THROMBOTIC THROMBOCYTOPENIC PURPURA AND HEMOLYTIC UREMIC SYNDROME DANA BARTLETT, BSN, MSN, MA, CSPI Dana Bartlett is a professional nurse and author. His clinical experience includes 16 years of ICU and ER experience and over 20 years of as a poison control center information specialist. Dana has published numerous CE and journal articles, written NCLEX material, written textbook chapters, and done editing and reviewing for publishers such as Elsevire, Lippincott, and Thieme. He has written widely on the subject of toxicology and was recently named a contributing editor, toxicology section, for Critical Care Nurse journal. He is currently employed at the Connecticut Poison Control Center and is actively involved in lecturing and mentoring nurses, emergency medical residents and pharmacy students. ABSTRACT Thrombotic thrombocytopenic purpura is a rare blood disorder. Patients often experience thrombocytopenia, anemia due to red blood cell destruction, and microvascular thrombosis, and the disease is often connected with an acquired autoimmune deficiency. When the thrombotic microangiopathy affects the kidneys and is caused by bacteria, it is known as hemolytic uremic syndrome. Etiology, complications, monitoring and treatment of the patient with thrombocytopenic purpura and hemolytic uremic syndrome are discussed. nursece4less.com nursece4less.com nursece4less.com nursece4less.com 1 Policy Statement This activity has been planned and implemented in accordance with the policies of NurseCe4Less.com and the continuing nursing education requirements of the American Nurses Credentialing Center's Commission on Accreditation for registered nurses. It is the policy of NurseCe4Less.com to ensure objectivity, transparency, and best practice in clinical education for all continuing nursing education (CNE) activities. Continuing Education Credit Designation This educational activity is credited for 2 hours. Nurses may only claim credit commensurate with the credit awarded for completion of this course activity. Pharmacology content 0.5 hours (30 minutes). Statement of Learning Need Health clinicians are required to be knowledgeable about the etiology of thrombotic thrombocytopenic purpura and hemolytic uremic syndrome, including complications. This blood disorder can become fatal if not recognized and left untreated. Clinicians need to be knowledgeable to educate patients about the disease risks and management. Course Purpose To help health clinicians develop an understanding of the etiology, diagnosis, monitoring and treatment of thrombotic thrombocytopenic purpura and hemolytic uremic syndrome. nursece4less.com nursece4less.com nursece4less.com nursece4less.com 2 Target Audience Advanced Practice Registered Nurses and Registered Nurses (Interdisciplinary Health Team Members, including Vocational Nurses and Medical Assistants may obtain a Certificate of Completion) Course Author & Planning Team Conflict of Interest Disclosures Dana Bartlett, BSN, MSN, MA, CSPI, William S. Cook, PhD, Douglas Lawrence, MA, Susan DePasquale, MSN, FPMHNP-BC – all have no disclosures. Acknowledgement of Commercial Support There is no commercial support for this course. Please take time to complete a self-assessment of knowledge, on page 4, sample questions before reading the article. Opportunity to complete a self-assessment of knowledge learned will be provided at the end of the course. nursece4less.com nursece4less.com nursece4less.com nursece4less.com 3 1. Thrombocytopenia is defined as a platelet count less than: a. 300 b. 90 c. 150 d. none of the above 2. True or False: In hereditary TTP, the ADAMTS13 gene is not flawed; whereas in acquired TTP, the gene is flawed. a. True b. False 3. Complications of TTP, bleeding, anemia, renal injury and neurological symptoms, can be serious and lead to a fatal outcome in about _____ percent of cases. a. 90% b. 25% c. 50% d. 30% 4. Acquired thrombotic thrombocytopenic purpura (TTP) is more common than hereditary TTP and it is seen mostly in a. individuals over age 50. b. Caucasians as opposed to African-Americans. c. men. d. in females, particularly during and after pregnancy. 