Goal directed hemostatic therapy for severe bleeding part one
Myron Yaster MD and David Jobes MD
Ah, the coagulation cascade…Are your eyes already glazing over? Does the very thought make you want to throw up? Are you having flashbacks to being held hostage in medical school or while you were studying for your board examinations? And, why oh why are they Roman Numerals? Indeed, maybe the only worse thing than the coagulation cascade is having to memorize the Krebs cycle. And yet in our daily practice, bleeding and massive hemorrhage is a frequent event that we have to expertly deal with perioperatively. So, imagine my surprise when I read today’s PAAD by Crochemore et al.,1 an ADULT ICU goal directed management paper and thought “WOW” or “Eureka”! It was like finding the Rosetta stone deciphering the hieroglyphics (or Roman Numerals) of hemostasis!
I immediately realized that this article would be invaluable to all of you. However, I needed help and called one of my mentors, Dr. David Jobes, who is an expert on this subject matter, to help. Even with his help, I/we couldn’t do it in a 5-6 minute read and decided to split this PAAD into 2 or really 3 parts. Even doing this, we simply can’t do justice to this article and we would encourage all of you to read the paper in its entirety or discuss it more fully in a journal club or teaching conference. (And for our readers who run educational national or international meetings, this paper is a blueprint in how to present this topic to a large audience.)
Finally, the article does not describe how to put this management program into your actual clinical practice. What are the roadblocks? Can they be overcome? Dr. Jobes will discuss the implementation issues in part 3. Myron Yaster MD
Original review article
Crochemore T, Görlinger K, Lance MD. Early Goal-Directed Hemostatic Therapy for Severe Acute Bleeding Management in the Intensive Care Unit: A Narrative Review. Anesth Analg. 2024 Mar 1;138(3):499-513. doi: 10.1213/ANE.0000000000006756. Epub 2024 Feb 16. PMID: 37977195; PMCID: PMC10852045.
Hemorrhage, and occasionally massive hemorrhage, I s a common perioperative event that we must expertly deal with in our everyday practice. In today’s PAAD, Crochemore et al.1 present an early goal-directed hemostatic management plan designed by the authors for the ADULT ICU but can just as easily be used in the pediatric ORs and ICUs. (Figure)
“Hemostasis is an interplay between the endothelium, primary hemostasis, procoagulant system, natural inhibitors as well as fibrinolytic and antifibrinolytic systems ( figure). In this model, coagulation takes place on cell surfaces in 4 steps (initiation, amplification, propagation, and stabilization).” Understanding this model is key to understanding treatment and is usually the point that most of us zone out and lose all hope. Not to worry, we will come back to it in Part 2 tomorrow when we discuss how we can use point of care testing to figure out how to treat coagulopathies. But first things first.
As with any perioperative emergency: Declare an emergency, call for help, go through your ABCs, and although not a step in this article, OPEN YOUR PEDI CRISIS app! Under the massive hemorrhage tab perform the following steps: Notify the blood bank and if it hasn’t already been done send a sample for Type and Cross. Activate your institution’s massive transfusion protocol, and consider RBC:FFP:Platelets in a 2:1:1 or 1:1:1 transfusion ratio. Use uncross matched O negative packed red blood cells until type specific or type and cross matched blood is available. Finally, the biochemical environment determined by pH, temperature, and Ca 2+, is critical for thrombin generation and clot formation, so treat any abnormalities.
OK, back to the article. Laboratory testing is essential and viscoelastic testing (VET) is the Rosetta stone in diagnosis and management rather than conventional coagulation testing like Prothrombin time (PT), international normalized ratio (INR), and activated partial thromboplastin time (aPTT).1-3 “Viscoelastic testing (VET) provides a quick and comprehensive graphical representation of the dynamics of the entire clot formation and lysis process that can be evaluated and reviewed at the point of care. The main technologies include rotational thromboelastometry (TEM, Tem Innovation GmbH), and thromboelastography (TEG, Haemonetics Corporation). However, more recently, the Quantra analyzer (HemoSonics LLC) is based on sonorheometry, and the ClotPro system (enicor GmbH; Haemonetics Corporation) based on thromboelastometry has been introduced into the market, too.4”1 A detailed description of thromboelastography and thromboelastometry is beyond the scope of this PAAD review and can be found in the article.
Viscoelastic testing has been shown to be effective in reducing bleeding, transfusion requirements, complication rates, and health care costs in perioperative settings by rationalizing the use of blood components and alternatives to transfusion such as hemostatic drugs, antifibrinolytics, and coagulation factor concentrates. Crochemore et al.1 propose “a functional classification of coagulation based on the physiology in 3 phases: thrombin generation, clot firmness, and clot stabilization (figure).
