The research question.
Explore the source record for details and available documents.
Biomedical Research↗
Biomedical subjects
Nancy M Heddle
Publications and source records attributed to Nancy M Heddle.
Clinical research design and reporting: always room for improvement!
Explore the source record for details and available documents.
Biomedical Research↗
The risk of bleeding in thrombocytopenic patients with acute myeloid leukemia.
BACKGROUND AND OBJECTIVES: Patients with acute myeloid leukemia are at risk of bleeding. The risk factors for different severities of bleeding are poorly studied. DESIGN AND METHODS: Data from Rebulla et al. were analyzed in an exploratory analysis using multivariate Cox regression analyses for time-to-first bleed with time-depend- ent covariates reflecting measures of clinical and laboratory variables on the previous day. The relationships of the variables with three bleeding categories were studied: mild bleeding (WHO grades 1 and 2) clinically significant (bleeding grades 2, 3 and 4) and severe (bleeding grades 3 and 4). RESULTS: Bleeding of any severity occurred in 149 (58.4%) of 255 patients. There were 743 days of bleeding over 7335 patient-days of observation. Risk factors for mild bleeding included increased body temperature and decreased platelet count; the risk was decreased with administration of antifungal medication or platelet transfusion on the previous day. Risk factors for clinically significant bleeding included grade 1 bleeding on the previous day, decreased platelet count and elevated body temperature. Decreased platelet count and mild bleeding on the previous day were risk factors for severe bleeding. Higher hemoglobin values were associated with a delay in the time-to-first clinically significant bleed. INTERPRETATION AND CONCLUSIONS: These results support clinical guidelines for increasing the platelet transfusion threshold in the presence of fever and support the use of milder bleeding symptoms as an outcome in clinical trials. The suggestion that hemo- globin concentration maybe predictive of bleeding risk supports the hypothesis that this maybe a valuable intervention in anemic thrombocytopenic patients at high risk of bleeding.
Adolescent↗
A review of randomized controlled trials comparing the effectiveness of hand held computers with paper methods for data collection.
BACKGROUND: Handheld computers are increasingly favoured over paper and pencil methods to capture data in clinical research. METHODS: This study systematically identified and reviewed randomized controlled trials (RCTs) that compared the two methods for self-recording and reporting data, and where at least one of the following outcomes was assessed: data accuracy; timeliness of data capture; and adherence to protocols for data collection. RESULTS: A comprehensive key word search of NLM Gateway's database yielded 9 studies fitting the criteria for inclusion. Data extraction was performed and checked by two of the authors. None of the studies included all outcomes. The results overall, favor handheld computers over paper and pencil for data collection among study participants but the data are not uniform for the different outcomes. Handheld computers appear superior in timeliness of receipt and data handling (four of four studies) and are preferred by most subjects (three of four studies). On the other hand, only one of the trials adequately compared adherence to instructions for recording and submission of data (handheld computers were superior), and comparisons of accuracy were inconsistent between five studies. CONCLUSION: Handhelds are an effective alternative to paper and pencil modes of data collection; they are faster and were preferred by most users.
Biomedical Research↗
In vivo recovery and survival of apheresis and whole blood-derived platelets: a paired comparison in healthy volunteers.
BACKGROUND: Methods of platelet preparation may alter the recovery and survival characteristics of platelets following transfusion. As suggested by a recent clinical trial, platelet recovery may be better preserved with apheresis platelet preparations than with platelets prepared from whole blood by the platelet-rich plasma (PRP) method. STUDY DESIGN AND METHODS: In vivo platelet recovery and survival of autologous leukoreduced (LR) apheresis platelets and autologous filter-LR PRP platelets were compared in 22 healthy volunteers using a paired crossover design. On the same day, each participant gave one apheresis platelet donation and one whole blood donation from which platelets were recovered from the PRP. The sequence of donations was randomly assigned for each participant. Following 5 days of storage and bacterial screening, a sample from each platelet product was labeled with either (51)chromium or (111)indium (randomly assigned) and both samples were simultaneously re-infused into the original donor. Recovery and gamma-function platelet survival were calculated for each platelet product using the multiple hit mathematical model. RESULTS: Five day stored LR-apheresis platelets had 18.8 percent better recovery, and 32.9 percent longer gamma-survival than filter-LR PRP platelets. Stored apheresis platelets had lower p-selectin expression and higher morphology scores than stored PRP platelets. CONCLUSIONS: Filter-LR PRP platelet preparation appears to adversely affect platelet recovery and survival characteristics. The reasons for this effect are not clear. These results may not apply to all apheresis and PRP methods of platelet preparation.
