DOCSLIB.ORG

Clinical Predictors and Genetic Determinants of Response to Warfarin Therapy in Kenyan Patients David Gitonga Nyamu

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Clinical Predictors and Genetic Determinants of Response to Warfarin Therapy in Kenyan Patients David Gitonga Nyamu UNIVERSITY OF NAIROBI CLINICAL PREDICTORS AND GENETIC DETERMINANTS OF RESPONSE TO WARFARIN THERAPY IN KENYAN PATIENTS DAVID GITONGA NYAMU, BPharm (UoN), MPharm (UoN), Fellow, Implementation Science (UoN/UMB) U80/52841/2018 Thesis Submitted in Fulfilment of Requirements for the Award of Doctor of Philosophy (PhD) in Clinical Pharmacy of the University of Nairobi Department of Pharmaceutics & Pharmacy Practice 2019 i ii SIMILARITY INDEX AND ORIGINALITY REPORT iii iv DEDICATION This work is dedicated to my family members, especially my wife, Lydia Gitonga, and our children, Alvin Gitonga and Belva Gitonga, who kept on motivating and reminding me that I was equal to the task whenever I felt down. Additionally, you patiently missed me at home during the tedious data collection, analysis and Thesis writing. Special dedication to my parents, for your endless love towards academics and for imparting the value of education on me early in childhood. v ACKNOWLEDGEMENTS I wish to recognize and thank all my supporters of academic dreams and aspiration throughout my entire education life. I wish to sincerely thank my great Supervisors, Professors: A.N. Guantai, G.O. Osanjo and E. Aklillu, for your relentless guidance and instilling in me the spirit of hard work through your very constructive criticisms. Thank you for taking huge portions of your busy schedules and dedicating it to my work without a single penny. Special gratitude to Professor Osanjo for thoroughly scrutinizing what went on the paper. Exceptional acknowledgements to Professor Guantai for your persistence and driving force towards completion of this Thesis. Many thanks to Institutional Review Board, Kenyatta National Hospital/University of Nairobi- Ethics and Research Committee (KNH/UoN-ERC) for approving the study protocol. Thanks to the Head of Department of Medicine (KNH), Dr Paul Etau, and Head of Department of Surgery, Dr Bernard Githae as well as section Head of Cardiothoracic Surgery, Dr Tom Omulo for granting permission to carry the study in the designated anticoagulation clinics. Thanks to Chairman, Department of Haematology & Blood Transfusion (UoN), Prof. W. Mwanda, for allowing me to carry out INR tests in the facility. I also wish to thank the members of staff in the haemato-oncology, cardiothoracic and medical clinics for their immeasurable support during data collection. Special thanks to my collaborators especially the National Commission for Science, Technology & Innovation (NACOSTI) for funding part of this study. I am grateful to University of Nairobi for waiving my tuition fees for the Doctorate study. Many thanks to the staff of African institute for Biomedical Science and Technology (AiBST) laboratory for allowing me store study samples as well as perform DNA extraction in the premises. Thanks to Professor Wallace Bulimo for freely allowing me to quantify the DNA yields in Wellcome Trust Research Laboratory. Gratitude to Dr Aron Abera of Inqaba Biotechnical Industries (Pty), South Africa, for allowing genetic testing in their laboratory. vi I am greatly indebted to all my research assistants of whom I could not do without. To name but a few, thanks to Ephraim Mugane (school of Nursing Sciences, UoN), John Nyakwaka Opiyo and Kenneth Meme (Bleeding Centre, KNH), Gladys Wambui Muthoni (Department of Pharmaceutics & Pharmacy Practice, UoN), Daniel Juma (Department of Pharmacology & Pharmacognosy, UoN) and Richard Achoki (Department of Pharmaceutics & Pharmacy Practice, UoN). Thanks to Philomena Wangui (South End Cybercafé) for providing free internet services when I absolutely needed it. I also acknowledge my biostatistician, Albert Kimtai Tele for providing statistical consultancy services as well as spending precious time in statistical analysis. Many thanks to all patients who were undergoing anticoagulation management at Kenyatta Hospital for willingly and tirelessly agreeing to participate as well as providing blood samples for the study. I thank the LORD ALMIGHTY for making me who I am and for giving me the greatest gift of all, life. vii TABLE OF CONTENTS SIMILARITY INDEX AND ORIGINALITY REPORT ........................................................... iii APPROVAL BY SUPERVISORS ............................................ Error! Bookmark not defined. DEDICATION ................................................................................................................ iv ACKNOWLEDGEMENTS ................................................................................................ vi TABLE OF CONTENTS ................................................................................................. viii LIST OF TABLES ............................................................................................................. xv LIST OF FIGURES .......................................................................................................... xix LIST OF EQUATIONS...................................................................................................... xx ABBREVIATIONS AND ACRONYMS .............................................................................. xxi DEFINITION OF TERMS .............................................................................................. xxiii PUBLICATIONS FROM THESIS WORK .......................................................................... xxv ABSTRACT .................................................................................................................. xxvi CHAPTER ONE: INTRODUCTION .................................................................................... 1 1.1: Background to the Research................................................................................................. 1 1.2: Demographics and Doses of Warfarin among Patients ........................................................ 2 1.3: Monitoring of Response to Warfarin Therapy ..................................................................... 3 1.4: Factors Impacting on Warfarin Dose Variations among Patients ........................................ 4 1.5: Statement of the Research Problem ..................................................................................... 7 1.6: Research Questions .............................................................................................................. 9 1.7: Objectives of the Study ...................................................................................................... 10 1.7.1: General Objective ........................................................................................................ 10 1.7.2: Specific Objectives ...................................................................................................... 10 1.8: Research Hypothesis .......................................................................................................... 11 1.9: Justification of the Study .................................................................................................... 12 viii CHAPTER TWO: LITERATURE REVIEW ......................................................................... 14 2.1: Perspectives of Literature Review ..................................................................................... 14 2.2: Types of Thrombotic Disorders ......................................................................................... 14 2.3: Epidemiology of Thromboembolic events ......................................................................... 15 2.4: Risk factors for Development of Thromboembolism ........................................................ 16 2.5: Long Term Management of Thromboembolic events ....................................................... 16 2.6: Mechanisms of Action of Warfarin.................................................................................... 17 2.7: Clinical Uses and Doses of Warfarin ................................................................................. 18 2.8: Practical Uses of Warfarin ................................................................................................. 19 2.9: Adverse Effects of Warfarin .............................................................................................. 20 2.10: Drug Interactions among Patients Receiving Warfarin Therapy ..................................... 21 2.11: Warfarin interactions with other diseases, drugs and herbs ............................................. 22 2.12: Monitoring of the Therapeutic Response to Warfarin ..................................................... 23 2.13: Management of Excessive Anticoagulation with warfarin ............................................. 23 2.14: Pharmacogenomics of Warfarin ....................................................................................... 23 2.14.1: Vitamin K Epoxide Reductase Complex (VKORC1) ................................................ 24 2.14.2: Cytochrome P450 2C9 (CYP 2C9) ............................................................................ 25 2.14.3: Cytochrome P450 4F2 (CYP 4F2) ............................................................................ 26 2.15: Pharmacogenomic Studies Characterizing Warfarin Metabolizing Enzymes ................. 28 2.15.1: Population Distribution of Allelic Frequencies of Warfarin Metabolizing Genes .... 29 2.15.2: Genetic Factors affecting the Response to Warfarin Therapy ................................... 31 2.16: Gaps in Literature ............................................................................................................
