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Anesth Analg 2004;99:353-356 © 2004 International Anesthesia Research Society doi: 10.1213/01.ANE.0000112318.76543.7C
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Abstract |
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Intracardiac thrombus formation during orthotopic liver transplantation can be a catastrophic event leading to death. Most often this devastating complication occurs after reperfusion and may be related to massive blood transfusion, marginal liver grafts, tendencies towards hypercoagulability, or the potential role of antifibrinolytics. We report a case of an intracardiac thrombus occurring during the hepatectomy stage (stage I) of orthotopic liver transplantation. Transesophageal echocardiography was used to quickly diagnose the thrombus, allowing rapid pharmacological intervention and later guide surgical evacuation of the intracardiac thrombus via the inferior vena cava.
IMPLICATIONS: Intracardiac thrombosis occurring during liver transplantation can be a catastrophic event leading to death. Understanding the causes and treatment of hypercoagulability during liver transplantation is important to reduce the risk of this complication.
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Introduction |
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TopAbstractIntroductionCase ReportDiscussionReferences |
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Intracardiac thrombus formation during orthotopic liver transplantation (OLT) can be a catastrophic event leading to death. Most often this devastating complication occurs after reperfusion and may be related to massive blood transfusion, presence of veno-venous bypass, marginal liver grafts, or tendencies towards hypercoagulability.
The potential role of antifibrinolytics drugs causing intracardiac thrombus formation during OLT has been described in the literature. Use of aminocaproic acid, or aprotinin, alone or in combination may have contributed to this problem (1–4). Most of these patients had associated pathology: retransplantation for graft rejection (3), sepsis in the weeks before liver transplantation (4), or renal failure that required hemodialysis (3,4).
Transesophageal echocardiography (TEE) is the only method that can prove formation of intracardiac clots by direct visualization. This capability allows diagnosis of the correct etiology of hemodynamic instability that may occur during OLT, especially after reperfusion (1).
We report a case of an intracardiac thrombus occurring during OLT that had several unique aspects. The intracardiac thrombus formed during the hepatectomy stage (stage I) of the OLT, not after reperfusion, and no antifibrinolytics were used. In addition, the patient was treated during surgery with hemofiltration. TEE was used to quickly diagnose the thrombus, allowing rapid pharmacological intervention and later guiding surgical evacuation of the intracardiac thrombus with a Yankauer suction. Similar to previous reports, the patient had contributing factors of sepsis several weeks before OLT and had renal failure at the time of transplantation.
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Case Report |
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TopAbstractIntroductionCase ReportDiscussionReferences |
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The patient was a 59-yr-old woman with autoimmune hepatitis who presented for OLT 2 mo after hospital admission for acute on chronic hepatic failure. Approximately 1 mo before transplantation, she had multifocal pulmonary infiltrates, suggesting an infectious pneumonia or hemorrhagic processes in addition to herpes zoster on the chest wall. Deterioration of mental status with hepatic encephalopathy, progressive renal and respiratory failure, and continued worsening of liver and coagulation functions complicated her pretransplant course.
On the day of transplant, the patient was comatose (Glasgow Coma Score 5). She was previously tracheally intubated and receiving mechanical ventilation, and her arterial blood pressure (BP) was maintained without vasopressor support. In addition, she exhibited anasarca and was anuric with blood urea nitrogen 55 mg/dL and creatinine 3 mg/dL. Renal failure was being treated for approximately 1 mo, with continuous veno-venous hemofiltration (CVVH) by Prisma® (Gambro Healthcare, Lakewood, CO).
Coagulation variables on the day of the transplant showed a platelet count of 54 x 103/mm3 (PLT; normal, 200–300 x 103/mm3), an increased prothrombin time of 42 s (PT; normal, 11.5–15 s), an International Normalized Ratio of 3.6 (INR; normal, 1), and an activated thromboplastin time of 38.6 s (aPTT; normal, 26–36 s). No anticoagulant drugs were used for the hemofiltration system because of the coagulopathic status of the patient with severe epistaxis requiring nasal tamponade 1 wk before transplantation.
