Susan D. Roseff

Guidelines for assessing appropriateness of pediatric transfusion

R ecent advances in donor screening, blood testing before transfusion, and modifications made to collected components, with irradiation as an example, make the blood supply safer than ever before. Nonetheless, blood components should only be transfused when risks and benefits have been carefully weighed.1-5 Particular consideration is required when transfusing preterm infants, the most heavily transfused patient group in the tertiary care setting, with the greatest potential for longevity.6-9 Recent data have demonstrated that transfusion practices vary tremendously, particularly in preterm infants.10 Establishing criteria for appropriate transfusion practice is important to ensure that clear-cut benefits are derived from the administration of this sometimes limited resource. In addition, the Joint Commission for the Accreditation of Health Care Organizations requires review of the appropriateness of all transfusions to correct transfusion practices that deviate from standard practice and that the use of blood and blood components be reviewed on a continuing basis, as part of a required performance-improvement function.11 Review for under-transfusion should also be considered. This paper has been written to help transfusion services and transfusion committees have a starting point to establish their own audit guidelines. References are included for each institution to evaluate as they embark upon this process. Transfusion medicine specialists who are not well versed in the special needs of neonates, as well as generalists who direct the transfusion service but lack specific expertise, can use this document and its references to initiate guideline development. These guidelines, representing the opinions of the authors and incorporating evidence-based data where it exists, have been designed to facilitate uniform transfusion practice whenever possible. Elements of transfusion practice, which should also be reviewed, include the documentation of informed consent as well as completion of transfusion records.11,12 Transfusion practice guidelines should not serve as medical indications for transfusion, nor can they be all inclusive. The appropriateness for most of these transfusion guidelines has been demonstrated in published reports. It should be pointed out that neonatal transfusion medicine is an evolving discipline. Because of the fragile clinical status of these small patients, it is difficult to design randomized controlled trials with enough statistical power to produce ironclad data. A great majority of the papers written about neonatal transfusion are practice oriented and derived by consensus. Therefore, adapting published literature to be used when creating transfusion audit guidelines for neonates should be done on an individualized basis.13-15 In certain selected clinical situations, transfusion events that deviate from the proposed guidelines may be considered appropriate. Scientific data, as well as a review of the patient’s chart, can be helpful in evaluating the appropriateness of transfusion events that deviate from guidelines.16,17 Physicians should clearly document, in writing, the indication for each transfusion administered and perform an assessment of the efficacy of the transfusion (e.g., relief of symptoms of anemia, cessation of bleeding). Parental informed consent, a process that includes delineating risks, benefits, and alternatives to transfusion, must be obtained in accordance with all applicable local, state, and national regulatory requirements. ObABBREVIATIONS: DIC = disseminated intravascular coagulation; ECMO = extracorporeal membrane oxygenation; ITP = idiopathic thrombocytopenic purpura; PCC = prothrombin complex concentrates; TA-GVHD = transfusion-associated GVHD; UCB = umbilical cord blood; WB = whole blood.

Health related quality of life in sickle cell patients: The PiSCES project

BackgroundSickle cell disease (SCD) is a chronic disease associated with high degrees of morbidity and increased mortality. Health-related quality of life (HRQOL) among adults with sickle cell disease has not been widely reported.MethodsWe administered the Medical Outcomes Study 36-item Short-Form to 308 patients in the Pain in Sickle Cell Epidemiology Study (PiSCES) to assess HRQOL. Scales included physical function, physical and emotional role function, bodily pain, vitality, social function, mental health, and general health. We compared scores with national norms using t-tests, and with three chronic disease cohorts: asthma, cystic fibrosis and hemodialysis patients using analysis of variance and Dunnetts test for comparison with a control. We also assessed whether SCD specific variables (genotype, pain, crisis and utilization) were independently predictive of SF-36 subscales, controlling for socio-demographic variables using regression.ResultsPatients with SCD scored significantly worse than national norms on all subscales except mental health. Patients with SCD had lower HRQOL than cystic fibrosis patients except for mental health. Scores were similar for physical function, role function and mental health as compared to asthma patients, but worse for bodily pain, vitality, social function and general health subscales. Compared to dialysis patients, sickle cell disease patients scored similarly on physical role and emotional role function, social functioning and mental health, worse on bodily pain, general health and vitality and better on physical functioning. Surprisingly, genotype did not influence HRQOL except for vitality. However, scores significantly decreased as pain levels increased.ConclusionSCD patients experience health related quality of life worse than the general population, and in general, their scores were most similar to patients undergoing hemodialysis. Practitioners should regard their HRQOL as severely compromised. Interventions in SCD should consider improvements in health related quality of life as important outcomes.

