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Sickle cell anemia

Sickle cell anemia

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Sickle cell anemia

  1. 1. Sickle cell anemia 1
  2. 2. Diagnosis  SCD is suggested by the typical clinical picture of chronic hemolytic anemia and vaso-occlusive crisis.  Electrophoresis confirms the diagnosis with the presence of homozygous HbS and can also document other hemoglobinopathies (eg, HbSC, HbS-beta+ thalassemia).
  3. 3.  the diagnosis of HbSC disease is made with Hb electrophoresis.  The peripheral blood smear may have some sickled cells and a high proportion of target cells. In addition, microcytic, dehydrated, dense RBCs are seen. These may contain crystal-like condensations.
  4. 4. Laboratory tests used in patients with SCD include the following:  Mandatory screening for HbS at birth in the United States; prenatal testing can be obtained via chorionic villus sampling  Hemoglobin electrophoresis  CBC count with differential and reticulocyte count  Serum electrolytes  Hemoglobin solubility testing  Peripheral blood smear  Pulmonary function tests (transcutaneous O 2 saturation)  Renal function (creatine, BUN, urinalysis)  Hepatobiliary function tests, (ALT, fractionated bilirubin)  CSF examination: Consider LP in febrile children who appear toxic and in those with neurologic findings (eg, neck stiffness, + Brudzinski/Kernig signs, focal deficits); consider CT scanning before performing LP  Blood cultures  ABGs  Secretory phospholipase A2 (sPLA2)
  5. 5. Imaging studies  Radiography MRI  CT scanning  Nuclear medicine scanning  Transcranial Doppler ultrasonography  Abdominal ultrasonography  Echocardiography  Transcranial near-infrared spectroscopy or cerebral oximetry
  6. 6. people with sickle trait generally are well and have the following characteristics:  Normal life expectancy  Not at excessive risk for infection  Not subject to painful crisis under normal circumstances  No anemia
  7. 7. the differential diagnosis may also include the following:  Valvular heart disease  Septic arthritis  Sepsis  Upper respiratory tract infection  Aortic arch syndrome  Facioscapulohumeral muscular dystrophy  Incontinentia pigmenti  Familial exudative vitreoretinopathy  Lupus erythematosus  Macroglobulinemia  Polycythemia vera  Talc and cornstarch emboli  Uveitis, including pars planitis
  8. 8. recommendations to decrease severity of complications :  Use of daily oral prophylactic penicillin up to age 5  Annual transcranial Doppler examinations between the ages of 2 and 16 years in patients with sickle cell anemia  Long-term transfusion therapy to prevent stroke in children with abnormal transcranial Doppler velocity (≥200 cm/s)  In patients with sickle cell anemia, preoperative transfusion therapy should be used to increase hemoglobin levels to 10 g/dL  Rapid initiation of opioids for the treatment of severe pain associated with a vasoocclusive crisis  Use of analgesics and physical therapy for the treatment of avascular necrosis 9
  9. 9. Clinical manifestations and complicatons of sickle cell disease  Acute Complications  Chronic Complications 10
  10. 10. Clinical manifestations and complicatons of sickle cell disease 11
  11. 11. 12
  12. 12. Hydroxyurea Therapy  For frequent and severe pain, long- term hydroxyurea is currently the accepted treatment. 13
  13. 13. Hydroxyurea Therapy  Indications for hydroxyurea include the following:  Frequent painful episodes (six or more per year)  History of acute chest syndrome  History of other severe vaso-occlusive events  Severe symptomatic anemia  Severe unremitting chronic pain that cannot be controlled with conservative measures  History of stroke or a high risk for stroke 14
  14. 14. Hydroxyurea Therapy  Patients receiving hydroxyurea require frequent blood testing and monitoring:  Due to increase the incidence of the development of leukopenia and/or thrombocytopenia. 15
  15. 15. Transfusion  Acute red cell exchange transfusion is indicated in the following situations:  Acute infarctive stroke  Severe acute chest syndrome  Multiorgan failure syndromes  Right upper quadrant syndrome  Priapism that does not resolve after adequate hydration and analgesia 16
  16. 16. Transfusion  Many anesthesiologists require a hemoglobin concentration of more than 10 g/dL prior to the procedure. 17
  17. 17. Treatment of iron overload  Three agents are used for iron chelation:  Deferoxamine  Deferasirox  deferiprone. 18
  18. 18. Treatment of iron overload  Deferoxamine is an efficient iron chelator.  It is administered as a prolonged infusion intravenously or subcutaneously for 5-7 days a week.  Although effective, there are significant challenges associated with its use that can result in non-compliance. 19
