Use of activated factor VII in severe acute hemorrhage

Acute hemorrhage is a sometimes serious complication that may arise in patients admitted to the intensive care unit with coagulopathy. The usual therapy is transfusion of blood components: fresh frozen plasma, platelets, fibrinogen, red cell concentrate and vitamin K. Tolerance or response can sometimes be poor. We present three patients aged 18 months, 4.5 and 10 years who suffered an acute episode of severe, life-threatening hemorrhage in the course of meningococcal sepsis (gastric hemorrhage), myelomonocytic leukemia (during splenectomy) and in the postoperative period after cardiovascular surgery. Traditional therapy was ineffective and activated factor VII was administered at doses of 50-70 microg/kg, with rapid control of bleeding.     

Use of recombinant factor VIIa (rFVIIa) to control intraoperative bleeding in pediatric brain tumor patients

Surgical bleeding during the resection of brain tumors in children may be related to tumor vascularity, pathology, and location. Despite improvements in neurosurgical technique, neuroanesthesia, and blood product replacement, bleeding can be life-threatening in these surgeries. We report eight pediatric patients in whom recombinant factor VIIa (rFVIIa) was used to control intraoperative bleeding during surgical resection of pediatric brain tumors. rFVIIa should be considered as a method to control intraoperative bleeding that is unresponsive to conventional interventions. Additional studies are needed to determine optimal patient selection and drug dosing, efficacy and safety.     

Control of bleeding associated with hemophagocytic syndrome in children: an audit of the clinical use of recombinant activated factor VII

This paper presents 2 cases of hemophagocytic lymphohistiocytosis (HLH) in whom recombinant factor VIIa (rFVIIa) was used for the management of hemorrhage. Both patients were diagnosed as HLH and were bleeding from the gut, which could not be controlled. Patients received rFVIIa at total doses of between 90 and 180 μg/kg body weight. Hemostatic affect was achieved in both of the patients but lasted only a short time. The response was achieved after 1 h of administration of rFVIIa, lasting for 24 h. The use of rFVIIa was well tolerated. These 2 patients suggest that rFVIIa is a beneficial agent in the management of hemorrhage in patients with HLH, although for a permanent homeostasis the control of primary disease is essential.     

Effectiveness of activated factor VII in postoperative bleeding after cardiac surgery with extracorporeal membrane oxygenation

A 4-year-old girl suffered severe postoperative chest tube drainage bleeding after cardiac transplant surgery requiring extracorporeal membrane oxygenation. Transfusions of platelets and fresh frozen plasma failed to decrease the bleeding. At 2.5 hours a dose of 180 mcg/kg of recombinant activated Factor VII was administered. The hemorrhage decreased from 45 ml/kg/h in the first 2.5 hours to 17 ml/kg/h in the next 2.5 hours. The same dose of recombinant activated Factor VII was administered and the hemorrhage suddenly decreased to 1.5 ml/kg/h in the next 2.5 hours, with subsequent disappearance. No adverse events related to activated Factor VII were observed. Recombinant activated Factor VII may be useful in some cases of severe postoperative bleeding in children after cardiac surgery. Randomized controlled studies are needed to confirm its safety and efficacy, and to evaluate the most suitable dose.     

Use of recombinant factor VIIa for bleeding in children with Glanzmann thrombasthenia

Glanzmann thrombasthenia is a very rare inherited platelet function disorder in which bleeding may be extremely difficult to stop. Recombinant factor VIIa is one of the alternative treatments for bleeding. The authors report here their experience with the use of factor VIIa, which may be useful for arresting bleeding in Glazmann thrombasthenia.     

A prospective pilot study of prophylactic treatment of preterm neonates with recombinant activated factor VII during the first 72 hours of life.

