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.     

复合微孔多聚糖止血粉在腹腔镜肾部分切除术中的应用

目的评价复合微孔多聚糖止血粉（MPH）在腹腔镜肾脏部分切除术中的安全性及有效性。 方法采用前瞻性研究,入组我院2014年至2018年期间收治的62例外向性生长肾肿瘤（CT直径3～4 cm）患者,均行腹腔镜肾部分切除术,将符合条件的患者随机分为MPH组（术中应用MPH止血）和对照组（常规止血）。对两组出血量、热缺血时间、止血时间、术后恢复情况进行比较。 结果两组患者热缺血时间及切除的肾脏组织重量差异无统计学意义（P>0.05）,MPH组在止血时间、出血量、术后住院时间、带管时间、引流量方面均小于对照组（P<0.05）。两组术后组间比较凝血功能差异无统计学意义。（P>0.05）。 结论MPH在腹腔镜肾部分切除术中的应用安全有效,为腹腔镜手术止血提供了一个有效的方法。     

Evaluation of microporous polysaccharide hemospheres as a novel hemostatic agent in open partial nephrectomy: favorable experimental results in the porcine model

PURPOSE: Microporous polysaccharide hemospheres (MPH, Medafor, Minneapolis, Minneapolis) are a novel hemostatic agent made from purified plant starch. MPH activates the clotting cascade and hyperconcentrates platelets and coagulation proteins, while enhancing a hemostatic plug. We evaluated the hemostatic efficacy of MPH compared with standard surgical technique in a porcine open partial nephrectomy model. MATERIALS AND METHODS: Standardized lower pole partial nephrectomy was consecutively performed in each kidney of 12 female pigs. Each pig was randomized to 2 groups, namely treatment with MPH application or control with the conventional surgical technique (oxidized cellulose with bolster sutures). The right kidney was harvested 1 half-hour after hemostasis was achieved and the left kidney was harvested after 7 days. RESULTS: Mean animal and resected renal tissue weight were comparable. Ischemic and hemostasis times were significantly decreased in the MPH treated group (2.67 and 4.67 minutes, respectively) vs the control group (8.33 and 7.75 minutes, respectively) (each p = 0.004). Blood loss was equivocal (0.88 gm in the treatment group vs 2.09 gm in the control group, p = 0.07). No hemostatic complications were noted in either group. No evidence of residual foreign material was found in the MPH group at 1 week. CONCLUSIONS: MPH provided rapid, effective and durable hemostasis in the porcine open partial nephrectomy model. Additional experimental and clinical evaluation is warranted to define the role of MPH assisted partial nephrectomy in humans.     

Recombinant factor VIIa (NovoSeven RT) use in high risk cardiac surgery

Objective: The use of recombinant factor VIIa (rFVIIa) (NovoSeven RT^®) to establish hemostasis during massive perioperative bleeding in cardiac surgery has been explored in several retrospective studies. While early results are promising, a paucity of data leaves many questions about its safety profile. We sought to further define its use and associated outcomes in a large cohort study at a single institution. Methods: A retrospective cohort study design was used, in which 236 patients received rFVIIa for bleeding after cardiac surgery. These patients were matched with a cohort of 213 subjects, who had similar operations during the same period of time. Primary end points included thrombo-embolic events, mortality, incidence of re-operation, use of blood products, and patient disposition at 30 days. Statistical significance was assessed at p < 0.05. Results: There was no statistically significant difference in the incidence of stroke (3.4%, 1.9%; p = 0.32), renal failure (8.5%, 7.0%; p = 0.57), or 30-day mortality (7.7%, 4.3%; p = 0.14) between the rFVIIa and the control groups, respectively. The rFVIIa group did experience a higher rate of re-operation for bleeding (11.0%, 1.9%; p = 0.0001) and had a two-fold increase in the use of each of the following: cryoprecipitate, fresh-frozen plasma, platelets, and packed red blood cells, relative to the control group (p < 0.00001). Conclusions: rFVIIa is an effective hemostatic agent for intractable bleeding in high-risk cardiac surgery with an acceptable safety profile. rFVIIa does not appear to be associated with increased postoperative complications, including thrombo-embolic events and death.     

