Uncontrolled bleeding continues to be a major cause of mortality in cardiac surgery, post-PPH and ICH [15
]. Consequently, rFVIIa is increasingly being used off-label as a „ generic hemostatic
agent“. The off-label use of this medications is appealing when standard therapies prove ineffective [16
]. A retrospective database analysis of off-label rFVIIa use in U.S. hospitals revealed that the off-label use of rFVIIa has increased more than 140-fold the majority of which were for off-label indications [17
This series examines the use of rFVIIa as a haemostatic agent in the management of intractable hemorrhage
. Table 5 shows the most common off-label uses of rFVIIa in our study. In this study, the most common off-label uses of rFVIIa were for cardiac surgery, ICH, and PPH, (33%, 18.8% and 11% respectively) which is comparable to that of other registries [18
]. The majority of patients received a single dose (60%) and the mortality rate in this study is 58%, which is comparable to those seen in previous studies [12
In coronary bypass surgery, national guidelines specify a transfusion threshold (e.g. 10 units of RBCs) that needs to be reached before rFVIIa should be given.
Refractory post cardiopulmonary bypass (CPB) hemorrhage is multifactorial and remains a major cause of mortality and morbidity [11
]. In addition, ICH is one of the most serious subtypes of stroke [15
]. There is good evidence from systematic reviews and randomized controlled trials that rFVIIa stops hemorrhage in adults with ICH if it is given within 4 hours of symptom onset [23
]. Furthermore, few controlled clinical trials have demonstrated prolonged survival after the use of rFVIIa for the treatment of ICH; however, Yank V et al evaluated the efficacy of rFVIIa use for cardiac surgery and intracranial hemorrhage. He concluded that limited available evidence suggests no survival advantages for rFVIIa use [24
]. Furthermore, case reports and case series suggest a potential benefit of rFVIIa in the management of severe PPH and upper gastrointestinal bleeding refractory to standard treatment [25
Differences in patient characteristics are likely to have a major impact on survival. Application of the modified Biss scoring system to our population showed consistent predictability and highlighted important differences that may influence future criteria for patient eligibility to receive rFVIIa. Patients with a high score were less likely to survive and patients with low score were more likely to survive. These results are in line with the original study [12
]. Survivors were younger age group and were less likely to have renal impairment reflecting lack of co morbidity. Impact on overall survival, with death resulting from multiorgan failure in the majority of non-survivors correlated to severity of co morbidities [12
]. The improved survival in obstetric indications also reflects the relatively younger age and lack of pre-existing co morbidity [29
Massive transfusion, accompanied by the development of dilutional coagulopathy frequently predicts mortality in patients with traumatic or surgical bleeding [31
] our finding, that non-survivors also were more likely to have received a greater than 10-unit red cell transfusion which supports the theory that earlier treatment with rFVIIa improves outcome by preventing the complications of massive transfusion, dilutional coagulopathy and ongoing blood loss. Survivors were also less likely to have coagulopathy. The presence of severe coagulopathy at the time of rFVIIa administration has been shown in previous series to adversely influence outcome and overall survival [22
] although this effect was not demonstrated in a larger study [21
]. Data from the Hemostasis Registry have demonstrated that lower platelet counts are independently associated with mortality in patients treated with rFVIIa [17
]. These conflicting reports highlight the advantage of using a prognostic score rather than a single prognostic indicator.
While some reports suggest the effect of hypothermia on coagulation enzymatic rates and platelet enzymatic and secretory rates, some studies failed to support these finding [10
]. Viuff et al concluded that the efficacy of rFVIIa was affected by the degree of hemodilution and type of volume expander, but not by acidosis or hypothermia [10
]. The ability of rFVIIa to enhance haemostatic parameters as evident from the improved TEG parameters at temperatures of 28-31°C in response to rFVIIa suggest that hypothermia is consistent with retention of enzymatic activity between 37 and 32°C in vitro and in vivo [33
]. Furthermore, Hall et al did not find an independent relationship between transfusion requirement or repeat dosing and temperature following rFVIIa administration [9
]. Therefore hypothermia was excluded from the modified Biss score.
Some randomized controlled trail of rFVIIa in trauma patients reported a trend toward reduced transfusion requirement and mortality [35
]. A number of studies have described the development of off-license rFVIIa treatment guidelines in various clinical contexts [30
]. Lack of randomized controlled trials results in practice guidelines based on weak recommendations, however, guidelines implementation improves patients outcome particularly when incorporating factors that are shown to influence outcome [39
]. Furthermore, high levels of guideline compliance were evident whenever the number of possible elements in the scoring system is small. Therefore the use of a prognostic score may help to predict survival in patients appearing eligible for treatment with rFVIIa and may help to justify the use of this expensive medication associated with potential side effects.