BACKGROUND
The wastage of red blood cell (RBC) units within the operative setting results in significant direct costs to health care organizations. Previous education‐based efforts to reduce wastage ...were unsuccessful at our institution. We hypothesized that a quality and process improvement approach would result in sustained reductions in intraoperative RBC wastage in a large academic medical center.
STUDY DESIGN AND METHODS
Utilizing a failure mode and effects analysis supplemented with time and temperature data, key drivers of perioperative RBC wastage were identified and targeted for process improvement.
RESULTS
Multiple contributing factors, including improper storage and transport and lack of accurate, locally relevant RBC wastage event data were identified as significant contributors to ongoing intraoperative RBC unit wastage. Testing and implementation of improvements to the process of transport and storage of RBC units occurred in liver transplant and adult cardiac surgical areas due to their history of disproportionately high RBC wastage rates. Process interventions targeting local drivers of RBC wastage resulted in a significant reduction in RBC wastage (p < 0.0001; adjusted odds ratio, 0.24; 95% confidence interval, 0.15‐0.39), despite an increase in operative case volume over the period of the study. Studied process interventions were then introduced incrementally in the remainder of the perioperative areas.
CONCLUSIONS
These results show that a multidisciplinary team focused on the process of blood product ordering, transport, and storage was able to significantly reduce operative RBC wastage and its associated costs using quality and process improvement methods.
Summary
Haemophilia A carriers have historically been thought to exhibit normal haemostasis. However, recent data demonstrates that, despite normal factor VIII (FVIII), haemophilia A carriers ...demonstrate an increased bleeding tendency. We tested the hypothesis that obligate haemophilia carriers exhibit an increase in clinically relevant bleeding. A cross‐sectional study was performed comparing haemophilia A carriers to normal women. Questionnaire assessment included a general bleeding questionnaire, condensed MCMDM‐1VWD bleeding assessment tool and Pictorial Bleeding Assessment Chart (PBAC). Laboratory assessment included complete blood count, prothrombin time, activated partial thromboplastin time, fibrinogen activity, FVIII activity (FVIII:C), von Willebrand factor antigen level, ristocetin cofactor, platelet function analyser‐100TM and ABO blood type. Forty‐four haemophilia A carriers and 43 controls were included. Demographic features were similar. Laboratory results demonstrated a statistically significant difference only in FVIII:C (82·5 vs. 134%, P < 0·001). Carriers reported a higher number of bleeding events, and both condensed MCMDM‐1 VWD bleeding scores (5 vs. 1, P < 0·001) and PBAC scores (423 vs. 182·5, P = 0·018) were significantly higher in carriers. Haemophilia A carriers exhibit increased bleeding symptoms when compared to normal women. Further studies are necessary to fully understand the bleeding phenotype in this population and optimize clinical management.
Introduction
Haemophilia A is an X‐linked recessive bleeding disorder that primarily affects males. Emerging data support evidence for increased bleeding in female haemophilia A carriers despite ...factor VIII activity within the normal range.
Aim
Data regarding the effect of increased bleeding on health‐related quality of life (HR‐QOL) in haemophilia A carriers is sparse. We tested the hypothesis that haemophilia A carriers have reduced HR‐QOL related to bleeding symptoms.
Methods
We conducted a cross‐sectional study at Vanderbilt University. Case subjects were obligate or genetically verified haemophilia A carriers age 18–60 years. Control subjects were mothers of children with cancer who receive care at the Vanderbilt paediatric haematology‐oncology clinic. Trained interviewers administered the Rand 36‐Item Health Survey 1.0, a validated questionnaire evaluating eight health concepts that may affect HR‐QOL, to each study participant. Mann–Whitney U‐tests were used to compare median scores for the eight health domains between the case and control groups.
Result
Forty‐two haemophilia A carriers and 36 control subjects were included in analyses. Haemophilia A carriers had significantly lower median scores for the domains of ‘Pain’ (73.75 vs. 90; P = 0.02) and ‘General health’ (75 vs. 85; P = 0.01) compared to control subjects.
