Recombinant FVIIa decreases perioperative blood transfusion requirement in burn patients undergoing excision and skin grafting--results of a single centre pilot study

BACKGROUND: Excision of burn wounds is frequently associated with a large volume of blood loss requiring allogeneic blood transfusion. We conducted a pilot study to investigate the effect of activated recombinant coagulation factor VII (rFVIIa) on the reduction of blood transfusion requirements in burn patients undergoing excision and skin grafting. METHODS: Eighteen consecutive patients scheduled for the surgery were randomised to receive either placebo or 40 microg/kg rFVIIa administered at first skin incision, and a second dose (40 microg/kg) at 90 min later. Blood transfusion requirements during, and up to 24h post-surgery per patient and percentage full thickness wound excised were compared. In addition, postoperative complications commonly seen in patients with burns as well as adverse events related to rFVIIa were monitored. RESULTS: rFVIIa significantly decreased the total number of units of blood components transfused per patient and percentage full thickness burn wound excised compared with placebo (0.9 versus 2.2, p=0.0013) including significant fewer red blood cell units (0.5 versus 1.1, p=0.004). We further observed a trend towards improved graft survival (p=0.1) and a reduction in multiple organ failures (p=0.08) in the rFVIIa-treated group. There were no adverse events, in particular thromboembolic events. CONCLUSION: rFVIIa might be useful in decreasing blood transfusion requirements in burn patients undergoing excision and skin grafting.     

Recombinant activated factor VII in the management of life-threatening bleeding in cardiac surgery.

OBJECTIVE: Massive perioperative bleeding is a potential complication of cardiac surgery, and may persist despite conventional interventions. RFVIIa is being increasingly used as additional therapy, and the aim of the present study was to describe our experience with rFVIIa in the management of life-threatening bleeding in adult cardiac surgery. METHODS: Retrospective chart review of 24 patients undergoing a variety of cardiac procedures was performed at Sahlgrenska University Hospital between January and August 2004. The patients developed life-threatening bleeding during or after surgery despite conventional medical therapy and transfusion of blood products, and received rFVIIa as additional therapy. RESULTS: RFVIIa was administered as a median bolus dose of 60 microg/kg. Nineteen patients received one dose of rFVIIa; the bleeding stopped or decreased in 18 of them. Five patients received repeated doses of rFVIIa. Fifteen patients were reexplored due to massive postoperative bleeding or cardiac tamponade and a surgical source of bleeding was identified in six of these patients. A statistically significant reduction in chest drain losses after administration of rFVIIa was demonstrated. No adverse reactions were noted. CONCLUSIONS: RFVIIa was successfully used as an additional therapy both during and after cardiac surgery, when bleeding was refractory to conventional methods. Bleeding stopped eventually in all patients and none of the patients exsanguinated.     

Use of activated recombinant coagulation factor VII in patients undergoing reconstruction surgery for traumatic fracture of pelvis or pelvis and acetabulum: a double-blind, randomized, placebo-controlled trial

Background. Activated recombinant coagulation factor VII (rFVIIa)effectively prevents and controls bleeding in patients withcoagulopathy. Data show that rFVIIa may reduce blood loss andeliminate the need for transfusion in patients with normal haemostasisundergoing major surgery. We assessed the efficacy of rFVIIain patients with normal haemostasis undergoing repair surgeryof major traumatic fracture of the pelvis or the pelvis andacetabulum, who were expected to have a large volume of bloodloss. Methods. We performed a double-blind, randomized, placebo-controlledtrial involving 48 patients undergoing major pelvic–acetabularsurgery. Patients were randomized to receive an i.v. bolus injectionof rFVIIa 90 µg kg^–1 or placebo as add-on therapyat the time of the first skin incision. All patients also receivedintraoperative salvaged red blood cells (RBC). Results. There was no significant difference in the total volumeof perioperative blood loss, the primary outcome variable, betweenthe rFVIIa and placebo groups. In addition, there were no differencesbetween the two groups in the total volume of blood components,including salvaged RBC transfused, number of patients requiringallogeneic blood components, total volume of fluids infused,total operating time, time taken after entry to the intensivecare unit to reach normal body temperature and acid–basestatus, and time spent in hospital. No adverse events, in particularthromboembolic events, were reported in either group. Conclusions. In patients with normal haemostasis undergoingrepair surgery of traumatic pelvic–acetabular fracture,the prophylactic use of rFVIIa does not decrease the volumeof perioperative blood loss.      