Load more

Recommended publications
  • An Atypical Case of Warfarin-Induced Skin Necrosis
    CASE REPORT An Atypical Case of Warfarin-Induced Skin Necrosis Lindsay R. Sklar, MD* *Wayne State University, Department of Dermatology, Dearborn, Michigan Anne Messman, MD, FACEP† †Sinai-Grace Hospital, Department of Emergency Medicine, Detroit, Michigan Section Editor: Rick A. McPheeters, DO Submission history: Submitted December 19, 2016; Revision received March 8, 2017; Accepted March 30, 2017 Electronically published October 11, 2017 Full text available through open access at http://escholarship.org/uc/uciem_cpcem DOI: 10.5811/cpcem.2017.3.33373 Skin necrosis is a relatively rare, potentially fatal side effect of warfarin. It is most commonly reported within 10 days of initiation of therapy in warfarin-naïve patients. We report an atypical case of warfarin-induced skin necrosis upon recommencement of warfarin in a non-naïve warfarin patient. [Clin Pract Cases Emerg Med. 2017;1(4):359–361.] INTRODUCTION were significant for a normal platelet level of 180,000/mm,³ Warfarin is currently the most widely prescribed oral partial thromboplastin time of 27.7 sec, prothrombin time of anticoagulant in North America. Thrombosis is a rare, 21.8 sec, and an international normalized ratio (INR) of 1.87. paradoxical, and potentially fatal adverse effect of the drug. Computerized tomography (CT) of the abdomen with and Skin necrosis occurs secondary to the development of without intravenous contrast showed no evidence of microthrombi and endothelial cell damage in the vessels of malignancy or hemorrhage. dermal and subcutaneous tissues. Since this rare The patient had been on the same warfarin regimen (7.5mg complication was first recognized in 1943, there have been three days a week and 10mg four days a week) for two years an estimated 300 cases reported, affecting approximately prior to presentation to our ED; it had been initiated after the 0.01-0.1% of patients on the drug.1 Typically, warfarin- development of a deep vein thrombosis and pulmonary induced skin necrosis presents within three to ten days of embolism.
    [Show full text]
  • Sepsis As a Cause of Acquired Protein C and Protein S Deficiency- a Case Report and Literature Review
    Central JSM Clinical Case Reports Case Report *Corresponding author Arun Kannan, Internal Medicine, Canton Medical Education Foundation, 1501 N Campbell Ave PO BOX Sepsis as a Cause of Acquired 245212 Tucson AZ 85712, USA, Tel: 3304121641; Fax: 5206265721; Email: Submitted: 14 December 2014 Protein C and Protein S Accepted: 30 December 2013 Published: 31 December 2013 Deficiency- a Case Report and Copyright © 2014 Kannan et al. Literature Review OPEN ACCESS Arun Kannan*, Sweta Chandra, Jose Lizcano, Christie Murphy Keywords Internal Medicine, Canton Medical Education Foundation, USA • Sepsis • Warfarin • Skin necrosis Abstract • Protein C, Protein S Warfarin Induced Skin Necrosis is a well-known and dreaded complication in patients who is being started on warfarin without adequate bridging with other anticoagulants. The mechanism is thought to be due to protein C deficiency acquired after initial exposure to warfarin. We present a rather unusual cause of protein C deficiency due to sepsis resulting in warfarin induced skin necrosis. 43 year old lady who has been on chronic warfarin therapy secondary to anti phospholipid syndrome was admitted to the hospital for acute ischemic cerebellar stroke. Warfarin was held due to acute thrombocytopenia. She was discharged to a facility after restarting the warfarin at the same dose. She presented back to the hospital with septic shock due to pneumonia. She was found to have multiple necrotic areas consistent with skin necrosis. Unfortunately, patient died due to multi organ failure despite goal directed therapy. This case demonstrates the importance of recognizing the sepsis as an acquired cause of protein C deficiency. ABBREVIATIONS therapy for 10 years was admitted to the hospital.
