Adequacy of hemostatic resuscitation improves therapeutic efficacy of recombinant activated factor VII and reduces reexploration rate for bleeding in postoperative cardiac surgery patients with refractory hemorrhage

Background: Excessive bleeding and surgical reexploration are common complications that increase the risk of multi-organ failure and prolonged hospitalization after cardiac surgery. Off-label use of recombinant activated factor VII (rFVIIa) is a recommended treatment for refractory bleeding. Objective: The objective of the study is to determine if the adequacy of hemostatic resuscitation enhances the efficacy of rFVIIa. Methods: This retrospective, observational, cohort study included patients who received rFVIIa for refractory postoperative bleeding after cardiac surgery. Patients were divided into two groups based on the presence or absence of adequate coagulation resuscitation before rFVIIa administration, defined as international ratio (INR) ≤1.5, platelet count ≥100 K/mL, and fibrinogen ≥200 mg/dL. The failure of rFVIIa treatment was defined as surgical reexploration within 24 h, thoracostomy drainage >400 mL/h within 6 h or transfusion of additional blood products or another rFVIIa dose within 6 h after initial rFVIIa dose. Results: Of the 3833 patients, screened who underwent cardiothoracic surgery procedures, 58 patients received rFVIIa for refractory postoperative bleeding. Successful hemostasis with rFVIIa was more likely in patients who were adequately resuscitated compared with those who were not (20 [71.4%] vs. 10 [33.3%], respectively; P = 0.0046). Multiple logistic regression analysis indicated that patients who were adequately resuscitated before rFVIIa were less likely to fail treatment (odds ratio, 0.16; 95% confidence interval [0.04–0.62]; P = 0.007). Conclusions: The therapeutic efficacy of rFVIIa is dependent on the adequacy of hemostatic resuscitation; restoration of normal serum fibrinogen, INR, and platelet counts >100 K/mL may provide an adequate substrate for rFVIIa to be effective in managing refractory postoperative cardiac surgical bleeding.

Impact on postoperative bleeding and cost of recombinant activated factor VII in patients undergoing heart transplantation.

Background: Cardiac transplantation can be complicated by refractory hemorrhage particularly in cases where explantation of a ventricular assist device is necessary. Recombinant activated factor VII (rFVIIa) has been used to treat refractory bleeding in cardiac surgery patients, but little information is available on its efficacy or cost in heart transplant patients. Methods: Patients who had orthotopic heart transplantation between January 2009 and December 2014 at a single center were reviewed. Postoperative bleeding and the total costs of hemostatic therapies were compared between patients who received rFVIIa and those who did not. Propensity scores were created and used to control for the likelihood of receiving rFVIIa in order to reduce bias in our risk estimates. Results: Seventy‑six patients underwent heart transplantation during the study period. Twenty‑one patients (27.6%) received rFVIIa for refractory intraoperative bleeding. There was no difference in postoperative red blood cell transfusion, chest tube output, or surgical re‑exploration between patients who received rFVIIa and those who did not, even after adjusting with the propensity score (P = 0.94, P = 0.60, and P = 0.10, respectively). The total cost for hemostatic therapies was significantly higher in the rFVIIa group (median $10,819 vs. $1,985; P < 0.0001). Subgroup analysis of patients who underwent redo‑sternotomy with left ventricular assist device explantation did not show any benefit for rFVIIa either. Conclusions: In this relatively small cohort, rFVIIa use was not associated with decreased postoperative bleeding in patients undergoing heart transplantation; however, it led to significantly higher cost.

Clinical Efficacy of Recombinant Activated Factor VII in Management of Postpartum Hemorrhage / 대한주산의학회잡지

PURPOSE: This study was aimed to investigate the clinical efficacy of recombinant activated factor VII (rFVIIa) for patients with intractable postpartum hemorrhage. METHODS: This was a retrospective study of ten patients who were treated with rFVIIa from July 2010 to February 2012 in one tertiary center. To evaluate each case, we used a standardized case record form. The primary outcome measures were response of rFVIIa, reduction of blood product requirement, changes of coagulation parameter. The response of rFVIIa was categorized to three groups: "complete responder", "partial responder", "poor responder". RESULTS: After the administration of rFVIIa, effect for bleeding was completely responded in 4 patients, partially responded in 6 patients, and poorly responded in none. A certain amount of reduction in blood product requirements was noted following rFVIIa administration, although no significant differences were observed statistically between before and after rFVIIa administration except RBC (P<0.01). Fibrinogen and INR were significantly reduced in all case types, but other coagulation parameters were not (P<0.01). CONCLUSION: The present results suggest that rFVIIa is a beneficial therapeutic option that could reduce blood loss and contribute to reduction of maternal morbidities and mortalities in patients with massive postpartum hemorrhage.

