Barbara J. Bryant

Pathogen inactivation: the definitive safeguard for the blood supply.

CONTEXT Pathogen inactivation provides a proactive approach to cleansing the blood supply. In the plasma fractionation and manufacturing industry, pathogen inactivation technologies have been successfully implemented resulting in no transmission of human immunodeficiency, hepatitis C, or hepatitis B viruses by US-licensed plasma derivatives since 1985. However, these technologies cannot be used to pathogen inactivate cellular blood components. Although current blood donor screening and disease testing has drastically reduced the incidence of transfusion-transmitted diseases, there still looms the threat to the blood supply of a new or reemerging pathogen. Of particular concern is the silent emergence of a new agent with a prolonged latent period in which asymptomatic infected carriers would donate and spread infection. OBJECTIVE To review and summarize the principles, challenges, achievements, prospective technologies, and future goals of pathogen inactivation of the blood supply. DATA SOURCES The current published English-language literature from 1968 through 2006 and a historical landmark article from 1943 are integrated into a review of this subject. CONCLUSIONS The ultimate goal of pathogen inactivation is to maximally reduce the transmission of potential pathogens without significantly compromising the therapeutic efficacy of the cellular and protein constituents of blood. This must be accomplished without introducing toxicities into the blood supply and without causing neoantigen formation and subsequent antibody production. Several promising pathogen inactivation technologies are being developed and clinically tested, and others are currently in use. Pathogen inactivation offers additional layers of protection from infectious agents that threaten the blood supply and has the potential to impact the safety of blood transfusions worldwide.

Ascertainment of iron deficiency and depletion in blood donors through screening questions for pica and restless legs syndrome

Pica and restless legs syndrome (RLS) are associated with iron depletion and deficiency. The presence of pica and RLS was prospectively assessed in blood donors.

Iron replacement therapy in the routine management of blood donors

BACKGROUND: Iron depletion or deficiency in blood donors frequently results in deferrals for low hemoglobin (Hb), yet blood centers remain reluctant to dispense iron replacement therapy to donors.

Capillary versus venous haemoglobin determination in the assessment of healthy blood donors

To determine the accuracy of fingerstick haemoglobin assessment in blood donors, the performance of a portable haemoglobinometer (HemoCue Hb 201+) was prospectively compared with that of an automated haematology analyzer (Cell‐Dyn 4000). Haemoglobin values obtained by the latter were used as the ‘true’ result.

A randomized, blinded, placebo-controlled trial of education and iron supplementation for mitigation of iron deficiency in regular blood donors.

The historical approach of offering dietary advice to donors with low hemoglobin (Hb) is ineffective for preventing iron deficiency in frequent donors. Alternative approaches to maintaining donor iron status were explored.

IVIg for Treatment of Severe Refractory Heparin-Induced Thrombocytopenia

BACKGROUND: Heparin‐induced thrombocytopenia (HIT) complicated by severe thrombocytopenia and thrombosis can pose significant treatment challenges. Use of alternative anticoagulants in this setting may increase bleeding risks, especially in patients who have a protracted disease course. Additional therapies are lacking in this severely affected patient population. METHODS: We describe three patients with HIT who had severe thromboembolism and prolonged thrombocytopenia refractory to standard treatment but who achieved an immediate and sustained response to IVIg therapy. The mechanism of action of IVIg was evaluated in these patients and in five additional patients with severe HIT. The impact of a common polymorphism (H/R 131) in the platelet IgG receptor Fc&ggr;RIIa on IVIg‐mediated inhibition of platelet activation was also examined. RESULTS: At levels attained in vivo, IVIg inhibits HIT antibody‐mediated platelet activation. The constant domain of IgG (Fc) but not the antigen‐binding portion (Fab) is required for this effect. Consistent with this finding, IVIg had no effect on HIT antibody binding in a solid‐phase HIT immunoassay (platelet factor 4 enzyme‐linked immunoassay). The H/R131 polymorphism in Fc&ggr;RIIa influences the susceptibility of platelets to IVIg treatment, with the HH131 genotype being most susceptible to IVIg‐mediated inhibition of antibody‐induced activation. However, at high doses of IVIg, activation of platelets of all Fc&ggr;RIIa genotypes was significantly inhibited. All three patients did well on long‐term anticoagulation therapy with direct oral anticoagulants. CONCLUSIONS: These studies suggest that IVIg treatment should be considered in patients with HIT who have severe disease that is refractory to standard therapies.

Evaluation of low red blood cell mean corpuscular volume in an apheresis donor population.

