Sepsis As a Cause of Acquired Protein C and Protein S Deficiency- a Case Report and Literature Review

Total Page:16

File Type:pdf, Size:1020Kb

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. Recently patient was admitted to the hospital for ischemic cerebellar APS: Antiphospholipid Syndrome; DVT: Deep Vein stroke and Warfarin was held due to acute thrombocytopenia. Thrombosis; PE: Pulmonary Embolism; WISN: Warfarin-Induced Warfarin was restarted again on the same dose (7.5 mg) with Skin Necrosis adequate bridging and sent to Nursing Home. About 10 days INTRODUCTION later patient was brought again with fever, hypotension. She was found to be in septic shock likely secondary to pneumonia and Warfarin-induced skin necrosis is a rare (prevalence of 0.01- admitted to Intensive Care Unit. She also complained of black 0.1% of warfarin treated patients) but potentially life threatening eschar lesions under inframammary and groin area. Upon further complication of anticoagulant therapy with an associated questioning it was revealed that lesion was of recent onset about morbidity and mortality requiring immediate drug cessation. 5-6 days after restarting Warfarin. It started as an erythematous Warfarin is a highly effective anticoagulant widely used for the lesion and within 48 hours it progressed to painful black lesions. primary and secondary prevention of thromboembolic disorders It was 6cm by 15 cm underneath the left breast and 7cm by 12cm in current medical practice. The drug is administered orally, in the left groin. Considering the septic shock, necrotizing fasciitis absorbed in the gastrointestinal tract, bound to serum albumin, was considered but it was ruled out by a surgeon. Warfarin metabolized by the hepatic CYP2C9 enzyme, and excreted as an was held and patient was put on heparin intravenously .Biopsy inactive metabolite into bile. Adverse effects associated with the use of warfarin include bleeding, hepatitis, priapism, alopecia, pruritic macular and papular eruption, purple toe syndrome werewas done consistent and it with revealed Warfarin skin Inducedwith superficial Skin Necrosis dermal (WISN). fibrin (cholesterol microembolization), and cutaneous necrosis. Unfortunatelythrombi, hemorrhage despite treatmentand ischemic patient changes. died due These to multi-organ findings failure. CASE PRESENTATION DISCUSSION 43 year old Caucasian female with a history of antiphospholipid syndrome (APLS), multiple DVTs and PEs on chronic Warfarin So far, in literature approximately 300 cases of (WISN) have Cite this article: Kannan A, Chandra S, Lizcano J, Murphy C (2014) Sepsis as a Cause of Acquired Protein C and Protein S Deficiency- a Case Report and Literature Review. JSM Clin Case Rep 2(2): 1028. Kannan et al. (2014) Email: Central been reported. The earliest symptoms of WISN appeared within multifactorial etiology. Recent reintroduction of warfarin and 10 days of restarting the warfarin with the peak incidence also coexistence of septic shock which is known to be one of the between days 3 and 6 (83-90% of cases) [1,2] (Figure 1). patient was already started on heparin by weight to bridge the WISN is a potentially catastrophic complication of warfarin therapycauses of as transient she had aacquired history ofprotein antiphospholipid C deficiency. syndrome Unfortunately with therapy that arises as a consequence of different half lives of multiple episodes of thrombosis in the past and level of protein different vitamin K dependent proteins. One day after initiation C and S could not be accessed. Patient was also started on broad of the usual doses of warfarin, the level of protein C almost spectrum antibiotics on admission due to being in septic shock, decreases by 50 %( same as factor VII). Rest of the vitamin K which could have further contributed to the acquired protein C dependent clotting factors have half life longer than that (48-60 hrs) and declines more slowly in the serum leading to a transient thus reducing vitamin K levels. imbalance in the proteins of the procoagulant-anticoagulant deficiency by reducing gut flora, intestinal malabsorption and system occurring