Conclusion
Haemophilia A carriers in our study demonstrated significantly lower median scores on the Rand 36‐item Health Survey 1.0 in the domains of ‘Pain’ and ‘General Health’ compared to women in the control group. Our findings highlight the need for further investigation of the effect of bleeding on HR‐QOL in this population.
Hemophilia A, the result of reduced factor VIII activity, is an X-linked recessive bleeding disorder. Previous reports of hemophilia A carriers suggest an increased bleeding tendency. Our objective ...was to determine the attitudes and understanding of the hemophilia A carrier bleeding phenotype, and opinions regarding timing of carrier testing from the perspective of both medical providers and affected patients. Data from this survey were used as preliminary data for an ongoing prospective study.
An electronic survey was distributed to physicians and nurses employed at Hemophilia Treatment Centers, and hemophilia A carriers who were members of Hemophilia Federation of America. The questions focused on the clinical understanding of bleeding symptoms and management of hemophilia A carriers, and the timing and intensity of carrier testing.
Our survey indicates that 51% (36/51) of providers compared with 78% (36/46) of carriers believe that hemophilia A carriers with normal factor VIII activity have an increased bleeding tendency (P<0.001); 72% (33/36) of hemophilia A carriers report a high frequency of bleeding symptoms. Regarding carrier testing, 72% (50/69) of medical providers recommend testing after 14 years of age, conversely 65% (29/45) of hemophilia A carriers prefer testing to be done before this age (P<0.001).
Hemophilia A carriers self-report a higher frequency of bleeding than previously acknowledged, and have a preference for earlier testing to confirm carrier status.
Period gene expression in mouse endocrine tissues Bittman, Eric L; Doherty, Leo; Huang, Liyue ...
American journal of physiology. Regulatory, integrative and comparative physiology
285, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Circadian rhythms are generated by the oscillating expression of the Per1 and Per2 genes, which are expressed not only in the central brain pacemaker but also in peripheral tissues. Hormones are ...likely to coordinate physiological function in time. We performed in situ hybridization to localize mPer1 and mPer2 mRNA to particular cell types and tissue compartments in adrenal, thyroid, and testis. BALB/c mice maintained in a 12:12-h light-dark cycle expressed mPer1 in adrenal medulla, particularly in late afternoon and early night. mPer2 mRNA was more intensely expressed in adrenal cortex, especially in afternoon and evening. mPer1 mRNA was detected in thyroid. mPer1 was found in some but not all seminiferous tubules of each mouse at all times of day. Quantitation in C57BL/6 mice revealed a significant increase in the number of heavily labeled seminiferous tubules early in the night. Consistent with in situ hybridization, immunocytochemistry showed PER1 protein in spermatocytes and spermatids (spermatogenic stages VII-XII). Staining in spermatogonia and interstitial cells was inconsistent. Double labeling with 5'-bromodeoxyuridine showed PER1 expression first occurring 5 days after DNA replication. We conclude that mPeriod genes are expressed in peripheral endocrine glands. Central regulation, adenohypophyseal control, and functional importance of expression and phase remain to be elucidated.
Abstract 3385
Hemophilia A, the result of reduced factor VIII (FVIII) activity, is an X-linked recessive bleeding disorder affecting one in 5,000 males born in the United States (U.S.). Females are ...designated heterozygous or carriers. While bleeding symptoms have been fully characterized in male patients with Hemophilia A, less is known about the female Hemophilia A carrier bleeding phenotype. Previous reports in Hemophilia A carriers suggest an increased bleeding tendency regardless of residual FVIII activity. Further, small studies suggest that Hemophilia A carriers report excessive bleeding symptoms including, but not limited to menorrhagia, epistaxis, surgical bleeding and hemarthrosis.
To determine the attitudes and understanding of Hemophilia A carrier testing from the perspective of both providers and affected patients. Our global hypothesis is that genetically verified Hemophilia A carriers with normal FVIII activity will have increased clinically relevant bleeding.
