Hematology Rosh Review/Smarty Pance (in progress question 8 on rosh review first heme assigned)

What does a complete blood count reveal in a transient aplastic crisis?

Severe anemia, thrombocytopenia, and leukopenia.

What does a bone marrow biopsy show in a transient aplastic crisis?

Severe aplasia and giant pronormoblasts with viral inclusions.

What symptoms may occur during oxidative stress in G6PD deficiency?

Sudden onset of jaundice, pallor, dark urine, abdominal pain, and back pain.

what is cheilosis

Superficial crusted fissures in the corners of the mouth

What induces oxidative stress on red blood cells?

Superoxide anion and hydrogen peroxide.

What is the treatment for a transient aplastic crisis caused by Parvovirus B19?

Supportive care and blood transfusion.

What does Parvovirus B19 cause in patients with hematological abnormalities?

Temporary suspension of erythropoiesis.

Cheilosis is noted in

iron deficiency anemia.

Chronic lymphocytic leukemia presents with a WBC count greater than

20000/microliter and absolute lymphocyte count of greater than 5000/microliter.

How much does the hemoglobin level usually fall in acute oxidative stress? (seen in glucose 6 phosphate deficiency)

3 g/dL to 4 g/dL.

What is polycythemia vera?

A condition characterized by elevated hemoglobin and hematocrit.

What is Parvovirus B19?

A virus associated with transient aplastic crisis. --invades RBC precursors --multiplies and destroys --causes a drop in hemoglobin (undedectable reticulocyte count)

Which vessels are more commonly affected by thrombosis in paroxysmal nocturnal hemoglobinuria?

Abdominal and cerebral vessels.

What are spherocytes?

Abnormally shaped red blood cells.

What are the three major variants of G6PD deficiency?

African, Mediterranean, and Asian variants.

What is the curative therapy for patients with life-threatening paroxysmal nocturnal hemoglobinuria?

Allogeneic hematopoietic stem cell transplantation.

What are the lab findings in acute oxidative stress? (seen in glucose 6 phosphate deficiency)

Anemia, reticulocytosis, elevated bilirubin.

What is the role of glutathione in red blood cells?

Antioxidant and oxidized in the neutralization process.

What is the mainstay of treatment for G6PD deficiency?

Avoiding sources of oxidative stress.

How many people worldwide are affected by G6PD deficiency?

Approximately 400 million.

When does hemolysis in paroxysmal nocturnal hemoglobinuria typically occur?

At night.

What may be seen on a peripheral blood smear during a hemolytic episode in G6PD deficiency?

Bite cells, blister cells, and Heinz bodies.

What can be seen on a peripheral blood smear during a hemolytic episode in glucose-6-phosphate dehydrogenase deficiency?

Blister cells, bite cells, Heinz bodies.

Which class of G6PD deficiency is the most severe?

Class I.

Which class of G6PD deficiency is the least severe?

Class V.

What can flow cytometry help determine in paroxysmal nocturnal hemoglobinuria?

Clone size.

Paroxysmal Nocturnal Hemoglobinuria

Cola-colored urine, dyspnea, fatigue Nighttime RBCs lack CD 55 and 59 Anemia Hemolysis Monitor for thrombosis Supportive care Treat with stem cell transplant, eculizumab

What can induce autoimmune hemolytic anemia?

Drugs, particularly cephalosporins.

What laboratory findings may be seen in paroxysmal nocturnal hemoglobinuria?

Elevated lactate dehydrogenase, increased reticulocyte count, and decreased haptoglobin.

What are the clinical manifestations of paroxysmal nocturnal hemoglobinuria?

Fatigue, dyspnea, cola-colored urine, jaundice, dysphagia, erectile dysfunction, and abdominal pain.

What is the most common enzymatic disorder of the red blood cells?

G6PD deficiency

What are some laboratory findings in G6PD deficiency?

Hemolytic anemia with increased reticulocytes, increased indirect bilirubin, and decreased haptoglobin.

G6PD Deficiency

History of taking antimalarials, sulfonylureas, quinolones, nitrofurantoin, fava beans Infection is also a cause for the hemolysis Labs will show Heinz bodies, presence of bite cells on the smear Consider testing prior to starting potential agents in patients who may be at risk X-linked recessive

What causes warm agglutinin?