Damage control management of experimental grade 5 renal injuries: further evaluation of FloSeal gelatin matrix

BACKGROUND: We developed a porcine grade 5 renal laceration damage control model to evaluate the hemostatic efficacy of FloSeal gelatin matrix (Baxter Healthcare, Corp., Deerfield, Ill). METHODS: Ten commercial swine underwent celiotomy, contralateral nephrectomy, and cooling to 32 degrees C after a well-established hypothermia protocol to simulate a damage control scenario. Following prospective randomization, a complex grade 5 renal injury was uniformly produced on the remaining kidney. Control animals (group 1, n = 5) were treated with direct manual compression with a gelatin sponge. Experimental animals (group 2, n = 5) were treated by application of FloSeal gelatin matrix followed by direct compression with a gelatin sponge. Operative blood loss and efficacy of hemostasis were compared. Creatinine levels were obtained daily until postoperative day 7. Abdominal computed tomography was performed at 10 days. RESULTS: Use of FloSeal gelatin matrix hemostatic sealant resulted in significantly less mean blood loss than gelatin sponge bolster compression alone (202.4 mL vs. 540.4 mL, respectively, p = 0.016). Hemostasis was complete in 60% (three out of five) of experimental animals after 2 minutes, but was incomplete in all control animals. After an initial increase, serum creatinine approached baseline by postoperative day 7 in all animals. Axial imaging 10 days postoperatively revealed no evidence of significant delayed perirenal hemorrhage. CONCLUSIONS: FloSeal gelatin matrix performed well as a rapidly deployable, effective hemostatic agent in a hypothermic grade 5 renal injury damage control model. The absence of delayed bleeding and nephrotoxicity suggests a possible increased role for FloSeal in the treatment of devastating renal injuries in damage control surgery.     

Microporous polysaccharide hemospheres for management of laparoscopic trocar injury to the spleen

BACKGROUND: Management of iatrogenic injuries during laparoscopy can be arduous. Recent advancements in surgical hemostatic agents have provided beneficial therapeutic alternatives. This project evaluates microporous polysaccharide hemospheres (MPH), with demonstrated efficiency achieving topical hemostasis, in the setting of intracorporeal laparoscopic splenic injury. METHODS: Four domestic female pigs were subjected to reproducible laparoscopic 12-mm and 5-mm trocar splenic injuries. Each surgery was an identical transperitoneal hand-assisted laparoscopic procedure. Hemostasis, or no bleeding after treatment, was achieved by measured dose applications of MPH. RESULTS: The MPH successfully achieved hemostasis for all splenic injuries except in 1 case, where a 12-mm lesion transected the splenic artery. The mean time to hemostasis, applications of MPH, and estimated blood loss for the 5- and 12-mm injuries were 165.3 +/- 45.7 and 200.7 +/- 106.5 seconds, 1.3 +/- .5 applications for both, and 12.0 +/- 4.6 and 17.7 +/- 9.1 g, respectively. CONCLUSIONS: MPH represents a powerful hemostatic agent that demonstrated complete hemostasis for iatrogenic splenic injury.     

The effect of recombinant factor VIIa on coagulopathic pigs with grade V liver injuries