BACKGROUND: Apheresis donors are routinely evaluated with a complete blood count (CBC). Low red blood cell mean corpuscular volume (MCV) values (<80 fL) in the presence of an acceptable hemoglobin (Hb; ≥12.5 g/dL) could be due to iron deficiency or hemoglobinopathy. The etiology of a low MCV in a healthy apheresis donor population was assessed.

Pasteurella multocida bacteremia in asymptomatic plateletpheresis donors: a tale of two cats

BACKGROUND: Bacterial contamination of platelet (PLT) concentrates occurs in 1 in 1000 to 1 in 3000 components and has been a leading cause of transfusion‐associated morbidity and mortality. Two cases of Pasteurella multocida bacteremia in asymptomatic plateletpheresis donors are reported. Clinical outcomes were profoundly different, emphasizing the importance of robust methods to detect bacterial contamination.

The strategies to reduce iron deficiency in blood donors randomized trial: design, enrolment and early retention

Repeated blood donation produces iron deficiency. Changes in dietary iron intake do not prevent donation‐induced iron deficiency. Prolonging the interdonation interval or using oral iron supplements can mitigate donation‐induced iron deficiency. The most effective operational methods for reducing iron deficiency in donors are unknown.

Transfusion medicine education: an integral foundation of effective blood management

M edical education and continuing medical education (CME) for transfusion medicine are integral and necessary elements for quality patient care. The misuse and overuse of blood components, and the sequelae resulting from this inappropriate use, increases the risk for patient morbidity. Unwarranted blood transfusions also add avoidable costs for hospitals at a time of diminishing financial resources. Prudent and conservative blood product use further helps to control inventory and prevent blood shortages. As education and direct intervention are required to ensure the appropriate use of pharmaceutical agents, we are also driven in a similar manner to inform our colleagues about the appropriate use and adverse effects of blood products. The current economic and regulatory climate demands that we act to facilitate and lead transfusion education for our clinical colleagues, and if we do not, hospital administrations soon will demand that we do so. In fact, the growing enthusiasm for patient blood management has created a long sought opportunity to enhance transfusion education for a more receptive audience. Decades have been spent discussing the necessary incorporation of transfusion medicine into medical education programs. The Transfusion Medicine Academic Awards (TMAA) program was started in 1983 by the National Heart, Lung, and Blood Institute to provide financial support to medical schools who wanted to strengthen transfusion education for their students. The participating medical centers published proposed transfusion medicine curricula twice: once in 1989 and again in 1995. Additional transfusion medicine–focused educational programs have been suggested for pediatrics (PedsTMAA) in 2006 and for laboratory medicine in 2010. These publications, however, only provided recommendations and did not dictate standards for medical trainee knowledge. Not surprisingly, these efforts have resulted in minimal changes to transfusion education or medical education requirements. As defined by the United States Medical Licensing Exams (USMLE), knowledge of blood components or transfusion practices is not identified as a fundamental topic for minimum competency standards for medical practice (Table 1). The USMLE does not require that students know the appropriate use of blood products during medical school at any level, and the only exam that specifically mentions blood products is the exam that occurs after the second year of medical education, before any direct clinical experience in many programs (Step 1). Perhaps as a consequence of these limited requirements, medical schools do not emphasize transfusion medicine education, making room for the more heavily tested topics. Karp and coworkers determined that 17% of medical schools provided no didactic lectures on transfusion medicine topics, and of those that do, only about 50% of them provided more than 1 or 2 hours of content. Also, more than 41% of students do not recall ever having a transfusion lecture, regardless of whether the student actually received one. Despite the limited number of formal training hours in transfusion medicine, medical school curricula do provide enough material for successful completion of USMLE exams. According to the USMLE Web site, in 2012, greater than 96% of MD degree first-time test takers pass all three of the Step exams on their first attempt. Knowledge of blood products and transfusion indications are simply not tested by the USMLE as an indicator of a new physician’s ability to assume independent responsibility without supervision. The deficiency in medical education for transfusion medicine starts early and is continued into professional life for housestaff and attendings. With little or no training in medical school with evidence-based practices to guide decisions, the use of transfusions are often based on individual clinical experience. Defining the extent of this deficiency has been the focus of multiple publications. Bryant and coworkers prospectively identified that 85.3% of referrals to the blood bank physician on-call required some form of physician education regarding the appropriateness of blood component orders. O’Brien and colleagues found that nonpathology PGY-1’s at one institution scored 24.0% to 67.1% correct on a standardized test that evaluated knowledge of the red blood cell (RBC) consent process and transfusion medicine general knowledge. Of particular concern, they found that none of the tested physicians could define the use of blood irradiation, and less than 10% knew the transfusion transmission risk for HIV and HCV. Salem-Schatz and coworkers found that less than 31% could answer questions regarding transfusion indications and, perhaps more revealing, found that attending physicians performed worse than residents, but revealed greater