DOCSLIB.ORG

Acquired Von Willebrand Disease As a Cause of Recurrent Mucocutaneous Bleeding in Primary Thrombocythemia: Relationship with Platelet Count

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Acquired Von Willebrand Disease As a Cause of Recurrent Mucocutaneous Bleeding in Primary Thrombocythemia: Relationship with Platelet Count Ann Hematol (1994) 69:81-84 Springer-Verlag 1994 P. J. J. van Genderen J. J. Michiels S. C. P. A. M. van der Poel-van de Luytgaarde H. H. D. M. van Vliet Acquired von Willebrand disease as a cause of recurrent mucocutaneous bleeding in primary thrombocythemia: relationship with platelet count Received 2 March 1994 / Accepted 20 May 1994 Summary We present a 4-year follow-up of a 42-year- von Willebrand factor deficiency. An inverse relation- old patient with primary thrombocythemia whose clini- ship between platelet number and plasma high-molecu- cal course was complicated by two major mucocuta- lar-weight multimers of von Willebrand factor was de- neous bleeding episodes. On both occasions an ac- monstrated. quired functional yon Willebrand factor deficiency was demonstrated. In contrast to what is reported in the lit- erature, an inverse relationship between platelet num- Case report ber and plasma high-molecular-weight multimers of von Willebrand factor was established. A 42-year-old woman was referred to our department in Decem- ber 1989 with upper abdominal complaints due to massive sple- Key words Primary thrombocythemia nomegaly. Ultrasound examination of the abdomen revealed an Myeloproliferative disorder . von Willebrand factor enlarged spleen of 20 cm and thrombosis of the splenic vein. Sub- Acquired von Willebrand disease Platelets sequent endoscopy showed esophageal varices. A slight thrombo- cytosis of 431 x 109 platelets per liter was established (Fig. 1). He- Bleeding moglobin levels, white cell count and differentiation, creatinine, urea, and liver function tests were all normal. Extended hemos- tatic analysis excluded the presence of a lupus anticoagulant anti- Introduction body and a deficiency of antithrombin III, protein C, and protein S. Bone marrow smear and biopsy material showed an increased cellularity of normal hematopoiesis, a pronounced increase of Primary thrombocythemia (PT), a clonal myeloprolifer- clustered megakaryocytes, and the presence of fine reticulin fi- ative disorder characterized by a persistent elevation of bers, but the absence of collagen fibers and osteosclerosis, compa- the platelet count, paradoxically predisposes to both tible with the diagnosis of PT [15]. The score for the leukocyte alkaline phosphatase stain was 129 (normal 20-100 U/ml). Splen- thrombosis and hemorrhages [13, 15]. Despite the iden- ectomy in December 1989 (spleen weight 788 g) was uneventful. tification of a broad array of specific structural, bio- In March 1990, the platelet count rose to about 3500 x 109/1; this chemical, and metabolic platelet defects in patients was associated with spontaneous mucocutaneous bleeding con- with PT, a convincing correlation between these defects sisting of easy bruising, recurrent ecchymoses after minor injuries, and the clinical complications of thrombosis and bleed- and melena, causing a fall of the hemoglobin level from 7.3 to 4.6 mmol/1. Extended coagulation tests revealed a functional defi- ing has never been established [13, 15]. ciency of plasma von Willebrand factor [yon Willebrand factor Several authors have described a decrease or ab- antigen (vWF:Ag) 1.36U/ml; ristocetin co-factor activity sence of plasma high-molecular-weight multimers of (vWF: RCoF) 0.40 U/ml, and collagen binding activity yon Willebrand factor (vWF) in patients with myelo- (vWF:CBA) 0.22 U/ml, normal values for all vWF-related activi- ties 0.60-1.40 U/ml)] and a prolonged Ivy bleeding time (> 15 proliferative disorders and associated bleeding tenden- rain; normal _< 4 min). Platelet aggregation tests were normal. cy [4, 5, 10]. We present here a 4-year follow-up of a From that time on we prospectively studied plasma von Wille- patient with PT whose clinical course was complicated brand factor activities in relation to the platelet count. Reduction by two bleeding episodes associated with an acquired of the platelet count with hydroxyurea resulted in disappearance of the bleeding symptoms and the functional yon Willebrand fac- tor defect and in a normalization of the Ivy bleeding time. At platelet counts between 700 and 1650 x 109/1 for more than 1 year P. J. J. van Genderen (N~I) J. J. Michiels neither the bleeding nor the functional von Willebrand factor de- S. C. P. A. M. van tier Poel-van de Luytgaarde fect (vWF:Ag varied from 1.22 to 2.00 U/ml; vWF:RCoF from H. H. D. M. van Vliet 0.64 to 1.72 U/ml, and vWF: CBA from 0.67 to 1.26 U/ml) recur- Department of Hematology, University Hospital Dijkzigt, red. Erasmus University, Dr. Molewater plein 40, Discontinuation of hydroxyurea because of side effects (head- NL-3015 GD Rotterdam, The Netherlands ache and nausea) in August 1992 resulted in a rapid increase in 82 Platelet count I (x 109/1) 4000 Splen~ctomy / 1989/1990 2.0 Ratio 3000 1.5 2000 /i i i",',,,, /",, ,' ., 1.0 '/":i" v''':'''I /'x V" .,'" 1000 0.5 I I I I I I 1 I I I 0 0 nov I dec I jan feb I mar I aprilI may I juneI july I may june july aug sept oct nov dec jan platelets ............ vWF:RCoF/vWF:Ag .......... vWF:CBA/vWF:Ag mucocutaneous bleedings Fig. 1 The clinical course of a patient with primary thrombocy- wells were incubated with 1/200 dilution in PBS-Tween-albumin themia was complicated by two mucocutaneous bleeding episodes of horseradish peroxidase-conjugated rabbit polyclonal immuno- at platelet counts above 2000 x 109/1. On both occasions a func- globulins to human vWF (Dakopatts, Denmark) for another 2 h tional von Willebrand factor deficiency was demonstrated; this at room temperature. After washing, 100 Ixl ABTS substrate solu- disappeared after reduction of the platelet count with hydroxyur- tion was added. After 15 min incubation the color development ea. Von Willebrand factor activities are expressed as the ratio of was stopped by the addition of 10 ixl concentrated acetic acid and either vWF: RCoF/vWF: Ag or vWF: CBA/vWF: Ag to denote the extinction was measured at 414 nm. The multimeric pattern of the amount of functionally active von Willebrand factor. The up- vWF was visualized according to Brosstad et al. [2]. per two horizontal lines represent the normal range for the The relationship between platelet count and plasma levels of vWF: RCoF/vWF: Ag and vWF: CBA/vWF: Ag ratios. The lower von Willebrand factor was analyzed by linear regression and two horizontal lines indicate the normal range for the platelet Spearman's rank correlation test. Statistical significance was ac- count cepted at p < 0.05. circulating platelets (platelet counts 3700-4000 x 109/1) and recur- Results rence of the mucocutaneous bleeding tendency, which was char- acterized by easy bruising, prolonged bleeding after minor cuts, The clinical course of the described patient was compli- and menorrhagia, causing a fall of the hemoglobin level from 7.0 cated by two major bleeding events. On both occasions to 3.7 mmol/1. Again, a functional von Willebrand factor defect (vWF:Ag 1.31 U/ml; vWF:RCoF 0.46 U/ml, and vWF: CBA 0.11 an acquired von Willebrand defect and a prolonged Ivy U/ml) and a prolongation of the bleeding time (> 15 min) were bleeding time were demonstrated, occurring at platelet demonstrated. The bleeding symptoms and the functional von counts above 2000 x 109/1 (Fig. 1). At times of manifest Willebrand factor defect disappeared after reduction of the plate- bleeding, the vWF: RCoF/vWF: Ag ratios and let count with hydroxyurea. The hemoglobin level completely re- covered with