Immunoglobulin G antibodies reacting to protein antigens on the RBC's at body temperature. --most common type

What causes cold agglutinin?

Immunoglobulin M antibodies reacting to polysaccharide antigens on the RBCs surface with cold exposure.

What can trigger hemolysis in paroxysmal nocturnal hemoglobinuria?

Infection, surgery, exercise, and alcohol use.

What are some other triggers of oxidative stress in G6PD deficiency?

Infections (such as pneumonia), diabetic ketoacidosis, and viral hepatitis.

Who is more commonly affected by G6PD deficiency?

Males, with a predilection for Black individuals.

What are the morphologic abnormalities in G-6-PD deficiency?

Minimal or no RBC morphologic abnormalities.

What percentage of patients with sickle cell disease have evidence of seroconversion to Parvovirus B19 by age 20?

More than two-thirds.

What are other complications of paroxysmal nocturnal hemoglobinuria?

Myelodysplasia and acute myelogenous leukemia.

What cofactor is required for the reduction of glutathione?

NADPH.

What is the result of Direct Coombs testing in paroxysmal nocturnal hemoglobinuria?

Negative.

What does G6PD generate?

Nicotinamide adenine dinucleotide phosphate plus hydrogen (NADPH).

What are some medications that can cause oxidative stress in G6PD deficiency?

Nitrofurantoin, primaquine, methylene blue, and dapsone.

What does glucose-6-phosphate dehydrogenase catalyze?

Oxidation of glucose-6-phosphate and NADPH.

What are the symptoms of acute oxidative stress in patients with glucose-6-phosphate dehydrogenase deficiency?

Pallor, jaundice, dark urine, abdominal/back pain.

What are the clinical manifestations of a transient aplastic crisis?

Pallor, weakness, and lethargy. typically no rash

Which patient population is Parvovirus B19 more common in?

Patients with sickle cell disease.

How are asymptomatic patients with paroxysmal nocturnal hemoglobinuria managed?

Periodic monitoring.

What are the common physical examination findings in patients with polycythemia vera?

Plethora, engorged retinal veins, and splenomegaly.

What happens to hemoglobin molecules in glucose-6-phosphate dehydrogenase deficiency?

Precipitate as Heinz bodies, leading to loss of function and cell death.

What is the function of glycophosphatidylinositol-anchor surface proteins?

Protect red blood cells from complement destruction.

What does NADPH do?

Protects red blood cells from oxidative stress.

How is the diagnosis of G6PD deficiency confirmed?

Quantitative NADPH assay.

What is paroxysmal nocturnal hemoglobinuria?

Rare acquired mutation of hematopoietic stem cells.

What does flow cytometry reveal in paroxysmal nocturnal hemoglobinuria?

Reduced levels of glycophosphatidylinositol-anchored proteins on peripheral blood cells.

What are the associated conditions with Parvovirus B19? (at risk for transient aplastic anemia)

Sickle cell disease, hereditary spherocytosis, and iron deficiency anemia.

What is the characteristic finding in reticulocyte counts during a transient aplastic crisis?

Significantly decreased counts.

What is thrombosis?

The formation of a blood clot in a blood vessel.

Which type of thrombosis is more common in paroxysmal nocturnal hemoglobinuria?

Venous thrombosis.

What are the two major types of autoimmune hemolytic anemia?

Warm agglutinin and cold agglutinin.

What triggers anemia in autoimmune hemolytic anemia?

Viral infection, autoimmune disease (systemic lupus erythematosus), malignancy (chronic lymphocytic leukemia), and exposure to cold.

What is glucose-6-phosphate dehydrogenase deficiency?

X-linked recessive deficiency affecting males.

What is Glucose-6-phosphate dehydrogenase (G6PD) deficiency?

X-linked recessive disorder affecting red blood cell enzyme G6PD.

Deficiency in these enzymes results in sideroblastic anemia

aminolevulinic acid dehydrogenase and aminolevulinic acid synthetase --> enzymes involved in the biosynthesis of protoporphyrin, a precursor molecule for hemoglobin production.

Purpura is typically noted in

bleeding disorders.

Acute lymphocytic leukemia is more common in

children and presents with blasts in the peripheral blood.

