Transfusion-related acute lung injury risk mitigation: an update.

Transfusion-related acute lung injury (TRALI) is a life-threatening complication of transfusion. Greater understanding of the pathophysiology of this syndrome has much improved during the last two decades. Plasma-containing components from female donors with leucocyte antibodies were responsible for the majority of TRALI fatalities before mitigation strategies were implemented. Over the past 15 years, measures to mitigate risk for TRALI have been implemented worldwide and they continued to evolve with time. The AABB requires that all plasma containing components and whole blood for transfusion must be collected from men, women who have not been pregnant, or women who have tested negative for human leucocyte antigen antibodies. Although the incidence of TRALI has decreased following the institution of TRALI mitigation strategies, TRALI is still the most common cause of transfusion-associated death in the United States. In this review, we focus on TRALI risk mitigation strategies. We describe the measures taken by blood collection facilities to reduce the risk of TRALI in the United States, Canada and European countries. We also review the literature for the effectiveness of these measures.

Safety and collection efficiency with a lower transfusion threshold for extracorporeal photopheresis in adult patients with graft-versus-host disease.

BACKGROUND: Extracorporeal photopheresis (ECP) is an established treatment for graft-versus-host disease (GVHD). Various haematocrit thresholds have been used to trigger red blood cells transfusion prior to ECP. Moderate-to-severe GVHD is frequently complicated by anaemia; the safety and collection efficiency with a lower haematocrit for ECP is unknown. METHODS: We prospectively enrolled 26 consecutive adult GVHD patients with haematocrits between 25% and 28·9% who received ECP on the CELLEX system. Preprocedural transfusion was withheld. We monitored the adverse events and transfusions avoided. A complete blood cell count with differential was performed on preprocedural peripheral blood and buffy coat collected. Lymphocyte fold enrichment (LFE) was compared between this cohort and two historical control groups with haematocrits of 29% or higher. RESULTS: Red Blood Cells transfusion was avoided in the lower-haematocrit cohort without adverse events. The median LFE was 4·5 (95%CI, 3·1-5·7) in the lower-haematocrit cohort and 5·2 (95%CI, 4·1-6·5) in the higher-haematocrit CELLEX-treated control group. The median difference was 0·7 (95%CI, -0·3 to 2·0, P = 0·14). It could not be established that the lower-haematocrit cohort was non-inferior to the higher-haematocrit control group with a prespecified non-inferiority margin of 1·3. However, LFE was significantly higher in the lower-haematocrit cohort than the higher-haematocrit UVAR XTS-treated control group (P < 0·01). CONCLUSION: Buffy coat can be collected for ECP using CELLEX in GVHD patients with a haematocrit of 25% or higher, with a collection efficiency superior to that in patients with higher haematocrits but treated using UVAR XTS. No increase in adverse events was observed at these lower haematocrits.

Platelet transfusion in thrombotic thrombocytopenic purpura.

BACKGROUND: Platelet (PLT) transfusion has been considered contraindicated in patients with thrombotic thrombocytopenic purpura (TTP). However, adverse clinical outcomes and death in patients with TTP after receiving PLT transfusion were based on case reports prior to routine use of plasma exchange (PEX) therapy. PLT transfusions are often required by the interventional radiologist before the insertion of a central venous catheter. In this study, we evaluate whether PLT transfusions are harmful in patients with TTP undergoing PEX. METHODS: We retrospectively reviewed the records of consecutive patients with the clinical diagnosis of TTP who received PEX at our institution between January 2004 and September 2014. An adverse event was defined as any complication including seizures, cerebrovascular accident, bleeding, thrombosis, myocardial infarction or death for any reason within 30 days from the PLT transfusion. Analyses were performed on only patients with ADAMTS13 activity <10%. RESULTS: Our cohort included 110 patients with the clinical diagnosis of TTP. Fifty-five patients had ADAMTS13-deficient TTP, 23 of whom received PLT at some point during disease course. The patients who received PLT transfusion were not different from those who did not in terms of age, gender, race, haematocrit, PLT count, creatinine, LDH and complications. The three patients who received PLT and died had malignancy and complicated disease course. None of them died from a thrombotic event. CONCLUSION: All deaths in the transfused group happened in very ill patients that had alternative causes of death. PLT transfusions in patients with TTP do not appear harmful in regard to thrombotic complications.

