Susan F Leitman

National Institutes of Health, Maryland, United States

Are you Susan F Leitman?

Claim your profile

Publications (220)1684.53 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Background Therapeutic phlebotomy is increasingly used in patients with transfusional siderosis to mitigate organ injury associated with iron overload (IO). Laboratory response variables and therapy duration are not well characterized in such patients.Study Design and Methods We retrospectively evaluated 99 consecutive patients undergoing therapeutic phlebotomy for either transfusional IO (TIO, n = 88; 76% had undergone hematopoietic transplantation) or nontransfusional indications (hyperferritinemia or erythrocytosis; n = 11). Complete blood cell count, serum ferritin (SF), transferrin saturation, and transaminases were measured serially. Phlebotomy goal was an SF level of less than 300 μg/L.ResultsMean SF levels before phlebotomy among TIO and nontransfusional subjects were 3093 and 396 μg/L, respectively. Transfusion burden in the TIO group was 94 ± 108 (mean ± SD) RBC units; approximately half completed therapy with 24 ± 23 phlebotomies (range, 1-103). One-third were lost to follow-up. Overall, 15% had mild adverse effects, including headache, nausea, and dizziness, mainly during first phlebotomy. Prior transfusion burden correlated poorly with initial ferritin and total number of phlebotomies to target in the TIO group. However, number of phlebotomies to target was strongly correlated with initial SF (R2 = 0.8; p < 0.0001) in both TIO and nontransfusional groups. ALT decreased significantly with serial phlebotomy in all groups (mean initial and final values, 61 and 39 U/L; p = 0.03).Conclusions Initial SF but not transfusion burden predicted number of phlebotomies to target in patients with TIO. Despite good treatment tolerance, significant losses to follow-up were noted. Providing patients with an estimated phlebotomy number and follow-up duration, and thus a finite endpoint, may improve compliance. Hepatic function improved with iron offloading.
    Transfusion 10/2014; · 3.57 Impact Factor
  • Kamille A. West, Susan F. Leitman, Willy A. Flegel
    Transfusion 09/2014; 54(9). · 3.57 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background Granulocyte–colony-stimulating factor (G-CSF)-mobilized autologous hematopoietic progenitor cells (HPCs) may be collected by apheresis of patients with chronic granulomatous disease (CGD) and severe combined immunodeficiency (SCID) for use in gene therapy trials. CD34+ cell mobilization has not been well characterized in such patients.Study Design and Methods We retrospectively evaluated CD34+ cell mobilization and collection in 73 consecutive CGD and SCID patients and in 99 age-, weight-, and G-CSF dose–matched healthy allogeneic controls.ResultsIn subjects aged not more than 20 years, Day 5 preapheresis circulating CD34+ counts were significantly lower in CGD and SCID patients than in controls; mean peak CD34+ cell counts were 58 × 106, 64 × 106, and 87 × 106/L, respectively (p = 0.01). The SCIDs had lower CD34+ collection efficiency than CGDs and controls; mean efficiencies were 40, 63, and 57%, respectively (p = 0.003). In subjects aged more than 20 years, the CGDs had significantly lower CD34+ cell mobilization than controls; mean peak CD34+ cell counts were 41 × 106 and 113 × 106/L, respectively (p < 0.0001). In a multivariate analysis, lower erythrocyte sedimentation rate (ESR) at mobilization was significantly correlated with better CD34+ cell mobilization (p = 0.007). In SCIDs, CD34 collection efficiency was positively correlated with higher red blood cell (RBC) indices (mean RBC volume, R2 = 0.77; mean corpuscular hemoglobin [Hb], R2 = 0.94; mean corpuscular Hb concentration, R2 = 0.7; p < 0.007) but not Hb.ConclusionsCGD and SCID populations are characterized by significantly less robust CD34+ HPC mobilization than healthy controls. The presence of active inflammation or infection as suggested by an elevated ESR may negatively impact mobilization. Among SCIDs, markedly reduced CD34 collection efficiencies were related to iron deficiency, wherein decreased RBC size and density may impair apheresis cell separation mechanics.
