PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-10 (10)
 

Clipboard (0)
None

Select a Filter Below

Journals
Year of Publication
Document Types
1.  Iron Replacement Therapy in the Routine Management of Blood Donors 
Transfusion  2011;52(7):1566-1575.
Background
Iron depletion/deficiency in blood donors frequently results in deferrals for low hemoglobin, yet blood centers remain reluctant to dispense iron replacement therapy to donors.
Study Design and Methods
During a 39-month period, 1236 blood donors deferred for hemoglobin <12.5 g/dL and 400 non-deferred control donors underwent health history screening and laboratory testing (CBC, iron studies). Iron depletion and deficiency were defined as ferritin of 9–19 mcg/L and <9 mcg/L in females and 18–29 mcg/L and <18 mcg/L in males. Deferred donors and iron-deficient control donors were given a 60-pack of ferrous sulfate 325 mg tablets, and instructed to take one tablet daily. Another 60-pack was dispensed at all subsequent visits.
Results
In the low hemoglobin group, 30% and 23% of females and 8% and 53% of males had iron depletion or deficiency, respectively, compared with 29% and 10% of females and 18% and 21% of males in the control group. Iron depleted/deficient donors taking iron showed normalization of iron-related laboratory parameters, even as they continued to donate. Compliance with oral iron was 68%. Adverse gastrointestinal effects occurred in 21% of donors. The study identified 13 donors with serious medical conditions, including eight with GI bleeding. No donors had malignancies or hemochromatosis.
Conclusion
Iron depletion or deficiency was found in 53% of female and 61% of male low hemoglobin donors, and in 39% of female and male control donors. Routine administration of iron replacement therapy is safe, effective, and prevents the development of iron depletion/deficiency in blood donors.
doi:10.1111/j.1537-2995.2011.03488.x
PMCID: PMC3690467  PMID: 22211316
2.  Changes in Exercise Capacity of Cardiac Asymptomatic Hereditary Hemochromatosis Subjects over 5-Year Follow up 
Objective
A long-term effect of hereditary hemochromatosis (HH) on aerobic exercise capacity (AEC) has not been well described.
Design
Forty-three HH and 21 volunteer control (VC) subjects who were asymptomatic underwent cardiopulmonary exercise testing using the Bruce protocol. AEC was assessed with minute ventilation (VE), oxygen uptake (VO2), and carbon dioxide production (VCO2) at baseline (BL) at a 5-year follow up (5Y) assessment. A paired t-test was used for analyses of normality data; otherwise, a Wilcoxon singed rank sum test was used.
Results
Thirty-three HH subjects and 18 VC subjects returned for a repeat CPX at 5Y (80% overall return rate). At 5Y, AEC was not different between the two groups. As compared with BL measurements, exercise time, peak VO2, and the VE/VCO2 slope did not differ statistically at 5Y between both groups. Iron depletion by phlebotomy for 5 years did not significantly affect AEC in newly diagnosed HH subjects at baseline (n=14) and cardiac arrhythmias during exercise tended to decrease after 5 years of therapy in this group.
Conclusions
The AEC of asymptomatic HH subjects treated with conventional therapy is not statistically affected by the disease over a 5-year period.
doi:10.1097/PHM.0b013e3182465f5f
PMCID: PMC3331951  PMID: 22311055
Hereditary Hemochromatosis; Exercise Capacity; Cardiopulmonary Exercise Test; Prospective Study
3.  Incidence of Cardiac Arrhythmias in Asymptomatic Hereditary Hemochromatosis Subjects with C282Y Homozygosity 
The American Journal of Cardiology  2011;109(6):856-860.
It is not well known whether systemic iron overload per se in hereditary hemochromatosis (HH) is associated with cardiac arrhythmias before other signs and symptoms of cardiovascular disease occur. In this study, we examined the incidence of cardiac arrhythmias in cardiac asymptomatic HH subjects (NYHA functional class I), and compared it to that in age/gender-matched normal volunteers. The 42 HH subjects and 19 normal volunteer control subjects recruited through the NHLBI-sponsored "Heart Study of Hemochromatosis" completed 48-hour Holter electrocardiography ambulatory monitoring at the baseline evaluation. The HH subjects were classified as newly diagnosed (Group A) and chronically treated subjects (Group B). All HH subjects had C282Y homozygosity, and the normal volunteers lacked any HFE gene mutations which are known to cause HH. Although statistically insignificant, the incidence of ventricular and supraventricular ectopy tended to be higher in the combined HH groups than the controls. Supraventricular ectopy was more frequently noted in Group B as compared to the controls (ectopy rate per hour; 11.1±29.9 vs. 1.5±3.5, P < 0.05 by Kurskal Wallis test). No examples of heart block, other than first degree atrioventricular node block, were seen in any of the subjects. The incidence of cardiac arrhythmias was not significantly reduced after 6 months of intensive iron removal therapy in Group A subjects. No life threatening arrhythmias were observed in our HH subjects. In conclusion, our data suggest that the incidence of cardiac arrhythmias is, at most, marginally increased in asymptomatic HH subjects. A larger clinical study is warranted to further clarify our observation.
