Richard J. Davey

Recruiting blood donors: challenges and opportunities

he American blood supply is marginal. The requirements for blood are increasing as the population ages and new and aggressive surgical and oncologic procedures are introduced. These demands require a steadily increasing supply of specialized blood products. Nevertheless, the blood supply has remained static. Every year in the US approximately 12.6 million units of whole blood are collected from approximately 8 million volunteer donors. Approximately 3 percent of the population donate an average of 1.6 times per year. Thirty years ago the donor history questions were brief and screening tests were limited. However, we now have a highly complex and heavily regulated process of qualifying blood donors and screening blood products. The donation process has become very complex, resulting in significant donor loss through deferral and disqualification. The blood supply is now extraordinarily safe, but at a high price in blood availability. Blood shortages are common, with special appeals now routine in summer months and over the winter holidays. These appeals are becoming less effective as the donating public hears repeated blood appeal messages. Also, the appeals seem to energize regular donors instead of attracting new donors. These regular donors may respond to an appeal but are then lost for the ensuing 8 weeks. The net effect is a negligible increase in donations and a “burnout” of regular donors. Donor recruiting specialists are very effective in organizing and conducting blood drives. New approaches, however, for engaging, qualifying, and retaining donors are required. I suggest that we consider the following changes in the way we approach and qualify donors. These suggestions are not new, but the time is right for a comprehensive approach to this issue. • Modifying deferral criteria and revising the donor history questionnaire; • Adjusting the Hb cutoff for donations; • Providing iron supplementation for women donors; • Allowing 16-year-olds to donate; • Recruiting hemochromatosis patients; • Considering the judicious use of donor incentives; and • Structuring the blood center as a community health resource.

Prevalence of thyroid abnormalities in patients with dermatitis herpetiformis and in control subjects with HLA-B8/-DR3

PURPOSE The prevalence of thyroid dysfunction as measured by the presence of overt thyroid disease, abnormal results of thyroid function tests, or antithyroid antibodies was compared in patients with dermatitis herpetiformis (DH) and a normal control group who had the HLA-B8/-DR3 haplotype. PATIENTS AND METHODS The study population consisted of 56 patients with DH and 26 control subjects with the HLA-B8/-DR3 haplotype. All were examined for thyroid function abnormalities and thyroid autoantibodies. RESULTS Patients with DH had a statistically significant increase in the prevalence of abnormal thyroid function test results and autoantibodies: 32% versus 4% for controls (Z = 2.01, p less than 0.02). In patients with DH, hypothyroidism was the most common thyroid abnormality (12 of 56) followed by hyperthyroidism (four of 56). Two patients had normal thyroid function test results with thyroid autoantibodies. Risk factors for thyroid abnormalities in patients with DH were increasing age (chi 2 = 6.55, p less than 0.02, significant) and the presence of thyroid microsomal antibodies. The HLA-B8/-DR3 haplotype was not a risk factor for thyroid abnormalities. CONCLUSION The findings suggest that thyroid disease is independently associated with DH. Examination of patients with DH should include thyroid function tests along with assays for antithyroid antibodies.

Acute coagulopathy following infusion of prothrombin complex concentrate

An acute coagulopathy developed in a 49 year old woman with severe liver disease after she received an infusion of prothrombin complex concentrate. The concentrate used in the infusion was subsequently studied by observing the effect of the concentrate on the partial thromboplastin times of various plasmas. The evidence suggests that activated coagulation factors, including activated factor X, were present in the concentrate, and probably played a role in initiating the acute change in the patients coagulation status. Mechanisms whereby liver disease predisposes toward the development of such a coagulopathy are discussed. It would appear that prothrombin complex concentrates should be used in patients with liver disease only with utmost caution.

The Clinical Significance of Anti‐H in an Individual with the Oh (Bombay) Phenotype

To evaluate the clinical significance of anti‐H present in individuals with the Oh (Bombay) phenotype, red blood cell 51chromium survival studies and related serological tests were undertaken in an Oh (Bombay) individual. A small sample of group O donor red blood cells was labeled with 51chromium and infused into the patient. The T ½ of the infused cells was six minutes, with two per cent of the cells surviving at 24 hours. A similar study using the patients own labeled red blood cells demonstrated 100 per cent survival at 24 hours. Initial laboratory studies indicated that the anti‐H was active in saline at 4, 22 and 37 C and by the indirect antiglobulin test. Analysis of the antibody in both pre‐and posttransfusion specimens showed it to have both IgM and IgG components. The anti‐H titer at 37 C rose from 1:4 prior to the infusion of the O cells to 1:32 one week postinfusion, and a partial hemolysin appeared. Saliva inhibition studies demonstrated that the antibody was neutralizable prior to the group O exposure but was not neutralizable one week post exposure. We conclude that the anti‐H present in this individual rapidly destroyed infused group O red blood cells. Individuals with the Oh (Bombay) phenotype should be transfused only with Oh (Bombay) blood.