Adult↗
A descriptive analysis of international transfusion practice and bleeding outcomes in patients with acute leukemia.
BACKGROUND: Recently, bleeding has been used in platelet (PLT) trials rather than surrogate outcomes. The purpose of this study was to provide a descriptive summary of data from PLT studies conducted in four countries and exploratory analyses to determine the relationship between bleeding and PLT count. STUDY DESIGN AND METHODS: A descriptive analysis was performed on original data from the Italian trigger study, the US TRAP study, the Canadian febrile reaction study, and a clinical chart review from one hospital site in the United Kingdom. The relationship between bleeding and PLT count was explored with the Italian data. RESULTS: A total of 897 patients with acute leukemia received 10,506 PLT transfusions. Grade 3 or Grade 4 WHO bleeding frequency was 28.1 percent (252/897) but varied by country: Italy, 10.8 percent (27/250); United States, 36.4 percent (217/598); Canada, 18.9 percent (7/37); and the United Kingdom, 8.3 percent (1/12). Grade 1 or Grade 2 bleeding was reported only in the Italian study (46.4%[116/250] and 11.6%[29/250], respectively). The relative rates of WHO Grade 2, 3, or 4 bleeding for PLT counts in the ranges of 0 to 4, 5 to 9, 10 to 14, and 15 to 19 (x10(9)/L) were 8.8, 1.9, 1.8, and 1.2, respectively, compared to those counts within the range of 20 to 29 (x10(9)/L). CONCLUSION: The study provides descriptive data on PLT use and frequency of bleeding. When PLT counts were 0x10(9) to 4x10(9) per L there was an eightfold increase in bleeding and a twofold risk increase when counts were 5x10(9) to 14x10(9) per L compared to the 20x10(9) to 29x10(9) per L reference range. The increased rate of bleeding at low counts occurred despite PLT therapy.
Acute Disease↗
Utilization of platelet transfusions in the intensive care unit: indications, transfusion triggers, and platelet count responses.
BACKGROUND: A description of current platelet (PLT) transfusion practice in the intensive care unit (ICU) is needed. STUDY DESIGN AND METHODS: All thrombocytopenic patients (PLT count, <150 x 10(9)/L) who received PLT transfusions were identified from a previous prospective study of consecutive medical-surgical ICU patients; trauma, orthopedic, and cardiac surgery were exclusions. Risk factors for ineffective transfusions were examined. RESULTS: Of 261 ICU patients, 118 (45.2%) had thrombocytopenia and a PLT count nadir of less than 50 x 10(9) per L (n = 22), 50 to 99 x 10(9) per L (n = 37), and 100 to 149 x 10(9) per L (n = 59). Twenty-seven (22.9%) patients received PLT transfusions (n = 76 transfusions) and 37 (31.4%) had major bleeding. PLT dose was approximately 3 to 4 x 10(11) per L transfusion. Therapeutic (n = 24) and prophylactic (n = 52) PLT transfusion triggers were 51 x 10(9) per L (interquartile range [IQR], 26 to 68) and 41 x 10(9) per L (IQR, 20 to 57), respectively, as measured at a median of 4.5 hours (IQR, <1.6 to 6.9) before transfusion. A single PLT transfusion resulted in a median PLT increase of 14 x 10(9) per L (IQR, -2 to 30) measured at 5.2 hours (IQR, 1.8 to 8.8) after the transfusion; however, no PLT count increase was observed after 17 transfusions given to 13 (48.1%) patients. No risk factors for ineffective transfusions were identified. CONCLUSIONS: Among critically ill patients, most PLT transfusions were administered to prevent, rather than to treat, bleeding, with a transfusion trigger of 40 to 50 x 10(9) per L. Nearly half of ICU patients who received transfusions failed to mount a PLT count increase after a single transfusion. Prospective studies are needed to determine the effects of PLT transfusions on bleeding and predictors of ineffective transfusions in the ICU.
