Proposal to Cease Testing Blood Donations for CMV

Proposal to Cease Testing Blood Donations for cytomegalovirusStatus PublicExecutive compendious (200 words)In response to SaBTO recommendations for replacing cytomegalovirus sero disconfirming cubicleular line components with leucodepleted smear components, an implementation project has been established pending approval from the scorecard. The proposed implementation date of January 2018 is assumeed a realist timeframe for this approach. Communication with clinicians indicates the acceptance of leucodepleted components as cytomegalovirus safe, replacing the selection of cytomegalovirus sero shun components. Information has been obtained regarding international practices and handling of leucodepletion with respect to cytomegalovirus.This paper sets out key data on the proposed replacement of CMV seronegative source products with leucodepleted relationship products, provides recommendations of the optimal strategy to achieve this, and takes into consideration affected role groups that may be affected.Action requested (bulleted list)The Board is asked toNote the implementation plans for the introduction of CMV safe blood productsApprove the proposal to cease yield of all CMV seronegative blood products that undergo leucodepletion and consider these products as CMV safeApprove the proposal to slip by the production of CMV seronegative red cell and platelet components for intra-uterine transfusions and neonatesApprove the proposal to continue the production of CMV seronegative granulocyte components for CMV seronegative patientsApprove the proposal to continue the production of CMV seronegative blood components for seronegative and seropositive heavy(predicate) women that require transfusions through with(predicate)out pregnancyAgree the recommendation to continue to implement CMV PCR as a back method for early detection for all haemopoietic stem cell and solid electric organ bribery recipientsPurpose of paper (1 paragraph)For over 30 years, there has been an ongoing debate regarding the use of CMV seronegative blood components versus the use of leucodepleted blood components. To date, the use of CMV seronegative blood products has been implemented to reduce the risk of infection of transfusion-transmitted cytomegalovirus in patients considered at risk. Leucodepletion has been performed on all blood products in the UK since 1999. This paper provides an overview on the use of CMV seronegative blood products in comparison to the use of leucodepleted blood components. This paper provides an assessment of patient groups that are considered at risk of CMV and considers advantages to ceasing of CMV examen in the UK. backclothCytomegalovirus (CMV) is a pervasive, cell-associated prototypic virus that is a member of the betaherpesvirus subfamily (Ziemann and Hennig, 2014 Ljungman, 2004). CMV mostly causes asymptomatic contagious disease or mononucleosis-like-infection in an immunocompetent host however, in an immunocompromised host it can result in chronic and persistent infection with devastating outcomes (Seed et al., 2015). Patient groups that are considered at risk of life-threatening transfusion-transmitted CMV infection includes CMV seronegative patients undergoing haematopoietic stem cell displaceation and solid organ transplantation, low birth weight and premature neonates, foetuses that require intrauterine transfusion, CMV seronegative pregnant women, and highly immunocompromised patients, such as those with malignant disease (Ziemann and Hennig, 2014 SaBTO, 2012).CMV infection is frequently encountered passim childhood and an estimated 50 60% of the adult creation in the United Kingdom (UK) are CMV positive (SaBTO, 2012). CMV infection can be transmitted both horizontally and vertically (Crough and Kannah, 2009). plane transmission occurs through contact with body fluids, such as urine and saliva, sexually through genital secretions, blood transfusion, and hematopoietic stem cell and organ transplant (SaBTO, 2012 Sia and Patel, 2000). Vertical transmission occurs from mother to child, via delivery and breast milk (Crough and Kannah, 2009). Additionally, congenital CMV infection is highly prevalent and may arise through a primary maternal infection during pregnancy (Crough and Kannah, 2009).Following exposure to CMV and the initial infection, the virus remains in a dormant resign (Ljungman, 2004). Seroconversion of the host occurs between 6 8 weeks and mounts an immune response, producing CMV specific immunoglobulin (IgG) (Seed et al., 2014). In the UK, there is an estimated seroconversion rate of 1% per annum (SaBTO, 2012). CMV therefore has a window period, in which there may be underlying viremia and high viral load (Liberman et al., 2011). Subsequently, a CMV seropositive individual is considered to have been infected, whilst at the same time considered potentially infectious due to the life-long persistence of the virus (SaBTO, 2012).Transfusion-transmitted CMV infection is regarded as a potential threat to the safety and adequateness of the blood supply for a multitude of reasons (Roback, 2002). Firstly, transfusion-transmission of CMV that is present in blood and blood components can result in the infection of nave recipients (Ziemann and Hennig, 2014 Ljungman, 2004). Secondly, transfusion-transmitted CMV is acknowledged as a primary source of infection, in which donor infectivity is an underlying reason, that may result in CMV disease (Ljungman, 2004). Thirdly, CMV seropositive recipients that are