BACKGROUND: Recombinant factor VIIa (rFVIIa) has been used to decrease bleeding in a number of settings including hemophilia, liver transplantation, intractable bleeding, and cirrhosis. Experience in the trauma setting is limited. This study was performed to determine whether rFVIIa would reduce bleeding after a grade V liver injury in hypothermic, dilutionally coagulopathic pigs when used as an adjunct to abdominal packing and to determine whether increasing the dose of the drug increased its hemostatic efficacy. METHODS: Thirty animals were randomized to receive 180 microg/kg of rFVIIa, 720 microg/kg of rFVIIa, or vehicle buffer control. After laparotomy and splenectomy, animals underwent a 60% blood volume isovolemic exchange transfusion with 5% human albumin. The animals' temperature was maintained at 33 degrees C and a standardized grade V liver injury was made with a liver clamp. Thirty seconds after injury, the abdomen was packed with laparotomy sponges, resuscitation was initiated, and blinded therapy was given. Animals were resuscitated to their baseline mean arterial pressure and the study was continued for 2 hours. Serial coagulation parameters were measured at the temperature they were drawn. After the study period, surviving animals were killed, posttreatment blood loss was measured, and an autopsy was performed. RESULTS: Ten animals were randomized to each group. After administration of study drug, factor VII clotting activity (FVII:C) was higher in the 720 microg/kg group than in the 180 microg/kg group (p < 0.01). FVII:C was higher in both treatment groups than in the control group (p < 0.01). The mean prothrombin time was shorter in the treatment groups than in the control group (p < 0.05). Mean arterial pressure was lower in the control group than in the treatment groups throughout the study (p < 0.01). Mean blood loss was less in the treatment groups than in the control group (p = 0.03). Mortality was not different between groups. There were no differences between the groups that received rFVIIa in any measured parameters except for FVII:C. Liver injuries were similar between groups and there was no evidence of microthrombosis on lung histology. CONCLUSION: rFVIIa reduces blood loss in hypothermic, dilutionally coagulopathic pigs with grade V injuries when used as an adjunct to packing. Increasing the dose does not enhance the hemostatic effect.     

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.     

Controlled clinical trial of a novel hemostatic agent in cardiac surgery. The Fusion Matrix Study Group

BACKGROUND: We performed a prospective randomized trial to compare FloSeal Matrix (Fusion Medical Technologies, Inc, Mountain View, CA), a gelatin-based hemostatic sealant, with Gelfoam-Thrombin (Gelfoam, Pharmacia and Upjohn, Kalamazoo, MI; Thrombin, Gentrac Inc, Middeton, WI) (control group) to control perioperative bleeding. METHODS: A total of 93 patients undergoing cardiac operations were randomized into the FloSeal or control group after standard surgical means to control bleeding had failed. The bleeding site was evaluated at 1, 2, 3, 6, and 10 minutes after applying the hemostatic agent. If bleeding stopped within 10 minutes, the application was considered to be successful. In the case of a failure, the surgeon could use any means preferred (except FloSeal) to achieve hemostasis. All bleeding sites in a patient were treated with the hemostatic agent to which the patient was randomized. Follow-up evaluation was performed at 12 to 36 hours and 6 to 8 weeks after operation. RESULTS: FloSeal stopped bleeding in 94% of the patients (first bleeding site only) within 10 minutes, compared to 60% in the control group (p = 0.001). At 3 minutes, successful hemostasis was achieved in 72% of the FloSeal group compared with 23% in the control group (p = 0.0001). There was no difference in the adverse event profile between the two groups. CONCLUSIONS: FloSeal Matrix demonstrated efficacy superior to that of Gelfoam-Thrombin and had a safety profile similar to that of Gelfoam-Thrombin when used as a topical hemostatic agent during cardiac surgery procedures.     

A multicenter, prospective, randomized trial evaluating a new hemostatic agent for spinal surgery