oral iron administration. vWF: CBA/vWF: Ag ratios were decreased at 0.40+0.13 and 0.19_+0.08, respectively, indicating a functional deficiency of vWF. Reduction of the platelet Material and methods count with hydroxyurea resulted in disappearance of the bleeding symptoms as well as of the acquired func- All hemostatic tests were performed using routine procedures. tional von Willebrand defect (Fig. 1) and in a normali- Platelets were counted electronically in blood anticoagulated with zation of the Ivy bleeding time. A significant inverse EDTA. Bleeding times were measured according to Ivy et al. [9]. relationship between the platelet count and the ratios Von Willebrand factor antigen was assayed by an ELISA using rabbit anti-human vWF and rabbit horseradish peroxidase-conju- of vWF:RCoF/vWF:Ag (r=-0.728, p<0.001) and gated anti-human vWF polyclonal antibodies [7]. Ristocetin co- vWF:CBA/vWF:Ag (r=-0.834, p<0.001) was de- factor activity was assayed with formalin-fixed platelets [11] (in- monstrated (Fig. 2). Analysis of the vWF multimers at tra-assay variation 10%; inter-assay variation 11%). The binding different levels of thrombocytosis (Fig. 3) revealed a of vWF to collagen was measured according to the ELISA-based progressive decrease of the high-molecular-weight mul- method of Brown and Bosak [3], with slight modifications (intra- assay variation 5%, inter-assay variation 9%). Microtiter plate timers of vWF with increasing platelet counts. wells (A/S Nunc, Roskilde, Denmark) were coated overnight at 4~ with 100 ~1 of a 0.2-mg/ml suspension of collagen (bovine achilles tendon, type I, Sigma, St. Louis, USA) in 20 mM acetic acid. After washing with PBS-Tween, 100 txl of a 1/40 dilution of the test plasmas in PBS-Tween-albumin were added to the wells and incubated for 2 h at room temperature. After rinsing, the 83 1.50 strated, resulting in a functional von Willebrand factor defect at platelet counts above 1000x109/1. With in- 0 creasing platelet counts both the vWF:RCoF/vWF:Ag o o 0 and vWF: CBA/vWF:Ag ratios progressively de- 1.00 "'""" .. creased, suggesting a deficiency of the high-molecular- im0 4~ O'.~,.
Load more

Recommended publications
  • The Impact of Thrombophilia in the Management Of
    S6 MPN III – Abstracts of the 8th International Hematology Expert Meeting / Leukemia Research 44 S1 (2016) S1–S12 Figure 1. Possible new treatment algorithm in polycythemia vera and essential thrombocythemia (CVR = cardiovascular risk factors). Adapted from: Tefferi A, Barbui T. Am J Hematol 2015;90(8):683–5 MPN III the Czech part of the international registry (“Registry”) of anagrelide (Thromboreductin®)-treated patients. The impact of thrombophilia in the management of MPN The recent analysis of the “Registry” [6] included altogether 1179 patients having MPD-T – either ET, PV or PMF according to PVSG criteria. In 812 J. Schwarz patients, the WHO/CZEMP diagnosis could be established: ET – 445 CZEMP (Czech Group for Ph– Myeloproliferative Disorders), Prague, Czech (54.8%), PMF – 206 (25.4%), PV – 107 (13.2%), and other (mostly MPN- Republic unclassifiable) – 54 (6.7%) cases. The M/F ratio was 2:3, the median age of The overall thrombotic risk in a normal healthy population is always based patients was 52 years (6–91 years) at diagnosis. The incidence of vascular on a combination of multiple risk factors present in one individual. The events was compared in the history (before entering the Registry) and risk parameters for arterial and venous events differ. MPD-T represents during follow-up (on anagrelide treatment). History and follow-up a situation in which the specific MPD-related risks (such as the JAK2 represented 4149 and 4742 patient-years, respectively. For arterial events, mutation) are combined with other risk factors present in the general there was a decrease in the incidence of events from 5.04 to 2.74 per 100 population.