doi:10.1016/j.amjcard.2011.11.011
PMCID: PMC3294140  PMID: 22196777
Arrhythmias; Hereditary Hemochromatosis; Holter electrocardiogram
4.  Effects of Granulocyte Colony Stimulating Factor on Monosomy 7 Aneuploidy in Healthy Hematopoietic Stem Cell and Granulocyte Donors 
Transfusion  2011;52(3):537-541.
Background
Reports of monosomy 7 in patients receiving granulocyte colony stimulating factor (G-CSF) have raised concerns that this cytokine may promote genomic instability. However, there are no studies addressing whether repeated administration of G-CSF produces monosomy 7 aneuploidy in healthy donors.
Study Design and Methods
We examined chromosomes 7 and 8 by fluorescent in situ hybridization (FISH) in CD34+ cells from 35 healthy hematopoietic stem cell transplant (HSCT) donors after G-CSF administration for 5 days, and by spectral karyotyping analysis (SKY) in four individuals to assess chromosomal integrity. We also studied 38 granulocyte donors who received up to 42 doses of G-CSF and dexamethasone (Dex) using FISH for chromosomes 7 and 8.
Results
We found no abnormalities in chromosomes 7 and 8 in G-CSF mobilized CD34+ cells when assessed by FISH or SKY, nor did we detect aneuploidy in G-CSF/Dex treated donors.
Conclusion
G-CSF does not promote clinically detectable monosomy 7 or trisomy 8 aneuploidy in HSCT or granulocyte donors. These findings should be reassuring to healthy HSCT and granulocyte donors.
doi:10.1111/j.1537-2995.2011.03313.x
PMCID: PMC3235244  PMID: 21883270
5.  Ten-year follow-up of unrelated volunteer granulocyte donors who have received multiple cycles of granulocyte–colony-stimulating factor and dexamethasone 
Transfusion  2009;49(3):513-518.
BACKGROUND
The combination of granulocyte–colony-stimulating factor (G-CSF) and dexamethasone is an effective granulocyte mobilization regimen. The short-term side effects of G-CSF are well studied, but the potential long-term effects of repeated G-CSF stimulation in unrelated volunteer granulocyte donors have not been reported.
STUDY DESIGN AND METHODS
Donors who had received G-CSF three or more times for granulocytapheresis between 1994 and 2002 were identified and attempts were made to contact them if they were no longer active donors. They were matched with control platelet (PLT) donors for sex, age, and approximate number of cytapheresis donations. A health history was obtained and complete blood counts (CBCs) and C-reactive protein (CRP) determined where feasible.
RESULTS
Ninety-two granulocyte donors were identified, and 83 of them were contacted. They contributed to 1120 granulocyte concentrates, or a mean of 13.5 granulocytapheresis procedures per donor (and a mean of 87.5 plateletpheresis procedures per donor). There was no difference in CBCs between the granulocyte donors and the control PLT donors. There was no difference in CRP between the two groups, and no difference in pre- and post–G-CSF CRP in a subset of 22 granulocyte donors. Predefined health events included malignancies, coronary artery disease, and thrombosis. At a median 10-year follow-up, there were seven such events in the granulocyte donors and five in the PLT donors.
CONCLUSION
Although the number of granulocyte donors studied is small and continued surveillance of healthy individuals after G-CSF is prudent, our data suggest that G-CSF/dexamethasone stimulation appears to be safe.
doi:10.1111/j.1537-2995.2008.01983.x
PMCID: PMC3424604  PMID: 19243544
6.  The determinants of granulocyte yield in 1198 granulocyte concentrates collected from unrelated volunteer donors mobilized with dexamethasone and granulocyte–colony-stimulating factor: a 13-year experience 
Transfusion  2008;49(3):421-426.
