A 54-year-old female JW patient (body weight, 50 kg) diagnosed with liver cirrhosis complicated by hepatitis B viral infection presented to the bloodless center in our institute to assess whether LDLT was possible. She had massive ascites without encephalopathy, but was in good physical condition otherwise. Initial laboratory findings were hemoglobin (Hb) of 8.1 g/dl, platelets 51 × 10⁹/L, prothrombin time (PT) 1.65 (international normalized ratio, INR), albumin 2.1 g/dl, creatinine 1.5 mg/dl, and total bilirubin 3.04 mg/dl. We discussed with a surgeon the possibility of LT without transfusion. Acceptable transfusion alternatives were confirmed after discussion with the Jehovah's Witnesses Hospital Liaison Committee and the patient. The patient refused to receive any red blood cells (RBCs), fresh frozen plasma, or platelet concentrate, but agreed to receive human albumin, recombinant factor VIIa and VIIIa, fibrinogen concentrate, cryoprecipitate, and intraoperative cell salvage (ICS) via a continuous circuit to the patient's circulation. She also accepted reinfusion of collected whole blood acquired from acute normovolemic hemodilution (ANH) provided via a continuous circuit. The organ transplantation ethics committee then met to decide whether those surgical restrictions were ethically acceptable because this was the first LT in an adult JW patient in South Korea. Following committee approval, the patient decided to undergo LT. Her son, who is not a JW, chose to donate his right hepatic lobe.

Erythropoiesis-stimulating agent (ESA) therapy with recombinant human erythropoietin (rHuEpo) and intravenous iron was initiated along with folic acid and vitamin B12 to increase the patient's red cell mass. Subcutaneous rHuEpo (Epokine®, CJ HealthCare, Seoul, Korea) at 10,000 IU and intravenous iron (Venoferrum®, JW Pharmaceutical, Seoul, Korea) at 200 mg were administered three times per week. After 9 weeks' administration, the Hb level increased to 13.1 g/dl and the patient was scheduled for surgery the next day. On arrival at the operating theater, monitoring was initiated with a five-lead ECG, noninvasive blood pressure cuff, pulse oximeter, and bispectral index sensor. Anesthesia was induced with propofol at 80 mg and, after the administration of rocuronium at 50 mg, the patient was intubated. Anesthesia was maintained with oxygen, air, desflurane, and continuous remifentanil and rocuronium infusion.

Hemodynamic monitoring included the right radial and femoral artery pressures, central and right femoral vein pressures, pulmonary artery and capillary wedge pressures, and cardiac output measurements via a Swan-Ganz catheter. A transesophageal echocardiography probe was inserted to monitor volume status and systolic function and to diagnose the cause of any sustained hypotension that occurred during surgery. The right radial artery was used for blood sampling and drainage of the patient's blood for ANH. After vascular catheterization, ANH was initiated. The patient's blood volume was estimated at 3,000 ml (60 ml/body weight, kg). The target Hb level was approximately 10.0 g/dl. We collected 960 ml of whole blood for ANH, which was divided into three CPDA-transfusion bags (320 ml each), while maintaining continuous infusion to the patient via the radial artery catheter. Briefly, we did not replace blood loss with fluid simultaneously as is usually done in ANH. No fluid was administered until after collection of the first 500 ml whole blood to prevent dilution of RBC, coagulation factors, and platelets. Thereafter, 750 ml 5% Albumin® (Green Cross Corp., Yongin, Korea) and 500 ml Plasma Solution A® (CJ HealthCare, Seoul, Korea) were administered to replace lost blood until ANH was completed. It took 15 min to obtain each unit. There were no changes in mean arterial pressure, heart rate, mixed venous oxygen saturation (SvO₂, maintained around 90%), or cardiac output during 45 min of ANH. Central venous pressure (CVP) decreased by 1 mmHg from the initial value of 4 mmHg. Pre-ANH Hb was 13.4 g/dl, platelets 32 × 10⁹/L, and fibrinogen 113 mg/dl. Post-ANH Hb was 10.8 g/dl, platelets 29 × 10⁹/L, and fibrinogen 82 mg/dl. To prevent fibrinolysis, 40 mg/kg tranexamic acid was administered intravenously for 20 min before the surgical incision and then continuously infused at a rate of 10 mg/kg/h. All blood from the surgical field was salvaged using a cell saver until biliary anastomosis was initiated. Plasma Solution A® was administered at a rate of 5 ml/kg/h during the surgery. Blood loss was replaced with Plasma Solution A® at a 1 : 3 ratio throughout the surgery unless there was sudden blood loss, which was replaced by 5% Albumin® at a 1 : 1 ratio. CVP was maintained at less than 5 mmHg throughout the dissection phase. Norepinephrine (0.1 to 0.27 µg/kg/min) was used as a primary vasopressor to maintain the mean arterial pressure at 65 mmHg or above. During the pre-anhepatic phase, approximately 7,300 ml ascitic fluid was drained. Acute hemorrhage occurred when the inferior vena cava was injured during mobilization of the diseased liver, which caused 350 ml of blood loss until prompt hemostasis using a total inferior vena cava (IVC) clamp. We began to transfuse salvaged blood approximately 1 h after starting surgery to maintain the hemoglobin level at around 9 g/dl. One hour after beginning the anhepatic phase, ANH blood was retransfused slowly from the recently collected blood, as is recommended within 6 h of collection. The Hb level was maintained above 9 g/dl until the end of the surgery. Fibrinogen decreased to 56 mg/dl 3 h postoperatively. Fibrinogen concentrate (Fibrinogen Inj®, Green Cross Corp., Yongin, Korea) at 3.0 g was administered intravenously, which increased the fibrinogen concentration to 136 mg/dl.

