Background and Purpose - Hematoma growth occurs in 38% of intracerebral hemorrhage (ICH) patients scanned by computed tomography (CT) within 3 hours of onset. Activated recombinant factor VII (rFVIIa) promotes hemosta...Background and Purpose - Hematoma growth occurs in 38% of intracerebral hemorrhage (ICH) patients scanned by computed tomography (CT) within 3 hours of onset. Activated recombinant factor VII (rFVIIa) promotes hemostasis at sites of vascular injury and may minimize hematoma growth after ICH. Methods - In this randomized, double- blind, placebo- controlled, dose- escalation trial, 48 subjects with ICH diagnosed within 3 hours of onset were treated with placebo (n= 12) or rFVIIa (10, 20, 40, 80, 120, or 160 μ g/kg; n=6 per group). The primary endpoint was the frequency of adverse events (AEs). Safety assessments included serial electrocardiography (ECG), troponin I and coagulation testing, lower extremity Doppler ultrasonography, and calculation of edema:ICH volume ratios. Results - Mean age was 61 years (range, 30 to 93) and 57% were male. At admission, mean National Institutes of Health Stroke Scale (NIHSS) score was 14 (range, 1 to 26), median Glasgow Coma Scale score was 14 (range, 6 to 15), and mean ICH volume was 21 mL (range, 1 to 151). Mean time from onset to treatment was 181 minutes (range, 120 to 265). Twelve serious AEs occurred, including 5 deaths (mortality 11% ). Six AEs were considered possibly treatment- related, including rash, vomiting, fever, ECG T- wave inversion, and 2 cases of deep vein thrombosis (placebo and 20- μ g/kg groups). No myocardial ischemia, consumption coagulopathy, or dose- related increase in edema:ICH volume occurred. Conclusion - This small phase II trial evaluated a wide range of rFVIIa doses in acute ICH and raised no major safety concerns. Larger studies are justified to determine whether rFVIIa can safely and effectively limit ICH growth.展开更多
Background &Aims:Upper gastrointestinal bleeding (UGIB)is a severe and frequent complication of cirrhosis. Recombinant coagulation factor VIIa (rFVIIa) has been shown to correct the prolonged prothrombin time in p...Background &Aims:Upper gastrointestinal bleeding (UGIB)is a severe and frequent complication of cirrhosis. Recombinant coagulation factor VIIa (rFVIIa) has been shown to correct the prolonged prothrombin time in patients with cirrhosis and UGIB. This trial aimed to determine efficacy and safety of rFVIIa in cirrhotic patients with variceal and nonvariceal UGIB. Methods: A total of 245 cirrhotic patients (Child Pugh <13; Child Pugh A = 20%, B = 52%, C = 28%) with UGIB (variceal = 66%, nonvariceal = 29%, bleeding source unknown = 5%) were randomized equally to receive 8 doses of 100 μg/kg rFVIIa or placebo in addition to pharmacologic and endoscopic treatment. The primary end point was a composite including: (1) failure to control UGIB within 24 hours after first dose, or (2) failure to prevent rebleeding between 24 hours and day 5, or (3) death within 5 days. Results: Baseline characteristics were similar between rFVIIa and placebo groups. rFVIIa showed no advantage over standard treatment in the whole trial population. Exploratory analyses, however, showed that rFVIIa significantly decreased the number of failures on the composite end point (P = 0.03) and the 24 hour bleeding control end point (P = 0.01) in the subgroup of Child Pugh B and C variceal bleeders. There were no significant differences between rFVIIa and placebo groups in mortality (5 or 42 day) or incidence of adverse events including thromboembolic events. Conclusions: Although no overall effect of rFVIIa was observed, exploratory analyses in Child Pugh B and C cirrhotic patients indicated that administration of rFVIIa significantly decreased the proportion of patients who failed to control variceal bleeding. Dosing with rFVIIa appeared safe. Further studies are needed to verify these findings.展开更多
To editor:Factor VII(FVII)is a determining factor in activating the exogenous coagulation pathway;F7 gene mutation decreases the FVII number or function.Factor VII deficiency(FVIID)is characterized by an isolated prol...To editor:Factor VII(FVII)is a determining factor in activating the exogenous coagulation pathway;F7 gene mutation decreases the FVII number or function.Factor VII deficiency(FVIID)is characterized by an isolated prolongation of the prothrombin time(PT)with a normal activated partial thromboplastin time(aPTT).Factor assay and genotyping for FVII can be done to confirm the diagnosis.1,2 Patients may present with menorrhagia,and bleeding tendencies may vary from slight gingival bleeding,epistaxis,and ecchymosis,to severe bleeding,such as gastrointestinal and intracranial bleeding.展开更多