    [Show full text]
  • Warfarin Therapy: Tips and Tools for Better Control
    David A. Garcia, MD; Michael J. Schwartz, MD Anticoagulation Clinic, Warfarin therapy: University of New Mexico Health Sciences Center, Albuquerque (Dr. Garcia); Tips and tools for better control Health Services at Columbia University, New York, NY (Dr. Schwartz, retired) Monitoring patients on warfarin therapy is challenging. [email protected] Th e tools highlighted here—from online forums and Dr. Garcia reported that he receives Web-based dosing calculators to patient education research support from, and serves as a consultant to, Bristol-Myers materials and self-monitors—can help. Squibb and serves as a consultant to Boehringer Ingelheim; Dr. Schwartz reported that he has no potential confl ict of interest relevant to this article. pproximately 4 million Americans are receiving long- PRACTICE term oral anticoagulation therapy to reduce the risk of RECOMMENDATIONS Aprimary and secondary thromboembolism.1,2 And, as › INR testing by an anti- the population ages, the number of patients on lifelong thera- coagulation management py with warfarin—the only oral anticoagulant available in the service or private clinician United States until dabigatran was approved by the US Food can be reduced to intervals of and Drug Administration late last year3—is expected to grow.4 as long as 4 weeks, but should Such patients present a challenge for family physicians. be more frequent when dos- Warfarin is notorious for having both a narrow therapeutic ing adjustments occur. B index and numerous drug and dietary interactions.5,6 To safe- › Weekly patient self-testing guard patients on warfarin therapy, frequent, and diligent, is associated with comparable monitoring is required.
    [Show full text]
  • Understanding Calcinosis and Calciphylaxis
    PRACTICE DEVELOPMENT Understanding calcinosis and calciphylaxis KEY WORDS Calcinosis cutis is a rare cause of non-healing leg ulceration. There are many factors Calcinosis cutis that can delay the healing of venous leg ulceration and the deposition of calcium in Calciphylaxis the skin known as calcinosis cutis is one of these factors. There are five distinct forms: Warfarin-induced skin dystrophic calcification, metastatic calcification, idiopathic calcification, iatrogenic necrosis calcification and calciphylaxis. Warfarin skin necrosis has common clinical features with calciphylaxis and is therefore included in this article, which describes the types of calcinosis cutis, their clinical presentations and limited treatment options. The aim is to highlight these unusual causes and to assist healthcare professionals when faced with a non-healing ulcer. eg ulceration can be defined as a defect in neurotransmission and the blood coagulation the dermis located on the leg (Franks et al, pathway. At a cellular level, it is implicated in 2016). Leg ulceration is a significant clinical cell-to-cell communication (Walshe and Fairley, Lproblem with the majority attributing venous 1995). In the skin, it is specifically concerned with hypertension as the underlying disease process with keratinocyte proliferation, differentiation and venous leg ulceration affecting 1% of the population adhesion (Smith and Yamada, 2002). in the western world (Posnett et al, 2009). However, The level of serum calcium is closely there is a multitude of causative factors of leg ulcers, controlled by the parathyroid hormone. with the term leg ulcer purely signifying the clinical Regardless of this regulation, it is possible for manifestation and not the underlying aetiology.
    [Show full text]
  • Warfarin-Induced Breast Necrosis: a Case Report
    CASE REPORT Warfarin-Induced Breast Necrosis: A Case Report Aghygh Heidari1, Feridoun Sabzi2 1 Department of Anesthesiology, Imam Ali Hospital, Kermanshah University of Medical Sciences, Kermanshah, Iran 2 Department of Cardiovascular Surgery, Imam Ali Hospital, Kermanshah University of Medical Sciences, Kermanshah, Iran Received: 2 Feb. 2016; Accepted: 6 Oct. 2016 Abstract- Warfarin-induced Breast necrosis (WIBN) is an exceedingly rare sequel to warfarin therapy. A close relationship was confirmed between congenital deficiency of protein C and S and warfarin usage. A predilection for this complication has been reported in fatty middle-aged women who are managing by warfarin. The sudden eruption of the bullous lesion, within mean three days after starting of warfarin therapy with or without echymous or petechia is the first sign of WIBN. The maintenance of INR in the low normal range, reducing the loading doses, especially in fatty cases may be a preventive measure in reducing risk and incidence of breast necrosis in the high-risk subjects. Early diagnosis and management are important to prevent significant tissue loss. A rare case of warfarin-related necrosis of the left breast following a mitral valve replacement is reported. Current knowledge and the preventing methods and treatment of this rare complication are reviewed. © 2018 Tehran University of Medical Sciences. All rights reserved. Acta Med Iran 2018;56(4):281-284. Keywords: Warfarin; Necrosis; Breast Introduction Early diagnosis of this rare clinical complication of warfarin allows the cardiac surgeon and cardiologist to Skin necrosis following warfarin usage has a wide make a preventive measure for progression of the range of incidence from 0.01 in low-risk subjects to disease.