Platelet transfusion: a clinical practice guideline from the AABB

BACKGROUND: The AABB (formerly, the American Association of Blood Banks) developed this guideline on appropriate use of platelet transfusion in adult patients. METHODS: These guidelines are based on a systematic review of randomized, clinical trials and observational studies (1900 to September 2014) that reported clinical outcomes on patients receiving prophylactic or therapeutic platelet transfusions. An expert panel reviewed the data and developed recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. RECOMMENDATION 1: The AABB recommends that platelets should be transfused prophylactically to reduce the risk for spontaneous bleeding in hospitalized adult patients with therapy-induced hypoproliferative thrombocytopenia. The AABB recommends transfusing hospitalized adult patients with a platelet count of 10 × 109 cells/L or less to reduce the risk for spontaneous bleeding. The AABB recommends transfusing up to a single apheresis unit or equivalent. Greater doses are not more effective, and lower doses equal to one half of a standard apheresis unit are equally effective. (Grade: strong recommendation; moderate-quality evidence). RECOMMENDATION 2: The AABB suggests prophylactic platelet transfusion for patients having elective central venous catheter placement with a platelet count less than 20 × 109 cells/L. (Grade: weak recommendation; low-quality evidence). RECOMMENDATION 3: The AABB suggests prophylactic platelet transfusion for patients having elective diagnostic lumbar puncture with a platelet count less than 50 × 109 cells/L. (Grade: weak recommendation; very-low-quality evidence). RECOMMENDATION 4: The AABB suggests prophylactic platelet transfusion for patients having major elective nonneuraxial surgery with a platelet count less than 50 × 109 cells/L. (Grade: weak recommendation; very-low-quality evidence). RECOMMENDATION 5: The AABB recommends against routine prophylactic platelet transfusion for patients who are nonthrombocytopenic and have cardiac surgery with cardiopulmonary bypass. The AABB suggests platelet transfusion for patients having bypass who exhibit perioperative bleeding with thrombocytopenia and/or evidence of platelet dysfunction. (Grade: weak recommendation; very-low-quality evidence). RECOMMENDATION 6: The AABB cannot recommend for or against platelet transfusion for patients receiving antiplatelet therapy who have intracranial hemorrhage (traumatic or spontaneous). (Grade: uncertain recommendation; very-low-quality evidence).(AU)

Insulin-like growth factor I mediates high-fat diet-induced adipogenesis in Osborne-Mendel rats.

To determine if high-fat (HF) diet-induced changes in adipose tissue cellularity are associated with the presence of paracrine growth factor(s) that alter preadipocyte proliferation, Osborne-Mendel rats were fed either a HF (76% energy) or a low-fat (LF, 12% energy) diet for 85 days. HF-fed rats had greater (P < 0.05) fat pad size, total fat cell number, number of small (30-70 microm) and large (80-140 microm) adipocytes, and percentage of 100- to 140-microm adipocytes compared with LF-fed rats. Preadipocytes in primary cell culture treated with inguinal adipose tissue conditioned medium (ATCM) prepared from HF-fed rats had greater (P < 0.05) proliferation compared with cultures treated with ATCM from LF-fed rats. Proliferative capacity of ATCM prepared from HF-fed rats was attenuated after the stripping of the medium of insulin-like growth factor I using an immunomagnetic bead separation system. These data are consistent with the concept that insulin-like growth factor I is involved in the paracrine regulation of adipogenesis.

Blood transfusion-acquired hemoglobin C.

Unexpected and confusing laboratory test results can occur if a blood sample is inadvertently collected following a blood transfusion. A potential for transfusion-acquired hemoglobinopathy exists because heterozygous individuals show no significant abnormalities during the blood donor screening process. Such spurious results are infrequently reported in the medical literature. We report a case of hemoglobin C passively transferred during a red blood cell transfusion. The proper interpretation in our case was assisted by calculations comparing expected hemoglobin C concentration with the measured value. A review of the literature on transfusion-related preanalytic errors is provided.

