183 results on '"Eyster ME"'
Search Results
2. Increased liver decompensation risk with atypical hepatitis C virus antibody levels
- Author
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Goedert, JJ Hatzakis, A Maloney, EM Eyster, ME and Multicenter Hemophilia Cohort Stud
- Abstract
Knowledge of serum markers of Liver decompensation would facilitate care of patients with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infections. HCV load and anti-c33c and anti-NS5 levels did not distinguish 28 HCV- and HIV-positive predecompensation patients from 28 matched control patients, whereas more patients than controls had high anti-c100(p) and low anti-c22(p). In multivariate analysis, decompensation was associated with high anti-c100(p) titer (greater than or equal to 1:4050; odds ratio [OR], 3.4; 95% confidence interval [CI], 1.1-11.5) and low anti-c22(p) (
- Published
- 2000
3. Phenotypic expressions of CCR5-Delta 32/Delta 32 homozygosity
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Nguyen, GT, Carrington, M, Beeler, JA, Dean, M, Aledort, LM, Blatt, PM, Cohen, AR, DiMichele, D, Eyster, ME, Kessler, CM, Konkle, B, Leissinger, C, Luban, N, O'Brien, SJ, Goedert, JJ, O'Brien, TR, and University of Groningen
- Subjects
hepatitis C virus ,lymphocytes ,therapy ,hypertension ,HIV-1 INFECTION ,DELETION ALLELE ,viruses ,chemokine ,DISEASE PROGRESSION ,virus diseases ,receptors ,HUMAN IMMUNODEFICIENCY VIRUS ,GENE ,AIDS ,hemophilia ,CORECEPTOR ,HIV-1 ,CHEMOKINE RECEPTORS ,epidemiology ,genetics ,CCR5 ,RESISTANCE - Abstract
Objective: As blockade of CC-chemokine receptor 5 (CCR5) has been proposed as therapy for HIV-1, we examined whether the CCR5-Delta 32/Delta 32 homozygous genotype has phenotypic expressions other than those related to HIV-1. Design: Study subjects were white homosexual men or men with hemophilia who were not infected with HIV-1. In this study, 15 CCR5-Delta 32/Delta 32 homozygotes were compared with 201 CCR5 wild-type (+/+) subjects for a wide range of clinical conditions and laboratory assay results ascertained during prospective cohort studies and routine clinical care. CCR5-Delta 32 genotype was determined by polymerase chain reaction, followed by single-stranded conformational polymorphism analysis. Results: Hypertension and conditions attributable to hemophilia were the only diagnoses frequently found in clinical records of CCR5-Delta 32/Delta 32 study subjects. Based on blood pressure measurement and treatment history, CCR5-Delta 32/Delta 32 homozygotes had a 2.8-fold higher prevalence of hypertension than age-matched CCR5-+/+ study subjects (95% confidence interval [CI], 1.2-6.4; p = .01); none of the homozygotes had severe hypertension. Hematologic measures were generally similar across the genotypes, but total lymphocyte counts were similar to 20% higher in CCR5-Delta 32/Delta 32 study subjects than in CCR5-+/+ study subjects (p
- Published
- 1999
4. Serum HIV-1 RNA levels and time to development of AIDS in the multicenter hemophilia cohort study
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OBrien, TR Blattner, WA Waters, D Eyster, ME Hilgartner, MW Cohen, AR Luban, N Hatzakis, A Aledort, LM and Rosenberg, PS Miley, WJ Kroner, BL Goedert, JJ
- Abstract
Objective.-To determine if the long-term incidence of the acquired immunodeficiency syndrome (AIDS) is related to human immunodeficiency virus type 1 (HIV-1) RNA levels measured early in HIV-1 infection. Design.-Epidemiologic cohort study. Setting.-Five hemophilia treatment centers in the United States. Subjects.-A total of 165 subjects with hemophilia and HIV-1 infection (age at HIV-1 seroconversion, 1-66 years) followed from 1979 to 1995. Methods.-The HIV-1 RNA level was measured by polymerase chain reaction over a range of 200 to 1 million or more HIV-1 RNA copies/mL. in archived serum specimens collected 12 to 36 months (median, 27 months) after the estimated date of HIV-1 seroconversion. Kaplan-Meier methods were used to examine the risk of AIDS and proportional hazards models were used to estimate relative hazards. Results.-The HIV-1 RNA values were similar in subjects younger than 17 years at seroconversion (median, 5214 copies/mL) and those 18 to 34 years old (median, 4693 copies/mL), but higher in those 35 years or older (median, 12 069 copies/mL) (P=.02 compared with each younger group). At 10 years after seroconversion, the proportions of subjects with AIDS were 72% among subjects with 100 000 or more HIV-1 RNA copies/mL measured 12 to 36 months after HIV-1 seroconversion (n=9), 52% among subjects with 10 000 to 99 999 copies/mL (n=55), 22% among subjects with 1000 to 9999 copies/mL (n=82), and 0% among subjects with fewer than 1000 copies/mL (n=19) (P
- Published
- 1996
5. HUMAN-IMMUNODEFICIENCY-VIRUS (HIV) TYPE-1 INFECTION STATUS AND IN-VITRO SUSCEPTIBILITY TO HIV-INFECTION AMONG HIGH-RISK HIV-1 SERONEGATIVE HEMOPHILIACS
- Author
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LEDERMAN, MM, JACKSON, JB, KRONER, BL, WHITE, GC, EYSTER, ME, ALEDORT, LM, HILGARTNER, MW, KESSLER, CM, COHEN, AR, KIGER, KP, GOEDERT, JJ, and University of Groningen
- Subjects
AIDS ,DIFFERENTIAL SUSCEPTIBILITY ,LYMPHOCYTES - Abstract
Blood samples were obtained from 16 hemophiliacs who had a 50%-94% defined risk of human immunodeficiency virus (HIV type 1 infection on the basis of treatment history and from 14 controls not at risk for HIV infection. HIV-1 was not detected in any of 12 patient samples by cocultivation nor in 14 patient samples by the polymerase chain reaction. Peripheral blood cells from 7 seronegative hemophiliacs at highest risk of seroconversion (94%) were less susceptible to HIV-1 infection in vitro than were cells from healthy controls (P
- Published
- 1995
6. INCIDENCE OF LYMPHOMAS AND OTHER CANCERS IN HIV-INFECTED AND HIV-UNINFECTED PATIENTS WITH HEMOPHILIA
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RABKIN, CS HILGARTNER, MW HEDBERG, KW ALEDORT, LM and HATZAKIS, A EICHINGER, S EYSTER, ME WHITE, GC KESSLER, CM LEDERMAN, MM DEMOERLOOSE, P BRAY, GL COHEN, AR and ANDES, WA MANCOJOHNSON, M SCHRAMM, W KRONER, BL and BLATTNER, WA GOEDERT, JJ
- Subjects
virus diseases - Abstract
Objective. - To determine the types and rates of cancers occurring in excess in the presence of infection with the human immunodeficiency virus type 1 (HIV-1). Design. - Cohort analytic study of HIV-infected and HIV-uninfected subjects followed for up to 12 years. Setting. - Fifteen hemophilia treatment centers. Patients. - A total of 1701 patients with hemophilia, of whom 1065 (63%) were HIV-1 seropositive. Main Outcome Measures. -Morphologic classification and incidence rates of cancers. Main Results. - The incidence of non-Hodgkin’s lymphoma after HIV seroconversion averaged 0.15 case per 100 person-years (95% confidence interval [Cl], 0.08 to 0.25) and rose exponentially with increasing duration of HIV infection. Although the greatest absolute risk of lymphoma was in the oldest age group, the relative increase compared with general population rates was 38-fold in subjects 10 to 39 years old and 12-fold in older subjects (P
- Published
- 1992
7. Blood safety decisions, 1982 to 1986: perceptions and misconceptions
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Zuck, TF, primary and Eyster, ME, additional
- Published
- 1996
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8. Randomized study of didanosine monotherapy and combination therapy with zidovudine in hemophilic and nonhemophilic subjects with asymptomatic human immunodeficiency virus-1 infection. AIDS Clinical Trial Groups
- Author
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Ragni, MV, primary, Amato, DA, additional, LoFaro, ML, additional, DeGruttola, V, additional, Van Der Horst, C, additional, Eyster, ME, additional, Kessler, CM, additional, Gjerset, GF, additional, Ho, M, additional, and Parenti, DM, additional
- Published
- 1995
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9. Increasing hepatitis C virus RNA levels in hemophiliacs: relationship to human immunodeficiency virus infection and liver disease. Multicenter Hemophilia Cohort Study
- Author
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Eyster, ME, primary, Fried, MW, additional, Di Bisceglie, AM, additional, and Goedert, JJ, additional
- Published
- 1994
