Several physiological antithrombotic proteins--including antithrombin, protein C, protein S, tissue factor pathway inhibitor, and components of the fibrinolytic system--act as inhibitors at strategic sites in the coagulation cascade to maintain normal blood fluidity under normal circumstances. The molecular basis of specific inherited hypercoagulable states has been recently elucidated. With the description of resistance to activated protein C, which is the commonest coagulation defect associated with thrombophilia, a specific primary hypercoagulable state can be identified in over 50% of patients with thrombophilia. Although the prevalence in the normal population of some "prothrombotic" mutations is remarkably high, most affected individuals do not have clinical thrombotic complications, so it is likely that clinically apparent hypercoagulable states result from multigene interactions, and that clinical episodes of thrombosis are precipitated by acquired prothrombotic insults in patients with an inherited predisposition to thrombosis.

We tested, under independent conditions, the reproducibility of evidence from two previous trials that homoeopathy differs from placebo. The test model was again homoeopathic immunotherapy. 28 patients with allergic asthma, most of them sensitive to house-dust mite, were randomly allocated to receive either oral homoeopathic immunotherapy to their principal allergen or identical placebo. The test treatments were given as a complement to their unaltered conventional care. A daily visual analogue scale of overall symptom intensity was the outcome measure. A difference in visual analogue score in favour of homoeopathic immunotherapy appeared within one week of starting treatment and persisted for up to 8 weeks (p = 0.003). There were similar trends in respiratory function and bronchial reactivity tests. A meta-analysis of all three trials strengthened the evidence that homoeopathy does more than placebo (p = 0.0004). Is the reproducibility of evidence in favour of homoeopathy proof of its activity or proof of the clinical trial's capacity to produce false-positive results?