Objective: To identify current treatment strategies for postpartum hemorrhage used by obstetricians (OB/GYNs) and hematologists (HEMs). Study Design: We conducted a survey of OB/GYNs (n = 220) and HEMs (n = 30) to des...Objective: To identify current treatment strategies for postpartum hemorrhage used by obstetricians (OB/GYNs) and hematologists (HEMs). Study Design: We conducted a survey of OB/GYNs (n = 220) and HEMs (n = 30) to describe the characteristics of current treatment strategies for postpartum hemorrhage. Surveys were administered via a structured questionnaire on a secure internet website from 5 - 12 October 2009. Results: The majority of OB/GYN and HEM respondents were practicing in a community hospital environment (77%). Of the OB/GYNs, the majority practiced at hospitals with over 2000 deliveries per year (77%). A majority (58%) of OB/GYNs were affiliated with hospitals that lacked a massive transfusion protocol to treat severe postpartum hemorrhage. Subsequent to uterine massage and additional oxytocin, the majority of OB/GYNs (73%), preferred the administration of Methergine? as the next level of intervention for postpartum hemorrhage. There was considerable variability in response to specific treatment strategies for several hypothetical case scenarios;however, the large majority of OB/GYNs favored obstetrical procedures over interventional radiology or administration of rFVIIa. A large majority (77%) of physicians who are familiar with rRVIIa as treatment for postpartum hemorrhage reported being very satisfied with the agent for this indication. Conclusions: An established, systematic treatment strategy among OB/GYNs emerged only in the case of mild postpartum hemorrhage.展开更多
Hemophagocytic lymphohistiocytosis （HLH） is a lifethreatening disorder due to hyperinflammation resulting in infiltration of different organs with extensive hemophagocytosis. Severe coagulopathy was one of the main ...Hemophagocytic lymphohistiocytosis （HLH） is a lifethreatening disorder due to hyperinflammation resulting in infiltration of different organs with extensive hemophagocytosis. Severe coagulopathy was one of the main reasons for death in HLH. Over secretion of plasminogen activator by activated macrophages leads to hyperfibrinolysis. We reported a 36-year-old woman who was diagnosed as HLH probably secondary to lymphoma. Massive bleeding from gut and retroperitoneal area were not able to be controlled by conventional hemostatic treatments. This patient received one dose recombinant activated factor Ⅶ （rFVlla） 3.6 mg （70 μg/kg）. Hemostatic effect was achieved in 0.5 hour and lasted 24 hours. Prothrombin time （PT） and activated partial thromboplastin time （APTT） were quickly corrected to normal ranges.Fibrinogen level elevated from 0.5 g/L before using rFVIla to 1.8 g/L 20 hours after. Although dexamethasone and etopside were administrated to treat HLH, this patient died from septic shock after persistent neutropenia. This suggests that rFVlla may be effective in the management of intractable hemorrhage in patients with HLH.展开更多
Recombinant factor VIIa(rFVIIa) is a new drug to prevent and control the hemorrhagic episode in certain patients.The rFVIIa is one type of recombinant protein,which gene is cloned and expressed in baby hamster kidney ...Recombinant factor VIIa(rFVIIa) is a new drug to prevent and control the hemorrhagic episode in certain patients.The rFVIIa is one type of recombinant protein,which gene is cloned and expressed in baby hamster kidney cells,and it can efficiently prevent the hemorrhage in liver transplantation without an increased risk of thrombotic complications.It also can be used in heart surgery and other operation to prevent the hemorrhage.This review will discuss its mechanism and application in liver transplantation.展开更多
文摘Background and Purpose - Hematoma growth occurs in 38% of intracerebral hemorrhage (ICH) patients scanned by computed tomography (CT) within 3 hours of onset. Activated recombinant factor VII (rFVIIa) promotes hemostasis at sites of vascular injury and may minimize hematoma growth after ICH. Methods - In this randomized, double- blind, placebo- controlled, dose- escalation trial, 48 subjects with ICH diagnosed within 3 hours of onset were treated with placebo (n= 12) or rFVIIa (10, 20, 40, 80, 120, or 160 μ g/kg; n=6 per group). The primary endpoint was the frequency of adverse events (AEs). Safety assessments included serial electrocardiography (ECG), troponin I and coagulation testing, lower extremity Doppler ultrasonography, and calculation of edema:ICH volume ratios. Results - Mean age was 61 years (range, 30 to 93) and 57% were male. At admission, mean National Institutes of Health Stroke Scale (NIHSS) score was 14 (range, 1 to 26), median Glasgow Coma Scale score was 14 (range, 6 to 15), and mean ICH volume was 21 mL (range, 1 to 151). Mean time from onset to treatment was 181 minutes (range, 120 to 265). Twelve serious AEs occurred, including 5 deaths (mortality 11% ). Six AEs were considered possibly treatment- related, including rash, vomiting, fever, ECG T- wave inversion, and 2 cases of deep vein thrombosis (placebo and 20- μ g/kg groups). No myocardial ischemia, consumption coagulopathy, or dose- related increase in edema:ICH volume occurred. Conclusion - This small phase II trial evaluated a wide range of rFVIIa doses in acute ICH and raised no major safety concerns. Larger studies are justified to determine whether rFVIIa can safely and effectively limit ICH growth.