Depression and Anxiety in Adults With Sickle Cell Disease: The Pisces Project

Objective: Depression and anxiety are common in sickle cell disease (SCD) but relatively little is known about their impact on SCD adults. This study measured prevalence of depression and anxiety in SCD adults, and their effects on crisis and noncrisis pain, quality-of-life, opioid usage, and healthcare utilization. Methods: The Pain in Sickle Cell Epidemiology Study is a prospective cohort study in 308 SCD adults. Baseline variables included demographics, genotype, laboratory data, health-related quality-of-life, depression, and anxiety. Subjects completed daily diaries for up to 6 months, reporting sickle cell pain intensity, distress, interference, whether they were in a sickle cell crisis, as well as health care and opioid utilization. Results: Two hundred thirty-two subjects who completed at least 1 month of diaries were studied; 27.6% were depressed and 6.5% had any anxiety disorder. Depressed subjects had pain on significantly more days than nondepressed subjects (mean pain days 71.1% versus 49.6%, p < .001). When in pain on noncrisis days, depressed subjects had higher mean pain, distress from pain, and interference from pain. Both depressed and anxious subjects had poorer functioning on all eight SF-36 subscales, even after controlling for demographics, hemoglobin type, and pain. The anxious subjects had more pain, distress from pain, and interference from pain, both on noncrisis pain days and on crisis days, and used opioids more often. Conclusions: Depression and anxiety predicted more daily pain and poorer physical and mental quality-of-life in adults with SCD, and accounted for more of the variance in all domains of quality-of-life than hemoglobin type. SCD = sickle cell disease; PiSCES = Pain in Sickle Cell Epidemiology Study; ED = emergency department; PHQ = patient health questionnaire; MOS SF-36 = Medical Outcome Study 36 item Short Form-36; MMSE = mini mental status examination.

Comparisons of High Versus Low Emergency Department Utilizers in Sickle Cell Disease

STUDY OBJECTIVE Patients with sickle cell disease often receive a substantial amount of their health care in the emergency department (ED) and some come to the ED frequently, seeking treatment for pain. As a result, patients with sickle cell disease are often stigmatized as opioid-seeking ED overutilizers. We describe the proportion of sickle cell disease patients who are high utilizers of the ED and compare them with other sickle cell disease patients on demographics, pain characteristics, health data, psychosocial characteristics, and quality of life. METHODS Two hundred thirty-two patients completed baseline data and at least 30 days of daily diary data. Baseline data included demographics, health data, and quality of life (Medical Outcome Study 36 Item Short Form). Daily diary data included ED utilization for sickle cell pain and descriptors of pain and distress. RESULTS Eighty-two (35.5%) patients were found to be high ED utilizers. Clinically important and statistically significant differences were found between high ED utilizers and all other sickle cell disease patients: lower hematocrit level, more transfusions, more pain days, more pain crises, higher mean pain and distress, and worse quality of life on Medical Outcome Study 36 Item Short Form physical function summary scales. After controlling for severity and frequency of pain, high ED utilizers did not use opioids more frequently than other sickle cell disease patients. CONCLUSION A substantial minority of sickle cell disease patients are high ED utilizers. However, high ED utilizers with sickle cell disease are more severely ill as measured by laboratory variables, have more pain, more distress, and have a lower quality of life.

