Lesley De Pietri

Thrombelastography-guided blood product use before invasive procedures in cirrhosis with severe coagulopathy: A randomized, controlled trial.

Bleeding is a feared complication of invasive procedures in patients with cirrhosis and significant coagulopathy (as defined by routine coagulation tests) and is used to justify preprocedure use of fresh frozen plasma (FFP) and/or platelets (PLT). Thromboelastography (TEG) provides a more comprehensive global coagulation assessment than routine tests (international normalized ratio [INR] and platelet count), and its use may avoid unnecessary blood product transfusion in patients with cirrhosis and significant coagulopathy (defined in this study as INR >1.8 and/or platelet count <50 × 109/L) who will be undergoing an invasive procedure. Sixty patients were randomly allocated to TEG‐guided transfusion strategy or standard of care (SOC; 1:1 TEG:SOC). The TEG group would receive FFP if the reaction time (r) was >40 min and/or PLT if maximum amplitude (MA) was <30 mm. All SOC patients received FFP and/or PLT per hospital guidelines. Endpoints were blood product use and bleeding complications. Baseline characteristics of the two groups were similar. Per protocol, all subjects in the SOC group received blood product transfusions versus 5 in the TEG group (100% vs. 16.7%; P < 0.0001). Sixteen SOC (53.3%) received FFP, 10 (33.3%) PLT, and 4 (13.3%) both FFP and PLT. In the TEG group, none received FFP alone (P < 0.0001 vs. SOC), 2 received PLT (6.7%; P = 0.009 vs. SOC), and 3 both FFP and PLT (not significant). Postprocedure bleeding occurred in only 1 patient (SOC group) after large‐volume paracentesis. Conclusions: In patients with cirrhosis and significant coagulopathy before invasive procedures, TEG‐guided transfusion strategy leads to a significantly lower use of blood products compared to SOC (transfusion guided by INR and platelet count), without an increase in bleeding complications. Remarkably, even in patients with significant coagulopathy, postprocedure bleeding was rare, indicating that TEG thresholds should be reevaluated. (Hepatology 2016;63:566–573)

Increased prothrombin time and platelet counts in living donor right hepatectomy: Implications for epidural anesthesia

The risks and benefits of adult‐to‐adult living donor liver transplantation need to be carefully evaluated. Anesthetic management includes postoperative epidural pain relief; however, even patients with a normal preoperative coagulation profile may suffer transient postoperative coagulation derangement. This study explores the possible causes of postoperative coagulation derangement after donor hepatectomy and the possible implications on epidural analgesia. Thirty donors, American Society of Anesthesiology I, with no history of liver disease were considered suitable for the study. A thoracic epidural catheter was inserted before induction and removed when laboratory values were as follows: prothrombin time (PT) > 60%, activated partial thromboplastin time < 1.24 (sec), and platelet count > 100,000 mmƒ£ (mm3). Standard blood tests were evaluated before surgery, on admission to the recovery room, and daily until postoperative day (POD) 5. The volumes of blood loss and of intraoperative fluids administered were recorded. Coagulation abnormalities observed immediately after surgery may be related mostly to blood loss and to the diluting effect of the intraoperative infused fluids, although the extent of the resection appears to be the most important factor in the extension of the PT observed from POD 1. In conclusion, significant alterations in PT and platelet values were observed in our patients who underwent uncomplicated major liver resection for living donor liver transplantation. Because the potential benefits of epidural analgesia for liver resection are undefined according to available data, additional prospective randomized studies comparing the effectiveness and safety of intravenous versus epidural analgesia in this patient population should be performed. (Liver Transpl 2004;10:1144–1149.)