    Transfusion 09/2014; · 3.57 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In adults with sickle cell disease (SCD), markers of iron burden such as serum ferritin are associated with excessive production of the angiogenic protein placenta growth factor (PlGF) and high estimated pulmonary artery pressure. Enforced PlGF expression in mice stimulates production of the potent vasoconstrictor endothelin-1, producing pulmonary hypertension. We now demonstrate heme-bound iron (hemin) induces PlGF mRNA more than 200-fold in a dose- and time-dependent fashion. In murine and human erythroid cells, expression of Erythroid Krüppel-like Factor (EKLF) precedes PlGF, and its enforced expression in human erythroid progenitor cells induces PlGF mRNA. Hemin-induced expression of PlGF is abolished in EKLF-deficient murine erythroid cells but rescued by conditional expression of EKLF. Chromatin immunoprecipitation reveals that EKLF binds to the PlGF promoter region. SCD patients show higher level expression of both EKLF and PlGF mRNA in circulating blood cells, and markers of iron overload are associated with high plasma level of PlGF and early mortality. Finally, PlGF association with iron burden generalizes to other human diseases of iron overload. Our results for the first time demonstrate a specific mechanistic pathway induced by excess iron that is linked in humans with SCD and in mice to markers of vasculopathy and pulmonary hypertension. Studies were registered at, identifiers: NCT00007150, NCT00023296, NCT00081523, and NCT00352430.
    Blood 06/2014; · 9.78 Impact Factor
  • Susan F Leitman
    [Show abstract] [Hide abstract]
    ABSTRACT: Hereditary hemochromatosis (HH) due to homozygosity for the C282Y mutation in the HFE gene is a common inherited iron overload disorder in whites of northern European descent. Hepcidin deficiency, the hallmark of the disorder, leads to dysregulated intestinal iron absorption and progressive iron deposition in the liver, heart, skin, endocrine glands, and joints. Survival is normal if organ damage is prevented by early institution of phlebotomy therapy. HH arthropathy is the symptom most affecting quality of life and can be debilitating. Genotype screening in large population studies has shown that the clinical penetrance of C282Y homozygosity is highly variable and can be very low, with up to 50% of women and 20% of men showing a silent phenotype. Targeted population screening for the HFE C282Y mutation is not recommended at present, but might be reconsidered as a cost-effective approach to management if counseling and care were better organized and standardized. Referral of patients to the blood center for phlebotomy therapy and use of HH donor blood for transfusion standardizes treatment, minimizes treatment costs, and may benefit society as a whole. Physician practices should be amended such that HH subjects are more frequently referred to the blood center for therapy.
    Hematology 12/2013; 2013:645-50. · 1.49 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Plerixafor (Mozobil) is a CXCR4 antagonist that rapidly mobilizes CD34(+) cells into circulation. Recently, plerixafor has been used as a single agent to mobilize peripheral blood stem cells for allogeneic hematopoietic cell transplantation. Although G-CSF mobilization is known to alter the phenotype and cytokine polarization of transplanted T cells, the effects of plerixafor mobilization on T cells have not been well characterized. In this study, we show that alterations in the T cell phenotype and cytokine gene expression profiles characteristic of G-CSF mobilization do not occur after mobilization with plerixafor. Compared with nonmobilized T cells, plerixafor-mobilized T cells had similar phenotype, mixed lymphocyte reactivity, and Foxp3 gene expression levels in CD4(+) T cells, and did not undergo a change in expression levels of 84 genes associated with Th1/Th2/Th3 pathways. In contrast with plerixafor, G-CSF mobilization decreased CD62L expression on both CD4 and CD8(+) T cells and altered expression levels of 16 cytokine-associated genes in CD3(+) T cells. To assess the clinical relevance of these findings, we explored a murine model of graft-versus-host disease in which transplant recipients received plerixafor or G-CSF mobilized allograft from MHC-matched, minor histocompatibility-mismatched donors; recipients of plerixafor mobilized peripheral blood stem cells had a significantly higher incidence of skin graft-versus-host disease compared with mice receiving G-CSF mobilized transplants (100 versus 50%, respectively, p = 0.02). These preclinical data show plerixafor, in contrast with G-CSF, does not alter the phenotype and cytokine polarization of T cells, which raises the possibility that T cell-mediated immune sequelae of allogeneic transplantation in humans may differ when donor allografts are mobilized with plerixafor compared with G-CSF.
