Hg Hendriks

Reduced transfusion requirements by recombinant factor VIIa in orthotopic liver transplantation : A pilot study

Background. Large transfusion requirements, i.e., excessive blood loss, during orthotopic liver transplantation (OLT) are correlated with increased morbidity and mortality. Recombinant factor VIIa (rFVIIa) has been shown to improve hemostasis in a variety of conditions, but has never been studied in liver transplantation. Methods. We performed a single-center, open-label, pilot study in adult patients undergoing OLT for cirrhosis Child-Pugh B or C, to assess efficacy and safety of rFVIIa. rFVIIa (80 &mgr;g/kg) was administered at the start of the operation, to be repeated according to predefined criteria. Packed red blood cells (RBC), fresh-frozen plasma, and platelet concentrates were administered according to predefined criteria. Perioperative transfusion requirements in study patients were compared with matched controls. Results. Six patients were enrolled in the study. All received a single dose of rFVIIa. Transfusion requirements (given as median, with range in parentheses) were lower in the study group than in matched controls: 1.5 (0–5) vs. 7 (2–18) units of allogeneic RBC (P =0.006), 0 (0–2) vs. 3.5 (0–23) units of autologous RBC (P =0.043), total amount of RBC 3 (0–5) vs. 9 (4–40) units (P =0.002). Transfused fresh-frozen plasma was 1 (0–7) vs. 8 (2–35) units (P =0.011). Blood loss was 3.5 L (1.4–5.3) vs. 9.8 L (3.7–35.0) (P =0.004). One study patient developed a hepatic artery thrombosis at day 1 postoperatively. Conclusions. A single dose of 80 &mgr;g/kg rFVIIa significantly reduced transfusion requirements during OLT. Further study is needed to establish the optimally effective and safe dose of rFVIIa in orthotopic liver transplantation.

An assessment of clinical interchangeability of TEG and RoTEM thromboelastographic variables in cardiac surgical patients.

BACKGROUND: Bedside thromboelastography is increasingly used, but an assessment of the clinical interchangeability of the 2 major systems, TEG® (Hemoscope) and RoTEM® (Pentapharm), has not been performed. METHODS: We measured blood samples from 46 cardiac surgical patients after induction of anesthesia with kaolin TEG® (kaoTEG), native TEG® (natTEG®), intrinsic RoTEM® (inTEM), and extrinsic RoTEM (exTEM). Each measurement consisted of reaction time (R), coagulation time (K), maximum amplitude (MA), and angle (&agr;). Bland–Altman plots and mixed-model analysis were used. To assess repeatability, we made 7 replicated measurements in rapid succession in 2 volunteers. RESULTS: One hundred sixty-six measurements were available for analysis. The R time of the kaoTEG® (345 ± 102 seconds, mean ± SD) was longer than that of the inTEM (179 ± 74 seconds, P < 0.001) and the exTEM (55 ± 28 seconds, P < 0.001). The K time of the kaoTEG® (78 ± 18s) was not different from that of the inTEM (75 ± 52 seconds, P = 0.60) but was longer than the K time of the exTEM (61 ± 24 seconds, P < 0.003). The MA of the kaoTEG® (71 ± 6.5 mm) was larger than the MA of the inTEM (67 ± 5.2 mm, P < 0.02) and almost similar to that of the exTEM (69 ± 6.3 mm). The &agr; of the kaoTEG® (72° ± 4.1°) was not significantly different from that of both the inTEM (76° ± 7°) and the exTEM (79° ± 4.5°). The variability for MA and &agr; was <10%. The repeatability of the R and K times was poor in both devices, whereas the repeatability of the MA and &agr; was sufficient for clinical purposes. CONCLUSIONS: The TEG® and RoTEM® measurements demonstrated a close correlation for the MA, but the &agr; did not for the R and K variables. The kaoTEG® had the best agreement with the exTEM measurement. Therefore TEG® and RoTEM® measurements are not completely interchangeable, and the clinical interpretation of thromboelastograhic data should be used with caution.

Blood loss in orthotopic liver transplantation : a retrospective analysis of transfusion requirements and the effects of autotransfusion of cell saver blood in 164 consecutive patients

&NA; Liver transplantation is associated with excessive blood loss. In order to identify factors influencing blood loss and to provide a basis for a pilot study to evaluate recombinant activated factor VII as a haemostatic agent, a retrospective study was performed in 164 consecutive patients with cholestatic or noncholestatic liver disease, who underwent orthotopic liver transplantation at a single centre between 1989 and 1996. Transfusion of allogeneic and autologous (cell saver) blood was used as a measurement of blood loss. Transfusion requirements were associated with age, gender, primary disease, Child‐Pugh classification, serum levels of activated partial thromboplastin time, antithrombin III, urea and creatinine, platelet number, year of transplantation, length of cold ischaemia time and autologous blood transfusion. Of these variables, Child‐Pugh classification (P = 0.001), urea (P = 0.0007), year of transplantation (P = 0.002), cold ischaemia time (P = 0.01) and autologous blood transfusion (P < 0.0001) were independent predictors of transfusion requirements by multivariate analysis. Thus, blood loss and transfusion requirements depend primarily on the severity of liver disease, quality of the donor liver, experience of the transplantation team and use of autologous (cell saver) blood transfusion. These findings emphasize the need for appropriate drug therapy and a critical reappraisal of current transfusion policy.