We employed a cross-sectional study design, and developed an electronic survey that was emailed to physicians and nurses employed at U.S. Hemophilia Treatment Centers (HTC). The email list was generated from listed current HTC providers on www.cdc.gov. A similar electronic survey was developed and distributed to female Hemophilia A carrier members of Hemophilia Federation of America. Questions were derived from the Female Universal Data Collection project questionnaire, and focused on the clinical understanding and management of Hemophilia A carriers. In addition, questions were developed to assess attitudes regarding the timing and intensity of testing. Data was analyzed using SPSS with descriptive statistics, Wilcoxon rank sum test and Pearson test.
In the provider survey there was a 49%(42/85) response rate from the physicians and 37% response rate (30/80) from nurses. Combined, 64% (47/72) had >10 years of clinical experience, 94% (68/72) work in primarily within an HTC and 97% (69/71) offer carrier testing. In the survey aimed at Hemophilia A carriers, a total of 38 responses were analyzed. The mean age was 35 ± 11 years, 76% (29/38) had a biologic son with Hemophilia A with 65% (24/37), 22% (8/37) and 14% (5/37) being severe, moderate or mild in severity. Carrier testing was performed after the age of 14 in 82% of those queried. When asked about the optimal timing of carrier testing, 78% (31/41) of physicians and 68% (19/28) of nurses recommend testing after 14 years of age while 69% (24/35) of carriers prefer testing to be done prior to this age (p<0.001). Furthermore, patients report that 82% (27/33) were not aware of their carrier status until after 14 years of age.
While 78% (28/36) of the carrier’s affected hemophiliac relatives receive care at an HTC only 26% (9/35) receive regular Hemophiliac care, and 67% (6/9) of those receiving regular care are followed at the same location as their affected hemophiliac relative. When queried, 51% (36/51) of providers compared to 78% (28/36) of carriers believe that Hemophilia A carriers with normal FVIII activity have an increased bleeding tendency (p<0.001). Carriers surveyed had a self-reported mean FVIII activity of 48% (range 17–129) and 69% (25/36) report a high frequency of bleeding symptoms including the following: menorrhagia 61% (23/38), recurrent miscarriages 52% (15/29), post-pregnancy bleeding 42% (16/38), oral bleeding 34% (13/38), post-surgical bleeding 32% (12/38), epistaxis 21% (8/38) and joint bleeding 11% (4/38).
Hemophilia A carriers report a higher frequency of bleeding than previously acknowledged. In contrast to preferences of Hemophilia specialists, Hemophilia A carriers prefer to know their carrier status prior to 14 years of age and be cared for in the same location as their affected relatives. Under recognition of Hemophilia A carrier bleeding is common amongst HTC providers, and data collected in a prospective cohort with appropriate controls is warranted.
No relevant conflicts of interest to declare.
Abstract 2231
Child maltreatment is a frequent cause of injury in the United States, occurring in approximately 695,000 children per year. Bleeding disorders can exacerbate and be confused with ...non-accidental injury (NAI); both of these diagnostic errors are life altering for the child and family. Despite the high incidence of child abuse and the independent relative high incidence of bleeding disorders, the optimal hemostatic evaluation is unclear for children who may be victims of NAI. Expert hematologic opinion recommends a multi-tiered approach, first investigating for common bleeding disorders, and subsequently investigating for rare defects in the coagulation and fibrinolytic pathways, if necessary. Further research is needed to develop evidence-based guidelines for the evaluation of bleeding disorders in children who may be victims of NAI.
To review and analyze a five-year history of the hematologic investigation of children who presented with bleeding and/or bruising that was suspicious for NAI at Vanderbilt Children's Hospital (VCH). Our hypothesis is that there is a lack of a systematic approach for the hemostatic evaluation of children who present with bleeding symptoms and concern for NAI.
