Preoperative Fibrinogen Level and Bleeding in Liver Transplantation for End-stage Liver Disease: A Cohort Study.

BACKGROUND: Liver transplantation is a high-risk surgery associated with important perioperative bleeding and transfusion needs. Uncertainties remain on the association between preoperative fibrinogen level and bleeding in this population. METHODS: We conducted a cohort study that included all consecutive adult patients undergoing a liver transplantation for end-stage liver disease in 1 center. We analyzed the association between the preoperative fibrinogen level and bleeding-related outcomes. Our primary outcome was intraoperative blood loss, and our secondary outcomes were estimated perioperative blood loss, intraoperative and perioperative red blood cell transfusions, reinterventions for bleeding and 1-y graft and patient survival. We estimated linear regression models and marginal risk models adjusted for all important potential confounders. We used restricted cubic splines to explore potential nonlinear associations and reported dose-response curves. RESULTS: We included 613 patients. We observed that a lower fibrinogen level was associated with a higher intraoperative blood loss, a higher estimated perioperative blood loss and a higher risk of intraoperative and perioperative red blood cell transfusions (nonlinear effects). Based on an exploratory analysis of the dose-response curves, these effects were observed below a threshold value of 3 g/L for these outcomes. We did not observe any association between preoperative fibrinogen level and reinterventions, 1-y graft survival or 1-y patient survival. CONCLUSIONS: This study suggests that a lower fibrinogen level is associated with bleeding in liver transplantation. The present results may help improving the selection of patients for further studies on preoperative fibrinogen administration in liver transplant recipients with end-stage liver disease.

Effect of intraoperative hypovolemic phlebotomy on transfusion and clinical outcomes in patients undergoing hepatectomy: a retrospective cohort study.

BACKGROUND: There is no consensus on how to best achieve a low central venous pressure during hepatectomy for the purpose of reducing blood loss and red blood cell (RBC) transfusions. We analyzed the associations between intraoperative hypovolemic phlebotomy (IOHP), transfusions, and postoperative outcomes in cancer patients undergoing hepatectomy. METHODS: Using surgical and transfusion databases of patients who underwent hepatectomy for cancer at one institution (11 January 2011 to 22 June 2017), we retrospectively analyzed associations between IOHP and RBC transfusion on the day of surgery (primary outcome), and with total perioperative transfusions, intraoperative blood loss, and postoperative complications (secondary outcomes). We fitted logistic regression models by inverse probability of treatment weighting to adjust for confounders and reported adjusted odds ratio (aOR). RESULTS: There were 522 instances of IOHP performed during 683 hepatectomies, with a mean (standard deviation) volume of 396 (119) mL. The IOHP patients had a 6.9% transfusion risk on the day of surgery compared with 12.4% in non-IOHP patients (aOR, 0.53; 95% confidence interval [CI], 0.29 to 0.98; P = 0.04). Total perioperative RBC transfusion tended to be lower in IOHP patients compared with non-IOHP patients (14.9% vs 22.4%, respectively; aOR, 0.72; 95% CI, 0.44 to 1.16; P = 0.18). In patients with a predicted risk of ≥ 47.5% perioperative RBC transfusion, 24.6% were transfused when IOHP was used compared with 56.5% without IOHP. The incidence of severe postoperative complications (Clavien-Dindo scores ≥ 3) was similar in patients whether or not IOHP was performed (15% vs 16% respectively; aOR, 0.97; 95% CI, 0.53 to 1.54; P = 0.71). CONCLUSIONS: The use of IOHP during hepatectomy was associated with less RBCs transfused on the same day of surgery. Trials comparing IOHP with other techniques to reduce blood loss and transfusion are needed in liver surgery.

