Heme Flashcards
How do you diagnose alpha thalassemia?
- CBC
- Hypochromic, microcytic anemia
- Normal or increased RBC count
- Normal or increased serum iron and iron stores (ferritin)
- Peripheral smear
- Target cells, teardrop cells, basophilic stippling, Heinz bodies (in Hb H disease)
- Hb electrophoresis
- Normal HbA, HbA2 and HbF
Dx of exclusion!
What is the clinical intervention for alpha thalassemia?
- Mild - no tx needed
- Moderate
- Folate (if high reticulocyte count), avoid oxidative stress, avoid iron supplementation
- Severe
- Weekly blood transfusions, vitamin C, folate
- Iron chelating agents
- Splenectomy
- Allogenic bone marrow transplant (definitive)
In a hemolytic anemia, what would you expect to see for the following lab values: peripheral smear, haptoglobin, indirect bilirubin, reticulocyte count, and LDH.
- Peripheral smear - increased reticulocytes (immature RBCs), schistocytes (bite cells)
- Haptoglobin - decreased; becomes depleted when it binds to free Hb with continued RBC destruction
- Indirect bilirubin - increases due to RBC destruction which overwhelms the liver’s ability to convert indirect bilirubin to direct bilirubin
- Reticulocyte count - increases due to increased RBC destruction
- LDH - increases; LDH is an enzyme that is released from destroyed RBCs
What is the clinical intervention for autoimmune hemolytic anemia?
- Warm (IgG Ab)
- 1st line - corticosteroids
- 2nd line - splenectomy or rituximab
- 3rd line - immunosuppressants (azathiprine, cyclophosphamide, cyclosporine)
- Cold (IgM Ab)
- Avoid cold exposure - mainstay
- Severe or symptomatic - transfusions, plasmapheresis, IVIG
What lab value will help to distinguish between autoimmune hemolytic anemia and hereditary spherocytosis?
Coombs test will be positive in autoimmune hemolytic anemia.
Which lab will help to distinguish between alpha and beta thalassemia?
Hemoblogin electrophoresis - in beta thalassemia Hb ratios will be abnormal whereas in alpha thalassemia Hb ratios will be normal
What is the patient population commonly affected in chronic myelogenous leukemia (CML)?
Patients > 50 YO
What are the physical exam and lab findings that you may see in CML?
- Splenomegaly
- Positive Philadelphia chromosome
- Increased WBC count
What is protein C? What is the inheritance pattern for protein C deficiency?
- Protein C - vitamin K dependent anticoagulation protein produced by the liver that stimulates fibrinolysis and clot lysis. It inactivates Factors 5 and 8
- Autosomal dominant
What is the most common inherited cause of hypercoagulability?
Factor V Leiden
What patient population is primarily affected in G6PD? What is the inheritance pattern? What can cause acute hemolysis in this disease?
- African American men
- X-linked recessive
- Infection (MC), drugs (sulfa drugs), foods (fava beans), chemicals
What will the peripheral smear show in G6PD? What is the clinical intervention?
- Schistocytes (bite cells), Heinz bodies
- Usually self-limiting. Avoid offending agents and hydrate. If severe anemia, give iron and folate supplements and blood transfusions if neecessary
What is the patho for Goodpasture syndrome?
Goodpasture syndrome is a small vessel vasculitis in which IgG antibodies are made against type IV collagen of the alveoli and glomerular basement membrane of the kidney. It is a type II hypersensitivity.
What would you see on biopsy in Goodpasture syndrome?
Linear IgG deposits in the glomeruli or alveoli on immunofluorescence
What is the patho for hemochromatosis? At what age do symptoms usually begin?
- Autosomal recessive disorder characterized by excess iron deposition in the parenchymal cells of the heart, liver, pancreas, and endocrine organs.
- Symptoms usually begin after 40 YO
What diagnosis would you suspect in a kid with GI symptoms, anemia, increased BUN/Cr, and thrombocytopenia?
Hemolytic uremic syndrome
Which coagulation pathway does Hemophilia A affect? What is the clinical intervention?
- Intrinsic (Factor VIII)
- Factor VIII infusion; Desmopressin can be used prior to procedures to prevent bleeding in mild disease
What is Henoch Schonlein purpura? What is the patient population that is most affected?
- IgA deposition in skin leading to an immune-mediated leukocytoclastic vasculitis
- MC occurs after URI sxs
- 90% of cases occur in kids between 3-15 YO
What are the symptoms of Henoch Schonlein purpura?
- Prodrome - HA, anorexia, fever
- Skin - rash on legs, symmetrical, palpable purpura
- GI - abdominal pain, vomiting
- Joints - pain in knees, ankles
- Renal - hematuria, proteinuria, subcutaneous edema
What is the clinical intervention for Henoch-Schonlein purpura?
- Supportive - self-limited (1-6 weeks), bed rest, hydration
- NSAIDS - joint pain
What is the patho for hereditary spherocytosis?
- Autosomal dominant
- Deficiency in RBC membrane and cytoskeletin (spectrin), leading to RBC fragility and sphere-shaped RBCs. These abnormal RBCs are detected and destroyed by the spleen (hemolysis)
What is the patient population commonly affected by Hodgkin’s lymphoma? What are physical exam and lab findings?
- 20 or 50 YO (bimodal distribution)
- Physical exam:
- Painless lymphadenopathy, hepatosplenomegaly, night sweats, weight loss, anorexia
- Labs
- Lymph node biopsy - Reed-Sternberg cells (“owl-eye” appearance) → pathognomonic
Describe the difference between physiologic and pathologic jaundice in the newborn.
- Physiologic - occurs because the liver is unable to efficiently conjugate bilirubin due to decreased UGT enzyme activity. Jaundice begins after 24 hours of life, peaks in days 3-5 and falls during the first week of life
- Pathologic - jaundice that occurs within the first 24 hours of life or persists for 10-14 days
What is the most common leukemia in adults overall? How is this disease diagnosed?
- Chronic lymphocytic leukemia
- Labs:
- CBC - absolute lymphocytosis
- Peripheral smear - small, well-differentiated normal-appearing lymphocytes with scattered smudge-cells (fragile B cells become crushed by cover slip during prep)
What are the lab findings for B12 deficiency? Folate deficiency?
- B12 deficiency - hypersegmented neutrophils, increased serum homocysteine, increased methylmalonic acid
- Folate deficiency - increased serum homocysteine only
What are the lab findings for multiple myeloma?
- Eletrophoresis - monoclonal M protein spike
- Urine protein electrophoresis - Bence Jones proteinuria
- CBC - roleaux formation (RBCs stacked like coins)
- Skull radiographs - “punched-out” lytic lesions
- Bone marrow biopsy - plasmacytosis > 10%
What is the patho for paroxysmal nocturnal hemoglobinuria? What is the symptom triad?
- RBCs are deficient in CD55 and CD59. Normally, these surface proteins protect RBCs from complement destruction. Deficiency leads to increased complement activation and intravascular RBC destruction
- Triad of hemolytic anemia (hemoglubinuria), pancytopenia, thrombosis (atypical veins)
What is the patho for pernicious anemia?
Autoimmune destruction or loss of gastric parietal cells which secrete intrinsic factor. Decreased production of intrinsic factor results in pernicious anemia
What mutations are responsible for polycythemia vera?
JAK2 V617F or exon 12 mutation
What can cause aplastic crisis in sickle cell anemia?
Parvovirus B19 infection