    [Show full text]
  • Immune Thrombocytopenia and JAK2V617F Positive Essential Thrombocythemia: Literature Review and Case Report
    Hindawi Case Reports in Hematology Volume 2017, Article ID 3725089, 4 pages https://doi.org/10.1155/2017/3725089 Case Report Immune Thrombocytopenia and JAK2V617F Positive Essential Thrombocythemia: Literature Review and Case Report M. A. Sobas,1 T. Wróbel,1 K. Zduniak,2 M. Podolak-Dawidziak,1 J. Rybka,1 M. BiedroN,1 M. Sawicki,1 J. Dybko,1 and K. Kuliczkowski1 1 Department of Haematology, Blood Neoplasms and Bone Marrow Transplantation, Medical University of Wrocław, Wrocław, Poland 2Department of Pathology, Medical University of Wrocław, Wrocław, Poland Correspondence should be addressed to M. A. Sobas; [email protected] Received 27 March 2017; Revised 28 May 2017; Accepted 27 June 2017; Published 20 July 2017 Academic Editor: Eduardo Arellano-Rodrigo Copyright © 2017 M. A. Sobas et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. We present the case where immune thrombocytopenia (ITP) and essential thrombocythemia (ET) sequentially appeared in the space of twenty-one years of follow-up. Impaired platelet production is present in both diseases, but clinical presentation and treatment are different. On the basis of this case history a possible role of autoimmunity as a predisposing factorto myeloproliferation has been discussed. 1. Introduction but proved one with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) [6]. Primaryimmunethrombocytopeniapreviouslycalledidio- pathic thrombocytopenic purpura or immune thrombocy- Here we present a case report of a patient with ITP who topenic purpura (ITP) is characterized by autoimmune- was diagnosed with ET, after 21 years of follow-up.
    [Show full text]
  • Essential Thrombocythemia Effective Date: July, 2021
    Guideline Resource Unit [email protected] Essential Thrombocythemia Effective Date: July, 2021 Clinical Practice Guideline LYHE-012 – Version 1 www.ahs.ca/guru Background Thrombocytosis, defined as a platelet count of ≥ 450 x 109/L, is common in clinical practice and can be related to primary or secondary causes. Essential thrombocythemia (ET), a primary cause, is a Philadelphia-negative classical myeloproliferative neoplasm (MPN) defined by clonal thrombocytosis1. Similar to other classical MPNs, mutually exclusive driver mutations including JAK2, CALR and MPL are responsible for the pathogenesis of ET with the most frequent mutation JAK2V617F found in 55% of ET, 15-30% having CALR and 4-8% having MPL, while 10-20% lack a driver mutation and are referred to as “triple negative”2. ET is complicated by thrombosis and bleeding risk with potential of transformation to myelofibrosis or alternative aggressive myeloid neoplasm. This guideline is to provide information regarding the diagnosis and management of ET based on our current standards. Guideline Questions 1. What diagnostic and baseline investigations are recommended for adult patients with suspected or confirmed ET? 2. What are the recommended treatment options for ET? 3. How do you manage extreme thrombocytosis? 4. How do you treat thrombosis in the setting of ET and other MPNs? 5. What is the current peri-operative and peripartum management strategies for ET/MPN patients? Search Strategy This guideline was generated using systematic literature searches of PubMed and MEDLINE databases, ASCO, EHA abstracts and proceedings, and ASH abstracts and proceedings. The search included practice guidelines, systematic reviews, meta-analyses, randomized controlled trials and clinical trials.
    [Show full text]
  • A Guide for People Living with Von Willebrand Disorder CONTENTS
    A guide for people living with von Willebrand disorder CONTENTS What is von Willebrand disorder (VWD)?................................... 3 Symptoms............................................................................................... 5 Types of VWD...................................................................................... 6 How do you get VWD?...................................................................... 7 VWD and blood clotting.................................................................... 11 Diagnosis................................................................................................. 13 Treatment............................................................................................... 15 Taking care of yourself or your child.............................................. 19 (Education, information, first aid/medical emergencies, medication to avoid) Living well with VWD......................................................................... 26 (Sport, travel, school, telling others, work) Special issues for women and girls.................................................. 33 Connecting with others..................................................................... 36 Can I live a normal life with von Willebrand disorder?............. 37 More information................................................................................. 38 2 WHAT IS VON WILLEBRAND DISORDER (VWD)? Von Willebrand disorder (VWD) is an inherited bleeding disorder. People with VWD have a problem with a protein
    [Show full text]
  • ER Guide to Bleeding Disorders