Aged↗
A study of the agreement between patient self-assessment and study personnel assessment of bleeding symptoms.
BACKGROUND: Clinical trials investigating new platelet transfusion therapies frequently require the assessment of bleeding for the study outcome. These assessments are commonly performed by study personnel and can be time-consuming. The purpose of this study was to assess whether patients were able to reliably assess their bleeding status on a daily basis. STUDY DESIGN AND METHODS: Patients admitted to hospital to receive chemotherapy for acute leukemia or to undergo allogeneic peripheral blood progenitor cell transplant were included. Patients were given an introduction to a form for documenting the occurrence of 16 bleeding symptoms. Patients completed this form and were examined daily by a study assessor. A weekly health record review was also performed by a study assessor. The agreement between raters was determined by calculating the raw agreement, chance-corrected agreement, and chance-independent agreement. RESULTS: Thirty-five patients completed 458 assessment forms that were paired with 559 forms completed by a study assessor with 450 matched forms available for analysis (mean, 12.86 per patient). Agreement for most individual bleeding symptoms was high. Thirteen items had agreement greater than 90 percent and all items had agreement greater than 77 percent. The lowest agreement was seen for skin symptoms: petechiae (89.2%), purpura (80.9%), and ecchymosis (77.6%). The negative predictive value of patient self-assessment was high (range, 71.1%-100%) whereas the positive predictive value was lower (range, 0%-86.5%). CONCLUSION: The reliability was very good between patients and study assessors with the patients reporting excellent negative predictive value and variable positive predictive value.
Adolescent↗
Bleeding risks associated with inheritance of the Quebec platelet disorder.
Quebec platelet disorder (QPD) is an autosomal dominant bleeding disorder associated with increased urokinase-type plasminogen activator in platelets and alpha-granule protein degradation. To determine bleeding risks and common manifestations of QPD, a history questionnaire was developed and administered to 127 relatives in a family with QPD. Data entry was done blinded to affected and unaffected status, determined by assays for platelet urokinase-type plasminogen activator (u-PA) and fibrinogen degradation. Odds ratios (ORs), with 95% confidence intervals (CIs), were determined for items queried. Summative bleeding scores for each individual were calculated using items with OR more than 1. Mean ages (34 years; range, 1-89 years) were similar for affected (n = 23) and unaffected (n = 104) family members. Affected individuals had higher mean bleeding scores (P <.0001) and a much higher likelihood (OR > 20) of having bleeding that led to lifestyle changes, bruises that spread lower or as large or larger than an orange or both, joint bleeds, bleeding longer than 24 hours after dental extractions or deep cuts, and received or been recommended other treatments (fibrinolytic inhibitors) for bleeding. Individuals with QPD and exposure(s) to hemostatic challenges had experienced excessive bleeding only when fibrinolytic inhibitors had not been used. These data illustrate that QPD is associated with increased risks of bleeding that can be modified by fibrinolytic inhibitors.
Adolescent↗
Universal leukoreduction and acute transfusion reactions: putting the puzzle together.
Explore the source record for details and available documents.
Acute Disease↗
Hypotensive transfusion reactions can occur with blood products that are leukoreduced before storage.