Living Donor Liver Transplantation with Left Liver Graft

Small‐for‐size syndrome in LDLT is associated with graft exposure to excessive portal perfusion. Prevention of graft overperfusion in LDLT can be achieved through intraoperative modulation of portal graft inflow. We report a successful LDLT utilising the left lobe with a GV/SLV of only 20%. A 43 year‐old patient underwent to LDLT at our institution. During the anhepatic phase a porto‐systemic shunt utilizing an interposition vein graft anastomosed between the right portal branch and the right hepatic vein was performed. After graft reperfusion splenectomy was also performed. Portal vein pressure, portal vein flow and hepatic artery flow were recorded. A decrease of portal vein pressure and flow was achieved, and the shunt was left in place. The recipient post‐operative course was characterized by good graft function. Small‐for‐size syndrome by graft overperfusion can be successfully prevented by utilizing inflow modulation of the transplanted graft. This strategy can permit the use of left lobe in adult‐to‐adult living donor liver transplantation.

The use of intrathecal morphine for postoperative pain relief after liver resection: a comparison with epidural analgesia.

An epidural catheter is used in some institutions for postoperative analgesia after liver surgery. However, anesthesiologists may not feel comfortable leaving a catheter in the epidural space because of concern about coagulation disturbances and possible bleeding complications caused by impaired liver function. In this study, we tested a single-shot intrathecal morphine technique and compared it to a continuous epidural naropine infusion for postoperative analgesia in liver surgery. Fifty patients were randomly assigned to an epidural analgesia group (EP group; n = 25) and an intrathecal analgesia group (IN group; n = 25). The quality of analgesia assessed by a visual analog scale (VAS), the side effects, and the additional IV analgesic requirements were recorded. We did not observe any signs of cord compression. Time to first pain drug requirement was longer in the EP group compared to the IN group (25 ± 18.5 h versus 12 ± 10.3 h; P < 0.05). In both groups, the VAS remained less than 30 mm throughout the 48-h follow-up period. Consumption of IV morphine with a patient-controlled analgesia device in the IN group was larger (mostly from 24 to 48 h after surgery) than the EP group (12.0 ± 5.54 mg versus 3.1 ± 2.6 mg, respectively; P < 0.01). The incidence of vomiting was 4% in both groups, whereas the incidence of pruritus (16% versus 0%) and nausea (16% versus 4%) was more frequent in the IN group. No postdural puncture headache and no spinal hematoma occurred. After liver resection, a single dose of intrathecal morphine followed by patient-controlled morphine analgesia can provide satisfactory postoperative pain relief. The quality of this treatment, according to the VAS, is not inferior to continuous epidural analgesia up to 48 h after surgery.

Thromboelastographic changes in liver and pancreatic cancer surgery: hypercoagulability, hypocoagulability or normocoagulability?

Background and objective Despite clinical and laboratory evidence of perioperative hypercoagulability, alterations in haemostasis after potentially haemorrhagic oncologic surgery are difficult to predict. This study aims to evaluate the entity, the extent and the duration of perioperative coagulative alterations following pancreas and liver oncologic surgery, by the use of both routine tests and thromboelastogram (TEG). Methods Fifty-six patients undergoing liver (n = 38) and pancreatic (n = 18) surgery were studied. The coagulation profile was evaluated by platelet count, prothrombin time-international normalized ratio, activated partial thromboplastin time, antithrombin III and TEG at the beginning, at the end of the operation and on postoperative days 1, 3, 5 and 10. Results All preoperative coagulative screening and TEG traces were normal before incision. In the postoperative period of the liver and pancreas groups, despite an increase in prothrombin time-international normalized ratio, a reduction in antithrombin III and platelet count and normal activated partial thromboplastin time and fibrinogen, TEG evidenced a normocoagulability in the liver group, with a major tendency towards hypocoagulability in the pancreas group, as evidenced by a transient increase in R-time and K-time between postoperative days 1 and 3. During the study period, four cases of pulmonary embolism, resolved with heparin infusion, were recorded, in the absence of laboratory and thromboelastographic evidence of hypercoagulability. Conclusion Despite laboratory tests evidencing hypocoagulability in both groups, TEG traces showed a normocoagulability in liver resections, whereas a transient thromboelastographic hypocoagulability was evident in patients undergoing pancreas surgery. The discrepancy between laboratory values and thromboelastographic variables was even more evident in patients undergoing major liver resections compared with minor ones. Our study supports the role of thromboelastography, despite its limitations, as a valuable tool for the evaluation of the perioperative whole coagulation process and hypercoagulability changes and to increase patient safety through better management of antithrombotic therapy.

