Joseph E. Palascak
University of Cincinnati
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Featured researches published by Joseph E. Palascak.
The New England Journal of Medicine | 1980
Jeanne M. Lusher; Sandor S. Shapiro; Joseph E. Palascak; A. Vijaya Rao; Peter H. Levine; Philip M. Blatt
The therapeutic efficacy of prothrombin-complex concentrates in patients with hemophilia and inhibitors (antibodies) to factor VIII has been increasingly debated. We therefore entered 51 hemophiliacs with factor VIII inhibitors into a double-blind randomized crossover study to compare two commercial prothrombin-complex concentrates (Konyne and Proplex) and an albumin placebo. Acute hemarthrosis of the elbow, knee, or ankle was treated with a single dose of a test preparation and assessed six hours later with objective and subjective criteria. In all measurements the concentrates were significantly more effective than the placebo. The data indicate that although prothrombin-complex concentrates, when used in a single dose, are only partially effective in the treatment of joint hemorrhage in hemophiliacs with inhibitors, their continued use for acute hemarthrosis is justified in the absence of any other effective and readily available therapy for this disorder.
Haemophilia | 2005
R. Parameswaran; Amy D. Shapiro; Joan Cox Gill; Craig M. Kessler; Thomas C. Abshire; Anne L. Angiolillo; Lisa N. Boggio; A. Cohen; Donna DiMichele; W. Hanna; Keith Hoots; J. Hord; Nigel S. Key; Barbara A. Konkle; Peter A. Kouides; E. Kurczynski; P. Marks; Joseph E. Palascak; S. Pipe; Margaret V. Ragni; G. Rivard; R. Shopnick; Michael Tarantino; Leonard A. Valentino; R. Watts; Gilbert C. White
Summary. Recombinant activated factor VII (rFVIIa), licensed in 1999 for treatment of haemophilia patients with inhibitors (HI), represents an important advance in the therapeutic armamentarium. Standard bolus dosing ranges from 90 to 120 mcg kg−1 every 2–3 h until arrest of bleeding. As licensure, clinical use of rFVIIa has increased and broadened. Clinicians now use a wide dose range, 90–300 mcg kg−1. High‐dose regimens may optimize thrombin generation or burst, and may allow for prolonged dose interval. The Hemophilia and Thrombosis Research Society (HTRS) maintains a registry database to study haemophilia treatment and related disorders, particularly treatment of acute bleeding in HI, acquired haemophilia, FVII deficiency and von Willebrands disease (VWD). To assess the effect of rFVIIa dose on efficacy and safety in the treatment of acute bleeding in HI, data from the HTRS database from January 2000 through June 2002 were analysed. Bleeding episodes were grouped by bolus rFVIIa dose range: <100, 100–150, 150–200 and >200 mcg kg−1. Investigator‐reported efficacy for the first 72 h of treatment was evaluated. Thirty‐eight congenital HI patients were treated for 555 bleeding episodes. Patient age range was 1–55 years (median: 14). Bleeding episodes were spontaneous (45%), caused by trauma (38%), or because of surgery, dental, diagnostic, or medical procedures (17%); bleeding occurred in joint, muscle, and intra/extracranial sites. Treatment location included: 80% at home, 12% at other facilities (treatment centres, ER, inpatient and OR), and 8% at both home/other facilities. Median total dose given over 72 h was 360 mcg kg−1 (range: 40–4281, mean: 537). Bleeding stopped in 87% of the episodes. Bleeding cessation rate was 84% for the three lower dose groups, and 97% for the highest dose group (P < 0.001). Five patients experienced nine adverse events (AEs). AE rates were <1% for <100, 5% for 100–150, 0% for 150–200, <1% for >200 mcg kg−1 dose group. Decreased therapeutic response accounted for eight of the nine AEs. These data, which represent the most comprehensive report of rFVIIa use since the USA licensure, demonstrate that bleeding episodes in HI patients can be treated safely and effectively at home and that doses up to 346 mcg kg−1 appear to be well‐tolerated. Additionally, rFVIIa doses >200 mcg kg−1 appear to significantly increase efficacy (97% in the high‐dose group, compared with 84% in the lower dose groups). Optimal dosing remains to be determined; specifically, what the lowest effective dose is and whether a single high‐dose bolus eliminates the need for repeated dosing. Recombinant FVIIa appears to have a wide safety margin that may allow dose escalation to address these questions.
