Anesth Analg 2005;101:1628-1630
© 2005 International Anesthesia Research Society
doi: 10.1213/01.ANE.0000184186.95127.E2
PEDIATRIC ANESTHESIA
Aortic Valve Repair in a Patient with Congenital Afibrinogenemia
Adarsh B. Lal, FFARCSI,
Ram Maruthavanan, MRCP, and
Nicholas B. Scott, FRCS(Ed), FFARCSI
Golden Jubilee National Hospital, Clydebank, United Kingdom
Address correspondence and reprint requests to Adarsh B. Lal, Consultant Anesthetist, Golden Jubilee National Hospital, Beardmore St., Clydebank G81 4HX, United Kingdom. Address e-mail to adarsh.lal{at}gjnh.scot.nhs.uk.
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Abstract
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We describe the management of cardiopulmonary bypass (CPB) in a patient with congenital afibrinogenemia (AF). Although this state is akin to the state after hirudin administration, where CPB has been successfully performed, heparinization is still essential to preserve other clotting factors and prevent excessive bleeding. Aprotinin further helps in preservation of clotting factors. There are case reports of thrombosis associated with AF, but aprotinin can be safely used because it is, by definition, an anticoagulant. Cryoprecipitate effectively restores the fibrinogen and produces normal clotting.
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Introduction
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Congenital afibrinogenemia (AF) is a rare, autosomal recessive disorder resulting from a genetic defect on chromosome 4 and characterized by unmeasurable fibrinogen and an inability of blood to clot. The bleeding diathesis is milder than that seen in hemophilia and von Willebrand Disease, because these patients generate excessive amounts of thrombin, thereby inducing platelet aggregation (1). They present a major clinical challenge, first, with regard to heparinization for bypass and, second, because fibrinogen replacement needs careful management because the plasma half-life of administered fibrinogen is reduced after surgery. Finally, case reports of thrombosis associated with AF complicate the administration of aprotinin in patients with a hemorrhagic risk (2,3).
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Case Report
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A 13-yr-old boy weighing 48 kg had had increasing palpitations and shortness of breath for 2 yr. Despite bruising easily, he led an active life and was otherwise well. However, after dental extraction the previous year, he had bled profusely, requiring blood transfusion. Echocardiography showed a bicuspid aortic valve with thickened calcified cusps, a peak gradient of 126 mm Hg, mean gradient of 60 mm Hg, and an area of 0.3 cm2, as assessed by the continuity equation.
Preoperative routine full blood count and chemical profile were normal. The fibrinogen level was not measurable. All other clotting factors were normal. Prothrombin time (PT) and activated partial thromboplastin time (APTT) were both markedly prolonged. Thromboelastogram (TEG®) (Fig. 1) showed a prolonged R interval and decreased maximum amplitude. A therapeutic test was conducted before surgery by administering 10 U of cryoprecipitate IV (4–6), resulting in a PT of 15.4 s, APTT of 29.5 s, and fibrinogen level 0.49 g/L. TEG® was also normal (Fig. 2).
After premedication with oral temazepam 20 mg, peripheral venous and radial arterial catheters were inserted, and anesthesia was induced using a target-controlled infusion of propofol at a concentration of 5 mg/L. Analgesia was achieved using target-controlled infusion alfentanil at a concentration of 150 µg/L. After IV pancuronium 0.1 mg/kg, the trachea was intubated and intermittent positive-pressure ventilation commenced. A central venous catheter was inserted into the right internal jugular vein, and after a test dose, a bolus of one million units of aprotinin was administered followed by an infusion rate of 1 mL · kg–1 · h–1.
After skin incision, no clot formation could be observed. Surgical valvotomy was performed on cardiopulmonary bypass (CPB) after the administration of heparin 15,000 IU, as per hospital protocol. The activated clotting time, before and after heparin, was more than 999 s. Aortic cross-clamp time was 19 min, and CPB time was 31 min. Once protamine 150 mg had been given, 20 U of cryoprecipitate was administered to increase the fibrinogen concentration to 1 g/L, at which level normal hemostasis is expected. At the end of surgery, activated clotting time and TEG® were normal with an attained fibrinogen level of 1.24 g/L. No blood products were required subsequently.
Postoperatively, chest drain losses were 62 mL in the first hour and 240 mL in the first 6 h. TEG®, PT, APTT, and fibrinogen concentrations were performed every 6 h for the first 24 h and every 12 h until 96 h (Table 1). The chest drains were removed at 24 h with a total loss of 810 mL. The fibrinogen level decreased to less than 0.5 g/L on the second day and, to avoid bleeding so soon after surgery, a further 10 U of cryoprecipitate was administered. The patient was discharged from hospital on the ninth postoperative day without further intervention.
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Discussion
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AF is a coagulation disorder with a single-factor deficiency. The missing fibrinogen may be replaced by administering either cryoprecipitate or lyophilized fibrinogen concentrates. Cryoprecipitate is obtained by thawing fresh frozen plasma (FFP) at 4°C. The collected supernatant plasma is rich in FVIII, von Willebrand factor, FXIII, fibronectin, and fibrinogen. However, this process may only remove approximately 30% of fibrinogen from the FFP (7).
The reduction of plasma fibrinogen to concentrations of 0.4–0.8 g/L by the administration of ancrod, creating a situation similar to AF, has been used to provide safe CPB, but these patients bleed more and require more cryoprecipitate and FFP than heparin-anticoagulated patients (8). Our patient received heparin to prevent the activation of factors XIa, Xa, IXa, and IIa, thus preserving the activity of each of these factors. Aprotinin-induced kallikrein inhibition prevents contact activation and further reduces the consumption of clotting factors. Aprotinin preserves organ function, has antiinflammatory properties (9,10), and has also decreases surgical mortality, reopening for bleeding, and blood transfusions (11). Thus, with preserved clotting factors and fibrinogen replenished by cryoprecipitate, coagulation was effectively normalized.
Patients with a single-factor deficiency adjust physiologically to rebalance their hemostatic, coagulation, and fibrinolytic systems (12). Thus, replacement therapy alone may result in a prothrombotic tendency, as evidenced by the short R time in the TEG® after cryoprecipitate administration (Fig. 2). We can recommend the sequential combination of aprotinin, heparin, and cryoprecipitate for the safe management of these patients.
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Footnotes
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Accepted for publication June 9, 2005.
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References
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Abstract
Introduction