RéSUMé: CONTEXTE: Il n'existe pas de consensus quant à la meilleure façon d'obtenir une pression veineuse centrale basse pendant une hépatectomie dans le but de réduire les pertes et les transfusions sanguines. Nous avons analysé les associations entre la phlébotomie hypovolémique peropératoire, les transfusions, et les résultats cliniques postopératoires chez les patients qui subissent une hépatectomie pour cancer. MéTHODE: À l'aide de bases de données chirurgicales et transfusionnelles de patients ayant subi une hépatectomie pour cancer dans un seul établissement (du 11 janvier 2011 au 22 juin 2017), nous avons rétrospectivement analysé les associations entre la phlébotomie hypovolémique peropératoire et les transfusions érythrocytaires le jour de la chirurgie (critère d'évaluation principal) et avec les transfusions périopératoires totales, les pertes sanguines peropératoires, et les complications postopératoires (critères d'évaluation secondaires). Nous avons utilisé des modèles de régression logistique avec pondération de probabilité inverse de traitement afin de tenir compte des facteurs de confusion et rapporté les rapports de cotes ajustés (RCa). RéSULTATS: Il y a eu 522 phlébotomies hypovolémiques peropératoires exécutées au cours de 683 hépatectomies, avec un volume moyen (écart type) de 396 (119) mL. Les patients ayant eu une phlébotomie hypovolémique peropératoire avaient un risque transfusionnel de 6,9 % le jour de la chirurgie, comparativement à 12,4 % pour les patients sans phlébotomie (RCa, 0,53; intervalle de confiance [IC] de 95 %, 0,29 à 0,98; P = 0,04). Les transfusions périopératoires totales d'érythrocytes tendaient à être moins fréquentes chez les patients ayant subi une phlébotomie hypovolémique peropératoire par rapport aux patients sans phlébotomie (14,9 % vs 22,4 %, respectivement; RCa, 0,72; IC 95 %, 0,44 à 1,16; P = 0,18). Pour les patients présentant un risque prédit de transfusion périopératoire d'érythrocytes ≥ à 47,5 %, 24,6 % de ceux qui ont eu une phlébotomie hypovolémique peropératoire ont été transfusés, comparativement à 56,5 % sans phlébotomie. L'incidence des complications postopératoires graves (scores de Clavien-Dindo ≥ 3) était semblable chez tous les patients, avec ou sans phlébotomie hypovolémique peropératoire (15 % vs 16 % respectivement; RCa, 0,97; IC 95 %, 0,53 à 1,54; P = 0,71). CONCLUSIONS: L'utilisation de la phlébotomie hypovolémique peropératoire pendant une hépatectomie était associée à un moins grand nombre de transfusions érythrocytaires le jour de la chirurgie. Des études qui compareront la phlébotomie hypovolémique peropératoire à d'autres techniques visant à réduire les pertes et les transfusions sanguines sont nécessaires en chirurgie hépatique.

TACO-BEL-3: a feasibility study and a retrospective audit of diuretics for patients receiving blood transfusion at ten hospitals.

BACKGROUND AND OBJECTIVES: Transfusion-associated circulatory overload (TACO) is the leading cause of transfusion-related morbidity and mortality. A recently completed pilot trial randomized patients to pre-transfusion furosemide versus placebo but had a slower than expected enrollment rate. We sought to determine whether the lack of recruitment was due to a paucity of eligible patients or excessively restrictive eligibility criteria. MATERIALS AND METHODS: At 10 sites, eligible patients were retrospectively identified by first screening blood bank databases over one month for all transfusion episodes meeting trial inclusion criteria, defined as non-surgical patients receiving single RBC unit transfusions. The age threshold was decreased from 65 to 50 years. The first 10 patients meeting inclusion criteria then underwent detailed chart review for the exclusion criteria. The incidence of TACO and furosemide use was also recorded. RESULTS: At the 10 sites, 11 969 red cell units were transfused over 1 month and 1356 met the inclusion criteria. Of the 100 charts reviewed, 60 (60%) had no exclusion criteria. Active bleeding was the most common reason for ineligibility. There were 813 eligible transfusion episodes. Of the eligible patients, 17 (28·3%) had evidence of congestive heart failure, and furosemide was prescribed in 24 (40%). Despite the use of a lower age threshold, three cases of TACO were detected with an incidence of 3%. CONCLUSION: A large number of transfusion episodes met eligibility criteria. With a 3% incidence of TACO, 50% decrease through the use pre-transfusion furosemide and a target consent rate of 30%, a definitive trial of approximately 3000 patients could be completed within 1 year.

Association between intraoperative rotational thromboelastometry or conventional coagulation tests and bleeding in liver transplantation: an observational exploratory study.

INTRODUCTION: Liver transplantation is associated with major blood loss and transfusions. Our objective was to evaluate the association between coagulation results (rotational thromboelastometry (ROTEM) and conventional coagulation tests) and intraoperative bleeding or perioperative red blood cell (RBC) transfusions in liver transplantation. METHODS: We measured ROTEM values and conventional coagulation tests at the beginning of surgery, after graft reperfusion and at the end of surgery. We did bivariate correlation and multivariable regression analyses to explore the association between test results and either intraoperative bleeding or perioperative RBC transfusions. RESULTS: We enrolled 75 consecutive patients. Median [Q1-Q3] intraoperative blood loss was 1400 mL [675-2300] and 59% of patients did not receive any RBC transfusion either intraoperatively or postoperatively. In multivariable analyses, FIBTEM maximal clot firmness (MCF) measured at the beginning of surgery was associated with lower intraoperative blood loss (ß = -106 mL for each mm; 95% CI, -203 to -9 mL). Both a higher haemoglobin concentration (multiplicative factor = 0.89 for each g/L; 95% CI, 0.84 to 0.95) and FIBTEM MCF measured at the end of surgery (multiplicative factor = 0.68 for each mm; 95% CI, 0.48 to 0.95) were associated with fewer postoperative RBC transfusions. CONCLUSION: FIBTEM MCF was strongly associated with intraoperative blood loss and postoperative transfusions while other coagulation results were not. This study might inform future clinical trials on ROTEM-based interventions in liver transplantation. STUDY REGISTRATION: Clinical Trials.gov: NCT02356068.

Severe immune thrombocytopenic purpura in critical COVID-19.

