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30 Cards in this Set
- Front
- Back
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What is adult vs fetal Hgb difference
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Adult - 2 alpha, 2 beta
Fetal - 2 alpha, 2 gamma gamma and beta switch about 2-3 months after birth Some delta |
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Hgb forms in existence
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Alpha, Beta predominate in adults
Gamma in fetal (with Alpha) Some delta expression |
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Sickle Cell Mutation
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Glutamate to Valine (hydrophilic to hydrophobic) on BETA globin
Seen on Hemoglobin Electrophoresis by smearing instead of clear bands |
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What is FS on newborn screen?
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Means they are making no A Hgb. F is fetal Hgb and S is sickle. Could be S/S, S/Bo, etc.
Sickle Cell Anemia Sickle Cell Beta Thalassemia Sickle Cell with HPFH |
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SB thalassemia
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One beta is sickle, one beta is thal
B thal mutations are either B(0) [make no normal beta chains] or B+ [make some normal beta chains] If you have some beta chains available you can make HbA. ie. if have B+ beta thalasemia can still make some HbA |
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Types of Beta thalassemia, how to detect
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Minor, Intermediate and Major
B/B - Normal B/Bo - Beta Thal Minor B/B+ - Beta Thal Minor B+/B+ - Beta Thal Intermedia B+/Bo - Beta Thal Intermedia Bo/Bo - Beta Thal Major (Cooley's Anemia) Beta Thal Intermedia - increased F and A2 (A2delta2), SOME HbA (b/c have some working B), MODERATE anemia, HYPOCHROMIA and MICROCYTOSIS, variable HSM, MAY need transfusions Beta Thal Major - HIGH F and A2, NO NO NO HbA (must be Bo/Bo), Severe hypochromic, microcytic anemia. TARGET CELLS, TEAR DROPS, organomegaly, growth failure, lifelong transfusions |
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Alpha Thalassemia types
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aa/aa; normal
aa/a-; Silent carrier aa/--; Thalassemia trait (minor) - Asian often, BUT risk of passing and getting a hydrops fetalis a-/a-; Thalaseemia trait (minor) - AA often a-/--; Hgb H disease (intermedia) --/--; Hydrops fetalis, need in utero transfusions |
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Effect of no alpha globins available, Neonates and Adult Globins
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Can see in minor alpha thalasemias rarely aa/-- or a-/a-, more in HgbH (a-/--)
Have Hb Barts (gamma 4) or HbH (beta 4) chains that are unstable, oxidized to intracellular Neonates Minor will have 5% Hb Barts Intermediate (Hb H) will have 40% Hb Barts Major will have nearly 100% Hb Barts and HbH |
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How to approach thalassemia pt, neonate considerations
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Check Hgb
a) Look for HbA first. If making any HbA then MUST have some Beta being produced and it is not major beta thalassemia. If not may be Alpha or B0/B0 b) Then HbA2, if it is high then not making much Beta c) If very little HbA or HbA2 then likely an alpha thalassemia, if high then Beta thal Neonate Alpha thal neonate - will have Hb Barts or HbH Beta thal neonate - MAY be normal since gamma is more than beta |
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Transfusion Guidelines for Thalassemias
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1) Determine blood type and minor antigens before first transfusion
2) Keep pre transfusion 9.5-11.5 Suppress ineffective erythropoiesis 3) Transfuse 10-20mL/kg 4) Avoid post transfusion Hb 16 5) Transfuse every 3-5 wks |
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Organ system complications seen in thalassemia
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Bones - small bones hands/feet, coarse cystic abnormalities, long bone thinning, dilated medullary cavity, widened skull and trabeculae leading to "hair on end"
Iron deposition - cardiac, liver - from chronic transfusions. Often die from cardiac deposits. Get hepatomegaly (parenchymal and phagocytes) that induces intralobular fibrosis Endocrine - Growth retardation, sexual maturation changes, HYPOTHYROIDISM, HYPOCALCEMIA, HYPERPHOSPHATEMIA, iron in zona glomerulosa, more mineralcorticoids, DIABETES Pulmonary - Pulm HTN esp in splenectomized pts |
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Exjade (Deferasirox), MOA, use
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iron chelator, oral tablet, chelated iron excreted in feces
Use: to reduce iron deposition in cardiac and liver tissue seen in chronic transfusions for thalassemic diseases |
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Transplant outcomes in Beta thal
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Matched sibling transplants for BETA THAL MAJOR (B0/B0) helps
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Sickle Cell Genotypes, Hb amount, smear
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HbSS (SBo): common, severe form, Hb is 6-9 gm/dL. Sickled RBC and polychromasia
HbSC: "milder", Hb 8-12 gm/dL, Target cells |
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Dx of Sickle Cell Disease
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Gel electrophoresis or isoelectric focusing
Sickle solubility testing should NEVER be used for diagnosis Newborn screening for all infants in US |
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Pathophysiology of Sickle Cell Disease, 2 conditions causing damage