A retrospective cohort study design was employed. ICD-9 codes for NAI (995.5, 995.50, 995.54, 995.55, 995.59) were used. 354 medical records from 2007 – 2011 were reviewed and screened for inclusion and exclusion criteria, resulting in 198 fully evaluable patients. Medical records were then queried for details of clinical and laboratory evaluation that occurred at the initial presentation concerning for NAI. We defined a basic hematologic evaluation as a CBC, PT and PTT; and a comprehensive hematologic evaluation as a CBC, PT, PTT, factor VIII, IX and XI activity and von Willebrand evaluation. Data was analyzed using SPSS; statistical analysis was performed using frequencies and Chi-Square analysis.
The mean age for the studied population was 445 days (max 4687 days, minimum 6 days); 37% were male. Bleeding symptoms included intracranial hemorrhage (ICH) (40%) and bruising (58% without associated ICH, 73% with and without associated ICH), with approximately 60% demonstrating additional non-hematologic symptoms (i.e. fractures, burns). Hematologic laboratory tests performed included CBC in 66%, PT in 58%, and PTT in 55%; factor activity levels in 12% (primarily consisted of factors VIII and IX); and von Willebrand disease evaluation in 12% of subjects. Table 1 shows the percentage of laboratory tests obtained in the patients based on symptoms at presentation.Table 1:Percentage of subjects with specific laboratory tests based on presenting symptomsTestICH +/− bruising (n = 31)Bruising only (n = 49)ICH + Non-Heme Symptoms (n = 58)Bruising + Non-Heme Symptoms (n = 60)CBC97863662PT97803145PTT90713145Factor Activity48655Von Willebrand45675
Abnormal coagulation labs were seen in 33% of performed PT and 55% of PTT tests; 55% of abnormal PTs and 44% of abnormal PTTs repeated. Our defined basic evaluation was completed in 79% of patients with ICH and 36% of patients without ICH (p <0.00). Our defined comprehensive evaluation was completed in 9% of patients with ICH and 2% of patients without ICH (p 0.32). Only 1% (2 of 198) children in our cohort were diagnosed with hematologic disorders that explain their increased bleeding symptoms.
Complete hematologic evaluation of children who present with bleeding symptoms and concern for NAI is inconsistent. While some children with other findings diagnostic for NAI may not require a hematologic work-up from a medico-legal perspective, it is still prudent to consider common bleeding disorders as a potential contributing factor in the severity of symptoms. At VCH, laboratory evaluation was obtained with greater frequency in patients with hematologic symptoms only. Given the variability of tests obtained and the disparity between expert opinion and our historical evaluation, further investigation into the optimal evaluation of these patients is warranted at this time. A prospective cohort study would allow comprehensive evaluation of all children suspected of NAI resulting in a clear understanding of laboratory abnormalities and incidence of bleeding disorders.
No relevant conflicts of interest to declare.
Abstract Acute non-hemolytic transfusion reactions, consisting of both allergic and febrile reactions, are common occurring in up to 10.2% of transfused blood products 1, however anaphylaxis, or ...severe allergic reactions, are rare following transfusion. The incidence of anaphylaxis is more common after the transfusion of plasma containing products with estimations from 1:10,000–33,000 units of platelets and 1:29,000–50,000 units of fresh frozen plasma (FFP) compared with 1:50,000–200,000 units of red blood cells 1,2. Despite the rare occurrence, the clinical significance of transfusion related anaphylaxis can be severe with 12 reported fatalities over a 5-year span 3. We report a case of FFP related anaphylaxis in a patient anticipating orthotopic liver transplant (OLT) with a unique peri-operative treatment plan.
