Giancarlo Maria Liumbruno

Zika virus and the never-ending story of emerging pathogens and Transfusion Medicine

In the last few years, the transfusion medicine community has been paying special attention to emerging vector-borne diseases transmitted by arboviruses. Zika virus is the latest of these pathogens and is responsible for major outbreaks in Africa, Asia and, more recently, in previously infection-naïve territories of the Pacific area. Many issues regarding this emerging pathogen remain unclear and require further investigation. National health authorities have adopted different prevention strategies. The aim of this review article is to discuss the currently available, though limited, information and the potential impact of this virus on transfusion medicine.

Recommendations for the transfusion management of patients in the peri-operative period. I. The pre-operative period

A thorough pre-operative evaluation is fundamental for stratifying haemorrhagic risk, for predicting transfusion needs in relation to the type of surgical intervention, as well as for evaluating the indications and eligibility of a patient for autotransfusion procedures, and the need for any adjuvant therapies (Grade of recommendation: 2C)1–3. The pre-operative assessment must include a careful review of the patient’s clinical documentation, a thorough personal and family history, focused particularly on revealing a suspected bleeding disorder, as well as a control of the laboratory tests. The evaluation must be carried out a reasonable time before the planned date of the intervention, for example 30 days before, in order to allow detailed diagnostic investigations or planning of appropriate therapeutic measures (Grade of recommendation: 2C)4.

Recommendations for the transfusion of red blood cells

The transfusion of red cell concentrates (RCC) is indicated in order to achieve a fast increase in the supply of oxygen to the tissues, when the concentration of haemoglobin (Hb) is low and/or the oxygen carrying capacity is reduced, in the presence of inadequate physiological mechanisms of compensation (table I)1–14. Table I Mechanisms of adaptation to anaemia Tissue oxygenation depends on various factors - the concentration of Hb; - the saturation of Hb, which, in turn, depends on the O2 tension and the affinity of the Hb for O2; - the O2 requirement, that is, the volume of oxygen needed by the tissues to carry out their aerobic function. Clinical factors that affect the physiological mechanisms of adaptation to anaemia5–8,15–19 - a reduced increase in cardiac output: hypovolaemia, coronary artery disease, disorders of heart valves, congestive heart disease, negative inotropic drugs; - decreased capacity to increase the extraction of O2: acute respiratory distress syndrome (ARDS), sepsis, systemic inflammatory response syndrome (SIRS), traumatic ischaemia-reperfusion damage syndrome; - altered gas exchange: chronic obstructive pulmonary disease (COPD), ARDS; - increased consumption of O2: fever, pain, stress, sepsis, SIRS, hyperventilation syndromes. When there is an indication to correct anaemia, but the situation is not urgent, strategies other than transfusion are preferred, such as the use of haematopoietic drugs (iron, vitamin B12, folic acid, recombinant erythropoietin)5–8,20. In order to reduce perioperative bleeding, it is important to suspend treatment with platelet anti-aggregants, adapt/neutralise anticoagulant therapy and use drugs such as antifibrinolytics and desmopressin9,20–23. Autotransfusion, carried out according to the criteria set out in the appropriate pre-operative request schemes (maximum surgical blood order schedule -MSBOS), and surgical and anaesthetic techniques to limit blood loss are useful strategies for decreasing the use of homologous blood (Grade of recommendation: 1C+)5,6,13,14,20–24.

Recommendations for the use of albumin and immunoglobulins

Human albumin is a physiological plasma-expander; its limited availability and high cost make it essential to define recommendations for its appropriate use, as an alternative to other therapeutic strategies including solutions of crystalloids and non-protein colloids, and have also stimulated numerous studies, which have sometimes reached contradictory conclusions1–8. In 1998 a meta-analysis of 30 randomised trials suggested that the use of albumin was associated with an increased mortality rate among critically ill patients9,10. This conclusion, also reached by two subsequent Cochrane reviews11,12, was not confirmed by a meta-analysis in 2001 or by more recent studies13–23. A review in 2006 showed that renal damage can be induced by the use of hydroxyethyl starch and gelatine in sepsis and surgery24. The limited power of all these studies could lie in their having combined results from heterogeneous types of patients with different baseline albumin concentrations25,26.

Beyond immunohaematology: the role of the ABO blood group in human diseases

The antigens of the ABO blood group system (A, B and H determinants, respectively) are complex carbohydrate molecules on the extracellular surface of red blood cell membranes1. However, along with their expression on red blood cells, ABO antigens are also highly expressed on the surface of a variety of human cells and tissues, including the epithelium, sensory neurons, platelets, and the vascular endothelium2. Thus, the clinical significance of the ABO blood group system extends beyond transfusion medicine and several reports have suggested an important involvement in the development of cardiovascular, oncological and other diseases3,4. Current knowledge on the association between the ABO blood group system and various human diseases are summarised in this narrative review.