OBJECTIVE: Intraventricular hemorrhage (IVH) in the preterm infant is a devastating complication, causing marked mortality and morbidity. A general hemostatic agent such as recombinant activated factor VII (rFVIIa) might have the potential to reduce the extent of severe IVH. DESIGN: Prospective, single-arm pilot study. SETTING: Level III neonatal intensive care unit. PATIENTS: Ten preterm infants between 23 and 28 wks of gestation. INTERVENTION: Administration of a 100-microg/kg rFVIIa bolus injection within the first 2 hrs of life, followed by 100 microg/kg rFVIIa every 4 hrs, for the first 72 hrs of life. MEASUREMENTS AND MAIN RESULTS: Cranial ultrasonography and flow studies of the major arteries and the venae cava, aorta, vena portae, and venae renales, was performed at study enrollment and at 12 hrs, 24 hrs, 48 hrs, and 72 hrs. Blood cell counts and coagulation studies were performed. End points of the study were occurrences of adverse events, with an emphasis on thrombotic events or disseminated intravascular coagulation (DIC). Ten preterm infants with a gestational age of 23 wks 1 day to 28 wks 3 days were included. None had venous thrombosis or cerebral infarction during or after the treatment. Neither platelet consumption nor DIC was observed. Two infants with an umbilical artery catheter had a thrombus at the catheter tip (one during infusion of the study drug), which was successfully treated with heparin. One had grade III IVH and died on day 6 of life; in another, grade II IVH progressed to grade III after termination of the drug. CONCLUSION: One hundred microg/kg rFVIIa does not accumulate if administered prophylactically to preterm infants of <28 wks of gestation every 4 hrs in the first 72 hrs of life. In this population, rFVIIa does not cause DIC. Thrombus formation was observed in two infants with umbilical artery catheters but in none of the infants with venous catheters. Embolic events were not observed. In this pilot study, which did not provide the sample size to assess any effect of rFVIIa on the incidence of IVH, 20% of the neonates went on to have grade III or IV IVH, which is similar to the rate in studies in which rFVIIa was not given.     

Recombinant factor VII for severe bleeding during extracorporeal membrane oxygenation following open heart surgery.

OBJECTIVES: Severe bleeding is a recognized complication during mechanical cardiopulmonary support with extracorporeal membrane oxygenation. We present the use of recombinant activated factor VII (rFVIIa) for severe, refractory bleeding during extracorporeal membrane oxygenation support after open-heart surgery for congenital heart disease. DESIGN: Retrospective review of all patients receiving rFVIIa on extracorporeal membrane oxygenation. SETTING: A pediatric extracorporeal membrane oxygenation center located within the cardiac intensive care unit of a tertiary care children's hospital. PATIENTS: Four patients treated with rFVIIa for refractory bleeding on extracorporeal membrane oxygenation. INTERVENTIONS: The patients received rFVIIa for severe, refractory blood loss despite applying clotting products and aprotinin infusion and excluding surgical reasons. MEASUREMENTS AND MAIN RESULTS: rFVIIa was given 4-7 hrs after commencing extracorporeal membrane oxygenation; a second identical dose was administered 4 hrs later. Bleeding decreased significantly in all patients within 30 mins after the first dose of rFVIIa; no side effects were observed. CONCLUSIONS: rFVIIa is effective to achieve control of refractory hemorrhage in patients on extracorporeal membrane oxygenation. Now a randomized controlled trial to evaluate risks and benefits of rFVIIa on patients undergoing extracorporeal membrane oxygenation is required.     

Single pretransplant bolus of recombinant activated factor VII ameliorates influence of risk factors for blood loss during orthotopic liver transplantation

Large blood loss and transfusions during liver transplantation (LTx) may lead to serious complications and have a negative impact on post-transplant mortality and morbidity. In the retrospective study we compared two groups of recipients of primary cadaveric liver transplantation: group I (study group), consisted of 28 patients with preoperative risk of high intraoperative blood loss, including severe uncorrected coagulopathy. This group was given a bolus of recombinant activated factor VII (rFVIIa) just before LTx. Group II (control group) included 61 patients without a particular risk for increased intraoperative blood loss. These patients were not given rFVIIa. We analyzed both groups for: coagulation parameters before, during and after surgery (INR, APTT, factor VII activity), blood and FFP transfusions, operative time, postoperative complications (vascular thrombosis, reoperation for bleeding), postoperative ICU stay, post-transplant hospitalization time and mortality. Patients from the study group (I) had significantly worse coagulation parameters than patients in the control group (II) at the start of the surgical procedure; however, after administration of a bolus of rFVIIa there was immediate correction of coagulation in all recipients. No significant differences in intraoperative blood transfusions were observed between study and control groups (1980 +/- 311.4 mL vs. 1527 +/- 154.2 mL, respectively), operating time (8.7 h vs. 8.9 h) or ICU and hospital stay (7.03 days vs. 6.15 days and 40.89 days vs. 41.1 days). Re-exploration because of bleeding was performed in three patients from group I (10.7%) and in seven patients (11.5%) from group II. No single case of vascular thrombosis was observed in the study group, while in the control group there were three hepatic artery thromboses, two portal vein thromboses and one hepatic vein thrombosis. We conclude that rFVIIa given preoperatively to liver transplant recipients with several risk factors for high intraoperative bleeding adjusts these patients to a normal risk group, without an increased risk for thrombotic complications.     