STUDY DESIGN: A prospective, randomized trial comparing Proceed, a gelatin-based hemostatic sealant (treatment), with Gelfoam-thrombin (control) in stopping intraoperative bleeding during spinal surgery. OBJECTIVES: To determine the effectiveness and safety of Proceed. SUMMARY OF BACKGROUND DATA: Proceed has been tested in animal models to determine its safety and effectiveness as a hemostatic agent. The current study was conducted under a Food and Drug Administration-approved Investigational Device Exemption to evaluate the effectiveness and safety of Proceed in humans. METHODS: For this study, 127 patients undergoing spinal surgery were randomized into either the treatment or control group after standard surgical means to control bleeding had failed. The bleeding site was evaluated at 1, 2, 3, 6, and 10 minutes after the hemostatic agent was applied. The application was considered successful if the bleeding stopped within 10 minutes. Follow-up evaluation was performed at 12 to 36 hours, then at 6 to 8 weeks after surgery. RESULTS: Proceed stopped bleeding in 98% of the patients (first bleeding site only) within 10 minutes, as compared with 90% of the control patients (P = 0.001). At 3 minutes, successful hemostasis had been achieved in 97% of the Proceed group, as compared with 71% of the control group (P = 0.0001). There was no difference in the adverse event profile between the two groups. CONCLUSIONS: A significantly larger number of bleeding sites had achieved hemostasis with Proceed than with Gelfoam-thrombin at 1, 2, and 3 minutes after application. Proceed was as safe as Gelfoam-thrombin when used for hemostasis during spinal surgery procedures.     

Hemostatic efficacy of two advanced dressings in an aortic hemorrhage model in Swine

BACKGROUND: An effective hemostatic agent capable of stopping severe arterial bleeding and sustaining hemostasis over a prolonged time is required. The U.S. Army recently distributed fibrin sealant (under an Investigational New Drug-approved protocol) and chitosan dressings among deployed medics for treating severe external hemorrhage on the battlefield. The purpose of this study was to evaluate the efficacy of these dressings, as compared with the standard gauze army field dressing, to provide initial and sustained hemostasis up to 96 hours in a lethal uncontrolled arterial hemorrhage model. METHODS: Anesthetized pigs were splenectomized and chronically instrumented for fluid/drug administration and continuous monitoring of vital signs. An infrarenal aortotomy was created using a 4.4-mm aortic hole punch and free bleeding was allowed for 5 seconds. While bleeding profusely, a dressing was applied and pressed into the wound for 4 minutes (occluding the distal flow) and then released. If hemostasis was not obtained, the dressing was replaced with a new one (maximum, two dressings per experiment) with another 4-minute compression. If hemostasis was achieved, the abdomen was closed; the animal was then recovered and monitored up to 96 hours. Initial hemostasis, duration of hemostasis, survival time, blood loss, and other variables were measured. RESULTS: Application of army field dressing (gauze) did not stop the arterial hemorrhage and led to exsanguination of all the pigs (n = 6) within 10 to 15 minutes of the injury. Chitosan dressing produced initial hemostasis in five of seven pigs. However, the dressings failed to maintain hemostasis for more than 1.6 hours (range, 28-102 minutes), resulting in secondary bleeding and death of the animals. Fibrin sealant dressing produced initial hemostasis in all the pigs (n = 6) and maintained hemostasis in five cases, with one failure at 2.2 hours. These pigs resumed normal activities and lived for the 96-hour experiment duration. Computed tomographic images and histologic sections of the aortas from surviving fibrin sealant dressing-treated animals showed formation of pseudoaneurysms and early granulation tissue at the aortotomy site. The posttreatment blood loss, duration of hemostasis, and survival time were significantly different in the fibrin sealant dressing group than the chitosan dressing and army field dressing groups. CONCLUSION: Both chitosan dressing and fibrin sealant dressing stopped initial arterial bleeding that could not be controlled by the standard army field dressing. However, although the fibrin sealant dressing secured hemostasis for up to 4 days, the chitosan dressing consistently failed within 2 hours after application. There may be a risk of rebleeding for high-pressure arterial wounds treated with chitosan dressings, particularly in situations where definitive care is delayed substantially.     

