Tobias JD:, Synthetic factor VIIa to treat dilutional coagulopathy during posterior spinal fusion in two children. Anesthesiology 2002;96:1522-1525.
Although excessive bleeding is a major risk associated with any surgical procedure, one of the more common surgical procedures associated with significant blood loss is posterior spinal fusion In pediatric-aged patients. When blood component therapies are used to replace blood loss, a dilutional coagulopathy can occur due to multiple factors. When prolongation of the prothrombin time (PT) and partial thromboplastin time (PTT) occurs in bleeding patients, treatment generally includes the administration of fresh frozen plasma (FFP) and cryoprecipitate if the fibrinogen level is low. Although this therapy is generally effective, repeated doses of FFP may be required, and occasionally, coagulation disturbances persist. The author reports two children who developed dilutional coagulopathy during posterior spinal fusion for neuromuscular scoliosis. When FFP failed to correct the coagulopathy, recombinant factor VIIa (rFVIIa, NovoSeven®, Novo Nordisk) was successfully used.
An 8-yr-old, 26-kg girl with neuromuscular scoliosis presented for posterior spinal fusion. Anesthetic care included controlled hypotension with remifentanil–isoflurane to maintain a mean arterial pressure of 55–65 mmHg. Aprotinin was administered in a dose of 30,000 units/kg/h, and the platelet count remained above 100,000/mm3. Eighteen hours postoperatively, when the coagulation function was abnormal again and failed to correct with a unit of FFP (280 ml), the decision was made to use rFVIIa, since the patient’s hematocrit had decreased from 30% to 23% and there was 590 ml of output into the surgical drain. After the infusion of rFVIIa, there <50 ml of sanguinous drainage from the wound and the drain was removed the next morning. Coagulation studies 24 h later remained within normal limits.
A 13-yr-old, 38-kg boy with neuromuscular scoliosis presented for posterior spinal fusion. Anesthetic care included controlled hypotension with remifentanil–isoflurane–labetolol to maintain a mean arterial pressure of 55–65 mmHg. Aprotinin was administered in a dose of 30,000 units/kg/h. Postoperatively, the patient’s platelet count remained above 100,000/mm3. Eighteen hours postoperatively, when the coagulation function was abnormal again, based on the previous inability of FFP to correct the abnormal coagulation function, the decision was made to use rFVIIa. Output over the 12 h from the surgical drains was 692 ml. After the infusion of synthetic factor VII, there was less than 50 ml of sanguinous drainage from the wound and the drain was removed the next morning. Coagulation studies 24 h later remained within normal limits.
A growing number of reports describe the successful use of rFVIIa in surgical patients who develop coagulopathy and bleeding after massive transfusion. The authors report that to date, there have been no major adverse effects associated with rFVIIa administration in pediatric-aged patients. As rFVIIa must interact with tissue factor (TF) released at the site of tissue injury, there should be limited risk of thromboembolic events. Although the coagulation profile (PT and PTT) will correct, rFVIIa will not increase other factor levels that are decreased related to either dilutional or consumptive effects. As such, once the factor VII levels have declined, unless there is replacement (exogenous administration or endogenous production) of these factor levels, the coagulation defect will recur. Based on the previous reports, the duration of effect of a 90 mcg/kg dose is 12 h and repeat monitoring of coagulation function is suggested.
Correction of the coagulation disturbance was not achieved in the 2 children reported after routine doses of FFP (20–30 ml/kg). Although the coagulation defect might have been corrected with additional FFP; in addition to rapidly correcting the coagulation defect, the authors suggest there are other potential advantages of rFVIIa that include no infectious disease risk, a much smaller volume allowing rapid administration, and an easy to use preparation that is quickly diluted and administered, compared to FFP that has to be thawed, necessitating a 30–45 preparation time. The authors suggest a more rapid administration and correction of the coagulation defect could theoretically lead to a reduction in blood loss, improved surgical visualization, and perhaps decreased surgical time. Data also suggests that rFVIIa improves platelet function, adding a secondary beneficial effect on coagulation function during the perioperative period. Adverse effects have been limited, including rare reports of anaphylactoid reactions. As rFVIIa is not proteolytically active by itself, but rather must react with TF to become active, there is a limited risk of excessive systemic thrombogenesis, and to date no increased incidence of thromboembolic complications has been noted. The authors emphasize this case report should not be taken as a suggestion to use rFVIIa whenever a coagulation disturbance cannot be corrected with FFP. The author chose to use factor VII given the high-risk population involved (neuromuscular scoliosis) and their known predisposition to intraoperative bleeding, dilutional coagulopathy with a blood loss of more than one blood volume, a normal fibrinogen level and normal platelet count, no readily reversible etiology of the coagulopathy (heparin or warfarin therapy), and failure of standard therapy (FFP). Given the potential use of rFVIIa, randomized investigations appear warranted to fully delineate the role of this agent in the treatment of perioperative coagulopathies in specific high-risk populations, and clinical scenarios.