Journal of Clinical Investigation | 1978
Jose Martinez; Joseph E. Palascak; D Kwasniak
To evaluate the possibility that the carbohydrate composition of fibrinogen may be altered in the dysfibrinogenemia associated with liver disease, we studied the sialic acid content of purified fibrinogen from 12 patients with liver disease and its relationship to the prolongation of the thrombin time. Purified fibrinogen showed that Aalpha-, Bbeta-, and gamma-chains when reduced and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and exhibited prolongation of the thrombin time similar to that of the plasma from which it was derived. Sialic acid content of the purified fibrinogen ranged from 12.7 to 71.4% higher in patient fibrinogens when compared to normal controls. A progressive delay in thrombin time was associated with increasing sialic acid content of the patient fibrinogen. Enzymatic removal of sialic acid from four of the abnormal fibrinogens resulted in a shortening of their thrombin times to the range of the desialylated normal control. Periodic acid-Schiff reagent stained only the Bbeta- and gamma-chains of the reduced patient fibrinogens after sodium dodecyl sulfate-polyacrylamide gel electrophoresis suggesting that the excess sialic acid is located on these two chains. These studies demonstrate a biochemical alteration of the functionally abnormal fibrinogen found in some patients with liver disease, and indicate that the excess sialic acid plays an important role in the functional defect of this protein.
Journal of Clinical Investigation | 1977
Joseph E. Palascak; Jose Martinez
To test the possibility that a functionally abnormal fibrinogen may exist in some patients with liver disease, we studied the plasma and purified fibrinogens of five patients whose plasma thrombin times were prolonged at least 40% over normal controls. In no patient was there evidence of disseminated intravascular coagulation and/or fibrinolysis. No abnormalities were detected by immunoelectrophoresis of plasmas or purified fibrinogens. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of reduced patient fibrinogens showed normal mobility and amount of Aalpha, Bbeta, and gamma chains. Alkaline polyacrylamide gel electrophoresis and gradient elution, DEAE-cellulose chromatography of admixtures of radio-iodinated patient (125)I-fibrinogen and normal (131)I-fibrinogen showed identical mobility in the gel and simultaneous elution from the column, respectively. Thrombin and Reptilase (Abbott Scientific Products Div., Abbott Laboratories, South Pasadena, Calif.) times of purified patient fibrinogens were prolonged, and calcium ions improved but did not completely correct these defects. Increasing amounts of thrombin progressively shortened the clotting times of patient fibrinogens but not to the level of normal. Addition of equal amounts of patient fibrinogen to normal fibrinogen resulted in a prolongation of the thrombin time of the normal protein. Thrombin-induced fibrinopeptide release was normal. Fibrin monomers prepared from patient plasmas and purified fibrinogens demonstrated impaired aggregation at low (0.12) and high (0.24) ionic strength. These studies demonstrate that some patients with liver disease and prolonged plasma thrombin times have a dysfibrinogenemia functionally characterized by an abnormality of fibrin monomer polymerization.
American Journal of Hematology | 1999
Zahida Yasin; Donald Quick; Perumal Thiagarajan; Denise Spoor; Juan Caraveo; Joseph E. Palascak
A patient with newly diagnosed multiple myeloma manifested by urine kappa light‐chain excretion and a small monoclonal spike (0.4 g/dl), presented with lower extremity deep venous thrombosis. A preheparin plasma‐activated partial thromboplastin time (aPTT) was prolonged at 68 sec (normal control 26‐42 sec). Additional studies confirmed the presence of lupus anticoagulant activity in the serum: the modified Russell Viper Venom Time (MRVVT) was 73 sec (normal control 24–42 sec) and with a 50:50 mix of the patients plasma and pooled normal plasma, the MRVVT remained prolonged. Kappa light chains (LC) were isolated from the patients urine and their purity confirmed by electrophoresis and immunofixation using specific immunoglobulin antisera. The patients LC mixed with pooled normal plasma demonstrated LA activity by in vitro clotting tests (plasma‐activated partial thromboplastin time 62 sec, with normal control of 45 sec), MRVVT of 44 sec with normal control of 35 sec. Purified urinary kappa light chains from a control patient with multiple myeloma and normal clotting studies, failed to prolong either the plasma‐activated partial thromboplastin time or the MRVVT. We hypothesize that kappa LC in our patient demonstrated LA activity, which was unique to these LCs. Paraproteins with LA activity, to date, have included only intact immunoglobulins (Ig). While intact Ig paraproteins have been reported to possess LA activity, this is the first report to our knowledge of light‐chain paraproteins possessing similar activity and resulting in clinically evident thrombosis. Light chain paraproteins could serve as useful models for further study of the mechanisms of activity of acquired LA inhibitors. Am. J. Hematol. 62:99–102, 1999.