  19. 19. Treatment of iron overload  Deferasirox:  it is administered orally.  Renal toxicity might be a limiting factor in its use, but it is generally safe.  Deferiprone:  is considered a second-line therapy, due to lack of effectivity comparing to other agents .  it selectively removes cardiac iron.  is most effective when used in combination with deferoxamine or deferasirox. 20
  20. 20. Erythrocytapheresis  Erythrocytapheresis is an automated red cell exchange procedure that removes blood that contains HbS from the patient while simultaneously replacing that same volume with packed red cells free of HbS. 21
  21. 21. Management of Ophthalmic Manifestations  Surgical procedures may be performed to treat retinal detachments, nonclearing vitreous hemorrhage, and epiretinal membranes.  prophylactic preoperative exchange transfusions or erythropheresis is recommended  patients with sickle cell disease are particularly prone to central retinal artery occlusion and optic atrophy, even with mildly elevated intraocular pressures, closely monitor the intraocular pressure. Do not allow it to exceed 25 mm Hg for longer than 24 hours. 22
  22. 22. Vaso-Occlusive Crisis Management  is treated with vigorous intravenous hydration and analgesics.  Intravenous fluids should be of sufficient quantity to correct dehydration and to replace continuing loss, both insensible and due to fever.  Normal saline and 5% dextrose in saline may be used.  Using hydroxyurea (hydroxycarbamide) significantly reduces the incidence of vaso- occlusive crisis and dactylitis in very young children  Predictors of admission included the following:  Higher pain score at triage  Older age  Increased systolic blood pressure 23
  23. 23. Treatment of Acute Chest Syndrome  Cause : vaso-occlusive episode , neutropenia due to use of hydroxyurea .  Incentive spirometry – In patients with chest or rib pain, to prevent ACS; should be considered in all patients with ACS  Antibiotics, with cover for atypical organisms, even if blood cultures and sputum cultures are negative  Anti-viral agents– If there is a clinical suspicion of H1N1 infection  Early simple transfusion should be considered early in patients with hypoxia; however, exchange transfusion is necessary in patients with severe clinical features or evidence of progression despite initial simple transfusion  Empiric antibiotics should be initiated and given intravenously, after obtaining samples for appropriate cultures. 24
  24. 24. Treatment of Acute Chest Syndrome  Narcotic agents may be used for more severe pain.  Other supportive therapy as careful hydration.  Volume overload must be avoided, as it may contribute to pulmonary infiltrates and exacerbate hypoxia.  Intensive care is indicated for patients in severe hypoxia or respiratory distress, as respiratory decompensation can rapidly require mechanical ventilation.  Treatment should also include oxygen therapy with close monitoring for hypoxemia with continuous pulse oximetry or frequent assessment of blood gases. 25
  25. 25. Management of Chronic Anemia  Women who are menstruating should be checked for coexisting iron deficiency .  Blood transfusion is indicated only in specific situations:  acute chest syndrome  stroke  abnormal findings on transcranial Doppler in children (for stroke prevention)  Pregnancy  general anesthesia  The aim is to decrease the concentration of HbS to 30% or less. Transfusion may also be required during aplastic crisis. 26
  26. 26. Management of Chronic Anemia  For anemic crisis with splenic sequestration  give early red cell transfusions because the process can rapidly progress to shock.  Do not allow hemoglobin (Hb) levels to rise to more than 10 g/dL, since the spleen may disgorge trapped cells, which can create a relative polycythemia and increased blood viscosity.  Transfusion is required in an aplastic crisis if the anemia is symptomatic (eg, dyspnea, signs of hypovolemia). Because aplastic crises are self-limited. 27
  27. 27. Prevention and Treatment of Infections  Cause : individuals with SCD are highly susceptible to bacterial and viral infections, largely due to functional asplenia that develops early in childhood.  immunization for all patients  prophylactic penicillin for all young children (eg, <5 years of age) 28