during the initial phase of anticoagulation Our literature search has so far exposed only two cases of which creates a hypercoagulable state. This leads to thrombotic occlusions of the microvasculature causing the necrosis as seen had similar catastrophic outcome as our patient- Death from in our patient. The effect is more pronounced when a higher dose multiorganacquired protein failure. C deficiency [13,14]. One of these patients of warfarin is administered. REFERENCES The commonest cause has been attributed to hereditary 1. Nalbandian RM, Mader IJ, Barrett JL, Pearce JF, Rupp EC. Petechiae, ecchymoses, and Necrosis of skin induced by coumarin congeners: protein C deficiency. [3-5]. Other condition causing WISN is rare, occasionally lethal complication of anticoagulant therapy. Jama. 1965; 192: 603-608. disseminatedacquired causes intravascular of protein coagulation, C deficiency chemotherapeutic like acute thrombosis, agents forwarfarin breast therapy,cancer [6,7 vitamin ], sepsis K [8,9],deficiency primary [5], antiphospholipid liver disease, 2. Horn JR, Danziger LH, Davis RJ. Warfarin-induced skin necrosis: report of four cases. Am J Hosp Pharm. 1981; 38: 1763-1768. syndrome [10], acute exacerbation of ulcerative colitis [11], protein C auto-antibody formation[12] (Figure 2). 3. McGehee WG, Klotz TA, Epstein DJ, Rapaport SI. Coumarin necrosis In our patient, the appearance of necrotic skin lesion which 1984; 101: 59-60. appeared on the 6-th day of reintroduction of warfarin therapy associated with hereditary protein C deficiency. Ann Intern Med. and later, on biopsy was proven to be WISN is speculated to have 4. Rose VL, Kwaan HC, Williamson K, Hoppensteadt D, Walenga J, Fareed 1986; 86: 653-655. J. Protein C antigen deficiency and warfarin necrosis. Am J Clin Pathol. 5. Presgrave P, Ma D. Genetic predisposition to venous thromboembolism: moleculer basis and a practical guide to management.Aust.NZ J. Phleb. 2000; 4: 39-45 6. Taher A, Shamsseddine A, Saghir N, Seoud M, Mourad F, Dabajah B, administration for locally advanced breast cancer. Case report. Eur J et al. Acquired protein C deficiency following cisplatinum-navelbine Gynaecol Oncol. 1999; 20: 323-324. 7. in patients with breast cancer receiving cyclophosphamide, Feffer SE, Carmosino LS, Fox RL. Acquired protein C deficiency Figure 1 Skin necrosis seen underneath her left breast thought to be due to depletion of Protein C and S. 8. methotrexate,Fisher CJ Jr, Yan and SB.5-fluorouracil. Protein C levelsCancer. as 1989; a prognostic 63: 1303-1307. indicator of outcome in sepsis and related diseases. Crit Care Med. 2000; 28: S49- 56. 9. Yan SB, Helterbrand JD, Hartman DL, Wright TJ, Bernard GR. Low levels of protein C are associated with poor outcome in severe sepsis. Chest. 2001; 120: 915-922. 10. Ruiz-Arguelles GJ, Ruiz-Arguelles A, Deleze M, Alarcón-Segovia antiphospholipid syndrome. Relationship to reactivity of D. Acquired protein C deficiency in a patient with primary anticardiolipin antibody with thrombomodulin. J Rheumatol. 1989; 16: 381-383. 11. The cause of thromboembolic complications]. Dtsch Med Wochenschr. Korsten S, Reis HE. [Acquired protein C deficiency in ulcerative colitis. Figure 2 1992; 117: 419-424. consistent with warfarin induced skin necrosis. Histopathological stain revealed dermal fibrin thrombi 12. Mitchell CA, Rowell JA, Hau L, Young JP, Salem HH. A fatal thrombotic JSM Clin Case Rep 2(2): 1028 (2014) 2/3 Kannan et al. (2014) Email: Central disorder associated with an acquired inhibitor of protein C. N Engl J 14. Parsi K, Younger I, Gallo J. Warfarin-induced skin necrosis associated Med. 1987; 317: 1638-1642. 57-61. 13. Argaud L, Guerin C, Thomas L, Fournier G. Extensive coumarin- with acquired protein C deficiency. Australas J Dermatol. 2003; 44: Intensive Care Med. 2001; 27: 1555. induced skin necrosis in a patient with acquired protein C deficiency. Cite this article Kannan A, Chandra S, Lizcano J, Murphy C (2014) Sepsis as a Cause of Acquired Protein C and Protein S Deficiency- a Case Report and Literature Review. JSM Clin Case Rep 2(2): 1028. JSM Clin Case Rep 2(2): 1028 (2014) 3/3.