World apheresis registry data from 2003 to 2007, the pediatric and adolescent side of the registry

OBJECTIVES Paediatric patients are a special group in apheresis. It is general accepted to use adult indications in paediatric patients, but data in this age group are rare. In order to provide more information of apheresis practise in children and young adults (<21a) we will report of knowledge learnt by data from the registry from 2003 until 2007. METHODS This is a web-based registry. A link is available from the WAA homepage (www.worldapheresis.org). So far data from 12,448 procedures have been included. Six hundred and twelve procedures were performed in 135 children and young adults (308 procedures<16a, 237 from 17 to 20a, and 67 with 21a) representing 5% of the total population. The median age was 14 years (range 1-21 years), 74 male and 61 female. These data were entered by 15 centres with a frequency of in median 18 aphereses in young patients per centre (range 1-287) from 2003 to 2007. RESULTS Main indications: haematological diseases and also nephrological, and neurological. The type of aphereses was mainly Leukapheresis (196, 33%), plasma exchange (149, 25%), photopheresis (127, 21%), and lipid aphereses (79, 13%). Blood access: peripheral vessels in 305 procedures (50%, compared to 73% in adults), central venous catheter in 239 (38%), and AV-fistula in 2% and 0.3%, and in 8 (1.31%) procedures an arterial line was used. Anticoagulation was mostly by ACD (71%), heparin (18% or the combination of both (3%). 39 adverse events (AE) were registered in 22 (=3.59%) of the procedures, mostly graded as mild. Treatment was interrupted in 14 procedures (2.29%). AEs were abdominal pain, anaphylactic shock, flush, hyper- and hypotension, nausea, vertigo, cephalea and need for sedation and technical problems with the device and problems with the venous access. The rate of AEs was similar for stem cell harvesting and for plasma exchange (4% and 4.7%, respectively). CONCLUSION The paediatric data compared to the whole registry data set are showing that aphereses are performed as safe in paediatrics as in adults. Centres are mostly handling only a few cases younger than 21. Therefore more exchange of information and experience in paediatric apheresis is warranted.

Reduction of the risk of bacterial contamination of blood components through diversion of the first part of the donation of blood and blood components.

The level of safety of transfusion therapy is now very high thanks to the combination of serological methods and genomic amplification used to screen for transmissible diseases and the meticulous care with which repeat, voluntary, unpaid donors are selected1–4. The main risk of transfusion-related infectious diseases is currently that of bacterial sepsis1,3–5. The risk of bacterial contamination of blood components is, in fact, estimated to be about three orders of magnitude greater than that of post-transfusional HIV and HCV infections5,6; the risk of bacterial sepsis causes by the transfusion of platelets is more than two orders of magnitude greater than the risk of the same viral infections5,6. According to a study published in 20047, the year in which bacteriological screening tests for platelet units were introduced in the USA3,8,9, the average prevalence of bacterial contamination in platelets from whole blood was 33.9/100,000 units, that of platelets from apheresis 51/100,000, while that of red cell concentrates was 2.6/100,000. The overall prevalence of bacterial contamination of units of cellular blood components was, therefore, about 1 in 3,000 donations (33.3/100,000)7,10. Table I reports the data on bacterial contamination of units of platelets and red blood cells derived from studies before 200311–19. More recent estimates indicate that bacterial culture tests on units of platelets are positive, and confirmed as such, in about 1 in 5,000 units (20/100,000)4. The risk of receiving platelet concentrates contaminated by bacteria is, therefore, considerably higher than the risk of post-transfusion infection by HIV, HCV, HBV and HTLV3,4. Table I Prevalence of bacterial contamination of cellular blood components recorded in studies before 2003

Intraoperative cell salvage in obstetrics: is it a real therapeutic option?

Obstetric hemorrhage is a leading cause of maternal and perinatal mortality worldwide. Intraoperative blood salvage is common practice in many surgical specialties but its safety in obstetrics is questioned for concerns on the risks of contamination of recovered blood with amniotic fluid (AF) and of maternal‐fetal alloimmunization. However, the role of cell salvage as a blood‐saving measure in obstetrics is progressively acquiring relevance thanks to the growing body of evidence regarding its quality and safety coming from over 800 documented procedures and more than 400 patients transfused with saved blood. Although the information about the outcomes of the patients treated and the allogeneic blood saving effect are still limited, modern cell savers remove most particulate contaminants and leukoreduction filtering of salvaged blood (SB) before transfusion adds further safety to this technique. Moreover, AF embolism is no longer regarded as an embolic disease and it is suggested that it is a rare anaphylactoid reaction to the fetal antigen. The contamination of the SB by fetal Rh‐mismatched red blood cells (RBCs) can be dealt with using RhIG; ABO incompatibility tends to be a minor problem since ABO antigens are not fully developed at birth. Antibodies can be formed against other fetal RBC antigens, but it should also be noted that the risk of alloimmunization of the mother from allogeneic transfusion is probably even greater. Therefore, intraoperative cell salvage in obstetrics should be considered in patients at high risk for hemorrhage or in cases where allogeneic blood transfusion is difficult or impossible.

Hemostasis, cancer, and ABO blood group: the most recent evidence of association

Human ABO blood group antigens are expressed on the surface of red blood cells and a variety of human cells and tissues. However, an increasingly number of studies show that the ABO blood group, in addition to its fundamental role in transfusion medicine and in several other disciplines, has a causal role in predisposing to several human diseases, including hemostasis and neoplastic disorders, which will be the focus of this narrative review.

Human T-lymphotropic virus and transfusion safety: does one size fit all?

Human T‐cell leukemia viruses (HTLV‐1 and HTLV‐2) are associated with a variety of human diseases, including some severe ones. Transfusion transmission of HTLV through cellular blood components is undeniable. HTLV screening of blood donations became mandatory in different countries to improve the safety of blood supplies. In Japan and Europe, most HTLV‐infected donors are HTLV‐1 positive, whereas in the United States a higher prevalence of HTLV‐2 is reported. Many industrialized countries have also introduced universal leukoreduction of blood components, and pathogen inactivation technologies might be another effective preventive strategy, especially if and when generalized to all blood cellular products. Considering all measures available to minimize HTLV blood transmission, the question is what would be the most suitable and cost‐effective strategy to ensure a high level of blood safety regarding these viruses, considering that there is no solution that can be deemed optimal for all countries.