Chronic myelogenous leukemia presents with

elevated WBC count, marked left shift in the myeloid series of cells, and positive for Philadelphia chromosome.

antimalarials that have definite risk of hemolysis in G6PD deficiency

mepacrine, pamaquine, pentaquine, primaquine

is the coombs test positive or negative in glucose-6-phosphate deficiency?

negative

antibiotics that have definite risk of hemolysis in G6PD deficiency

nitrofurans, quinolones, chloramphenicol, sulfonamides

Hereditary spherocytosis presents with a normocytic

normochromic anemia and many spherocytes.

Acute myelogenous leukemia presents with

pancytopenia and presence of blasts in the peripheral blood.

Vitamin B12 deficiency

pernicious anemia

Diagnosis of hereditary spherocytes is confirmed with a?

positive osmotic fragility test. The direct Coombs test would be negative and would not be helpful in diagnosing

What would be the expected finding on the peripheral smear in a patient with warm autoimmune hemolytic anemia?

spherocytes

Decreased vibratory sense is noted in

vitamin B12 deficiency.

What is paroxysmal nocturnal hemoglobinuria?

A disorder characterized by the destruction of red blood cells.

What is the half-life of the normal wild-type glucose-6-phosphate dehydrogenase D?

62 days.

What is G-6-PD deficiency?

A condition characterized by low G-6-PD enzyme activity.

What complications can result from Parvovirus B19 infection? (in transient aplastic crisis)

Acute splenic sequestration, stroke, and congestive heart failure.

What is the treatment for glucose-6-phosphate dehydrogenase deficiency?

Avoiding foods or medications causing oxidative stress.

How is G-6-PD deficiency diagnosed?

By measuring G-6-PD enzyme activity level.

What is the first-line therapy for paroxysmal nocturnal hemoglobinuria?

Complement inhibitors, such as eculizumab.

What are some food-related causes of oxidative stress in G6PD deficiency?

Fava beans and bitter lemon.

What foods or medications can cause oxidative stress in patients with glucose-6-phosphate dehydrogenase deficiency?

Fava beans, bitter lemon, nitrofurantoin, primaquine, dapsone.

How many classes of G6PD deficiency are there?

Five: I, II, III, IV, and V.

What is the best screening test for paroxysmal nocturnal hemoglobinuria?

Flow cytometry.

Are most patients with G6PD deficiency symptomatic?

No, most are asymptomatic under normal circumstances.

What is the initial diagnostic tool of choice for G6PD deficiency?

Heinz preparation.

What is autoimmune hemolytic anemia?

Immunologic-mediated destruction of red blood cells due to autoantibodies against someones RBCs --spherocytes often found on blood smear in warm autoimmune hemolytic anemia --agglutination found in cold autoimmune hemolytic anemia

What may be required in severe cases of anemia in G6PD deficiency?

Iron and folic acid supplementation, along with blood transfusions.

What is the cause of paroxysmal nocturnal hemoglobinuria?

Mutation in the PIGA gene on the X chromosome.

Is recurrence likely after a transient aplastic crisis caused by Parvovirus B19?

No, due to the development of immunity following initial infection.

What treatment may be needed for patients with severe anemia in paroxysmal nocturnal hemoglobinuria?

Red blood cell transfusions.

What is the leading cause of death in patients with paroxysmal nocturnal hemoglobinuria?

Thrombosis.

Iron deficiency anemia is diagnosed with?

a serum ferritin.

Iron deficiency anemia typically presents with

microcytic hypochromic red blood cells

Glucose-6-phosphate dehydrogenase catalyzes

the oxidation of glucose-6-phosphate to 6-phosphogluconolactone and the oxidation of nicotinamide adenine dinucleotide phosphate to nicotinamide adenine dinucleotide phosphate hydrogen, a cofactor in glutathione metabolism. -->Superoxide anion and hydrogen peroxides, byproducts of the reaction between hemoglobin and oxygen, induce oxidative stress on the red blood cells. -->Under normal circumstances, red blood cells contain adequate concentrations of glutathione, a sulfhydryl-containing compound that functions as an antioxidant. Glutathione is oxidized (inactivated) in the oxidant neutralization process. Reduction of glutathione requires nicotinamide adenine dinucleotide phosphate hydrogen as a cofactor.