Recommended publications
  • Protein S Deficiency Presenting with Hemorrhage in a Term Neonate
    : Curre re nt a R C e Ayari et al., Health Care Current Reviews 2018, 6:1 h v t i l e a w DOI: 10.4172/2375-4273.1000219 e s H Health Care: Current Reviews ISSN: 2375-4273 Review Article Open Access Protein S Deficiency Presenting with Hemorrhage in a Term Neonate Fairouz Ayari*, Takoua Bensmail, Essid Latifa, Wiem Barbaria and Samia Kacem Neonatology Intensive Care Unit of the Maternity and Neonatology Center, Tunis, Tunisia Abstract Unexplained bleeding symptoms in otherwise healthy full-term usually present a diagnostic challenge for treating physicians requiring prompt and accurate laboratory investigations to ensure appropriate treatment and possibly avoid long-term morbidity. We report a case of a term neonate with severe protein S deficiency manifested by systemic hemorrhage and multiple organ failure at 9 days of age. We review how protein S influences the coagulation and the fibrinolytic pathways, discussing therapeutic approaches of neonates with purpura fulminans. Keywords: Protein S deficiency; Blood sample; Thrombophilic dis- resuscitation with 20 ml/kg bodyweight (BW) saline solution and, after order blood sampling, intravenous administration of 10 mg vitamin K, 20 ml/kg BW fresh frozen plasma, 20 ml/kg BW packed red blood cells Introduction (5 transfusion cycles), 20 mg/kg BW Phenobarbital and vasoactive Protein S (PS) is an antithrombotic plasma protein that acts mainly drugs. Cerebral ultrasound revealed intraventricular haemorrhage, as a cofactor of activated protein C (APC) anticoagulant activity in the abdominal ultrasound showed splenic hemorrhage and cardiac degradation of factor Va and activated factor VIII [1]. PS circulates in ultrasound showed a floating intracardiac thrombus.
    [Show full text]
  • 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]
  • Protein C and S Deficiency in Deep Vein Thrombosis Patients Referred to Iranian Blood Transfusion Organization, Kermanshah
    Protein C and S Deficiency in Deep Vein Thrombosis Patients Referred to Iranian Blood Transfusion Organization, Kermanshah Mehrdad Payandeh, 1 Mohammad Erfan Zare, 1, 2 Atefeh Nasir Kansestani, 1, 2 Kamran Ma nsouri, 1, 3 Zohreh Rahimi, 1, 4 Amir Hossein Hashemian, 5 Ebrahim Soltanian, 6 Hoshang Yousefi, 6 1Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran 2Student Research Committee, Kermanshah University of Medical Scien ces, Kermanshah, Iran 3Department of Molecular Medicine, School of advanced Medical Technologies, Tehran University of Medical Sciences, Tehran, Iran 4Department of Biochemistry, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Ir an 5Department of Biostatistics, Faculty of Public Health, Kermanshah University of Medical Sciences, Kermanshah, Iran 6Research Center of Iranian Blood Transfusion Organization, Kermanshah, Iran Corresponding Author : Mohammad Erfan Zare, BSC student of M edical Lab Sciences. Medical Biology Research Center, P.O.Box: 1568, Sorkheh Lizheh, Kermanshah University of Medical Sciences, Kermanshah, Iran. E-mail : [email protected] Tel: +98 831 4276473 Fax: +98 831 4276471 Abstract Introduction: Normal homeostas is system has several inhibitor mechanisms in front of the amplifier’s natural clotting enzyme to prevent fibrin clots in the vessels. The main inhibitors of coagulation pathway are antithrombin (AT), protein C and protein S. Patients with hereditary defic iency of coagulation inhibitors are susceptible to venous thromboembolism (VTE). One of the major clinical manifestations of VTE is deep vein thrombosis (DVT). The present study has investigated the frequency of protein C and S deficiency among DVT patients that by using of these results and results from our previous study; we determined the most important hereditary risk factors for DVT in the Kermanshah Province of Iran with the Kurdish ethnic background.
    [Show full text]
  • The Beat: a Publication of the North American Thrombosis Forum
    DECEMBER 2020 A publication of the North American Thrombosis Forum In Memoriam Inside NATF would like to dedicate this issue of to Rajan The Beat In Memoriam ...........1 Laddu. Rajan passed away on November 8, 2020 after suffering a massive pulmonary embolism (PE). Food for Thought: Vitamins, Rajan had several PEs over the years and was actively involved with Diet, and Anticoagulation ..1 NATF. He worked tirelessly to promote blood clot awareness within his community, serving as a patient advocate and establishing A Brother, A Sister, and a the Global Thrombosis Forum (GTF) with his grandfather, Dr. Atul Clotting Disorder: Joelle Laddu. and Matthew’s Story .....1 Throughout his life, Rajan faced physical health challenges and Upcoming Support became determined to help others by going into the healthcare Groups and Events .......2 field. He graduated with honors from Washington University in St. Louis and was in his first year of podiatry school at Kent State Cooking Safely on University College of Podiatric Medicine. He had a passion for Anticoagulation ..........3 ancient Latin and Greek studies, film, music (especially classic rock), and writing poetry. NATF Board and Staff .....6 Rajan will be deeply missed by everyone in the NATF community. A Brother, A Sister, and a Clotting Disorder: Joelle and Matthew’s Story Rajan Laddu In the spring of 2001, Matthew Hochman felt some unusual pain in his right calf. As an avid basketball player, he thought he’d Food for Thought: Vitamins, Diet, and pulled a muscle during a game. Anticoagulation “My calf felt like a rock, and the pain persisted for several weeks Tara Lech, PharmD is an Anticoagulation and Cardiovascular Clinical and began to move up my leg.