Recombinant activated factor VII decreases bleeding without increasing arterial thrombosis in rabbits

PURPOSE: To compare the effects of recombinant activated factor VII (rFVIIa) and platelet-rich plasma (PRP) in an experimental model of bleeding and arterial thrombosis. METHODS: The Folts model was used in 60 rabbits. After anesthesia, the carotid artery was exposed and a 75% stenosis was induced. A compression injury of the artery triggered a series of cyclic flow reductions (CFRs). After counting baseline CFRs, animals were assigned randomly to one of four groups (n = 15 in each): control, PRP, rFVIIa and placebo. Control animals received 10 mL.kg(-1) of saline while 10 mL.kg(-1) of a hydroxyethyl starch solution (200,000/6%/0.5) were infused in the three other groups. CFRs were measured again, followed by treatment with PRP, rFVIIa or placebo and by a final measurement of CFRs. At the end of each observation period, an ear immersion bleeding time (BT) was measured and a blood sample was drawn for the evaluation of hematological variables. Microvascular bleeding was evaluated at the end of the experiment in grams of blood shed from liver and spleen sections. Results are presented as median (range). RESULTS: rFVIIa shortened the BT and decreased microvascular bleeding as compared with placebo [60 (35-100) sec vs 110 (50-140) sec, P = 0.0019 and 9 (4-24) g vs 17 (5-28) g, P = 0.002, respectively]. rFVIIa did not increase CFRs [3(0-9) vs |(0-5), P = 0.11]. CONCLUSION: rFVIIa led to a decrease in BT and microvascular bleeding but did not significantly affect arterial thrombosis in rabbits.     

Control of bone bleeding at the sternum and iliac crest donor sites using a collagen-based composite combined with autologous plasma: results of a randomized controlled trial

In a randomized controlled trial, hemostatic effectiveness of a collagen-based composite (experimental group) was compared with standard hemostatic methods (ie, electrocautery and collagen sponge) (control group) at two bone sites. Hemostatic success, time to "controlled bleeding," and time to "complete hemostasis" were determined at the sternal edge following median sternotomy (n=64) and at the iliac crest following bone graft harvest (n=19). Almost twice the percentage of sternal edge patients (83% versus 44%, P=.002) and nearly three times the percentage of iliac crest patients (83% versus 29%, P<.05) achieved complete hemostasis in the experimental group compared to controls. Time to controlled bleeding and complete hemostasis for all bone sites also favored the experimental group over the control group at highly significant levels (P<.0001 for most comparisons). There were no adverse events related to experimental treatment use. The results support the use of this investigational hemostatic agent to control cancellous bone bleeding.     

Acute coagulopathy after reperfusion of the liver graft in children correction with recombinant activated factor VII

BACKGROUND: Several studies have proven that massive blood loss increases postoperative morbidity and mortality in liver graft recipients. Since we have successfully corrected coagulopathy preoperatively using an intravenous (IV) bolus of recombinant activated factor VII (rFVIIa) in 2 patients with fulminant liver failure, we observed that there was rapid reversal of preexisting advanced coagulopathy in another 40 patients with high risk for intraoperative bleeding by this treatment immediately before transplantation. Recently to control hemostasis we have administered rFVIIa also to patients presenting with acute coagulopathy and nonsurgical bleeding after graft reperfusion as described herein. MATERIALS AND METHODS: We have used rFVIIa in 7 children presenting with severe coagulopathy and nonsurgical bleeding after liver graft reperfusion. The dosage of rFVIIa ranged between 37 and 148 mcg/kg. An antifibrinolytic agent (aprotinin, tranexamic acid) was administered simultaneously. RESULTS: APTT before rFVIIa was 86.10 to 183 seconds, (mean, 132.1 +/- 39.88), after the bolus of rFVIIa 49.4 to 206.1 (mean, 112.7 +/- 58.53), and at the end of surgery 71.70 to 180 (mean, 110.3 +/- 40.98). INR after reperfusion was 1.82 to 3.91 (mean, 2.56 +/- 0.67), 1.03 to 1.92 (mean, 1.54 +/- 0.35) after rFVIIa, and 1.74 to 5.58 (mean, 2.64 +/- 1.35) at the end of surgery. Before rFVIIa administration intraoperative blood transfusions after graft reperfusion were 900 to 4200 mL of red blood cells (RBC) (0.82-5.4 total blood volume) and after reperfusion 0 to 1800 mL of RBC (0-2.5 TBV). No postoperative vascular complications were observed. CONCLUSIONS: A single dose of rFVIIa effectively reverses the severe coagulopathy developing after graft reperfusion, establishing effective hemostasis in liver transplant recipients without an increased risk of thrombotic complications.     