    [Show full text]
  • Probable Fondaparinux-Associated Bullous Hemorrhagic Dermatosis
    PRACTICE | CASES CPD Probable fondaparinux-associated bullous hemorrhagic dermatosis Catherine Anne Lovatt MD, Wen Qing Wendy Ye MD MSc, Haroon Yousuf MD MHSc n Cite as: CMAJ 2021 May 31;193:E801-4. doi: 10.1503/cmaj.202747 90-year-old woman was admitted to a tertiary hospital with hypoxia secondary to pulmonary edema and KEY POINTS on going antibiotic therapy following an infected hip • Bullous hemorrhagic dermatosis is an uncommon nonimmune prosthesis.A The patient’s medical history included heparin- adverse drug reaction to heparin-based anticoagulants induced thrombocytopenia following administration of dalte- including unfractionated heparin, low-molecular-weight parin, atrial fibrillation (CHADS2 score of 3) and lower gastrointes- heparin and fondaparinux that typically occurs within 7 days of tinal bleeding related to diverticular disease. The patient did not drug exposure. report any skin allergies. On admission, she was 4 weeks post- • The reaction is more common in older adults, and lesions are usually found on the extremities. removal of right hip hardware, débridement and revision to a cemented right hip hemiarthroplasty for methicillin-sensitive • There are typically no changes to coagulation tests such as the international normalized ratio, partial thromboplastin time or Staphylococcus aureus infection, and was completing a 6-week the prothrombin time. course of cephalexin and rifampin. She had previously taken • Bullous hemorrhagic dermatosis is self-resolving, although apixaban for stroke prophylaxis but, before admission, her apixa- careful monitoring of bleeding, and supportive management ban was switched to warfarin because of its interaction with such as wound care and transfusion of blood products, may rifampin. However, given the interaction between warfarin and be required.
    [Show full text]
  • Allentown Cmeconference
    ALLENTOWN CME CONFERENCE Sam Study Group - Early Childhood Illness............................................................................................. Menopause and Post Gynecological Reproductive Care ....................................................................... Pulmonary Function Tests – Basic Interpretation for Primary Care ...................................................... Dyslipidemia – New Guidelines .............................................................................................................. Transitioning Patients with Autism from Pediatric to Adult Practices ................................................... Herbs, Supplements and Athletes .......................................................................................................... Tools to Treat Adult Patients with Obesity: An Update on Bariatric Surgery and Pharmacologic Agents Case Studies of Common Behavioral Health Scenarios.......................................................................... Opioid Prescribing: Safe Practice, Changing Lives ................................................................................. Act 31 Child Abuse Recognition .............................................................................................................. Integrating Genetic Testing into Family Medicine - Part I, an Overview .............................................. Drugs of Abuse .......................................................................................................................................
