Graham D. Sher

A randomized controlled trial comparing the frequency of acute reactions to plasma-removed platelets and prestorage WBC-reduced platelets

BACKGROUND: Removal of the plasma supernatant from platelets before transfusion is effective in preventing acute reactions to platelets caused by cytokines. Prestorage WBC reduction of platelets may be even more effective at preventing reactions as the WBCs are removed and WBC‐derived cytokines do not accumulate in this component. This study evaluates the effectiveness of plasma removal and two methods of prestorage WBC reduction for preventing acute reactions to platelets.

A multivariable model for predicting the need for blood transfusion in patients undergoing first-time elective coronary bypass graft surgery

BACKGROUND: The incidence of blood transfusion in coronary artery bypass graft (CABG) surgery remains high. Preoperative identification of those at high risk for requiring blood will allow for the cost‐effective use of some blood conservation modalities. Multivariable analysis techniques were used in this study to develop a prediction rule for such a purpose.

Predictive ability of sequential surveys in determining donor loss from increasingly stringent variant Creutzfeldt-Jakob disease deferral policies

BACKGROUND:  Predonation screening questions about travel increase the safety of the blood supply from diseases such as variant Creutzfeldt‐Jakob disease (vCJD) and malaria. This study examines the ability of sequential surveys to predict actual travel deferrals and the operational validity of travel questions.

Comparison of Cytotoxic Aldehyde Generation in Beta-Thalassemia Patients Chelated with Deferoxamine or Deferiprone (L1) Versus NO Chelation

The mechanism of iron-induced organ failure in iron overload disorders is not known, but it is conjectured that excess iron-catalyzed free radical generation contributes to organ damage. We hypothesized that free radical generation, quantified by the presence of 20 separate cytotoxic aldehydes in plasma, would be significantly increased in non-chelated beta-thalassemia major patients, in comparison to those chelated with either deferiprone (L1) or deferoxamine (desferal). We also report on red cell glutathione peroxidase activity in these patient groups, an enzyme involved in averting the damaging effects of free radicals. Ten patients were chelated with nightly subcutaneous infusions of desferal and 10 received the experimental oral chelator L1. Body iron burden was assessed by serum ferritin and hepatic iron concentrations. In comparison to non-chelated controls, significant decreases of 62% and 64% in total cytotoxic aldehyde concentrations were observed in patients chelated with desferal and L1, respectively (p < 0.001). Significantly lower red cell glutathione peroxidase activity was also observed in non-chelated controls, in comparison to those chelated with either desferal or L1 (p < 0.001). This is the first report on the concentrations of cytotoxic aldehydes in non-chelated beta-thalassemia major patients, and the first to report on the effects of L1 against cytotoxic aldehyde formation in plasma of patients with iron-overload.

A retrospective observational study of leucoreductive strategies to manage patients with acute myeloid leukaemia presenting with hyperleucocytosis.

Acute myeloid leukaemia (AML) patients with hyperleucocytosis have higher early mortality, lower complete remission (CR) and overall survival (OS). Whether different pre‐induction leucoreduction strategies can improve outcome is unknown. A single centre retrospective cohort study was conducted on AML patients with a white blood cell count (WBC) >100 × 109/l between 1987 and 1997, and on all AML patients between 1998 and 2006, to determine (a) the effect of four different leucoreductive strategies (leukapheresis, hydroxycarbamide, leukapheresis and hydroxycarbamide or no pre‐induction leucoreduction) on early (day 28) mortality, CR, and OS; and (b) whether a high presenting WBC remains a negative predictor of OS in patients surviving induction (first 28 d). In the 1998‐2006 cohort (n = 702), higher WBC was associated with higher early mortality and lower OS but its effects were greatly diminished in patients who survived the first 28 d (Hazard Ratio 1·094 vs. 1·002). A WBC of 34·1 × 109/l had the highest sensitivity (75·6%) and specificity (67·4%) for early mortality. None of the four leucoreduction strategies differed significantly in early mortality, CR, or OS in patients with WBC>100 × 109/l (n = 166). The number of leucostatic signs was a significant predictor of early mortality (P < 0·0001) and OS (P = 0·0007). The results suggest that AML patients with hyperleucocytosis should be induced, if eligible, without pre‐induction leucoreduction.

Prevalence of GBV-C/Hepatitis G Virus Viremia and Anti-E2 in Canadian Blood Donors

Background and Objectives: GB virus C (GBV‐C)/hepatitis G virus (HGV) is a recently recognized parenterally and sexually transmitted agent. The prevalence of GBV‐C/HGV markers in Canadian blood donors has not been previously studied and was therefore determined. Materials and Methods: Blood donors [identity unlinked (IU), short‐term temporarily deferred (STTD) and autologous groups] and donor samples with antibodies to hepatitis C (anti‐HCV) or hepatitis B core were tested for GBV‐C/HGV RNA and for antibodies to E2 antigen (anti‐E2). Results: GBV‐C/HGV RNA was found in 1.1% and anti‐E2 in 7.3% of the combined IU/STTD donor group. Viremia was much more common in anti‐HCV‐positive samples (12.5%); anti‐E2 was present in >50% of this group. In the STTD group, female gender was significantly associated with viremia. Conclusion: GBV‐C/HGV infection is relatively common in Canadian donors, and a small proportion are viremic. The association of female gender and viremia was unexpected. Further study is needed to clarify the epidemiology and natural history of GBV‐C/HGV infection.