BACKGROUND
The combination of granulocyte–colony-stimulating factor (G-CSF [filgrastim]) and dexamethasone (G-CSF/dex) is an effective granulocyte mobilization regimen, but the variables that affect donor neutrophil response and granulocyte collection yield are not well characterized.
STUDY DESIGN AND METHODS
A computerized database containing records of 1198 granulocyte collections from 137 unrelated volunteer apheresis donors during a 13-year period was retrospectively analyzed. Donors were categorized by age, sex, and cumulative number of granulocyte donations. Complete blood counts at baseline and after G-CSF/dex stimulation were recorded. The outcome variables include the pre-procedure absolute neutrophil count (preANC), which reflects G-CSF/dex stimulation, and the granulocyte product yield per liter processed (BagGranYield/L).
RESULTS
Higher baseline ANC and platelet (PLT) counts were significantly associated with higher preANC while a larger number of prior granulocytapheresis procedures was associated with lower preANC. Total filgrastim dose (used in weight-based dosing) did not significantly impact preANC or the granulocyte yield; weight-based dosing at 5 μg per kg and a uniform 480-μg dose produced equivalent preANC. PreANC and weight were the key determinants of granulocyte yield (BagGranYield/L).
CONCLUSION
Apheresis donors with higher baseline PLT counts and ANCs have higher ANCs after G-CSF/dex stimulation; donor age, weight, and sex do not have a significant impact. A uniform G-CSF dose of 480 μg is as effective as weight-based dosing at 5 μg per kg. Donor ANC monitoring should be considered after serial granulocytapheresis procedures.
doi:10.1111/j.1537-2995.2008.01997.x
PMCID: PMC3421027  PMID: 19040597
7.  Gravity sedimentation of granulocytapheresis concentrates with hydroxyethyl starch efficiently removes red blood cells and retains neutrophils 
Transfusion  2010;50(6):1203-1209.
BACKGROUND
Transfusion of granulocytapheresis concentrates can be limited by the volume of incompatible donor red blood cells (RBCs) in the component. Efficient reduction of RBCs in granulocyte units would result in safe transfusion of RBC-incompatible units.
STUDY DESIGN AND METHODS
Granulocyte concentrates were collected by continuous-flow apheresis from granulocyte–colony-stimulating factor (G-CSF) and dexamethasone-stimulated volunteer donors, with 6% hydroxyethyl starch (HES) added continuously during apheresis as a RBC sedimenting agent to enhance granulocyte collection efficiency. After collection, the component was placed in a plasma extractor for 4 hours. A sharp line of demarcation between the starch-sedimented RBCs and the granulocyte-rich supernatant developed, and the supernatant was transferred to a sterilely docked transfer pack. RBC reduction and white blood cell recovery were determined.
RESULTS
Gravity sedimentation was performed on 165 granulocyte concentrates. Mean sedimentation time was 267 minutes (range, 150–440 min). RBC depletion was 92% (range, 71%–99%) with mean residual RBC content of 3.2 ± 1.4 mL. Twelve percent of components contained less than 2 mL of RBCs. Mean granulocyte and platelet (PLT) recoveries were 80 and 81%, respectively. There were no transfusion reactions or signs of hemolysis after transfusion of 66 RBC-incompatible granulocyte concentrates (RBC volume, 1.6–8.2 mL). The remaining concentrates were used for topical or intrapleural applications.
CONCLUSIONS
RBCs were significantly reduced and granulocytes and PLTs effectively retained in G-CSF/ steroid–mobilized granulocyte components collected with HES and processed by gravity sedimentation. This procedure allows safe transfusion of RBC-incompatible sedimented granulocyte units and may be used to expand the pool of available granulocyte donors for specific recipients.
doi:10.1111/j.1537-2995.2009.02576.x
PMCID: PMC3421031  PMID: 20113453
8.  Does Oxidative Stress Modulate Left Ventricular Diastolic Function in Asymptomatic Subjects with Hereditary Hemochromatosis? 
Echocardiography (Mount Kisco, N.y.)  2009;26(10):1153-1158.