Successful reversal of deleterious coagulopathy by recombinant factor VIIa

Effective treatment of severe or uncontrolled bleeding is a challenge for physicians in the operating room and intensive care unit. However, even aggressive conventional therapy may ultimately fail in some patients. Administration of recombinant activated factor VII (rFVIIa) may be the only remaining therapeutic option to stop life-threatening coagulopathic bleeding. We here describe the clinical course of 5 patients exhibiting severe continuous bleeding that could not be stopped by surgical intervention and appropriate hemostatic management but resolved after a mean dose of 90 microg/kg of rFVIIa (range, 90-120 microg/kg). Four of the five patients recovered completely, and one patient died after developing sepsis in multiorgan failure. In all patients, bleeding from wound surfaces stopped within minutes of the administration of rFVIIa. Coagulation measurements improved, and transfusion requirements declined considerably. No adverse effects associated with rFVIIa were observed.     

Efficacy and safety of repeated perioperative doses of recombinant factor VIIa in liver transplantation.

Patients undergoing orthotopic liver transplantation (OLT) have excessive blood loss during surgery that requires blood transfusions, leading to increased postoperative morbidity and mortality. We studied the efficacy and safety of activated recombinant factor VII (rFVIIa) in reducing transfusion requirements in OLT. This multicenter, randomized, double-blind, placebo-controlled trial enrolled patients undergoing OLT because of cirrhosis (Child-Turcotte-Pugh class B or C). Patients received a repeated intravenous bolus regimen of rFVIIa 60 or 120 microg/kg or placebo. The primary efficacy endpoint was the total number of red blood cell (RBC) units transfused during the perioperative period. A total of 182 patients were analyzed for efficacy and 183 for safety. No significant effect of rFVIIa was observed on the number of RBC units transfused or intraoperative blood loss compared with the placebo group. A significantly higher number of patients in the rFVIIa study groups avoided RBC transfusion. Administration of rFVIIa but not placebo restored the preoperative prolonged prothrombin time to normal value during surgery. Patients receiving rFVIIa and placebo did not experience a significant difference in rate of thromboembolic events. Additionally, there was no statistically significant effect of rFVIIa treatment on hospitalization rate, total surgery time, and the proportion of patients undergoing retransplantation. In conclusion, use of rFVIIa during OLT significantly reduced the number of patients requiring RBC transfusion. There was no increase in thromboembolic events with rFVIIa administration compared with placebo.     

Safety and hemostatic effect of recombinant activated factor VII in cirrhotic patients undergoing partial hepatectomy: a multicenter, randomized, double-blind, placebo-controlled trial

BACKGROUND: Coagulopathy caused by cirrhosis may contribute to excessive bleeding during hepatectomy. We evaluated the hemostatic effect and safety of recombinant factor VIIa (rFVIIa) in cirrhotic patients undergoing partial hepatectomy. METHODS: Patients were randomized to rFVIIa 50 or 100 mug/kg or placebo, administered intravenously 10 minutes before surgery and every second hour during surgery. The primary efficacy end points were the proportion of patients receiving red blood cell (RBC) transfusions and the amount of RBCs transfused. The RBC transfusion trigger was blood loss of 500 mL. Safety end points included thromboembolic and adverse events. RESULTS: No statistically significant effect of rFVIIa treatment on efficacy end points was observed. Serious and thromboembolic adverse events occurred at similar incidences in the study groups. CONCLUSIONS: Using blood loss as a transfusion trigger, the efficacy of rFVIIa in reducing the requirement for RBC transfusion was not established in this study. No safety concerns were identified.     

