ISSN:
1432-055X
Keywords:
Schlüsselwörter: Antithrombin III – Blutgerinnung – Gerinnungskonzentrate – PPSB – Terminale Leberinsuffizienz
;
Key words: Antithrombin III – Blood coagulation – Liver disease – PPSB
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Description / Table of Contents:
Abstract. Patients with end-stage liver disease frequently develop combined coagulopathies due to increased procoagulant and fibrinolytic turnover as well as thrombocytopenia. The onset of clinical symptoms of a haemorrhagic diathesis requires balanced substitution of coagulation factors, since fresh frozen plasma alone does not always maintain a sufficient haemostatic potential in these patients. This substitution commonly follows standard rules based on the assumption that 0.5 – 1 IU of a coagulation factor or inhibitor concentrate given per kg body weight will increase its endogenous activity by 1%. We set out to investigate the validity of this standard regime in patients with end-stage liver disease scheduled for orthotopic liver transplantation. Patients and methods. Fifty-one adult patients were prospectively studied. In 37 patients with antithrombin III (AT III) activity 〈70%, an AT III preparation (Kybernin, Behring, Marburg, Germany) was given preoperatively (mean dose 2616±207 IU) following standard calculations in order to increase endogenous activity to 80%. Twenty-seven of the patients had chronic hepatic failure (CHF group) with histologically proven cirrhosis and 10 had acute hepatic failure (AHF group). Blood samples were drawn prior to a 15-min infusion of AT III concentrate and 30 min thereafter. In 14 patients with prothrombin time (PT) 〈40%, AT III levels had been corrected earlier during the clinical course to achieve activities 〉70%. Prothrombin complex (PPSB, Beriplex, Behring, Marburg, Germany) was substituted (mean dose 2304±289 IU) to increase procoagulant activity to PT 〉60%. Blood samples were drawn in the same fashion as in the AT III group. The amounts of AT III and PPSB concentrates (Δ AT III, [IU/kg]; Δ PPSB [IU/kg]) required to increase AT III activity and PT, respectively, by 1% were calculated. Results. Standard calculations for AT III substitution indicated AT III recovery in all 37 patients who received AT III concentrate. However, there was a statistically significant difference between patients with CLF and ALF. In patients with CLF, Δ AT III was found to be 0.8 IU/kg (±0.1 SEM) and in those with ALF it was 1.5 IU/kg (±0.1 SEM) (P〈0.05, t-test). In patients treated with PPSB concentrate, Δ PPSB was 1.6 U/kg (±0.2 SEM) for both CLF and ALF groups. Conclusions. In patients with end stage liver disease standard rules for substitution with AT III-concentrate are adequate only for patients with CLF. In patients with ALF higher AT III doses are required to achieve the expected effect on endogenous AT III activity. Procoagulant activity, as reflected by PT, can be increased by 1% when 1.6 IU/kg PPSB concentrate is given. However, this study shows the effects of coagulation concentrates only 30 min after administration. An increased volume of distribution and increased turnover may explain the poor recovery of AT III activity in the ALF group, indicating that the dose of coagulation concentrate should be estimated against the background of the patient's clinical symptoms and diagnosis.
Notes:
Zusammenfassung. Die Validität der klinischen Anhaltsregel, mit der Substitution von 0,5 bis 1,0 E pro kg Körpergewicht die Aktivität eines Gerinnungsfaktors bzw. -inhibitors um 1% steigern zu können, wurde für ein PPSB-Konzentrat sowie für ein Antithrombin III (AT-III)-Konzentrat an 51 erwachsenen Patienten mit terminaler Leberinsuffizienz geprüft. Die Substitution wurde im Rahmen der OP-Vorbereitung zur orthotopen Lebertransplantation durchgeführt und Quickwerte (%) und AT-III-Aktivität (%) wurden vor und nach Substitution bestimmt. Bei den 37 mit AT III substituierten Patienten (mittlere Substitutionsdosis 2616 E±207 SD) wiesen 27 ein chronisches Leberversagen auf (CLV-Gruppe, histologisch gesicherte Leberzirrhose), 10 zeigten ein akutes Leberversagen (ALV-Gruppe). Im Mittel waren in der CLV-Gruppe 0,8 E (±0,2 SEM) AT-III-Konzentrat und in der ALV-Gruppe 1,5 E (±0,2 SEM) AT-III-Konzentrat erforderlich (*p〈0,05), um die AT-III-Aktivität um 1% pro kg Körpergewicht anzuheben. Bei den 14 mit PPSB substituierten Patienten betrug die mittlere Substitutionsdosis 2304 E (±289 SD), und es waren im Mittel 1,6 E PPSB (±0,4 SEM) pro kg Körpergewicht zur Steigerung des Quickwerts um 1% erforderlich. Als Ursache der erhöhten Substitutionserfordernis für PPSB und AT III bei Patienten mit terminaler Leberinsuffizienz kommen ein vergrößertes Verteilungsvolumen und ein erhöhter Umsatz und Verbrauch in Betracht.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/s001010050046
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