COVID-19 is a new disease with many undescribed clinical manifestations. We report herein a case of severe immune thrombocytopenic purpura (ITP) in a critical COVID-19 patient. A patient presented a severe episode of immune thrombocytopenia (< 10 × 109/L) 20 days after admission for a critical COVID-19. This thrombocytopenia was associated with a life-threatening bleeding. Response to first-line therapies was delayed as it took up to 13 days after initiation of intravenous immunoglobulin and high-dose dexamethasone to observe an increase in platelet count. COVID-19 may be associated with late presenting severe ITP. Such ITP may also be relatively resistant to first-line agents. Hematological manifestations of COVID-19, such as the ones associated with life-threatening bleeding, must be recognized.

Simulation-based education for transfusion medicine.

BACKGROUND: The administration of blood products is frequently determined by physicians without subspecialty training in transfusion medicine (TM). Education in TM is necessary for appropriate utilization of resources and maintaining patient safety. Our institution developed an efficient simulation-based TM course with the goal of identifying key topics that could be individualized to learners of all levels in various environments while also allowing for practice in an environment where the patient is not placed at risk. STUDY DESIGN AND METHODS: A 2.5-hour simulation-based educational activity was designed and taught to undergraduate medical students rotating through anesthesiology and TM elective rotations and to all Clinical Anesthesia Year 1 (CA-1) residents. Content and process evaluation of the activity consisted of multiple-choice tests and course evaluations. RESULTS: Seventy medical students and seven CA-1 residents were enrolled in the course. There was no significant difference on pretest results between medical students and CA-1 residents. The posttest results for both medical students and CA-1 residents were significantly higher than pretest results. The results of the posttest between medical students and CA-1 residents were not significantly different. CONCLUSION: The TM knowledge gap is not a trivial problem as transfusion of blood products is associated with significant risks. Innovative educational techniques are needed to address the ongoing challenges with knowledge acquisition and retention in already full curricula. Our institution developed a feasible and effective way to integrate TM into the curriculum. Educational activities, such as this, might be a way to improve the safety of transfusions.

Utilization of cross-matched or HLA-matched platelets for patients refractory to platelet transfusion.

BACKGROUND: Use of cross matching or HLA matching for donor selection is the basis of managing patients refractory to platelet (PLT) transfusion. Because of changes in patient care, we evaluated the effect of cross matching and HLA matching in patients refractory to PLT transfusion. STUDY DESIGN AND METHODS: We identified all patients who received either HLA-matched or cross-matched PLTs during a 3-year period at our medical center. Patient records were reviewed and laboratory data were collected. One- to 4-hour corrected count increments (CCIs) were calculated for transfusions given up to 72 hours before receiving these specialized units and the HLA-matched or cross-matched units themselves. RESULTS: Thirty-two patients were identified who received a total of 354 PLT transfusions. Of these, 161 were from unselected apheresis, 152 were cross matched, and 41 were HLA selected. The median CCI for random-donor transfusions was 0 (range, 0 × 10(9)-10.5 × 10(9)/L), for cross-matched PLT transfusions 1.7 × 10(9)/L (0 × 10(9)-5.1 × 10(9)/L), and for HLA-matched transfusions 1.2 × 10(9)/L (0 × 10(9)-13.9 × 10(9)/L). Only 25 and 30% of cross-match-compatible or HLA-selected units, respectively, gave 1- to 4-hour CCIs of more than 5.0 × 10(9)/L compared to 12% of the transfusions from random donors. There were no significant differences in the 1- to 4-hour CCIs when comparing random units with HLA-selected or cross-match-compatible units. There was also no significant difference when comparing the HLA-matched and cross-match-compatible PLT units with each other. CONCLUSIONS: The use of cross-match-compatible or HLA-matched units did not provide better increments in PLT count when compared to random nonselected units. Clinical factors may overpower immunologic matching.

The influence of bleeding on trigger changes for platelet transfusion in patients with chemotherapy-induced thrombocytopenia.

BACKGROUND: For patients with thrombocytopenia without bleeding risk factors, a platelet transfusion trigger of 10 × 10(9) /L is recommended. No studies have evaluated the clinicians' decision-making process leading to trigger changes. STUDY DESIGN AND METHODS: We report on the evaluation of trigger changes and the relation with bleeding. Eighty patients previously enrolled in the SPRINT trial represent the patient population for the current analysis. RESULTS: Seventy-four patients had a starting trigger of 10 × 10(9) /L. Only a minority of patients treated with chemotherapy alone (3/12, 25%) and autologous transplant (6/15, 40%) had a change in their trigger in contrast to the majority of allogeneic transplant (37/47, 79%; p = 0.001 and p = 0.009, respectively, when compared to allogeneic transplant group). Bleeding was the main reason reported by clinicians for a trigger change, but the occurrence of significant bleeding (Grade 2-4) was similar in patients with or without a trigger change (51 and 54%, p = 1.00). Clinicians were influenced by the bleeding system: grade 1 mucocutaneous bleeding leading to a trigger change was overrepresented (71% of cases), as was grade 2 genitourinary bleeding not leading to a trigger change (57% of cases). CONCLUSION: A universal trigger of 10 × 10(9) /L may not be maintained in a diverse population of patients with their respective bleeding risk factors. Because the trigger is changed often, it may not be as effective as previously believed.