exposed to blood products containing CMV may cause reactivation of the potential virus or reinfection from a new strain (Ziemann and Hennig, 2014 Ljungman, 2004). However, the risk of transfusion-transmitted CMV infection has been significantly reduced through the implementation of leucodepletion and production of specific CMV negative blood and blood products (Ziemann and Hennig, 2014).Since November 1999, all blood products (unless state otherwise) produced by the UK blood attend are leucodepleted (Guidelines for the Blood Transfusion Services in the United Kingdom, 2013). Initially, this was a response taken to reduce the risk of variant Creutzfeldt-Jakob (vCJD) disease in blood transfusions however, this risk reduction strategy has proven beneficial in additional areas of transfusion science and blood safety (Guidelines for the Blood Transfusion Services in the United Kingdom, 2013). The UK precondition for leucodepletion is more than 90% of leucocyte-depleted components should contain less than 1 x 106 leucocytes and more than 99% of components should contain less than 5 x 106 leucocytes (SaBTO, 2012). The judicial admission for 99% of components is regarded as the level in which blood components are deemed CMV safe (SaBTO, 2012).Leucodepletion has considerably reduced the risk of transfusion-transmitted CMV, to a level that mirrors the selection of CMV negative blood products (Ljungman, 2004 Bowden et al., 1 995). However, it has yet to be shown to what extent the techniques are comparable and how this may affect patient groups considered at risk of CMV infection (Ljungman, 2004). It is classic to note that whilst leucodepletion removes most white cells from blood products, it is not 100% effective (Kumar, 2006). Therefore, there is a residual risk of CMV transmission in blood products of recently infected donors (Kumar, 2006). This occurs in the window period of the virus from 6 8 weeks to 1 year following seroconversion, in which the virus may be present in the remaining plasma or white cells (SaBTO, 2012 Ziemann et al., 2010 Drew and Roback, 2007).CMV transmission can occur in both donors that have an fighting(a) infection, including primary or reactivated, or latent infection (Azevedo, 2015). The leading mechanism of transfusion-transmitted CMV infection is through mononuclear cells that are believed to harbour a latent infection (Ljungman, 2004). CMV is thought to persist in cir culating monocytes, in which an estimated 1 in 10,000 and 1 in 100,000 peripheral blood monocular cells carry CMV (SaBTO, 2012). Pennington et al (2001) conducted a study that provided evidence to suggest that leucodepletion filters are highly effective in removing mononuclear cells and may reduce CMV levels to 0.1 viral copies per mL in leucodepleted blood. Furthermore, blood products that have been leucodepleted are monitored continuously, development flow cytometry, to assess efficiency (SaBTO, 2012). Moreover, the prospect of having a component issued that contains a leucocyte count above the UK specification can be calculated (SaBTO, 2012).In regards to testing for transfusion-transmitted CMV, there are two main methods that are used. This includes serological testing and Nucleic Acid Technology (NAT) testing (SaBTO, 2012). Serological testing involves the use of antibody screening which is accomplished through the use of enzyme immunoassay (EIA) tests that detect total CMV an tibody (Ross, 2011). Screening for CMV infection using serology is the most prevalent method used and is based on the agglutination principle (Ross, 2011 Ljungman, 2004). The method offers several advantages as it is fast, highly sensitive, and highly specific, constituting an ideal screening test (Ross, 2011). This method, however, is associated with two key limitations. Firstly, the window period presents a challenge in regards to activation of the primary infection and seroconversion (Ljungman, 2004). Secondly, there is a risk of obtaining senseless negative screening results (Ljungman, 2004). Therefore, there is a risk that CMV may be transmitted via a CMV seronegative component (SaBTO, 2012).In addition to serology, NAT testing is used to detect CMV deoxyribonucleic acid and subsequent infection (Ross, 2011). Several qualitative and quantitative assays are available for this method (SaBTO, 2012). This screening method is associated with disagreement in the sensitivity and sp ecificity of available assays (Roback et al., 20032001). Studies have highlighted inter-laboratory variation for samples containing low viral load (Pang et al, 2009 Wolff et al., 2009). As a result, a CMV DNA reference has been unquestionable for comparison of results when sensitivity is a challenge (Ross, 2011).To produce a supply of CMV negative blood and blood components, several donations are screened each year. Overall, an estimated 25 40% of donors are CMV antibody positive, dependent on age. The production and use of CMV negative blood components forms a significant undertaking for the blood service. harmonize to the report released by the Advisory Committee on the Safety of Blood, Tissues, and Organs (SaBTO) in March 2012, in the last 5 years, the progeny of CMV negative platelets and red cells has increased. The report notes that NHSBT charge 7.76 for CMV negative red cells and platelets, covering the inventory and screening costs. This amounts to a total of 2.5 million per annum, in which 230,000 is dedicated to pheresis platelets and 2,270,000 to red cells.The number of donations that are screened is greater