1.
Recombinant activated factor VIIa for the treatment of bleeding in major abdominal surgery including vascular and urological surgery: a review and meta-analysis of published data
von Heymann C, Jonas S, Spies C, Wernecke KD, Ziemer S, Janssen D, Koscielny J
Critical Care. 2008;12((1):):R14.
Abstract
BACKGROUND The purpose of this study was to determine the role of recombinant activated factor VII (rFVIIa) in abdominal, vascular, and urological surgery. METHODS We conducted meta-analyses of case series and placebo-controlled studies reporting on the treatment or prophylaxis of bleeding with rFVIIa regarding 'reduction or cessation of bleeding', 'mortality', and 'thromboembolism'. RESULTS All case reports (n = 15 case reports and 17 patients) documented an effect of rFVIIa in the treatment of bleeding. A meta-analysis of 10 case series revealed a reduction or cessation of bleeding in 39 out of 50 patients after administration of rFVIIa (estimated mean effect 73.2%, 95% confidence interval [CI] 51.0% to 95.4%) and a mean probability of survival of 53.0% (95% CI 26.4% to 79.7%). Among the rFVIIa responders, 19 out of 29 patients (66%) survived versus 1 out of 10 rFVIIa nonresponders (P = 0.003). Six out of 36 patients from the case series had a thromboembolic complication (estimated mean probability 16.5%, 95% CI 1.2% to 31.8%). Compared with a meta-analysis of eight placebo-controlled studies, no increased risk of thromboembolism was seen after administration of rFVIIa. CONCLUSION The meta-analysis of case series showed that, in a mean of 73% patients, rFVIIa achieved at least a reduction of bleeding and that the probability of survival is increased in patients responding to rFVIIa. rFVIIa was not associated with an increased risk of thromboembolism compared with placebo.
2.
Evaluation of erythropoietic activity on the basis of the red cell and reticulocyte distribution widths during epoetin beta therapy in patients undergoing cardiac surgery
Sowade O, Sowade B, Gross J, Brilla K, Ziemer S, Franke W, Stephan P, Scigalla P, Warnke H
Acta Haematologica. 1998;99((1):):1-7.
Abstract
The changes in the red cell and reticulocyte distribution widths during preoperative treatment with recombinant human erythropoietin (rhEPO) were evaluated in a double-blind, placebo-controlled trial in cardiac surgery patients. The increases in the reticulocyte count, in the hemoglobin and in all distribution widths are the expression of the marked preoperative stimulation of erythropoiesis in the patients treated with rhEPO. Only placebo patients with a hemoglobin < or = 7.5 mmol/l or a transferrin > 4.0 g/l at baseline showed an increase in the red cell distribution width or in the reticulocyte hemoglobin distribution width on oral iron therapy alone. While the reticulocyte count and the distribution widths of red cells in the rhEPO patients decreased postoperatively, only the increases in the distribution widths of reticulocytes after the second postoperative day indicate that stimulation oferythropoiesis had taken place. In patients with a low hemoglobin or a high transferrin the rhEPO therapy should be preceded by iron therapy in order to raise the hemoglobin level and reduce the cost of treatment.
3.
The effect of preoperative recombinant human erythropoietin therapy on platelets and hemostasis in patients undergoing cardiac surgery
Sowade O, Ziemer S, Sowade B, Franke W, Messinger D, Ziebell E, Scigalla P, Warnke H
Journal of Laboratory & Clinical Medicine. 1997;129((3):):376-83.
Abstract
In a double-blind, randomized, placebo-controlled trial we evaluated the effects of the administration of recombinant human erythropoietin (5 x 500 U epoetin beta/kg body weight intravenously over a 14-day period before surgery) in patients undergoing cardiac surgery and in whom autologous blood donation was contraindicated on platelet count, platelet distribution width, mean platelet volume (MPV), and certain hemostaseologic parameters. All patients received 3 x 70 IU heparin/kg per day s.c. from 2 days before operation. No thromboembolic events were associated with epoetin beta therapy during the study period. The thrombocytic parameters showed no significant changes in the placebo group before surgery, and the preoperative hematocrit increase in the epoetin beta group was accompanied with an MPV drop (in contrast to the known MPV rise in recombinant human erythropoietin-treated patients with uremia) by a mean of 0.85 fl and a platelet distribution width rise by 3.3% without a significant change in platelet count. In the epoetin beta group the coagulation time (K) of thromboelastogram (TEG) showed an increase from 4.8 to 5.4 minutes by the seventh study day and after the initiation of heparin therapy a further increase to 7.5 minutes. The higher preoperative K increase in the epoetin beta group may partly be a result of the MPV reduction, because smaller platelets are less reactive, a fact underlined by the negative correlation between the preoperative changes of MPV and reaction time of TEG (r = -0.58, p = 0.0148). In contrast, in the placebo group the K of TEG increased only after the start of heparin therapy (from 5.1 to 6.4 minutes). The significant drop in MPV in the epoetin beta group and the higher increase in K of TEG and the other investigated hemostatic parameters do not suggest any increased thromboembolic risk during the preoperative epoetin beta therapy. Therefore this treatment seems to be a safe way for increasing mean hematocrit by approximately 0.06 within the normal range and reducing the homologous blood requirement in patients undergoing elective cardiac surgery.