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10. Human immunodeficiency virus-related conditions in children and adults with hemophilia: rates, relationship to CD4 counts, and predictive value
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Eyster, ME, primary, Rabkin, CS, additional, Hilgartner, MW, additional, Aledort, LM, additional, Ragni, MV, additional, Sprandio, J, additional, White, GC, additional, Eichinger, S, additional, de Moerloose, P, additional, and Andes, WA, additional
- Published
- 1993
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11. Changing causes of death in Pennsylvania's hemophiliacs 1976 to 1991: impact of liver disease and acquired immunodeficiency syndrome [letter]
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Eyster, ME, primary, Schaefer, JH, additional, Ragni, MV, additional, Gorenc, TJ, additional, Shapiro, S, additional, Cutter, S, additional, Kajani, MK, additional, Abrams, J, additional, Barron, LE, additional, and Odenwelder, A, additional
- Published
- 1992
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12. Silent infections with human immunodeficiency virus type 1 are highly unlikely in multitransfused seronegative hemophiliacs [see comments]
- Author
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Gibbons, J, primary, Cory, JM, additional, Hewlett, IK, additional, Epstein, JS, additional, and Eyster, ME, additional
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- 1990
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13. The bleeding time is longer than normal in hemophilia
- Author
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Eyster, ME, Gordon, RA, and Ballard, JO
- Abstract
Bleeding times were performed on 71 hemophiliacs using the Simplate II device. Eight patients receiving Indocin or Motrin for hemophilic arthropathy were evaluated separately from the remaining 63 who had a mean bleeding time of 7.65 +/- 3.20 min (1 SD) compared to the control group of 5.35 +/- 1.49 min (p less than 0.005). No difference was found when 26 mild hemophiliacs who had received less than 10,000 U of clotting factor concentrate the previous year and no infusions in at least 3 mo were compared with 28 severe hemophiliacs who had received greater than 20,000 U of clotting factor concentrate the previous year and had been infused within 1 mo of testing. Ten patients (16%) had bleeding times greater than 10 min. Bleeding times remained prolonged on repeat evaluations in 7 of these patients, 3 of whom had mild disease and all of whom had normal platelet aggregations in response to arachidonic acid. We conclude that the bleeding time is longer than normal in hemophilia. This abnormality is not related to disease severity, recent transfusions, or the use of nonsteroidal antiinflammatory drugs.
- Published
- 1981
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14. Antibodies reactive with human T cell leukemia viruses in the serum of hemophiliacs receiving factor VIII concentrate
- Author
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Goedert, JJ, Sarngadharan, MG, Eyster, ME, Weiss, SH, Bodner, AJ, Gallo, RC, and Blattner, WA
- Abstract
The third member of the family of T cell leukemia viruses (HTLV III) has been proposed as the primary etiologic agent of the acquired immunodeficiency syndrome (AIDS). A high risk of AIDS has been reported among patients with hemophilia, particularly those with factor VIII deficiency who receive commercial clotting factor concentrates. In a prevalence survey conducted between September 1982 and April 1984, initial serum samples from 74% of hemophiliacs who had ever been treated with commercial factor VIII concentrate, 90% of those frequently treated with factor VIII concentrate, and 50% of those treated with both factor VIII and factor IX concentrates had antibodies reactive against antigens of HTLV III, compared with none of the hemophiliacs treated only with factor IX concentrate or volunteer donor plasma or cryoprecipitate. Two of the seropositive patients have developed AIDS-related illnesses, and a third patient died of bacterial pneumonia. One initially seronegative patient developed antibodies against HTLV III during the study and is currently well. The predominant antibody specificities appear directed against p24 and p41, the presumed core and envelope antigens of HTLV III, suggesting that factor VIII concentrate may transmit the p24 and p41 antigens of HTLV III. However, the presence of infectious retroviruses in clotting factor concentrates and the effectiveness of screening and viral neutralization procedures remain to be determined.
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- 1985
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15. Long-term follow-up of hemophiliacs with lymphocytopenia or thrombocytopenia
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Eyster, ME, Whitehurst, DA, Catalano, PM, McMillan, CW, Goodnight, SH, Kasper, CK, Gill, JC, Aledort, LM, Hilgartner, MW, and Levine, PH
- Abstract
Immunologic abnormalities resembling those seen in patients with the acquired immunodeficiency syndrome (AIDS) are frequently observed in multitransfused but otherwise healthy individuals with hemophilia. To determine whether there was clinical or laboratory evidence to suggest an abnormality of immunoregulation in persons with hemophilia before the recognition of AIDS, we examined data collected by the Hemophilia Study Group from 1975 to 1979 on 1,551 patients with factor VIII deficiency. The prevalence of lymphocytopenia and thrombocytopenia in patients over 5 years of age on entry was found to be 9.3% (94/1,013) and 5.0% (26/518), respectively. These rates were significantly different from a normal population (P less than .00001 and less than .0003). No cases meeting the definition of AIDS were noted during the study. However, on follow-up in 1984 of a cohort of 79 patients with thrombocytopenia or lymphocytopenia on two or more occasions during the study, eight patients (10%) with AIDS-related abnormalities, including idiopathic thrombocytopenic purpura, non-Hodgkin's lymphoma, generalized lymphadenopathy, and oral moniliasis without obvious cause were identified. Of the 79 patients, liver disease accounted for five of the ten deaths (12.6% mortality) observed during a minimum follow-up of five years after detection of cytopenia. Only one death was attributed to bleeding in the absence of liver disease. We conclude that (a) the frequency of lymphocytopenia and thrombocytopenia was increased in multitransfused factor VIII-deficient hemophiliacs before the advent of AIDS, and (b) persistent lymphocytopenia and thrombocytopenia appear to be strongly associated with liver disease, which was the leading cause of death in a cohort of hemophiliacs followed five or more years.
- Published
- 1985
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16. Identification of the molecular defect in the erythrocyte membrane skeleton of some kindreds with hereditary spherocytosis
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Goodman, SR, Shiffer, KA, Casoria, LA, and Eyster, ME
- Abstract
We have localized the molecular alteration in the membrane skeleton of two of four kindreds with hereditary spherocytosis (HS) to an alteration in the spectrin-protein-4.1 interaction due to a defective spectrin molecule. The defective spectrin-protein-4.1 interaction in these kindreds (referred to as type I HS) leads to a weakened spectrin- protein-4.1-actin ternary complex, which in turn may lead to the friable membrane skeleton and suggested membrane instability related to this disorder. Type I HS spectrin binds approximately 63% as much protein-4.1 as normal spectrin (with equal affinity). This defect does not correlate with splenic function or erythrocyte age in the circulation. However, the approximately 37% reduction in binding of protein-4.1 to HS spectrin approaches the theoretical value of 50% expected in this autosomal dominant disorder. All other type I membrane skeletal interactions (spectrin-syndein, spectrin heterodimer- heterodimer, syndein-band-3) were found to be normal. It would appear therefore that the defective HS spectrin-protein-4.1 interaction in type I hereditary spherocytosis may be the primary molecular defect rather than a secondary phenomena.
