Presentation is loading. Please wait.

Presentation is loading. Please wait.

© Copyright Annals of Internal Medicine, 2011 Ann Int Med. 155 (5): ITC3-1. * For Best Viewing: Open in Slide Show Mode Click on icon or From the View.

Similar presentations


Presentation on theme: "© Copyright Annals of Internal Medicine, 2011 Ann Int Med. 155 (5): ITC3-1. * For Best Viewing: Open in Slide Show Mode Click on icon or From the View."— Presentation transcript:

1 © Copyright Annals of Internal Medicine, 2011 Ann Int Med. 155 (5): ITC3-1. * For Best Viewing: Open in Slide Show Mode Click on icon or From the View menu, select the Slide Show option * To help you as you prepare a talk, we have included the relevant text from ITC in the notes pages of each slide

2 © Copyright Annals of Internal Medicine, 2011 Ann Int Med. 155 (5): ITC3-1. in the clinic Sickle Cell Disease

3 © Copyright Annals of Internal Medicine, 2011 Ann Int Med. 155 (5): ITC3-1. Common Genotypes of Sickle Cell Disease  Sickle cell trait (“HbAS”)  Person carries sickle hemoglobin gene (HbS) and also has some normal hemoglobin (HbA)  HbS ≤40% total hemoglobin; usually no symptoms  Cells don’t deform when deoxygenated  Sickle cell anemia (sickle-cell disease, “HbSS”)  HbS homozygosity; most / all HbA replaced with HbS  Most common + most severe of sickle cell variations  Complications due to sickled cells shape + thickness

4 © Copyright Annals of Internal Medicine, 2011 Ann Int Med. 155 (5): ITC3-1. Other Common Genotypes of Sickle Cell Disease  HbSC disease  Compound heterozygosity for HbS and HbC genes  HbSE disease  Compound heterozygosity for HbS and HbE genes  HbS-β-thalassemia disease  Compound heterozygosity for HbS and a β 0 - or β + - thalassemia gene  HbSO Arabia  Compound heterozygosity for HbS and HbO Arabia  HbSD Los Angeles (Punjab)  Compound heterozygosity for HbS and HbD

5 © Copyright Annals of Internal Medicine, 2011 Ann Int Med. 155 (5): ITC3-1. Who should be screened for sickle cell anemia and sickle cell trait?  All U.S. newborns  Test also detects sickle cell trait carriers  At risk individuals pregnant or planning pregnancy  Determining who is at risk can be difficult  Maternal & paternal family history: best guide for determining individual HbS screening  Individuals with hyphema or hematuria

6 © Copyright Annals of Internal Medicine, 2011 Ann Int Med. 155 (5): ITC3-1. What screening and diagnostic tests are available?  To detect HbS: high-performance liquid chromatography  In newborns, children, adults  Some labs use isoelectric focusing  When genetic counseling needed: DNA-based test  Establishes parental globin gene mutations  If positive: DNA-based testing of chorionic villus samples or amniotic fluid cells  Before considering prenatal Dx, counsel parents:  On risks of procedure and consequences of positive Dx  On likelihood of affected fetus and options for termination

7 © Copyright Annals of Internal Medicine, 2011 Ann Int Med. 155 (5): ITC3-1.  Pathophysiology includes:  Abnormal erythrocyte volume regulation  Impaired nitric oxide bioavailability  Reperfusion injury  Inflammation and oxidant damage  Abnormal intercellular interactions  Endothelial injury  Leukocyte and platelet activation  HbS gene most prevalent in persons of African, Arabian, and Asian-Indian ancestry

8 © Copyright Annals of Internal Medicine, 2011 Ann Int Med. 155 (5): ITC3-1. CLINICAL BOTTOM LINE: Screening…  Screening can lead to prompt diagnosis  Screening helps prevent serious complications  Screening provides information for family planning

