Red Blood Cell Disorders Erin Smith AOA Heme/Onc Review November 22, 2009

Hb 12.5 Hct 37 Platelet count 217 RBC count 3.7 A 25 y/o woman has a 3 yr h/o arthalgias. PE shows no joint deformity, but she appears pale. Lab studies are shown. Peripheral blood smear shows hypochromatic and microcytic RBC’s. Total serum Fe and ferritin levels are within normal limits. Hb electrophoresis shows an elevated Hb A2 level of 5.8%. Which of the following is the most likely diagnosis? A) Autoimmune hemolytic anemia B) Beta thalassemia minor C) Infection with Plasmodium vivax D) Anemia of chronic disease E) Iron deficiency anemia Hb 12.5 Hct 37 Platelet count 217 RBC count 3.7

Answer B) Beta thalassemia minor C) Infection with Plasmodium vivax A) Autoimmune hemolytic anemia B) Beta thalassemia minor C) Infection with Plasmodium vivax D) Anemia of chronic disease E) Iron deficiency anemia Beta thalassemia and iron deficiency anemia both have hypochromic and microcytic RBC’s. Normal serum ferritin excludes iron deficiency anemia and anemia of chronic disease.

A 30 y/o woman has a constant feeling of lethargy A 30 y/o woman has a constant feeling of lethargy. On PE, she is afebrile and has a pulse of 80/min, respirations 15/min, and BP 110/70. The spleen tip is palpable, but there is no abdominal pain or tenderness. Lab studies show Hb of 11.7, platelet count of 159, and WBC count of 5390. Peripheral blood smear shows spherocytosis and the RBC’s have an increased osmotic fragility. An inherited abnormality in which of the following RBC components best accounts for these findings? A) Glucose-6-phosphate dehydrogenase B) Membrane cytoskeletal defect C) Alpha globin chain D) Heme E) Beta globin gene F) Carbonic anhydrase

Answer A) Glucose-6-phosphate dehydrogenase B) Membrane cytoskeletal defect C) Alpha globin chain D) Heme E) Beta globin gene F) Carbonic anhydrase Hereditary spherocytosis is caused by a mutation in ankyrin or spectrin that causes an increase in osmotic fragility of the RBC membrane. These deformed cells are destroyed in the spleen.

A 69 y/o female has been feeling increasingly tired and weak for 4 months. On PE she is afebrile. There is no hepatosplenomegaly or lymphadenopathy. Lab studies show Hb of 9.3, platelet count of 250, and WBC count of 6820. The peripheral smear is shown. Which of the following conditions should be suspected as the most likely cause of these findings? A) Pernicious anemia B) Gastrointestinal blood loss C) Aplastic anemia D) Beta thalassemia major E) Warm autoimmune hemolytic anemia

Answer A) Pernicious anemia B) Gastrointestinal blood loss C) Aplastic anemia D) Beta thalassemia major E) Warm autoimmune hemolytic anemia The RBC’s show microcytosis and hypochromia which is found in iron deficiency. The most common cause in the elderly is due to chronic blood loss from the GI tract. RBC’s are normal in patients with aplastic anemia. Microcytosis can accompany thalassemias but this would already be diagnosed at an earlier age. Autoimmune HA have a normocytic anemia.

A 40 y/o man has had pain and burning on urination for the past week A 40 y/o man has had pain and burning on urination for the past week. On PE, he is febrile and has a pulse of 92/min, RR 18/min, and BP 80/45. Digital rectal exam indicates a tender, enlarged prostate. Scattered ecchymoses are present over the trunk and extremities. Blood cx is + for Klebsiella pneumoniae. The blood smear is shown. These findings are indicative of which of the following? A) Hereditary spherocytosis B) Autoimmune hemolytic anemia C) Microangiopathic hemolytic anemia D) Iron deficiency anemia E) Megaloblastic anemia

Answer A) Hereditary spherocytosis B) Autoimmune hemolytic anemia C) Microangiopathic hemolytic anemia D) Iron deficiency anemia E) Megaloblastic anemia The patient has Gram negative sepsis leading to DIC. The fragmented RBC’s known as shistocytes or helmet cells are typical of conditions that can produce a microangiopathic HA such as DIC, TTP, SLE, HUS, and malignant HTN. Autoimmune HA there is extravascular hemolysis.