Tratamento da hemorragia pulmonar maciça com fator VII recombinante ativado em prematuro de muito baixo peso / Treatment of massive pulmonary hemorrhage with activated recombinant factor VII in a very low birth weight premature

Neste relato, apresenta-se um caso de prematuro com 33 semanas de idade gestacional e 1.310 gramas, nascido de parto cesariano por retardo de crescimento intrauterino e alterações de fluxo uteroplacentário. Na evolução, apresentou sinais de choque séptico, com hipotensão e necessidade de dopamina e adrenalina contínuas. No sextodia de vida, observou-se hipoxemia refratária a altos parâmetros de ventilação mecânica. O quadro evoluiu com insuficiência renal, sem diurese após o uso de furosemida contínuo. Teve hemorragia pulmonar maciça, sem resposta às transfusões de plasma e plaquetas convencionais. Respondeu ao tratamento com dose de 120 μg/kg do fatorVII recombinante ativado. Após o controle do sangramento, foi instalado cateter para diálise peritoneal contínua, e o recém-nascido recuperou-se gradativamente das disfunções de múltiplos órgãos. Recebeu alta da unidade de terapia intensiva aos 49 dias de vida. Em conclusão, o fator VII recombinante ativado é uma alternativa eficaz de agentepan-hemostático para o controle de hemorragias pulmonares agudas graves no recém-nascido que não responde às manobras ventilatórias e ao uso de concentrados de hemocomponentes.

In this report, the authors present the case of a male premature with 33 weeks of gestation and weighing 1,310 grams, born from cesarean section indicated by retarded intrauterine growth and changes in uteroplacental flow. He showed signs of septic shock with hypotension and needed continuous adrenaline and dopamine. On the sixth day oflife, hypoxemia refractory to high mechanical ventilation parameters was observed. He developed renal failure, without diuresis after continuous furosemide. There was massive pulmonary hemorrhage unresponsive to transfusions of plasma and platelets. He responded to treatment with a dose of recombinant factor VIIa (120 μg/kg). After controlof the bleeding, a catheter for continuous peritoneal dialysis was inserted and the baby gradually recovered from multiple organ dysfunction. He was discharged from the neonatal intensive care unit at 49 days of life. Concluding, the recombinant factor VIIa is an effective pan-hemostatic agent for control of severe acute pulmonary hemorrhagein the newborn that does not respond to ventilatory maneuvers and to the use of conventional blood derivates.

Post-operative Bleeding due to Acquired Hemophilia Successfully Treated with Recombinant Factor VIIa: Case Report

Acquired hemophilia is a rare but potentially life-threatening hemorrhagic disorder caused by the development of autoantibodies against coagulation factor VIII. Concentrates of human factor VIII, desmopressin, activated prothrombin complex concentrates, recombinant activated factor VII can all be used to control episodes of acute bleeding. The recent availability of bypassing agents like recombinant activated factor VII has been shown to be clinically safe and effective as treatment for acute bleeding. In this case report, a 67 year-old male patient with Rh negative blood type developed gross hematuria and bleeding after transurethral resection due to prostatic hypertrophy. After vesicocutaneous fistular reduction operation, post-operative bleeding was presented. The acute bleeding was controlled successfully by the combined treatment with recombinant activated factor VII (Novo seven(R)) and prednisone.