BACKGROUND: Leukoreduction before storage, rather than bedside white blood cell filtration, is recommended to prevent hypotensive transfusion reactions. STUDY DESIGN AND METHODS: Investigation of hypotensive transfusion reactions during radical prostatectomy in two patients on angiotensin-converting enzyme inhibitors. In Patient A, hypotension occurred during the transfusion of each of the following blood products: 2 units of autologous blood deposited and leukoreduced (LR) before storage; 3 units of allogeneic red cells LR before storage; and 2 units of non-LR acute normovolemic hemodilution (ANH) whole blood. When each of the transfusions was stopped, the blood pressure recovered. In Patient B, hypotension occurred during the transfusion of non-LR ANH whole blood. All implicated units were administered rapidly using a blood infuser at 37 degrees C. Bradykinin (BK) and des-Arg9-BK formation and degradation and the activity of kinin-degrading metallopeptidases were measured in plasma samples from both patients. RESULTS: Degradation of des-Arg9-BK was severely impaired and the activity of aminopeptidase P severely reduced in Patient A, but not in Patient B. BK degradation was mildly impaired in both patients. CONCLUSION: Hypotensive reactions can occur with blood products that are LR before storage and non-LR ANH. An inherent defect in the metabolism of kinins may be a risk factor for the development of hypotensive transfusion reactions.
Adenocarcinoma↗
Intravenous (IV) anti-D and IV immunoglobulin achieve acute platelet increases by different mechanisms: modulation of cytokine and platelet responses to IV anti-D by FcgammaRIIa and FcgammaRIIIa polymorphisms.
Intravenous (IV) anti-D and IV immunoglobulin (IVIG) slow the Fcgamma receptor (FcgammaR)-mediated destruction of antibody-coated platelets in patients with immune thrombocytopenic purpura (ITP). This pilot study explored the mechanism of these immunoglobulin preparations by measuring interleukin-10 (IL-10), monocyte chemoattractant protein-1 (MCP-1), IL-6 and tumour necrosis factor alpha (TNFalpha), before and after infusion and by assessing the effect of FcgammaRIIa and FcgammaRIIIa polymorphisms on both cytokine and haematologic responses to anti-D. Following IVIG, only IL-10 was increased at 2 h and MCP-1 on day 7 (P < 0.05). In contrast, 2 h after anti-D infusion, plasma levels of all four cytokines were increased (P < 0.01); five of six patients with the highest MCP-1, IL-6 and TNFalpha levels had chills. Higher IL-10 levels correlated with platelet increases at 24 h and haemoglobin decreases at day 7 (P < 0.025). Patients with the FcgammaRIIa-131HH genotype had significantly higher MCP-1, IL-6 and TNFalpha levels. Patients with the FcgammaRIIIa-158VF genotype had higher platelet increments at day 7 (P < 0.05). Soluble CD16 (sCD16) was increased 2 h after IV anti-D; day 7 levels correlated with day 7 haemoglobin decreases (P < 0.01). In conclusion, the relationship of FcgammaRIIa and FcgammaRIIIa polymorphisms with both cytokine levels and platelet increments implicated these receptors in responses to anti-D and supported different mechanisms of FcgammaR interaction to those seen with IVIG.
Adolescent↗
A retrospective 11-year analysis of obstetric patients with idiopathic thrombocytopenic purpura.
Numerous studies have examined the outcomes of infants born to mothers with idiopathic thrombocytopenic purpura (ITP). Fewer studies have discussed the morbidity of obstetric patients with ITP. We describe a retrospective study of 92 women with ITP during 119 pregnancies over an 11-year period. Most women had thrombocytopenia during pregnancy. At delivery, women in 98 pregnancies (89%) had platelet counts lower than 150 x 109/L; most had mild to moderate thrombocytopenia. For many, the pregnancy was uneventful; however, women had moderate to severe bleeding in 25 pregnancies (21.5%). Women in 37 pregnancies (31.1%) required treatment to increase platelet counts. During delivery, 44 women (37.3%) received epidural analgesia without complications, with most having a platelet count between 50 and 149 x 109/L. Most deliveries (82.4%) were vaginal. Bleeding was uncommon at delivery. Infant platelet counts at birth ranged from 12 to 436 x 109/L; 25.2% of infants had platelet counts lower than 150 x 109/L, and 9% had platelet counts lower than 50 x 109/L. Eighteen infants (14.6%) required treatment for hemostatic impairment. Two fetal deaths occurred. One was caused by hemorrhage. ITP in pregnancy carries a low risk, but mothers and infants may require therapy to raise their platelet counts.
