Febrile non-haemolytic transfusion reaction occurrence and potential risk factors among the U.S. elderly transfused in the inpatient setting, as recorded in Medicare databases during 2011-2012.

BACKGROUND AND OBJECTIVES: Febrile non-haemolytic transfusion reaction (FNHTR) is an acute transfusion complication resulting in fever, chills and/or rigours. Study's objective was to assess FNHTR occurrence and potential risk factors among inpatient U.S. elderly Medicare beneficiaries, ages 65 and older, during 2011-2012. MATERIALS AND METHODS: Our retrospective claims-based study utilized large Medicare administrative databases. FNHTR was ascertained via ICD-9-CM diagnosis code, and transfusions were identified by recorded procedure and revenue centre codes. The study ascertained FNHTR rates among the inpatient elderly overall and by age, gender, race, blood components and units transfused. Multivariate logistic regression analyses were used to assess potential risk factors. RESULTS: Among 4 336 338 inpatient transfusion stays for elderly during 2011-2012, 2517 had FNHTR diagnosis recorded, an overall rate of 58.0 per 100,000 stays. FNHTR rates (per 100,000 stays) varied by age, gender, number of units and blood components transfused. FNHTR rates were substantially higher for RBCs- and platelets-containing transfusions as compared to plasma only. Significantly higher odds of FNHTR were identified with greater number of units transfused (P < 0.01), for females vs. males (OR = 1.15, 95% CI 1.04-1.27), and with 1-year histories of transfusion (OR = 1.25, 95% CI 1.10-1.42), lymphoma (OR = 1.22, 95% CI 1.02-1.46), leukaemia (OR = 1.90, 95% CI 1.56-2.31) and other diseases. CONCLUSIONS: Our study shows increased FNHTR occurrence among elderly with greater number of units and with RBCs- and platelets-containing transfusions, suggesting need to evaluate effectiveness of prestorage leucoreduction in elderly. The study also suggests importance of prior recipient alloimmunization and underlying health conditions in the development of FNHTR.

Clotting factor product administration and same-day occurrence of thrombotic events, as recorded in a large healthcare database during 2008-2013.

BACKGROUND: Thrombotic events (TEs) are serious adverse events that can occur following administration of clotting factors (CFs). OBJECTIVES: To evaluate occurrence of same-day TEs for different CF products and potential risk factors. METHODS: A retrospective cohort study of individuals exposed to CF products during 2008-2013 was conducted using a large commercial insurance database. CF products were identified by procedure codes, and TEs were ascertained via diagnosis codes. Crude same-day TE rates (per 1000 persons exposed) were estimated overall and by congenital factor deficiency (CFD) status, CF products, age and gender. Multivariable logistic regression analyses were used to control for confounding. Laboratory analysis was used to compare the procoagulant activities of FIX products. RESULTS: Of 3801 individuals exposed to CFs, 117 (30.8 per 1000) had same-day TEs recorded. The crude same-day TE rate was higher for CF users without CFD, 70.2 (102 of 1452), as compared with those with CFD, 6.4 (15 of 2349) (RR, 11.0; 95% CI, 6.4-18.9). For individuals without CFD, a significantly increased same-day TE risk was identified for factor IX complex (OR, 6.92; 95% CI, 3.11-15.40), factor VIIa (OR, 9.42; 95% CI, 4.99-17.78) and other products when compared with fibrin sealant. An increased risk of a TE was found with older age (≥ 45 years), history of TEs and underlying health conditions. The laboratory identified elevated procoagulant activity in Profilnine(®) and Benefix(®) . CONCLUSIONS: The study shows an increased same-day TE risk for CF users without CFD and suggests substantial off-label CF use. The study findings also show elevated same-day TE rates for different CF products and suggest the importance of product properties and patient factors.

A prospective comparison of platelet collection with the CS-3000 blood cell separator using the closed system and open system kits.

Each of 30 donors had two plateletapheresis procedures on the CS-3000 Blood Cell Separator (Fenwal Laboratories, Deerfield, IL). During one procedure, platelets were collected with the Closed System Apheresis Kit for Extended Platelet Storage (Fenwal); during the other procedure the Open System Apheresis Kit (Fenwal) was used. The same operator performed the entire collection process and all laboratory studies for both procedures for each donor. There was a statistically significant lower yield with the Closed System Kit (mean: 4.51 x 10(11) platelets) than with the Open System Kit (mean: 4.76 x 10(11) platelets) (P = 0.03). There was no significant difference in lymphocyte contamination. The relatively small magnitude of the difference, however, means that product quality, longer storage time, and cost are more important considerations in selecting a kit for use.