    [Show full text]
  • Mallory Prelims 27/1/05 1:16 Pm Page I
    Mallory Prelims 27/1/05 1:16 pm Page i Illustrated Manual of Pediatric Dermatology Mallory Prelims 27/1/05 1:16 pm Page ii Mallory Prelims 27/1/05 1:16 pm Page iii Illustrated Manual of Pediatric Dermatology Diagnosis and Management Susan Bayliss Mallory MD Professor of Internal Medicine/Division of Dermatology and Department of Pediatrics Washington University School of Medicine Director, Pediatric Dermatology St. Louis Children’s Hospital St. Louis, Missouri, USA Alanna Bree MD St. Louis University Director, Pediatric Dermatology Cardinal Glennon Children’s Hospital St. Louis, Missouri, USA Peggy Chern MD Department of Internal Medicine/Division of Dermatology and Department of Pediatrics Washington University School of Medicine St. Louis, Missouri, USA Mallory Prelims 27/1/05 1:16 pm Page iv © 2005 Taylor & Francis, an imprint of the Taylor & Francis Group First published in the United Kingdom in 2005 by Taylor & Francis, an imprint of the Taylor & Francis Group, 2 Park Square, Milton Park Abingdon, Oxon OX14 4RN, UK Tel: +44 (0) 20 7017 6000 Fax: +44 (0) 20 7017 6699 Website: www.tandf.co.uk All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without the prior permission of the publisher or in accordance with the provisions of the Copyright, Designs and Patents Act 1988 or under the terms of any licence permitting limited copying issued by the Copyright Licensing Agency, 90 Tottenham Court Road, London W1P 0LP. Although every effort has been made to ensure that all owners of copyright material have been acknowledged in this publication, we would be glad to acknowledge in subsequent reprints or editions any omissions brought to our attention.
    [Show full text]
  • Purpura Fulminanis
    ISSN: 2689-4610 Case Report JOJ Dermatol & Cosmet Volume 1 Issue 3 - December 2018 Copyright © All rights are reserved by Khadiga Ahmed Ismail DOI: 10.19080/JOJDC.2018.01.555564 Purpura Fulminanis Mahmoud Khalifa Marzouq1, Khadiga Ahmed Ismail2,3*, Ahmed Mahmoud Khalifa4 and Osama Mahmoud Khalifa5 1Consaltant of Dermatology and Venereology, King Faisal specialized Hospital, Saudi Arabia 2Department of Laboratory Medicine, Taif University, Saudi Arabia 3Department of Parasitology, Ain-Shams University, Egypt 4Department Forensic and Toxicology, Ain-Shams University, Egypt 5Faculty of Medicine, Ain-Shams University, Egypt Submission: December 05, 2018; Published: December 20, 2018 *Corresponding author: Khadiga Ahmed Ismail, Department of Laboratory Medicine & Department of Parasitology, King Faisal specialized Hospital & Ain-Shams University, Saudi Arabia Abstract Purpura Fulminanis (PF) is an emergency progressive thrombotic disorder in which there is skin necrosis, Disseminated Dntravascular Coagulation (DIC) and multiorgan failure. It may complicate severe sepsis or may occur as an autoimmune response to other infection as varicella. management promptly. We present a case of purpura fulminanis who died, unfortunately, after 8 days due to severe sepsis. Also, it may associate with severe heritable deficiency of protein C or protein S. PF is a rapidly fatal disease, so it needs rapid diagnosis and Keywords: Purpura Fulminanis; Disseminated Dntravascular Coagulation; Coronary Artery Bypass Grafting; Disseminated Intravascular Coagulation;
    [Show full text]
  • Warfarin-Induced Skin Necrosis Within Psoriatic Plaques
    UC Davis Dermatology Online Journal Title Warfarin-induced skin necrosis within psoriatic plaques Permalink https://escholarship.org/uc/item/4gf5r5qk Journal Dermatology Online Journal, 25(6) Author Eichhoff, Gerhard Publication Date 2019 DOI 10.5070/D3256044495 License https://creativecommons.org/licenses/by-nc-nd/4.0/ 4.0 Peer reviewed eScholarship.org Powered by the California Digital Library University of California Volume 25 Number 6| June 2019| Dermatology Online Journal || Photo Vignette 25(6):13 Warfarin-induced skin necrosis within psoriatic plaques Gerhard Eichhoff MD PhD FRACP Affiliations: Dermatology Service Capital & Coast and Hutt Valley District Health Board, Wellington Regional Hospital, New Zealand Corresponding Author: Gerhard Eichhoff MD, PhD, Wellington Regional Hospital, PB 7902, New Zealand, Tel: 64-43855999, Email: [email protected] dermatosis on the same place as that of healed Abstract cutaneous lesions [7]. In current medical practice, A myriad of different phenomena exist in the warfarin, a vitamin K antagonist, is one of the most dermatological literature which are based on the frequently used anticoagulants for primary and concept of locus minores resistentiae. The most secondary prevention of thromboembolic disorders. commonly described phenomenon is the Koebner With a prevalence of 0.01%–0.1%, warfarin-induced phenomenon, which is classically associated with the skin necrosis (WISN) is a rare complication with a high emergence of psoriatic lesions post trauma. Warfarin- morbidity [3]. The presented case describes WSIN induced skin necrosis (WISN) is a rare but severe side effect that leads to necrosis of the skin, within psoriatic plaques. predominantly on areas with increased subcutaneous fat.