    The Journal of Immunology 11/2013; · 5.36 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Hematopoietic stem cells can be procured from unrelated donors via either the bone marrow (BM) aspiration or peripheral blood stem cell (PBSC) collection methods. There is no evidence from prospective randomized trials in the unrelated donor setting about the relative health-related quality-of-life (HRQoL) benefits/costs to donors. The goals of this prospective longitudinal investigation were to describe and compare the donation-related HRQoL experiences of 332 BM and PBSC donors. Donors were interviewed before donation, 48 hours after donation, weekly until fully recovered, and at 6 and 12 months after donation. Before donation, BM donors had lower confusion, fewer concerns, and were more prepared for donation. Shortly after donation, BM donors reported more physical side effects. BM donors also reported more donation-related impact on their social activities. However, BM donors reported somewhat better psychological status and were more likely to indicate that the donation made their lives more meaningful. There were virtually no longer term differences in the experiences of the 2 donor groups, including no recovery time difference beginning 3 weeks after donation. Although BM donors may experience the process as more physically stressful and more psychologically beneficial in the short term, the longer term HRQoL consequences of BM and PBSC donors are similar.
    Biology of Blood and Marrow Transplantation 10/2013; 20(1). · 3.35 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The risk of graft-rejection after allogeneic hematopoietic cell transplantation using conventional cyclophosphamide-based conditioning is increased in patients with bone marrow failure syndromes (BMFS) who are heavily transfused and often HLA-alloimmunized. Fifty-six patients with BMFS underwent fludarabine-based reduced-intensity conditioning and allogeneic peripheral blood progenitor cell (PBPC) transplantation at a single institution. The conditioning regimen consisted of intravenous cyclophosphamide, fludarabine and equine anti-thymocyte globulin. GVHD prophylaxis included cyclosporine A alone or in combination with either mycophenolate mofetil or methotrexate. To reduce the risk of graft-rejection/failure, un-manipulated G-CSF mobilized PBPCs obtained from an HLA-identical or single HLA-antigen mismatched relative were transplanted rather than donor bone marrow. Despite a high prevalence of pre-transplant HLA-alloimmunization (41%) and a heavy prior transfusion burden, graft-failure did not occur with all patients having sustained donor lympho-hematopoietic engraftment. The cumulative incidence of grade II-IV acute-GVHD and chronic-GVHD was 51.8% and 72% respectively; with 87.1% surviving at a median follow up of 4.5 years. A multivariate analysis showed pre-transplant alloimmunization and rapid donor T-cell engraftment (≥95% donor by day 30) were both significantly (P<0.05) associated with the development of chronic-GVHD (adjusted HR 2.13and 2.99 respectively).These data show fludarabine-based PBPC transplantation overcomes the risk of graft-failure in patients with BMFS, although rapid donor T-cell engraftment associated with this approach appears to increase the risk of chronic-GVHD. ( identifier: NCT00003838).
    American Journal of Hematology 06/2013; · 3.48 Impact Factor
  • Transfusion 05/2013; 53(5):1146-7. · 3.57 Impact Factor
  • Transfusion 05/2013; 53(5):1144-6. · 3.57 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In experimental models, ex vivo induced T cell rapamycin-resistance occurred independent of T-helper 1 (Th1)/T-helper 2 (Th2) differentiation and yielded allogeneic CD4(+) T cells of increased in vivo efficacy that facilitated engraftment and permitted graft-versus-tumor (GVT) effects while minimizing graft-versus-host disease (GVHD). To translate these findings, we performed a phase II multi-center clinical trial of rapamycin-resistant donor CD4(+) Th2/Th1 (T-Rapa) cells after allogeneic matched-sibling donor hematopoietic cell transplantation (HCT) for therapy of refractory hematologic malignancy. T-Rapa cell products, which expressed a balanced Th2/Th1 phenotype, were administered as a pre-emptive donor lymphocyte infusion (DLI) at day 14 post-HCT. After T-Rapa cell infusion, mixed donor/host chimerism rapidly converted and there was preferential immune reconstitution with donor CD4(+) Th2 and Th1 cells relative to regulatory T cells and CD8(+) T cells. The cumulative incidence probability of acute GVHD was 20% and 40% at days 100 and 180 post-HCT, respectively. There was no transplant-related mortality. Eighteen of 40 patients (45%) remain in sustained complete remission (range of follow-up: 42 to 84 months). These phase II clinical trial results demonstrate the safety of this low-intensity transplant approach, and indicate the feasibility of subsequent randomized studies to compare T-Rapa cell-based therapy to standard transplantation regimens. Study registered at:; NCT 00077480.
