Eur J Cardiothorac Surg 2001;19:219-220
© 2001 Elsevier Science NL
Novel approach to bleeding in patients undergoing cardiac surgery with liver dysfunction
Robert G. Stuklis,
Denise F. O'Shaughnessy,
Sunil K. Ohri
Department of Cardiothoracic Surgery and Haematology, Southampton General Hospital, Southampton, UK
Received 18 September 2000;
received in revised form 28 November 2000;
accepted 29 November 2000.
Corresponding author. Department of Cardiothoracic Surgery, Mailpoint 46, Southampton General Hospital, Tremona Rd, Southampton, SO16 6YD, UK. Tel.: +44-23-8077-7222; fax: +44-23-8079-6614
e-mail: rstuklis{at}yahoo.com
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Abstract
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We describe two patients with significant liver dysfunction (Child–Pugh class B) who underwent cardiac surgery at our institution facilitated by the use of a prothrombin complex concentrate for the management of postoperative bleeding.
Key Words: Prothrombin complex concentrate • Liver dysfunction • Cardiac surgery
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1. Introduction
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Patients with significant liver dysfunction undergoing cardiac surgery pose a major haemostatic challenge in the postoperative period. We describe our experiences with two such patients in whom the prothrombin complex concentrate (PCC) Beriplex® (Centeon Pharma GmbH, Marburg, Germany) was used. Use of this concentrated preparation of prothrombin complex factors II, VII, IX, and X successfully reduced bleeding when traditional therapies failed (i.e. fractionated blood products). Although its use in liver transplantation is well described [1], little has been published to date about its use in cardiac surgery.
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2. Patient 1
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A 38-year-old male was diagnosed with severe aortic stenosis and diffuse coronary artery disease. He also had marked hepatic congestion from severe congestive cardiac failure and alcoholic liver disease (Child–Pugh class B) [2]. Aortic valve replacement and coronary bypass grafting was undertaken with aprotinin using the high dose regimen [3]. Blood loss was more than 1 l in the first half hour post operatively despite a rigorous and lengthy attempt at haemostasis in the operating theatre. Despite transfusing 8 units fresh frozen plasma (FFP) and 10 units of cryoprecipitate (Cryo), coagulation studies remained abnormal. Fibrinogen and D-Dimer levels were normal but the international normalized ratio (INR) was 1.8. Specific coagulation factor assays were performed and showed a low level of factor VII (38 U/dl; NR: 50–150 U/dl). Other factors were at the lower limit of their normal ranges. PCC was given (500 units) and blood loss rapidly settled. The remainder of his postoperative course was unremarkable.
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3. Patient 2
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A 49-year-old male on warfarin for a mechanical aortic valve presented in pulmonary oedema with severe jaundice. He had become increasingly jaundiced over the previous year from hepatic congestion and alcoholic liver disease (Child–Pugh class B). After rapid transfer to the operating room acute on chronic aortoventricular disconnection was found. High dose aprotinin was also used for this case. A second prosthetic valve was inserted and aortoventricular continuity restored. Again we found the INR was rapidly normalised by PCC (500 units) after large volumes of FFP/Cryo failed (specific factor assays were not performed because of preoperative warfarin therapy). Postoperative drainage was minimal.
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4. Comment
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Patients with significant liver dysfunction undergoing cardiac surgery have a high incidence of complications related to their degree of coagulopathy [4–5]. In addition to fibrinolysis induced by cardiopulmonary bypass (CPB), hepatic ischaemia causes an imbalance between activators and inhibitors of the fibrinolytic system. Platelet dysfunction and thrombocytopaenia are well documented following CPB and are further exaggerated in these patients. Coagulation factors are reduced after CPB due to a combination of consumption during bypass and poor hepatic synthetic function. Therefore in the face of such bleeding the usual strategy is to use antifibrinolytic drugs, platelet and plasma transfusions. Problems arise with the efficacy of plasma because large volumes must be administered to boost coagulation factor levels in patients with significant deficiencies. PCC's have the advantage of rapidly delivering high concentrations of coagulation factors in low volumes, e.g. typical single dose of 500 units PCC is approximately equivalent to 2 l plasma (500 units of Beriplex® is made up to 20 ml and delivered no faster that 1 ml/min).
PCC's are generally used for the treatment of prothrombin complex factor deficiencies where other therapies are inadequate [6]. Examples include congenital coagulation deficiencies, acute warfarin toxicity and bleeding associated with liver parenchymal damage. Because of its concentrated nature and the possibility of harbouring activated factors they have in the past been associated with disseminated coagulopathy (DIC) and other thrombotic complications. Current generation products have activated coagulation factors at a minimum and are counterbalanced with coagulation inhibitors anti-thrombin III, proteins C and S to minimize this risk further but close laboratory monitoring for DIC is still mandatory [7]. Current generation PCC's are also highly purified and therefore viral transmission risk should be less than the equivalent multiple units of FFP that are often needed for patients with liver dysfunction following cardiac surgery [8]. Cost is also an issue as they are approximately ten times more expensive relative to fractionated blood products on a unit basis.
In conclusion, we would not advocate the routine use of this treatment. The significant bleeding experienced by our two patients may have stopped with standard therapy. However, when confronted with uncontrollable bleeding in patients after cardiac surgery with documented liver dysfunction PCC's provide a rapid, safe and efficacious adjunct to standard therapies. These should always be administered on the rational basis of specific factor analysis if possible. Further studies are required to quantify its risks and benefits in the setting of cardiac surgery.
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References
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Abstract
1. Introduction
