Walter Sunny Dzik

Reversal of drug-induced anticoagulation: old solutions and new problems

Anticoagulant drugs are taken by millions of patients throughout the world. Warfarin has been the most widely prescribed anticoagulant for decades. In recent years, new oral anticoagulants have been approved for use, are being positioned as alternatives to warfarin, and represent an enormous market opportunity for pharmaceutical companies. Requests for urgent reversal of anticoagulants are not uncommon especially in the setting of critical bleeding. This review summarizes information on reversal of warfarin by vitamin K, plasma, prothrombin complex concentrates, and recombinant VIIa. In addition, we emphasize the lack of current evidence supporting reversibility of the new oral direct thrombin inhibitors and Factor Xa inhibitors. This review is presented to assist transfusion medicine specialists, hematologists, and other clinicians who prescribe blood components for reversal of drug‐induced anticoagulation.

A systematic review of transfusion-associated graft-versus-host disease.

Transfusion-associated graft-versus-host disease (TA-GVHD) is a rare complication of blood transfusion. The clinicolaboratory features of TA-GVHD and the relative contributions of recipient and component factors remain poorly understood. We conducted a systematic review of TA-GVHD reports. The HLA relationship between donor and recipient was classified as D = 0 when no donor antigens were foreign to the recipient vs D ≥ 1 when ≥1 donor antigen disparity occurred. We identified 348 unique cases. Criteria for component irradiation were met in 48.9% of cases (34.5% immune-compromised, 14.4% related-donor), although nonirradiated components were transfused in the vast majority of these (97.6%). Components were typically whole blood and red cells. When reported, component storage duration was ≤10 days in 94%, and 23 (6.6%) were leukoreduced (10 bedside, 2 prestorage, and 11 unknown). Among 84 cases with HLA data available, the category of D = 0 was present in 60 patients (71%) at either HLA class I or II loci and was more common among recipients without traditional indications for component irradiation. These data challenge the historic emphasis on host immune defects in the pathogenesis of TA-GVHD. The dominant mechanism of TA-GVHD in both immunocompetent and compromised hosts is exposure to viable donor lymphocytes not recognized as foreign by, but able to respond against, the recipient.

Errors in patient specimen collection: application of statistical process control

BACKGROUND: Errors in the collection and labeling of blood samples for pretransfusion testing increase the risk of transfusion‐associated patient morbidity and mortality. Statistical process control (SPC) is a recognized method to monitor the performance of a critical process. An easy‐to‐use SPC method was tested to determine its feasibility as a tool for monitoring quality in transfusion medicine.

Survival after ultramassive transfusion: a review of 1360 cases

Information about patient survival after transfusion of multiple blood volumes is limited, and most reports have focused on trauma patients.

Hyperhemolysis syndrome in a patient without a hemoglobinopathy, unresponsive to treatment with eculizumab.

Hyperhemolysis is a serious transfusion reaction, most often described in patients with hemoglobinopathies. Hyperhemolysis is characterized by the destruction of host red blood cells (RBCs), in addition to donor RBCs, via an unknown mechanism.

Treatment with or without plasma exchange for patients with acquired thrombotic microangiopathy not associated with severe ADAMTS13 deficiency: a propensity score–matched study

Therapeutic plasma exchange (TPE) is a proven treatment for thrombotic thrombocytopenic purpura (TTP) characterized by severe ADAMTS13 deficiency, but the efficacy of TPE in suspected TTP with an ADAMTS13 activity level of more than 10% remains controversial.

