National Blood Authority Australia

Annual Report 2010–11

Part 4: HORIZON SCANNING

4.3 BLOOD MANAGEMENT

Western Australia became the first jurisdiction in the world to adopt a system-wide program of patient blood management. It includes blood tests several weeks before scheduled surgery so anaemia can be treated and emphasis on surgical techniques which minimise blood loss. This program is credited with reducing WA’s use of red blood cells per 1,000 population from 30 in 2007–08 to 28.49 in 2010–11. This compares to a national average of 35.

Use of anaemia drugs

Caution continues in the use of erythropoiesis-stimulating agents (ESAs):

  • The American Society of Hematology and the American Society of Clinical Oncology updated their recommendations. According to their joint guidelines24, physicians need to use caution when giving ESAs to cancer patients who have anaemia caused by chemotherapy; and with rare exceptions, ESAs should not be given to cancer patients who are not receiving chemotherapy25.
  • In June 2011 the FDA made a safety announcement, Modified dosing recommendations to improve the safe use of ESAs in chronic kidney disease. This recommended more conservative dosing.
  • Researchers from the University of Minnesota, led by Hassan N. Ibrahim, say that while blood transfusions increase the risk of adverse outcomes in anaemic renal transplant recipients, treatment with ESAs does not26.

Nevertheless, product developments in this space continue strongly.

  • Affymax says that four late-stage trials for its anaemia drug Hematide showed that the therapy is non-inferior to Amgen’s Epogen and Aranesp, putting it on a path to file for FDA approval. However, cardio-risks in a patient subgroup captured the attention of analysts who expected the FDA to require another clinical trial.
  • Lipoxen revealed encouraging Phase II trial results for its long-acting erythropoietin (EPO) candidate ErepoXen. It is being developed as a long acting form of EPO for the treatment of anaemia in renal disease patients.
  • ProMetic Life Sciences presented data on its orally active PBI-1402 compound at the 15th Congress of the European Hematology Association held in Spain in June 2010. It demonstrated a reduction in the need for blood transfusions in chemotherapy-induced anaemic patients.

RISK IDENTIFICATION

Activities to raise awareness of the importance of the appropriateness of the use of products emerged on different products and from a number of studies.

  • An analysis of more than 31,000 patients who underwent isolated coronary artery bypass grafting (CABG) surgery showed that receiving one or more blood transfusions conferred a nearly threefold increased risk of operative mortality, compared to not receiving a transfusion.
  • In October 2010, the UK National Patient Safety Agency (NPSA) issued new guidance aimed at reducing delays in providing blood for patients in emergency situations. Acute care organisations are advised to draw up a local protocol for dealing with massive blood loss and agree a trigger phrase understood by all staff to activate the protocol (see page 71–3 on the Australian Patient Blood Management Critical Bleeding/Massive Transfusion Guideline module).
  • The Critical Care Canada Forum in Toronto heard that clinicians were failing to adhere to clinical guidelines regarding frozen plasma transfusions and that the requirement to use a standard order form increased compliance.
  • In the USA the Centers for Biologics Evaluation and Research distributed the summary of transfusion fatality reports received by the FDA for the period 1 October 2009–30 September 2010. They judged 40 of the fatalities to be transfusion-related, while in 24 further instances transfusion could not be ruled out as the cause. There were instances of TRALI. There were still fatal reactions to bacterial-contaminated platelet transfusion, although the USA has platelet concentrate microbial screening. However, there were no bacterial contamination fatalities from apheresis derived platelet pools. There were two ABO haemolysis deaths, one due to clerical error.

Chemical agents to limit bleeding from trauma or procedure

Novo Seven

Although its principal use is as a clotting agent in the treatment of haemophilia patients, rFVIIa is also used as an aid to coagulation in non-haemophilia patients.

A recent study reviewed the use of rFVIIa in patients without haemophilia27. It concluded that clinically significant benefits of rFVIIa as a general haemostatic agent in patients without haemophilia remain unproven. Given its potential risks, such use cannot be recommended and in most cases it should be restricted to clinical trials.

Two studies28 reported in the Annals of Internal Medicine on 19 April again raised concerns about off-label use of rFVIIa. One concluded that off-label use of rFVIIa in the [USA] hospital setting far exceeds use for approved indications. These patterns raise concern about the application of rFVIIa to conditions for which strong supporting evidence is lacking. The second concluded that limited available evidence for five off-label indications suggests no mortality reduction with rFVIIa use. For some indications, it increases thromboembolism..

Physical barriers

Sealants and clotting bandages can both assist in reducing blood loss. There have been several new developments during the year.

Genetic factors

French doctors announced the country’s first ‘saviour sibling’, conceived through in-vitro fertilisation and genetically selected to ensure he did not carry the gene for beta-thalassemia but was a close enough match to provide his sibling’s treatment cells from his umbilical cord blood.

A patient with beta-thalassemia became transfusion-free after gene therapy. Researchers fixed the faulty gene responsible for the condition in some of the patient’s own bone marrow stem cells and re-infused them. The team at Brigham and Women’s Hospital and Harvard Medical School in Boston and at the University of Paris now plan to treat patients who have sickle cell disease with gene therapy.

Patterns of transfusion

New research29 suggests patients having heart surgery who receive fewer blood transfusions do just as well as those who receive more.

A researcher has suggested that in patients requiring large volumes of blood products or displaying coagulopathy after injury, early and aggressive administration of blood component therapy may actually reduce the aggregate amount of blood required30.

A study of 81 patients treated with platelet-rich plasma after total knee replacement surgery found that only 2.4 per cent of the patients needed a blood transfusion, compared with the typical transfusion rates of 30–50 per cent31.

Dr Henry Cryer, UCLA Chief of trauma and emergency surgery, received a research grant from the National Trauma Institute (NTI) to study the use of fresh whole blood for transfusions at civilian trauma centres. Recent military studies indicate that transfusion of fresh whole blood may be more beneficial than individual blood components in patients with severe haemorrhage.

Scientists have developed a mathematical model reflecting how red blood cells change in size and haemoglobin content during their four-month lifespan. They said their research may allow prediction of who is likely to become anaemic, using routine hospital tests.

Iron deficiency is common during pregnancy. Intravenous iron given just once over a one-hour infusion was found to be effective and safe for iron-deficient women in a single-centre study reported at a poster session of the American Congress of Obstetricians and Gynecologists 59th Annual Clinical Meeting32.

Platelets

Of particular interest is the UK-led trial of prophylactic platelet study (TOPPS) currently underway. This two-stage, randomised controlled trial of prophylaxis versus no-prophylaxis platelet transfusions in haematology/oncology patients following chemotherapy is investigating to what extent prophylactic platelet transfusions are clinically effective. Doses of platelets for this indication are a significant proportion of the total number of platelets transfused in Australia. If the findings are positive the level of demand for platelets could change.

The Canadian Cardiovascular Society has provided evidence-based recommendations on the use of antiplatelet therapy across all indications. These first-ever guidelines give physicians and other health professionals clear procedural recommendations, including how long a patient should take dual antiplatelet therapy, with appropriate use beyond a year. The full guidelines appeared in the Canadian Journal of Cardiology in 2011.

Platelets in the blood arise from cells known as megakaryocytes. Researchers at the Children’s Hospital of Philadelphia found that mature megakaryocytes infused into mice could generate platelets of normal size and function. They hope it might be possible to treat individuals with thrombocytopenia through mature megakaryocyte infusion.