    Bleeding disorders ER guide to bleeding disorders 1 Table of contents 4 General Guidelines 4–5 national Hemophilia Foundation guidelines 5–10 Treatment options 10 HemopHilia a Name:__________________________________________________________________________________________________ 10–11 national Hemophilia Foundation guidelines Address:________________________________________________________________________________________________ 12 dosage chart Phone:__________________________________________________________________________________________________ 14–15 Treatment products 16 HemopHilia B In case of emergency, contact: ______________________________________________________________________________ 16 national Hemophilia Foundation guidelines Relation to patient:________________________________________________________________________________________ 17 dosage chart 18 Treatment products 19 HemopHilia a or B with inHiBiTors Diagnosis: Hemophilia A: Mild Moderate Severe 20 national Hemophilia Foundation guidelines Inhibitors Inhibitors Bethesda units (if known) ____________________________________ 21 Treatment products Hemophilia B: Mild Moderate Severe 22–23 Von willeBrand disease Inhibitors Inhibitors Bethesda units (if known) ____________________________________ 23–24 national Hemophilia Foundation guidelines von Willebrand disease: Type 1 Type 2 Type 3 Platelet type 25 Treatment products 27 Bibliography Preferred product:_________________________________________________________________________________________ Dose for life-threatening
    [Show full text]
  • Essential Thrombocythemia Facts No
    Essential Thrombocythemia Facts No. 12 in a series providing the latest information for patients, caregivers and healthcare professionals www.LLS.org • Information Specialist: 800.955.4572 Introduction Highlights Essential thrombocythemia (ET) is one of several l Essential thrombocythemia (ET) is one of a related “myeloproliferative neoplasms” (MPNs), a group of closely group of blood cancers known as “myeloproliferative related blood cancers that share several features, notably the neoplasms” (MPNs) in which cells in the bone “clonal” overproduction of one or more blood cell lines. marrow that produce the blood cells develop and All clonal disorders begin with one or more changes function abnormally. (mutations) to the DNA in a single cell; the altered cells in l ET begins with one or more acquired changes the marrow and the blood are the offspring of that one (mutations) to the DNA of a single blood-forming mutant cell. Other MPNs include polycythemia vera and cell. This results in the overproduction of blood cells, myelofibrosis. especially platelets, in the bone marrow. The effects of ET result from uncontrolled blood cell l About half of individuals with ET have a mutation production, notably of platelets. Because the disease arises of the JAK2 (Janus kinase 2) gene. The role that this from a change to an early blood-forming cell that has the mutation plays in the development of the disease, capacity to form red cells, white cells and platelets, any and the potential implications for new treatments, combination of these three cell lines may be affected – and are being investigated. usually each cell line is affected to some degree.
    [Show full text]
  • Immune Thrombocytopenic Purpura with Subsequent Development of JAK2 V617F-Positive Essential Thrombocythemia: Case Report
    ISSN: 2640-7914 DOI: https://dx.doi.org/10.17352/ahcrr CLINICAL GROUP Received: 13 July, 2021 Case Report Accepted: 03 August, 2021 Published: 04 August, 2021 *Corresponding author: Marisabel Hurtado-Castillo, Immune thrombocytopenic PGY-3, Internal Medicine, Department of Medicine at NYU, 536 Ovington Avenue Apartment 3, Brooklyn NYC 11209, USA, Tel: 718-312-9641; purpura with subsequent Email: Keywords: Immune thrombocytopenic purpura; development of JAK2 Essential thrombocythemia; JAK-STAT signaling path- way; JAK2(V617F) mutation V617F-positive essential https://www.peertechzpublications.com thrombocythemia: Case Report Marisabel Hurtado-Castillo1*, Brian Flaherty2 and Morris Jrada2 1PGY-3, Internal Medicine, Department of Medicine at NYU, Brooklyn, NY, USA 2Clinical Assistant Professor, Department of Medicine at NYU Grossman School of Medicine, Brooklyn, NY, USA Abstract The sequential occurrence of Immune Thrombocytopenic Purpura (ITP) and Essential Thrombocythemia (ET) has been reported in the literature on a few occasions, as these are two hematologic disorders with distinct etiologies and patients usually have contrasting clinical presentations. Our case highlights the sequential occurrence of ITP, followed by Janus kinase 2 (JAK2) (V617F)-positive ET in a 64-year-old white woman, after four years of follow-up. The pathophysiology relating to these two conditions is incompletely understood, however, JAK2(V617F) mutation has been found in all the cases reported. Early identifi cation of JAK2(V617F) mutation in a patient with a
    [Show full text]
  • Living with Von Willebrand Disease This Booklet Has Been Prepared to Help You Understand Von Willebrand Disease