than the number of donations that are issued as CMV negative. In addition, not all donations screened will deliver a negative result. Subsequently, it has been proposed that the use and production of CMV negative components is reviewed. SaBTO recommends the use of a single inventory and accepting leucodepleted blood products as CMV safe. This is outlined in instalment 6.Proposal6.1 This proposal has been written to ask the blood centre to consider ceasing CMV testing for an agreed list of blood products and in its replacement, support the use of leucodepleted blood components that are considered CMV safe.6.2The proposal of ceasing CMV testing for the replacement of leucodepleted components that are considered CMV safe is associated with several advantages.Inventory managementManagement of a single inventory would offer an advantage to blood banks and hospitals. This would be a preferred method to the current used for ease of access. NHSBT must ensure CMV negative components are available across the country on multiple NHS sites. To achieve this, NHSBT fall approximately 95,000 n the delivery of CMV negative components.WastageThe Belgian Blood Service have produced a report that states implementation of pathogen reduction in platelets to inactivate CMV may result in an overall hang in the wastage of platelets. A 1.5% reduction is estimated, which would result in a saving of 0.22 million.Improved compliance with safety initiatives simplification in the wastage of blood products and implementation of a single inventory would alter the target of 80% platelets by apheresis to be met sooner. Furthermore, this would support transfusion related acute lung injury (TRALI) prevention, as the number of male platelet donors would increase due to enhanced recruitment strategies. This would further enable costs of HLA antibody scr eening of potential female platelet donors to be avoided. decline in hospital blood bank workloadBecause of the removal of CMV seronegative components, the workload in hospitals and blood banks would decrease. Staff would no longer have to spend time ordering or checking platelets as CMV negative components. This would have a direct positive impact on the stock management. Staff that may potentially be free from the responsibility associated with CMV negative products will be able to invest their time elsewhere, to improve the efficiency of the blood service.Reduction in clinical errorsThe Serious Hazards of Transfusion (SHOT) have reported from 2000 to 2010, 1040 reports were loadd stating special requirements were not met. Of these, 83 were attributed to the inappropriate selection of blood components that were not CMV negative. 65 were attributed to selection of blood components that were both CMV negative and irradiated components. However, none of these cases reported CMV tran smission.6.3The proposed implementation date of this project is January 2018. Further clinical guidance is to be requested from SaBTO who will instruct in the implementation plan of this proposal.6.4Consideration must be given to specific patient groups that are considered at risk of CMV infection. This includesHaematopoietic stem cell transplant patientsLeucodepleted blood products can be used for all patient groups post haemopoietic stem cell transplantationPatients receiving transfusions and may need a transplant also may receive leucodepleted productsCMV PCR should be used to assess CMV infection for patient groups to enable early detection and treatmentIntra-uterine transfusions and neonatesCMV negative components should be provided for intra-uterine transfusions and neonates (up to 28 days post expected due date)All blood products produced at a reduce size for neonates should be CMV seronegativePregnant patientsCMV seronegative blood products should be provided to pregnancy wo men, regardless of CMV status.Components should also be provided for transfusions throughout pregnancy, for example in the case of haemoglobinopathies.HIV and immunodeficient patientsThese patients should receive leucodepleted blood as there is no evidence to suggest a benefit with the use of CMV seronegative componentsOrgan transplant patientsOrgan transplant patients should receive leucodepleted blood onlyCMV PCR should be used to assess CMV infection for patient groups to enable early detection and treatmentGranulocytesGranulocyte components provided should be CMV seronegative for all patients as these components cannot be leucodepleted6.5Potential impact on blood centre employees includes the reduction in workload. Considerations needs to be given towards how this workload can be replaced. Consideration also needs to be given towards the possibility of redundancy, as a resultant effect of this proposal.6.6The gore must be aware of the clinical and financial benefits of this pr oposal however, the board should also be aware of potential limitations regarding the operation of the proposal. The board should also be aware of potential legal repercussions should someone become infected with CMV through a blood component.6.7Stakeholders that will need to be involved include both internal and external. Internal stakeholders will include the manager of the NHSBT site and the head of testing. External stake holders will need to advance public awareness regarding the change in production of seronegative CMV components. Doctors will also need to be aware of the changes implemented to CMV negative components and be aware of who this applies for. 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