Pain Site Frequency and Location in Sickle Cell Disease: the PiSCES Project

ABSTRACT Treatment options for sickle cell disease (SCD) pain could be tailored to pain locations. But few epidemiologic descriptions of SCD pain location exist; these are based on few subjects over short time periods. We examined whether SCD pain locations vary by disease genotype, gender, age, frequency of pain, depression, pain crisis or healthcare utilization. We enrolled 308 adults with SCD in 2002–2004. Subjects kept daily pain diaries for up to 6 months, including a body chart. Mixed model and generalized estimating equations were employed for analyses. Two hundred and sixty subjects completed at least one body chart. An average of 3.3/16 sites (25%) were painful. The number of pain sites varied by age, depression, frequent pain days, crisis and unplanned hospital/ED utilization. Lower back, knee/shin and hip, hurt on average more than a third of pain days, while jaw and pelvis hurt on fewer than 10% of days. Odds of a crisis were increased substantially when pain was in the arm, shoulder, upper back, sternum, clavicle, chest or pelvis (OR > 1.5) while the odds of unplanned utilization were substantially increased for the sternum, clavicle and chest (OR > 2.0). Pain in SCD varies considerably both within and between subjects, although it occurs most commonly in the lower back and lower extremities. The number and location of pain sites vary significantly by age, frequent pain, crisis and utilization. Identification and understanding of combinations of pain location and intensity may help to understand the etiology of SCD and improve SCD management.

The role of catastrophizing in sickle cell disease : The PiSCES project

Abstract In several types of chronic pain, catastrophizing has been related to higher pain intensity, and health care utilization but it has not been explored extensively in sickle cell disease (SCD). The objective of the study was to identify the role of catastrophizing in SCD, specifically in relation to painful crises, non‐crisis pain, and responses to pain. Two hundred and twenty SCD adults were enrolled in a prospective cohort study of pain and completed between 30 and 188 daily diaries in 6 months. The Catastrophizing subscale (CAT) of the Coping Strategy Questionnaire (CSQ) was administered at baseline and at study exit. Depression and quality of life were measured by the Patient Health Questionnaire and SF‐36, respectively, at baseline. The CAT mean was 13.6 (SD = 8.4) and higher CAT was correlated with greater depression severity (r = 0.48; p < 0.001) and poorer quality of life in all domains (r = −0.24 to −0.47; p < 0.001). There was no significance difference between CAT mean baseline and exit scores, and the measures were strongly correlated within patients (r = 0.69; p < 0.001). No difference was found between higher and lower catastrophizers in intensity of pain, distress, interference, and health service utilization, both on crisis or non‐crisis SCD‐related pain days, after controlling for depression. Adults with SCD had a higher mean catastrophizing score than found in studies of other chronic pain conditions that are not lifelong and life‐threatening. CAT scores were not correlated with pain parameters or utilization. The role of catastrophizing in other conditions cannot be generalized to SCD.

Refining the value of secretory phospholipase A2 as a predictor of acute chest syndrome in sickle cell disease: results of a feasibility study (PROACTIVE)

Acute chest syndrome (ACS) is defined as fever, respiratory symptoms and a new pulmonary infiltrate in an individual with sickle cell disease (SCD). Nearly half of ACS episodes occur in SCD patients already hospitalized, potentially permitting pre‐emptive therapy in high‐risk patients. Simple transfusion of red blood cells may abort ACS if given to patients hospitalized for pain who develop fever and elevated levels of secretory phospholipase A2 (sPLA2). In a feasibility study (PROACTIVE; ClinicalTrials.gov NCT00951808), patients hospitalized for pain who developed fever and elevated sPLA2 were eligible for randomization to transfusion or observation; all others were enrolled in an observational arm. Of 237 enrolled, only 10 were randomized; one of the four to receive transfusion had delayed treatment. Of 233 subjects receiving standard care, 22 developed ACS. A threshold level of sPLA2 ≥ 48 ng/ml gave optimal sensitivity (73%), specificity (71%) and accuracy (71%), but a positive predictive value of only 24%. The predictive value of sPLA2 was improved in adults and patients with chest or back pain, lower haemoglobin concentration and higher white blood cell counts, and in those receiving less than two‐thirds maintenance fluids. The hurdles identified in PROACTIVE should facilitate design of a larger, definitive, phase 3 randomized controlled trial.