Thrombin generation is determined by enzymatic coagulation factors and can be modified by the biochemical environment, anticoagulants, inhibitors, and coagulation factor deficiencies. This phase is represented by CT (clotting time) in ROTEM.5 Clot firmness is determined by fibrin polymerization, platelet aggregation, and platelet-fibrin-interaction. This can be modified by factor XIII (FXIII) and colloids.5,6 This phase can be altered by deficiency of any of these components and corresponds to early (amplitude 5 or 10 minutes after CT: A5 and A10) and late clot firmness parameters (maximum clot firmness: MCF) in ROTEM.5 Clot stabilization is determined by fibrinolysis, FXIII, and platelet-mediated clot retraction, and is represented by maximum lysis (ML), lysis onset time (LOT), and lysis index at 30, 45, and 60 minutes after CT (LI30, LI45, and LI60).5 FIBTEM is the most sensitive and specific assay for the detection of hyperfibrinolysis.7 The combination of EXTEM (sensitive to fibrinolysis and platelet-mediated clot retraction), FIBTEM (not sensitive to platelet-mediated clot retraction but very sensitive to fibrinolysis), and APTEM (not sensitive to fibrinolysis but to platelet-mediated clot retraction) can be used to differentiate between hyperfibrinolysis and platelet-mediated clot retraction.8 Fortunately, the latter is not associated with bleeding and does not require therapy with antifibrinolytics9.”1
In tomorrow’s PAAD, we will review how Corchemore et al. propose using this classification system and VET to guide therapy.
Send your thoughts and comments to Myron who will post in a Friday Reader response.
References
1. Crochemore T, Görlinger K, Lance MD. Early Goal-Directed Hemostatic Therapy for Severe Acute Bleeding Management in the Intensive Care Unit: A Narrative Review. Anesthesia and analgesia 2024;138(3):499-513. (In eng). DOI: 10.1213/ane.0000000000006756.
2. Pavoni V, Gianesello L, Conti D, et al. "In Less than No Time": Feasibility of Rotational Thromboelastometry to Detect Anticoagulant Drugs Activity and to Guide Reversal Therapy. J Clin Med 2022;11(5) (In eng). DOI: 10.3390/jcm11051407.
3. Wikkelsø A, Wetterslev J, Møller AM, Afshari A. Thromboelastography (TEG) or rotational thromboelastometry (ROTEM) to monitor haemostatic treatment in bleeding patients: a systematic review with meta-analysis and trial sequential analysis. Anaesthesia 2017;72(4):519-531. (In eng). DOI: 10.1111/anae.13765.
4. Núñez-Jurado D, Santotoribio JD, Noval-Padillo J. ClotPro Viscoelastometry Evaluation in Cardiac Surgery With Cardiopulmonary Bypass. Journal of cardiothoracic and vascular anesthesia 2023;37(3):392-398. (In eng). DOI: 10.1053/j.jvca.2022.11.022.
5. Napolitano M, Siragusa S, Mariani G. Factor VII Deficiency: Clinical Phenotype, Genotype and Therapy. J Clin Med 2017;6(4) (In eng). DOI: 10.3390/jcm6040038.
6. Santos AS, Oliveira AJF, Barbosa MCL, Nogueira J. Viscoelastic haemostatic assays in the perioperative period of surgical procedures: Systematic review and meta-analysis. Journal of clinical anesthesia 2020;64:109809. (In eng). DOI: 10.1016/j.jclinane.2020.109809.
7. Yoshii R, Sawa T, Kawajiri H, Amaya F, Tanaka KA, Ogawa S. A comparison of the ClotPro system with rotational thromboelastometry in cardiac surgery: a prospective observational study. Sci Rep 2022;12(1):17269. (In eng). DOI: 10.1038/s41598-022-22119-x.
8. Hartmann M, Lorenz B, Brenner T, Saner FH. Elevated Pre- and Postoperative ROTEM™ Clot Lysis Indices Indicate Reduced Clot Retraction and Increased Mortality in Patients Undergoing Liver Transplantation. Biomedicines 2022;10(8) (In eng). DOI: 10.3390/biomedicines10081975.
9. Katori N, Tanaka KA, Szlam F, Levy JH. The effects of platelet count on clot retraction and tissue plasminogen activator-induced fibrinolysis on thrombelastography. Anesthesia and analgesia 2005;100(6):1781-1785. (In eng). DOI: 10.1213/01.Ane.0000149902.73689.64.