    Focused Care for Bleeding Disorders Living with von Willebrand disease This booklet has been prepared to help you understand von Willebrand disease. It contains general educational material and is not intended to constitute medical advice or the rendering of medical care. Accredo is not licensed to practice medicine. The diagnosis and treatment of bleeding disorders should only be done by, or under the direction of, a qualified doctor. The patient’s doctor should always be consulted with regard to the patient’s medical treatment. You’ve been diagnosed with a bleeding disorder. You may be scared, confused or uncertain about where to go for the information you need. We understand ... and we’re here to help. At Accredo, a specialty pharmacy, our team of specialty-trained pharmacists, nurses and care advocates are solely focused on treating bleeding disorders and Leslie, RN understand how to help you manage your diagnosis. That’s why we’ve Bleeding Disorders provided this comprehensive guide to living with von Willebrand Educator disease – it’s just one more way we’re here to support you and help you live your best life. What is von Willebrand disease? Common symptoms .................................................................................. 3 How von Willebrand disease affects the body .............................................. 3 Types of von Willebrand disease ................................................................ 4 How did I get von Willebrand disease? ....................................................... 4 How is
    [Show full text]
  • Erythromelalgic Microvascular Disturbances, Major Thrombosis
    & Throm gy b o o l e o t m Journal of Hematology & a b o m l e i c H D f o i s l e a Thromboembolic Diseases ISSN: 2329-8790 a Michiels, J Hematol Thromb Dis 2014, 2:5 n s r e u s o J DOI: 10.4172/2329-8790.1000149 Review Article Open Access Erythromelalgic Microvascular Disturbances, Major Thrombosis and Hemorrhagic Manifestations of Thrombocythemia in Patients with Essential Thrombocythemia and Polycythemia Vera: Therapeutic Implications Jan Jacques Michiels* Academic Hospital Dijkzigt, Erasmus University Rotterdam (EUR 1974-1998), Department of Hematology, Antwerp University Hospital, Belgium, and Goodheart Institute, Bloodcoagulation and Vascular Medicine Center, Rotterdam, (1998-2014) The Netherlands Abstract Aspirin responsive erythromelalgia is the presenting symptom of thrombocythemia in patients with essential thrombocythemia (ET) and polycythemia vera (PV). Skin punch biopsies taken from the affected areas of erythromelalgia and acrocyanotic compications show typical arteriolar inflammation, fibromuscular intimal proliferation and thrombotic occlusions. If left untreated both microvascular and major thrombosis frequently do occur in thrombocythemia in ET and PV patients, but can easily be cured and prevented by low dose aspirin. The stratification as low, intermediate and high thrombotic risk in the retrospective Bergamo studies has been performed in ET patients not treated with aspirin. The risk of thrombosis in aspirin treated ET and PV is not age dependent when on low dose aspirin, and does recur when not on low dose aspirin during follow-up. The persistence of the Bergamo definition of low, intermediate and high thrombotic risk in the 2012 International Prognostic Score of Thrombosis in ET (IPSET) is applicable for JAK2 mutated ET and PV patients not on aspirin and has led to significant overtreatment with hydroxyurea.
    [Show full text]
  • First-Line Idiopathic Thrombocytopenic Purpura Therapies – Benefits and Limitations
    Rodeghiero.qxp 6/3/08 12:11 Page 25 Coagulation Disorders Platelet Disorders First-line Idiopathic Thrombocytopenic Purpura Therapies – Benefits and Limitations a report by Francesco Rodeghiero and Marco Ruggeri Department of Haematology, San Bortolo Hospital, Vicenza DOI: 10.17925/EOH.2007.0.0.25 Idiopathic thrombocytopenic purpura (ITP) is a primary acquired time. The use of anti-DIg in order to delay or avoid splenectomy proved disease of adults and children characterised by transient or persistent ineffective in at least two prospective studies.16,17 The efficacy of decrease of the platelet count.1,2 Bleeding may be severe and is usually high-dose dexamethasone in inducing a higher rate of durable related to the platelet count. When platelet count is lower than remissions remains unsettled. 20–30x109/l, bleeding is manifested by variably extensive purpura and mucosal haemorrhages; occasionally, in the case of a much lower In a recent paper, Cheng and colleagues18 reported their experience platelet count, this can be severe enough to cause a cerebral of treating 125 new cases of severe ITP with one course of high-dose haemorrhage. Haemorrhagic deaths are reported in fewer than 1% of dexamethasone. A good response was reached in 85% of patients cases. When a safe platelet count (more than 20–30X109/l) cannot be and it was durable in up to 45%. In 50% of those relapsing, a maintained, the mortality rate is greatly increased and proportional to second durable response was achieved with a second course. These the time at risk and age of the patient, reaching an age-adjusted death promising results were confirmed in a subsequent multicentre rate of 13/100 patient-years.3–6 prospective Italian study19 in which high-dose dexamethasone was given every 14 days for up to four cycles, with an initial response rate The diagnosis is one of exclusion, based on the absence of additional of 85.6%.