Upon arrival in the operating room, CVVH, maintained with an M 100 Preset® (AN 69 HF Membrane, Hospal, France) device and warmer, was restarted after additional IV access, and monitoring catheters were inserted.
The patient’s vital signs were stable with BP of 110/55 mm Hg, heart rate of 72 bpm, central venous pressure (CVP) of 21 mm Hg, pulmonary artery pressure of 38/27 mm Hg, cardiac output of 7.6 L/min, and mixed venous oxygen saturation (SvO2) of 80%. Baseline thrombelastography (TEGÒ Analyzer Hemoscope, Skokie, IL) was performed and is shown in Figure 1. No antifibrinolytic drugs were used during the surgery. Baseline TEE (Omniplane II®, Hewlett Packard, Palo Alto, CA) routinely used at our institution showed biventricular dilation with mild mitral regurgitation, moderate tricuspid regurgitation, mild aortic insufficiency, good left and right ventricular function, a small pericardial effusion, and bilateral pleural effusions.
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The patient’s initial hematocrit was 21%, and this was treated with 3 U of red blood cells. No fresh frozen plasma was administered to the patient at this time, based on the hypercoagulable TEG®. Three hours after the incision, during the hepatectomy (stage I), the patient’s BP slowly decreased to 95/45 mm Hg, and her CVP decreased to 5 mm Hg. This was treated with fluid administration (500 mL of 5% albumin). A few minutes later, for no apparent reason, systolic BP quickly decreased to 38 mm Hg, and end-tidal CO2 decreased from 31 to 21 mm Hg. An arterial blood sample sent immediately before the event arrived clotted to the blood gas lab. In addition, we noted that the CVVH system clotted and failed at the same time.
TEE showed significant intracardiac thrombus with a free-floating thrombus in the right atrium (RA), although there was no clot visualized in the pulmonary artery (Fig. 2). The patient was immediately given 3000 U of heparin and a total of 1.1 mg of epinephrine IV. An epinephrine infusion of 0.05 µg · kg–1 · min–1 was started, and her BP recovered to 120/78 mm Hg within 3 min. An additional 2000 U of heparin IV was given. Pulmonary artery pressure and CVP were normal after this event, measuring 24/17 mm Hg and 5 mm Hg, respectively, and left and right ventricular (RV) functions were similar to the baseline examination.
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Immediately after the event, a blood sample was sent for antithrombin III (AT III), protein C, and protein S plasma concentrations. All of the physiologic inhibitors of coagulation factors were decreased at the time of the thrombus formation: protein C <10% (normal, 70%–140%), protein S 27% (normal, 60%–145%), and AT III 27% (normal, 80%–120%), which demonstrated an active pro-coagulant state (1).
Because the patient recovered from the initial hypotension, it was decided to proceed with the OLT. Piggyback technique, without veno-venous, was planned for the implantation of the donor graft because of the intracardiac thrombus formation.
When the hepatectomy was complete, TEE showed residual intracardiac thrombus still present in the RA and RV. The clot was not visualized in the pulmonary artery, and it was then decided that this presented a risk for migration into the pulmonary artery upon reperfusion. Therefore, the hepatic vein cuff prepared for piggyback anastomosis was opened, and a Yankauer Medi-Vac® suction device (Allegiance Healthcare, McGaw Park, IL) was guided by TEE through the inferior vena cava into the RA to evacuate the intracardiac thrombus. Evacuation of the intracardiac thrombus as well as reperfusion of the donor liver graft proceeded uneventfully. Heparin effect was reversed with 50 mg of protamine, administrated after reperfusion based on the TEG®. Total blood product transfusion for the procedure included 9 U of red blood cells, 10 U of fresh frozen plasma, and 2 U of PLT concentrate (six pools each).