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Point mutation at position 6 of beta globin (Glutamic acid to Valine
Upon deoxygenation the HbS molecule polymerizes within the RBC leading to shape changs Sickled RBC are rigid and obstruct small blood vessels leading to tissue necrosis Lysis of RBCs upregulates endothelial dysfunction (decreased NO) leads to Pulm HTN, leg ulcers, priapism, stroke WBCs adhere to endothelium, then RBCs bind leading to vaso-occlusion which can cause pain crisis, ACS, osteonecrosis |
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Dx for FS newborn screen
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ONLY have fetal and Sickle globin expression. Could only be S/S or S/B0 (which is essentially SS, b/c would make some A if had any normal B expression)
DEFINITELY have sickle cell, don't need sickle screen, immediately do prophylaxis penicillin for pneumococcus |
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Leading cause of sepsis in sickle cell, at risk group, treatment, course of treatment
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Pneumococcus, high risk at younger than 2 years
If see patient later in life still on penicillin with sickle cell they probably had splenectomy or got an pneumococcal infection Vaccinate Penicillin prophylaxis for <3 year olds with sickle cell. Can stop at age 5 if never got pneumococcal infection or had a splenectomy. Parents must aggressively seek medical care for all febrile events |
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Sickle Cell Anemia Acute Painful Event Presentation, Tx
Schedule |
Sudden onset of pain - extremities, back, sternum/ribs
Dactylitis - Hand-foot syndrome, painful swelling of hands, feet Tx: Analgesia (NSAIDs, opioids), and hydration Schedule: Time lag btw pain and administration, request for severe pain rather than prior to pain (avoid peaks and valleys), nurse pt relationship |
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Complications of sickle cell disease
How do pts present to ER |
Splenic Sequestration
Gallstones Acute Chest Syndrome Avascular Necrosis Stroke Admitted for other reasons but get ACS in hospital |
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Differentiating causes of Severe Anemia in sickle cell pts
Acute splenic sequestration vs parvovirus |
Acute Splenic Sequestration - RETICULOCYTOSIS and THROMBOCYTOPENIA (b/c cells can't get out of spleen)
Parvovirus - Reticulocytopenia and NORMAL platelets Both have the anemia can lead to shock and may present with splenomegaly |
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Splenic Sequestration, At risk, Presentation, Complications, Treatment
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At risk: children under 2
Presentation: anemia, thrombocytopenia and splenomegaly Complications: may cause hypovolemic shock and death if acute Tx: RBC transfusions, 50% recurrent. Splenectomy if recurs or especially severe |
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Aplastic Crisis
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Parvovirus shuts down RBC precursors
Since sickle cell is a hemolytic anemia and not making more get aplastic crisis Differentiate from splenomegaly b/c aplastic crisis has no compensatory reticulocytosis |
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Gallstones Cause, Presentation, Tx
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Cause: Chronic hemolysis leads to pigmented (bilirubin) stones
Presentation: Occur in 40% of pts by adulthood. ABDOMINAL PAIN, VOMITING, JAUNDICE Tx: cholecystecomy if symptomatic |
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Acute Chest Syndrome Presentation, Cause
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Cause: Infection, sickling, fat embolism (BIG) or atelectasias
Presentation: New pulmonary infiltrate, fever, pain, dyspnea, hypoxia, increased WBC Lower lobes most commonly involved, may have pleural effusions . USUALLY UNILATERAL At dx most have FEVER, COUGH, CHEST PAIN |
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Infections that can lead to ACS in sickle cell pts
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Chlamydia, Mycoplasma, or other bacteria
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Avascular Necrosis cause, main location, prevalence in sickle cell
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Occurs in all SCD genotypes
Osteonecrosis where collateral circulation limited Main location: Femoral, humeral heads Prevalence - 30-50% adults |
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Stroke in SCD, prevalence, presentation, at risk group, cause, complications, screening
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At risk: 7% of children with HbSS
Cause: Thrombotic or infarctive event involving large intracranial arteries Presentation: Weakness, aphasia, seizures, LOC. 1/3 are SILENT infarcts Complications: permanent neurological damage and long-term disability Screening: Transcranial Doppler Ultrasonography to measure flow velocity. Strokes at greater risk with increased velocity (>170cm/sec is conditional; >200cm/sec is abnormal) |
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Hydroxyurea, MOA, use, clinical benefits
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Beneficial for SCA, increases fetal hemoglobin (HbF), decreases WBC, oral capsules, safe
Clinical benefits: Reduces pain, dactylitis, hospitalizations, acute chest syndrome, transfusion req. |
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Treating SCD and preventing complications
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Transfusions and standard care
Exjade (Deferasirox) - Iron chelator Hydroxyurea Stem Cell transplantation - cure but only 15% of pts have HLA matched sibling, needs high dose chemo and radiation and likely leads to sterility |