    [Show full text]
  • Utility of Current Thrombophilia Screening in Young Patients with Stroke and TIA
    Open access Original article Stroke Vasc Neurol: first published as 10.1136/svn-2018-000169 on 12 September 2018. Downloaded from Utility of current thrombophilia screening in young patients with stroke and TIA Vafa Alakbarzade,1 Alice Taylor,2 Marie Scully,2 Robert Simister,1 Arvind Chandratheva1 To cite: Alakbarzade V, Taylor A, ABSTRACT transient ischaemic attack (TIA) is not Scully M, et al. Utility of current Introduction Approximately 40% of strokes in established. thrombophilia screening in young adults are cryptogenic. The diagnostic yield of Thrombophilias are broadly defined as young patients with stroke thrombophilia screening remains controversial. We aimed and TIA. Stroke and Vascular inherited or acquired coagulation disorders to determine utility of current thrombophilia testing for 3 4 Neurology 2018;0: e000169. predisposing to thrombosis. Antithrombin doi:10.1136/svn-2018-000169 young patients with stroke and transient ischaemic attack (AT), protein C and S deficiency, factor V (TIA). Leiden (FVL) and factor II mutations are ► Additional material is Methods We present a retrospective review of all patients published online only. To view with stroke and TIA ≤60 years presenting to University rare inherited thrombophilias associated please visit the journal online College London Hospital stroke unit and daily TIA clinic with an increased risk of venous thrombosis, (http:// dx. doi. org/ 10. 1136/ svn- from 1 January 2015 to 1 August 2016. Consecutive but their relation to arterial ischaemic stroke 2018- 000169). 5–16 clinical records and thrombophilia tests, including factor and TIA is less well established. Accu- Received 31 May 2018 V Leiden (FVL), prothrombin G20210A mutation (PGM), rate diagnosis and clinical relevance of AT, Revised 7 August 2018 antiphospholipid antibody (APA), and protein S, C and protein C and S deficiency to acute stroke Accepted 17 August 2018 antithrombin (AT) levels, were reviewed.
    [Show full text]
  • Inherited Thrombophilia Protein S Deficiency
    Inherited Thrombophilia Protein S Deficiency What is inherited thrombophilia? If other family members suffered blood clots, you are more likely to have inherited thrombophilia. “Inherited thrombophilia” is a condition that can cause The gene mutation can be passed on to your children. blood clots in veins. Inherited thrombophilia is a genetic condition you were born with. There are five common inherited thrombophilia types. How do I find out if I have an They are: inherited thrombophilia? • Factor V Leiden. Blood tests are performed to find inherited • Prothrombin gene mutation. thrombophilia. • Protein S deficiency. The blood tests can either: • Protein C deficiency. • Look at your genes (this is DNA testing). • Antithrombin deficiency. • Measure protein levels. About 35% of people with blood clots in veins have an inherited thrombophilia.1 Blood clots can be caused What is protein S deficiency? by many things, like being immobile. Genes make proteins in your body. The function of Not everyone with an inherited thrombophilia will protein S is to reduce blood clotting. People with get a blood clot. the protein S deficiency gene mutation do not make enough protein S. This results in excessive clotting. How did I get an inherited Sometimes people produce enough protein S but the thrombophilia? mutation they have results in protein S that does not Inherited thrombophilia is a gene mutation you were work properly. born with. The gene mutation affects coagulation, or Inherited protein S deficiency is different from low blood clotting. The gene mutation can come from one protein S levels seen during pregnancy. Protein S levels or both of your parents.