- Published
- 1982
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17. Central nervous system bleeding in hemophiliacs
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Eyster, ME, Gill, FM, Blatt, PM, Hilgartner, MW, Ballard, JO, and Kinney, TR
- Published
- 1978
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18. Carriers with excessively low factor VIII procoagulant activity (VIII AHF): a study of two unrelated families with mild hemophilia A
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Eyster, ME, Ladda, RL, and Bowman, HS
- Abstract
Two unrelated families are described with mild hemophilia A in whom six obligate carriers had unusually low VIII AHF levels. In each family, successive generations of males were affected with hemophilia A as determined by low VIII AHF in the presence of normal VIII AGN and VIII VWF levels. In the first family, two of five obligate carriers had low VIII AHF levels associated with clinical bleeding and one other had a history of bleeding. While receiving oral contraceptives, one of these two carriers was found to have a normal VIII AHF level. In the second family, four cousins below age 10 who were obligate carriers had significantly low VIII AHF levels, while a paternal aunt and paternal grandmother who were also obligate carriers had VIII AHF levels within the normal range. Hemorrhagic diathesis in multiple obligate carriers in these families is not readily explained by the Lyon hypothesis, and suggests that these families may be exmaples of an unusual allelic form of hemophilia A or that they may be transmitting several independent genes affecting VIII AHF levels. Our experience suggests that VIII AHF levels should be determined on all obligate or possible carriers prior to surgery to identify those individuals at risk for postoperative bleeding. Furthermore, it is suggested that hormonal therapy might be effective in the management of carriers with low levels of VIII AHF and clinical bleeding.
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- 1977
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19. IgE myeloma with osteoblastic lesions
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Rogers, JS 2d, Spahr, J, Judge, DM, Varano, LA, and Eyster, ME
- Abstract
A 69-yr-old man with persistent anemia had multiple myeloma with an IgE- type kappa M component and Bence Jones proteinuria. Bone x-rays revealed occasional lytic lesions associated with a diffuse sclerotic reaction throughout the skeleton. Special bone histologic studies utilizing tetracycline labeling, undercalcified sections, and microradiography confirmed active osteoblastic activity. This case was compared with the four previously reported cases of IgE myeloma, one of which also had osteosclerosis.
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- 1977
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20. 3-YEAR INCIDENCE OF AIDS IN 5 COHORTS OF HTLV-III-INFECTED RISK GROUP MEMBERS
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GOEDERT, JJ, BIGGAR, RJ, WEISS, SH, EYSTER, ME, MELBYE, M, WILSON, S, GINZBURG, HM, GROSSMAN, RJ, DIGIOLA, RA, SANCHEZ, WC, GIRON, JA, EBBESEN, P, GALLO, RC, BLATTNER, WA, GOEDERT, JJ, BIGGAR, RJ, WEISS, SH, EYSTER, ME, MELBYE, M, WILSON, S, GINZBURG, HM, GROSSMAN, RJ, DIGIOLA, RA, SANCHEZ, WC, GIRON, JA, EBBESEN, P, GALLO, RC, and BLATTNER, WA
- Published
- 1986
21. RISK OF AIDS AFTER HERPES-ZOSTER
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MELBYE, M, GROSSMAN, RJ, GOEDERT, JJ, EYSTER, ME, BIGGAR, RJ, MELBYE, M, GROSSMAN, RJ, GOEDERT, JJ, EYSTER, ME, and BIGGAR, RJ
- Published
- 1987
22. Pennsylvania state-wide hemophilia program: summary of immediate reactions with the use of factor VIII and factor IX concentrate
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Prager, D, primary, Djerassi, I, additional, Eyster, ME, additional, Gill, FM, additional, Kajani, NK, additional, Lewis, JH, additional, Lusch, C, additional, Rice, S, additional, and Shapiro, SS, additional
- Published
- 1979
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23. Combined factor V-VIII deficiency: a case report with studies of factor V and VIII activation by thrombin
- Author
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Hultin, MB, primary and Eyster, ME, additional
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- 1981
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24. DOAC compared with warfarin for VTE in low weight patients: A retrospective cohort study conducted through the VENUS network.
- Author
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Martin KA, Lancki N, Kreuziger LB, Li C, Eyster ME, Sanfilippo K, Woller SC, and Rosovsky RP
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- Humans, Retrospective Studies, Anticoagulants therapeutic use, Rivaroxaban therapeutic use, Factor Xa Inhibitors therapeutic use, Administration, Oral, Warfarin therapeutic use, Venous Thromboembolism drug therapy
- Abstract
Competing Interests: Declaration of competing interest The following authors declare no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper: CL, MEE, KS, SW, LBK. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: RPR received research grants to her institution from BMS and Janssen and is a consultant to BMS and Janssen. KAM received a research grant to her institution from Janssen Scientific Affairs.
- Published
- 2023
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25. Correction to: DOAC compared with warfarin for VTE in patients with obesity: a retrospective cohort study conducted through the VENUS network.
- Author
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Martin KA, Lancki N, Li C, Eyster ME, Sanfilippo K, Woller IA, Woller SC, Kreuziger LB, and Rosovsky RP
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- 2023
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26. DOAC compared with warfarin for VTE in patients with obesity: a retrospective cohort study conducted through the VENUS network.
- Author
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Martin KA, Lancki N, Li C, Eyster ME, Sanfilippo K, Woller IA, Woller SC, Kreuziger LB, and Rosovsky RP
- Subjects
- Adult, Humans, Anticoagulants adverse effects, Retrospective Studies, Rivaroxaban adverse effects, Hemorrhage chemically induced, Hemorrhage drug therapy, Obesity complications, Obesity drug therapy, Administration, Oral, Warfarin adverse effects, Venous Thromboembolism etiology, Venous Thromboembolism chemically induced
- Abstract
The effectiveness and safety of direct oral anticoagulants (DOAC) compared with warfarin remains uncertain in obese patients. We assessed the comparative effectiveness and safety of DOACs with warfarin for the treatment of VTE among obese patients. This multi-center retrospective cohort study included adults with a BMI ≥ 35 kg/m
2 or weight ≥ 120 kg prescribed either DOAC (apixaban, dabigatran, edoxaban, rivaroxaban) or warfarin for a VTE diagnosis. The primary outcome was the 12-month rate of recurrent VTE. The secondary outcome was the 12-month rate of major bleeding. Among 5626 patients, 67% were prescribed warfarin and 33% were prescribed a DOAC. The 12-month VTE recurrence rate was 3.6% (67/1823) for patients treated with DOAC compared with 3.8% (143/3664) for patients treated with warfarin [odds ratio for recurrent VTE on warfarin versus DOAC (OR) (95% CI).07 (0.80, 1.45)]. The 12-month major bleeding rate was 0.5% (10/1868) for patients on DOAC versus 2.4% (89/3758) on warfarin [OR 4.25 (2.19, 8.22)]. Similar proportions of recurrent VTE occurred across BMI thresholds on DOAC and warfarin: for BMI ≥ 35 kg/m2 (N = 5412), 3.6% versus 3.8%, respectively [OR 1.08 (0.80, 1.46)]; for BMI ≥ 40 kg/m2 (N = 2321), 4.4% versus 3.5%, respectively [OR 0.80 (0.51, 1.26)]; and for BMI ≥ 50 kg/m2 (N = 560), 3.1% versus 3.7%, respectively [OR 1.18 (0.39, 3.56)]. Similar proportions of recurrent VTE occurred in patients with obesity treated for VTE with DOACs and warfarin. DOACs were associated with lower major bleeding compared to warfarin in patients with obesity and VTE., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)- Published
- 2023
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27. Physician perceptions and use of reduced-dose direct oral anticoagulants for extended phase venous thromboembolism treatment.