    [Show full text]
  • Hypercoagulability Syndromes
    REVIEW ARTICLE Hypercoagulability Syndromes Robert H. Thomas, MD ypercoagulability can be defined as the tendency to have thrombosis as a result of certain inherited and/or acquired molecular defects. Clinical manifestations of hy- percoagulability can be devastating and even lethal. In the past 20 years, the origin of most of these diverse hypercoagulability syndromes has been elucidated. Cur- Hrently, hypercoagulability disorders can be correctly diagnosed in approximately 80% to 90% of patients. Defining the cause of hypercoagulability may determine the type and duration of treat- ment for the associated thrombosis. The discovery of an occult carcinoma allows for the possibil- ity of early and possibly curative treatment. Finding a genetic defect in coagulation allows for test- ing of asymptomatic family members as well. The purpose of this review is to provide internists with a logical approach to the identification and treatment of hypercoagulability syndromes. Arch Intern Med. 2001;161:2433-2439 Most commonly, thrombosis is the result depending on the ethnic backgrounds of of more than one “hit.” For example, pa- persons in a particular geographic area. tients with the factor V Leiden defect may be asymptomatic until they start taking oral Disorder Incidence, % contraceptives. Patients with antithrom- Antiphospholipid antibody 28 syndrome bin deficiency may go on without inci- Activated protein C resistance 25 dent until they undergo a hernia repair. Elevated coagulation factor VIII 25 Also, multiple genetic defects predispose levels one to thrombosis much more than does Malignancy 15 a single defect.1,2 Some defects are known Sticky platelet syndrome 14 to be more powerful predictors than oth- Protein C deficiency 10 ers.
    [Show full text]
  • A 52-Year-Old Man with Ecchymotic Leg Ulcers
    Journal of the Louisiana State Medical Society CLINICAL CASE OF THE MONTH A 52-Year-Old Man With Ecchymotic Leg Ulcers Seema Walvekar, MD; Jessica L. Johnson, PharmD, BCPS; Emily Kauffman, DO; Rachna Jetly, MD; Bennett P. deBoisblanc, MD, FCP, FACCP, FCCM CASE PRESENTATION He was transfused with packed red blood cells and fresh frozen plasma. Therapy for presumed warfarin-induced A 52-year-old man presented to the emergency depart- skin necrosis (WISN), i.e. heparin or recombinant activated ment with a one-day history of pain and bluish discoloration protein C infusion, was withheld due to the elevated INR, of the tips of the great toes of both his feet that rapidly pro- thrombocytopenia, and a low hemoglobin level. gressed to worsening pain, swelling, and discoloration of Skin punch biopsy of the purpura over his legs showed both feet and legs. His past medical history was significant separation of the stratum corneum, focal necrosis of acrosyr- for many years of heavy alcohol use and an episode of un- inx, and thrombosis of blood vessels throughout the dermis provoked venous thromboembolism two months prior to and subcutaneous tissue (Figure 2). There was no evidence presentation. At that time, he was found to be heterozygous of vasculitis. He ultimately developed limb gangrene, re- for Factor V Leiden mutation. After initial anticoagulation quiring bilateral above knee amputations. with fondaparinux, he was started on warfarin 7.5 mg daily. A removable inferior vena cava filter was placed for unclear DISCUSSION indications. In the emergency department, his review of systems was remarkable for a one-day history of melena Skin necrosis is a rare complication of anticoagula- with hematemesis.
    [Show full text]