Prophylactic treatment of a small child with severe factor VII deficiency using repeat dosing from a single vial of recombinant activated factor VII

We report our experience with a small child with severe factor VII deficiency and a history of frequent and spontaneous life-threatening hemorrhage. The patient has received several years of successful prophylactic treatment with an every 3-day infusion program in which she receives recombinant activated factor VII (rVIIa) using multiple doses from a single reconstituted vial over a 72-hr period. Comparison is made to prophylactic treatment in this same patient using plasma-derived factor VII (PDVII) using a prothrombin complex concentrate (PCC).     

Parental presence during pediatric invasive procedures.

Parental presence during pediatric invasive procedures is becoming more common, yet it remains a controversial issue related to providing family-centered care. A literature review related to this important issue was performed. Credible arguments supporting parental presence during invasive procedures as well as opposing arguments were discussed. One must consider both views in order to create a nonbiased analysis of the issue. Parental presence during invasive procedures raises critical debates related to maintaining or altering the continuum of holistic patient care. Additional research would provide an objective approach to the problem. Development of an evidence-based protocol would provide a framework for this issue.     

Use of recombinant factor VIIa for refractory hemorrhage during extracorporeal membrane oxygenation.

OBJECTIVE: To describe the outcome and treatment of two patients with recombinant factor VIIa (rFVIIa) for severe hemorrhage associated with extracorporeal membrane oxygenation (ECMO). DESIGN: Case report. SETTING: A 38-bed pediatric intensive care unit and 20-bed pediatric cardiac intensive care unit at a tertiary care children's hospital. Patient: Two patients with life-threatening hemorrhagic complications associated with ECMO requiring massive transfusion of blood products. INTERVENTIONS: Administration of repeated doses of rFVIIa at 90 microg/kg/dose. MEASUREMENT AND MAIN RESULTS: Patient 1 was an 11-yr-old male with a dilated cardiomyopathy who had undergone an orthotopic heart transplant treated with venoarterial ECMO postoperatively for right ventricular dysfunction. Patient 2 was a 13-yr-old male treated with venoarterial ECMO for cardiopulmonary failure from necrotizing staphylococcal pneumonia. Both patients had severe hemorrhage from the cannulation sites and thoracostomy tubes requiring massive transfusion to maintain intravascular blood volume and replace clotting factors. Both patients were treated with rFVIIa every 2-4 hrs and attained hemostasis. Patient 1 was administered three doses and Patient 2 was administered ten doses. No evidence of abnormal thrombus formation was noted in their respective ECMO circuits. CONCLUSIONS: The efficacy of rFVIIa in reducing intractable bleeding postcardiac surgery and in other coagulopathic states is being investigated. Despite theoretical concerns of thrombosis, these cases illustrate that there may be a role for the cautious use of rFVIIa in treating severe and intractable hemorrhage associated with ECMO.     

Medicolegal issues in pediatric neurosurgical practice.

The medical profession has an increasing interface with the profession of law and in no specialty is this more apparent than in pediatric neurosurgery. The areas of interface include the neurosurgeon as a defendant, as an expert witness, and as an ethicist. The role of a neurosurgical defendant may be eased if he/she is aware of the legal principles involved in malpractice litigation. This article discusses the doctrine of 'standard of care' as it applies presently in malpractice cases. The accepted defenses to a claim of breach of standard of care are outlined. The history of the principle of 'informed consent' is discussed briefly, as well as its present application. The position of the mature minor and emancipated minor in the process of informed consent is described. Finally, a few recommendations for avoidance of malpractice are suggested.     

Use of recombinant factor VIIa prior to lumbar puncture in pediatric patients with acute leukemia

The persistence of abnormal coagulation test results after standard treatment with fresh frozen plasma (FFP) poses significant problems in children with acute leukemia requiring a diagnostic lumbar puncture and intrathecal chemotherapy. We report the prophylactic use of a single dose of 90 microg/kg recombinant activated factor VII (rFVIIa) in three children and the rapid correction of abnormal coagulation test results previously not corrected by FFP. Administration of rFVIIa was useful in avoiding a delay of diagnostic lumbar punctures and intrathecal chemotherapy. Hemorrhagic complications and adverse effects of rFVIIa were not observed. Prospective evaluation of this indication and dose appears warranted. (c) 2005 Wiley-Liss, Inc.     

Intraoperative uses of ultrasound in the pediatric neurosurgical patient.

Ultrasound imaging has become a common method for intraoperative evaluation of the central nervous system. Real-time monitoring aids in guidance for aspiration of fluid collections and placement of catheters as well as the localization and evaluation of masses, and confirmation of their complete removal. Color Doppler is useful in the evaluation of blood flow in arteriovenous malformations, aneurysms, and neoplasms. Consultation among the ultrasound staff, neuroradiologists, and neurosurgeons before the operative procedure maximizes the usefulness of ultrasound, thus aiding in the success of surgery.