Hemostatic balance in patients with liver cirrhosis: Report of a consensus conference

Patients with cirrhosis present with hemostatic alterations secondary to reduced availability of pro-coagulant and anti-coagulant factors. The net effect of these changes is a rebalanced hemostatic system. The Italian Association of the Study of the Liver (AISF) and the Italian Society of Internal Medicine (SIMI) promoted a consensus conference on the hemostatic balance in patients with cirrhosis. The consensus process started with the review of the literature by a scientific board of experts and ended with a formal consensus meeting in Rome in December 2014. The statements were graded according to quality of evidence and strength of recommendations, and approved by an independent jury. The statements presented here highlight strengths and weaknesses of current laboratory tests to assess bleeding and thrombotic risk in cirrhotic patients, the pathophysiology of hemostatic perturbations in this condition, and outline the optimal management of bleeding and thrombosis in patients with liver cirrhosis.

Coagulopathy in Liver Diseases: Complication or Therapy?

Coagulopathy in cirrhosis is a composite condition where liver synthetic deficit rebalances coagulation to a parallel reduction of both pro- and anticoagulant factors. Cirrhosis is therefore no longer considered a hypocoagulable state but rather a more unstable hemostatic balance with a lower threshold for tipping toward thrombosis or bleeding. Tendency to bleeding in cirrhosis is due to the reduction in the synthesis of procoagulants and a low platelet count as well as hyperfibrinolysis. Variceal hemorrhage is a frequent bleeding complication in decompensated cirrhosis. However, the possible contribution of coagulopathy as a precipitant or an aggravating factor is poorly documented and further data are required to clarify its real contributing role. Moreover, apart from the gastrointestinal tract, the occurrence of spontaneous and procedure-related bleeding elsewhere in the body, whilst not uncommon, is less than would be expected. By contrast, a large-scale population-based study has shown the propensity towards venous thrombosis in patients with liver diseases. Portal vein thrombosis (PVT) is a critical but frequent event occurring in up to 40% of patients with liver cirrhosis. PVT causes deterioration of the clinical course, the complications of portal hypertension and an increase in post-transplant mortality. The pathogenesis of PVT includes both local alterations, like blood flow reduction and endothelial activation, and systemic derangement. Systemic prohemostatic alterations include high von Willebrand factor, low ADAMTS-13, low levels of anticoagulants (antithrombin, proteins C and S) and increases in procoagulants like factor VIII. Low-molecular-weight heparin such as enoxaparin has proven to be safe and effective in both the treatment and prevention of PVT. In addition, patients in prophylaxis with enoxaparin showed a lower rate of decompensation and a better survival without bleeding complications. In such patients, circulating bacterial DNA, endotoxemia and markers of inflammation were attenuated compared to controls. These results therefore suggest a possible connection between enoxaparin, decrease of endotoxemia and reduction of portal hypertension. The approach to the coagulopathy in patients with liver diseases is changing: while the main goal for clinicians so far has been to reduce the risk of bleeding, the results of these new studies highlight the importance of preventing or treating thrombophilic disorders like PVT to avoid microcirculatory damage and eventually liver decompensation.

