Administration Of Recombinant Activated Factor VII Research Articles

Pharmaceutical management of hemorrhagic stroke: Optimizing outcomes following intracranial hemorrhage evacuation

Stroke can be mainly categorized into hemorrhagic and ischemic stroke. Intracerebral hemorrhage (ICH) is a subtype of hemorrhagic stroke that is caused due to unconstrained bleeding within the parenchyma of the brain. ICH is one of the major conditions that have a high rate of disease and a high rate of death in a given population. Risk factors for ICH emerged to be age, male gender, hypertension, and intake of alcohol in huge quantities. The frequency of ICH is increased where hypertension is mainly untreated. To improve the prognosis and outcomes of an ICH patient, we need to perform emergent evacuation of blood from the brain parenchyma and prevent edema formation while restricting further neuronal damage due to surgical intervention. Evidence-based guidelines exist for ICH and form the basis for a care framework. The pharmaceutical management of ICH from current literature includes an aggressive reduction in blood pressure, tranexamic acid use, and recombinant activated factor VII administration. In addition, advanced imaging, surgical evacuation of ICH, and minimally invasive surgery techniques for hematoma evacuation could provide great benefits to patients with a large ICH.

A role for very low-dose recombinant activated factor VII in refractory bleeding after cardiac surgery: Lessons from an observational study

ObjectivesAlthough off-label use of recombinant activated factor VII against refractory bleeding is incorporated in current guideline recommendations, safety concerns persist predominantly with respect to thromboembolic complications. We analyzed the safety and efficacy of recombinant activated factor VII at a very low dose in cardiosurgical patients with refractory bleeding. MethodsThis prospective study includes 1180 cardiosurgical patients at risk of bleeding. Goal-directed substitution was based on real-time laboratory testing and clinical scoring of the bleeding intensity. All patients who fulfilled the criteria for enhanced risk of bleeding (n = 281) were consequently included in the present analysis. Patients in whom refractory bleeding developed despite substitution with specific hemostatic compounds (n = 167) received a single shot of very low-dose recombinant activated factor VII (≤20 μg/kg). Mortality and risk of thromboembolic complications, and freedom from stroke and acute myocardial infarction in particular, were analyzed (vs patients without recombinant activated factor VII) by multivariable logistic and Cox regression analyses, as well as Kaplan–Meier estimates. ResultsThere was no increase in rates of mortality (30-day mortality 4.2% vs 7.0% with P = .418; follow-up survival 85.6% at 13.0 [interquartile range, 8.4-15.7] months vs 80.7% at 10.2 [interquartile range, 7.2-16.1] months with P = .151), thromboembolic complications (6.6% vs 9.6% with P = .637), renal insufficiency, need for percutaneous coronary intervention, duration of ventilation, duration of hospital stay, or rehospitalization in patients receiving very low-dose recombinant activated factor VII compared with patients not receiving recombinant activated factor VII. Complete hemostasis without any need for further hemostatic treatment was achieved after very low-dose recombinant activated factor VII administration in the majority of patients (up to 88.6% vs 0% with P < .001). The key results were confirmed after adjustment by propensity score–based analyses. ConclusionsWhen combined with early and specific restoration of hemostatic reserves after cardiac surgery, very low-dose recombinant activated factor VII treatment of refractory bleeding is effective and not associated with any apparent increase in adverse events.

Outcomes Following Three-Factor Inactive Prothrombin Complex Concentrate Versus Recombinant Activated Factor VII Administration During Cardiac Surgery

To compare outcomes following inactive prothrombin complex concentrate (PCC) or recombinant activated factor VII (rFVIIa) administration during cardiac surgery. Retrospective propensity-matched analysis. Academic tertiary-care center. Patients undergoing cardiac surgery requiring cardiopulmonary bypass who received either rFVIIa or the inactive 3-factor PCC. Outcomes following intraoperative administration of rFVIIa (263) or factor IX complex (72) as rescue therapy to treat bleeding. In the 24 hours after surgery, propensity-matched patients receiving PCC versus rFVIIa had significantly less chest tube outputs (median difference -464 mL, 95% confidence interval [CI] -819 mL to -110 mL), fresh frozen plasma transfusion rates (17% v 38%, p = 0.028), and platelet transfusion rates (26% v 49%, p = 0.027). There were no significant differences between propensity-matched groups in postoperative stroke, deep venous thrombosis, pulmonary embolism, myocardial infarction, or intracardiac thrombus. Postoperative dialysis was significantly less likely in patients administered PCC versus rFVIIa following propensity matching (odds ratio = 0.3, 95% CI 0.1-0.7). No significant difference in 30-day mortality in patients receiving PCC versus rFVIIa was present following propensity matching. Use of rFVIIa versus inactive PCCs was significantly associated with renal failure requiring dialysis and increased postoperative bleeding and transfusions.