Evaluation of microporous polysaccharide hemospheres for parenchymal hemostasis during laparoscopic partial nephrectomy in the porcine model.

OBJECTIVES: We evaluated the efficacy of Microporous Polysaccharide Hemospheres (MPH) for parenchymal hemostasis during laparoscopic partial nephrectomy (LPN) in the porcine model. METHODS: Six female farm pigs underwent a transperitoneal right lower-pole LPN during occlusion of the renal hilum. Renal parenchyma was excised using cold Endoshears. MPH was applied to the defect and the hilar clamp released. Animals were kept alive for one week. Before sacrifice, left LPN was similarly performed using MPH. Study variables included blood loss, number of MPH applications, hilar clamp time, hemostasis time, perioperative complications, and abnormalities noted at sacrifice. RESULTS: Hemostasis was achieved in all kidneys solely by using MPH. The average excised specimen represented 5.6% (range, 3.6 to 8.5) of renal weight. Mean hilar clamp and hemostatic times were 12.8 minutes (range, 6 to 18) and 2 minutes (range, 1 to 3), respectively. Hemostasis occurred after one MPH application in 8 kidneys (67%). In 3 kidneys, additional MPH powder was required to treat minor residual bleeding. In the remaining kidney, a second standard MPH application was required for hemostasis. No operative complications were encountered. No hematomas or residual MPH was found at necropsy; however, small urinomas were found in 2 of 6 kidneys. CONCLUSIONS: In the experimental porcine model, this initial study suggests that MPH provides effective parenchymal hemostasis during laparoscopic resection of an exophytic kidney lesion.     

A novel hemostatic agent: the potential role of recombinant activated factor VII (rFVIIa) in anesthetic practice.

PURPOSE: To review the role of recombinant factor VIIa in anesthetic practice. SOURCE: A review of the published literature. MAIN FINDINGS: The mechanism of action of rFVIIa suggests enhancement of hemostasis limited to the site of injury without systemic activation of the coagulation cascade. In addition to its indication for use in patients with hemophilia, use of rFVIIa for treatment of uncontrolled massive hemorrhage in various peroperative settings appears to be rational, safe, and effective. Published results suggest that in trauma patients rFVIIa may play a role as an adjunctive hemostatic measure in addition to surgical hemostatic techniques There is preliminary evidence that hemorrhagic complications (eg. epistaxis, vaginal bleeding) associated with profound thrombocytopenia can be reversed with rFVIIa even at platelet counts below 10,000 per microL. Various case reports outlining the successful treatment with recombinant factor VIIa of patents experiencing intractable bleeding after valve replacement surgery, and with severe hemorrhage during therapy with left ventricular assist device, indicate the potential therapeutic efficacy of this agent in cardiac surgical procedures. Additionally, rFVIIa has been used successfully for treatment of massive postoperative bleeding following general surgery. CONCLUSIONS: rFVIIa is a novel hemostatic agent that shows promise in non-hemophiliac patents of a significant therapeutic role in variety of coagulopathic and hemorrhagic conditions in clinical situations ranging from thrombocytopenia, disseminated intravascular coagulation and transfusion-related coagulopathy, as well as in patients experiencing massive blood loss undergoing orthotopic liver transplantation, cardiac, orthopedic and genitourinary surgery.     

Prospective, randomized, controlled clinical trial of a novel matrix hemostatic sealant in children undergoing adenoidectomy.