5. Acute renal failure is characteristic of a. rheumatoid arthritis. b. thrombotic thrombocytopenic purpura. c. activity of von Willebrand factor. d. hemolytic uremic syndrome. nursece4less.com nursece4less.com nursece4less.com nursece4less.com 4 Introduction Thrombotic thrombocytopenic purpura is a rare blood disorder. Patients often experience thrombocytopenic anemia due to red blood cell destruction, and microvascular thrombosis. This disorder is often connected with an acquired autoimmune deficiency. When the thrombotic microangiopathy affects the kidneys and is caused by bacteria, it is known as hemolytic uremic syndrome. The causes and complications of thrombotic thrombocytopenic purpura, which include bleeding are important for health clinicians to understand, specifically the monitoring and treatment required to support safe and appropriate care of affected individuals to avoid complications that may lead to death. A case study is included, which may be seen in the hospitalized patient who present with thrombocytopenia, to illustrate how some patients with thrombotic thrombocytopenic purpura may manifest symptoms, including appropriate diagnostic testing and treatment options, such as pharmacological treatment and supportive care. Thrombocytopenia: Epidemiology And Pathogenesis Platelets play an important role in hemostasis, which is the process of a blood clot being formed from the fluid part of blood. When there is injury to the vessel wall, platelets create a hemostatic plug to stop the bleeding. If there is a problem with platelet production or function, or if platelet destruction is occurring, thrombocytopenia can ensue and lead to significant bleeding complications. Normal platelet count is between 150 and 350 x 9 10 /L, and thrombocytopenia is defined as a platelet count less than 150. Thrombotic Thrombocytopenic Purpura Thrombotic thrombocytopenic purpura (TTP) is a rare blood disorder characterized by severe thrombocytopenia and microangiopathic hemolytic nursece4less.com nursece4less.com nursece4less.com nursece4less.com 5 anemia, both of which can cause microthrombi and organ ischemia.1-4 The disease can be acquired or hereditary and the acquired form is more common. Acquired TTP affects approximately 4.5 people per million per year and hereditary (also called congenital or idiopathic, and known formally as Upshaw Schulman syndrome) affects approximately 2.9 people per million per year.5 Acquired TTP is more common in females, particularly during and after pregnancy; the most common age of those affected is between 30 and 50 years of age, and the disease is more common in African-Americans.6 Hereditary TPP is more common in children7 but adults can develop hereditary TTP. Thrombotic thrombocytopenic purpura is a potentially dangerous disease, and, if left untreated, the mortality rate has been reported to be as high as 90%.8 Hereditary TTP is caused by an inherited deficiency of ADAMTS13, an enzyme that helps to regulate normal functioning of von Willebrand factor.4,7 Von Willebrand factor is a glycoprotein that is involved in platelet adhesion (and thus blood clotting) and when ADAMTS13 is lacking the activity of von Willebrand factor is increased, resulting in widespread platelet adhesion and blood clotting.9,10 A deficiency in ADAMTS13 is the underpinning of hereditary TTP but these gene mutations do not completely explain the disease. Sibling studies show that the clinical course of hereditary TTP can be quite different patient to patient despite the presence of the same ADAMTS13 mutations.11,12 The level of ADAMTS13 deficiency does not necessarily correlate with expression of the disease,13 and hereditary TTP typically requires an environmental stressor or trigger to manifest.4,14 These stressors or triggers are listed in Table 1.6,15-26 For detailed information about drug- induced TTP the reader is referred to Al-Nouri, 2015.20 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 6 Hereditary TTP Triggers Acute infections, i.e., HIV, pancreatitis Alcohol Drugs, particularly cyclosporine, quinine, and tacrolimus Malignancies Pregnancy Systemic lupus erythematosus Acquired TTP is caused by autoimmune antibodies that decrease the activity and level of the ADAMTS13 enzyme.5 In the great majority of cases of acquired TTP there is no obvious cause for the formation of these antibodies,6,27 and this is called primary or idiopathic acquired TTP. Acquired TTP may also be caused - or associated with – autoimmune disorders like systemic lupus erythematosus (SLE) or rheumatoid arthritis, drugs, human immunodeficiency virus (HIV) infection, liver disease, malignancies, pregnancy, and solid organ transplantation.5,27,28 This is called secondary acquired TTP. There is some evidence that acquired TTP, as with hereditary TTP, requires a stimulus to be expressed and the ADAMTS13 deficiency alone cannot explain the disease.29 Hemolytic Uremic Syndrome Hemolytic uremic syndrome is characterized by hemolytic anemia, thrombocytopenia, and acute renal failure30 and there are two forms of the disease, typical and atypical. Both typical and atypical hemolytic uremic syndrome (HUS) cause direct injury to the kidneys (from the Shiga toxin nursece4less.com nursece4less.com nursece4less.com nursece4less.com 7 itself or by mechanical damage from microthrombi), thrombocytopenia, and a prothrombotic state that causes microthrombi