Hemorragia alveolar secundaria a lupus eritematoso generalizado, tratada con factor VII recombinante activado: reporte de un caso y revisión de la literatura / Alveolar hemorrhage secondary to generalized systemic lupus erithematosus treated with recombinant activated factor VII: case report and literature review

La hemorragia alveolar es una complicación grave del lupus eritematoso generalizado (LEG), asociada a una elevada mortalidad. El tratamiento de esta complicación se apoya en el uso de corticoesteroides, ciclofosfamida; en algunas series, se recomienda el uso de metrotexate, azatioprina y plasmaféresis. En la literatura se encuentra un solo caso informado en el cual se informa el empleo del factor VII recombinante activado (FVIIra) como opción terapéutica para la hemorragia secundaria a alveolitos, refractaria al tratamiento habitual. Presentamos el caso de una paciente que desarrolló hemorragia alveolar grave con diagnóstico previo de LEG y que se manejó con FVIIra.

Alveolar hemorrhage is a severe complication of systemic lupus erithematosus (SLe) associated with high mortality. Treatment includes administration of steroids and cyclophosphamide. Additionally, some reports have recommended the use of plasmapheresis, azathioprine and methotrexate. There is a single case reported in the literature in which recombinant activatedfactor VII (rFVIIa) was used to control severe hemorrhage secondary to alveolitis unresponsive to standard treatment. We report the case of a patient with SLE who developed severe alveolar hemorrhage unresponsive to standard measures, but who was successfully treated with rFVIIa.

Clinical Experience with Recombinant Activated Factor VII in a Surgical Patient with Coagulation Factor VII Deficiency: A case report / 대한마취과학회지

A 33-yr old female patient with coagulation factor VII deficiency was scheduled for laparoscopic oophorectomy under the diagnosis of ovarian teratoma. Plasma concentration of factor VII of this patient was 9 IU/dl (normal range; 60-140 IU/dl) and the prothrombin time INR (International Normalization Ratio) was 1.79 (normal range; 0.8-1.2) on the day before the operation. Total 1,200microgram (30microgram/kg) of recombinant activated factor VII (rFVIIa) was administered just before the start of the laparoscopic procedure, which was accomplished safely without severe hemorrhage or other complications. Postoperative course was uneventful. In addition, this article provides the clinical implication of rFVIIa in terms of hemostasis management in hemophiliacs and surgical patients.

Recombinant Factor VIIa Treatment for Acute Intracerebral Hemorrhage / 대한뇌혈관외과학회지

Intracerebral hemorrhage is a lethal stroke type with a high morbidity and mortality. Hematoma growth is one of the independent determinants of neurological and functional outcomes after intracerebral hemorrhage. Attenuation of growth is an important therapeutic strategy. Hemostatic therapeutic intervention, given ultra-early in the course of intracerebral hemorrhage, may thus improve clinical outcomes by arresting ongoing bleeding and limiting in turn the size of the hematoma. Recombinant factor VIIa is a hemostatic drug approved to treat bleeding in hemophilia or other coagulopathy; it has also been reported to arrest bleeding in nonhemophilic cases. We reviewed of the published articles specifically addressing clinical trials of recombinant factor VIIa treatment for acute intracerebral hemorrhage and evaluate the safety and feasibility of it.

Successful Hemostasis after Dental Extraction with the Use of Recombinant Activated Factor VII in a Factor VII Deficient Patient / Oral Science International

We report our experience of successful hemostasis after dental extraction with the use of rFVIIa in a FVII deficient patient. Preoperative PT% was 25%, and FVII was less than 3%. Thirty minutes before tooth extraction, 1.2 mg of rFVIIa was injected. At the beginning of the operation, PT% was more than 200%, FVII was 336%, and the hemostasis after dental extraction was excellent. rFVIIa was used effectively and safely for dental extraction in this case of FVII deficiency.

A Case of Successful Treatment of Childhood Intractable Gastrointestinal Hemorrhage with Low Dose Recombinant Activated Factor VII (NovoSeven (R)) / 대한소아혈액종양학회지

Recombinant activated factor VII (rFVIIa, NovoSeven (R)) was initially developed for the treatment of bleeding in patients with hemophilia having antibodies against factor VIII or IX, and factor VII deficiency. Although the precise mode of action is still elusive and there are just several hypotheses, recently case reports have suggested a role of rFVIIa in the management of intractable or life-threatening bleeding in some non-hemophilic patients who do not respond to conventional treatments. We report the successful use of rFVIIa in a pediatric patient with intractable gastrointestinal bleeding.