    Blood 02/2013; · 9.78 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: Pica and restless legs syndrome (RLS) are associated with iron depletion and deficiency. The presence of pica and RLS was prospectively assessed in blood donors. STUDY DESIGN AND METHODS: During a 39-month period, 1236 donors deferred for fingerstick hemoglobin (Hb) level of less than 12.5 g/dL and 400 nondeferred "control" donors underwent health screening and laboratory testing (complete blood count, ferritin, iron, transferrin). Pica and RLS were assessed by direct questioning. Deferred donors and iron-deficient control donors were given 325 mg of ferrous sulfate daily for 60 days. Reassessments were performed and additional iron tablets dispensed at subsequent visits. RESULTS: Pica was reported in 11% of donors with iron depletion or deficiency, compared with 4% of iron-replete donors (p < 0.0001). Pagophagia (ice pica) was most common and often of extraordinary intensity. Female sex, younger age, and lower mean cell volume and transferrin saturation values were strongly associated with pica. Donors with pica given iron reported a marked reduction in the desire to consume the nonnutritive substance by Days 5 to 8 of therapy, with disappearance of symptoms by Days 10 to 14. RLS was reported in 16% of subjects with iron depletion or deficiency compared with 11% of iron-replete donors (p = 0.012). Iron replacement generally resulted in improvement of RLS symptoms; however, at least 4 to 6 weeks of iron therapy was necessary. CONCLUSION: The presence of pica is associated with a high probability of iron depletion or deficiency in blood donors; however, RLS lacks a strong correlation in this population. Screening questions for pagophagia may be useful in the ascertainment of iron deficiency in donors and may identify those who would benefit from oral iron.
    Transfusion 01/2013; · 3.57 Impact Factor
  • A J Patel, R Wesley, S F Leitman, B J Bryant
    [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND AND OBJECTIVES: To determine the accuracy of fingerstick haemoglobin assessment in blood donors, the performance of a portable haemoglobinometer (HemoCue Hb 201+) was prospectively compared with that of an automated haematology analyzer (Cell-Dyn 4000). Haemoglobin values obtained by the latter were used as the 'true' result. MATERIAL AND METHODS: Capillary fingerstick samples were assayed by HemoCue in 150 donors. Fingerstick samples from two sites, one on each hand, were obtained from a subset of 50 subjects. Concurrent venous samples were tested using both HemoCue and Cell-Dyn devices. RESULTS: Capillary haemoglobin values (HemoCue) were significantly greater than venous haemoglobin values (HemoCue), which in turn were significantly greater than venous haemoglobin values by Cell-Dyn (mean ± SD: 14·05 ± 1·51, 13·89 ± 1·31, 13·62 ± 1·23, respectively; P < 0·01 for all comparisons among groups). Nine donors (6%) passed haemoglobin screening criteria (≥12·5 g/dl) by capillary HemoCue, but were deferred by Cell-Dyn values (false-pass). Five donors (3%) were deferred by capillary sampling, but passed by Cell-Dyn (false-fail). Substantial variability in repeated fingerstick HemoCue results was seen (mean haemoglobin 13·72 vs. 13·70 g/dl, absolute mean difference between paired samples 0·76 g/dl). Hand dominance was not a factor. CONCLUSIONS: Capillary samples assessed via a portable device yielded higher haemoglobin values than venous samples assessed on an automated analyzer. False-pass and false-fail rates were low and acceptable in the donor screening setting, with 'true' values not differing by a clinically significant degree from threshold values used to assess acceptability for blood donation.
    Vox Sanguinis 01/2013; · 3.30 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Although peripheral blood stem cells (PBSC) have replaced bone marrow (BM) as the most common unrelated donor progenitor cell product collected, a direct comparison of concurrent PBSC vs. BM donation experiences has not been performed. We report a prospective study of 2726 BM and 6768 PBSC donors who underwent collection from 2004-2009. Pain and toxicities were assessed at baseline, during G-CSF administration, on the day of collection, within 48 hours of donation, and weekly until full recovery. Peak levels of pain and toxicities did not differ between the two donation processes for most donors. Among obese donors, PBSC donors were at increased risk of grade 2-4 pain as well as grade 2-4 toxicities during the peri-collection period. In contrast, BM donors were more likely to experience grade 2-4 toxicities at one week and pain at one week and one month after the procedure. BM donors experienced slower recovery, with 3% still not fully recovered at 24 weeks, while 100% of PBSC donors had recovered. Other factors associated with toxicity included obesity, increasing age, and female gender. In summary, this study provides extensive detail regarding individualized risk patterns of PBSC vs. BM donation toxicity, suggesting donor profiles that can be targeted with interventions to minimize toxicity.