    [Show full text]
  • PROTEIN C DEFICIENCY 1215 Adulthood and a Large Number of Children and Adults with Protein C Mutations [6,13]
    Haemophilia (2008), 14, 1214–1221 DOI: 10.1111/j.1365-2516.2008.01838.x ORIGINAL ARTICLE Protein C deficiency N. A. GOLDENBERG* and M. J. MANCO-JOHNSON* *Hemophilia & Thrombosis Center, Section of Hematology, Oncology, and Bone Marrow Transplantation, Department of Pediatrics, University of Colorado Denver and The ChildrenÕs Hospital, Aurora, CO; and Division of Hematology/ Oncology, Department of Medicine, University of Colorado Denver, Aurora, CO, USA Summary. Severe protein C deficiency (i.e. protein C ment of acute thrombotic events in severe protein C ) activity <1 IU dL 1) is a rare autosomal recessive deficiency typically requires replacement with pro- disorder that usually presents in the neonatal period tein C concentrate while maintaining therapeutic with purpura fulminans (PF) and severe disseminated anticoagulation; protein C replacement is also used intravascular coagulation (DIC), often with concom- for prevention of these complications around sur- itant venous thromboembolism (VTE). Recurrent gery. Long-term management in severe protein C thrombotic episodes (PF, DIC, or VTE) are common. deficiency involves anticoagulation with or without a Homozygotes and compound heterozygotes often protein C replacement regimen. Although many possess a similar phenotype of severe protein C patients with severe protein C deficiency are born deficiency. Mild (i.e. simple heterozygous) protein C with evidence of in utero thrombosis and experience deficiency, by contrast, is often asymptomatic but multiple further events, intensive treatment and may involve recurrent VTE episodes, most often monitoring can enable these individuals to thrive. triggered by clinical risk factors. The coagulopathy in Further research is needed to better delineate optimal protein C deficiency is caused by impaired inactiva- preventive and therapeutic strategies.
    [Show full text]
  • Hereditary Protein S Deficiency Presenting Acute Pulmonary Embolism
    CASE REPORT pISSN 1225-7737/eISSN 2234-8042 Yeungnam Univ J Med 2014;31(1):52-55 http://dx.doi.org/10.12701/yujm.2014.31.1.52 Hereditary protein S deficiency presenting acute pulmonary embolism Jiwan Kim, Sung Hea Kim, Sang Man Jung, Sooyoun Park, HyungMin Yu, Sanghee An, Seonghui Kang, Hyun-Joong Kim Department of Cardiovascular Medicine, Konkuk University School of Medicine, Seoul, Korea Protein S deficiency is one of the several risk factors for thrombophilia and can cause blood clotting disorders such as deep vein thrombosis and pulmonary embolism. A 54-year-old man was admitted with the complaint of dyspnea and was diagnosed with pulmonary embolism. The patient had very low level of free protein S, total protein S antigen, and protein S activity (type I protein S deficiency). In history taking, we found that his mother, 78 year old, had a history of same disease 10 years ago, and confirmed the pronounced low level of protein S. The patient’s son also had very low level of protein S, however there had not been any history of pulmonary embolism yet. This case study suggests that asymptomatic persons with a family history of protein S deficiency and pulmonary embolism should be checked regularly for early detection of the disease, as protein S deficiency can be suspected. Keywords: Pulmonary embolism; Protein S deficiency; Family history INTRODUCTION CASE Protein S deficiency is a blood clotting disorder that affects A 54-year-old man was admitted in the hospital with dysp- just a few thousand people worldwide. Decreased total or nea (NYHA functional class III) and left foot edema for 3 free protein S antigen levels and impaired function lead to months.
    [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]
  • 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.
    [Show full text]
  • An Adolescent with Protein S Deficiency Terence A
    J Am Board Fam Pract: first published as 10.3122/jabfm.7.6.523 on 1 November 1994. Downloaded from Thrombolysis In Pulmonary Embolism: An Adolescent With Protein S Deficiency Terence A. Degan, MD Pulmonary embolism is rare in nonhospitalized The initial working diagnosis of status asthma children, and essentially all will have a serious was made, but when a peak expiratory flow rate of underlying disorder or predisposing factor. 1 This 460 L/min was found, a ventilation-perfusion report presents a case of an adolescent boy whose lung scan was ordered .(Figure 2). This scan re­ condition was successfully treated with recombi­ vealed a high probability for massive pulmonary nant tissue plasminogen activator (rt-PA); he was emboli. A subsequent family history revealed that subsequently found to have protein S deficiency. both his brother and mother had been hospital­ Alteplase (Activase), a recombinant tissue plas­ ized for deep venous thrombosis in the past. Also minogen activator, was approved in June 1990 by noted was a very minor injury that had occurred the Food and Drug Administration for use in the to his left calf 2 weeks earlier. Sera was then management of acute massive pulmonary embo­ drawn for proteins Sand C, antithrombin III, and lism in adults. Urokinase and streptokinase had anticardiolipin antibody. Next, 70 mg of rt-PA both been approved for this indication by 1978. (1.3 mg/kg) was given intravenously at an infu­ There are no studies comparing thrombolytic sion rate of 2 hours and was immediately fol­ therapy (followed by heparin) with heparin alone lowed by an intravenous heparin bolus and infu­ in children with acute pulmonary embolism.
    [Show full text]