Red cell survival studies in a patient with anti-Tca.

A radiolabeled, allogenic red cell survival study was performed on a patient who lacked the Cromer-related antigen Tca and who had developed the corresponding antibody. Red cell survival was 92% at 1 hour and 88% at 24 hours. Monocyte monolayer assays (MMA) and IgG subclass determinations were performed on samples from: (1) 1965, the period of initial antibody formation; (2) approximately two years before the red cell survival study; and (3) four months after the study. All samples reacted w+ to 1+ by the antiglobulin test. The earliest sample contained IgG1, IgG2, and IgG4 anti-Tca. Because there were 20.5% reactive monocytes in the MMA (normal range 0-3%), this antibody may have produced extravascular red cell destruction. In contrast to the initial example, the samples before and after the red cell survival study both contained IgG2 and IgG4 subclasses with 1.3% and 2.2% MMA reactivity, respectively. The current pattern of antibody subclass, the lack of reactivity in the MMA, and a red cell survival of 88% at 24 hours indicate that short-term transfusion support would have been well tolerated. This contrasts to the in vitro results obtained with the earliest sample, which suggest a clinically significant antibody. This appears to be the first report of a red cell alloantibody that remained serologically reactive but underwent a loss of its IgG1 fraction, which appeared capable of red cell destruction based on the MMA results.

Evaluation of IVAC Variable Pressure Volumetric Pump Model 560 for the delivery of red blood cells, adenine-saline added.

Mechanical pump systems for the delivery of intravenous solutions have been used for the transfusion of red blood cells. In this study, the IVAC Variable Pressure Volumetric Pump Model 560 was evaluated for that purpose using flow rates of 70 mL/hour and 999 mL/hour through 16-, 19-, and 23-gauge needles and an 18-gauge angiocatheter. The largest degree of hemolysis induced by the delivery system resulted in a mean increase of plasma hemoglobin of 150 mg/L (15 mg/dL); this is equivalent to the loss of 0.03% of the red blood cells. When programmed to deliver 15 mL of red blood cells, the IVAC 560 delivered 15.0 +/- 0.3 mL at a rate of 70 mL/hour and 14.9 +/- 0.3 mL at 999 mL/hour. The authors conclude that the IVAC 560 can be used to deliver red blood cells with a minimal, acceptable level of hemolysis. It also delivers an accurate and precise volume of red blood cells that may be an aid to the transfusionist.

Multicompartment analysis of the effects of plasmapheresis. Application to lipid kinetics in humans.

The quantitative effect of plasmapheresis on concentrations of intravascular solutes is described by a minimal two-compartment model, which allows exit to and entry from a nonplasma body pool of the solute. This novel method is simple and capable of determining endogenous metabolic turnover of physiologically important plasma constituents in both therapeutic and experimental settings. The model was suggested by the therapeutic use of plasmapheresis in hyperlipidemia, and the turnover rates of triglyceride and cholesterol were calculated for one patient treated with chronic plasmapheresis. It is concluded that at least a two-compartment model is necessary to quantitatively describe the effect of plasmapheresis on any substance that undergoes appreciable endogenous turnover (metabolic clearance rate greater than 1.1 times plasmapheresis rate when both rates are in units of volume per time). Calculation of endogenous turnover rate with the use of measurements of the concentration of a solute in plasma before and after plasmapheresis and in the total plasmapheresate and measurement of the volume of plasma removed, volume of plasma substitute infused, and total plasmapheresis time is detailed. This method avoids the use of isotopic labeling experiments. In turn, the endogenous turnover rate may predict the efficacy of therapeutic plasmapheresis.

Preoperative crossmatch ordering and blood use in elective hysterectomy.

Preoperative crossmatch guidelines have been shown to improve crossmatch ordering practices. To refine crossmatch ordering, specific characteristics of 258 patients who underwent abdominal hysterectomy and 277 patients who underwent vaginal hysterectomy were correlated with blood transfusion by univariate and multivariate analyses. Abdominal hysterectomy patients with pelvic inflammatory disease with adhesions and/or abscess were significantly more likely to require blood transfusion. Specimen weight correlated significantly with blood transfusion only for patients with ovarian pathology. Blood use was independently correlated with reduced preoperative hemoglobin and with estimated blood loss. Vaginal hysterectomy patients who had a colporrhaphy were more likely to require blood transfusion. Preoperative crossmatch recommendations made on the basis of these results reduce costs and increase the efficiency of predeposit autologous transfusion programs and preoperative crossmatch ordering practices.