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Groat D, Martin KA, Rosovsky RP, Sanfilippo KM, Gaddh M, Kreuziger LB, Eyster ME, and Woller SC
- Abstract
Background: The direct oral anticoagulants (DOACs), apixaban and rivaroxaban, have been studied for extended-phase treatment of venous thromboembolism (VTE). Yet, scant evidence exists surrounding clinician practice and decision-making regarding dose reduction., Aims: Report clinician practice and characteristics surrounding dose reduction of DOACs for extended-phase VTE treatment., Methods: We conducted a 16-question REDCap survey between July 14, 2021, and September 13, 2021, among ISTH 2021 Congress attendees and on Twitter. We explored factors associated with dose reduction using logistic regression. We used k-means clustering to identify distinct groups of dose-reduction decision-making. Random forest analysis explored demographics with respect to identified groups., Results: Among 171 respondents, most were attending academic physicians from North America. Clinicians who treated larger volumes of patients had higher odds of dose reduction. We identified five clusters that showed distinct patterns of behavior regarding dose reduction. Cluster 1 rarely dose reduces and likely prescribes rivaroxaban over apixaban; cluster 2 dose reduces frequently, does not consider age when dose-reducing, is least likely to temporarily reescalate dosing, and prescribes apixaban and rivaroxaban equally; cluster 3 dose reduces <50% of the time, and temporarily reescalates dosing during increased VTE risk; cluster 4 dose reduces frequently, temporarily reescalates dosing, and is most likely to prescribe apixaban over rivaroxaban; and cluster 5 dose reduces most frequently, and takes the fewest risk factors into consideration when deciding to dose reduce., Conclusions: Most clinicians elect to dose-reduce DOACs for extended-phase anticoagulation. The likelihood of a clinician to dose reduce increases with volume of patients treated. Clinician prescribing patterns cluster around VTE risk factors as well as reescalation during high-risk periods., (© 2022 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH).)
- Published
- 2022
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28. Postoperative bleeding complications in patients with hemophilia undergoing major orthopedic surgery: A prospective multicenter observational study.
- Author
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Kleiboer B, Layer MA, Cafuir LA, Cuker A, Escobar M, Eyster ME, Kraut E, Leavitt AD, Lentz SR, Quon D, Ragni MV, Thornhill D, Wang M, Key NS, and Buckner TW
- Subjects
- Anticoagulants therapeutic use, Humans, Postoperative Complications prevention & control, Postoperative Hemorrhage prevention & control, Prospective Studies, Retrospective Studies, Antifibrinolytic Agents, Arthroplasty, Replacement, Hip adverse effects, Hemophilia A complications, Hemophilia A drug therapy, Venous Thromboembolism prevention & control
- Abstract
Background: Persons with hemophilia (PWH) are at risk for chronic hemophilic arthropathy (HA). Joint replacement surgery may be used to relieve intractable pain and/or restore joint function., Objectives: This multicenter, prospective, observational cohort study evaluated the rate of bleeding during the postoperative period after total hip (THA) or knee arthroplasty (TKA)., Patients/methods: We included PWH of any severity ≥18 years of age who were undergoing THA or TKA. Clinical decisions were made at the discretion of the treating physician according to local standards of care. Clinical data were prospectively recorded. Major bleeding was defined as bleeding in a critical site, bleeding that resulted in either a 2 g/dl or greater decrease in hemoglobin during any 24-h period, or transfusion of two or more units of packed red blood cells., Results: One hundred thirty-one procedures (98 TKA and 33 THA) were performed, 39 (29.8%) of which were complicated by major bleeding, including 46% of THA and 25% of TKA. The risk of major bleeding was increased in THA compared to TKA (OR 2.50, p = .05), and by the presence of an inhibitor (OR 4.29, p = .04), increased BMI (OR 4.49 and 6.09 for overweight and obese, respectively, compared to normal BMI, each p < .01), and non-use of an antifibrinolytic medication (OR 3.00, p = .03). Neither continuous clotting factor infusion (versus bolus infusion) nor pharmacologic thromboprophylaxis were associated with bleeding risk., Conclusions: The bleeding risk remains substantial after THA and TKA in PWH, despite factor replacement. Use of antifibrinolytic medications is associated with decreased risk., (© 2022 International Society on Thrombosis and Haemostasis.)
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- 2022
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29. Multiyear Factor VIII Expression after AAV Gene Transfer for Hemophilia A.
- Author
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George LA, Monahan PE, Eyster ME, Sullivan SK, Ragni MV, Croteau SE, Rasko JEJ, Recht M, Samelson-Jones BJ, MacDougall A, Jaworski K, Noble R, Curran M, Kuranda K, Mingozzi F, Chang T, Reape KZ, Anguela XM, and High KA
- Subjects
- Adolescent, Adult, Follow-Up Studies, Genotype, Glucocorticoids adverse effects, Glucocorticoids therapeutic use, Hemophilia A genetics, Hemophilia A prevention & control, Hepatocytes metabolism, Humans, Immunosuppression Therapy, Male, Middle Aged, Young Adult, Dependovirus, Factor VIII genetics, Factor VIII metabolism, Genetic Therapy, Genetic Vectors, Hemophilia A blood
- Abstract
Background: The goal of gene therapy for patients with hemophilia A is to safely impart long-term stable factor VIII expression that predictably ameliorates bleeding with the use of the lowest possible vector dose., Methods: In this phase 1-2 trial, we infused an investigational adeno-associated viral (AAV) vector (SPK-8011) for hepatocyte expression of factor VIII in 18 men with hemophilia A. Four dose cohorts were enrolled; the lowest-dose cohort received a dose of 5 × 10
11 vector genomes (vg) per kilogram of body weight, and the highest-dose cohort received 2 × 1012 vg per kilogram. Some participants received glucocorticoids within 52 weeks after vector administration either to prevent or to treat a presumed AAV capsid immune response. Trial objectives included evaluation of the safety and preliminary efficacy of SPK-8011 and of the expression and durability of factor VIII., Results: The median safety observation period was 36.6 months (range, 5.5 to 50.3). A total of 33 treatment-related adverse events occurred in 8 participants; 17 events were vector-related, including 1 serious adverse event, and 16 were glucocorticoid-related. Two participants lost all factor VIII expression because of an anti-AAV capsid cellular immune response that was not sensitive to immune suppression. In the remaining 16 participants, factor VIII expression was maintained; 12 of these participants were followed for more than 2 years, and a one-stage factor VIII assay showed no apparent decrease in factor VIII activity over time (mean [±SD] factor VIII activity, 12.9±6.9% of the normal value at 26 to 52 weeks when the participants were not receiving glucocorticoids vs. 12.0±7.1% of the normal value at >52 weeks after vector administration; 95% confidence interval [CI], -2.4 to 0.6 for the difference between matched pairs). The participants had a 91.5% reduction (95% CI, 88.8 to 94.1) in the annualized bleeding rate (median rate, 8.5 events per year [range, 0 to 43.0] before vector administration vs. 0.3 events per year [range, 0 to 6.5] after vector administration)., Conclusions: Sustained factor VIII expression in 16 of 18 participants who received SPK-8011 permitted discontinuation of prophylaxis and a reduction in bleeding episodes. No major safety concerns were reported. (Funded by Spark Therapeutics and the National Heart, Lung, and Blood Institute; ClinicalTrials.gov numbers, NCT03003533 and NCT03432520.)., (Copyright © 2021 Massachusetts Medical Society.)- Published
- 2021
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30. Diagnosing dehydrated hereditary stomatocytosis due to a KCNN4 Gardos channel mutation: understanding challenges through study of a multi-generational family.
- Author
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Waldstein S, Arnold-Croop S, Carrel L, and Eyster ME
- Abstract
Competing Interests: The authors have declared no conflict of interest.
- Published
- 2021
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31. Prothrombotic variants as modifiers of clinical phenotype in four related individuals with haemophilia A.
- Author
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Carrel L, Arnold-Croop S, Achtermann T, Chen F, Cheng Y, Liu D, and Eyster ME
- Subjects
- Humans, Phenotype, Hemophilia A complications, Hemophilia A genetics
- Published
- 2021
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- View/download PDF
32. Investigation of discordant phenotype in mild Hemophilia A using whole exome sequencing.
- Author
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Cygan PH, Arnold-Croop SE, Weidman EA, Chen F, Liu DJ, Eyster ME, and Carrel L
- Subjects
- Factor VIII genetics, Humans, Phenotype, Hemophilia A genetics, Exome Sequencing
- Abstract
Competing Interests: Declaration of competing interest The authors state that they had no interests which might be perceived as posing a conflict or bias. M.E. Eyster has received research support from Bayer, Baxalta, Spark Therapeutics, Novo Nordisk, and Sanofi.
