Liviana Catalano

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

Na+/H+ exchange inhibition attenuates left ventricular remodeling and preserves systolic function in pressure‐overloaded hearts

Cardiac hypertrophy is a homeostatic response to elevated afterload. Na+/H+ exchanger (NHE) inhibition reduces the hypertrophic response in animal models of left ventricular hypertrophy (LVH) and myocardial infarction. We examined the effect of chronic treatment with cariporide, a selective inhibitor of Na+/H+ exchanger isoform 1 (NHE‐1), on left ventricular (LV) systolic and diastolic function under pressure overload conditions. Male CD‐1 mice were randomized to receive either a control diet or an identical diet supplemented with 6000 p.p.m. of cariporide. Cardiac pressure overload was induced by thoracic aortic banding. LV dimension and systolic and diastolic function were assessed in sham and banded mice by echocardiography and cardiac catheterization 2 and 5 weeks after surgery. Histological analysis was also performed. After 2 weeks of pressure overload, the vehicle‐treated banded mice (Veh‐Bd) had enhanced normalized LV weight (about +50%) and normal chamber size and function, whereas cariporide‐treated banded mice (Car‐Bd) showed a preserved contractility and systolic function despite a marked attenuation of LVH. Diastolic function did not differ significantly among groups. After 5 weeks, the Veh‐Bd developed LV chamber enlargement and systolic dysfunction as evidenced by a 16% increase in LV end‐diastolic diameter, a 36% decrease in myocardial contractility, and a 26% reduction in percent fractional shortening. In contrast, Car‐Bd showed an attenuated increase in LV mass, normal chamber size, and a maintained systolic function. A distinct histological feature was that in banded mice, cariporide attenuated the development of cardiomyocyte hypertrophy but not the attendant myocardial fibrosis. In conclusion, the results of the present study indicate that (i) the hypertrophic response to pressure overload is dependent on NHE‐1 activity, and (ii) at the 5‐week stage, banding‐induced deterioration of LV performance is prevented by NHE‐1 inhibition.

The role of antenatal immunoprophylaxis in the prevention of maternal-foetal anti-Rh(D) alloimmunisation.