Removal of an infected right atrial mass in a patient with sickle cell disease.

The use of indwelling central catheters for hyperalimentation, chemotherapy, and long-term venous access is increasing. We report the successful removal of an infected right atrial mass associated with the use of a central catheter in an adult with sickle cell disease. The clinical options for the treatment of infected atrial thrombus as well as the challenge of performing cardiopulmonary bypass in patients with sickle cell disease are briefly discussed.

Quality assessment and improvement of transfusion practices.

A successful quality assessment program simultaneously creates, sustains and documents excellence in patient care. As clinical practices evolve, it helps to assure their continuing improvement. The program strives to eliminate unnecessary transfusions as the cornerstone of transfusion safety. It should be conducted in a professional, nonadversarial, and educational manner.

The use of leukocyte-reduced blood components.

Many of the risks and discomforts associated with blood transfusion may be avoided by removing the contaminating leukocytes from cellular blood components. Leukocyte reduction prevents many febrile reactions that occasionally occur following red cell transfusion and prevents some febrile reactions following platelet transfusion. Prophylactic use of leukocyte-reduced components may prevent primary HLA alloimmunization, which is a principle cause of the refractoriness to platelet transfusion seen in many multiply transfused, thrombocytopenic patients. Leukocyte-reduced components are equally effective in the prevention of CMV as seronegative blood.

Autologous fibrin sealant reduces pain after tonsillectomy.

OBJECTIVES/HYPOTHESIS: Pain is a major cause of morbidity after tonsillectomy. Although various efforts have been made to reduce pain, the use of oral analgesics, which can have adverse side effects, remains the standard of care. It is hypothesized that fibrin sealant, used to achieve hemostasis and enhance healing in many surgical procedures, might help decrease pain after this operation. STUDY DESIGN: A prospective, randomized, blinded study was performed on 20 children aged 5 to 17 years who were undergoing tonsillectomy, to evaluate the efficacy of FIBRIN SEALANT in reducing postoperative pain. METHODS: All patients pre-donated 40 mL of blood from which autologous concentrated fibrinogen was prepared by cryoprecipitation. In the fibrin sealant group, fibrinogen and topical bovine thrombin were sprayed onto the surgical site to form fibrin sealant at the conclusion of tonsillectomy. The 10 patients in the control group (C) received no fibrin sealant. Patients rated their level of pain immediately after surgery and at regular intervals for 3 days after surgery using the Wong-Baker Faces Pain Rating Scale (1-6). Emesis, postoperative bleeding, medications, and adverse events were also evaluated. RESULTS: At 7.00 P.M. on postoperative day (POD) 0, the mean +/- SD fibrin sealant group pain score (2.9+/-0.41 units) was significantly lower than for the C group (4.1+/-0.43 units; P < or = .05). There was also a trend in favor of less pain in the fibrin sealant group at 7:00 P.M. on POD 1, with a mean of 3.5+/-0.43 units versus 2.4+/-0.48 units for C (P = .15). The odds of a patient in C experiencing emesis were 8.16 times higher, (P < or = .05) than for patients in the fibrin sealant group. CONCLUSIONS: Fibrin sealant significantly reduced pain the evening after pediatric tonsillectomy and also decreased the chance of experiencing emesis. Thus fibrin sealant may be clinically useful as an adjunct to tonsillectomy.

Fibrin glue from stored human plasma. An inexpensive and efficient method for local blood bank preparation.