    Blood 10/2012; · 9.78 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Randomized trials have shown that the transplantation of filgrastim-mobilized peripheral-blood stem cells from HLA-identical siblings accelerates engraftment but increases the risks of acute and chronic graft-versus-host disease (GVHD), as compared with the transplantation of bone marrow. Some studies have also shown that peripheral-blood stem cells are associated with a decreased rate of relapse and improved survival among recipients with high-risk leukemia. We conducted a phase 3, multicenter, randomized trial of transplantation of peripheral-blood stem cells versus bone marrow from unrelated donors to compare 2-year survival probabilities with the use of an intention-to-treat analysis. Between March 2004 and September 2009, we enrolled 551 patients at 48 centers. Patients were randomly assigned in a 1:1 ratio to peripheral-blood stem-cell or bone marrow transplantation, stratified according to transplantation center and disease risk. The median follow-up of surviving patients was 36 months (interquartile range, 30 to 37). The overall survival rate at 2 years in the peripheral-blood group was 51% (95% confidence interval [CI], 45 to 57), as compared with 46% (95% CI, 40 to 52) in the bone marrow group (P=0.29), with an absolute difference of 5 percentage points (95% CI, -3 to 14). The overall incidence of graft failure in the peripheral-blood group was 3% (95% CI, 1 to 5), versus 9% (95% CI, 6 to 13) in the bone marrow group (P=0.002). The incidence of chronic GVHD at 2 years in the peripheral-blood group was 53% (95% CI, 45 to 61), as compared with 41% (95% CI, 34 to 48) in the bone marrow group (P=0.01). There were no significant between-group differences in the incidence of acute GVHD or relapse. We did not detect significant survival differences between peripheral-blood stem-cell and bone marrow transplantation from unrelated donors. Exploratory analyses of secondary end points indicated that peripheral-blood stem cells may reduce the risk of graft failure, whereas bone marrow may reduce the risk of chronic GVHD. (Funded by the National Heart, Lung, and Blood Institute-National Cancer Institute and others; number, NCT00075816.).
    New England Journal of Medicine 10/2012; 367(16):1487-96. · 54.42 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: The ability to distinguish increased platelet (PLT) destruction from PLT hypoproduction is important in the care of patients with marrow failure syndromes and patients receiving high-dose chemotherapy. The measurement of immature circulating PLTs based on RNA content using an automated counter is now feasible. This study evaluated the impact of recent PLT transfusion on measurement of immature PLT variables. STUDY DESIGN AND METHODS: The immature PLT fraction (IPF) and absolute immature PLT number (AIPN) were measured using a hematology analyzer before and after PLT transfusion in nine transfusion-dependent patients with marrow failure secondary to aplastic anemia, myelodysplasia, or transplantation conditioning. IPF and AIPN were also measured serially over 5 days of storage in three plateletpheresis components collected from normal donors. RESULTS: PLT transfusion did not significantly change the mean AIPN in transfused patients. In contrast, IPF decreased significantly from 6.6 ± 4.6% on Day -1 to 2.3 ± 1.4% on Day 0 before returning to 4.3 ± 2.3% on Day +1. In the PLT component, AIPN and IPF% increased significantly over 5 days of storage, most likely due to an artifact of the staining and detection process for stored PLTs, no longer detected in vivo once the PLTs were transfused. CONCLUSION: PLT transfusion decreases the IPF due to the resultant increase in circulating PLT count. However, PLT transfusion does not change the circulating AIPN, validating this assay as a reflection of ongoing PLT production by the marrow in various clinical settings, regardless of proximity to PLT transfusion.
    Transfusion 10/2012; · 3.57 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: A long-term effect of hereditary hemochromatosis (HH) on aerobic exercise capacity (AEC) has not been well described. Forty-three HH and 21 volunteer control subjects who were asymptomatic underwent cardiopulmonary exercise testing using the Bruce protocol. AEC was assessed with minute ventilation (V(E)), oxygen uptake (V(O)(2)), and carbon dioxide production (V(CO)(2)) at baseline and at a follow-up assessment after 5 yrs. A paired t test was used for analyses of normality data; otherwise, Wilcoxon's signed rank-sum test was used. Thirty-three HH subjects and 18 volunteer control subjects returned for a repeat cardiopulmonary exercise testing at the fifth-year follow-up (80% overall return rate). At the fifth-year follow-up, AEC was not different between the two groups. Compared with baseline measurements, exercise time, peak V(O)(2), and the V(E)/V(CO)(2) slope did not differ statistically at the fifth-year follow-up between both groups. Iron depletion through phlebotomy for 5 yrs did not significantly affect AEC in newly diagnosed HH subjects at baseline (n = 14) and cardiac arrhythmias during exercise tended to decrease after 5 yrs of therapy in this group. The AEC of asymptomatic HH subjects treated using conventional therapy is not statistically affected by the disease during a 5-yr period.
