- Email: [email protected]
Simultaneous hepatic artery and portal vein thrombosis after living donor liver transplantation
Simultaneous Hepatic Artery and Portal Vein Thrombosis After Living Donor Liver Transplantation J. Kaneko, Y. Sugawara, J. Togashi, Y. Kishi, N. Akamatsu, and M. Makuuchi ABSTRACT Simultaneous hepatic artery and portal vein thrombosis rarely occurs after liver transplantation. The etiology is unknown. Of 213 patients (72 children and 141 adults) that underwent living donor liver transplantation (LDLT) from January 1996 to March 2003, 4 (2%) developed simultaneous thrombosis at 3 hours to 7 days (median, 4 days) after the operation. Emergent thrombectomy was performed in three patients; the remaining patient was registered in the Japan organ transplant network. All of the patients died due to hepatic failure (range, 18 hours to 6 days after the diagnosis; median, 2 days). Portal vein, hepatic artery, and hepatic vein velocity in the liver graft were measured every 12 hours by Doppler ultrasonography for 2 weeks after liver transplantation. These parameters were stable until just before the simultaneous thrombosis. These findings indicate that protocol Doppler ultrasonography can diagnose, but not predict, this fatal complication.
S
IMULTANEOUS HEPATIC ARTERY and portal vein thrombosis after liver transplantation is a lifethreatening event.1 We performed protocol Doppler ultrasonography twice a day for 2 weeks postoperatively. Previous reports suggested that the resistive index of the hepatic artery predicts hepatic artery thrombosis.2 Prompt diagnosis is useful for improving graft survival.3 We evaluated the significance of protocol Doppler ultrasound examinations as a predictor of simultaneous thrombosis in our series of 213 living donor liver transplantations (LDLTs). PATIENTS AND METHODS LDLT was performed in 213 patients (72 children under 18 years of age, 141 adults; 109 males, 104 females) from January 1996 to March 2003. Indications included biliary atresia (n ⫽ 68), viral hepatitis-related liver cirrhosis (n ⫽ 56), cholestatic diseases (n ⫽ 54), fulminant hepatic failure (n ⫽ 16), cryptogenic cirrhosis (n ⫽ 10), and metabolic diseases (n ⫽ 9). The patients and their families provided informed consent for all treatment modalities. The most common type of graft was left liver with or without the caudate (n ⫽ 80), followed by right liver (n ⫽ 68), left lateral sector (n ⫽ 51), and right lateral sector (n ⫽ 14). The donor and recipient hepatic arteries were anastomosed end-to-end with an interrupted 9-0 monofilament suture under a microscope. The portal vein was anastomosed with 6-0 monofilament. Anticoagulant therapy with prostaglandin E1 (0.01 g/kg per hour) and a protease inhibitor (mesilate gabexate; 1 mg/kg per hour) were administered intravenously for 14 days starting immediately after the operation. Antithrombin III concentrates, heparin, and low-molecular heparin were also used.4
Portal vein, hepatic artery, resistive index, and hepatic vein velocity in the liver graft were measured every 12 hours by Doppler ultrasonography (SSD 6500, Aloka Co Ltd, Tokyo, Japan) for 2 weeks after liver transplantation. The resistive index was determined as: (diastolic maximum flow velocity ⫺ systolic maximum flow velocity)/systolic maximum flow velocity. Aspartate aminotransferase (international normalized ratio) and total bilirubin levels were measured every day for 2 weeks after LDLT.
RESULTS
Hepatic artery thrombosis (HAT) developed in seven patients (3%) and portal vein thrombosis (PVT) in nine patients (4%). All patients survived revascularization without retransplantation. Four patients (2%) developed simultaneous thrombosis within 1 week in the postoperative course (range, 3 hours to 7 days; median, 4 days). See Table 1 for patient demographics. The duration of the operation From the Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan. This work was supported by a grant-in-aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan and Grants-in-aid for Research on HIV/AIDS and Research on Measures for Intractable Diseases from the Ministry of Health, Labor and Welfare of Japan. Address reprint requests to Y. Sugawara, MD, Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Japan. E-mail: [email protected]
© 2004 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/04/$–see front matter doi:10.1016/j.transproceed.2004.10.065
Transplantation Proceedings, 36, 3087–3089 (2004)
3087
3088
KANEKO, SUGAWARA, TOGASHI ET AL Table 1. Demographics of the Patients Complicated With Simultaneous Thrombosis Patient no.