Little is known about the early mechanisms mediating left ventricular (LV) diastolic dysfunction in patients with hereditary hemochromatosis (HH). However, the increased oxidative stress related to iron overload may be involved in this process, and strain rate (SR), a sensitive echocardiography derived measure of diastolic function, may detect such changes. Thus, we evaluated the relationship between left ventricular diastolic function measured with tissue Doppler SR and oxidative stress in asymptomatic HH subjects and control normal subjects. Ninety-four consecutive visits of 43 HH subjects, age 30 to 74 (50 ± 10, mean ± SD) and 37 consecutive visits of 21 normal volunteers age 30 to 63 (48 ± 8) were evaluated over a three-year period. SR was obtained from the basal septum in apical 4 chamber views. All patients had confirmed C282Y homozygosity, a documented history iron overload and were New York Heart Association functional class I. Normal volunteers lacked HFE gene mutations causing HH. In the HH subjects, the SR demonstrated moderate, but significant correlations with biomarkers of oxidative stress; however, no correlations were noted in normal subjects. The biomarkers of iron overload per se did not show significant correlations with the SR. Although our study was limited by the relatively small subject number, these results suggest that a possible role of oxidative stress to affect LV diastolic function in asymptomatic HH subjects and SR imaging may be a sensitive measure to detect that effect.
doi:10.1111/j.1540-8175.2009.00956.x
PMCID: PMC3397801  PMID: 19725855
hereditary hemochromatosis; left ventricular diastolic function; oxidativestress; strain rate; iron overload; cohort study
9.  Expression of growth differentiation factor 15 is not elevated in individuals with iron deficiency secondary to volunteer blood donation 
Transfusion  2010;50(7):1532-1535.
BACKGROUND
Low serum hepcidin levels provide a physiologic response to iron demand in patients with iron deficiency (ID). Based on a discovery of suppressed hepcidin expression by a cytokine named growth differentiation factor 15 (GDF15), it was hypothesized that GDF15 may suppress hepcidin expression in humans with ID due to blood loss.
STUDY DESIGN AND METHODS
To test this hypothesis, GDF15 and hepcidin levels were measured in peripheral blood from subjects with iron-deficient erythropoiesis before and after iron supplementation.
RESULTS
Iron variables and hepcidin levels were significantly suppressed in iron-deficient blood donors compared to healthy volunteers. However, ID was not associated with elevated serum levels of GDF15. Instead, iron-deficient subjects’ GDF15 levels were slightly lower than those measured in the control group of subjects (307 ± 90 and 386 ± 104 pg/mL, respectively). Additionally, GDF15 levels were not significantly altered by iron repletion.
CONCLUSIONS
ID due to blood loss is not associated with a significant change in serum levels of GDF15.
doi:10.1111/j.1537-2995.2010.02601.x
PMCID: PMC3282986  PMID: 20210929
10.  Intracoronary infusion of autologous mononuclear cells from bone marrow or G-CSF mobilised apheresis product may not improve remodelling, contractile function, perfusion or infarct size in a swine model of large myocardial infarction 
European heart journal  2008;29(14):1772-1782.
Background
In a blinded, placebo controlled study, we investigated whether intracoronary infusion of autologous mononuclear cells from G-CSF mobilised apheresis product or bone marrow (BM) improved sensitive outcome measures in a swine model of large MI.
Methods and Results
Four days after LAD occlusion and reperfusion, cells from BM or apheresis product of saline (Placebo) or G-CSF injected animals were infused into the LAD. Large infarcts were created: baseline ejection fraction (EF) by MRI of 35.3 ± 8.5%, no difference between the Placebo, G-CSF and BM groups (p=0.16 by ANOVA). At 6 weeks EF fell to a similar degree in the Placebo, G-CSF and BM groups (−7.9±6.0%, −8.5±8.8% and −10.9±7.6%, p=0.78 by ANOVA). Left ventricular volumes and infarct size by MRI deteriorated similarly in all 3 groups. Quantitative PET demonstrated significant decline in FDG uptake rate in the LAD territory at follow-up, with no histological, angiographic or PET perfusion evidence of functional neovascularisation. Immunofluorescence failed to demonstrate transdifferentiation of infused cells.
Conclusion
Intracoronary infusion of mononuclear cells from either bone marrow or G-CSF mobilised apheresis product may not improve or limit deterioration in systolic function, adverse ventricular remodelling, infarct size or perfusion in a swine model of large MI.
doi:10.1093/eurheartj/ehn216
PMCID: PMC2575008  PMID: 18502738
Angiogenesis; imaging; myocardial infarction; myogenesis; stem cell

Results 1-10 (10)