Change of coagulation after NovoSeven® use for bleeding during cardiac surgery.

Objectives Recombinant activated factor VII has been used for the treatment of hemophilia, factor VII deficiency, and Glanzmann's thrombasthenia. Off-label uses have recently been increasing, and there are reports that recombinant activated factor VII is effective for the treatment of excessive bleeding during or after cardiovascular surgery. We retrospectively reviewed the effectiveness of recombinant activated factor VII and its influence on the coagulation system as a treatment for uncontrollable bleeding during cardiovascular surgery. Methods Between April 2009 and May 2015, recombinant activated factor VII was used to treat uncontrollable bleeding during cardiovascular surgery in 17 patients at our hospital. The indications for recombinant activated factor VII administration were critical uncontrollable bleeding during surgery and normal platelet and fibrinogen levels. Results Blood loss significantly decreased in every case after recombinant activated factor VII administration ( p < 0.05). No adverse thromboembolic events were encountered. The prothrombin time-international normalized ratio, activated partial thromboplastin time, fibrin degradation product and D-dimer levels decreased significantly after recombinant activated factor VII administration. One day later, all blood coagulation test values were almost within the normal ranges. Conclusions Recombinant activated factor VII has a strong hemostatic action, but it is necessary to exclude surgical bleeding to exhibit the hemostatic effect. Administration that does not comply with the indications for recombinant activated factor VII may lead to serious complications such as thromboembolism. In properly selected patients, recombinant activated factor VII is an effective agent for the treatment of uncontrollable bleeding during cardiovascular surgery.

Recombinant Activated Factor VII Administration after Pulmonary Embolectomy: Case Report

Bleeding management in cardiac surgery could be a great challenge for the surgeon and a life-threatening moment for the patient. Despite the fact that recombinant activated factor VII is now widely accepted as a useful adjunct in the management of postcardiotomy coagulopathy, its use in the course of recent thromboembolic event is rarely described. We hereby present a case of rescue recombinant activated factor VII administration to manage a severe coagulation disorder during surgical pulmonary embolectomy performed under cardiopulmonary bypass.

Human recombinant activated factor VII for upper gastrointestinal bleeding in patients with liver diseases

Mortality from upper gastrointestinal bleeding in patients with liver disease is high. Recombinant human activated factor VII (rHuFVIIa) has been suggested for patients with liver disease and upper gastrointestinal bleeding. To assess the beneficial and harmful effects of rHuFVIIa in patients with liver disease and upper gastrointestinal bleeding. We searched the Cochrane Hepato-Biliary Group Controlled Trials Register (December 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (Issue 4, 2011), MEDLINE (1948 to December 2011), EMBASE (1980 to December 2011), Science Citation Index Expanded (1900 to December 2011), and LILACS (December 2011). We sought additional randomised trials from the reference lists of the trials and reviews identified through the electronic searches. Randomised clinical trials. Outcome data from randomised clinical trials were extracted and were presented using random-effects model meta-analyses. Data on the risk of bias in the included trials were also extracted. We included two trials with 493 randomised participants with various Child-Pugh scores. The trials had a low risk of bias. The rHuFVIIa administration did not reduce the risk of mortality within five days (21/288 (7.3%) versus 15/205 (7.3%); risk ratio (RR) 0.88, 95% confidence interval (CI) 0.48 to 1.64, I(2) = 49%) and within 42 days (5/286 (1.7%) versus 36/205 (17.6%); RR 1.01, 95% CI 0.55 to 1.87, I(2) = 55%) when compared with placebo. Trial sequential analysis demonstrated that there is sufficient evidence to exclude that rHuFVIIa decreases mortality by 80%, but there is insufficient evidence to exclude smaller effects. The rHuFVIIa did not increase the risk of adverse events by number of patients (218/297 (74%) and 164/210 (78%); RR 0.94, 95% CI 0.84 to 1.04, I(2) = 1%), serious adverse events by adverse events reported (164/590 (28%) versus 123/443 (28%); RR 0.91, 95% CI 0.75 to 1.11, I(2) = 0%), and thromboembolic adverse events (16/297 (5.4%) versus 14/210 (6.7%); RR 0.80, 95% CI 0.40 to 1.60, I(2) = 0%) when compared with placebo. We found no evidence to support or reject the administration of rHuFVIIa for patients with liver disease and upper gastrointestinal bleeding. Further adequately powered randomised clinical trials are needed in order to evaluate the proper role of rHuFVIIa for treating upper gastrointestinal bleeding in patients with liver disease. Although the results are based on trials with low risk of bias, the heterogeneity and the small sample size result in rather large confidence intervals that cannot exclude the possibility that the intervention has some beneficial or harmful effect. Further trials with alow risk of bias are required to make more confident conclusions about the effects of the intervention.