Graft type Graft weight (g) Age/gender Indication Duration until thrombosis Duration between thrombosis and thrombectomy Duration between thrombosis and death ABO compatibility Lymphocyte cross-match PT-INR prior to thrombosis Total bilirubin prior to thrombosis (mg/dL)
1
2
3
4
LL 230 10 mo/M BA 5d 3h 18 h Compatible Negative 1.45 2.8
L⫹C 431 21 y/M Wilson’s disease 7d 3h 30 h Compatible Negative 1.42 2.8
L 294 7 y/F Primary hyperoxaluria 3h 2h 6d Identical Negative 1.35 1.8
RLS 403 58 y/F PBC 4d No thrombectomy 3d Compatible Negative 2.15 3.3
Abbreviations: LL, left lateral sector; L ⫹ C, left liver with caudate lobe; L, left liver; RLS, right lateral sector; BA, biliary ateresia; PBC, primary biliary cirrosis; PT-INR, prothrombin time international normalized ratio.
ranged from 585 to 950 minutes (median 720 minutes) and estimated blood loss per body weight was 22 to 61 mL/kg (48 mL/kg). The operative and postoperative courses were uneventful in all patients before the thrombosis was diagnosed. Simultaneous thrombosis was diagnosed by the findings of ultrasonography: no inflow or an alternating flow pattern in the hepatic vein. After the development of simultaneous thrombosis, thrombectomy was performed in three patients. Times of diagnosis until thrombectomy ranged from 2 to 3 hours. In the remaining patient, retransplantation was considered and the patient was registered in the Japan organ transplant network without thrombectomy. The liver function parameters, however, dramatically deteriorated. All of the patients died due to hepatic failure (range, 18 hours to 6 days after the diagnosis; median, 2 days). The hepatic artery flow velocity, resistive index, and portal vein flow velocity of these four patients were stable
Fig 1. Changes in parameters of hepatic and portal vein before thrombosis in four patients.
until just before simultaneous thrombosis (Fig 1). Similarly, aspartate aminotransferase, total bilirubin, and prothrombin time (international normalization ratio) decreased satisfactorily until just before simultaneous thrombosis (Fig 2).
DISCUSSION
Simultaneous HAT and PVT as diagnosed by Doppler ultrasonography rarely occur after whole liver transplantation. However, Doppler ultrasonography is generally not performed routinely. Nolten and Sproat5 reported a qualitative change in the Doppler waveform over time in HAT. Although the waveform was initially normal in appearance, it progressed to absent diastolic flow, dampening of the systolic peak, and eventual loss of the hepatic arterial signal. In the present study, these waveform changes were not observed before simultaneous HAT and PVT. We found that the ultrasonographic and biochemical findings were well maintained before simultaneous thrombosis. Emergent thrombectomy caused severe ischemia-reperfusion injury.
Fig 2. Changes in aspartate aminotransferase (AST), internalized normalized ratio (INR), and total bilirubin levels before thrombosis in four patients.
