The deleterious effects of ambient air pollution on human health have been consistently documented by many epidemiologic studies worldwide, and it has been calculated that globally at least seven million deaths are annually attributable to the effects of air pollution. The major air pollutants emitted into the atmosphere by a number of natural processes and human activities include nitrogen oxides, volatile organic compounds, and particulate matter. In addition to the poor ambient air quality, there is increasing evidence that indoor air pollution also poses a serious threat to human health, especially in low-income countries that still use biomass fuels as an energy resource. This review summarizes the current knowledge on ambient air pollution in financially deprived populations.

^* Based upon the report of a joint World Health Organization/International Society on Thrombosis and Haemostasis Meeting held in London, 12-14 October 1998. Published with permission of the World Health Organization.

Von Willebrand's disease is an inherited bleeding disorder with a prevalence as high as 1 to 2 percent in the general population, according to screening studies. However, its prevalence is deemed to be only 30 to 100 cases per million on the basis of symptomatic referrals, a prevalence that is similar to that of hemophilia A. This article discusses major advances in our understanding of the pathophysiology, molecular basis, and management of von Willebrand's disease.

Congenital or immunomediated deficiencies of the metalloprotease that cleaves physiologically von Willebrand factor (vWF) reduce or abolish the degradation of ultralarge vWF multimers that cause the formation of intravascular platelet thrombi in patients with thrombotic thrombocytopenic purpura (TTP). There is little knowledge on the behavior of the protease in other physiological and pathologic conditions. Such knowledge is important to evaluate the specificity of low protease plasma levels in the diagnosis of TTP. Using an enzyme immunoassay, the protease was measured in 177 control subjects of different ages, in 26 full-term newborns, and in 69 women during normal pregnancy. Because TTP is often associated with multiorgan involvement and acute phase reactions, clinical models of these pathologic conditions were also investigated, including decompensated liver cirrhosis (n = 42), chronic uremia (n = 63), acute inflammatory states (n = 15), and the preoperative and postoperative states (n = 24). Protease levels were lower in healthy persons older than 65 than in younger persons. They were low in newborns but became normal within 6 months, and they were lower in the last 2 trimesters of pregnancy than in the first. Protease levels were also low in patients with cirrhosis, uremia, and acute inflammation, and they fell in the postoperative period. There was an inverse relation between low protease and high plasma levels of vWF antigen and collagen-binding activity. In conclusion, low plasma levels of the vWF cleaving protease are not a specific beacon of TTP because the protease is also low in several physiological and pathologic conditions.

The success story of hemophilia care first began in the 1970s, when the availability of plasma-derived concentrates of coagulation factor VIII (FVIII) and factor IX (FIX) provided efficacious treatment of bleeding in patients with hemophilia A and B. This positive scenario was consolidated in terms of greater safety and availability in the 1990s, when the first recombinant coagulation factors were produced. This meant that, instead of only treating episodic bleeding events, prophylaxis regimens could be implemented as a preventive measure. Following the demonstration of its superiority in the frame of two randomized clinical trials, prophylaxis became evidence-based standard of care. In high-income countries, these achievements have led to a patients’ life expectancy being extended to close to that of the general male population. Alongside this, the last decade has witnessed further spectacular therapeutic progress, such as the availability of coagulation factors with a longer plasma half-life that allow for wider intervals between treatment. Moreover, new therapeutic products based on new mechanisms other than the replacement of the deficient factor, have become available (emicizumab) or are at an advanced stage of development. This review celebrates the success story of hemophilia care, while also discussing current limitations, issues and as yet unmet needs. The prospects of cure by means of gene therapy are also outlined.