Abstract Investigation for bleeding disorders in the context of suspected non-accidental injury (NAI) is inconsistent. We reviewed the hematologic evaluation of children who presented with symptoms ...of bleeding and/or bruising suspicious for NAI to determine the frequency of hematologic tests, abnormal hematologic laboratory results, and hematologic diagnoses. A retrospective cohort study design was employed at two freestanding academic children's hospitals. ICD-9 codes for NAI were used to identify 427 evaluable patients. Medical records were queried for the details of clinical and laboratory evaluations at the initial presentation concerning for NAI. The median age for the population was 326 days (range 1 day–14 years), 58% were male. Primary bleeding symptoms included intracranial hemorrhage (31.8%) and bruising (68.2%). Hematologic laboratory tests performed included complete blood cell count in 62.3%, prothrombin time (PT) in 55.0%, and activated partial thromboplastin time (aPTT) in 53.6%; fibrinogen in 27.6%; factor activity in 17.1%; von Willebrand disease evaluation in 14.5%; and platelet function analyzer in 11.7%. Prolonged laboratory values were seen in 22.5% of PT and 17.4% of aPTT assays; 66.0% of abnormal PTs and 87.5% of abnormal aPTTs were repeated. In our cohort, 0.7% (3 of 427) of the population was diagnosed with a condition predisposing to bleeding. In children with bleeding symptoms concerning for NAI, hemostatic evaluation is inconsistent. Abnormal tests are not routinely repeated, and investigation for the most common bleeding disorder, von Willebrand disease, is rare. Further research into the extent and appropriate timing of the evaluation is warranted.
▪
Introduction: Cardiovascular disease (CVD) is a disease of aging. While men with hemophilia were initially thought to be protected from CVD, it is now clear that atherothrombotic events do occur. ...The objective of this study is to determine the prevalence of CVD and CV risk factors in older men with moderate and severe hemophilia.
Methods: A U.S. national cross-sectional study began enrollment in 10/2012. Included are men with moderate or severe congenital hemophilia A or B (FVIII or IX level ≤ 5%), age 54-73. Men with an additional bleeding disorder (besides liver dysfunction) were excluded. After informed consent, CV risk factors, medications, and thrombotic event history were obtained from patient interview and chart review. A fasting blood sample was assayed centrally.
Results: As of 7/24/2015, 194 of 200 planned subjects were recruited with enrollment to be completed by 9/2015 and analysis by 12/2015. Planned interim analysis on 165 subjects from 19 U.S. Hemophilia Treatment Centers is presented here. The majority were white (148; 89.7%) or African American (14; 8.5%). Mean age was 61 years (SD: 5; range: 54-73). Most used factor on demand, with only 30.3% (50/165) on prophylaxis, defined as ≥2 doses of FVIII or ≥ 1 dose FIX/week. Eight (4.9%) had a current inhibitor. Viral infection was common; 61.2% had hepatitis C, and 28.5% HIV.
Hypertension (HTN) was reported in 61.2% of subjects, dyslipidemia in 35.1%, and diabetes (DM) in 21.8%; 49.1% had ever smoked, 55.2% denied engaging in at least moderate physical activity and 43.0% had a family history of CVD. Average BMI was 28 kg/m2 (30.3% obese) and waist circumference 96 cm (32.1% enlarged). Fasting blood work showed an abnormally elevated: creatinine in 26.7% subjects (mean, SD) (1.1 mg/dl, 0.5), CRP in 9.7% (5.2 mg/L, 13.7), total cholesterol in 23.0% (174.1 mg/dl, 38.8), triglycerides in 27.9% (129.1 mg/dl, 68.3), LDL in 21.8% (105.1 mg/dl, 34.7); and low HDL in 42.4% (43.2 mg/dl, 11.8).
A minority, 14 subjects (8.5%) reported prior angina or atrial fibrillation/flutter; 5 (3.0%) leg deep venous thrombosis; 4 (2.4%) myocardial infarction (MI) or pulmonary embolism; 3 (1.8%) coronary artery stent placement; 2 (1.2%) transient ischemic event (TIA); and 1 (0.6%) coronary artery angioplasty, CABG, or peripheral arterial disease history.
The prevalence rate of CVD (defined as angina, MI, TIA, or ischemic or embolic stroke) was 9.7% (16 subjects), significantly lower than the 23% prevalence of CVD in similar aged men without hemophilia in the longitudinal Atherosclerosis Risk in Communities (ARIC) cohort (p-value <0.001). None of the men with CVD were on antiplatelet or anticoagulant medications.