- Published
- 2020
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33. Total knee replacement with and without emicizumab: a unique comparison of perioperative management.
- Author
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Evans MS, Davis C, and Eyster ME
- Published
- 2020
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34. A novel type 2N VWF gene mutation: a case report.
- Author
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Evans MS and Eyster ME
- Subjects
- Diagnosis, Differential, Genetic Testing, Hemorrhage, Humans, Male, Mutation, Hemophilia A diagnosis, von Willebrand Disease, Type 2 diagnosis, von Willebrand Factor genetics
- Abstract
: Men and boys who present with bleeding associated with low factor VIII levels and normal von Willebrand studies are assumed to have hemophilia A until proven otherwise. However, routinely available coagulation assays cannot easily distinguish mild hemophilia A from the 2N variant of von Willebrand disease. We present a case that highlights the difficulties of recognizing this diagnosis, the role of genetic testing, and the identification of a 2N variant that has not been previously described.
- Published
- 2018
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35. A cross-sectional analysis of cardiovascular disease in the hemophilia population.
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Sood SL, Cheng D, Ragni M, Kessler CM, Quon D, Shapiro AD, Key NS, Manco-Johnson MJ, Cuker A, Kempton C, Wang TF, Eyster ME, Kuriakose P, von Drygalski A, Gill JC, Wheeler A, Kouides P, Escobar MA, Leissinger C, Galdzicka S, Corson M, Watson C, and Konkle BA
- Subjects
- Aged, Cross-Sectional Studies, Female, Hemophilia A complications, Hemophilia B complications, Humans, Male, Middle Aged, Electrocardiography, Hemophilia A epidemiology, Hemophilia B epidemiology, Myocardial Infarction epidemiology, Myocardial Infarction etiology, Myocardial Infarction physiopathology, Stroke epidemiology, Stroke etiology, Stroke physiopathology
- Abstract
Men with hemophilia were initially thought to be protected from cardiovascular disease (CVD), but it is now clear that atherothrombotic events occur. The primary objective of the CVD in Hemophilia study was to determine the prevalence of CVD and CVD risk factors in US older men with moderate and severe hemophilia and to compare findings with those reported in age-comparable men in the Atherosclerosis Risk in Communities (ARIC) cohort. We hypothesized if lower factor levels are protective from CVD, we would see a difference in CVD rates between more severely affected and unaffected men. Beginning in October 2012, 200 patients with moderate or severe hemophilia A or B (factor VIII or IX level ≤ 5%), aged 54 to 73 years, were enrolled at 19 US hemophilia treatment centers. Data were collected from patient interview and medical records. A fasting blood sample and electrocardiogram (ECG) were obtained and assayed and read centrally. CVD was defined as any angina, any myocardial infarction by ECG or physician diagnosis, any self-reported nonhemorrhagic stroke or transient ischemic attack verified by physicians, or any history of coronary bypass graft surgery or coronary artery angioplasty. CVD risk factors were common in the population. Compared with men of similar age in the ARIC cohort, patients with hemophilia had significantly less CVD (15% vs 25.8%; P < .001). However, on an individual patient level, CVD events occur and efforts to prevent cardiovascular events are warranted. Few men were receiving secondary prophylaxis with low-dose aspirin, despite published opinion that it can be used safely in this patient population., (© 2018 by The American Society of Hematology.)
- Published
- 2018
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- View/download PDF
36. Development of an inhibitor in a man with mild haemophilia A.
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Evans MS and Eyster ME
- Subjects
- Aged, 80 and over, Factor VIII immunology, Factor VIII therapeutic use, Humans, Male, Hemophilia A drug therapy, Hemophilia A immunology, Isoantibodies immunology
- Published
- 2017
- Full Text
- View/download PDF
37. Development of a novel automated screening method for detection of FVIII Inhibitors.
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Evans MS, Donaldson KJ, and Eyster ME
- Subjects
- Automation, Blood Coagulation Tests, Factor VIII analysis, Factor VIII immunology, Female, Hemophilia A diagnosis, Humans, Male, Predictive Value of Tests, Sensitivity and Specificity, Autoantibodies blood, Factor VIII antagonists & inhibitors, High-Throughput Screening Assays methods
- Abstract
Introduction: Factor VIII activity is routinely determined by measuring the activated partial thromboplastin time (aPTT) of a patient plasma sample and determining percent activity from a standard curve. To maximize the detection of a clotting factor inhibitor, a subjective assessment of parallelism of a patient curve compared with a standard curve is performed. We developed and validated an automated objective method to assess parallelism as a rapid screening tool for detection of an inhibitor to factor VIII during routine FVIII assays., Methods: We performed FVIII assays on a subset of FVIII-deficient patients with hemophilia A with and without inhibitors. Utilizing a ratio of the slopes from parallelism curves obtained by an independent Microsoft excel program in patients compared with a normal standard curve, we determined a cutoff ratio predictive for presence of an inhibitor., Results: A cutoff ratio of patient to control slopes of <0.45 for the detection of an inhibitor to FVIII was 100% sensitive and 91.6% specific, with a positive predictive value of 92.3% and a negative predictive value of 100%., Conclusion: Utilizing a ratio of the slopes from parallelism curves in patients with and without an inhibitor, we developed and validated a rapid, automated, and objective method to assess parallelism as an added screening tool for detection of an inhibitor to factor VIII during routine FVIII assays on a STAGO-based coagulation platform. This simple automated method has the potential to detect inhibitors to other clotting factors., (© 2017 John Wiley & Sons Ltd.)
- Published
- 2017
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38. Safety and efficacy of BAY 94-9027, a prolonged-half-life factor VIII.
- Author
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Reding MT, Ng HJ, Poulsen LH, Eyster ME, Pabinger I, Shin HJ, Walsch R, Lederman M, Wang M, Hardtke M, and Michaels LA
- Subjects
- Adolescent, Adult, Aged, Body Weight, Child, Drug Administration Schedule, Half-Life, Humans, Male, Middle Aged, Patient Safety, Protein Domains, Severity of Illness Index, Treatment Outcome, Young Adult, Factor VIII pharmacology, Hemophilia A drug therapy, Hemorrhage drug therapy, Polyethylene Glycols pharmacology
- Abstract
Essentials Recombinant factor VIII BAY 94-9027 conjugates in a site-specific manner with polyethylene glycol. BAY 94-9027 was given to patients with severe hemophilia A as prophylaxis and to treat bleeds. BAY 94-9027 prevented bleeds at dose intervals up to every 7 days and effectively treated bleeds. BAY 94-9027 treatment was mainly well tolerated and no patient developed factor VIII inhibitors. Click to hear Dr Tiede's perspective on half-life extended factor VIII for the treatment of hemophilia A SUMMARY: Background BAY 94-9027 is a B-domain-deleted prolonged-half-life recombinant factor VIII (FVIII) that conjugates in a site-specific manner with polyethylene glycol. Objective Assess efficacy and safety of BAY 94-9027 for prophylaxis and treatment of bleeds in patients with severe hemophilia A. Patients/methods In this multinational, phase 2/3, partially randomized, open-label trial, men aged 12-65 years with FVIII < 1% and ≥ 150 exposure days to FVIII received BAY 94-9027 for 36 weeks on demand or prophylactically at intervals determined following a 10-week run-in period on 25 IU kg
-1 body weight two times per week. Patients with > 1 bleed during the run-in subsequently received 30-40 IU kg-1 two times per week; patients with ≤ 1 bleed were eligible for randomization to every-5-days (45-60 IU kg-1 ) or every-7-days (60 IU kg-1 ) prophylaxis (1 : 1) for 26 additional weeks until randomization arms were filled. Patients who were eligible but not randomized continued twice-weekly prophylaxis. The primary efficacy outcome was annualized bleeding rate (ABR). Results The intent-to-treat population included 132 patients (prophylaxis, n = 112; on demand, n = 20). Median ABR (quartile [Q1; Q3]) for patients treated two times per week who were not eligible for randomization (n = 13) improved after dose increase (17.4 [14.3; 26.0] to 4.1 [2.0; 10.6]). Median ABR for patients randomized to every-5-days treatment (n = 43) was 1.9 (0; 4.2), similar to patients eligible for randomization but who continued treatment two times per week (n = 11). Median ABR for 32/43 patients (74%) who continued every-7-days prophylaxis until study end was 0.96 (0.0; 4.3). Six hundred and thirty-six of 702 bleeds (90.6%) were controlled with ≤ 2 infusions. No patient developed a FVIII inhibitor. Conclusions BAY 94-9027 prevented bleeding across three individually tailored dose regimens and was effective for treatment of bleeds., (© 2016 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.)- Published
- 2017
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39. Moderate X-chromosome inactivation skewing underlies factor VIII activity in symptomatic carriers from a family with mild haemophilia A.