Lessons learned from Trypanosoma cruzi test implementation

Trypanosoma cruzi causes Chagas disease. Humans become infected through T. cruzi-infected insect bites, transmission from mother to fetus, organ transplantation, and blood transfusion. An estimated 300,000 people in the United States and Canada are infected; most infections occur in those emigrating from South America but a small number of autochthonous cases have also emerged in the United States. Once infected, low-level parasitemia persists indefinitely. T. cruzi remains viable in stored whole blood and citrated blood samples stored at refrigerator and room temperatures, respectively. In Mexico and Central and South America, approximately 20% of transfusion recipients of parasitemic blood become infected. Studies conducted in Miami and Los Angeles in the 1990s found T. cruzi seroprevalence rates of 1 per 7500 to 1 per 9000 donors. Interestingly, none of the 18 recipients of blood from a subsequently identified seropositive donor had evidence of infection. In contrast, in a more recently reported study conducted in Mexico, four of nine surviving recipients of blood from T. cruzi-infected donors were in turn confirmed seropositive. In the United States and Canada, seven transfusionassociated Chagas cases are known to have occurred since the 1980s. Six involved platelet (PLT) transfusions; the component in the seventh case remains unknown. The six infected donors were born or resided in endemic Latin American countries. In light of increasing immigration of persons to the United States from endemic regions and the current paradigm of a “zero-risk” blood supply, various mitigation strategies for preventing transfusion-associated Chagas cases emerged. Donor history screening alone was rejected in the United States since only threequarters of infected donors are identified via questioning and thousands of noninfected donors are inconvenienced. Leukoreduction showed modest benefit. Serologic screening, therefore, became the default position. The latter message, transmitted to potential test-kit manufacturers by the U.S. Food and Drug Administration (FDA) at the Blood Product Advisory Committee meeting in September 1989 and more specifically in September 2002, led to development, clinical trials, and subsequent approval of a T. cruzi screening test in December 2006. A second test, in 2010, received approval. Universal screening began in the United States in 2007, before an FDA mandate. Spain implemented selective testing in 2005 and Canada in 2009 to 2010. In 2009, after acquiring 2 years of universal testing data, many blood centers in the United States moved to a “test every donor once” strategy, retaining universal testing in selected areas in the south where incident cases may occur. As reported in this issue of TRANSFUSION, Custer and coworkers found a seroprevalence rate of 1:33,039 donations and 1:13,292 donors among 2.9 million donations and 1.2 million unique donors tested between January 2007 and December 2009. Risk factors included those born in Mexico (1:800 donors) and Central or South America (1:200). Prevalence varied by geographic region and was highest at donation sites in the Central Coast of California (1:5200 donors), Las Vegas, and parts of Texas. Seropositive donors cited bites from reduviid bugs and having lived in rural areas of endemic countries. Approximately 20% of confirmed seropositive donors had “no known risk factors” including travel in endemic countries and thus are presumed autochthonous cases. Costeffectiveness analysis showed

Men who have had sex with men and blood donation: is it time to change our deferral criteria?

757,000 per qualityadjusted life-year (QALY) saved. Cantey and colleagues investigated the potential for T. cruzi autochthonous transmission in seropositive confirmed blood donors who had not lived outside the United States and donated to the Blood Systems and American Red Cross, United States T. cruzi Infection Study (USTC). Through April 30, 2010, these blood collection agencies identified 1084 T. cruzi-confirmed seropositive donors from approximately 29 million donations (1:26,700). Fiftyfour were eligible for the USTC and 37 enrolled. Enrollees were divided into a group whose tests were confirmed by Centers for Disease Control and Prevention (CDC) serologic assays (n = 15) and those with tests nonconfirmed at the CDC (n = 22). Only two of the latter had consistent repeat-reactive results with the initially approved T. cruzi antibody test, but 21 of 21 tested by the second approved assay were negative. Among the concordant group, eight traveled to an endemic country and three to rural areas in an endemic country, but none resided there more than 2 weeks. All lived in a state with a T. cruzi vector or a known infected mammalian reservoir and most participated in work-related or leisure activities in those states. By extrapolating USTC data, U.S. vector-borne cases approximate 1:354,000 to 1:485,000 tested. Benjamin and colleagues reviewed reported transfusion-transmitted T. cruzi cases in North America and Spain: seven from the United States, five from Spain, two from Canada, and one from Mexico. Implicated donors were born in Bolivia, Argentina, Brazil, Chile, and Paraguay. TRANSFUSION 2012;52:1849-1851.

Donor criteria for men who have sex with men: a Canadian perspective.

Journal of the International Association of Physicians in AIDS Care Men who have had sex with other men even once, since 1977, are permanently deferred as blood donors. This policy was put in place several years ago when it was recognized that men who have sex with men (MSM) represented a group at risk for HIV. The policy is not unique to the United States and Canada, since most industrialized countries apply the same rule, or one that is very similar. Many have expressed the view that such a policy, while it may have been justified in the early days of the HIV epidemic, is now overly cautious and has the unfortunate effect of stigmatizing gay men who would donate blood.

A comparison of health care and blood supply system structures

The indefinite deferral for MSM even once since 1977 was instituted in the United States in the early 1980s, before the causal agent for AIDS was identified, when MSM was noted to be a particularly high-risk group. The Canadian Red Cross Society (CRCS) followed suit, and this criterion was in place in Canada until July 2013, when both Canadian Blood Services and Hema-Quebecchangedtoa5-yeardeferralfromlastMSM contact. Although from a practical perspective, this change will allow few gay men to donate blood, it is nonetheless significant, as it is the first change to be made to this policy since it was implemented more than 25 years