Effects of recombinant activated factor VII on coagulation measured by thromboelastography in liver transplantation

Besides the conventional laboratory tests, thromboelastography (TEG) is used to monitor hemostasis during liver transplantation. A previous pilot study suggested a beneficial effect of recombinant activated factor VII (rFVIIa) on transfusion requirements in liver transplantation. In the present study, we assess the effects of rFVIIa on coagulation variables and TEG. In six study patients, the prothrombin time (PT), the activated partial thromboplastin time (aPTT) and TEG variables [reaction time (r), kinetic time (k), or clot formation time, α angle (α), and maximal amplitude (MA)] were recorded before and after the administration of a bolus of 80 μg/kg rFVIIa. These patients were compared with six controls who did not receive rFVIIa. In contrast with the control group, a significant shortening of PT (P = 0.028) and aPTT (P = 0.028), r (P = 0.046) and k (P = 0.043) values, and a significant incline of the α angle (P = 0.028) were noticed after injection of rFVIIa, whereas MA increased not significantly (P = 0.075). rFVIIa rapidly improved coagulation variables in liver transplant patients including PT and aPTT. Of the TEG variables, r, k and α angle significantly improved, and MA showed a trend to increase. These data suggest that rFVIIa not only influences the speed of clot formation, but also the physical properties of the clot, which cannot be detected by routine coagulation tests.

Development of a Severe von Willebrand Factor/ADAMTS13 Dysbalance During Orthotopic Liver Transplantation

Patients with liver disease show profound changes in their hemostatic system, which may further change during liver transplantation. We previously demonstrated that highly elevated levels of the platelet adhesive protein von Willebrand factor (VWF) in patients with cirrhosis lead to an increased VWF‐dependent platelet deposition under flow as compared to healthy controls. In this study we examined VWF parameters during the course of liver transplantation. We collected serial plasma samples from 20 patients undergoing liver transplantation in which we determined plasma levels of VWF and the VWF‐cleaving protease ADAMTS13. Furthermore, we performed functional tests of VWF‐dependent platelet adhesion. We found persistently elevated levels of VWF during and after liver transplantation. The capacity of VWF to interact with platelets normalized during the course of transplantation, and flow‐mediated VWF‐dependent platelet adhesion remained at levels far exceeding those observed in healthy individuals during and after transplantation. Plasma levels of ADAMTS13 dropped during transplantation, and in four patients levels below 10% of normal were observed after reperfusion. We observed the development of a hyperreactive primary hemostatic system, as evidenced by high levels of fully functional VWF and a temporary ADAMTS13 deficiency, during liver transplantation, and speculate that these changes contribute to postoperative thrombotic complications.

Accuracy of non-invasive measurement of haemoglobin concentration by pulse co-oximetry during steady-state and dynamic conditions in liver surgery

BACKGROUND The Masimo Radical 7 (Masimo Corp., Irvine, CA, USA) pulse co-oximeter(®) calculates haemoglobin concentration (SpHb) non-invasively using transcutaneous spectrophotometry. We compared SpHb with invasive satellite-lab haemoglobin monitoring (Hb(satlab)) during major hepatic resections both under steady-state conditions and in a dynamic phase with fluid administration of crystalloid and colloid solutions. METHODS Thirty patients undergoing major hepatic resection were included and randomized to receive a fluid bolus of 15 ml kg(-1) colloid (n=15) or crystalloid (n=15) solution over 30 min. SpHb was continuously measured on the index finger, and venous blood samples were analysed in both the steady-state phase (from induction until completion of parenchymal transection) and the dynamic phase (during fluid bolus). RESULTS Correlation was significant between SpHb and Hb(satlab) (R(2)=0.50, n=543). The modified Bland-Altman analysis for repeated measurements showed a bias (precision) of -0.27 (1.06) and -0.02 (1.07) g dl(-1) for the steady-state and dynamic phases, respectively. SpHb accuracy increased when Hb(satlab) was <10 g dl(-1), with a bias (precision) of 0.41 (0.47) vs -0.26 (1.12) g dl(-1) for values >10 g dl(-1), but accuracy decreased after colloid administration (R(2)=0.25). CONCLUSIONS SpHb correlated moderately with Hb(satlab) with a slight underestimation in both phases in patients undergoing major hepatic resection. Accuracy increased for lower Hb(satlab) values but decreased in the presence of colloid solution. Further improvements are necessary to improve device accuracy under these conditions, so that SpHb might become a sensitive screening device for clinically significant anaemia.

Intact thrombomodulin-mediated regulation of fibrinolysis during and after liver transplantation, despite a profoundly defective thrombomodulin-mediated regulation of coagulation.

K . RU ITENBEEK ,* J . C . M. ME I J ERS , J . ADELME I J ER ,* H . G . D . HENDR IKS ,§ R . J . PORTE and T . L I SMAN* *Surgical Research Laboratory and Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen; Department of Experimental Vascular Medicine, Academic Medical Centre, University of Amsterdam, Amsterdam; and §Department of Anesthesiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands

Thromboelastographic evaluation of recombinant factor VIIa in a child with Glanzmann's thrombasthenia

(2). Only tachycardia (42%) and incomplete RBBB (7%) occurred significantly more often in patients who were confirmed by imaging to indeed have PE than patients with other etiologies. In the same study complete RBBB was found in only 4% of cases of confirmed PE, and it was not diagnostic. Even the classic S1Q3T3 pattern, with a reported prevalence of 12% in massive PE, may occur frequently enough in patients falsely suspected of having PE so as to limit its usefulness as a diagnostic criterion (2,5,6). Statistical analysis is complicated by the numerous possible combinations of findings that may exist on any given ECG. Given that the ECG alone is of limited value in the diagnosis of PE, clinicians must consider the clinical presentation in its entirety (7). Typically, it is prudent to pursue confirmatory imaging studies, such as a CT scan, before proceeding with definitive treatment for PE. The article by Rosenberger et al. indicates that TEE lacks the sensitivity to play this role. The most important role of the ECG is to trigger further evaluation that can lead to definitive diagnosis and prompt treatment of this life-threatening condition.