The operation concluded without further events, and the patient was transferred to the intensive care unit (ICU) in stable condition. No further workup for lower extremity thrombosis was performed. She was discharged from the hospital in 2 mo and is doing well.
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Discussion |
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TopAbstractIntroductionCase ReportDiscussionReferences |
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Most of the published case reports of intracardiac thrombus and pulmonary thromboembolism during OLT occurred within a few minutes after graft reperfusion. The potential role of antifibrinolytic drugs was debated in most of them (1–4). The significant difference in this case is that the thrombus formation occurred during the dissection stage of the OLT (stage I) and without the use of antifibrinolytic therapy. Despite rapid onset of clotting as demonstrated by TEG®, coagulation variables (PLT, PT, aPTT, INR) measured the day of transplant showed a coagulopathic status.
Other relevant characteristics of this case include a long ICU stay and a history of sepsis. In addition, multisystem organ failure (kidneys or liver) may have resulted in an imbalance between the coagulation and fibrinolytic systems (5). These factors, combined with a decreased clearance of activated coagulation factors in the presence of liver insufficiency, may have lead to a more intense activation of coagulation (6).
AT III, protein C, and protein S measurements were performed only for further diagnostic information because they did not immediately aid in the intraoperative management of the patient. These findings were consistent with the baseline TEG® (short reaction time), demonstrating a hypercoagulable tendency at the beginning of the case. The combination of acute on chronic liver failure, with recent epistaxis, and significantly increased PT and INR, led to the decision not to anticoagulant the patient in the ICU before surgery, and the dialysis team in the operating room continued this treatment approach.
Kettner et al. (7) demonstrated that patients undergoing OLT have increased levels of endogenous heparinoids. Our clinical experience shows that a small dose of heparin (<5000 UI or 50–70 UI/kg) usually has an amplified effect on hypercoagulable TEG® tracings, producing a straight-line pattern (no reaction), as shown in Figure 3. Administration of heparin to patients with pulmonary embolism is beneficial in preventing further clot formation while allowing endogenous fibrinolysis to proceed (8). In addition, DeWolf et al. (9,10) have shown that small-dose prophylactic heparin in OLT can prevent pulmonary thromboembolism and is not associated with excess bleeding.
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Other treatment options include, but are not limited to, surgical embolectomy with or without cardiopulmonary bypass or the use of thrombolytic drugs. Both have been associated with a frequent complication rate (1). The risk and benefit of AT III and activated protein C administration is not yet defined in clinical trials, but the decision to administer them empirically can be based on clinical judgment (11,12).
The long-term use of CVVH in this patient could have been a contributing factor for PLT activation and destruction. Generation of thrombin is a key event in biocompatible/incompatible reactions. The mechanism by which thrombin is generated on a polymer surface in an extracorporeal circuit is not yet fully understood (13). Because the TEE probe was left in place during the surgery, and the thrombus was suddenly present, it is possible that a thrombus formed in the CVVH system and embolized to the heart. This finding is consistent with the fact that the CVVH system clotted and failed at the same time. In our case, using a Yankauer suction passed through the interior vena cava into the RA under TEE guidance to evacuate the intracardiac thrombus was a very successful method at preventing the thrombus from migrating into the pulmonary artery.
TEE is the only method that can document formation of cardiac clots during surgery. It allowed the clot to be visualized and guided the surgeon during the transcaval intracardiac embolectomy. Without TEE, prompt diagnosis and treatment may not be possible where salvage intervention is time related.
The decision not to use anticoagulant drugs during intraoperative CVVH can predispose patients to clot formation, even in those who are recognized to be coagulopathic (14), and especially in patients with hypercoagulable TEG® patterns. Use of heparin, low molecular weight heparin, antiplatelet drugs such as prostaglandin E1, or direct thrombin inhibitors such as lepirudin or hirudin are other therapeutic options to prevent thrombotic complications in patients undergoing intraoperative dialysis (14–16).
