Background on Factor VIIa
While waiting for the conference call to begin, in case anyone wants some clinical background on Factor VIIa, I took this from NowUpToDate, a subscription medical resource, so no link provided. Note the reference to 92% off label use. Also, the cost is astounding for the existing recombinant product.
Indications — A recombinant DNA-produced activated factor VII (VIIa) is commercially available (Novo-Seven®). Its FDA-approved indication in the United States is for bypassing inhibitors to factors VIII and IX in patients with hemophilia A and B, respectively. (See "Factor VIII and factor IX inhibitors in patients with hemophilia", section on Recombinant human factor VIIa). This product is currently licensed in Europe for the above indications as well as for treatment of congenital factor VII deficiency and Glanzmann's thrombasthenia [14].
Off-label use — This agent has been increasingly employed in an great number of "off- label" pediatric and adult settings [15]. In one multi-institutional audit of 701 patients identified as having received this product, 92 percent were for "off-label" settings, such as the prevention of bleeding in a patient with an existing coagulopathy and/or hepatic insufficiency and an impending surgical or invasive procedure [16]. Available information on the efficacy and side effects of recombinant human factor VIIa in such settings is largely anecdotal [15-21]:
Major surgery or treatment of bleeding in patients with congenital or acquired factor VII deficiency [20,22-25], at a suggested dose of 15 to 30 microg/kg at 12 hour intervals [26].
Treatment of patients in whom excessive warfarin-associated bleeding was present and/or rapid reduction of anticoagulation was required. (See "Correcting excess anticoagulation after warfarin", section on Significant bleeding or INR >20 and see "Management of warfarin-associated intracerebral hemorrhage", section on Recombinant factor VIIa).
Treatment of the coagulopathy of severe liver dysfunction (dose range 5 to 120 microg/kg) [20]. (See "Overview of the treatment of fulminant hepatic failure", section on Coagulopathy and see "Gastroenterologic procedures in patients with disorders of hemostasis", section on Liver failure and see "General principles of the management of variceal hemorrhage", section on Hemodynamic resuscitation).
Treatment of patients with type 3 von Willebrand disease who have developed antibodies to von Willebrand factor. (See "Treatment of von Willebrand disease", section on Recombinant Factor VIIa).
Treatment of certain inherited disorders of platelet function (eg, Glanzmann thrombasthenia, Bernard-Soulier syndrome), when the presence of anti-platelet glycoprotein antibodies makes platelet transfusion no longer a viable option. (See "Refractoriness to platelet transfusion therapy", section on Recombinant factor VIIa and see "Congenital and acquired disorders of platelet function", section on Recombinant factor VIIa).
Reduction of perioperative blood loss in patients undergoing retropubic prostatectomy (IV bolus dose of 20 to 40 microg/kg) [27] or control of severe bleeding in patients undergoing cardiac surgery (dose range 13 to 91 microg/kg) [28,29].
Treatment of patients with factor XI deficiency. (See "Factor XI deficiency", section on Recombinant factor VIIa).
Management of acute intracerebral hemorrhage. (See "Hypertensive intracerebral hemorrhage", section on Hemostatic therapy).
A registry has been developed to capture clinical experiences with the investigational use of this product in the management of severe bleeding (www.haemostasis.com) [14,30]. However, the utility of this agent for the treatment of uncontrolled hemorrhage in the absence of an inherited bleeding disorder (eg, trauma, surgical bleeding, upper gastrointestinal bleeding) is uncertain [20,21,31-34].
This agent is prohibitively expensive; a single dose of 90 microg/kg to an 80 kg person costs approximately $4,500.00 [21]. However, In some highly selected clinical conditions, a judicious short term use of the drug may be indicated, justifying its cost.
Side-effects — The reported incidence of thromboembolic complications following use of this agent has ranged from 1 to 2 percent [18,34] to as high as 9.8 percent [16,35]. In a review of adverse events reported to the US Food and Drug Administration concerning this agent, there were 168 reports describing 185 thromboembolic events [36]. Unlabeled indications accounted for 151 (90 percent) of the reports. Events included thromboembolic cerebrovascular accidents, acute myocardial infarction, arterial thrombosis, pulmonary embolus, venous thrombosis, including deep vein thrombosis, and clotted access devices. In 36 of the 50 reported deaths, the probable cause of death was the thromboembolic event.
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