不同方法评估重度烧伤清创植皮术患儿术中出血量准确性的比较

目的 比较手术面积和手术面积与血容量乘积(手术面积×血容量)评估重度烧伤清创植皮术患儿出血量的准确性.方法 拟行切削痂、清创植皮手术的重度烧伤患儿20例,年龄7 d～8岁,性别不限,体重4～22 kg,烧伤后5～10 d,烧伤面积15%～50%,手术面积10%～46%.计算术中总出血量,手术面积和手术面积×血容量与总出血量行直线相关和直线回归分析.结果 手术面积和手术面积×血容量与总出血量的相关系数分别为0.776和0.889,比较差异有统计学意义(P＜0.05);总出血量(Y)与手术面积(X1)、手术面积×血容量(X2)直线回归方程分别为:Y=25.094X1-122.431和Y=0.020X2+16.142.结论 与手术面积比较,手术面积×血容量能更准确地评估重度烧伤清创植皮术患儿的术中出血量.

Abstract：

Objective To evaluate the accuracy of different methods for estimating blood loss during burn wound excixion and skin grafting in pediatric patients with severe burn. Methods Twenty pediatric patients of both sexes aged 7 days-8 yr weighing 4-22 kg undergoing burn wound excision and skin grafting were enrolled in this clinical study. Two methods were used for estimating blood loss during operation: Method Ⅰ: surgical surface area (SSA). MethodⅡ: the product of SSA and blood volume (BV). Total blood loss was calculated: total blood loss = BV ( Hct0 - Hctx ) ÷ Hct0 + Tx. Hct0 =Hct before operation. Hctx =Hct at the end of operation. Tx =total amount of blood transfusion. Results The correlation between the total blood loss and SSA was 0.776. The correlation between the total blood loss and the product of SSA and BV was 0.889. The difference was statistically significant. Conclusion The product of SSA and BV is more accurate in estimating blood loss during burn wound excision and skin grafting in children with severe burn.     

Recombinant factor VIIa (NovoSeven) as a hemostatic agent after surgery for congenital heart disease

BACKGROUND: Postoperative bleeding and blood product requirements can be substantial in children undergoing open-heart surgery, and reexploration is required in 1% of cases. Recombinant activated factor VII (rFVIIa, NovoSeven, NovoNordisk, Denmark) is a hemostatic agent approved for the treatment of hemophilic patients with inhibitors to factor VIII or factor IX. It has also been used with success in other conditions. We present our experience with rFVIIa treatment for uncontrolled bleeding after open-heart surgery in five pediatric patients. METHODS: The study group consisted of five patients after open-heart surgery with excessive blood loss. The patients were treated with rFVIIa after failure of conventional treatment to control the bleeding. Blood loss, blood product consumption, and coagulation test results were recorded before and after rFVIIa administration. RESULTS: In all cases, blood loss decreased considerably after rFVIIa administration (mean 7.8 ml x kg(-1) x h(-1)), almost eliminating the need for additional blood products, and the prolonged prothrombin time normalized. In two patients with thrombocytopathy, rFVIIa helped to discriminate surgical bleeding from bleeding caused by a defect in hemostasis. No side effects of rFVIIa treatment were noted. CONCLUSIONS: These cases support the impression that RFVIIa is efficient and safe in correcting hemostasis in children after cardiopulmonary bypass when other means fail. However, the data are still limited, and more extensive research is needed.     