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Cygan PH, Carrel L, and Eyster ME
- Subjects
- Humans, Factor VIII genetics, Hemophilia A genetics, X Chromosome Inactivation genetics
- Published
- 2016
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40. Long term survival in persons with hemophilia and chronic hepatitis C: 40 year outcomes of a large single center cohort.
- Author
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Eyster ME, Kong L, Li M, and Schreibman IR
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Antiviral Agents therapeutic use, Child, Child, Preschool, Cohort Studies, Disease Progression, Female, Follow-Up Studies, HIV Infections mortality, Hemophilia A therapy, Hemorrhage, Hepatitis C, Chronic mortality, Humans, Infant, Male, Middle Aged, Survival Rate, Treatment Outcome, Young Adult, von Willebrand Diseases, HIV Infections drug therapy, Hemophilia A complications, Hepatitis C, Chronic drug therapy
- Abstract
We studied the course of chronic HCV infections in a cohort of 222 persons with hemophilia (PWH) and von Willebrand disease followed at our center since 1973. Twenty two (10%) developed end stage liver disease (ESLD). Forty years after HCV infection, cumulative incidence of ESLD was 12.3% and overall survival was 45.5%. Those who were infected with HCV only (n = 100) had a survival of 75.2%, while those infected with HIV (n = 122) had a survival of 24% (P < 0.001). Survivals were significantly longer for those infected with HCV at younger age (< 15 years) compared to those infected over age 30 years (P = 0.014). Cause specific deaths for ESLD and bleeding were 8.8% and 8.3% respectively. For HIV negative subjects, the annual hazard of death from ESLD and bleeding was near zero for the first 10 years, and then rose slowly over the next 20 years to 0.4/100py for ESLD and 0.2/100py for bleeding. Sixty subjects completed 79 treatment episodes. Sustained viral response rates increased from 7/21 (33%) between 1990 and 2001, to 17/29 (58%) between 2002 and 2011, and to 27/29 (93%), since 2012 with the advent of the directly acting antiviral agents. These results confirm the very slow ESLD progression rate in HIV negative PWH. However, the risk of death from both ESLD and bleeding increases steadily with longer duration of HCV infection. More aggressive surveillance to detect those with early fibrosis is needed now that curative treatment is possible in >95% of individuals. Am. J. Hematol. 91:E335-E340, 2016. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)
- Published
- 2016
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41. Prospective, multicenter study of postoperative deep-vein thrombosis in patients with haemophilia undergoing major orthopaedic surgery.
- Author
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Buckner TW, Leavitt AD, Ragni M, Kempton CL, Eyster ME, Cuker A, Lentz SR, Ducore J, Leissinger C, Wang M, and Key NS
- Subjects
- Adult, Arthroplasty, Replacement, Hip adverse effects, Arthroplasty, Replacement, Knee adverse effects, Cohort Studies, Hemophilia A therapy, Hemophilia B therapy, Humans, Male, Middle Aged, Postoperative Complications prevention & control, Postoperative Hemorrhage etiology, Postoperative Hemorrhage prevention & control, Prospective Studies, Venous Thromboembolism etiology, Venous Thromboembolism prevention & control, Venous Thrombosis diagnostic imaging, Venous Thrombosis prevention & control, Hemophilia A complications, Hemophilia A surgery, Hemophilia B complications, Hemophilia B surgery, Postoperative Complications etiology, Venous Thrombosis etiology
- Abstract
Perioperative clotting factor replacement is administered to reverse the inherent haemostatic defect in persons with haemophilia (PWH), potentially increasing their risk for developing venous thromboembolism (VTE) postoperatively. It was our objective to determine the prevalence of VTE in PWH undergoing total hip or knee arthroplasty (THA, TKA). Patients with haemophilia A or B who underwent THA or TKA were enrolled in this prospective, multicentre observational cohort study. Lower extremity venous duplex ultrasound was performed prior to surgery and 4-6 weeks after surgery. Eleven centres enrolled 51 subjects, 46 of whom completed the study. Six subjects (13.0 %) were treated with bypass agents perioperatively; the remaining 40 subjects received factor VIII or IX replacement. Intermittent pneumatic compression devices were utilised postoperatively in 23 subjects (50 %), and four subjects (8.7 %) also received low-molecular-weight heparin prophylaxis. One subject (2.2 %) with moderate haemophilia A was diagnosed with symptomatic distal deep-vein thrombosis (DVT) on day 6 following TKA. One subject (2.2 %) with severe haemophilia A was diagnosed with pulmonary embolism on day 9 following bilateral TKA. No subjects had asymptomatic DVT. Eighteen subjects (39.1 %) had major bleeding, and three subjects (6.5 %) experienced minor bleeding. The observed prevalence of ultrasound-detectable, asymptomatic DVT in PWH following TKA or THA in this study was low, but the incidence of symptomatic VTE (4.3 %, 95 % CI, 0.5-14.8 %) appeared similar to the estimated incidence in the general population without thromboprophylaxis.
- Published
- 2016
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42. Anemia and the Need for Intravenous Iron Infusion after Roux-en-Y Gastric Bypass.
- Author
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Kotkiewicz A, Donaldson K, Dye C, Rogers AM, Mauger D, Kong L, and Eyster ME
- Abstract
The frequency of anemia, iron deficiency, and the long-term need for IV iron following Roux-en-y gastric bypass (RYGB) surgery has not been well characterized. Three-hundred and nineteen out of 904 consecutive subjects who underwent RYGB at Penn State Hershey Medical Center from 1999 to 2006 met the inclusion criteria for a preoperative complete blood count (CBC) and at least one CBC >6 months following surgery. Cumulative incidence of anemia 7 years post procedure was 58%. Menstruation status and presence of preoperative anemia were predictive of anemia by univariate analysis and multivariable Cox regression (P = 0.0014 and 0.044, respectively). Twenty-seven subjects, primarily premenopausal women, representing 8.5% of the cohort and 22% of the 122 anemic subjects, needed intravenous (IV) iron a mean of 51 months postoperatively for anemia unresponsive or refractory to oral iron. The risk for development of anemia necessitating IV iron therapy following RYGB is highest in menstruating women and continues to increase for many years, even in post-menopausal women. Well-designed prospective studies are needed to identify the incidence of iron deficiency anemia and the patient populations at increased risk for requiring IV iron replacement after RYGB surgery.
- Published
- 2015
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43. Evaluation of von Willebrand factor phenotypes and genotypes in Hemophilia A patients with and without identified F8 mutations.