There was no fibrinolysis on thromboelastography or oozing in the surgical field during the operation. Graft reperfusion was accomplished without any cardiovascular instability. SvO₂ remained high during the entire operation, suggesting that there was no global oxygen supply/demand imbalance. The operation concluded uneventfully and the patient was transferred to the intensive care unit (ICU) while intubated. The total anesthesia duration was 8 h and the operation time was 6.6 h. Total blood loss was 940 ml. Plasma Solution A® at 4,800 ml, 5% Albumin® at 1,000 ml, and 470 ml of salvaged blood were administered. Urine output was around 900 ml.

Postoperatively, Hb was 11.9 g/dl, platelets 19 × 10⁹/L, PT 2.49 INR, and fibrinogen 122 mg/dl (Table 1). The postoperative recovery was uneventful and the patient did not receive any blood products. She was discharged on postoperative day 15 without any complications. She is still in good health 5 years after surgery

A 47-year-old male JW patient suffering from alcoholic liver cirrhosis presented for LDLT. He had diabetes that was controlled with insulin and was administered ESA therapy with rHuEpo, which increased his hematocrit in preparation for bloodless surgery. After 27 episodes of ESA therapy over the six months before LDLT, the Hb level increased from 7.4 to 10.8 g/dl. Preoperative evaluations (echocardiography, pulmonary function test, esophagoduodenoscopy, chest radiography, and electrocardiogram) were within normal limits. Laboratory tests revealed Hb of 10.8 g/dl, platelets 46 × 10⁹/L, PT 1.84 INR, fibrinogen 159 mg/dl, and albumin 3.2 g/dl.

Anesthesia was induced with pentothal sodium at 400 mg, and after administration of vecuronium at 10 mg, the patient was intubated. Anesthesia was maintained with oxygen, air, and sevoflurane. Hemodynamic monitoring included the right radial and femoral artery pressures, central and right femoral vein pressures, pulmonary artery and capillary wedge pressures, and cardiac output measurements via a Swan-Ganz catheter. Despite insertion of the Swan-Ganz catheter, cardiac output was not checked, so we monitored only SvO₂. To maintain the body temperature during surgery, fluid was heated with a Level 1® Fast Flow Fluid Warmer (Smiths Industries, Rockland, MA, USA) and peripheral vascular access was blocked to prevent infusion of cold fluids.

During the intraoperative period, vecuronium was infused continuously (1.0 µg/kg/min) and sevoflurane was replaced with isoflurane after positioning the retractor. We regulated the concentration of isoflurane while aiming for 40 to 60 on the bispectral index. During the pre-anhepatic phase, there were no ascites and 500 ml of Hextend® (CJ HealthCare) was infused. We used regular insulin because the patient's glucose was 219 mg/dl and dopamine (5.0 µg/kg/min) was administered continuously for hemodynamic stability. Arterial blood gas analysis was performed every 1 h to monitor the Hb level. The authors administered 300 ml salvaged blood whenever the Hb level dropped below 9 g/dl. The lowest Hb level was 6.7 g/dl during the anhepatic phase. Continuous infusion of norepinephrine (0.05 µg/kg/min) was started before reperfusion and tranexamic acid at 500 mg was injected twice during the anhepatic and postreperfusion phase. There was no evidence of fibrinolysis on thromboelastometry, which was monitored at least every 2 h during surgery. To reduce blood loss, we used ICS except during biliary opening until the end of surgery. To conserve fluid effectively, we wrung out the gauze pads prior to removing them from the abdominal cavity.

During the 12 h and 30 min of surgical time, 8,300 ml Plasma Solution A®, 2,050 ml 5% Albumin®, 900 ml half normal saline, 1,000 ml Hextend®, and 2,065 ml of salvaged blood were infused. Urine output was 570 ml and estimated blood loss was about 2,500 ml. After surgery, the patient was transferred to the ICU while still intubated with continuation of dopamine (5 µg/kg/min) and norepinephrine (0.2 µg/kg/min).

The last blood test before the end of anesthesia revealed Hb of 10.5 g/dl, platelets 39 × 10⁹/L, PT 7.75 INR, and fibrinogen 49 mg/dl (Table 2). The patient was extubated on the first postoperative day. Although he could not receive a transfusion of fresh frozen plasma or cryoprecipitate, PT was decreased and fibrinogen was increased with 2.18 INR and 211 mg/dl, respectively about 7 days after LDLT.

On postoperative day 17, leakage of the hepaticojejunostomy and small bowel perforation were suspected, so the patient underwent a second operation for resection and anastomosis of the small bowel. Continuous renal replacement therapy was initiated and maintained until postoperative day 28. He was transferred to the ward 36 days after LDLT, but was reintubated and transferred to the ICU on postoperative day 60 due to hypotension and respiratory failure. He died on postoperative day 76 due to several complications including intra-abdominal infection, pneumonia, and chronic renal failure.