Journal of Parenteral and Enteral Nutrition | 1987
Dave M. Lutomski; Joseph E. Palascak; Robert H. Bower
Intravenous lipids have been shown to have varying effects on coagulation parameters. A patient with short bowel syndrome and recurrent thrombotic episodes who required both intravenous lipids and anticoagulation is described. A constant infusion of a soybean oil emulsion (Intralipid) in his parenteral nutrient solution was demonstrated to interfere with the anticoagulant effect of warfarin. Termination of the infusion and rechallenge with warfarin resulted in prolongation of his prothrombin time to the therapeutic range. Reinstitution of a lipid-free parenteral nutrition regimen has allowed for successful continuation of warfarin therapy.
Haemophilia | 2005
James J. Goedert; Jaime Siegel; Kay Miller; Michael M. Lederman; Alexis A. Thompson; Brittan Browning; Susan Gamerman; Kevin McRedmond; Janice S. Withycombe; Ralph A. Gruppo; Gina Stack; Jeanne M. Lusher; Linda Percy; Diane J. Nugent; Marianne McDaniel; Catherine S. Manno; Regina B. Butler; Amanda Wade; Anne L. Angiolillo; Naomi L.C. Luban; Christine Guelcher; Michael Tarantino; Suzi Greer; Joan Cox Gill; Jodie Nelson; Gilbert White; Michael W. Fried; Aime L. Grimsley; Donna DiMichele; Ilene Goldberg
Summary. Before the mid‐1980s, haemophilia often was unknowingly treated with contaminated plasma products, resulting in high rates of human immunodeficiency virus (HIV‐1), hepatitis C virus (HCV) and hepatitis B virus (HBV) infections. To estimate the impact of these infections, a new cohort was established. All HCV‐seropositive patients, age 13–88 years, at 52 comprehensive haemophilia treatment centres were eligible. Cross‐sectional data collected during April 2001 to January 2004 (median June 2002) were analysed. Plasma HIV‐1 and HCV RNA were quantified by polymerase chain reaction. Highly active antiretroviral therapy (HAART) was defined as use of at least three recommended medications. Among 2069 participants, 620 (30%) had HIV‐1. Of 1955 with known HBV status, 814 (42%) had resolved HBV and 90 (4.6%) were HBV carriers. Although 80% of the HIV‐1‐positive participants had ≥200 CD4+ cells μL−1, only 59% were on HAART. HIV‐1 RNA was undetectable in 23% of those not taking antiretroviral medications. Most (72%) participants had received no anti‐HCV therapy. HCV RNA was detected less frequently (59%) among participants treated with standard interferon plus ribavirin (P = 0.0001) and more frequently among HIV‐1‐positive than HIV‐1‐negative participants (85% vs. 70%, P < 0.0001). HIV‐1‐positive participants were more likely to have pancytopenia and subclinical hepatic abnormalities, as well as persistent jaundice, hepatomegaly, splenomegaly and ascites. HAART recipients did not differ from HIV‐negative participants in the prevalence of ascites. The clinical abnormalities were more prevalent with older age but were not confounded by HBV status or self‐reported alcohol consumption. Eleven participants presented with or previously had hepatocellular carcinoma or non‐Hodgkin lymphoma. Although prospective analysis is needed, our data reveal the scale of hepatic and haematological disease that is likely to manifest in the adult haemophilic population during the coming years unless most of them are successfully treated for HIV‐1, HCV or both.
Journal of Laboratory and Clinical Medicine | 1998
Allan J. Erslev; Joseph E. Palascak; Bahu S. Shaikh; Jose Martinez
A family with autosomal dominant macrothrombocytopenia is described. Despite severe thrombocytopenia, only a moderate hemorrhagic tendency was observed. Kinetic studies revealed a normal platelet survival, normal megakaryocytic numbers, and normal bone marrow responsiveness. The rate of platelet production was set low, despite moderately impaired hemostasis and thrombocytopenia; it apparently was set to maintain another platelet parameter at an optimal level. Measurements of total circulating platelet mass and platelet surface suggested that the platelet production was set to maintain the platelet surface rather than the platelet mass at a normal value.