    American journal of physical medicine & rehabilitation / Association of Academic Physiatrists 02/2012; 91(5):418-24. · 1.56 Impact Factor
  • Biology of Blood and Marrow Transplantation 02/2012; 18(2):S259-S260. · 3.35 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Iron depletion or deficiency in blood donors frequently results in deferrals for low hemoglobin (Hb), yet blood centers remain reluctant to dispense iron replacement therapy to donors. During a 39-month period, 1236 blood donors deferred for a Hb level of less than 12.5 g/dL and 400 nondeferred control donors underwent health history screening and laboratory testing (complete blood counts, iron studies). Iron depletion and deficiency were defined as a ferritin level of 9 to 19 and less than 9 µg/L in females and 18 to 29 and less than 18 µg/L in males. Deferred donors and iron-deficient control donors were given a 60-pack of 325-mg ferrous sulfate tablets and instructed to take one tablet daily. Another 60-pack was dispensed at all subsequent visits. In the low-Hb 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 or -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 gastrointestinal bleeding. No donors had malignancies or hemochromatosis. Iron depletion or deficiency was found in 53% of female and 61% of male low-Hb donors and in 39% of female and male control donors. Routine administration of iron replacement therapy is safe and effective and prevents the development of iron depletion and deficiency in blood donors.
    Transfusion 12/2011; 52(7):1566-75. · 3.57 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: 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 the present study, we examined the incidence of cardiac arrhythmia in cardiac asymptomatic subjects with HH (New York Heart Association functional class I) and compared it to that in age- and gender-matched normal volunteers. The 42 subjects with HH and the 19 normal control subjects were recruited through the National Heart, Lung, and Blood Institute-sponsored "Heart Study of Hemochromatosis." They completed 48-hour Holter electrocardiography ambulatory monitoring at the baseline evaluation. The subjects with HH were classified as newly diagnosed (group A) and chronically treated (group B) subjects. All subjects with HH had C282Y homozygosity, and the normal volunteers lacked any HFE gene mutations known to cause HH. Although statistically insignificant, the incidence of ventricular and supraventricular ectopy tended to be greater in the combined HH groups than in the controls. Supraventricular ectopy was more frequently noted in group B compared to in the controls (ectopy rate per hour 11.1 ± 29.9 vs 1.5 ± 3.5, p < 0.05, using the Kruskal-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 the group A subjects. No life-threatening arrhythmias were observed in our subjects with HH. In conclusion, our data suggest that the incidence of cardiac arrhythmias is, at most, marginally increased in asymptomatic subjects with HH. A larger clinical study is warranted to further clarify our observation.
    The American journal of cardiology 12/2011; 109(6):856-60. · 3.58 Impact Factor

Publication Stats

11k Citations
1,684.53 Total Impact Points


  • 1987–2014
    • National Institutes of Health
      • • Center for Clinical Research
      • • Chemical Biology Laboratory
      • • Branch of Surgery
      Maryland, United States
  • 1989–2013
    • National Institute of Allergy and Infectious Diseases
      • Laboratory of Immunoregulation
      Maryland, United States
  • 2012
    • Moffitt Cancer Center
      Tampa, Florida, United States
  • 2009–2012
    • University of Utah
      Salt Lake City, Utah, United States
  • 2011
    • University of Texas Medical Branch at Galveston
      • Department of Pathology
      Galveston, Texas, United States
  • 1999–2011
    • National Heart, Lung, and Blood Institute
      • Hematology Branch
      Maryland, United States
  • 2007
    • Virginia Commonwealth University
      • Department of Physical Therapy
      Richmond, VA, United States
  • 2005
    • National Human Genome Research Institute
      Maryland, United States
  • 2001–2005
    • Walter Reed Army Institute of Research
      Silver Spring, Maryland, United States
    • National Eye Institute
      Maryland, United States
  • 2002
    • The National Institute of Diabetes and Digestive and Kidney Diseases
      베서스다, Maryland, United States
  • 1988–2002
    • National Cancer Institute (USA)
      • Surgery Branch
      Bethesda, MD, United States
  • 2000
    • National Marrow Donor Program
      Minneapolis, Minnesota, United States
  • 1991
    • George Washington University
      • Children's National Medical Center
      Washington, Washington, D.C., United States