Heme Flashcards
Peutz-Jeghers syndrome has what features? What is management?
Autsomal dominant unregulated tissue growth (particularly GI)
Hyperpigmented mucocutaneous macules (lips, buccal mucosa, palms/soles)
Hamartomatous polyps in GI tract –> occult bleeding or intestinal obstruction
Increased risk for GI, breast, genital tract cancers
Management: Annual anemia screening, cancer screening (eg upper/lower endoscopy)
Desmopressin can be used for what coagulopathy?
von Willebrand disease
Anti-D Ig can be first-line therapy for what coagulopathy?
ITP - only works if they are Rh(D)+ and Coombs-negative
Who is more likely to develop chronic ITP (lasts >1 year) rather than <3 months self-resolved? What is appropriate testing and management?
Those with mild initial presentation and no preceding viral trigger
Bone marrow exam and blood tests for infection and autoimmune disease; if negative, management similar to ITP
What is first-line therapy for ITP?
Children: Glucocorticoids, IVIG, or anti-D if bleeding; otherwise observe if cutaneous only (platelet cutoff of 30,000 applies to adults only)
What is second-line therapy for chronic ITP?
Rituximab
Thrombopoietin receptor agonists
Splenectomy if refractory
Treatments for hereditary spherocytosis
Folic acid supplementation
Blood transfusion
Splenectomy
What tests are used to confirm hereditary spherocytosis?
Acidified glycerol lysis (osmotic fragility)
Eosin-5-maleimide binding tests
Why can polycythemia of newborn cause?
Respiratory distress, cyanosis, apnea
Irritabiliy, jitteriness
Hypoglycemia, hypocalcemia - due to increased cellular uptake
Name the Hemoglobin of these diseases:
Normal
Beta-thalassemia minor
Beta-thalassemia major
Sickle cell trait
Sickle cell disease
Normal: Hgb A (2 alpha 2 beta)
Beta-thalassemia minor: Increased Hgb A2 (2 alpha 2 delta), decreased Hgb A
Beta-thalassemia major: Vastly increased Hgb A2, F; absent Hgb A
Sickle cell trait: Increased Hgb S, vastly decreased Hgb A
Sickle cell disease: Vastly increased Hgb S, F; absent Hgb A
What is a skeletal consequence of untreated beta thalassemia major?
Skeletal abnormalities due to extramedullary hematopoiesis
What is a complication of beta thalassemia major treatment?
Blood transfusion-dependent iron overload - use chelation therapy to avoid damage to liver, kidneys, and endocrine glands
What causes the destruction of cartilage and bone in hemophilic arthropathy?
Hemosiderin deposition –> synovial inflammation –> fibrosis and destruction
Best seen on MRI but may be visible on x-ray if severe
What is the mechanism of G6PD deficiency RBC death?
Lack of NADPH –> lack of glutathione –> oxidation –> denature/precipitate Hgb into Heinz bodies –> reduced RBC flexibility –> cell damage (bite cells) and lysis in reticuloendothelial system
What is the mechanism of penicillin and cephalosporin-induced immune-mediated hemolytic anemia?
Bind to RBC surface and act as hapten for IgG attachment –> RBC destruction by splenic macrophages –> extravascular hemolysis
What virus can cause aplastic crisis of RBCs in those predisposed to RBC lysis (hereditary spherocytosis, sickle cell disease, etc.)?
Parvovirus
Sickle cell trait has what most common renal issue? What are less common renal and non-renal issues?
Microscopic/gross hematuria from sickling in renal medulla
Hyposthenuria - impairment in concentrating ability - nocturia and polyuria
Less common:
UTI, particularly during pregnancy
Splenic infarction at high altitudes
Hereditary spherocytosis is more common in what population?
Northern European, autosomal dominant
What is paroxysmal nocturnal hemoglobinuria? Manifestations?
Acquired, complement-mediated hemolytic anemia
Hemolytic anemia
Cytopenias
Hypercoagulability
Diagnosed by CD55 and CD59 absence
What does dactylitis in an infant suggest?
Vaso-occlusive crisis in sickle cell disease
Also has erythema and warmth, may be preceded by trigger (eg dehydration)
+/- low-grade fever
Older patients should be considered for autoimmune disorders (eg psoriatic arthritis, ankylosing spondylitis)
Sickle cell predisposes to what bacterial osteomyelitis?
Salmonella
S aureus is most common cause in all patients
Hemoglobin < what is concerning for pathologic etiology in infant?
