Comment on Comparison of three transfusion protocols prior to central venous catheterisation in patients with cirrhosis; a randomised controlled trial

Abstract

We read with interest Rocha et al.'s report of three transfusion regimens in critically ill patients with chronic liver disease (CLD)1.Rocha L.L. Neto A.S. Pessoa C.M.S. et al.Comparison of three transfusion protocols prior to central venous catheterization in patients with cirrhosis: a randomized controlled trial.J Thromb Haemost. 2020; 18: 560-570Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar and wish to highlight some concerns. First, empiric fresh frozen plasma (FFP) is no longer the current standard of care before low bleeding risk procedures. As the authors acknowledge, international normalized ratio does not predict bleeding in patients with CLD, with global hemostatic assays demonstrating overall rebalanced coagulation.2.Lisman T. Porte R.J. Pathogenesis, prevention, and management of bleeding and thrombosis in patients with liver diseases.Res Pract Thromb Haemost. 2017; 1: 150-161Abstract Full Text Full Text PDF PubMed Scopus (83) Google Scholar The UK survey cited by the authors to support the use of FFP highlighted usage was inappropriate in the preprocedure setting and, of note, no FFP use was reported before central venous catheter insertion.3.Desborough M.J. Hockley B. Sekhar M. et al.Patterns of blood component use in cirrhosis: a nationwide survey.Liver Int. 2012; 36: 522-529Crossref Scopus (43) Google Scholar Multiple international guidelines recommend against performing coagulation screens before low‐risk procedures. Additionally, these guidelines further recommend against FFP transfusion in the preprocedure setting because of a lack of efficacy and the potential to increase venous pressure and thereby procedural bleeding risk.4.O'Leary J.G. Greenberg C.S. Patton H.M. Caldwell S.H. AGA clinical practice update: coagulation in cirrhosis.Gastroenterology. 2019; 157: 34-43Abstract Full Text Full Text PDF PubMed Scopus (196) Google Scholar, 5.Biancofiore G. Blasi A. De Boer M.T. et al.Perioperative hemostatic management in the cirrhotic patient: a position paper on behalf of the Liver Intensive Care Group of Europe (LICAGE).Minerva Anestesiol. 2019; 85: 782-798Crossref PubMed Scopus (30) Google Scholar, 6.Green L. Bolton‐Maggs P. Beattie C. et al.British Society of Haematology Guidelines on the spectrum of fresh frozen plasma and cryoprecipitate products: their handling and use in various patient groups in the absence of major bleeding.Br J Haematol. 2018; 181: 54-67Crossref PubMed Scopus (89) Google Scholar A recent study measuring thrombin generation pre‐/post‐FFP in patients with CLD with bleeding or the periprocedural setting further confirmed the lack of hemostatic effect with a minimal increase (5.7%) in thrombin‐generating capacity following FFP. Of note, 96% of the cohort demonstrated thrombin generation profile within normal limits before FFP transfusion.7.Rassi A.B. d'Amico E.A. Tripodi A. et al.Fresh frozen plasma transfusion in patients with cirrhosis and coagulopathy: effect on conventional coagulation tests and thrombomodulin‐modified thrombin generation.J Hepatol. 2020; 72: 85-94Abstract Full Text Full Text PDF PubMed Scopus (51) Google Scholar Second, this raises questions regarding the study design as randomization to FFP with the intention of correcting prolonged coagulation times lacks a scientific rationale. Furthermore, given the reported incidence of clinically significant bleeding associated with central venous catheter insertion in those with coagulopathy is <0.2%,8.Fisher N.C. Mutimer D.J. Central venous cannulation in patients with liver disease and coagulopathy – a prosepective audit.Intensive Care Med. 1999; 25: 164-171Crossref Scopus (139) Google Scholar, 9.Mumtaz H. Williams V. Hauer‐Jensen M. Central venous catheter placement in patients with disorders of hemostasis.Am J Surg. 2000; 180: 503-505Abstract Full Text Full Text PDF PubMed Scopus (90) Google Scholar, 10.Tercan F. Ozkan U. Oguzkurt L. US‐guided placement of central vein catheters in patients with disorders of hemostasis.Eur J Radiol. 2008; 65: 253-256Abstract Full Text Full Text PDF PubMed Scopus (57) Google Scholar there was no reasonable expectation of any additional transfusion requirement postprocedure, rendering the primary outcome (proportion of patients transfused) uninformative with regard the efficacy of the intervention. The outcomes in the “standard care” and restrictive arms were determined entirely by the randomized intervention and were predictable before any patient participation. Finally, we disagree that larger multicenter studies are required to confirm these findings. There is no evidence base to use the coagulation screen to predict bleeding in CLD. There is clearly a need to raise awareness of the futility of using international normalized ratio as a marker of bleeding risk and to assess alternate markers, such as thromboelastography and/or thrombin generation with the caveat that FFP is unlikely to have any role in the nonbleeding patient with CLD. None. See also Rocha LL, Neto AS, Pessoa CMS, et al. Comparison of three transfusion protocols prior to central venous catheterization in patients with cirrhosis: A randomized controlled trial. J Thromb Haemost. 2020; 18: 560‐570. https://doi.org/10.1111/jth.14672 and Rocha LL, Corrêa TD. Reply to “Comment on ‘Comparison of three transfusion protocols prior to central venous catheterization in patients with cirrhosis; a randomized controlled trial’“. J Thromb Haemost. 2020; 18:754‐755. https://doi.org/10.1111/jth.14737