9 © Copyright Annals of Internal Medicine, 2011 Ann Int Med. 155 (5): ITC3-1. What should prompt consideration of undiagnosed sickle cell disease?  Suspicious symptoms  Frequent, unexplained pain  Splenomegaly  Stroke at young age  Pneumonia with anemia requiring transfusion  Osteonecrosis in femur heads and humerus  Rare complications  Leg ulcers, priapism, nephropathy+renal failure, severe anemia  Complications occurring with advancing age  Sickle retinopathy, liver disease  Infections  Major cause of death in children and adults

10 © Copyright Annals of Internal Medicine, 2011 Ann Int Med. 155 (5): ITC3-1. What should be looked for on the physical exam when sickle cell disease is suspected?  Swelling and tenderness over affected areas and low-grade fever (in acute, painful episodes)  Consolidation, rales, rhonchi, wheezing (acute chest syndrome)  Cardiac enlargement and systolic murmurs (common)  Enlarged liver  Asplenia, no splenic dullness on percussion  Splenomegaly (in HbSC disease and HbS–β-thalassemia)  Sickle retinopathy

11 © Copyright Annals of Internal Medicine, 2011 Ann Int Med. 155 (5): ITC3-1. What lab tests should be ordered in the evaluation of possible sickle cell disease?  In untreated sickle cell anemia  Erythrocytes (normocytic or macrocytic); microcytosis  Sickle solubility test  High-performance liquid chromatography  After diagnosis established  Baseline CBC and reticulocyte counts  Red cell antigen phenotyping  Blood urea nitrogen, creatinine, urine albumin, electrolytes, bilirubin, lactate dehydrogenase, serum ferritin, alanine transaminase, aspartate transaminase, alkaline phosphatase  Chest radiographs and pulmonary function tests  Pulse oximetry  Echocardiography to estimate the TRV

12 © Copyright Annals of Internal Medicine, 2011 Ann Int Med. 155 (5): ITC3-1. What are complications of sickle cell trait?  Most carriers can’t concentrate urine normally  Due to renal medullary abnormalities  Important to hydrate adequately  Increased risk hematuria  Due to papillary necrosis (usually benign and self-limited)  2-fold higher risk thromboembolic disease  4-fold higher risk pulmonary embolism  Splenic infarction rare  Preop screen: needed w/ open-heart or complicated intra- thoracic procedures where hypoxia intrinsic to procedure

13 © Copyright Annals of Internal Medicine, 2011 Ann Int Med. 155 (5): ITC3-1. Which patients with sickle cell disease should be referred to a specialist?  General internist, pediatrician, or family physician can manage routine maintenance + common complications  Consult appropriate specialists as needed  All patients with sickle cell disease: hematologist with expertise in hemoglobinopathies (annually)  Pulmonary complications: pulmonologist or cardiologist  Severe acute chest syndrome: hematologist and critical care specialist  Pregnancy: high-risk obstetrician and hematologis t

14 © Copyright Annals of Internal Medicine, 2011 Ann Int Med. 155 (5): ITC3-1. CLINICAL BOTTOM LINE: Diagnosis and evaluation…  Suspicious symptoms: undiagnosed sickle cell disease  Frequent, unexplained pain  Splenomegaly  Stroke at young age  Pneumonia with anemia requiring transfusion  Osteonecrosis in femur heads and humerus  H&P and lab tests used to confirm diagnosis and evaluate patient

15 © Copyright Annals of Internal Medicine, 2011 Ann Int Med. 155 (5): ITC3-1. What drugs should be considered for the primary treatment of sickle cell anemia?  Hydroxyurea  Only FDA-approved drug for primary Rx  Begin early, before irreversible vasculopathy and organ damage develop  Reduces of acute painful events and acute chest syndrome  Reduces mortality 40% and reduces hemolysis  Fewer hospitalizations, reduced medical costs  Improved physical capacity

