Consensus Panel Sees Little Evidence of a Beneficial Effect from Blood Transfusions

An exhaustive review and analysis of the medical literature by a panel of experts at the 1st International Consensus Conference on Transfusion and Outcomes (ICCTO) held in April 2009 in Phoenix (Arizona, USA) concluded that there is little evidence to support a beneficial effect from the greatest number of blood transfusions currently being given to patients.

The vast majority of studies show an association between red blood cell transfusions and higher rates of complications such as heart attack, stroke, lung injury, infection and kidney failure and death.

The ICCTO conference brought together 15 leading international physicians and scientists in the fields of anesthesiology, intensive care, hematology, oncology, surgery, and patient blood management, and was monitored by the Food and Drug Administration, the American and the Australian Red Cross, the Joint Commission, along with government health officials, and other organizations.

"The results of the conference firmly establish the view that, rather than being a benign procedure, blood transfusion is associated with increased risk of medical complications," said Aryeh Shander, M.D., Chief of the Department of Anesthesiology, Critical Care Medicine, Pain Management and Hyperbaric Medicine at Englewood Hospital and Medical Center in Englewood, NJ and a founding member of the Society for the Advancement of Blood Management (SABM).

A review of available statistical data shows that allogeneic blood transfusion improves outcomes in only 11% of clinical scenarios for patients without trauma or active hemorrhage.

"The evidence tells us to restrict the practice of transfusion and to avoid unnecessarily transplanting stored blood that could harm a patient's recovery," Shander noted.

Transfusion and safety
Safety concerns with blood transfusions initially came to the public's awareness with the realization that infectious agents such as HIV could be transmitted via blood transfusion. Careful screening and testing have resulted in the risk of known infectious agents being transmitted via blood being reduced to extremely low levels. Since then, concern has emerged amongst many in the medical profession that transfusion itself may be a risk factor for adverse patient outcomes. It has been known for some time that blood undergoes many physical and chemical changes during storage, losing its ability to supply oxygen to vital organs and triggering inflammatory and immune reactions when transfused. It is now thought by some that these storage-related problems may result in negative outcomes to patients.

The 1st International Consensus Conference on Transfusion and Outcomes (ICCTO) was organized by two professional medical societies, the USA based Society for the Advancement of Blood Management (SABM) and the international Medical Society for Blood Management (MSBM). Both educational organizations comprise networks of practitioners from a wide variety of medical and scientific disciplines who are dedicated to improving patient outcomes and the advancement of optimal patient blood management in clinical practice through education, cooperation and research. The societies facilitate cooperation among existing and future patient blood management/blood conservation, bloodless medicine and surgery programs as well as enhance the clinical and scientific aspects of transfusion practice.

During the consensus conference leading physicians and scientists from around the world reviewed more than 550 articles and case studies published over the last 13 years. They arrived at a consensus about transfusion and its relation to patient outcomes. The overwhelming majority of evidence supports the view that, rather than being the benign procedure many view it as, blood transfusion is associated with increased risk of infection and medical complications.

Comments Shander. “The time has come for the medical community at large to use patient blood management to improve patient outcomes by avoiding unwarranted and unnecessary blood transfusions.”

Efficacy assessment
Blood transfusion came into medical use decades ago, however, it has never been subject to the same rigorous safety and efficacy assessment process applied today to other drugs and treatments before they are approved for use. This has resulted in a great deal of uncertainty and lack of knowledge among physicians as to whether a patient should or should not be transfused. As a consequence, there is enormous variation in transfusion practice between countries, states within countries, hospitals and even between clinicians within the same institution.

The accepted ‘consensus conference’ process using the RAND-UCLA method was chosen to unravel some of this uncertainty. This method involves a comprehensive review of all published scientific studies on a treatment, after which a panel of experts assesses a series of patient scenarios using the scientific literature to determine whether the treatment has evidence to support that it will improve the patient's outcome.

The 1st International Consensus Conference on Transfusion and Outcomes (ICCTO) panelists also considered what has come to be known as the Bradford Hill Criteria for establishing causation, the process Sir Austin Bradford Hill and Sir Richard Doll used in the 1960s to establish that cigarette smoking caused such diseases as lung cancer and emphysema.

Long term review
The ICCTO literature review searched for all studies on blood transfusion and outcomes published in the last 13 years. 555 studies met study inclusion criteria and were analyzed by each panelist in preparation for the conference.

A great majority of these studies were initiated to investigate the benefits of transfusions, and instead either found no benefit or identified negative outcomes associated with blood transfusions. Only a small minority of clinical scenarios, were associated with suggested improved outcome.

The panel confined this initial ICCTO analysis to stable non-bleeding patients. Approximately sixty percent of the 90 million units collected around the globe each year (14 million units annually in the USA) are given to such patients.

"Given what we now know, donor transfusions should be limited only to surgery patients who are experiencing major bleeding that is difficult to control quickly," said James Isbister, MD, Clinical Professor of Medicine at the University of Sydney, and a founding member of MSBM. "We hope the conference will help all physicians and the public become aware of the many negative outcomes associated with transfusion, and call for blood management strategies to improve patient outcomes."