The future of transfusion and Africa

T he number of people on Earth is expected to dramatically increase in the next few decades. Based on current trends, world population, which passed 7 billion in 2011, is expected to reach 9 billion in just 25 years and peak at 11 billion in 2050. Nearly all this growth will occur in economically less-developed nations. Fertility rates in wealthy nations are low and life expectancy is high and neither is expected to substantially change; in contrast, life expectancy in disadvantaged nations is expected to increase from current levels (<45 years) to 66 years by midcentury. Regionally, the greatest rate of growth is projected to occur in Africa (Fig. 1). In fact, of the nine countries expected to account for one-half of the increase in world’s population, four of them are in Africa: Nigeria, Democratic Republic of the Congo, Uganda, and Ethiopia. Because transfusion needs are likely to mirror population expansion as medical sophistication advances worldwide, the greatest growth in transfusion medicine in our century is likely to occur in disadvantaged nations, especially those of sub-Saharan Africa. Accompanying the imperatives of growth in human population are the demands on transfusion therapy dictated by anemia. The current worldwide health impact of anemia is staggering, accounting for nearly 10% of the global burden of all human disability. In 2010, the prevalence of anemia was approximately 32% of all humans and reached 60% in subSaharan Africa. The greatest burden of anemia falls on children less than 5 years of age, much of this due to malaria and malnutrition. Because anemia due to malaria accounts for up to 70% of pediatric blood transfusions in sub-Saharan Africa, efforts to control malaria can favorably affect the demand for blood. Indeed, a national approach to combat malaria, such as Ghana’s National Malaria Control Program, has been shown to decrease the rate of pediatric transfusion. Today, sub-Saharan Africa struggles with the growing demand placed on transfusion services. Although millions of units are transfused each year, current blood product collections fail to meet medical needs. In fact, although sub-Saharan Africa is home to 12% of the world’s population, it accounts for only 4% of the world’s donated blood supply. Blood inventories are outstripped by demand (Fig. 2). Thus, regional population growth combined with increasing demand result in a serious short-fall in the blood supply. Transfusion medicine bears witness each day to preventable deaths that result from insufficient blood availability. Nevertheless, there have been serious efforts to improve the supply of blood in sub-Saharan Africa, as is outlined in a report from the US Centers for Disease Control. Gradual progress has been made in 14 African nations during the period 2008 to 2010; the amount of blood collected has increased in 11 nations, while the proportion of units reactive for human immunodeficiency virus (HIV) has decreased in 12 nations. Despite these advances, of the 14 nations with reported data, median collection rates were only 4.4 per 1000 population. Much of the activity of blood collection, testing, and transfusion lies entirely at the hospital level with a dependence on replacement blood donors. However, efforts to improve blood safety and availability at the national level continue and excellent examples of programs with centralized blood collection and pathogen testing exist. The President’s Emergency Plan for AIDS Relief (PEPFAR) provides essential support to the development of a safe and sufficient blood supply in selected African nations. PEPFAR has promoted advances in operational systems of blood donor recruitment, processing and testing to improve transfusion safety. In contrast to programs designed to enhance the blood supply, few programs have focused on hospital transfusion services and the bedside practice of transfusion therapy. Notable recent activity includes PEPFAR efforts to establish clinical guidelines and hemovigilance

Transfusion Medicine in Sub-Saharan Africa: Conference Summary.

In November 2014, a 3-day conference devoted to transfusion medicine in sub-Saharan Africa was held in Kampala, Uganda. Faculty from academic institutions in Uganda provided a broad overview of issues pertinent to transfusion medicine in Africa. The conference consisted of lectures, demonstrations, and discussions followed by 5 small group workshops held at the Uganda Blood Transfusion Service Laboratories, the Ugandan Cancer Institute, and the Mulago National Referral Hospital. Highlighted topics included the challenges posed by increasing clinical demands for blood, the need for better patient identification at the time of transfusion, inadequate application of the antiglobulin reagent during pretransfusion testing, concern regarding proper recognition and evaluation of transfusion reactions, the expanded role for nurse leadership as a means to improve patient outcomes, and the need for an epidemiologic map of blood usage in Africa. Specialty areas of focus included the potential for broader application of transcranial Doppler and hydroxyurea therapy in sickle cell disease, African-specific guidelines for transfusion support of cancer patients, the challenges of transfusion support in trauma, and the importance of African-centered clinical research in pediatric and obstetric transfusion medicine. The course concluded by summarizing the benefits derived from an organized quality program that extended from the donor to the recipient. As an educational tool, the slide-audio presentation of the lectures will be made freely available at the International Society of Blood Transfusion Academy Web site: http://www.isbtweb.org/academy/.

Utilization Management in the Blood Transfusion Service

The scope of activity of the Blood Transfusion Service (BTS) makes it unique among the clinical laboratories. The combination of therapeutic and diagnostic roles necessitates a multi-faceted approach to utilization management in the BTS. We present our experience in utilization management in large academic medical center.

Reports on clinical transfusion medicine in the early days of TRANSFUSION.

F ifty years ago, when TRANSFUSION had just begun to establish the academic foundation of our profession, the term “transfusion medicine” had not yet arrived. Although we called our field “blood banking” then, the early pages of our journal are filled with a substantial amount of clinical medicine. A brief review of the considerations of the early volumes is revealing—indeed, some clinical concerns of that time are now largely resolved and yet the majority remain with us today! During our review we noted several oddities including a surprisingly up-to-date account of the use of previously frozen autologous marrow as rescue therapy after myelosuppressive chemotherapy; the completely out-ofdate practice of routinely adding soluble blood group A and B substance to group O units to neutralize ABO antibodies when transfusing whole blood to A or B recipients; the first (and arguably last) account of magnetoelectrophoresis; and what can only be described as an eye-catching account of the transfusion of unmodified corpse blood written by the now well-known Jack Kevorkian. Of greater importance, the earliest volumes address several clinical issues including noninfectious adverse events such as febrile transfusion reactions, human error in the laboratory, the proper indications for blood use including transfusion during cardiac surgery, and the effects of blood storage on physiologic oxygen delivery.