Modification of Cotrel-Dubousset's original hook constructs for idiopathic scoliosis.

We performed a retrospective review of 41 patients (ages 9-18 years) who underwent posterior spinal fusion with either Isola or Cotrel-Dubousset (CD) instrumentation to determine whether the presence of an apical hook on the thoracic convexity affected initial and long-term sagittal and coronal correction in adolescent idiopathic scoliosis surgery. A study group of 38 female and three male patients was evaluated (2-5 years of follow-up). Twenty-three patients (Group A) were treated with an up-going hook at the convex apex of the thoracic curve, and 18 patients (Group B) with similar curves were instrumented without an apical hook. Results showed that Group A's average preoperative coronal curve of 48 degrees decreased to 17 degrees , whereas Group B's preoperative average of 52 degrees decreased to 25 degrees . At follow-up, no statistical significance was noted in either coronal curve correction (p = 0.203) or sagittal kyphosis (p = 0.38) between Groups A and B. We conclude that omission of the up-going hook at the apex of the thoracic convexity can reduce postoperative discomfort in patients undergoing posterior spinal fusion, without sacrificing curve correction or balance.

Dietary fat type influences protein consumption in rats given 8-hydroxy-2-(Di-n-propylamino)tetralin.

Our previous work indicates that type and level of dietary fat influences selection of protein and carbohydrate diets. Serotonin (5HT) appears to be involved in this feeding behavior. In the present study, we examined the effects of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) on feeding behavior, and fenfluramine on in vitro 5HT and 5-hydroxyindoleacetic acid (5HIAA) release from the brain in rats fed tallow or corn oil. Male, Sprague-Dawley rats were given a diet containing corn oil or tallow for 2 days. In Experiment 1, rats received an injection of 8-OH-DPAT (a 5HT1A agonist) or saline and were then allowed to select from two diets: low protein/high carbohydrate or high protein/low carbohydrate. Prior exposure to tallow caused an increased intake of protein and 8-OH-DPAT blunted this effect. In Experiment 2, the dorsal raphe from rats fed tallow or corn oil was superfused with fenfluramine or vehicle. Superfusates were collected for analysis of 5HT and 5HIAA. Fenfluramine increased serotonin release in tallow-fed animals as compared to basal. These results suggest that serotonin may be involved in mediating tallow's effect on macronutrient selection.

Cluster of allele losses within a 2.5 cM region of chromosome 10 in high-grade invasive bladder cancer.

A limited number of previous studies have indicated a low frequency of chromosome 10 allele losses and deletions in bladder cancers. We investigated the involvement of chromosome 10 in advanced bladder cancers. Loss of heterozygosity (LOH) was analysed in 19 microsatellite loci in 20 grade III invasive transitional cell carcinomas. Nine (45%) of the 20 tumors had at least one allele loss on the long arm of chromosome 10. The short arm of chromosome 10 was not affected. The most frequent LOH occurred at D10S215, where four (29%) of 14 of the informative cases had an allele loss. The minimal region with allele losses was located between the centromeric marker D10S1644 and the telomeric marker D10S541, which are separated by 2.52 cM. The results strongly suggest the existence within that region of a tumor suppressor gene or genes for advanced bladder cancer.

Effect of glucose and 2-deoxyglucose on hypothalamic GABA release in lactating rats.

Gamma-amino butyric acid (GABA), an inhibitory neurotransmitter, has been implicated in the control of feeding behavior. This study was conducted to investigate the in vitro release of GABA in the basal medial hypothalamus (BMH) of hyperphagic lactating (L) and control nonlactating (NL) rats. Pregnant Sprague-Dawley rats (n = 10) were ad lib fed a semipurified powdered diet during the last 6 days of pregnancy until day 19 of lactation. Nonpregnant (n = 10) animals served as controls. Body weights and food intake were recorded every other day. Lactating rats demonstrated an increase in body weight as well as food intake as compared to nonlactating animals. At sacrifice, the BMH was removed and perfused (0.1 ml/min) with Kreb's Ringer buffer (KRB) ("basal" medium) using a Brandel perifusion system. KRB containing glucose (100 mM) or 2-deoxyglucose (2DG) (100 mM) was also applied to the tissue. Potassium stimulation was carried out to test for the viability of the tissues. Samples were collected every 10 min, derivatized with O-Phthalaldehyde and analyzed via HPLC. Glucose depressed, and 2DG enhanced GABA release compared to basal levels. There were no significant differences in GABA release between lactating and nonlactating groups. These data suggest that GABA release is responsive to metabolic changes in the brain.