For more information:

• Society for the Advancement of Blood Management (SABM)
• Medical Society for Blood Management (MSBM).
• MedPage Today: Group Questions Appropriateness of Most Blood Transfusions

Also read these Pubmed Abstracts:

• Shiba H, Ishida Y, Wakiyama S, Iida T, Matsumoto M, et al. Negative Impact of Blood Transfusion on Recurrence and Prognosis of Hepatocellular Carcinoma After Hepatic Resection. J Gastrointest Surg. 2009 Jul 7. [Epub ahead of print]
• Lane A, Crosby ET. Blood management for hip reconstruction surgery. Orthop Clin North Am. 2009 Jul;40(3):417-25.
• Saxena A, Yan TD, Chua TC, Fransi S, Almohaimeed K, et al. Risk Factors for Massive Blood Transfusion in Cytoreductive Surgery: A Multivariate Analysis of 243 Procedures. Ann Surg Oncol. 2009 May 1. [Epub ahead of print]
• Katz EA. Blood transfusion: friend or foe. AACN Adv Crit Care. 2009 Apr-Jun; 20(2):155-63; quiz 165.
• Harostock M 3rd, Filler JJ, Burak DA, McDonnell BE, Emilcar J, et al. Comparison of transfusion requirements for conventional and miniaturized extracorporeal circuits.
  Heart Surg Forum. 2008;11(3):E188-92.
• Muñoz M, García-Erce JA, Villar I, Thomas D. Blood conservation strategies in major orthopaedic surgery: efficacy, safety and European regulations. Vox Sang. 2009 Jan;96(1):1-13.
• Fabron A Jr, Lopes LB, Bordin JO. Transfusion-related acute lung injury. J Bras Pneumol. 2007 Apr;33(2):206-12
• Davies L, Brown TJ, Haynes S, Payne K, Elliott RA, McCollum C. Cost-effectiveness of cell salvage and alternative methods of minimising perioperative allogeneic blood transfusion: a systematic review and economic model. Health Technol Assess. 2006 Nov;10(44):iii-iv, ix-x, 1-210
• Bux J. Transfusion-related acute lung injury (TRALI): a serious adverse event of blood transfusion. Vox Sang. 2005 Jul;89(1):1-10
• Blumberg N. Allogeneic transfusion and infection: economic and clinical implications. Semin Hematol. 1997 Jul;34(3 Suppl 2):34-40

How to help your patients:

• Time magazine: Bloodless Surgery

A Tumor Suppressor Gene Inactivated in Myeloproliferative Neoplasms

Research by Dr. Francois Delhommeau MD, and his team at the Saint-Antoine Hospital, Paris, France (Hôpital Saint Antoine, Service d’hématologie, 184, rue du Faubourg Saint Antoine, 75012 Paris) on treatment advances in leukemia and lymphoma, presented as late-breaking news during the 50th Annual Meeting of the American Society of Hematology in San Francisco, CA,(December 6 – 9, 2008), led to the discovery of a new tumor suppressor gene called TET2 (Ten-Eleven Translocation–2).

Because TET2 is altered in 14 percent of patients with myeloproliferative disorders, the discovery provides scientists with a greater understanding of the underlying biology of these conditions, as well as a potential target for the development of future treatments.

All blood cells start out as hematopoietic, or blood-forming, stem cells and have the potential to become mature red blood cells, white blood cells, or platelets. Myeloproliferative disorders develop when the DNA of a stem cell is altered in the bone marrow, causing the overproduction of some blood cells.

Previous research has detected mutations in other genes– JAK2 and MPL – in the blood stem cells of patients with myeloproliferative disorders. These JAK2 and MPL defects cause the overproduction of mature malignant blood cells, but multiple lines of evidence suggest that these are not the only molecular lesions responsible for abnormalities in the stem cell in these disorders. Greater analysis of blood cell development in myeloproliferative disorders with the JAK2 V617F mutation led researchers to identify two subsets of patients. The first subset of patients (85 percent) had an overproduction of malignant cells mainly dependent on the late stages of blood cell differentiation, far downstream from the stem cell. In contrast, a second subset of patients (15 percent) had an early expansion of very immature malignant progenitor cells, close to the stem cell.

Researchers then hypothesized that the second subset of patients had a pre-existent molecular defect able to promote the early expansion of the malignant cells. With high-resolution arrays, researchers were able to identify one single gene, TET2, which belongs to a family of three genes of unknown function.

Researchers then further analyzed cells in five patients with TET2 mutations, which demonstrated that TET2 defects target hematopoietic stem cells. Moreover, they show that in these five patients TET2 inactivation precedes the JAK2 V617F mutation, suggesting that this new molecular lesion could be an early event in cancer stem cell formation.

To further test these findings, researchers sequenced TET2 in 181 unselected JAK2 V617F patients with myeloproliferative disorders. TET2 mutations were found in 25 of the 181 patients, resulting in an overall 14 percent frequency.

For more information, read:

• Delhommeau F, Dupont S, James C, Masse A, et al. TET2 Is a Novel Tumor Suppressor Gene Inactivated in Myeloproliferative Neoplasms: Identification of a Pre-JAK2 V617F Event. (Late-Breaking Abstracts) Blood (ASH Annual Meeting Abstracts) 2008 112: Abstract LBA-3

Also read PubMed abstracts:

• Delhommeau F, Pisani DF, James C., et al. Oncogenic mechanisms in myeloproliferative disorders. Cell Mol Life Sci. 2006 Dec;63(24):2939-53
• Delhommeau F, Dupont S, Tonetti C, Massé A. et al. Evidence that the JAK2 G1849T (V617F) mutation occurs in a lymphomyeloid progenitor in polycythemia vera and idiopathic myelofibrosis. Blood. 2007 Jan 1;109(1):71-7. Epub 2006 Sep 5.