The first description of haemolytic disease of the newborn (HDN) can be traced back to 1609 and was made by a French midwife, Louise Bourgeois, who, from 1600, worked at the royal court of King Henry IV and Queen Marie de Medicis1–4. In the treatise that Bourgeois wrote in 1609 she described the birth of two twins3: the first had hydrops and died immediately, while the second, initially in a better condition, rapidly became jaundiced and, after having developed neurological symptoms (kernicterus), died 3 days after being born. Hydrops foetalis and kernicterus were correctly interpreted as two aspects of the same pathology only in 19325, when Diamond described foetal erythroblastosis secondary to severe haemolysis, although the cause was still unknown. A few years later, in 1938, Ruth Darrow correctly identified the (antibody-related) pathogenesis of HDN6, although erroneously attributing foetal haemoglobin the role of the culprit antigen, which was suggested to have induced a maternal antibody response after crossing the placenta. The true pathogenesis of the disease was definitively clarified in 1940 with the discovery of the Rhesus (Rh) blood group system by Landsteiner and Wiener7 and with the subsequent identification, in 1941, by Levine8, of the Rh(D) antigen. This antigen was, in fact, identified, in D-negative mothers, as being the cause of the immunisation occurring following transplacental passage of foetal D-positive red blood cells. The subsequent passage of maternal anti-D immunoglobulin G (IgG) across the placenta into the foetal circulation was recognised as the final event able to cause the spectrum of clinical events that characterise HDN. It did not take long before the risk of immunisation could be quantified1,3: i) 16% in the case of a Rh(D)-negative mother and a Rh(D)-positive, ABO-compatible foetus; ii) 2% in the case of a Rh(D)-negative mother and a Rh(D)-positive, ABO-incompatible foetus (about 20% of the cases); iii) overall risk of immunisation: 13.2%. Before 1945, about 50% of all foetuses with HDN died of kernicterus or hydrops foetalis. Subsequently, thanks to the progress in treatment, in industrialised countries the mortality decreased to 2–3%; this mortality rate was then very considerably further reduced (100-fold) with the introduction of anti-D immunoprophylaxis to prevent maternal-foetal anti-Rh(D) alloimmunisation 9. At the beginning of the 1960s, Stern demonstrated experimentally that the administration of anti-D IgG could prevent sensitisation to the Rh(D) antigen10; in the same period, other studies clarified the mechanism of Rh iso-immunisation in pregnancy and introduced the clinical practice of passive immunisation with anti-D IgG to protect Rh(D)-negative women from sensitisation against Rh(D)-positive red blood cells11–14. The successes obtained in studies of Rh(D)-negative male volunteers formed the experimental basis for clinical trials in pregnant Rh(D)-negative women15; these trials demonstrated that post-partum immunoprophylaxis decreased the incidence of post-pregnancy anti-Rh(D) immunisation from 12–13% to 1–2%15,16. Subsequently, in 1977, it was shown that 1.8% of Rh(D)-negative women, despite post-natal prophylaxis, continued to develop anti-D antibodies because of small transplacental haemorrhages during pregnancy17,18. One year later, a Canadian study by Bowman et al. showed, in 1,357 Rh(D)-negative primagravida, that the incidence of Rh(D) alloimmunisation could be reduced to 0.1% by prophylaxis with antenatal anti-D IgG, in addition to post-partum prophylaxis19. There is currently sufficient evidence demonstrating that antenatal anti-D prophylaxis also reduces the risk of Rh(D) immunisation in the next pregnancy to below the level of 0.4%. Forty years after Zipursky and Israels first proposed the use of anti-D IgG to reduce the incidence of Rh alloimmunisation in pregnancy14, immunoprophylaxis has drastically reduced the cases of Rh-induced HDN; nevertheless, this pathology continues to be relevant in 0.4 of 1,000 births (0.04%)20, for various reasons21: i) the possible occurrence of anti-D immunisation during the pregnancy (which occurs in about 1% of Rh(D)-negative women carrying a Rh(D)-positive foetus22); ii) the lack of efficacy of immunoprophylaxis because of the administration of an insufficient dose of anti-D IgG that is not congruent with the volume of the foetal-maternal haemorrhage; iii) immunoprophylaxis not administered; iv) possible errors in typing the pregnant or puerperal woman or the neonate; v) possible errors in transfusion therapy in women of child-bearing age.

Hepatitis E: an old infection with new implications.

The availability of safe blood and blood products is an important public health issue. Improvements in donor screening and testing, pathogen inactivation1 and removal methods, the use of serological tests with greater diagnostic efficacy and the introduction of nucleic acid testing (NAT) have resulted in a substantial drop in transfusion-transmitted infections over the last two decades2. Nonetheless, blood supplies remain vulnerable to emerging and re-emerging infections. In recent years, numerous infectious agents found worldwide have been identified or reconsidered as potential threats to blood supplies3–5. Hepatitis E virus (HEV) has long been considered an enterically transmitted virus causing self-limiting acute viral hepatitis. The disease is endemic in many developing countries, but in recent years an increasing number of autochthonous and sporadic HEV infections have been described in developed countries6. This virus usually causes an acute self-limiting hepatitis, but in some cases fulminant hepatic failure resulting in morbidity and mortality may occur, especially in at-risk groups such as the elderly, pregnant women and patients with pre-existing liver disease or those who are immunocompromised. Furthermore, recent seroprevalence studies are questioning the concept of the low circulation of HEV in developed countries7. This narrative review aims at providing a comprehensive view of HEV and its possible “role” in transfusion medicine.

Pressure overload causes cardiac hypertrophy in β1-adrenergic and β2-adrenergic receptor double knockout mice

