Tailoring of medical treatment: hemostasis and thrombosis towards precision medicine

摘要

By integrating genetic, biomarker, phenotypic, and psychosocial characteristics that distinguish one patient from others with similar clinical presentations, the aim of precision medicine is to target treatments to individual needs. Presently, simplified individual pharmacokinetic analyses spare hemophilia patients from unnecessary exposure to replacement treatments and ultimately reduce costs. Likewise, successful clopidogrel use in vascular medicine is based on the integration of genomics, lifestyle and environmental data. Beyond the development of medical devices that are unique to a patient, or treatments tailored to specific molecular and non-molecular targets, through the use of big biobanks and electronic medical records that integrate biological information with clinical data, it is likely that algorithms will be developed to classify individuals into subpopulations differing by their susceptibility to bleeding and/or thrombosis, by the severity of their diseases, and/or by their response to specific treatments. An inherent risk of such strategies is differential access to treatments for individual patients, families, and communities, since costs for therapies depend on the size of the target population. Fostering standardization of care in the era of precision medicine implies a public health perspective and a supportive institutional environment to harmonize the interests shared by healthcare providers, patients and communities, to acknowledge the individual roles and responsibilities in decision-making, and to balance the generation of long-term knowledge and short-term health gains. Integrating efficacy, safety, and cost-effectiveness is a challenge for precision medicine and the opportunity for it to generate early measurable health benefits and to live up to its promise.A 19-year old patient was referred to our Hemophilia and Thrombosis Center because of an ischemic stroke (confirmed by magnetic resonance imaging) that occurred after 3 months of oral contraceptive use. The girl was the daughter of a patient already attending the Center for type I von Willebrand disease, but her personal and family history had been uneventful. The reason for the referral was to decide whether she should be given long-term treatment with a low dose of aspirin. The laboratory work-up revealed that, in addition to type I von Willebrand disease, she was homozygous for the prothrombin G20210A mutation, and the same thrombophilic mutation was found in other members of the family. Heterozygous factor V Leiden or the G20210A prothrombin mutation may compensate for low factor VIII or IX levels in hemophilia, resulting in more efficient thrombin generation and ensuing attenuation of clinical symptoms~(~(1)) and the risk of thrombotic complications.~(~(2)) This information was interpreted to account for the poor bleeding tendency of the patient. She was informed that: (i) despite recommendations concerning drugs to avoid in patients with von Willebrand disease, chronic daily treatment with low-dose aspirin (100 mg/day) was conceivably helpful in her case, and (ii) prophylaxis with low-molecular weight heparin/warfarin would be possible in specific, at-risk situations. Over the last 10 years in which she took low-dose aspirin daily, she had no inappropriate bleeding events, no stroke recurrence, and had two successful pregnancies.