Acquired haemophilia a presenting in postpartum period - case report

Acquired haemophilia A is a rare autoimmune disorder caused by factor VIII (FVIII) inhibitors. Patients may present with catastrophic bleeding, despite having no prior history of bleeding disorders. Acquired haemophilia A is a rare complication of pregnancy, typically appearing in the postpartum period. The patients usually present with bleeding related to vaginal delivery or Caesarean section. Management includes control of haemorrhage and eradication of the FVIII inhibitor. Acquired haemophilia A was diagnosed in our patient after profuse vaginal bleeding related to vaginal delivery (FVIII level 2%; FVIII inhibitor titar 16 BJ). Red cell, fresh frozen plasma and cryoprecipitate transfusions, as well as vaginal packing were ineffective. The administration of recombinant activated factor VII (rFVIIa) (NovoSeven) proved effective in stopping the bleeding. To facilitate eradication of the inhibitor prednisone (30 mg orally/d) was added. After 3 weeks of treatment, the inhibitor FVIII titar was reduced to 50%. Acquired postpartum haemophilia must be always considered in the differential diagnosis of postpartum haemorrhage. According to our experience and reported literature (case reports and small series), initial haemodynamic stabilization after rFVIIa (NovoSeven) administration followed by immunosuppressive therapy is highly successful. Thus, most women presenting with acguired hemophilia A in the portpartum period has favourable prognosis.

Probable right atrial thrombus immediately after recombinant activated factor VII administration

We report the finding of a probable right atrial thrombus in a 33-yr-old male patient with severe head, chest, and abdominal trauma. Refractory coagulopathy and gross haemodynamic instability ensued, which was only partially controlled with massive blood product transfusion and high-dose inotropic support during laparotomy. Continuous transoesophageal echocardiography revealed a probable atrial thrombus partially occluding the right ventricular inflow tract, which appeared immediately after the patient received 100 microg kg(-1) of recombinant activated factor VII (rFVIIa) via a left internal jugular central line. This is the first report documenting an immediate temporal relationship between rFVIIa administration and a space-occupying lesion compatible with localized thrombosis, despite ongoing severe systemic coagulopathy. We review the clinical use of rFVIIa and discuss possible factors contributing to this event.

Use of Recombinant Activated Factor VII (Novoseven) in Trauma and Surgery: Analysis of Outcomes Reported to an International Registry

The objective was to evaluate the efficacy and safety of recombinant activated factor VII in patients with massive bleeding. Forty-five patients with severe massive hemorrhage requiring>or= 14 transfusion units of packed red blood cells received recombinant activated factor VII. Postdrug blood loss and transfusion requirements were assessed, and mortality was compared with predicted outcomes. Blood loss was markedly reduced in 40 of 43 (93.0%) patients, and transfusion requirements decreased after recombinant activated factor VII administration. Mortality rate in trauma patients who had massive hemorrhage was significantly reduced compared with predictions using scoring systems. This may be associated with the use of recombinant activated factor VII. This study failed to demonstrate an improvement in surgical patients. The absence of concurrent controls prevents definitive conclusions regarding actual safety or efficacy of recombinant activated factor VII.

Postpartum inhibitor to factor VIII: treatment with high‐dose immunoglobulin and dexamethasone

Spontaneous occurrence of an acquired inhibitor to factor VIII (FVIII) is a rare event. About 50% of cases are idiopathic. Among younger people, inhibitors are often found in the postpartum period. Treatment must be administered either to overcome haemorrhagic symptoms or to eradicate the inhibitor. Several approaches have been proposed for inhibitor eradication, based on immunosuppressive drugs such as corticosteroids, cyclophosphamide and azathioprine, with varying results. High‐dose immunoglobulin (HDIg) has been recently proposed as first‐line therapy. We report on four cases with acquired inhibitor to FVIII occurring 4–8 months after delivery. At diagnosis, inhibitor titre was &lt; 5 Bethesda units mL–1 (BU mL–1) in three cases and &gt; 5 BU mL–1 in one. Factor VIII coagulant activity (FVIII:C) was &lt; 1 U dL–1&gt; in three cases and 12 U dL–1 in one. We treated the patients with HDIg (400 mg kg–1 day–1 for 5 consecutive days) and dexamethasone (24 mg day–1 for 5–7 consecutive days), administered at the same time. In three women, the inhibitor was suppressed in 2–50 weeks. After an off‐therapy period ranging from 20 to 104 weeks, the FVIII:C was persistently normal and the inhibitor undetectable. The fourth woman remained unresponsive. In two cases, recombinant activated factor VII administration stopped the bleeding. Thus, intermediate‐ to high‐dose dexamethasone and HDIg given at the same time could be a successful and safe therapeutic approach for a rapid and complete remission from the development of FVIII inhibitors.