European surgeons have used fibrin glue extensively during thoracic, cardiovascular, and general surgical operations. Until now, however, it has been available only as a commercial preparation made from pooled human plasma, and it has not been approved by the U.S. Food and Drug Administration for use in the United States because of a high associated risk of hepatitis and acquired immune deficiency syndrome. Methods of obtaining fibrinogen, an essential component of fibrin glue, from cryoprecipitate or fresh frozen plasma have been published recently. However, the cryoprecipitate method results in relatively low concentrations of fibrinogen, which can reduce glue effectiveness. The fresh frozen plasma method is more expensive and does not meet the standards of the American Association of Blood Banks for the "closed" system required for safe handling and management of blood component products. Both the cryoprecipitate and the fresh frozen plasma methods result in waste of unstable clotting factors. These factors are necessary to replace human plasma clotting deficiencies but are not necessary for the production of fibrin glue. The authors have developed an efficient, high-concentration blood bank method for producing and maintaining a local supply of a safer and less expensive but equally effective material derived from stored human plasma. This material is produced using approved blood bank techniques for a "closed" system in blood component production, thus reducing the risks of contamination and infection, and its fibrinogen concentration is higher than that of standard cryoprecipitate. The cost of 1 unit of this fibrin glue is comparable to that for 1 unit of cryoprecipitate and less than that for 1 unit of fresh frozen plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

Strategies for the prevention of post-transfusion hepatitis.

Hepatitis is a common and potentially serious adverse effect of blood transfusion. A large number of strategies have been developed or proposed to reduce the incidence of post-transfusion hepatitis (PTH). The education of physicians regarding the risks of hemotherapy and the judicious use of blood must be the cornerstone of any substantial reduction in PTH. The use of volunteer rather than paid donors is associated with a much reduced incidence of PTH. Deferral of donors implicated in PTH is also helpful. Other proposed strategies include donor alanine amino-transferase levels, donor anti-HBc testing, the provision of immune globulin to recipients, and the inactivation, removal, or immune neutralization of the virus from blood products. In the absence of a blood substitute, autologous transfusion is an excellent means of improving transfusion safety. The incidence of PTH type B should decrease as an increasing proportion of donors and recipients are immunized by vaccine and as increasingly sensitive tests for HBsAg become available. The development of a serologic test and vaccine for non-A, non-B hepatitis would be outstanding accomplishments, but their absence underscores the need to pursue vigorously other means of reducing the incidence of the disease.

Effect of oxygen and temperature on the potassium efflux of irradiated, stored red blood cells.

Gamma irradiation of blood is performed to prevent transfusion-associated graft-versus-host disease and can result in an accelerated efflux of intracellular potassium (K+). The oxygen content of the blood and the temperature at which the irradiation is carried out are two variables reported to affect this shift; they were investigated in two separate studies. Study A-Four units of AS-5 red blood cells were each split equally into four transfer bags. One set of transfer bags was stored at 4 degrees C for 42 days (Control), the second set (IRR) was irradiated and stored. The third and fourth groups were oxygenated; the third set (+O2) was placed at 4 degrees C. The fourth set (IRR+O2) was irradiated, then stored. Supernatant K+ and hemoglobin increased in the IRR + O2 group over IRR and Control, +O2 did not rise compared to Control. Study B-Six units of CPDA-1 whole blood were each equally separated into four transfer bags. The first set of bags was placed at 4 degrees C, the second set was irradiated and then stored (IRR). The third group of bags was irradiated and given an 8-hour 22 degrees C incubation prior to storage at 4 degrees C (IRR-22). The fourth set was irradiated, placed at 37 degrees C for 2 hours, then stored. Supernatant K+ was lower during the first 7 days of storage for the IRR-22 and IRR-37 groups compared to IRR, but these increased to IRR levels by day 35. Irradiation of blood products results in an accelerated K+ shift that can be exacerbated by the presence of oxygen. The injury can be partially and temporarily corrected by a post-irradiation incubation at 22 degrees C or 37 degrees C.

Cerebrovascular accident during a delayed hemolytic transfusion reaction in a patient with sickle cell anemia.

A 28-year-old woman with sickle cell anemia suffered a left hemispheric cerebrovascular accident associated with severe right-sided weakness during a delayed hemolytic transfusion reaction owing to anti-rh' (C) and anti-S. The anti-rh' (C) had been identified four years earlier at a different hospital but neither the patient, her family, nor any member of the staff of the hospital where she was transfused was aware of this information. It is postulated that spherocytes, formed during hemolysis, could slow capillary flow, thereby increasing red cell sickling and producing vaso-occlusion. The patient had no clinically apparent neurologic complications during the preceding 24 years and has had no further neurologic events during the subsequent 20 months. This patient's reaction underscores the compelling need for sensitive pre-transfusion tests as well as the obligation to inform patients and their families of the presence and potential consequences of alloantibodies in the event of future transfusion.