Aging and sense of control.

Three groups representing different phases of the developmental lifecycle--12 senior citizens, 67 young adults, and 14 healthy middle-aged normal adults--were assessed using a multidimensional control inventory. Senior citizens had a healthy over-all sense of control comparable to those of the other two groups and a significantly lower (healthier) negative sense of control. They also were significantly more likely to endorse acceptance as a way of addressing areas of concern and to complement self as a source of control with a sense of control coming from others (including God, belief in a higher power).

Hepatitis B surface antigenemia in blood donors following vaccination.

BACKGROUND: Detection of hepatitis B surface antigen (HBsAg) in recently vaccinated adults has not previously been reported. Transient detectable HBsAg has been observed in newborn infants immunized with a recombinant hepatitis B vaccine. STUDY DESIGN AND METHODS: Over a 1-year period, eight HBsAg-positive blood donors mentioned during donor notification that they had been vaccinated for hepatitis B virus 1 to 3 days before donation. Follow-up tests for HBsAg, antibodies to HBsAg, and antibodies to hepatitis B core antigen were performed 3 to 37 weeks after immunization. Four months later, a group of 19 donors who were coworkers received hepatitis B vaccination and then donated blood the next day. The coworkers were observed for duration of antigenemia. RESULTS: A total of nine cases of transient, confirmed (neutralizable) antigenemia occurred in healthy individuals who donated blood 1 to 3 days following vaccination with a recombinant hepatitis B vaccine. Follow-up testing showed no evidence of infection by hepatitis B virus. One (5.3%) of 19 blood donors vaccinated as a group had antigenemia at Day 1 but not on Days 2 and 3 following immunization. CONCLUSION: Individuals recently vaccinated for hepatitis B may test positive for HBsAg and become permanently disqualified as blood donors. Therefore, blood collection centers should consider temporary deferral of potential donors who recently received hepatitis B vaccine.

Multiple false reactions in viral antibody screening assays after influenza vaccination.

In December 1991, US blood centers reported an unusual increase in donations that tested falsely reactive for antibodies to two or more (multiple false positive) of the following viruses: human immunodeficiency virus type 1 (HIV-1), human T-cell lymphotrophic virus type I (HTLV-I), and hepatitis C virus. Many of these donations were from people who had recently received the 1991-1992 influenza vaccine, raising the possibility that this vaccine had somehow specifically caused the problem of multiple false reactivity. A case-control study of 101 affected donors and 191 matched controls found that recent receipt of any brand of influenza vaccine was significantly associated with testing multiple false positive (p < 0.05), as was a history of recent acute illness (p < 0.05) and of allergies (p < 0.05). Surveillance for monthly rates of multiple reactive donations from May 1990 through December 1992 linked the seasonal cluster of multiple false-positive donations to the use of viral screening test kits thought to react nonspecifically to donor immunoglobulin M. There was no similar increase in multiple false-positive donations during the 1992-1993 influenza vaccination season after the HIV-1 and hepatitis C virus tests were replaced; however, the number of donations that were falsely reactive for only HTLV-I almost doubled, indicating that false reactivity was not specifically associated with the 1991-1992 influenza vaccine. Retesting of affected donors found that the duration of HTLV-I and hepatitis C virus false reactivity was 3-6 months. The cluster of multiple false-positive donations in 1991 was most likely caused by the test kits used, rather than by the influenza vaccine.

How frequently is emergency contraception prescribed?

