Written by: Mediware Consulting and Analytics on Monday, December 30, 2013 Posted in: Blood Management

Blood Management Year in Review – Part I

This is Part I of a blog based upon my Blood Management University year-end webinar by the same title, where I tried to hit the high points of the transfusion medicine literature.

Having been involved in implementing and continuously improving blood management programs for the past 20 years, I find it both gratifying and challenging to try and sort out the most pertinent articles since there has been an explosion of publications in this area.

Transfusion in Upper GI Hemorrhage

I rank the article by Villanueva et al, Transfusion Strategies for Acute Upper Gastrointestinal Bleeding1, as the most significant article of the year for three reasons:

  1. This is the 20th prospective randomized trial for red blood cell transfusion strategies, and this challenging patient population was specifically excluded from the landmark TRICC trial;
  2. GI bleeding is a major consumer of blood products within hospitals, typically showing up in the top five group of transfused patients (cardiac surgery, critical care, orthopedics and oncology rounding out the list);
  3. The number of GI bleeding patients is likely to increase with the advent of novel oral anticoagulant drugs (NOACs) such as rivaroxaban, apixaban and dabigatran. A recent review in the GI literature noted that FDA trials for approval of these agents showed a 45% higher incidence of GI bleeding with these drugs vs. warfarin (Coumadin®), and that in “real world” scenarios this incidence will be much higher2.

In brief, the Villanueva study was a randomized controlled trial (RCT) involving 921 patients admitted with acute upper GI hemorrhage who were randomized to be transfused at hemoglobin thresholds of either < 9.0 gm/dL (liberal strategy) or < 7.0 gm/dL (restrictive strategy).  In virtually all outcome categories, the patients in the restrictive arm had significantly better outcomes:

  • 60% reduction in transfusion exposure;
  • 45% reduction in mortality (4% absolute reduction);
  • 40% reduction in rate of re-bleeding;
  • 67% reduction in emergent surgeries;
  • 17% reduction in length of stay (2 day absolute reduction).

An accompanying editorial put this study into perspective, and emphasizes why we need to accelerate the integration of high quality evidence such as this into clinical practice.  Based upon an absolute reduction in mortality of 4%, for every 25 patients managed with the restrictive protocol a life could be saved, a calculation known as “number needed to treat”3.  Since mid-size hospitals admit about 250 of these patients annually, this protocol could save 10 lives a year at most hospitals and perhaps 12,000 lives a year across the US!

Transfusion in Oncology Patients

It is an oddity that there has not been a randomized trial for red blood cell therapy given the high incidence of transfusion in these patients.  I am happy to report there is now a pilot trial underway looking at liberal vs. restrictive RBC strategies in Oncology patients known as the TRIST TrialTransfusion of RBCs in Stem Cell Transplantation4 – but the trial results won’t be published until early 2014.

The big news in Oncology transfusion practice this year was the publication of two platelet therapy RCTs designed to evaluate a prophylactic vs. therapeutic approach.  Wandt has been a longtime advocate of the therapeutic approach, and he was lead author on a trial of 391 patients in Germany undergoing chemotherapy for AML or stem cell therapy randomized to receive platelets for prophylaxis (platelet count <10,000/µL) or therapeutic (transfuse for moderate bleeding- WHO grade 2) indications5.  Stanworth was lead author of a similar RCT with 600 patients in the UK and Australia6.  Both studies showed a substantial decrease in platelet utilization in the therapeutic group (30 – 40% reduction) but the therapeutic group patients also had a shorter time to first bleed and more days with bleeding.  In addition, the Stanworth study showed a tendency to more serious adverse events in the therapeutic group, and the Wandt study showed a higher rate of non-fatal grade 4 bleeds (mostly CNS) in the therapeutic group.  While Wandt still maintains that a subgroup of patients can benefit from a therapeutic approach (autologous SCT patients who had ‘non-inferior’ outcomes in both studies), most US physicians remain skeptical of a therapeutic approach for any patient given our medical- legal environment.  I thought the most interesting finding of these studies was that patients in both treatment groups had a significant amount of bleeding, often at much higher platelet thresholds than 10,000/µL.  The provocative questions that come to mind are:

  • Are there additional tests, beyond a platelet count, that can be used to assess risk for bleeding in oncology patients?  This might include platelet function testing or the immature platelet fraction.
  • Are there other ways, beyond platelet transfusions, to reduce bleeding and transfusion in Oncology patients with thrombocytopenia? This might include measures to reduce iatrogenic blood loss and drugs such tranexamic acid and DDAVP.

Selected references

  1. Villanueva C, Colomo A, Bosch A, et al. Transfusion strategies for acute upper gastrointestinal bleeding. N. Engl. J. Med. 2013;368(1):11–21. Available at: http://www.nejm.org/doi/abs/10.1056/NEJMoa1211801
  2. Holster IL, Valkhoff VE, Kuipers EJ, Tjwa ETTL. New oral anticoagulants increase risk for gastrointestinal bleeding: a systematic review and meta-analysis. Gastroenterology. 2013;145(1):105–112.e15. Available at: http://www.ncbi.nlm.nih.gov/pubmed/23470618
  3. Laine L. Blood transfusion for gastrointestinal bleeding. N. Engl. J. Med. 2013;368(1):75–6. Available at: http://www.nejm.org/doi/abs/10.1056/NEJMe1212009
  4. Tay J, Tinmouth A, Fergusson D, Allan D. Transfusion of red cells in hematopoietic stem cell transplantation (TRIST): study protocol for a randomized controlled trial. Trials. 2011;12(1):207. Available at: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3187728&tool=pmcentrez&rendertype=abstract
  5. Wandt H, Schaefer-Eckart K, Wendelin K, et al. Therapeutic platelet transfusion versus routine prophylactic transfusion in patients with haematological malignancies: an open-label, multicentre, randomised study. Lancet. 2012;380(9850):1309–16. Available at: http://www.ncbi.nlm.nih.gov/pubmed/22877506
  6. Stanworth SJ, Estcourt LJ, Powter G, et al. A no-prophylaxis platelet-transfusion strategy for hematologic cancers. N. Engl. J. Med. 2013;368(19):1771–80. Available at: http://www.nejm.org/doi/abs/10.1056/NEJMoa1212772