  28. 28. Prevention and Treatment of Infections  Antibiotics are indicated when an infection is suspected :  body temperature is higher than 38° C  recommend the use of broad-spectrum antibiotics in the patient who is systemically ill or has chest involvement.  parenteral antibiotics for hospitalized patients include cephalosporins (eg, ceftriaxone, cefuroxime) and macrolides for acute chest syndrome.  For discharged patients oral antibiotics (eg, amoxicillin-clavulanic acid, clarithromycin, cefixime) are useful in selected cases.  If the patient has localized bone tenderness, the antibiotic selected should provide coverage for S typhimurium and S aureus. 29
  29. 29. Prevention and Treatment of Infections  Penicillin prophylaxis and vaccination :  Begin at age 2 months with 125 mg bid of penicillin V or G  at 3 years, increase the dose to 250 mg bid. Prophylaxis should continue until age 5 years or the early teens.  Protein-conjugated pneumococcal vaccines (PCVs) , The 7-serotype PCV (PCV7) in combination with penicillin prophylaxis and PPV23 booster vaccination .  prevention against S pneumoniae infection. The vaccine is given at age 2 years, with a booster dose at age 5 years.  Meningococcal prophylaxis is administered as a single quadrivalent vaccine when the child is older than 2 years. 30
  30. 30. Treatment of Gallstones  Cause : gallstones are produced from excess bilirubin, which is caused by the constant breakdown of red blood cells. Biliary sludge (formed when excess bile settles in the duct) can also lead to gallstones.  For patient with acute cholecystitis :  Can receive antibiotics and general supportive care and may consider elective cholecystectomy several weeks after the acute episode subsides.  Elective laparoscopic cholecystectomy for symptomatic disease.  supportive care for cholecystitis if stones are visualized.  Elective cholecystectomy has been used for asymptomatic patients with cholelithiasis, to avoid the possible future need for an emergent procedure.  But still controversial 31
  31. 31. Treatment of Gallstones  supportive care for cholecystitis if stones are visualized:  Prophylactic antibiotic coverage with levofloxacin (Levaquin, 500 mg PO qd) and metronidazole (500 mg PO bid), which should provide coverage against the most common organisms  Antiemetics, such as oral/rectal promethazine (Phenergan) or prochlorperazine (Compazine), to control nausea and to prevent fluid and electrolyte disorders  Analgesics, such as oral oxycodone/acetaminophen (Percocet) or hydrocodone/acetaminophen (Vicodin) 32
  32. 32. Control of Chronic and acute pain 33
  33. 33. Control acute pain  Initiate analgesic therapy within 30 minutes of triage, or 60 minutes of registration  In patients with mild to moderate pain, continue treatment with NSAIDs in those who report relief with these agents, unless contraindicated  In patients with severe pain, rapidly initiate treatment with parenteral opioids  Reassess pain every 15-30 minutes until the patient reports that pain is under control; readminister opioids if necessary for continued severe pain  The drug should be given intravenously, hourly at first. Once the effective dose is established, it should be administered every 3 hours.  Meperidine is not recommended , due to CNS toxicity . 34
  34. 34. Control chronic pain  The weak opiates (eg,codeine and hydrocodone) are commonly used first. Sustained-release long-acting oral morphine is reserved for more severe cases.  Hydroxyurea and tCAs may decrease the frequency and severity of pain episodes.  Nonpharmacological approaches to pain management may have a substantial impact. These include physical therapy, heat and cold application, acupuncture and acupressure, hypnosis, and transcutaneous electric nerve stimulation (TENS). 35
  35. 35. Medications  Oxycodone and aspirin  Aspirin inhibits platelet aggregation; has analgesic and anti-inflammatory properties.  Methadone  Morphine sulfate  Oxycodone and acetaminophen  It is the drug of choice for patients who are hypersensitive to aspirin.  for patients who are hypersensitive to aspirin.  Fentanyl  fentanyl is not commonly associated with histamine release.  Nalbuphine  Codeine  pathways, altering perception and response to pain.  Codeine/acetaminophen 36
  36. 36. NSAIDs  Ketorolac  Acetaminophen  Ibuprofen  Aspirin  All are analgesic , anti inflammatory 37
  37. 37. Stroke Prevention  Adults with SCD should be managed according to the 2014 AHA/ASA primary stroke prevention guidelines.  Secondary stroke prevention guidelines include recommendations for controlling risk factors and the use of antiplatelet agents.  Regular blood transfusions (to reduce HbS to < 30%-50% total hemoglobin), hydroxyurea, bone marrow transplantation , bypass surgery for advanced occlusive disease.