HEPATIC ARTERY AND PORTAL VEIN THROMBOSIS
Simultaneous thrombosis is fatal without emergency retransplantation. Reports on this complication are limited and the etiology of simultaneous thrombosis is usually unknown. Langnas and associates1 reported one patient complicated with protein C deficiency. Protocol Doppler ultrasonography enabled us to make a prompt diagnosis of simultaneous thrombosis and to consider retransplantation. REFERENCES 1. Langnas AN, Marujo W, Stratta RJ, et al: Vascular complications after orthotopic liver transplantation. Am J Surg 161:76, 1991
3089 2. Kaneko J, Sugawara Y, Akamatsu N, et al: Prediction of hepatic artery thrombosis by protocol Doppler ultrasonography in pediatric living donor liver transplantation. Abdom Imaging 29: 603, 2004 3. Sakamoto Y, Harihara Y, Nakatsuka T, et al: Rescue of liver grafts from hepatic artery occlusion in living-related liver transplantation. Br J Surg 86:886, 1999 4. Sugawara Y, Kaneko J, Akamatsu N, et al: Anticoagulant therapy against hepatic artery thrombosis in living donor liver transplantation. Transplant Proc 34:3325, 2002 5. Nolten A, Sproat IA: Hepatic artery thrombosis after liver transplantation: temporal accuracy of diagnosis with duplex US and the syndrome of impending thrombosis. Radiology 198:553, 1996
S
IMULTANEOUS HEPATIC ARTERY and portal vein thrombosis after liver transplantation is a lifethreatening event.1 We performed protocol Doppler ultrasonography twice a day for 2 weeks postoperatively. Previous reports suggested that the resistive index of the hepatic artery predicts hepatic artery thrombosis.2 Prompt diagnosis is useful for improving graft survival.3 We evaluated the significance of protocol Doppler ultrasound examinations as a predictor of simultaneous thrombosis in our series of 213 living donor liver transplantations (LDLTs). PATIENTS AND METHODS LDLT was performed in 213 patients (72 children under 18 years of age, 141 adults; 109 males, 104 females) from January 1996 to March 2003. Indications included biliary atresia (n ⫽ 68), viral hepatitis-related liver cirrhosis (n ⫽ 56), cholestatic diseases (n ⫽ 54), fulminant hepatic failure (n ⫽ 16), cryptogenic cirrhosis (n ⫽ 10), and metabolic diseases (n ⫽ 9). The patients and their families provided informed consent for all treatment modalities. The most common type of graft was left liver with or without the caudate (n ⫽ 80), followed by right liver (n ⫽ 68), left lateral sector (n ⫽ 51), and right lateral sector (n ⫽ 14). The donor and recipient hepatic arteries were anastomosed end-to-end with an interrupted 9-0 monofilament suture under a microscope. The portal vein was anastomosed with 6-0 monofilament. Anticoagulant therapy with prostaglandin E1 (0.01 g/kg per hour) and a protease inhibitor (mesilate gabexate; 1 mg/kg per hour) were administered intravenously for 14 days starting immediately after the operation. Antithrombin III concentrates, heparin, and low-molecular heparin were also used.4
Portal vein, hepatic artery, resistive index, and hepatic vein velocity in the liver graft were measured every 12 hours by Doppler ultrasonography (SSD 6500, Aloka Co Ltd, Tokyo, Japan) for 2 weeks after liver transplantation. The resistive index was determined as: (diastolic maximum flow velocity ⫺ systolic maximum flow velocity)/systolic maximum flow velocity. Aspartate aminotransferase (international normalized ratio) and total bilirubin levels were measured every day for 2 weeks after LDLT.
RESULTS
Hepatic artery thrombosis (HAT) developed in seven patients (3%) and portal vein thrombosis (PVT) in nine patients (4%). All patients survived revascularization without retransplantation. Four patients (2%) developed simultaneous thrombosis within 1 week in the postoperative course (range, 3 hours to 7 days; median, 4 days). See Table 1 for patient demographics. The duration of the operation From the Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan. This work was supported by a grant-in-aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan and Grants-in-aid for Research on HIV/AIDS and Research on Measures for Intractable Diseases from the Ministry of Health, Labor and Welfare of Japan. Address reprint requests to Y. Sugawara, MD, Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Japan. E-mail: [email protected]
© 2004 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/04/$–see front matter doi:10.1016/j.transproceed.2004.10.065
Transplantation Proceedings, 36, 3087–3089 (2004)
3087
3088
KANEKO, SUGAWARA, TOGASHI ET AL Table 1. Demographics of the Patients Complicated With Simultaneous Thrombosis Patient no.