PROBLEM ADDRESSED: Floseal is a novel matrix hemostatic sealant composed of collagen-derived particles and topical bovine-derived thrombin. It is applied as a high-viscosity gel for hemostasis and has been clinically proven to control bleeding. This study is a prospective, randomized, controlled clinical trial of Floseal sealant compared to traditional suction cautery hemostasis in children undergoing adenoidectomy. METHODS AND MEASURES: Seventy patients (mean age 7.0 yrs, 45.7% male) with obstructive sleep apnea underwent traditional cold steel adenoidectomy with an adenoid curette and were then randomized to receive the hemostatic sealant (Floseal) or cautery to obtain hemostasis. Patients were crossed over to the other hemostatic technique if hemostasis was not achieved after more than 100 mL of blood loss or 15 minutes elapsed time. Objective data collected included time to hemostasis and blood loss during hemostasis. Visual analog scales (VAS) were used to record subjective data by the operating surgeon including bleeding following adenoid pack removal (0 = none, 3 = brisk) and ease of operation (1 = extremely easy, 6 = extremely difficult). Parents recorded diet on a journal and were contacted by phone at postoperative day 7 and questioned with regard to return to regular diet and use of narcotics. RESULTS: Compared to patients in the cautery group (n = 35), Floseal patients (n = 35) had significantly shorter times to hemostasis (0.6 +/- 1.3 minutes vs 9.5 +/- 5.4 minutes [mean +/- SD], P < 0.001), less blood loss (2.5 +/- 9.2 mL vs 29.4 +/- 27.1 mL, P < 0.001), less subjective bleeding (0.0 +/- 0.6 vs 2.0 +/- 0.7, [median 4-point VAS +/- SD], P < 0.001), and subjectively easier operations (2.6 +/- 1.0 vs 5.2 +/- 1.0 [mean 6-point VAS +/- SD], P < 0.001). Furthermore, Floseal patients returned to regular diet earlier (2.7 +/- 0.7 vs 4.1 +/- 0.5 days [mean +/- SD], P < 0.001) and had less use of narcotics at 7 days postoperatively (40% vs 69%, P < 0.05). Lastly, three patients in the cautery group were crossed over to the Floseal group, but no Floseal subjects were crossed over to the cautery group. The retail cost of Floseal is US 85 dollars. Operating room costs are estimated at US 12 dollars/minute. Reducing the operative length by 8.9 minutes on average produces a cost savings of US 106.80 dollars per operation. There were no complications in either experimental group including postoperative hemorrhage, hospitalization, blood transfusion, or aspiration. CONCLUSIONS: Floseal matrix hemostatic sealant is a safe, efficacious, easy, and cost-effective technique for obtaining hemostasis in children undergoing adenoidectomy. Limitations of the study include the fact that it is nonblinded, which does allow for some bias in the subjective data recorded. However, utilizing 4 different operating surgeons, 3 of whom were not affiliated with the study, minimized this. CLINICAL SIGNIFICANCE OF STUDY: This study demonstrates the safety and efficacy of a novel hemostatic sealant in children undergoing adenoidectomy. Floseal matrix hemostatic sealant can be used as a first-line hemostatic agent, and it is a good tool in the armamentarium of otolaryngologists who encounter significant bleeding following adenoidectomy.     

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.     

Activated recombinant factor VII in orthotopic liver transplantation

Orthotopic liver transplantation (OLT) is affected by important alterations of hemostasis. The aim of this study was to evaluate the efficacy of recombinant factor VII activated (rFVIIa) to reduce intraoperative bleeding during OLT. METHODS: Twenty OLT patients were assigned in double-blind way to a rFVIIa group or a control group. Inclusion criteria were hemoglobin > 8 g/dL: INR > 1,5 and fibrinogen > 100 mg/dL. We administered a single bouls of rFVIIa (40 microg/kg) or placebo. We determined INR, partial thromboplastin time, fibrinogen, ATIII, and blood cell counts. Blood products were administered as follows: 4 units of fresh frozen plasma when INR > 1.5, and 1 unit of RBC for Hb < 10 g/dL. The study ended 6 hours after the bolus. RESULTS: No thromboembolic events occurred. The INR was different between rFVIIa group and the controls at T0 (1.9 vs 1.6 P < .021) and during T1 (1.2 vs 1.6 P < .004). The total transfused red blood cells was 300 mL +/- 133 in rFVIIa group and 570 mL +/- 111 in control group (P < .017). The total fresh frozen plasma was 600 mL +/- 154 in rFVIIa group and 1400 mL +/- 187 in control group (P < .001). Total blood loss was greater in the control group than the rFVIIa group: 1140 mL +/- 112 vs 740 mL +/- 131 (P < .049). DISCUSSION: The use of rFVIIa during OLT can reduce the risk of bleeding during surgery. The literature has described cases who did not benefit from the treatment. An adequate cut-off of INR, allowed us to treat only patients at greater bleeding risk.     

