Heme/Onc Week #1 Review

MCV 80-100 fL

Normocytic anemia

MCV < 80 fL

Microcytic anemia

MCV > 100 fL

Macrocytic anemia

Presents with jaundice, splenomegaly, dark urine

Hemolytic anemia

Decreased haptoglobin + increased indirect bilirubin + increased LDH

Hemolytic anemia

Schistocytes on peripheral smear

Hemolytic anemia

Causes of intrinsic, hereditary hemolysis

G6PD deficiency, Sickle cell disease, Thalassemia, Hereditary spherocytosis

Causes of hypochromic, microcytic anemia

Iron deficiency anemia, thalassemia, lead toxicity

Causes of normocytic anemia

Anemia of chronic disease, renal disease

Causes of macrocytic anemia

B12 deficiency, folate deficiency

Most common cause of anemia worldwide

Iron deficiency anemia

Most commonly caused by chronic blood blood loss in the US (i.e. menstruation, occult GI blood loss)

Iron deficiency anemia

Dietary deficiency is most common cause worldwide

Iron deficiency anemia

Possible signs include pica, koilonychia

Iron deficiency anemia

↓ ferritin, ↑ TIBC, ↓ transferrin saturation, & ↓ serum iron

Iron deficiency anemia

Earliest laboratory sign is low ferritin

Iron deficiency anemia

High RDW

Iron deficiency anemia

Managed with oral ferrous sulfate 325 mg every other day (taken with vitamin C)

Iron deficiency anemia

Most common in children < 6 y/o

Lead poisoning anemia

Primarily associated with ingestion or inhalation of environmental lead

Lead poisoning anemia

May present with neurologic symptoms

Lead poisoning anemia

Detectable blood level is 3.5 mcg/dL, which necessitates referral for treatment

Lead poisoning anemia

Basophilic stippling on peripheral smear

Lead poisoning anemia

Protein needed for vitamin B12 absorption

Intrinsic factor

Length of B12 storage in liver

3 years

Pernicious anemia is most common cause

Vitamin B12 deficiency

Associated with Crohn's disease, H2 blockers, PPIs, metformin, chronic alcohol use, & vegan diet

Vitamin B12 deficiency

Signs/symptoms include glossitis, paresthesias, and decreased vibration & position sense

Vitamin B12 deficiency

Hyper-segmented neutrophils on peripheral blood smear

Vitamin B12 deficiency, Folate deficiency

Elevated homocysteine + elevated methylmalonic acid (MMA)

Vitamin B12 deficiency

Managed with IM cyanocobalamin

Vitamin B12 deficiency

Length of folic acid storage in the body

2-3 months

Most commonly caused by inadequate dietary intake

Folate Deficiency

Elevated homocystine + normal methylmalonic acid (MMA)

Folate Deficiency

Implicated medications include methotrexate, trimethoprim, & pyrimethamine

Folate Deficiency

Oral folic acid first line for management

Folate Deficiency

Increased ferritin + decreased TIBC

Anemia of chronic disease

Erythropoetin can be used for treatment in renal disease

Anemia of chronic disease

Decreased production of globin chains

Thalassemia

Microcytic anemia with normal/increased serum iron and no response to iron replacement therapy

Thalassemia

Most common hemoglobinopathy

Thalassemia

1 alpha thalassemia deletion (3 functioning genes)

Silent carrier

2 alpha thalassemia deletions (2 functioning genes)

Alpha Thalassemia Minor

3 alpha thalassemia deletions (1 functioning gene)

Hemoglobin H Disease

4 alpha thalassemia deletions (0 functioning genes)

Alpha Thalassemia Major

Presence of Hemoglobin H on Hb electrophoresis

Hemoglobin H Disease

Hemoglobin Barts (gamma globin tetramers) on Hb electrophoresis

Alpha-Thalassemia Major

Hydros fetalis is possible complication

Alpha-Thalassemia Major, Hemolytic disease of the newborn

2 beta thalassemia point mutations

Beta-Thalassemia Major

Severe anemia presenting in infants 6-12 months with no symptoms at birth

Beta-Thalassemia Major

1 beta thalassemia point mutation

Beta-Thalassemia Minor

Elevated hemoglobin A2 and hemoglobin F on Hb eletrophoresis

Beta-Thalassemia

Most common in those of Mediterranean descent

Beta-Thalassemia

"Chipmunk facies"