Graft type Graft weight (g) Age/gender Indication Duration until thrombosis Duration between thrombosis and thrombectomy Duration between thrombosis and death ABO compatibility Lymphocyte cross-match PT-INR prior to thrombosis Total bilirubin prior to thrombosis (mg/dL)
1
2
3
4
LL 230 10 mo/M BA 5d 3h 18 h Compatible Negative 1.45 2.8
L⫹C 431 21 y/M Wilson’s disease 7d 3h 30 h Compatible Negative 1.42 2.8
L 294 7 y/F Primary hyperoxaluria 3h 2h 6d Identical Negative 1.35 1.8
RLS 403 58 y/F PBC 4d No thrombectomy 3d Compatible Negative 2.15 3.3
Abbreviations: LL, left lateral sector; L ⫹ C, left liver with caudate lobe; L, left liver; RLS, right lateral sector; BA, biliary ateresia; PBC, primary biliary cirrosis; PT-INR, prothrombin time international normalized ratio.
ranged from 585 to 950 minutes (median 720 minutes) and estimated blood loss per body weight was 22 to 61 mL/kg (48 mL/kg). The operative and postoperative courses were uneventful in all patients before the thrombosis was diagnosed. Simultaneous thrombosis was diagnosed by the findings of ultrasonography: no inflow or an alternating flow pattern in the hepatic vein. After the development of simultaneous thrombosis, thrombectomy was performed in three patients. Times of diagnosis until thrombectomy ranged from 2 to 3 hours. In the remaining patient, retransplantation was considered and the patient was registered in the Japan organ transplant network without thrombectomy. The liver function parameters, however, dramatically deteriorated. All of the patients died due to hepatic failure (range, 18 hours to 6 days after the diagnosis; median, 2 days). The hepatic artery flow velocity, resistive index, and portal vein flow velocity of these four patients were stable
Fig 1. Changes in parameters of hepatic and portal vein before thrombosis in four patients.
until just before simultaneous thrombosis (Fig 1). Similarly, aspartate aminotransferase, total bilirubin, and prothrombin time (international normalization ratio) decreased satisfactorily until just before simultaneous thrombosis (Fig 2).
DISCUSSION
Simultaneous HAT and PVT as diagnosed by Doppler ultrasonography rarely occur after whole liver transplantation. However, Doppler ultrasonography is generally not performed routinely. Nolten and Sproat5 reported a qualitative change in the Doppler waveform over time in HAT. Although the waveform was initially normal in appearance, it progressed to absent diastolic flow, dampening of the systolic peak, and eventual loss of the hepatic arterial signal. In the present study, these waveform changes were not observed before simultaneous HAT and PVT. We found that the ultrasonographic and biochemical findings were well maintained before simultaneous thrombosis. Emergent thrombectomy caused severe ischemia-reperfusion injury.
Fig 2. Changes in aspartate aminotransferase (AST), internalized normalized ratio (INR), and total bilirubin levels before thrombosis in four patients.
HEPATIC ARTERY AND PORTAL VEIN THROMBOSIS
Simultaneous thrombosis is fatal without emergency retransplantation. Reports on this complication are limited and the etiology of simultaneous thrombosis is usually unknown. Langnas and associates1 reported one patient complicated with protein C deficiency. Protocol Doppler ultrasonography enabled us to make a prompt diagnosis of simultaneous thrombosis and to consider retransplantation. REFERENCES 1. Langnas AN, Marujo W, Stratta RJ, et al: Vascular complications after orthotopic liver transplantation. Am J Surg 161:76, 1991
3089 2. Kaneko J, Sugawara Y, Akamatsu N, et al: Prediction of hepatic artery thrombosis by protocol Doppler ultrasonography in pediatric living donor liver transplantation. Abdom Imaging 29: 603, 2004 3. Sakamoto Y, Harihara Y, Nakatsuka T, et al: Rescue of liver grafts from hepatic artery occlusion in living-related liver transplantation. Br J Surg 86:886, 1999 4. Sugawara Y, Kaneko J, Akamatsu N, et al: Anticoagulant therapy against hepatic artery thrombosis in living donor liver transplantation. Transplant Proc 34:3325, 2002 5. Nolten A, Sproat IA: Hepatic artery thrombosis after liver transplantation: temporal accuracy of diagnosis with duplex US and the syndrome of impending thrombosis. Radiology 198:553, 1996