Objective Cardiac hypertrophy arises as an adaptive response to increased afterload. Studies in knockout mice have shown that catecholamines, but not α1-adrenergic receptors, are necessary for such an adaptation to occur. However, whether β-adrenergic receptors are critical for the development of cardiac hypertrophy in response to pressure overload is not known at this time. Methods and results Pressure overload was induced by transverse aortic banding in β1-adrenergic and β2-adrenergic receptor double knockout (DβKO) mice, in which the predominant cardiac β-adrenergic receptor subtypes are lacking. Chronic pressure overload for 4 weeks induced cardiac hypertrophy in both DβKO and wild-type mice. There were no significant differences between banded mice in left ventricular weight to body weight ratio, in the left ventricular wall thickness, in the cardiomyocyte size or in the expression levels of the load-sensitive cardiac genes such as ANF and β-MHC. Additionally, the left ventricular systolic pressure, an index of afterload, and cardiac contractility, evaluated as dp/dtmax, the maximal slope of systolic pressure increment, and Ees, end-systolic elastance, were increased at a similar level in both wild-type and DβKO banded mice, and were significantly greater than in sham controls. Conclusion Despite chronic activation of the cardiac β-adrenergic system being sufficient to induce a pathological hypertrophy, we show that β1-adrenergic and β2-adrenergic receptors are not an obligatory component of the signaling pathway that links the increased afterload to the development of cardiac hypertrophy.

West Nile virus in the transfusion setting with a special focus on Italian preventive measures adopted in 2008-2012 and their impact on blood safety

. The majority of WNV infections in humans are asymptomatic while approximately 20% of infected individuals develop, after an incubation period of 3-14 days, a mild febrile illness for 3-6 days (West Nile fever, WNF) characterised by a variety of non-specific symptoms that do not allow WNF to be distinguished from other infectious illnesses on clinical examination. In less than 1% of infected individuals, particularly the elderly or immunocompromised subjects

Propranolol causes a paradoxical enhancement of cardiomyocyte foetal gene response to hypertrophic stimuli.

Pathological cardiac hypertrophy is associated with the expression of a gene profile reminiscent of foetal development. The non selective β‐adrenoceptor antagonist propranolol is able to blunt cardiomyocyte hypertrophic response in pressure‐overloaded hearts. It remains to be determined whether propranolol also attenuates the expression of hypertrophy‐associated foetal genes.

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.

The first data from the haemovigilance system in Italy.

BACKGROUND Haemovigilance is defined as the surveillance of adverse reactions occurring in donors and in recipients of blood components and as epidemiological surveillance of donors. The ultimate purpose of haemovigilance is to prevent the repetition of adverse events and reactions. Since the 2002/98/EC Directive came into force, the introduction of haemovigilance systems has become a priority for all countries in the European Community. The Italian haemovigilance system is essentially in line with the Directive, although it does not include surveillance of adverse events in donors and does not have a national level of registration of severe incidents connected with the collection, processing and storage of blood and blood components. Epidemiological surveillance of donors has been performed nationally since 1989 for HIV and since 1999 for HBV, HCV and Treponema pallidum. Surveillance of adverse events in recipients was started at the end of 2004. MATERIALS AND METHODS The national form proposed for notifying adverse reactions (PETRA) was prepared by the National Institute of Health and distributed to all Transfusion Structures. RESULTS The data collected (adverse reactions, errors, and near miss errors) came from 21.0% of the Transfusion Structures in 2004 and 38.4% in 2005. The system monitored 49.6 % of all the units distributed in Italy. Overall 1,495 adverse reactions were reported, which is equivalent to 0.8 reactions/1,000 units of blood components distributed. There were 16 reports of errors involving transfusions to the wrong patient. Not all the Transfusion Structures sent their data using the PETRA form. From the 986 PETRA forms received, it was possible to analyse the relevance of the transfusion, the outcome of the patient, the type of blood component involved, the type of error and the type of near miss error. CONCLUSIONS This study is the first Italian report on transfusion errors and adverse reactions.

Convalescent plasma: new evidence for an old therapeutic tool?

Passive immunisation for the prevention and treatment of human infectious diseases can be traced back to the 20(th) century. The recent Ebola virus outbreak in West Africa has turned the spotlight onto the possible use of convalescent whole blood and convalescent plasma in the treatment of infectious diseases because they are the only therapeutic strategy available in some cases, given the unavailability of vaccines, drugs or other specific treatments. Convalescent blood products could be a valid option in the treatment/prophylaxis of several infectious diseases both in association with other drugs/preventive measures and as the only therapy when a specific treatment is not available. However, there are still some issues to consider in determining the advisability of implementing a large-scale convalescent plasma transfusion programme.