    [Show full text]
  • Essential Thrombocythemia Characterization: Mutational, Cytokine, and Thrombotic Profiling
    Research Article Published: 21 May, 2019 Journal of Hematology and Oncology Forecast Essential Thrombocythemia Characterization: Mutational, Cytokine, and Thrombotic Profiling Hernandez-Matias L1, Maysonet-Cruz J2, Calzada-Jorge N1, Pérez-Donato L1, Torres Rivera W3, Ramírez-Rodríguez J1, Laureano-Torres F1, Méndez LB3, Ríos O1, Menéndez-Pérez J1, Washington AV1* and Hunter-Mellado R2 1Department of Biology, University of Puerto Rico, Rio Piedras Campus, San Juan, Puerto Rico 2Retrovirus Research Center, Universidad Central del Caribe, School of Medicine, Bayamón, Puerto Rico 3Department of Pathology and Laboratory Medicine, School of Science and Technology, Universidad del Este, Carolina, Puerto Rico Abstract Essential Thrombocythemia (ET) is characterized by a persistent thrombocytosis associated with mutations in Janus Kinase 2 (JAK2V617F), Myeloproliferative Leukemia protein (MPL), and/ or Calreticulin (CALR). Although ET mutational background has been defined for some sub populations, the proportion and diversification of ET mutations have not been defined for the Puerto Rican population. Furthermore, its cytokine profiling and clinical characteristics have also yet to be defined. In order to understand and further provide better treatment for the ET Puerto Rican cohort, this study defines the proportion of common ET mutations, cytokine profiles, plasma levels of Lysyl Oxidase (LOX), soluble Trem-Like Transcript-1 (sTLT-1) and, correlates these levels to the patients’ clinical background. Results show that JAK2V617F, CALR, and MPL mutations were present in the ET Puerto Rican cohort in the proportions of 52%, 18%, and 4% respectively. It was also found that TWEAK/TNSF12 was significantly lower and, that MMP-1, IL-35, IL-8, IFN-α2, IL- 19, IL-22, IL-28A/IFNλ2, and IL-29/IFNλ1 were significantly higher in ET patients when compared to controls.
    [Show full text]
  • The Voice of the Patient: Hemophilia A, Hemophilia B, Von Willebrand Disease and Other Heritable Bleeding Disorders
    The Voice of the Patient A series of reports from the U.S. Food and Drug Administration’s (FDA’s) Patient-Focused Drug Development Initiative Hemophilia A, Hemophilia B, von Willebrand Disease and Other Heritable Bleeding Disorders Public Meeting: September 22, 2014 Report Date: May 2016 Center for Biologics Evaluation and Research (CBER) U.S. Food and Drug Administration (FDA) 1 Table of Contents Introduction ..............................................................................................................3 Overview of bleeding disorders ................................................................................................ 3 Meeting overview ..................................................................................................................... 4 Report overview and key themes .............................................................................................. 5 Topic 1: Disease Symptoms and Daily Impacts That Matter Most to Patients 6 Perspectives on symptoms ........................................................................................................ 7 Perspectives on the overall impact of bleeding disorders on daily life ..................................... 9 Topic 2: Patient Perspectives on Current Approaches to Treatments ............11 Perspectives on current treatment for conditions or symptoms .............................................. 12 Perspectives on an ideal treatment .......................................................................................... 16
    [Show full text]