Recombinant coagulation factor VIIa in major liver resection: a randomized, placebo-controlled, double-blind clinical trial

BACKGROUND: Prevention of bleeding episodes in noncirrhotic patients undergoing partial hepatectomy remains unsatisfactory in spite of improved surgical techniques. The authors conducted a randomized, placebo-controlled, double-blind trial to evaluate the hemostatic effect and safety of recombinant factor VIIa (rFVIIa) in major partial hepatectomy. METHODS: Two hundred four noncirrhotic patients were equally randomized to receive either 20 or 80 microg/kg rFVIIa or placebo. Partial hepatectomy was performed according to local practice at the participating centers. Patients were monitored for 7 days after surgery. Key efficacy parameters were perioperative erythrocyte requirements (using hematocrit as the transfusion trigger) and blood loss. Safety assessments included monitoring of coagulation-related parameters and Doppler examination of hepatic vessels and lower extremities. RESULTS: The proportion of patients who required perioperative red blood cell transfusion (the primary endpoint) was 37% (23 of 63) in the placebo group, 41% (26 of 63) in the 20-microg/kg group, and 25% (15 of 59) in the 80-microg/kg dose group (logistic regression model; P = 0.09). Mean erythrocyte requirements for patients receiving erythrocytes were 1,024 ml with placebo, 1,354 ml with 20 microg/kg rFVIIa, and 1,036 ml with 80 microg/kg rFVIIa (P = 0.78). Mean intraoperative blood loss was 1,422 ml with placebo, 1,372 ml with 20 microg/kg rFVIIa, and 1,073 ml with 80 microg/kg rFVIIa (P = 0.07). The reduction in hematocrit during surgery was smallest in the 80-microg/kg group, with a significant overall effect of treatment (P = 0.04). CONCLUSIONS: Recombinant factor VIIa dosing did not result in a statistically significant reduction in either the number of patients transfused or the volume of blood products administered. No safety issues were identified.     

Recombinant Coagulation Factor VIIa in Major Liver Resection: A Randomized, Placebo-controlled, Double-blind Clinical Trial

Background: Prevention of bleeding episodes in noncirrhotic patients undergoing partial hepatectomy remains unsatisfactory in spite of improved surgical techniques. The authors conducted a randomized, placebo-controlled, double-blind trial to evaluate the hemostatic effect and safety of recombinant factor VIIa (rFVIIa) in major partial hepatectomy.

Methods: Two hundred four noncirrhotic patients were equally randomized to receive either 20 or 80 [mu]g/kg rFVIIa or placebo. Partial hepatectomy was performed according to local practice at the participating centers. Patients were monitored for 7 days after surgery. Key efficacy parameters were perioperative erythrocyte requirements (using hematocrit as the transfusion trigger) and blood loss. Safety assessments included monitoring of coagulation-related parameters and Doppler examination of hepatic vessels and lower extremities.

Results: The proportion of patients who required perioperative red blood cell transfusion (the primary endpoint) was 37% (23 of 63) in the placebo group, 41% (26of 63) in the 20-[mu]g/kg group, and 25% (15 of 59) in the 80-[mu]g/kg dose group (logistic regression model; P = 0.09). Mean erythrocyte requirements for patients receiving erythrocytes were 1,024 ml with placebo, 1,354 ml with 20 [mu]g/kg rFVIIa, and 1,036 ml with 80 [mu]g/kg rFVIIa (P = 0.78). Mean intraoperative blood loss was 1,422 ml with placebo, 1,372 ml with 20 [mu]g/kg rFVIIa, and 1,073 ml with 80 [mu]g/kg rFVIIa (P = 0.07). The reduction in hematocrit during surgery was smallest in the 80-[mu]g/kg group, with a significant overall effect of treatment (P = 0.04).     

Intraoperative use of recombinant activated factor VII (rFVIIa)

Recombinant activated factor VII (rFVIIa, Novoseven, Novo Nordisk, Denmark) was introduced as a prohemostatic agent in the early 80s: the only indication approved in USA by Food and Drug Administration (FDA) is the spontaneous bleeding in congenital hemophilia patients who developed inhibitors to FVIII and FIX. Recently, EMEA approved the use of rFVIIa in congenital hemophilia patients with inhibitors undergoing surgery, in subjects with congenital FVII deficiency undergoing surgical or invasive procedures, in patients with acquired hemophilia and in case of Glanzmann's thromboasthenia. Out of these approved indications, the off label use of rFVIIa is rapidly expanding, particularly in surgical patients with acquired coagulation disorders in order to manage severe, uncontrolled bleeding nonresponsive to conventional therapeutic measures or to reduce blood loss and transfusion requirements in potentially bleeding surgical procedures (major liver surgery, liver transplantation, major abdominal or obstetric surgery, trauma surgery). This paper reviews the more recent data coming from retrospective or prospective studies performed in different surgical settings: so far, the major point to be addressed is the place for rFVIIa as an adjunctive but sometimes lifesaving treatment to control haemostasis and critical bleeding in surgery and critically ill patients.     