Adrenal Cortex Hormones↗
Developing a tracking system for coagulation factor concentrates in southern Ontario.
BACKGROUND: In response to the transfusion- transmitted AIDS epidemic, Canadian authorities recommended the development of tracking systems and improved reporting of adverse events. This study describes the development of a verifiable and comprehensive regional tracking system for coagulation factor concentrates. STUDY DESIGN AND METHODS: The Hamilton- Niagara Regional Hemophilia Program received distribution and utilization data from Canadian Blood Services, 26 regional hospitals, and 70 individuals with bleeding disorders on home-based therapy. Purpose-specific software, the Canadian Hemophilia Assessment and Resource Management System (CHARMS), was used to store, monitor, analyze, and validate data. RESULTS: During a 1-year period (2001), all factor concentrates distributed in this region were accounted for. A higher proportion of FVIII and FIX concentrates (88 vs. 12%) was infused at home than in hospitals, and a higher proportion (63 vs. 28%) was used to prevent than to treat bleeds. During a period of shortage, a 5-percent reduction in utilization of both FVIII and FIX concentrates was documented. One recall was managed swiftly and efficiently. Two patients reported allergic skin reactions. CONCLUSION: A verifiable tracking system has been developed that can provide ongoing data for both clinical and administrative purposes. Data collection from patients needs to be made more efficient and real-time recording is an important future objective. Such a system can be instituted locally for less than 1.5 percent of the cost of the factor concentrate used.
Adolescent↗
Methodologic issues in the use of bleeding as an outcome in transfusion medicine studies.
BACKGROUND: Prophylactic platelet transfusions are given to thrombocytopenic patients to prevent bleeding. The benefit of platelet transfusions has frequently been assessed by measuring the count increment; however, more recently, an assessment of bleeding has been used because it is a more clinically relevant outcome measure. The purpose of this study was to identify platelet transfusion trigger studies that used bleeding as an outcome measure, compare and contrast methods used to document bleeding and analyze bleeding outcomes, and identify and discuss methodologic issues to consider when bleeding is used as a study outcome. STUDY DESIGN AND METHODS: A systematic search to identify platelet transfusion trigger studies was performed. Relevant articles were reviewed to identify how bleeding data was captured and analyzed, and methodologic considerations were identified. RESULTS: Seven articles meeting the predefined entry criteria were identified. Methods used to document bleeding included chart review and clinical assessment. The frequency of assessment and the type of personnel performing the assessment were variable. Four approaches to analysis were identified: descriptive; comparison of the proportions of patients having at least one bleed; comparison of patient days with bleeding expressed as a proportion of the total days at risk of bleeding; and time-to-event (first bleed) analysis. CONCLUSION: Methodologic issues for consideration when designing a clinical study with bleeding as the outcome measure included approaches to minimize bias in the documentation and classification of bleeding and selection of an analysis approach that is appropriate to the question being asked. The need for development of a valid and reliable bleeding scale was also identified.
Data Collection↗
Laboratory diagnosis of immune heparin-induced thrombocytopenia.
Immune heparin-induced thrombocytopenia (HIT) is a distinct immunohematologic syndrome in which laboratory detection of the pathogenic HIT antibodies is diagnostically useful. Assays can be broadly classified as platelet activation assays (which detect HIT antibodies based on their characteristic platelet-activating properties) and antigen assays (which measure antibodies reactive against platelet factor 4 complexed with heparin or other polyanions). Available tests vary considerably in their sensitivity-specificity profiles for detecting the antibodies and in their predictive values. The high sensitivity of certain assays means that HIT can be readily ruled out (high negative predictive value). However, because heparin-treated patients often generate nonpathogenic antibodies, a positive test does not necessarily indicate clinical HIT. Laboratory methods for detecting HIT antibodies have undergone an evolution similar to that of red blood cell serology and which parallels the Goldilocks tale, that is, progression from too insensitive (too hard) to too sensitive (too soft) to "just right." However, optimal diagnostic information requires that laboratory test results be interpreted in the appropriate clinical context.