The September 11, 2001 disaster and the New York blood supply

Collection of umbilical cord blood (UCB) sometimes occurs in sites remote from the laboratory responsible for further processing. During shipment UCB is maintained in its liquid phase. The addition of cell culture media may provide beneficial effects on maintenance and viability of hematopoietic progenitor cells. If additives are used they should be suitable for infusion into humans. In a previous study the effects of two infusible-grade and five “invitro-use-only” media on the preservation of PBPC were evaluated.1 Storage in STM-Sav, one of the infusiblegrade solutions, resulted in better preservation of viable, functional hematopoietic progenitor cells when compared to the other infusible-grade solution and was as effective as in-vitro-use-only culture media. Based on these results we investigated the effectiveness of STM-Sav for storage of UCB for up to 72 hours at 4 C and room temperature by comparing it to controls stored under the same conditions without any additives other than the anticoagulant CPD. Umbilical cord blood was collected into Baxter transfer bags containing 20 mL CPD. At t = 0 hours (1-6.5 h [mean 2.1 h] after collection) a sample was removed for testing. The remaining content was equally divided into four 150 mL transfer pack bags (#4R2001, Baxter). STMSav was added to two of the bags in a volume equal to the volume of the cord blood already present. The bags that contained no additive had been clamped in the middle to provide equal surface/volume ratios for each UCB. Each one STM-Sav bag and one CPD-only control bag was then maintained at 4 C or in an insulated container at 20–24 C (RT). Samples for testing were removed at t = 24 and t = 72 h from each bag. The parameters measured included nucleated cell (NC) counts performed on a Coulter STKS cell counter and differentials (microscopic evaluation). Percentages of CD34+ and CD3+ cells and cell viability were measured by flow cytometry with gating2. Progenitor assays (CFU-GM) were performed using a standardized method3. Cells were plated in duplicate in two different concentrations (C1 = 3.0 104 NC/well and C2 = 5.0 104 NC/well) and mean frequency of CFU-GM per 105 NC was calculated based on the number of cells plated. Solution pH was measured using an ABL 505 or ABL 520 blood gas analyzer. Data were statistically analyzed using the paired Student’s t-test with a level of significance of p < 0.05. No significantly different change in the number of viable CD34+ cells, TNC and CD3+ cells was found at 24 hours and 72 hours if compared to t = 0 for all four storage conditions (Table 1). Interestingly, there was a continuous rise of CD3+ cells over time at 4 C with simultaneously dropping counts at RT. This resulted in significantly higher CD3+ counts at 4 C compared to RT for each storage solution at 24 hours and 72 hours. At 72 hours CFU-GM recoveries were significantly higher after storage in STM-Sav at 4 C compared to storage in CPD at 4 C (C1 and C2) and RT (C1). Only when the UCB was stored in STM-Sav at 4 C no significant decrease in the recovery of CFU-GM after storage (24 h and 72 h) was found (C1 and C2). The pH was significantly higher at 24 h and 72 h when STM-Sav was added compared to cord blood in CPD (Table 2). The cell viabilities are shown in Table 2. Viabilities of <95 percent for individual units were only found in a few UCBs that were stored in CPD. The single lowest measurement was 91.5 percent (CPD at RT at 72 hrs). In summary, all storage conditions resulted in com-

Transfusion-Associated Graft-Versus-Host Disease and the Irradiation of Blood Components

Transfusion-associated graft-versus-host disease (TA-GVHD) is a rare but lethal disorder caused when viable donor lymphocytes engraft and proliferate in a susceptible transfusion recipient. Patients with immune deficiency disorders, hematologic malignancies and bone marrow transplants are at risk to TA-GVHD, as are premature newborns and transfusion recipients who are HLA heterozygous for an HLA-haplotype that is shared with an HLA homozygous donor. Irradiation of blood components with 2500 cGy will inactivate donor lymphocytes and prevent TA-GVHD. Platelets and granulocytes are not functionally impaired by this radiation dose, but red cells sustain detectable damage. Red cell units irradiated and stored for 42 days have significantly higher supernatant recovery of chromium-51 labeled cells is sub-optimal. Based on these data, the maximum permissible storage time for irradiated red cells has been reduced to 28 days.

51Chromium survival of Yt(a+) red cells as a determinant of the in vivo significance of anti‐Yta

A case is presented in which anti‐Yta produced a moderately accelerated removal of chromium‐labeled Yt(a+) red blood cells (T1/2, 96 hours). Other reported examples of anti‐Yta either have rapidly removed transfused Yt(a+) red blood cells or have permitted apparently normal survival of these cells. In light of this wide variation in in vivo potency of anti‐Yta, it is recommended that chromium red blood cell survival studies be done before transfusion of Yt(a+) red blood cells in sensitized individuals.

The Uses of Radiolabeled Red Cells in Transfusion Medicine

The ability to radiolabel and follow the red cell in vivo has been of great value to the clinician and the investigator. An understanding of the advantages and disadvantages of the three nuclides used in transfusion medicine--51Cr, 99mTc, and 111In--allows the selection of the appropriate nuclide for the task at hand. For red cell life-span studies and for red cell survivals extending over one hour, 51Cr is the label of choice. The most accurate method for determining the zero-time (100% survival) point for a life span or survival study is to ascertain the RCM of the subject using autologous red cells labeled with another nuclide, preferably 99mTc. RCM studies done independently from a 51Cr survival should be performed using 111In labeled red cells. Red cell survivals are most often used to determine transfusion compatibility or to evaluate blood storage systems. There are important differences in the conduct and interpretation of red cell survivals for these two purposes. Although other promising methods for evaluating the in vivo survival of red cells are under investigation, it is likely that the radiotracers now available will continue to play a primary role in performing these studies in the future.

HLA Antigens in Angioimmunoblastic Lymphadenopathy

Excerpt To the editor: Angioimmunoblastic lymphadenopathy is a rare clinicopathologic entity that is characterized by lymphadenopathy, systemic autoimmune features, and a high potential for lymphoi...