- Author
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Boylan B, Rice AS, De Staercke C, Eyster ME, Yaish HM, Knoll CM, Bean CJ, and Miller CH
- Subjects
- Adolescent, Adult, Biomarkers blood, Blood Coagulation Tests, Case-Control Studies, Child, DNA Mutational Analysis, Factor VIII metabolism, Genetic Predisposition to Disease, Hemophilia A blood, Hemophilia A diagnosis, Hemorrhage blood, Hemorrhage diagnosis, Hemorrhage genetics, Heterozygote, Homozygote, Humans, Male, Phenotype, Predictive Value of Tests, Protein Binding, United States, Young Adult, von Willebrand Factor metabolism, Blood Coagulation genetics, Factor VIII genetics, Hemophilia A genetics, Mutation, von Willebrand Factor genetics
- Abstract
Background: Hemophilia A (HA) is an X-linked bleeding disorder caused by a deficiency in factor VIII (FVIII). von Willebrand disease (VWD) is characterized by a quantitative or qualitative defect in von Willebrand factor (VWF). Patients with VWD with severely low VWF or VWD Type 2N (VWD2N), a VWD subtype distinguished by defective VWF binding to FVIII, may have reduced FVIII levels secondary to their VWD. These patients superficially resemble patients with HA and pose a potential for misdiagnosis., Objectives: To investigate the unexplained cause of bleeding in HA patients without known FVIII mutations by assessing plasma VWF antigen (VWF:Ag), FVIII binding capacities and VWF genotypes., Patients/methods: Thirty-seven of 1027 patients with HA studied as part of the Hemophilia Inhibitor Research Study lacked identifiable F8 mutations. These patients (cases) and 73 patients with identified F8 mutations (controls) were evaluated for VWF:Ag, a patient's VWF capacity to bind FVIII (VWF:FVIIIB) and VWF sequence., Results: Four cases had VWF:Ag < 3 IU dL(-1) and VWF mutations consistent with Type 3 VWD. Six cases and one control were heterozygous for mutations previously reported to cause Type 1 VWD (VWD1) (n = five cases and one control) or predicted to be deleterious by Polyphen2 and SIFT prediction tools (n = 1 case). One control had VWF:Ag < 30 IU dL(-1) and seven patients (four cases and three controls), including two cases who were heterozygous for a known VWD2N mutation, had reduced VWF:FVIIIB., Conclusions: These data emphasize that some patients diagnosed with HA require VWF assessments in order to achieve a comprehensive diagnosis and an optimal treatment strategy., (© 2015 International Society on Thrombosis and Haemostasis.)
- Published
- 2015
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44. Correlates of high hepatitis C virus RNA load in a cohort of HIV-negative and HIV-positive individuals with haemophilia.
- Author
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Gadalla SM, Preiss LR, Eyster ME, and Goedert JJ
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Cohort Studies, HIV Infections blood, HIV Infections drug therapy, Hemophilia A blood, Hepatitis C blood, Humans, Liver Function Tests, Logistic Models, Lymphocyte Count, Male, Middle Aged, Platelet Count, Viral Load, Viremia blood, Viremia virology, Young Adult, HIV isolation & purification, HIV Infections virology, Hemophilia A virology, Hepacivirus genetics, Hepatitis C virology, RNA, Viral blood
- Abstract
Hepatitis C virus (HCV) treatment failure and disease progression are more likely with high HCV-RNA load. Correlates of high HCV-RNA load in individuals with haemophilia are largely unknown. Among 1266 interferon naïve HCV-infected individuals with haemophilia, we compared those with high (> 2 x 10⁶ HCV-RNA copies/mL) to lower viral load, overall and stratifying on HIV co-infection status using logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI). Overall, high HCV load was independently associated with longer duration of HCV infection (P(trend)=0.0001), body mass index ≥ 25 kg/m² (OR=1.4, 95% CI=1.1-1.9), and HIV co-infection (OR=1.4, 95% CI=1.0-1.8). Among 795 HIV-negative participants, high HCV-RNA load was associated with older age at HCV acquisition (OR=1.9 for > 15 years vs ≤ 2 years, P(trend)=0.008), and lower AST/platelet ratio (P(trend)=0.01), in addition to longer duration of HCV infection (P(trend)=0.0008), and body mass index ≥ 25 kg/m² (OR=1.6, P=0.005). Among 471 HIV-positive individuals, anti-retroviral therapy (ART) was the only variable associated with high HCV-RNA load (OR=1.8, CI=1.1-2.9 for combination ART; OR=1.8, CI=0.9-3.4, for other ART vs no treatment). High HCV-RNA load with haemophilia is more likely with longer duration of infection, older age at infection, higher body mass index, and antiretroviral therapy. These findings may help identify individuals at increased risk of HCV treatment failure and progression to end-stage liver disease., (© 2010 Blackwell Publishing Ltd.)
- Published
- 2011
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45. Coping with the HIV epidemic 1982-2007: 25-year outcomes of the Hershey Haemophilia Cohort.
- Author
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Eyster ME
- Subjects
- Adult, Child, Cohort Studies, Disease Outbreaks, HIV Infections complications, HIV Infections transmission, Hemophilia A complications, Humans, Male, Pennsylvania epidemiology, Prognosis, Survival Analysis, Transfusion Reaction, HIV Infections epidemiology, Hemophilia A epidemiology
- Published
- 2008
- Full Text
- View/download PDF
46. Chronic hepatitis B and other correlates of spontaneous clearance of hepatitis C virus among HIV-infected people with hemophilia.
- Author
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Melendez-Morales L, Konkle BA, Preiss L, Zhang M, Mathew P, Eyster ME, and Goedert JJ
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, CD4 Lymphocyte Count, Female, HIV Infections immunology, Hepacivirus isolation & purification, Hepatitis C, Chronic transmission, Hepatitis C, Chronic virology, Humans, Male, Middle Aged, RNA, Viral blood, Remission, Spontaneous, Viral Load, HIV Infections complications, Hemophilia A complications, Hepatitis B, Chronic complications, Hepatitis C, Chronic complications
- Abstract
Objective: To identify correlates of spontaneous hepatitis C virus (HCV) clearance among people with human immunodeficiency virus (HIV) co-infection., Design: Baseline (2001-2004) analysis of a cohort study of people with hemophilia., Methods: Detailed questionnaire data were used to identify dates of primary HCV and HIV infections and to categorize sex; race; alcohol use; interferon treatment; hepatitis B virus (HBV) status; and HIV/AIDS history, treatment and current status. Spontaneous HCV clearance was defined as nondetection of HCV RNA by polymerase chain reaction assay in paired annual plasma, excluding those treated with interferon. Chi-squared, Fisher exact test, and logistic regression were used to identify correlates of clearance., Results: Among 478 HIV-infected participants, 61 (12.8%) had cleared HCV. Among the 31 participants with chronic HBV (as well as HIV), 16 (51.6%) had cleared HCV. With chronic HBV, HCV clearance was increased 11.2-fold (95% confidence interval, 5.1-24.8), after adjusting for sex, race, and hemophilia severity. Excluding the participants with chronic HBV, the prevalence of HCV clearance was 10.1%; and it was significantly reduced among males (9.7%, P = 0.05), blacks (1.6%, P = 0.01), and participants with severe hemophilia (8.2%, P = 0.02). HCV clearance was not associated with HIV RNA detection in plasma, CD4 cell count, anti-HIV therapy, AIDS history, ages at or years of HIV or HCV infection, or alcohol consumption., Conclusions: HCV clearance is unambiguously and markedly increased with chronic HBV infection among HIV co-infected people.
- Published
- 2007
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47. Upper gastrointestinal bleeding in haemophiliacs: incidence and relation to use of non-steroidal anti-inflammatory drugs.
- Author
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Eyster ME, Asaad SM, Gold BD, Cohn SE, and Goedert JJ
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Case-Control Studies, Cohort Studies, Female, Gastrointestinal Hemorrhage etiology, Hemarthrosis drug therapy, Hemophilia A drug therapy, Humans, Male, Middle Aged, Multicenter Studies as Topic, Prospective Studies, Risk Factors, Anti-Inflammatory Agents, Non-Steroidal adverse effects, Gastrointestinal Hemorrhage chemically induced, Helicobacter pylori, Hemarthrosis complications, Hemophilia A complications
- Abstract
This multicentre study sought to estimate the incidence of upper gastrointestinal (UGI) bleeding in haemophiliacs and its relationship to use of non-steroidal anti-inflammatory drugs (NSAIDs). Cox models were used to estimate relative hazards (RH) with 95% confidence intervals (CI) for postulated risk factors. Conditional logistic regression and stored sera were used to assess UGI bleeding risk with Heliobacter pylori seropositivity in cases compared with closely matched controls. During a mean of 17.4 months (range 2-34), 2285 participants, ages 13-89 (mean 36.5) were followed for 3309 person-years (py). Forty-two experienced a UGI bleeding event (incidence 1.3 per 100 py), most from ulcer (11), gastritis (four), varices (five) and Mallory Weiss tears (eight). RH was significantly increased with traditional NSAID use for <1 month (OR: 3.66; 95% CI: 1.1-11.9), but not with coxibs use. RH was significantly and independently increased with age >46 years (3.5; 95% CI: 1.1-10.6) and hepatic decompensation (4.4; 95% CI: 1.7-11.6). Likelihood of bleeding was substantially but not significantly increased (OR: 4.6; 95% CI: 0.3-83.9) with H. pylori seropositivity. These findings suggest that coxibs are a safer alternative than traditional NSAIDs in the treatment of haemophilic arthropathy.