Clinical Laboratory Techniques↗
Platelet transfusions in children: results of a randomized, prospective, crossover trial of plasma removal and a prospective audit of WBC reduction.
BACKGROUND: Febrile nonhemolytic transfusion reactions (FNHTRs) complicate 2 to 37 percent of platelet transfusions in adults, but the incidence of such reactions in children is not known. The effectiveness of plasma reduction after storage and WBC reduction of platelet concentrates before storage was studied in pediatric recipients of platelet transfusions. STUDY DESIGN AND METHODS: In the first study, a prospective randomized crossover design was used in which patients received either unmodified whole-blood-derived or apheresis platelets or platelets from which most of the plasma supernatant had been removed just before transfusion. The second study was a prospective audit of recipients of prestorage WBC-reduced platelets. Children between 3 months and 17 years of age were eligible for both studies. Patients were assessed for signs and symptoms that are characteristic of a reaction during, immediately after, and 2 hours following transfusion. RESULTS: There were 226 platelet transfusions administered to 66 children. One hundred and sixty transfusions were given to 35 children enrolled in the randomized study, and 66 transfusions were given to 33 children during the audit. In the randomized study, nine of the 75 transfusions of unmodified platelets (12%) and six of 85 transfusions of poststorage plasma-removed platelets (7%) were associated with an FNHTR (p=0.42). In the audit, three of 66 transfusions of prestorage WBC-reduced platelets (5%) were associated with an FNHTR. Allergic reactions occurred with 5 percent (4 of 75), 6 percent (5 of 85), and 6 percent (4 of 66) of platelet transfusions, respectively. CONCLUSION: FNHTRs appear to be less common among pediatric recipients of platelet transfusions than in adults. In our two studies, there was a trend toward a lower frequency of FNHTRs with poststorage plasma removal and prestorage WBC reduction than with standard platelets, but this was not significant.
Adolescent↗
A randomized controlled trial comparing the frequency of acute reactions to plasma-removed platelets and prestorage WBC-reduced platelets.
BACKGROUND: Removal of the plasma supernatant from platelets before transfusion is effective in preventing acute reactions to platelets caused by cytokines. Prestorage WBC reduction of platelets may be even more effective at preventing reactions as the WBCs are removed and WBC-derived cytokines do not accumulate in this component. This study evaluates the effectiveness of plasma removal and two methods of prestorage WBC reduction for preventing acute reactions to platelets. STUDY DESIGN AND METHODS: Platelets given to adults with hematologic malignancies were randomly allocated to one of three types: plasma supernatant removed and a platelet storage solution added, whole blood-derived platelets that are prestorage WBC reduced by filtration before storage, and prestorage WBC-reduced apheresis platelets. Patients were monitored before, during, and after transfusion, and the severity of reactions was graded on a Likert scale. RESULTS: A total of 129 patients from four centers were given 1190 platelet transfusions. The overall frequency of reactions was 13.6 percent (162 of 1190), 21.3 percent (36 of 169) for the plasma-removed platelets, 11.4 percent (59 of 517) for random donor WBC-reduced platelets, and 13.3 percent (67 of 504) for apheresis WBC-reduced platelets (p=0.384). The overall frequency of severe reactions was 4.1 percent with plasma-removed platelets, 1.7 percent for whole blood-derived, prestorage WBC-reduced platelets, and 1.4 percent for prestorage WBC-reduced apheresis platelets. CONCLUSION: The frequency of reactions to plasma-removed platelets and prestorage WBC-reduced platelets was not significantly different; however, the power of the study for this comparison was low. There was no difference in the frequency of reactions to the two types of prestorage WBC-reduced platelets. The frequency of severe reactions to prestorage WBC-reduced platelets is low, occurring in only 1 to 2 percent of transfusions.
Adolescent↗