Compared to never smokers, ever smokers had a significant odds ratio (OR) of 3.5 (95% CI 1.1-11.3) of CVD. For HTN, dyslipidemia, and DM, the OR (95% CI) of CVD were 2.0 (0.6-6.6), 2.0 (0.7-5.6), and 1.2 (0.4-4.0), respectively. Positive family history (OR 1.4 (0.5-3.8)) and low-level physical activity (1.1 (0.4-3.3)) also suggested some association with increased CVD risk. Higher triglycerides (1.2 (0.4-3.7)) and lower HDL (1.4 (0.5-3.9)) tended to increase CVD risk, but obesity was not a risk factor.
Men using prophylaxis appeared less likely to have CVD (3/50, 6.0%) than men not on prophylaxis (13/115, 11.3%), OR 0.5 (0.1-1.8), although the difference was not statistically significant. HIV+ men (2/47, 4.3%) were also less likely to have CVD compared to non-HIV+ men (14/115, 12.2%), OR 0.3 (0.07-1.5), but not significantly so. Current use of anti-HTN medications (42.4% of all subjects), cholesterol lowering agents (17.6%), and DM medications (13.3%) did not decrease CVD risk. Analysis of cause and effect is limited by the cross-sectional design.
Conclusions: In this interim analysis of an ongoing national cross-sectional study, older men with moderate to severe hemophilia commonly report risk factors for CVD, including HTN (61.2%), dyslipidemia (35.2%) and renal insufficiency (26.7%). Despite this, the prevalence of reported CVD is low at 9.7%, suggesting that men with hemophilia may be protected from forming pathogenic thrombi. Smoking significantly increased the OR of CVD events among men with hemophilia. More data are needed to determine if the approach to prophylaxis or other therapies should be altered in this population. We plan to formally compare the prevalence of CVD and CV risk factors with similarly aged men in the ARIC database once enrollment is complete.
Sood:Bayer: Research Funding. Ragni:Vascular Medicine Institute: Research Funding; Tacere Benitec: Membership on an entity's Board of Directors or advisory committees; CSL Behring: Research Funding; Baxalta: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Biomarin: Research Funding; Biogen: Research Funding; Alnylam: Research Funding; Bristol Myers Squibb: Research Funding; Bayer: Research Funding; Genentech Roche: Research Funding; SPARK: Research Funding; Shire: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Research Funding; Dimension: Research Funding. Quon:Baxter: Other: Advisory Board, Speakers Bureau; Bayer: Other: Advisory Board; Biogen: Other: Advisory Board, Speakers Bureau; Novo Nordisk: Other: Advisory Board, Speakers Bureau; Grifols: Speakers Bureau. Shapiro:Baxalta, Novo Nordisk, Biogen, ProMetic Life Sciences, and Kedrion Biopharma: Consultancy; Baxalta, Novo Nordisk, Biogen,: Membership on an entity's Board of Directors or advisory committees; Biogen: Speakers Bureau; Bayer Healthcare, Baxalta, Biogen, CSL Behring, Daiichi Sankyo, Kedrion Biopharma, Octapharma, OPKO, ProMetic Life Sciences, PTC Therapeutics, and Selexys: Research Funding. Cuker:Bracco: Consultancy; Genzyme: Consultancy; T2 Biosystems: Research Funding; CSL Behring: Consultancy. von Drygalski:CSL Behring: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Hematherix Inc: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties; Novo Nordisk: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Baxalta: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Biogen: Honoraria, Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees. Gill:Baxalta, Bayer, and CSL-Behring: Membership on an entity's Board of Directors or advisory committees. Leissinger:Novo Nordisk: Membership on an entity's Board of Directors or advisory committees, Research Funding; Biogen: Research Funding; Bayer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Kedrion: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding; Baxter: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees; CSL Behring: Membership on an entity's Board of Directors or advisory committees, Research Funding. Konkle:Pfizer: Consultancy; CSL Behring: Consultancy; Octapharma: Research Funding; Baxalta: Consultancy, Research Funding; Biogen: Consultancy, Research Funding; Novo Nordisk: Consultancy.
PDF