- Published
- 2007
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- View/download PDF
48. HCV kinetics, quasispecies, and clearance in treated HCV-infected and HCV/HIV-1-coinfected patients with hemophilia.
- Author
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Shire NJ, Horn PS, Rouster SD, Stanford S, Eyster ME, and Sherman KE
- Subjects
- AIDS-Related Opportunistic Infections complications, AIDS-Related Opportunistic Infections virology, Adult, Alanine Transaminase blood, Antiviral Agents pharmacology, CD4-Positive T-Lymphocytes drug effects, Female, Follow-Up Studies, HIV Infections complications, HIV Infections drug therapy, HIV-1 genetics, Hepatitis C complications, Hepatitis C virology, Humans, Interferon-alpha pharmacology, Male, Middle Aged, RNA, Viral analysis, Remission Induction, Ribavirin pharmacology, Viral Load, AIDS-Related Opportunistic Infections drug therapy, Antiviral Agents therapeutic use, Hemophilia A complications, Hepacivirus drug effects, Hepatitis C drug therapy, Interferon-alpha therapeutic use, Ribavirin therapeutic use
- Abstract
Hepatitis C virus (HCV) treatment response rates remain low in HCV/HIV-1-coinfected individuals compared with those with HCV alone. Persons with inherited coagulation disorders have high rates of HCV and HIV-1 infection, but HCV treatment trials in this patient population are scarce. We hypothesized that differences by infection status in HCV viral kinetics would be associated with differences in HCV quasispecies complexity over time and with treatment response disparities. Coinfected and monoinfected patients were enrolled in a treatment trial for pegylated-interferon alpha-2a (peg-IFN) + ribavirin. Patients were treated for 48 weeks and followed for an additional 24. Quantitative HCV RNA was tested at multiple times during and after treatment. Viral kinetic parameters associated with response were estimated with a mathematical model. Quasispecies emergence was determined via heteroduplex complexity assay. Twenty-two patients were HCV RNA-positive at baseline, with no significant demographic or virological differences by infection status. Five of eleven (45%) of monoinfected and 3 of 11 (27%) of coinfected patients achieved sustained viral response (SVR). Peg-IFN efficacy (epsilon) of 90% or greater was associated with probability of end-of-treatment response (ETR) (P = .001) and SVR (P = .06). Patients with SVR had lower baseline quasispecies complexity than those without SVR (P = .07). Those with epsilon of 90% or greater also had lower baseline complexity (P = .07). Coinfection status mediated changes in complexity over time (P = .04). In conclusion, low pretreatment quasispecies complexity may predict peg-IFN response; early peg-IFN response is critical for sustained HCV clearance and is altered in coinfection. Further studies are warranted.
- Published
- 2006
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49. Evaluation of the efficacy and safety of etoricoxib in the treatment of hemophilic arthropathy.
- Author
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Tsoukas C, Eyster ME, Shingo S, Mukhopadhyay S, Giallella KM, Curtis SP, Reicin AS, and Melian A
- Subjects
- Adolescent, Adult, Aged, Child, Cyclooxygenase 2, Cyclooxygenase 2 Inhibitors adverse effects, Double-Blind Method, Etoricoxib, Female, Headache etiology, Hemarthrosis complications, Hemarthrosis enzymology, Humans, Lactones administration & dosage, Lactones adverse effects, Male, Membrane Proteins antagonists & inhibitors, Middle Aged, Pyridines adverse effects, Respiratory Tract Infections etiology, Sulfones adverse effects, Treatment Outcome, Cyclooxygenase 2 Inhibitors administration & dosage, Hemarthrosis drug therapy, Hemophilia A complications, Hemophilia A enzymology, Pyridines administration & dosage, Sulfones administration & dosage
- Abstract
This 2-part, double-blind, placebo-controlled study was conducted to determine the safety and efficacy of etoricoxib, a COX-2 selective inhibitor, for the treatment of hemophilic arthropathy. In part 1 (6 weeks), 102 patients (> or = 12 years old) with hemophilic arthropathy were randomized to receive 90 mg etoricoxib once daily or placebo (1:1 ratio). In part 2 (6 months), 51 patients taking placebo in part 1 were randomized to receive 90 mg etoricoxib or 25 mg rofecoxib once daily; patients taking etoricoxib in part 1 continued the same treatment. Efficacy end points included Patient Assessment of Arthropathy Pain, Patient Global Assessment of Arthropathy Disease Status, and Investigator Global Assessment of Arthropathy Disease Status. Safety was evaluated at each study visit. Etoricoxib provided significant improvement in all end points versus placebo (P < .001). Fewer patients taking etoricoxib discontinued due to a lack of efficacy versus placebo (P = .048). During part 2, efficacy was maintained; etoricoxib and rofecoxib demonstrated similar results. The most common adverse experiences were upper respiratory infection and headache. The incidence of joint bleeding during part 1 was similar between etoricoxib (66.7%) and placebo (72.6%) and during part 2 between etoricoxib (77.0%) and rofecoxib (78.9%). We conclude that etoricoxib provided superior efficacy versus placebo for the treatment of hemophilic arthropathy and was generally safe and well tolerated.
- Published
- 2006
- Full Text
- View/download PDF
50. Correlates of spontaneous clearance of hepatitis C virus among people with hemophilia.
- Author
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Zhang M, Rosenberg PS, Brown DL, Preiss L, Konkle BA, Eyster ME, and Goedert JJ
- Subjects
- Adolescent, Adult, Age Factors, Blood Component Transfusion, Child, Child, Preschool, Cohort Studies, Female, Hemophilia A complications, Hemophilia A therapy, Hemophilia B complications, Hemophilia B therapy, Humans, Male, Middle Aged, Plasma, Remission, Spontaneous, Retrospective Studies, Virus Inactivation, Hemophilia A blood, Hemophilia B blood, Hepacivirus, Hepatitis C blood, RNA, Viral blood
- Abstract
People with hemophilia were formerly at very high risk of infection with hepatitis C virus (HCV). Approximately 20% of HCV-infected patients spontaneously clear the virus. To identify correlates of spontaneous clearance of HCV, we studied a cohort of HCV-infected hemophilic subjects without human immunodeficiency virus infection who had never been treated with interferon. Plasma HCV RNA was persistently undetectable in 192 (27.0%) of 712 HCV-seropositive subjects. In multivariate analyses, HCV clearance was more likely in subjects infected with HCV at younger age, especially with infection before age 2 years (40.1%) compared with after age 15 years (14.9%, P(trend) < .0001), and with relatively recent infection, especially after 1983 (42.8%) compared with before 1969 (18.2%, P(trend) < .0001). HCV clearance was marginally reduced with African ancestry (19%) and greatly increased with chronic hepatitis B virus (HBV) infection (59.1%, P = .001). Resolved HBV infection, coagulopathy types and severity, types of clotting factor treatment, and sex were not associated with HCV clearance. In conclusion, hemophilic subjects coinfected with chronic HBV and those infected with HCV before age 2 years or after 1983 were significantly more likely to spontaneously clear HCV viremia. These data highlight and clarify the importance of nongenetic determinants in spontaneous recovery from HCV infection.
- Published
- 2006
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