Developing a blood conservation program in cardiac surgery

The beneficial effects of blood transfusions have been described and widely accepted. Multiple factors, including shortages, costs, infectious risks, immunologic risks, and the risk/benefit ratio to the patient, have made the medical community reassess the guidelines for transfusion. Cardiac surgery presents a unique subset of patients, because intervention at multiple stages in the care of these patients is possible to decrease the need for transfusion. An algorithm for a cardiac surgery program was developed and a reassessment performed. Once it was seen that no detrimental effect on patient care occurred, the program was expanded, was enhanced, and subsequently has been offered to the rest of the health care system. This program has resulted in a decrease in cost while maintaining patient outcomes. The success of the program is believed to be a result of the multidisciplinary approach taken, with a commitment from all members of the blood reduction team being the key component of this success.

Alcohol Abuse in Sickle Cell Disease: The Pisces Project

Alcohol abuse is common in patients with chronic painful medical disorders, but it has not been studied in sickle cell disease (SCD). In a prospective cohort study of SCD adults, 31.4% were identified as abusing alcohol. There were no significant differences between alcohol abusers and nonabusers on demographics, biological variables, depression, anxiety, measures of crisis and noncrisis pain, or opioid use, but abusers reported more pain relief from opioids than nonabusers did. Alcohol abusers had fewer unscheduled clinic visits, emergency room visits, hospital days, and any health care utilization for SCD, but this was only significant for emergency room visits. Quality of life was similar between both groups, except that alcohol abusers unexpectedly had better overall physical summary scores. Alcohol abusers were more likely to report coping by ignoring pain, diverting attention, and using particular self-statements.

Daily home opioid use in adults with sickle cell disease: The PiSCES project

BACKGROUND Although opioid prescribing in sickle cell disease (SCD) can be controversial, little is published about patterns of opioid use. OBJECTIVE To report on home opioid use among adults with SCD. DESIGN Cohort study. PARTICIPANTS Adults with SCD (n=219) who completed daily pain diaries for up to 6 months and had at least one home pain day. MAIN MEASURES Use of long-acting or short-acting opioids, other analgesics, or adjuvants; the proportion of home days, home pain days, and home crisis days with opioid use; these two outcomes according to patient characteristics. KEY RESULTS Patients used opioids on 12,311 (78 percent) of 15,778 home pain days. Eighty-five patients (38.8 percent) used long-acting opioids with or without short-acting opioids and 103 (47.0 percent) used only short-acting opioids. Twenty-one (9.6 percent) patients used only non-opioid analgesics and 10 (4.6 percent) used no analgesics. Both pain intensity and pain frequency were higher among opioid users (analysis of variance [ANOVA], p<0.0001). Opioid users used hydroxyurea more often than nonusers, even when controlling for mean pain on pain days. Among all patients, significant relationships were found between any opioid use and somatic symptom burden, SCD stress, negative coping, and physical and mental quality of life (QOL); the relationship with SCD stress and physical QOL remained when controlled for mean pain. Among opioid users, similar associations were found between frequency of opioid use and some disease-related and psychosocial variables. CONCLUSIONS In this adult SCD sample, opioids were used by the majority of patients. Pain was the overwhelming characteristic associated with use, but disease-related and psychosocial variables were also associated.