A pilot study evaluating the efficacy of a fully acetylated poly-N-acetyl glucosamine membrane formulation as a topical hemostatic agent.

BACKGROUND: Topical hemostatic agents are frequently needed for control of intraoperative bleeding. Currently available topical products each have potential drawbacks, making a more effective topical hemostatic agent desirable. This study was performed to evaluate the effectiveness of a particular formulation of a newly available polysaccharide polymer, poly-N-acetyl glucosamine (p-GlcNAc), as a topical hemostatic agent for use in the operating room. Swine splenic incision and splenic capsular stripping hemorrhage models were initially used, with a subsequent pilot human study then performed. METHODS: For the swine splenic incision model, anesthetized immature female Yorkshire white swine had a 3 x 8 mm incision created on the spleen. One of 3 agents (p-GlcNAc membrane, oxidized cellulose, or absorbable collagen) was sequentially applied to individual wounds and digitally compressed for 20 seconds. The wound was observed without pressure for 2 minutes. Up to 8 wounds per animal were created in 7 animals. For the swine splenic capsular stripping model a 2 x 2 cm area of capsular stripping on the surface of the spleen to a depth of 3 mm was created. Either p-GlcNAc membrane or oxidized cellulose was applied and digitally compressed for 60 seconds, followed by observation without pressure for 2 minutes. Six wounds per animal were created in 2 animals. If bleeding persisted in either model, a new cycle of compression was applied. These steps were repeated until hemostasis was achieved. No change in hemodynamics or coagulation factors was observed in either model. Subsequently, 10 consecutive patients undergoing elective small-bowel surgery were enrolled on pilot study. A 5 x 3 x 3 mm cruciate incision was created midway between the mesenteric and antimesenteric borders of the small bowel. Either p-GlcNAc membrane formulation or oxidized cellulose was applied (the sequence alternated per patient) with a 400-mg weight used for even, direct pressure. A second cruciate incision was then created on the contralateral side of the bowel to evaluate the second material. The number of applications required for hemostasis was assessed. Hemodynamics, small-bowel pathologic condition, and hematologic parameters were evaluated. RESULTS: The p-GlcNAc membrane required fewer cycles of compression in the swine splenic incision model to achieve hemostasis than either absorbable collagen or oxidized cellulose (1.25 vs 2.58 and 3.41, respectively; P < .01) and caused more effective immediate cessation of bleeding (79% for p-GlcNAc vs 17% for both absorbable collagen and oxidized cellulose). With the more traumatic splenic capsular stripping model, p-GlcNAc required fewer cycles of compression to achieve hemostasis than oxidized cellulose (average, 2.5 versus 6.8 respectively; P < .01) and was able to achieve hemostasis with greater efficacy (50%) in 2 applications than did oxidized cellulose (0%; P < .01). When used in the human pilot study, p-GlcNAc membranes required fewer cycles of compression than oxidized cellulose (2.5 vs 5.4, respectively; P < .002), was able to stop bleeding with greater efficacy in 1 cycle of compression (50% vs 0%, respectively; P < .01), and ultimately accomplished hemostasis in 80% of the cases as opposed to 20%. CONCLUSIONS: On the basis of its greater hemostatic efficacy as compared with collagen or oxidized cellulose-based products, p-GlcNAc holds promise as an effective topical hemostatic agent and deserves further evaluation.