identical ascent profiles, we detected a significant delay in clot formation, but increased clot strength by day 7 at 5,200 m. The latter finding may be accounted for by the significant rise in platelet count and fibrinogen concentration that occurred during acclimatization. Platelet function assays revealed evidence of platelet hyper-reactivity, with shortened PFA-100 closure times and increased platelet aggregation in response to adenosine diphosphate. Post-expedition results were consistent with the normalization of coagulation following descent to sea level. These robust findings indicate that hypoxia increases platelet reactivity and, with the exception of the paradoxical delay in thromboelastometry clotting time, suggest a prothrombotic phenotype at altitude. Further work to elucidate the mechanism of platelet activation in hypoxia will be important and could impact upon the management of patients with acute or chronic hypoxic respiratory diseases who are at risk of thrombotic events.

Anticoagulants may be indicated during pregnancy for the treatment or prophylaxis of venous thromboembolism and, in patients with mechanical prosthetic cardiac valves, for the prevention of valve thrombosis and systemic embolisation. Occasionally, anticoagulation is also indicated in pregnant women with valvular or congenital heart disease. Maternal mortality statistics highlight pulmonary embolism as a leading cause of maternal death in the Western world. These statistics, and the increasing understanding of risk factors for thrombosis, are leading to an increase in usage of anticoagulant drugs during pregnancy and the puerperium. Knowledge of the basic pharmacology, potential adverse effects, clinical indications and the special considerations relating to use of these agents during pregnancy is, therefore, important for obstetricians. Heparin is the anticoagulant of choice for prevention and treatment of venous thrombosis during pregnancy, as it does not cross the placenta. Warfarin should generally be avoided in pregnant women because it crosses the placenta and may give rise to fetal abnormalities. On the other hand, as the efficacy of heparin in the prevention of systemic embolisation from prosthetic cardiac valves is still unproven, warfarin remains the anticoagulant of choice in the middle of pregnancy for such patients.

We describe a method for the isolation of small quantities of large poly (A)+ mRNA from blood vessels of the rat as well as from distinct cell layers of the rat aorta. The poly (A)+ mRNA isolated by this method is suitable for use in reverse transcription polymerase chain reaction (RT-PCR) amplification of low abundance messages. In this method, anesthetized rats are perfused with ice-cold phosphate-buffered paraformaldehyde to allow for the in situ fixation of many of the main arteries of the rat. Following the in situ fixation of the rat vasculature, selected blood vessels can be removed, cleaned, and poly (A)+ mRNA purified. In addition, the distinct cell layers of the paraformaldehyde-fixed aorta can be mechanically separated and poly (A)+ mRNA purified selectively from each. The application of this method to the study of enzymes involved in cyclic nucleotide-mediated cell-signaling is illustrated by the cloning of two cyclic AMP phosphodiesterases from rat arteries, and from the selective amplification of message for these enzymes from different cell layers isolated from the rat aorta. This method should be applicable to determine if selected mRNAs are present in selected blood vessels of the rat, or within distinct cell layers of particular large blood vessels.

Prevention offers the best approach to limiting morbidity and mortality from deep vein thrombosis and pulmonary embolism in obstetric patients. The use of anticoagulant drugs during pregnancy, however, can be problematic, from the maternal or the fetal point of view. Deciding on the best management is further limited by the lack of controlled clinical trials in the obstetric setting. From the data available, it can be recommended that anticoagulant prophylaxis should be targeted at groups of patients at high risk of thrombosis during pregnancy and the puerperium. Heparin is the agent of choice in most situations during pregnancy for the prophylaxis of venous thrombosis, while warfarin is still the most effective agent for the prevention of systemic embolism from artificial cardiac valves. Prophylactic measures against venous thrombosis are probably underused in the puerperium. Controlled clinical studies are urgently required to optimize prophylaxis of venous thromboembolism associated with pregnancy, and large studies may be more feasible in the puerperium when the incidence of thromboembolism is highest.

Editor,—Disseminated fungal infection is an important cause of morbidity and mortality in immunocompromised patients, often due to candida and aspergillus species. Endogenous endophthalmitis is a recognised complication.1 We present, to our knowledge, the first reported case of endogenous intraocular infection with the emerging pathogen Ochroconis gallopava , acquired following treatment for chronic lymphocytic leukaemia (CLL). ### CASE REPORT A 69 year old man presented with a 4 day history of painless loss of vision in the left eye after receiving four courses of fludarabine (25 mg/m2 over 5 days) for CLL. Standard infection prophylaxis following myelosuppression included oral fluconazole 50 mg once daily. His neutropenia improved (7.96×109/l) but profound lymphopenia persisted (0.11×109/l). Visual acuity was right eye 6/6+4 and left eye hand movements. The right eye was normal throughout. Anterior uveitis, hypopyon, lens opacity, and vitritis compromised left funduscopy. A lymphoproliferative or infective aetiology was suspected. Anterior chamber paracentesis …