<9; remember that physiologic anemia of infancy can present with nadir around 11 at age 2-3 months in term infants
How do TTP and ITP treatments differ?
TTP: Plasma exchange (removes anti-ADAMTS13 Ab and replaces ADAMTS13)
ITP: IVIG
Heinz bodies of G6PD deficiency appear on what stain?
Special crystal violet stain (not Wright stain)
What RBC observation on peripheral smear is due to asplenia or functional hyposplenism?
Howell-Jolly bodies on Wright stain - RBC nuclear remnants normally removed by spleen
What would you observe on peripheral smear with lead poisoning?
Basophilic stippling - multiple, scattered, blue granules within RBC cytoplasm
Due to precipitation of ribosomal ribonucleic acid
Infant iron deficiency treatment
Oral iron therapy; recheck Hgb in 4 weeks; if risen 1, then continue iron for 2-3 months after Hgb normalizes
Is G6PD deficiency managed with splenectomy?
No - avoidance of hemolytic triggers
Testicular enlargement can be seen in what heme malignancy?
ALL - along with SVC syndrome and pancytopenia
As opposed to in children, where can ALL potentially be located in adolescents and adults?
Thymus - anterior mediastinal mass - T-ALL
How to calculate corrected reticulocyte count?
retic x hematocrit/45%
What is treatment for hyperbilirubinemia in newborn after phototherapy?
Exchange transfusion - unconjugated bilirubin >25 or if rapid rate of rise unresponsive to phototherapy
Hydroxyurea side effects
Macrocytosis
Myelosuppression
How is MCHC affected in:
Iron deficiency anemia
Beta thalassemia
Hereditary spherocytosis
Decreased in IDA, beta thalassemia
Increased in hereditary spherocytosis
What does vitamin K do?
Essential for enzymatic carboxylation and activation of II, VII, IX, and X
How do platelets appear in Bernard-Soulier syndrome?
Unusually large, low platelets
Prolonged bleeding time
Due to mutation in GPIb-alpha, GPIb-beta, and GPIX
What mutation causes cyclic neutropenia or severe congenital neutropenia (as opposed to benign familial neutropenia)? What is treatment?
Mutations in neutrophil elastase
Treat with G-CSF
What lab count is the definition of neutropenia? What is severe and less likely to be due to myelosuppression?
ANC <1500
ANC <500 is severe
ANC <200 seen in severe congenital neutropenia, along with monocyte elevation
Pulse ox sat ~85% without further improvement suggests what?
Methemoglobinemia - Fe+3 –> Hgb structure change –> increased affinity for O2 at other sites –> left shift –> decreased oxygen delivery
85% is due to absorption of light at different wavelengths
Will also see >5% saturation gap between pulse ox and ABG - due to ABG only analyzing unbound arterial oxygen, showing falsely elevated O2 saturation, shown as normal PaO2
What is co-oximetry testing?
Analyzes hemoglobin absorption wavelengths for Hgb, methemoglobin, and carboxyhemoglobin
Methemoglobinemia treatments
Methylene blue - reduced by NADPH so that it can reduce methemoglobin
High-dose vitamin C if unavailable or contraindicated (G6PD deficiency)
What is the side effect of hydroxyurea?
Macrocytic aplasia - inhibits ribonucleoside reductase, preventing creation of DTP
Myelosuppression, low reticulocyte count
What is Mentzer index?
MCV/RBC ratio
<13: suggests thalassemia
Increased erythrocyte adenosine deaminase activity
Diamond-Blackfan anemia
Diamond-Blackfan anemia treatment
Steroids if >=1 yo, RBC transfusions if <1 yo or steroid-resistant; consider BMT
Fanconi anemia treatment
Allogeneic hematopoietic cell transplantation
Androgen therapy (e.g. oxymetholone), growth factors (e.g. G-CSF, GM-CSF), blood transfusion
Diamond-Blackfan vs Fanconi anemia - inheritance
D-B: Autosomal dominant
Fanconi: Autosomal recessive or X-linked
RBM8A gene
Thombocytopenia absent radius syndrome - autosomal recessive
Hypomegakaryocytic thrombocytopenia and bilateral radial bone aplasia in presence of thumbs
Kasabach-Merritt syndrome
Life-threatening coagulopathy of infancy like DIC - attributed to aggressive benign vascular tumors
Can cause reactive hemarthrosis, congestive heart failure, GI bleeding
Would see enlarging, firm, purpuric cutaneous or soft tissue lesions; do not biopsy due to bleeding risk
Surgical resection is definitive
