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Toronto Notes 2019 Hemolytic Anemia
Clinical Features
• HbAS(sicklecelltrait):patientwillbeasymptomaticexceptduringextremehypoxiaorinfection increased risk of renal medullary carcinoma
• SCD-SS(HbSS)
■ chronic hemolytic anemia
■ jaundice in the first yr of life
■ retarded growth and development ± skeletal changes
■ splenomegaly in childhood; splenic atrophy in adulthood
• SCD-SSoftenpresentswithacutepainepisode 1. aplastic crises
◆ toxins and infections (especially parvovirus B19) transiently suppress bone marrow 2. splenic sequestration crises
◆ usually in children; significant pooling of blood in spleen resulting in acute Hb drop and shock
◆ uncommon in adults due to asplenia from repeated infarction 3. vaso-occlusive crises (infarction)
◆ may affect various organs causing ischemia-reperfusion injury (especially in back, chest, abdomen, and extremities), fever, and leukocytosis
◆ can cause a stroke or a silent myocadial infarction
◆ precipitated by infections, dehydration, rapid change in temperature, pregnancy, menses, and
alcohol
4. acute chest syndrome
• SCD-SC (most common compound heterozygote)
■ 1:833 live births in African-Americans, common in West Africa
■ milder anemia than HbSS
■ similar complications as HbSS, although typically milder and less frequent (exception is proliferative
sickle retinopathy, glomerulonephritis, and avascular necrosis) ■ spleen not always atrophic in adults
Investigations
• sickle cell prep (detects sickling of RBCs under the microscope in response to O2 lowering agent): determines the presence of a HbS allele, but does not distinguish HbAS from HbSS
• HbelectrophoresisdistinguishesHbAS,HbSS,HbSC,andothervariants
• allnewbornsindevelopedcountriestypicallyscreenedforSCD
Hematology H21
Table 13. Investigations for Sickle Cell Disease
Organs Affected by Vaso-Occlusive Crisis
Organ
Brain
Eye Liver Lung
Gallbladder Heart Spleen
Kidney
Intestines Placenta Penis
Digits Femoral and Humeral Head Bone
Ankle
Problem
Ischemic or hemorrhagic stroke, vasculopathy Hemorrhage, blindness Infarcts, RUQ syndrome Chest syndrome, long-term pulmonary hypertension Stones
Hyperdynamic flow murmurs Enlarged (child); atrophic (adult)
Hematuria, loss of renal concentrating ability, proteinuria
Acute abdomen Stillbirths
Priapism
Dactylitis Avascular necrosis
Infarction, infection Leg ulcers
CBC
Peripheral Blood Hb Electrophoresis
Treatment
HbAS
Normal
Normal; possibly a few target cells
HbA fraction of 0.65 (65%) HbS fraction of 0.35 (35%)
HbSS
Increased reticulocytes, decreased Hb, decreased Hct
Sickled cells
No HbA, only HbS and HbF (proportions change with age); normal amount of HbA2
• geneticcounselling
• HbAS:notreatmentrequired
• HbSC:treatmentasperHbSS,butisdictatedbysymptomseverity • HbSS
1. folic acid to prevent folate deficiency
2. hydroxyurea to enhance production of HbF
NIH Consensus Development Conference Statement: Hydroxyurea Treatment for Sickle Cell Disease
Ann Intern Med 2008;148:932-938
Efficacy: Strong evidence for adolescents and adults and there is emerging data supporting its use in children. In the single RCT, the Hb level was higher in hydroxyurea recipients than placebo recipients after 2 yr (difference, 6 g/L), as was HbF (absolute difference, 3.2%). The median number of painful crises was 44% lower than in the placebo arm. The 12 observational studies that enrolled adults reported a relative increase in HbF of 4-20% and a relative reduction in crisis rates by 68-84%. Hospital admissions declined by 18-32%. Effectiveness: Data is limited. It seems to be highly effective but is currently underutilized.
Short-Term Harms (within 6 mo): Dose-related leukopenia, thrombocytopenia, anemia, and decreased reticulocyte count. Others include decreased sperm production and dry skin. Long-Term Harms: Birth defects in offspring of people receiving the drug, growth delays in children receiving the drug, and cancer in both children and adults who receive the drug.
◆ mechanism of action: stops repression of Hb-γ chains and/or initiates differentiation of stem cells in which this gene is active
◆ presence of HbF in the SS cells decreases polymerization and precipitation of HbS
◆ N.B. hydroxyurea is cytotoxic and may cause bone marrow suppression 3. treatment of vaso-occlusive crisis
◆ supportive care: oxygen, hydration (reduces viscosity), correct acidosis, analgesics/opiates
◆ indication for exchange transfusion: Hb <50-60 g/L, SCD complications (acute chest syndrome,
aplastic crisis, hepatic or splenic sequestration, stroke), prevention of complications, pre-
operative
◆ less routinely: antimicrobials for suspected infection
4. prevention of crises
◆ establish diagnosis
◆ avoid conditions that promote sickling (hypoxia, acidosis, dehydration, fever) ◆ vaccination in childhood (pneumococcus, meningococcus, H. influenzae b) ◆ prophylactic penicillin (age 3 mo-5 yr)
◆ good hygiene, nutrition, and social support
5. screen for complications
◆ regular blood work (CBC, reticulocytes, iron indices, BUN, LFTs, and creatinine)
◆ urinalysis annually (proteinuria and glomerulopathy)
◆ transcranial doppler annually until 16 yr old (stroke prevention)
◆ retinal examinations annually from 8 yr old (screen for retinopathy)
◆ echocardiography once in late childhood/early adulthood (screen for pulmonary hypertension)