A 1993 survey of 294 reproductive health care providers, family practitioners and emergency room physicians investigated the frequency of prescribing emergency contraception. Hormonal emergency contraception had been prescribed by respondents an average of 3.4 times in the preceding 12 months. Almost one-third of the prescriptions were for rape victims, the majority written by emergency physicians. Fifteen IUD insertions for emergency contraception were performed in the preceding year. Few respondents had ever discussed emergency contraception with patients or had literature available on the topic.

PIP: In 1993, 294 US health care providers completed a questionnaire designed to determine how frequently they prescribe emergency contraception. These practitioners included obstetrician-gynecologists (OB-GYNs), family practitioners, nurse practitioners, physician assistants, nurse-midwives, and emergency physicians. This group prescribed emergency hormonal contraception a total of 1009 times in the last 12 months for a mean of 3.4 prescriptions/professional. 31.02% of all such prescriptions were for rape victims. More than 66% of prescriptions for rape victims were written by emergency physicians. OB-GYNs were the most likely group to have ever prescribed hormonal emergency contraception and to have prescribed it within the last 12 months while family practitioners were the least likely group to do both (76% vs. 39% and 65% vs. 25%, respectively). The mean number of times of prescribing emergency contraception in the last 12 months among practitioners who had prescribed hormonal emergency contraception ranged from 1.8 among family practitioners to 5.8 among emergency physicians. The median annual number of emergency contraception prescriptions per provider was just 1 (range 0-200). A nurse practitioner at a college health service had prescribed emergency contraception 200 times. Only 8 practitioners inserted an IUD for emergency contraception (15 insertions). Around 90% never or rarely discussed emergency contraception with their patients. Just 10% had literature on emergency contraception available. About 66% of those who had no literature were interested in having this literature available for patients. These results show that emergency contraception is rarely used in the US, perhaps because the US Food and Drug Administration has not approved oral contraceptives and IUDs for emergency contraceptive use.

Effects of dietary fat on food intake and brain uptake and oxidation of fatty acids.

The present study was designed to investigate (a) whether dietary fat manipulation, quantitatively and/or qualitatively, may influence the transport of fatty acids into the brain and oxidation of fatty acids in the hypothalamus; and (b) if an inhibitor of fatty acid oxidation changed food intake on these diets. Rats were fed for 4 wk 5% or 34% corn oil or tallow diets that were isocaloric and isonitrogenous. It was found that rats fed corn oil diets had significantly higher brain uptake index of palmitate than did rats fed tallow diets. In a second experiment, rats were fed either 30% corn oil or tallow diets and injected with either saline or mercaptoacetate (MA). Both saturated fat diets and mercaptoacetate injection reduced lateral hypothalamic, but not ventromedial hypothalamic fatty acid oxidation. Mercaptoacetate increased food intake only in the corn oil fed rats. It is proposed that these uptake and metabolic changes contribute to alterations in either energy expenditure or feeding behavior.

Vagotomy and mercaptoacetate influence the effect of dietary fat on macronutrient selection by rats.

We have previously shown that rats fed saturated fat prefer a high protein, low carbohydrate diet, whereas animals fed unsaturated fat prefer a low protein, high carbohydrate diet. The purpose of the present study was to determine whether this "saturated fat effect" requires 1) the oxidation of the dietary fat and 2) an intact hepatic vagus nerve. Male Sprague-Dawley rats were vagotomized (hepatic branch) or sham-operated and injected with either mercaptoacetate (fatty acid oxidation inhibitor) or saline. Next, half of each group was given saturated fat (beef tallow) or unsaturated fat (corn oil) by gastric tube. All animals were given a choice between two mixed diets that differed in protein and carbohydrate. Sham-operated rats fed saturated fat ate more of the protein diet than did rats fed unsaturated fat. Vagotomy attenuated the intake of the protein diet in animals fed saturated fat. Mercaptoacetate or vagotomy had no effect on diet selection in rats fed unsaturated fat. These data indicate that the effect of saturated fat on diet selection requires an intact hepatic vagus and may be modulated by fatty acid oxidation. Furthermore, the mechanism for altering diet selection can be induced after a single meal.

Effects of a fat substitute, sucrose polyester, on food intake, body composition, and serum factors in lean and obese Zucker rats.