文摘Background &Aims:Upper gastrointestinal bleeding (UGIB)is a severe and frequent complication of cirrhosis. Recombinant coagulation factor VIIa (rFVIIa) has been shown to correct the prolonged prothrombin time in patients with cirrhosis and UGIB. This trial aimed to determine efficacy and safety of rFVIIa in cirrhotic patients with variceal and nonvariceal UGIB. Methods: A total of 245 cirrhotic patients (Child Pugh <13; Child Pugh A = 20%, B = 52%, C = 28%) with UGIB (variceal = 66%, nonvariceal = 29%, bleeding source unknown = 5%) were randomized equally to receive 8 doses of 100 μg/kg rFVIIa or placebo in addition to pharmacologic and endoscopic treatment. The primary end point was a composite including: (1) failure to control UGIB within 24 hours after first dose, or (2) failure to prevent rebleeding between 24 hours and day 5, or (3) death within 5 days. Results: Baseline characteristics were similar between rFVIIa and placebo groups. rFVIIa showed no advantage over standard treatment in the whole trial population. Exploratory analyses, however, showed that rFVIIa significantly decreased the number of failures on the composite end point (P = 0.03) and the 24 hour bleeding control end point (P = 0.01) in the subgroup of Child Pugh B and C variceal bleeders. There were no significant differences between rFVIIa and placebo groups in mortality (5 or 42 day) or incidence of adverse events including thromboembolic events. Conclusions: Although no overall effect of rFVIIa was observed, exploratory analyses in Child Pugh B and C cirrhotic patients indicated that administration of rFVIIa significantly decreased the proportion of patients who failed to control variceal bleeding. Dosing with rFVIIa appeared safe. Further studies are needed to verify these findings.
文摘To editor:Factor VII(FVII)is a determining factor in activating the exogenous coagulation pathway;F7 gene mutation decreases the FVII number or function.Factor VII deficiency(FVIID)is characterized by an isolated prolongation of the prothrombin time(PT)with a normal activated partial thromboplastin time(aPTT).Factor assay and genotyping for FVII can be done to confirm the diagnosis.1,2 Patients may present with menorrhagia,and bleeding tendencies may vary from slight gingival bleeding,epistaxis,and ecchymosis,to severe bleeding,such as gastrointestinal and intracranial bleeding.
文摘Objective: To identify current treatment strategies for postpartum hemorrhage used by obstetricians (OB/GYNs) and hematologists (HEMs). Study Design: We conducted a survey of OB/GYNs (n = 220) and HEMs (n = 30) to describe the characteristics of current treatment strategies for postpartum hemorrhage. Surveys were administered via a structured questionnaire on a secure internet website from 5 - 12 October 2009. Results: The majority of OB/GYN and HEM respondents were practicing in a community hospital environment (77%). Of the OB/GYNs, the majority practiced at hospitals with over 2000 deliveries per year (77%). A majority (58%) of OB/GYNs were affiliated with hospitals that lacked a massive transfusion protocol to treat severe postpartum hemorrhage. Subsequent to uterine massage and additional oxytocin, the majority of OB/GYNs (73%), preferred the administration of Methergine? as the next level of intervention for postpartum hemorrhage. There was considerable variability in response to specific treatment strategies for several hypothetical case scenarios;however, the large majority of OB/GYNs favored obstetrical procedures over interventional radiology or administration of rFVIIa. A large majority (77%) of physicians who are familiar with rRVIIa as treatment for postpartum hemorrhage reported being very satisfied with the agent for this indication. Conclusions: An established, systematic treatment strategy among OB/GYNs emerged only in the case of mild postpartum hemorrhage.
文摘Hemophagocytic lymphohistiocytosis （HLH） is a lifethreatening disorder due to hyperinflammation resulting in infiltration of different organs with extensive hemophagocytosis. Severe coagulopathy was one of the main reasons for death in HLH. Over secretion of plasminogen activator by activated macrophages leads to hyperfibrinolysis. We reported a 36-year-old woman who was diagnosed as HLH probably secondary to lymphoma. Massive bleeding from gut and retroperitoneal area were not able to be controlled by conventional hemostatic treatments. This patient received one dose recombinant activated factor Ⅶ （rFVlla） 3.6 mg （70 μg/kg）. Hemostatic effect was achieved in 0.5 hour and lasted 24 hours. Prothrombin time （PT） and activated partial thromboplastin time （APTT） were quickly corrected to normal ranges.Fibrinogen level elevated from 0.5 g/L before using rFVIla to 1.8 g/L 20 hours after. Although dexamethasone and etopside were administrated to treat HLH, this patient died from septic shock after persistent neutropenia. This suggests that rFVlla may be effective in the management of intractable hemorrhage in patients with HLH.
文摘Recombinant factor VIIa(rFVIIa) is a new drug to prevent and control the hemorrhagic episode in certain patients.The rFVIIa is one type of recombinant protein,which gene is cloned and expressed in baby hamster kidney cells,and it can efficiently prevent the hemorrhage in liver transplantation without an increased risk of thrombotic complications.It also can be used in heart surgery and other operation to prevent the hemorrhage.This review will discuss its mechanism and application in liver transplantation.