Determinants of blood loss during primary burn excision

BACKGROUND: Excisional therapy for burn wounds is frequently associated with large operative blood losses. Our objective was to identify patient and operative factors that affect surgical blood loss and determine strategies to minimize hemorrhage. METHODS: Data from 92 consecutive pediatric patients with severe burns (>40% total body surface area) were evaluated. Patient demographics, burn characteristics, operative factors, and clinical course variables were correlated with blood loss. Blood loss at the time of initial total burn excision was determined by a standardized, previously validated method. Data were analyzed sequentially and cumulatively through univariate and cross-sectional multivariate linear regression. RESULTS: Demographic factors that correlated with increased blood loss were older age, male sex, and larger body size. Area of full-thickness (third-degree) burn correlated with blood loss, whereas total burn size did not. High wound bacteria counts (derived from quantitative tissue cultures), total wound area excised, and operative time were the strongest predictors of the volume of operative hemorrhage. Blood loss increased with delay to primary burn excision at a maximum at 5 to 12 days after burn injury. CONCLUSIONS: Early definitive surgical therapy before extensive bacterial colonization and rapid operative excision is a strategy that may decrease operative hemorrhage and transfusion requirements during burn surgical procedures.     

Recombinant Factor VIIa for Life-Threatening Hemorrhage in Trauma Patients: Review of the Literature

Abstract The control of hemorrhage and coagulopathy is a vital component of trauma care, and failure to achieve hemostasis can contribute to mortality. Recombinant factor VIIa (rFVIIa) is a well-established therapy for bleeding episodes and surgical prophylaxis in hemophilia patients with inhibitors. However, there has been increasing utilization of rFVIIa in the treatment of trauma-related blood loss in patients without pre-existing coagulopathy. This paper reviews published experience in this area. Database searches identified 126 rFVIIa-treated trauma patients reported in 15 publications between November 1999 and November 2004. Ages ranged from 20 months to 88 years, and the majority of patients (68.7%) had suffered blunt injury. In most cases, rFVIIa was used as a salvage therapy when bleeding continued despite the appropriate application of available conventional hemostatic methods. Doses of rFVIIa varied widely (36–178 μg/kg), with patients receiving a single dose or multiple doses separated by an interval of 2–12 h. Efficacy of treatment (reduction in blood loss, transfusion requirements and mortality) was reported for 79.4% of subjects. Most publications also described shortening or normalization of coagulation parameters following rFVIIa administration. No non-thrombotic adverse events were noted in any patient, but five cases (4.0%) of thromboembolic events were recorded. Recently reported clinical trial data offer support to these anecdotal observations. In conclusion, data appear to support the utility of rFVIIa as an adjunctive therapy for the reduction of hemorrhage and transfusion requirements in trauma patients. However, further information relating to the use of rFVIIa in the trauma setting is required.     

Effect of topical and subcutaneous epinephrine in combination with topical thrombin in blood loss during immediate near-total burn wound excision in pediatric burned patients.