Transoesophageal echocardiography during liver transplantation

Liver transplantation (LT) has become the standard of care for patients with end stage liver disease. The allocation of organs, which prioritizes the sickest patients, has made the management of liver transplant candidates more complex both as regards their comorbidities and their higher risk of perioperative complications. Patients undergoing LT frequently display considerable physiological changes during the procedures as a result of both the disease process and the surgery. Transoesophageal echocardiography (TEE), which visualizes dynamic cardiac function and overall contractility, has become essential for perioperative LT management and can optimize the anaesthetic management of these highly complex patients. Moreover, TEE can provide useful information on volume status and the adequacy of therapeutic interventions and can diagnose early intraoperative complications, such as the embolization of large vessels or development of pulmonary hypertension. In this review, directed at clinicians who manage TEE during LT, we show why the procedure merits a place in challenging anaesthetic environment and how it can provide essential information in the perioperative management of compromised patients undergoing this very complex surgical procedure.

Predictive factors of short term outcome after liver transplantation: A review

Liver transplantation represents a fundamental therapeutic solution to end-stage liver disease. The need for liver allografts has extended the set of criteria for organ acceptability, increasing the risk of adverse outcomes. Little is known about the early postoperative parameters that can be used as valid predictive indices for early graft function, retransplantation or surgical reintervention, secondary complications, long intensive care unit stay or death. In this review, we present state-of-the-art knowledge regarding the early post-transplantation tests and scores that can be applied during the first postoperative week to predict liver allograft function and patient outcome, thereby guiding the therapeutic and surgical decisions of the medical staff. Post-transplant clinical and biochemical assessment of patients through laboratory tests (platelet count, transaminase and bilirubin levels, INR, factor V, lactates, and Insulin Growth Factor 1) and scores (model for end-stage liver disease, acute physiology and chronic health evaluation, sequential organ failure assessment and model of early allograft function) have been reported to have good performance, but they only allow late evaluation of patient status and graft function, requiring days to be quantified. The indocyanine green plasma disappearance rate has long been used as a liver function assessment technique and has produced interesting, although not univocal, results when performed between the 1(th) and the 5(th) day after transplantation. The liver maximal function capacity test is a promising method of metabolic liver activity assessment, but its use is limited by economic cost and extrahepatic factors. To date, a consensual definition of early allograft dysfunction and the integration and validation of the above-mentioned techniques, through the development of numerically consistent multicentric prospective randomised trials, are necessary. The medical and surgical management of transplanted patients could be greatly improved by using clinically reliable tools to predict early graft function.

Reduced Transfusion During OLT by POC Coagulation Management and TEG Functional Fibrinogen: A Retrospective Observational Study.

Background Patients undergoing orthotopic liver transplantation are at high risk of bleeding complications. Several Authors have shown that thromboelastography (TEG)-based coagulation management and the administration of fibrinogen concentrate reduce the need for blood transfusion. Methods We conducted a single-center, retrospective cohort observational study (Modena Polyclinic, Italy) on 386 consecutive patients undergoing liver transplantation. We assessed the impact on resource consumption and patient survival after the introduction of a new TEG-based transfusion algorithm, requiring also the introduction of the fibrinogen functional thromboelastography test and a maximum amplitude of functional fibrinogen thromboelastography transfusion cutoff (7 mm) to direct in administering fibrinogen (2012-2014, n = 118) compared with a purely TEG-based algorithm previously used (2005-2011, n = 268). Results After 2012, there was a significant decrease in the use of homologous blood (1502 ± 1376 vs 794 ± 717 mL, P < 0.001), fresh frozen plasma (537 ± 798 vs 98 ± 375 mL, P < 0.001), and platelets (158 ± 280 vs 75 ± 148 mL, P < 0.005), whereas the use of fibrinogen increased (0.1 ± 0.5 vs 1.4 ± 1.8 g, P < 0.001). There were no significant differences in 30-day and 6-month survival between the 2 groups. Conclusions The implementation of a new coagulation management method featuring the addition of the fibrinogen functional thromboelastography test to the TEG test according to an algorithm which provides for the administration of fibrinogen has helped in reducing the need for transfusion in patients undergoing liver transplantation with no impact on their survival.