Effect of gamma irradiation on the in vivo recovery of stored red blood cells.

Gamma irradiation of blood components is used to prevent posttransfusion graft versus host disease. This process has been demonstrated to cause an increase in the permeability of the red blood cell membrane to potassium and sodium. Because of this red cell membrane lesion, it is important to investigate the effect of irradiation on the posttransfusion recovery of stored red blood cells. In the present study, the 24-hour posttransfusion recovery of AS-1 red cells irradiated with 30 Gy one or 14 days after collection and stored for a total of 35 days was compared to the recovery of unirradiated red blood cells stored for 35 days. There was no significant difference in the mean 24-hour posttransfusion recovery of 51Cr labeled red blood cells among any of the groups studied. Each group had a mean recovery > 75 percent. The mean potassium and hemoglobin concentrations at the end of 35 days of storage were significantly higher in both of the irradiated groups compared to the unirradiated group, but were not significantly different from each other. Under the conditions of this study, gamma irradiation did not significantly affect the 24-hour posttransfusion recovery of red blood cells stored for 35 days.

Hemolysis during leukocyte-reduction filtration of stored red blood cells.

Hemolysis has been reported in red blood cells (RBCs) that have undergone leukocyte-reduction filtration. This study investigated whether the age of RBCs or the filter type affected hemolysis. One hundred eighty units of RBCs (adenine-saline added) were leukocyte-reduced by filtration. At each of the 6 weeks of shelf life, 10 units were filtered with the "BPF4" filter, 10 units with the "Purecell RCQ" filter, and 10 units with the "Sepacell" filter. Filtration was performed with strict adherence to the manufacturers' directions. Pre- and post-filtration samples were assayed for plasma hemoglobin by measuring the plasma absorbances at 578 nm and 562 nm. The increase of plasma hemoglobin concentration following filtration was significantly greater (p < 0.05) in older units, compared to fresher units, when the Sepacell and BPF4 filters were used. For example, the increase of plasma hemoglobin at week 6 (83.47 mg/dl:Sepacell, 128.93 mg/dl BPF4) was significantly greater than at week 1 (7.07 mg/dl Sepacell, 4.77 mg/dl BPF4) (Sepacell: p=0.008; BPF4: p=0.006). For units stored 1, 2, 4, 5, or 6 weeks, the increase of plasma hemoglobin concentration post-filtration was significantly greater with the BPF4 filter, compared to the Purecell RCQ filter (p <0.045); for units stored 5 weeks, the increase in plasma hemoglobin concentration post-filtration was significantly greater with the BPF4 filter compared to the Sepacell filter (p = 0.009). Mean filtration times were significantly longer in older units compared to fresh units. This study shows that increased storage duration of RBCs (adenine-saline added) is attended by greater hemolysis during leukocyte-reduction filtration and by prolongation of the filtration time. In addition, the amount of hemolysis may be influenced by the type of filter.

Fibrin sealant: clinical use and the development of the University of Virginia Tissue Adhesive Center.

The utilization of fibrin sealants to augment hemostasis, seal tissues, and facilitate targeted delivery of drugs is increasing. In 1985, a hospital-based program was established to provide autologous and allogeneic cryoprecipitate that serves as a fibrin sealant when combined with bovine thrombin. To date, more than 4,000 patients have been treated with this product at our institution, with an efficacy rate greater than 90%. Collaboration among surgical services and the blood bank fostered multispecialty expertise with this product that led, in 1997, to the establishment of the University of Virginia Tissue Adhesive Center. The Tissue Adhesive Center is a multidisciplinary center whose physician director and nursing and administrative support staff facilitate basic research, laboratory investigation, and preclinical and clinical trials with collaborators throughout the university. The Tissue Adhesive Center also provides educational programs and clinical consultation, and tracks and participates in peer review of sealant use. The licensure of a commercially produced, virally inactivated, pooled-plasma fibrin sealant in May 1998 provided an alternative source of adhesive. Utilization of the commercial product surpassed use of the blood bank product in April 1999. At present, use of the commercial product is approximately 3 times that of the blood bank-produced sealant. This report reviews the clinical uses of fibrin sealant, its regulatory history, the production of fibrin sealants, the evolution of a blood bank fibrin sealant program, the development of the Tissue Adhesive Center, and the utilization of commercial and blood bank-produced sealant at our university hospital.