Beta-Thalassemia Major

Episodic hemolytic anemia in response to oxidative stress

G6PD deficiency

Triggers include nitrofurantoin, dapsone, primaquine, fava beans, or infection

G6PD deficiency

"Bite" cells or Heinz bodies on peripheral smear

G6PD deficiency

(+) Direct Coombs/antiglobulin test

Autoimmune hemolytic anemia

IgG antibodies activated by protein antigens on self RBC surface at body temperatures

Warm AIHA

IgM antibodies against polysaccharides bind to the RBC surface especially at colder temperatures

Cold AIHA

Autosomal recessive disorder affecting the beta globin gene

Sickle Cell Disease

Clinical manifestations are due to hemolytic anemia and vaso-occlusion

Sickle Cell Disease

Diagnosis confirmed by hemoglobin electrophoresis

Sickle Cell Disease

Sickled erythrocytes on peripheral smear

Sickle Cell Disease

Howell-jolly bodies on peripheral smear indicate functional asplenia

Sickle Cell Disease

Hb S majority on hemoglobin electrophoresis

Sickle Cell Disease

Hydroxyurea is mainstay of treatment

Sickle Cell Disease

Prophylactic penicillin in children

Sickle Cell Disease

Deficiency in red cell membrane & cytoskeleton proteins leads to increased RBC fragility, & sphere-shaped RBCs

Hereditary Spherocytosis

MCHC ≥ 36 g/dL

Hereditary Spherocytosis

(+) Osmolality fragility test

Hereditary Spherocytosis

EMA binding is preferred confirmatory test

Hereditary Spherocytosis

Splenectomy is curative in severe cases

Hereditary Spherocytosis

Chronic hemolytic anemia from birth

Pyruvate Kinase Deficiency

Rare, acquired hematopoietic stem cell mutation resulting in complement-mediated hemolytic anemia

Paroxysmal Nocturnal Hemglobinuria

Flow cytometry test is best screening test

Paroxysmal Nocturnal Hemoglobinuria

Suspect in patients with thrombosis at an unusual site or early age

Paroxysmal Nocturnal Hemoglobinuria

Managed with complement (C5) inhibitors such as Ravulizumab

Paroxysmal Nocturnal Hemoglobinuria

Pancytopenia due to hematopoietic stem cell failure

Aplastic anemia

Clinically manifests with bleeding, easy bruising, frequent infections, & fatigue

Aplastic anemia

Diagnosis confirmed by hypocellularity on bone marrow biopsy

Aplastic anemia

≥ 2 cytopenias on peripheral smear (anemia with corrected retic count < 1%, neutrophil count < 500, or platelet count < 20,000)

Aplastic anemia

C282Y mutation of HFE gene on chromosome 6

Hereditary hemochromatosis

Increased incidence in northern Europeans

Hereditary hemochromatosis

Decreased hepcidin leads to increased intestinal iron absorption

Hereditary hemochromatosis

Iron accumulates in liver, marrow, endocrine organs, cardiac tissue, and joints

Hereditary hemochromatosis

May present with bronze diabetes, cirrhosis, cardiomyopathy, hypogonadism

Hereditary hemochromatosis

Increased ferritin + increased transferrin saturation

Hereditary hemochromatosis

Increased susceptibility to Yersinia & Vibrio vulnificus

Hereditary hemochromatosis

Regular phlebotomy is mainstay of treatment

Hereditary hemochromatosis

Phlebotomize to hematocrit < 45% + daily low dose aspirin

Polycythemia vera

Myeloproliferative disorder with bone marrow overproduction of erythroid cells

Polycythemia vera

Major criteria are 1) increased Hgb/Hct, 2) bone marrow biopsy showing hypercellularity, 3) JAK2 mutation presence

Polycythemia vera

Minor criteria is low or subnormal EPO level

Polycythemia vera

Diagnosed by 3 major or 2 minor + 1 major criteria

Polycythemia vera

Peak incidence 60-65 years

Polycythemia vera

JAK 2 mutation

Polycythemia vera

Aquagenic pruritis

Polycythemia vera

Possible physical exam findings include hepatospenomegaly, facial flushing, & engorged retinal veins

Polycythemia vera

Increased hematocrit due to hypoxia (i.e. COPD)

Secondary erythrocytosis