Haemophilia | 2016
Kenneth E. Sherman; R. Ke; Susan D. Rouster; Enass A. Abdel-hameed; C. Park; Joseph E. Palascak; Alan S. Perelson
Chronic hepatitis C virus (HCV) infection is an important source of morbidity and mortality among haemophiliacs. Limited data are available regarding treatment intervention using direct‐acting antivirals (DAAs) and theoretical concerns regarding accumulation of drug‐associated resistance variants (RAVs) remain. We conducted a pilot study of treatment with telaprevir/pegylated interferon‐alfa/ribavirin to evaluate treatment response and the role of lead‐in DAA therapy on mutational selection of resistance variants.
Haemophilia | 2015
J. L. Agne; N. Ahmad; Joseph E. Palascak; R. Khaled; N. A. Karim
Menorrhagia affects approximately 30% of postmenarcheal women and may be a symptom of an underlying bleeding disorder. Philipp et al. found that 47% of women with a clinical diagnosis of menorrhagia had an underlying haemostatic defect due to treatment with anticoagulants, Von Willebrand disease (VWD) or platelet dysfunction [1]. The risk of bleeding in patients receiving oral anticoagulation with vitamin K antagonists varies among different studies. In a review of observational studies addressing this issue, the average annual rates of fatal, major and minor bleeding were 0.8%, 4.9% and 15% respectively [2]. Inherited or acquired platelet disorders may also be a cause of unexplained menorrhagia, especially among African American women. VWD is the most common hereditary disorder of haemostasis affecting approximately 1% of the general population [3]. Single coagulation factor deficiencies are uncommon, but rarely deficiencies in factor V, VII and XI have been documented in women with heavy menses [4]. Haemophilia A [factor VIII (FVIII) deficiency] and B (FIX deficiency) are rare in females due to an X-linked inheritance, but may occur in female heterozygotes with high lyonization. When menorrhagia is coupled with additional symptoms of recurrent epistaxis, excessive bleeding with minor trauma and excessive bleeding after dental or surgical procedures, clinical suspicion for a bleeding disorder is increased and should prompt further clinical investigation. Here, we present two Caucasian sisters (full siblings) with past medical histories notable for easy bruising, epistaxis, menorrhagia and excessive bleeding with minor operative procedures who were evaluated in our haematology clinic for haemostatic work-up. Patient 1 was a 23-year-old Caucasian female, referred by her primary care provider after developing a large haematoma in her left buttock after a fall. The patient had a past medical history notable for frequent self-limited epistaxis until the age of eight, menorrhagia since menarche at age 12, depression and migraine headaches. The patient had been prescribed oral contraceptives (norethindrone-ethinyl estradiol) for menorrhagia and Fioricet for recurrent migraines, but no medications that might increase bleeding risk. Her physical examination was negative except for an extensive haematoma on her left buttock (Fig. 1). Family history revealed that the patient’s 28-year-old sister (Patient 2) had a childhood history of mild epistaxis, easy bruising and excessive bleeding post-tonsillectomy which was never fully evaluated. Patient 2 was subsequently referred to be tested for hereditary coagulopathy at 32 weeks of a twin gestation in her first pregnancy. Given Patient 1’s history, physical findings and a positive family history of bleeding, haemostatic studies were obtained for both Patient 1 (while she was on oral contraceptives) and Patient 2 in pregnant and non-pregnant state (Table 2). Patient 1 was found to have a prolonged activated partial thromboplastin time of 41.1 s and a low FVIII level of 14%. Her von Willebrand factor (vWFFx) level was within normal limits. Patient 2 was also found to have a low FVIII level of 28% in the non-pregnant state and a normal vWFFx level. Both patients exhibited normal levels of vWF antigen and normal vWF multimer pattern (Table 1). Because of a prolonged aPTT and low FVIII level, Patient 2 had subsequent genetic testing, which revealed homozygous mutation (Arg854Gln; chromosome 12) consistent with the diagnosis of VWD type 2N, also known as VWD Normandy. Though genetic testing could not be obtained on Patient 1, she was presumptively diagnosed with VWD type 2N because of FVIII findings similar to Patient 2. With a presumptive diagnosis of VWD type 2N, Patient 1 was counselled to continue oral contraceptives. Humate-P replacement was recommended for any future operative procedures or childbirth in the absence of normal FVIII levels. Patient 2 was advised to have Humate-P available for her upcoming Caesarean section. However, she was able to undergo successful Caesarean section on 2/13/12 without requiring Humate-P replacement as monitoring during the latter stage of her pregnancy showed that her FVIII:C level had normalized (Table 2). Correspondence: Nagla Abdel Karim, MD, Division of Hematology and Oncology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA. Tel.: +513 558 2115; fax: + 513 558 2124; e-mail:[email protected]