Use of a Yankauer suction passed through the inferior vena cava into the RA under TEE guidance to evacuate an intracardiac thrombus combined with a small dose of heparin (5000 UI) and cardiac resuscitation (epinephrine) was a very successful method of rescuing our patient from this potential lethal complication. Not all patients presenting with this problem may respond to this approach. When a hypercoagulable TEG® is encountered early in OLT, one should considered prophylactic administration of small-dose heparin.
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References |
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TopAbstractIntroductionCase ReportDiscussionReferences |
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- Gologorsky E, De Wolf AM, Scott V, et al. Intracardiac thrombus formation and pulmonary thromboembolism immediately after graft reperfusion in 7 patients undergoing liver transplantation. Liver Transpl 2001; 7: 783–9.[Web of Science][Medline]
- Fitzsimons MG, Peterfreund RA, Raines DE. Aprotinin administration and pulmonary thromboembolism during orthotopic liver transplantation: report of two cases. Anesth Analg 2001; 92: 1418–21.
[Free Full Text] - O’Connor CJ, Roozeboom D, Brown R, Tuman KJ. Pulmonary thromboembolism during liver transplantation: possible association with antifibrinolytic drug and novel treatment options. Anesth Analg 2000; 91: 296–9.
[Abstract/Free Full Text] - Sopher M, Braunfeld M, Shackleton C, et al. Fatal pulmonary embolism during liver transplantation. Anesthesiology 1997; 87: 429–32.[Web of Science][Medline]
- Morris PE, Duncan Hite R, Ohl C. Relationship between the inflammation and coagulation pathways in patients with severe sepsis: implications for therapy with activated protein C. BioDrugs 2002; 16: 403–17.[Medline]
- Cheema SPS, Webster NR, Dunn F, Bellamy MC. Mediators of fibrinolysis in orthotopic liver transplantation. Clin Transplant 1996; 10: 24–7.[Medline]
- Kettner SC, Gonano C, Seebach F, et al. Endogenous heparin-like substances significantly impair coagulation in patients undergoing orthotopic liver transplantation. Anesth Analg 1998; 86: 691–5.[Abstract]
- Tai NRM, Atwal AS, Hamilton G. Modern management of pulmonary embolism. Br J Surg 1999; 86: 853–68.[Web of Science][Medline]
- DeWolf AM, Ramsey G, Teruya J, et al. Hypercoagulability and pulmonary thromboembolism (PE) during liver transplantation (LTX): what is the role of heparin administration? Liver Transpl Surg 2001; 7: C-5 (18).
- DeWolf AM, Ramsey G, Teruya J, et al. Hypercoagulability and pulmonary thromboembolism during liver transplantation: what is the role of heparin administration? Liver Transpl Surg 2003; 9: C-40 (157).
- Kohler M. Antithrombin (AT) substitution: sense or nonsense? Anaesthesia 1998; 53: 52–4.
- Haynes G, Lazarchick J, Palesch Y, et al. Antithrombin III activity associated with disseminated intravascular coagulation in orthotopic liver transplantation. Anesthesiology 1998; 89: 412A.
- Hong J, Larsson A, Nilsson Ekdahl K, et al. Contact between a polymer and whole blood: sequence of events leading to thrombin generation. J Lab Clin Med 2001; 138: 139–45.[Medline]
- Davenport A. Is there a role for continuous renal replacement therapies in patients with liver and renal failure. Kidney Int Suppl 1999; 72: S62–6.
- Mudaliar JH, Liem TK, Nichols WK, et al. Lepirudin is a safe and effective anticoagulant for patients with heparin-associated antiplatelet antibodies. J Vascular Surgery 2001; 34: 17–20.[Web of Science][Medline]
- Saner F, Hertl M, Broelsch CE. Anticoagulation with hirudin for continuous veno-venous hemodialysis in liver transplantation. Acta Anaesthesiol Scand 2001; 45: 914–8.[Medline]
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