Bleeding is a major concern during burn wound excision. To evaluate the efficacy of epinephrine to control blood loss, a prospective cohort of 42 pediatric patients were examined. Half of the patients received topical epinephrine to excised wounds and donor sites and subcutaneous epinephrine to scalp donor sites during total burn excision, while the other half did not. Both groups of patients received bovine topical thrombin sprayed at a concentration of 1000 U/ml. Mean blood loss in the epinephrine group was 1090 ml (range 20-4000), with a blood loss of 0.48+/-0.12 ml/cm2 excised, while the control group was 1271 ml (range 40-3750) and 0.51+/-0.15 ml/cm2. Differences in preoperative and postoperative hematocrits were respectively -3.4+/-7.8 and -4.6+/-7.5. The groups were not statistically different in this analysis. Subgroup analysis by age, burn size and time of burn to excision showed no differences. No complications or side effects of the use of the vasopressor solution occurred. In conclusion, no differences in blood loss were found between the groups. The routine use of local epinephrine during total wound excision in combination with topical thrombin in pediatric patients operated within 24 h after the admission may not be necessary. The effect of topical thrombin on blood loss should be analyzed separately.     

Treatment of refractory bleeding after cardiac operations with low-dose recombinant activated factor VII (NovoSeven): a propensity score analysis.

BACKGROUND: Recombinant activated factor VII (rFVIIa) has been increasingly used to stop life-threatening bleeding following cardiac operations. Nonetheless, the issue of dosing, given the expense and potential for thrombotic complications, is still of major concern. We report our experience with small-dose rFVIIa in patients with refractory bleeding after cardiac surgery. METHODS AND RESULTS: From September 2005 to June 2007, 40 patients (mean age 70.1+/-9.2 years, 52.5 males) received a low dose of rFVIIa (median: 18 microg/kg, interquartile range: 9-16 microg/kg) for refractory bleeding after cardiac surgery. Forty propensity score-based greedy matched controls were compared to the study group. Low dose of rFVIIa significantly reduced the 24-h blood loss: 1610 ml [ 1285-1800 ml] versus 3171 ml [2725-3760 ml] in the study and control groups, respectively (p<0.001). Thus, hourly bleeding was 51.1 ml [34.7-65.4 ml] in patients receiving rFVIIa and 196.2 ml/h [142.1-202.9 ml] in controls (p<0.001). Furthermore, patients receiving rFVIIa showed a lower length of stay in the intensive care unit (p<0.001) and shorter mechanical ventilation time (p<0.001). In addition, the use of rFVIIa was associated with reduction of transfusion requirements of red blood cells, fresh frozen plasma and platelets (all, p<0.001). Finally, treated patients showed improved hemostasis with rapid normalization of coagulation variables (partial thromboplastin time, international normalized ratio, platelet count, p<0.001). In contrast, activated prothrombin time and fibrinogen did not differ between groups (p=ns). No thromboembolic-related event was detected in our cohort. CONCLUSIONS: In our experience low-dose rFVIIa was associated with reduced blood loss, improvement of coagulation variables and decreased need for transfusions. Our findings need to be confirmed by further larger studies.     

The role of recombinant factor VIIa in the treatment of life-threatening haemorrhage in blunt trauma

BACKGROUND: Recombinant factor VIIa (rFVIIa) is a novel haemostatic agent originally developed to treat bleeding in haemophiliacs. Several case reports suggest effectiveness of rFVIIa in the treatment of patients without pre-existing bleeding disorders. The aim of this study is to evaluate treatment with recombinant (rFVIIa) in blunt trauma patients with uncontrolled bleeding. PATIENTS AND METHODS: This study was designed as a retrospective case review. Consecutive patients with life-threatening uncontrolled bleeding due to blunt trauma who were treated with rFVIIa were selected. Data were obtained from medical records. RESULTS: A total of eight blunt trauma patients were treated with rFVIIa for uncontrolled bleeding. After treatment the need for transfusion of red blood cells (RBC) decreased significantly from 31.3 +/- 15.8 to 6.1 +/- 6.8 units (P = 0.003), fresh frozen plasma (FFP) from 13.3 +/- 6.6 to 5 +/- 6.3 units (P = 0.02), and platelets from 3.6 +/- 1.8 to 1.5 +/- 2.3 units (P = 0.01). Three patients died of non-bleeding complications. The other five fully recovered. CONCLUSION: Treatment with rFVIIa reduced or stopped bleeding in all patients. No adverse events were registered. Prospective studies are mandatory to elucidate the role of rFVIIa in blunt trauma.     