16 © Copyright Annals of Internal Medicine, 2011 Ann Int Med. 155 (5): ITC3-1. What is the role of blood transfusion?  Simple transfusions reduce HbS levels more gradually  Require only peripheral venous access and rapidly available  Lower alloimmunization risk; greater hyperviscosity risk  Exchange transfusions reduce HbS levels more rapidly  Take more time to start and more complicated venous access  Lower hyperviscosity risk; higher alloimmunization risk  Preop: simple transfusion can reduce postop complications  Stroke: exchange transfusion can reduce recurrence  Acute chest syndrome  Patient may not need transfusion if no hypoxia + chest infiltrates minor, fever minimal, blood count changes small  Don’t use repeated transfusion to manage routine crisis

17 © Copyright Annals of Internal Medicine, 2011 Ann Int Med. 155 (5): ITC3-1. What is the role of bone marrow transplantation in sickle cell anemia?  Transplantation mortality rate: ≈5%  Event-free survival: 84%  Rejection or disease recurrence: ≈10%  When successful, disease is “cured”  Patient no longer anemic  Long-term, stable engraftment sufficiently eliminates the phenotype of sickle cell disease  Myeloablative stem cell transplantation largely limited to children <16 yrs old with severe disease

18 © Copyright Annals of Internal Medicine, 2011 Ann Int Med. 155 (5): ITC3-1. What are the features of sickle cell anemia over a patient's lifetime?  Major clinical features in the first decade…  Severe life-threatening infection  Acute chest syndrome  Splenic sequestration  Stroke; pain; dactylitis  Major clinical features in young adulthood and beyond…  Sickle vasculopathy likely to progress despite few symptoms  Chronic organ damage leads to pulmonary vasculopathy  Deteriorating pulmonary function and renal failure  Late effects of cerebrovascular disease

19 © Copyright Annals of Internal Medicine, 2011 Ann Int Med. 155 (5): ITC3-1. How does pain manifest in sickle cell disease? Clinical Features of the Acute Painful Episode  Some patients always in pain; others rarely  Pain distribution and duration varies  Pain most often occurs in back, chest, extremities, joints  Cause unclear: unrelated to “new sickling”; blood film unhelpful  Physical findings limited  Frequent episodes associated with poor prognosis  Directly related to packed cell volume; indirectly related to HbF

20 © Copyright Annals of Internal Medicine, 2011 Ann Int Med. 155 (5): ITC3-1. How should pain be managed?  Most pain successfully managed at home  Many patients can sense the beginning of an episode  Use nonopioid analgesics, then oral opioids if needed  Up fluid intake, use rest, warm baths, heating pads, massage  Pain requiring medical intervention  Usually treated in the hospital ED  Initiate parenteral opioids and adjust dosage as needed  Individualize Rx (analgesic doses can vary considerably)  Monitor for oversedation, hypoxia, and low respiratory rate

21 © Copyright Annals of Internal Medicine, 2011 Ann Int Med. 155 (5): ITC3-1. How are episodes requiring further treatment and continuously increased use and dose of opioids managed? Causes of Persistent Severe Pain  Progressive tissue damage  Inadequate treatment  Tolerance  Hyperalgesia  Changes at receptors  Maladaptive behavior  Decision to initiate long-term opiate therapy  Define cause of pain  Determine pain intensity + effect on functioning, QOL  Document evaluation and treatment plan  Monitor closely

22 © Copyright Annals of Internal Medicine, 2011 Ann Int Med. 155 (5): ITC3-1. How common is the acute chest syndrome in sickle cell disease?  Features: fever, chest pain, cough, and lung infiltrates  Affects >50%  Mortality higher in adults than children (<10% cases fatal)  Second most common reason for hospitalization  Causes: infarction, pulmonary infection, atelectasis, embolism, in situ thrombosis  Frequent postop complication, even after preop transfusion  Fat embolism from necrotic bone marrow causes most severe acute chest events

23 © Copyright Annals of Internal Medicine, 2011 Ann Int Med. 155 (5): ITC3-1. How is the acute chest syndrome in sickle cell disease managed?  Transfusions  Antibiotics  Hydration (avoid overhydration)  Respiratory therapy with bronchodilators  Incentive spirometry  Maintenance of tissue oxygenation  Oxygen: if hypoxic or tachypneic; in respiratory distress  Opioids: balance pain relief w/ respiratory suppression risk  Patients who deteriorate rapidly: admit to ICU

