To the Editor: Dr O’Connell and colleagues1 reviewed thromboembolic complications of recombinant human coagulation factor VIIa (rFVIIa) as reported to the US Food and Drug Administration (FDA) MEDWATCH database. As with any medication, rFVIIa has both positive and negative effects; therefore, risks and benefits must be considered before administering the drug. In our trauma practice, we cannot know which of our patients with life-threatening hemorrhage are also at risk for ischemic stroke, myocardial infarction, or other thrombotic complications. We are cautious with rFVIIa use in the presence of arterial injury and will not use it in patients undergoing extracorporeal circulatory support. However, some patients have dilutional coagulopathy severe enough to warrant the use of almost any therapy to salvage them from hemorrhagic shock, regardless of risk.2 A recent randomized, placebo-controlled, double-blind trial of the use of rFVIIa in patients with trauma did not find an increased risk of thromboembolic events.3 This study, however, excluded patients older than 65 years, who would be most likely to experience adverse thromboembolic events.
Less clear to us is the risk-benefit ratio for off-label rFVIIa use in patients who are not in extremis. One frequent use of rFVIIa is the reversal of warfarin therapy in patients presenting with active bleeding, such as those patients with subdural hematoma. Coagulation may be normalized more rapidly than with traditional administration of plasma, with a decreased risk of fluid overload. It would therefore be helpful to know how many of the reported thromboembolic complications described by O’Connell et al were observed in patients who were taking warfarin analogs or platelet inhibitors before the rFVIIa dose, what proportion of the prophylactic use was in patients with conditions such as cirrhosis that are associated with coagulopathies, and what proportion was in patients with normal coagulation systems.
Finally, the comments on the study of rFVIIa in patients with intracranial hemorrhage4 were valuable, because this was the first prospective study to suggest a dose-response effect in the thromboembolic complication rate. Understanding the risks of rFVIIa will be enhanced if reports to MedWatch include the dose of drug administered, other procoagulant therapies, underlying pathophysiology, and the timing of complications. Such detail may help in designing future trials of rFVIIa.
Financial Disclosures: Dr Dutton reported serving as a research design consultant for Novo Nordisk, the manufacturers of rFVIIa. Dr Stein reported that her research is funded by Novo Nordisk. No authors have an ownership position or direct financial interest in Novo Nordisk. No other authors reported financial disclosures.
Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature
Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal
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