Recombinant activated factor VII in critical bleeding after orthotopic liver transplantation

Critical bleeding throughout the intraoperative phase of orthotopic liver transplantation (OLT) strongly increases patient mortality and intensive care unit (ICU) stay. The aim of this study was to report our experience on the use of recombinant activated factor VII (rFVIIa) in postoperative critical bleeding after OLT. In 7 patients with persistent severe bleeding after application of a standard transfusion protocol, we administered a 90 microg/kg bolus of rFVIIa and if necessary eventually repeated it after 3 hours. We recorded the blood loss and the need for transfusions before and after the rFVIIa therapy. Blood losses and need for platelets significantly decreased after rFVIIa administration; a nonsignificant decrease in red blood cells and fresh frozen plasma transfusions also occurred. In 6 patients treatment with rFVIIa was effective; only 1 patient died because of hemorrhagic shock and no thromboses were detected among the treated patients. Awaiting stronger evidence from randomized controlled trials, we suggest that in some challenging cases of massive bleeding rFVIIa should be considered a useful option to control bleeding.     

Use of recombinant factor VIIa for adjunctive hemorrhage control in trauma and surgical patients

Recombinant factor VIIa (rFVIIa) has recently been described for patients with ongoing massive bleeding in a number of different clinical scenarios. A retrospective chart review was conducted at a public level I trauma center in order to describe the use of rFVIIa in trauma and surgical patients with massive bleeding despite surgical control. Fifteen trauma and general surgical patients underwent major operative procedures and developed coagulopathy requiring massive blood product transfusion. All patients had continued life-threatening hemorrhage despite surgical control of bleeding. The mean base deficit was 6 and arterial lactate was 9.0 mmol/L. An initial dose of rFVIIa was given intravenously, followed by a second dose if there was evidence of at least a partial response. Twelve of 15 patients who had been expected to die from hemorrhage survived for greater than 48 hours, and 7 survived to hospital discharge. A partial or complete hemostatic response to rFVIIa was noted in 12 of 15 patients. The number of blood products received after administration of rFVIIa was significantly reduced and the International Normalized Ratio (INR) decreased. Our experience demonstrates that rFVIIa may reduce or completely arrest coagulopathic bleeding in trauma and surgical patients after vascular control.     

Use of activated recombinant factor VII for severe coagulopathy post ventricular assist device or orthotopic heart transplant

Background  

Ventricular assist devices(VAD) implantation/removal is a complex surgical procedure with perioperative bleeding complications occurring in nearly half of the cases. Recombinant activated factor VII (rFVIIa) has been used off-label to control severe hemorrhage in surgery and trauma. We report here our experience with rFVIIa as a rescue therapy to achieve hemostasis in patients undergoing orthotopic heart transplant (OHT) and/or VAD implantation.     

Candida infection in massively burned patients

Immunosuppressed burned patients receiving antibiotics for suppression of bacterial infection are ideal hosts for opportunistic fungi. Massive excision of burns with autograft and homograft coverage has radically changed the course of disease. Three hundred ninety-three patients were admitted to the Shriners Burns Institute, of whom 125 patients had fungus cultured during their hospitalization and 42 patients subsequently developed involvement of three or more organs. Twenty-one of the 42 patients developed Candida septicemia requiring amphotericin B or flucytosine therapy. The mean third-degree burn in patients with Candida septicemia was 65% total body surface area compared to three-organ involvement/no clinical sepsis at 38% mean third-degree burn. Patients developing candidemia did so during the first week postburn and 7 days after excision therapy. It is hypothesized that massive burns with immunosuppression are further suppressed by repeated surgical intervention, anesthesia, and perioperative use of broad-spectrum antibiotics, further predisposing these patients to early development of Candida septicemia. With early recognition of burn wound invasion by routine biopsies, wound swabs, and early amphotericin therapy, the mortality has been reduced to 14% compared to 60-90% reported in other series.