24 © Copyright Annals of Internal Medicine, 2011 Ann Int Med. 155 (5): ITC3-1. What other conditions complicate sickle cell anemia?  Pulmonary vasculopathy & abnormal pulmonary function  Infection  Retinopathy  Anemia  Leg ulcers  Priapism  Renal disease  Digestive system disease  Neurocognitive dysfunction

25 © Copyright Annals of Internal Medicine, 2011 Ann Int Med. 155 (5): ITC3-1. As patients with sickle cell disease live longer, what new health issues are emerging?  Cardiomegaly and heart murmurs  Contractility usually normal and overt CHF uncommon  Hypertension  Cause of ventricular hypertrophy and HF  May contribute to sickle nephropathy and renal failure  Chest pain  Very common but MI unusual

26 © Copyright Annals of Internal Medicine, 2011 Ann Int Med. 155 (5): ITC3-1. Is pregnancy more complicated in women with sickle cell disease?  Most managed without regular transfusions  Identify red cell phenotype & alloantibodies: so pheno- typically matched blood can be used if needed  Multiple-birth pregnancies benefit from transfusion  Obstetric complications and C-section more common  Prenatal testing needed  Establish Hb phenotype and HbF level  Blood counts; serum chemistries; hepatitis A,B,C; HIV testing  Urinalysis; urine culture; rubella antibody titer; serum ferritin

27 © Copyright Annals of Internal Medicine, 2011 Ann Int Med. 155 (5): ITC3-1. Are patients with sickle cell disease at particularly high risk during surgery?  Surgery and anesthesia safe but not complication-free  Blood transfusion: major issue preoperatively  Preparation: hydration; optimization of pulmonary status  Be vigilant toward detecting acute chest syndrome Prevent acute chest syndrome after surgery with…  Rapid mobilization  Incentive spirometry and bronchodilators  Close monitoring of oxygen saturation

28 © Copyright Annals of Internal Medicine, 2011 Ann Int Med. 155 (5): ITC3-1. How should end organ damage be monitored, treated, and prevented?  If patient stable  follow every 4 to 6 months  Perform blood counts  Monitor renal and liver function  Test for baseline pulmonary function  Obtain baseline and periodic estimation of TRV  Periodically evaluate for sickle retinopathy  Ophthalmologist visit

29 © Copyright Annals of Internal Medicine, 2011 Ann Int Med. 155 (5): ITC3-1. CLINICAL BOTTOM LINE: Treatment and management…  Sickle cell disease has protean manifestations  Optimum care consists of:  Direct drug therapy with hydroxyurea  Prompt diagnosis  Prompt treatment of complications

30 © Copyright Annals of Internal Medicine, 2011 Ann Int Med. 155 (5): ITC3-1. What should patients be taught about preventing disease complications?  Good self-management can help prevent complications  Awareness of acute pain episode beginning  Use rest, hydration, warm baths to arrest development  Avoidance extremes of temperature  Cold, windy conditions associated with painful episodes  Maintenance of good hydration  Lower legs: protect from trauma, keep well- moisturized  To avoid leg ulcers

31 © Copyright Annals of Internal Medicine, 2011 Ann Int Med. 155 (5): ITC3-1. What should patients be taught about prenatal screening and management of pregnancy?  Discuss prenatal screening and its implications  Preferably during planning  At least in the first weeks of pregnancy  Manage pregnancies in a high-risk obstetrics clinic  Consult with a hematologist

32 © Copyright Annals of Internal Medicine, 2011 Ann Int Med. 155 (5): ITC3-1. CLINICAL BOTTOM LINE: Patient education…  Teach patients to recognize the early signs of an acute crisis  Encourage regular medical follow-up from a primary care provider with access to a sickle cell center


Download ppt "© Copyright Annals of Internal Medicine, 2011 Ann Int Med. 155 (5): ITC3-1. * For Best Viewing: Open in Slide Show Mode Click on icon or From the View."

Similar presentations


Ads by Google