Sucrose polyester, a fat substitute, has shown promise in reducing blood cholesterol and body weight of obese individuals. Effects of this compound in the Zucker rat, a genetic model of obesity, are unknown. Thus, we examined food intake, body weight, body composition, and several metabolic parameters in sera of lean and obese female Zucker rats. Eight-week-old lean and obese animals were given a choice between a control diet (15% corn oil) and fat substitute diet (5% corn oil and 10% sucrose polyester) for 2 days. Next, one-half of the lean and obese groups received control diet; the remaining lean and obese rats received fat substitute diet for 18 days. Cumulative food intake was depressed in fat substitute groups relative to control-fed animals; however, this effect was more predominant in obese animals. Obese rats consuming fat substitute diet (O-FS) gained less weight as compared to obese control-fed animals (O-C). Lean rats given fat substitute (L-FS) did not have significantly different body weights as compared to the L-C group. Fat substitute groups, combined, had lower body fat and higher body water as compared to controls. The O-FS group had lower serum glucose and insulin and higher fatty acid levels compared to the O-C group. There were no differences in serum cholesterol, HDL, or triglyceride levels due to fat substitute diet. These data suggest that the obese Zucker rat is unable to defend its body weight when dietary fat is replaced with sucrose polyester.

Multiple unconfirmed-reactive screening tests for viral antibodies among blood donors.

BACKGROUND: In December 1991, the United States Food and Drug Administration received reports of blood donations with unconfirmed reactivity on screening tests for antibodies to human immunodeficiency virus, human T-lymphotropic virus type I, and hepatitis C virus (HCV). Of 91 donors with these test results, 57 (63%) reported a recent influenza vaccination. STUDY DESIGN AND METHODS: To determine the extent of unconfirmed reactivity, the time at which it began, and its association or nonassociation with specific manufacturers' tests, a nationwide survey of blood centers was conducted. A case-donation was defined as a blood donation that was repeatedly reactive, but not confirmed positive, on at least two of the three tests from May 1990 through December 1991. RESULTS: Among 14 million donations screened by 110 centers, 582 case-donations were identified. An increase in case-donations was evident in the fall of 1990 (2.8/100,000 donations). In 1991, rates increased from 0.9 per 100,000 donations in the first quarter to 1.3, 3.2, and 19.7 in subsequent quarters. A significantly higher rate of case-donations was observed among donations tested with one of the two available anti-HCV screening tests (8.0 vs. 1.2/100,000 donations; risk ratio = 6.8; 95% CI = 5.4-8.5). CONCLUSION: Although unconfirmed reactivity on multiple screening tests appeared to be seasonal, its documentation prior to the availability of influenza vaccine in 1991 and higher rates among donations tested with one manufacturer's anti-HCV test indicated that test-specific factors were also involved.

Platelet activation and fibrinopeptide formation in pulmonary hypertension.

Intravascular thrombosis is postulated to cause or to contribute to the development of uncharacterized ("primary") pulmonary hypertension (PPH). To assess whether there is ongoing platelet-fibrin thrombosis in patients with PPH, we measured specific markers of platelet activation: platelet factor 4 (PF4) and beta-thromboglobulin (BTG); of fibrin formation: fibrinopeptide A (FPA); and of fibrin dissolution: fibrinopeptide BB1-42 (FPBB1-42) in peripheral venous blood from 10 patients with PPH (group 2). Results were compared with those of normal volunteers (group 1, n = 9) and with results from patients with pulmonary hypertension secondary to congenital heart disease (group 3, n = 7). Both groups 2 and 3 exhibited severe pulmonary hypertension (mean pulmonary arterial pressure = 62 +/- 20 mm Hg and 70 +/- 13 mm Hg, respectively). Mean level of PF4, BTG, FPA, and FPBB1-42 in patients with pulmonary hypertension, either primary or secondary to congenital heart disease, did not differ from levels in normal subjects. Within group 2, levels of platelet proteins and fibrinopeptides did not differ between patients who were classified clinically as having plexogenic arteriopathy vs thromboembolic disease. These observations suggest that a sustained state of abnormal platelet activation and fibrin formation or dissolution is not present in patients with established pulmonary hypertension.