  38. 38. Stroke Prevention  Transfusion therapy, aimed at keeping the proportion of HbS below 30%.  Erythrocytapheresis , This procedure allows rapid reduction of HbS concentrations to be less than 30% without significantly increasing total hemoglobin concentration post transfusion.  hydoxyurea or bone marrow transplantation might be an option for children at high risk for stroke in whom RBC transfusion is contraindicated.  hydroxyurea/phlebotomy can be use as second line , but transufusion and exchange is the first line . 39
  39. 39. Treatment of Priapism  Cause : Sickle cells can block the blood vessels in the penis.  At the onset of priapism, patients should be advised to drink extra fluids, use oral analgesics, and attempt to urinate.  A nightly dose of pseudoephedrine (30 mg orally) may prevent priapism in some cases.  For episodes that last more than 2 hours, patients should go to the emergency department to receive intravenous hydration and parenteral analgesia.  If detumescence does not occur within 1 hour after arrival in the emergency department, penile aspiration followed by irrigation .  if early intervention with irrigation fails, red cell exchange transfusions to reduce the HbS level to less than 30% .  to prevent recurrent priapism use phosphodiesterase type 5 inhibitors (eg, sildenafil, tadalafil). 40
  40. 40. Sickle cell nephropathy  Cause : hypoxia and ischemia.  More distal tubular dysfunction may impair renal acidification and potassium secretion, leading to an incomplete form of distal renal tubular acidosis and hyperkalemia.  Risk factors associated with progression of chronic kidney disease (CKD) to end-stage renal disease (ESRD) include the following [5] :  Hypertension  Nephrotic range proteinuria  Severe anemia  Vasoocclusive crisis  Acute chest syndrome  Stroke  βS-gene haplotype  Pulmonary hypertension  Parvovirus B19 infection 41
  41. 41. Sickle cell nephropathy  The recommended hemoglobin (Hb) target should be an Hb concentration of no greater than 10-10.5 g/dL.  Blood transfusions or erythrocyte-stimulating agents (ESA), such as erythropoietin or darbepoetin alfa .  But transfusion and exchange is superior , as it provide patient with a higher amount of Hb A , compare to patient own blood .  ESA dosing may be higher in individuals receiving hydroxyurea due to its inherent bone marrow suppressive effect. 42
  42. 42. Treatment of Leg Ulcers  Cause : Leg ulcers may result from venous stasis and chronic hypoxia and may become infected.  Leg ulcers are treated with debridement and antibiotics.  Zinc oxide occlusive dressing (Unna boot) and leg elevation .  Transfusion may accelerate healing.  Skin grafting may be necessary in recalcitrant cases. 43
  43. 43. Treatment of Pulmonary Hypertension  Cause : chronic intravascular hemolysis, older age, renal insufficiency, cardiovascular disease, cholestatic hepatopathy, systolic hypertension, high hemolytic markers, iron overload, and a history of priapism.  Treatment : hydroxyurea and chronic transfusion have been used.  Enothelin-1 receptor antagonists (eg, bosentan)  phosphodiesterase inhibitors (eg, sildenafil).  Cor pulmonale treat as patient with right side heart failure . 44
  44. 44. Stem Cell Transplantation  allogeneic marrow transplantation  who qualify for stem cell transplantation ?  First, donors must be human leukocyte antigen (HLA) compatible and full siblings (those with sickle trait are acceptable) 45
  45. 45.  second, candidates should be limited to patients younger than 16 years with HbSS or HbS–β-0 thalassemia who have evidence of disease severity demonstrated by the following:  Stroke  Recurrent acute chest syndrome  Recurrent severe crisis pain (>2 episodes/y for several years)  Recurrent priapism  Impaired neuropsychological function with evidence of cerebral infarction  Sickle cell nephropathy  Bilateral proliferative retinopathy and major visual impairment in at least one eye  Osteonecrosis of multiple joints  Red cell alloimmunization with more than 2 antibodies during long-term transfusion therapy 46 Stem Cell Transplantation
  46. 46. Investigational Treatments  Nitric oxide inhalation has been investigated in the treatment of pulmonary hypertension.  Topical GM-CSF has been reported to hasten the healing of leg ulcers.  topical granulocyte-macrophage colony-stimulating factor  Butyrate was studied to decrease vaso-occlusive crisis.  Arginine has been proposed to use as a precursor of nitric oxide production. 47
  47. 47. Avascular necrosis  treatmeant : not bearing weight at the site.  need to make career and lifestyle adjustments. Occupational retraining and physical therapy.  surgical intervention with hip replacement or other orthopedic procedures are needed.  Cause : result from chronic hypoxia in weight-bearing joints, commonly the femoral head. 48
  48. 48. Treatment of Other Complications  Avascular necrosis of the femoral and humeral heads:  May result from chronic hypoxia in weight-bearing joints, commonly the femoral head  Treat by: 1. Not bearing weight at the site. 2. make career and lifestyle adjustments. 3. Occupational retraining and physical therapy may be needed. 4. Surgical intervention with hip replacement or other orthopedic procedures may be needed.  Psychological problems, such as depression, anxiety, and chronic pain behavior. Ensure an appropriate physician-patient relationship. Anxiolytics and amitriptyline may be used
  49. 49. Long-Term Monitoring  For patients with minimal symptoms, a visit with blood work every 3-4 months is reasonable. Others may need much more frequent observation.  proliferative sickle retinopathy (PSR); once stabilized, visits every 3-6 months may be adequate. When intraocular pressures are stabilized, the patient can be monitored every 6 months.  Pneumococcal and influenza vaccination is safe in patients with functioning kidney transplants.  The use of live vaccines is contraindicated due to the immunosuppressive therapy that these patients require. 50
  50. 50. Antiemetic  Promethazine 51

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