The transfusion of plasma carries significant risk that should be weighed against its perceived benefit, especially when FFP is prophylactically used. Poten­tial serious complications include transfusion-asso­ciated lung injury and volume overload as well as transfusion-transmitted infection. Allergic reactions to plasma are common and may, in rare cases, be life threatening.

Pathogen inactivation is a process by which blood components are treated in a manner that damages nucleic acids, thus rendering the components free of infectious pathogens.56 One of these plasma compo­nents, Octaplas (Octapharma USA, Hoboken, New Jersey), is available for use in the United States. Oc­taplas is prepared from pools of about 1,000 donor units and then subjected to solvent detergent treat­ment for pathogen inactivation and reallocated into units of about 200 mL, which is similar to a standard unit of FFP.57 The solvent detergent treatment spares coagulation factors so that the product is considered to be similar to FFP.

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Granulocyte Transfusion

Infections — particularly fungal infections — continue to be a source of morbidity and mortality in patients with neutropenia because of aggressive chemotherapy or hematopoietic stem cell transplantation. With a granulocyte count below 1,000, the risk of infection is increased, and this risk is even further increased based on the duration of neutropenia. During the 1970s, sev­eral studies established that granulocyte transfusion was associated with improved survival rates in patients with gram-negative sepsis and granulocytopenia for at least 10 days.58-60 No carefully controlled studies of granulocyte transfusion exist in other clinical settings. However, as our ability to manage neutropenia and to treat gram-positive and gram-negative sepsis has im­proved with the use of newer antibiotics, the value of granulocyte transfusions has become questionable.61,62 Granulocyte transfusions in the 1970s up to the pres­ent contained about 1 × 1010 granulocytes and were obtained from donors, most of whom were stimulated with dexamethasone. The advent of granulocyte col­ony-stimulating factor (G-CSF) and its resultant use in patients to increase granulocyte counts and mobi­lize hematopoietic stem cells led to the possibility of using G-CSF stimulation of blood donors in order to obtain larger numbers of granulocytes for transfusion. When it is combined with dexamethasone, G-CSF can result in granulocyte counts of up to 40,000/μL with a yield of up to 8 × 1010 granulocytes.63,64 Small stud­ies of these transfusions have suggested efficacy.65,66 However, no studies adequately establish the clinical value of granulocyte transfusions. A multicenter trial managed by the National Marrow Donor Program in 5 US centers studied 40 patients with infection and neutropenia.67 Survival rates with complete or par­tial response rates 4 weeks after initiating transfu­sions were 38% for invasive mold infection, 40% for bacteremia/candidemia, and 60% for severe bacterial infection.67 Thus, evidence suggests that granulocyte transfusion therapy is feasible and may be clinical­ly effective. A recently completed large, multicenter clinical trial did not show benefit from granulocyte transfusions except in a small subgroup of patients who received very high doses of granulocytes.68 These result suggest it is possible that granulocyte transfusions may be clinically beneficial if very high doses of cells are given.68 Currently, if granulocyte transfusions are to be used, then cells obtained from dexamethasone and G-CSF–stimulated donors are rec­ommended to obtain a substantial number of cells. These transfusions can provide an increased granulo­cyte count to more than 5,000/μL in many patients,66 and subsequent transfusions can maintain counts in this range.67 Indications for considering granulocyte transfusion include bacterial of fungal infections of the blood or proven tissue infections of bacteria of fungi unresponsive to antibiotics. Response to trans­fusion should not be evaluated on a daily basis, but granulocyte transfusions should be considered as a course of therapy similar to antibiotics. Therefore, transfusions should be continued for a minimum of 5 days or until the infection has been resolved.

Granulocytes should be transfused as soon as possible after collection because storage time is lim­ited.69-71 Transfusion of a unit of granulocytes should not take more than 2 hours. Reactions to granulocyte transfusions are relatively common and generally sim­ilar to a febrile nonhemolytic transfusion reaction. Severe pulmonary reactions have been reported when granulocytes were infused in close proximity to am­photericin, but whether this represents a major risk or applies to other antifungals is not clear. It is best to separate the transfusion of granulocytes from am­photericin infusion by at least 2 hours.

Outpatient Transfusion

With improvements in medical treatments and longer survival rates among patients with cancer, the man­agement of anemia and thrombocytopenia on an out­patient basis has become an important consideration. In patients with acute myeloid leukemia or high-risk myelodysplastic syndromes, the availability of highly effective antimicrobials and transfusion support has allowed a shift in care from inpatient to outpatient settings.72 In these patient populations, outpatient management of cytopenias has been shown to be safe and effective in both the postconsolidation and postinduction therapy periods.73,74

Outpatient treatment has several potential bene­fits, including reduced cost and resource utilization, improved quality of life, and decreased incidence of nosocomial infections.75 Important factors involved in outpatient management include establishing ther­apy guidelines, determining the location where the therapy takes place, and patient education. Commu­nication with the local blood bank is also important, particularly with regard to special products.

Indications and guidelines for inpatient transfu­sion are well established. However, it is not clear whether these should be applied or modified for out­patient transfusion. Thus, because no national guide­lines exist for outpatient transfusions, each institution must determine its own indications.

On one hand, the rational and physiology of the management of anemia or thrombocytopenia are the same for inpatients or outpatients, and, thus, pos­sibly the guidelines and indications for transfusion should be the same. By contrast, patients are living in a different environment as outpatients. They are less acutely ill, less fragile, and more stable and thus should be more resilient. However, they are more removed from easy and quick access to medical care. Their care is provided by intermittent outpatient clinic visits that may involve travel and inconvenience. Thus, it is appropriate to manage transfusion to provide the stability and continuity that enables the patient to function in the outpatient setting. It might also be appropriate to transfuse larger-than-usual inpatient doses of the component if doing so extends the time to the next clinic visit. For example, larger doses of platelets extend the time to the next transfusion,76,77 and, if the sole reason for a patient to return for a clinic visit is for a platelet count to determine the need for the next transfusion, then a larger dose can extend the time for the next clinic visit. Doing so provides a better quality of life for the patient and may also be more cost effective, although no such studies have been done to determine whether this is true.

Another consideration is the laboratory value as the indication for the transfusion. For instance, if the hemoglobin level is slightly above 7 g/dL and the hospital’s guideline for RBC transfusion is 7 g/dL, then the transfusion might be considered to be inappro­priate in the quality system monitoring. By contrast, if a return clinic visit is not needed for 1 or 2 weeks, then it would be inappropriate to have the patient return sooner simply to repeat the hemoglobin level to determine when the hemoglobin concentration is less than 7 g/dL so the transfusion would meet the hospital guideline. It seems that more appropriate care would be to transfuse the patient at that visit despite a hemoglobin concentration above the lev­el recommended by the guideline. Thus, transfusing 2 units of RBCs or transfusing at a hemoglobin con­centration of 8 g/dL or even 9 g/dL could be consid­ered appropriate in the outpatient setting.

The topic of indications for outpatient transfu­sions is not established and deserves considerable analysis and discussion because of different patient life situations. We also need to determine ways in which to offer the most cost-effective methods for providing care in the outpatient setting.