Three days after starting the prophylactic antimalarial drug primaquine, a 23 y/o African American passes dark reddish-brown urine. He is surprised by this, since he has been healthy up to now. CBC shows a mild normocytic anemia, but the peripheral smear shows precipitates of denatured globin (Heinz bodies) with scattered bite cells. Which of the following is the most likely diagnosis? A) Beta thalassemia minor B) Glucose 6- Phosphate dehydrogenase deficiency C) Autoimmune hemolytic anemia D) Pyruvate kinase deficiency E) Microangiopathic hemolytic anemia F) Alpha Thalassemia

Answer B) Glucose 6- Phosphate dehydrogenase deficiency A) Beta thalassemia minor B) Glucose 6- Phosphate dehydrogenase deficiency C) Autoimmune hemolytic anemia D) Pyruvate kinase deficiency E) Microangiopathic hemolytic anemia F) Alpha Thalassemia G6PD deficiency causes oxidative damage to RBC’s with exposure to primaquine, sulfonamides, nitrofurantoin, phenacetin, and aspirin. Infection can also cause RBC oxidation and lysis.

A 60 y/o man has developed widespread ecchymoses over the skin in the past month. His medical history includes a diagnosis of mucinous adenocarcinoma of the rectum. On PE, he appears cachectic and pale. An abdominal CT scan shows multiple hepatic masses. Lab studies reveal PT of 30 sec, PTT of 55 sec, platelet count of 15200, fibrinogen level of 75, and fibrin split product levels that are very elevated. Which of the following morphologic findings is most likely to present on the peripheral blood smear? A) Howell- Jolly bodies B) Teardrop cells C) Macro- ovalocytes D) Schistocytes E) Target cells

Answer B) Teardrop cells C) Macro- ovalocytes D) Schistocytes A) Howell- Jolly bodies B) Teardrop cells C) Macro- ovalocytes D) Schistocytes E) Target cells This is an example of DIC with associated microangiopathic HA. Howell- Jolly bodies are caused by asplenia. Micro-ovalocytes are due to megaloblastic anemias. Teardrop cells are due to myelofibrosis. Targets are due to HbC disease or severe liver disease.

Hb 11.2 Hct 33.3 Platelet count 240 RBC count 2.69 MCV 91 WBC count A 50 y/o man sees his physician because he has experienced chronic fatigue and weight loss for the past 3 months. There are no remarkable findings on PE. Labs are shown. ANA test is positive. Which of the following is the most likely diagnosis? A) Anemia of chronic disease B) Aplastic anemia C) Microangiopathic hemolytic anemia D) Iron deficiency anemia E) Megaloblastic anemia F) Thalassemia minor Hb 11.2 Hct 33.3 Platelet count 240 RBC count 2.69 MCV 91 WBC count 7550 Serum Fe 80 TIBC 145 Serum Ferritin 565

Answer A) Anemia of chronic disease B) Aplastic anemia C) Microangiopathic hemolytic anemia D) Iron deficiency anemia E) Megaloblastic anemia F) Thalassemia minor The patient has a positive ANA test which is commonly seen in rheumatologic diseases like SLE. Increased ferritin concentration and reduced TIBC are hallmarks of anemia of chronic disease, such as an autoimmune process. Increased cytokine levels cause sequestration of storage iron in macrophages.

Hb 10.6 Hct 31.6 Platelet count 378 RBC count 2.69 MCV 118 Retic count A 39 y/o woman complains of abdominal pain and intermittent low volume diarrhea for the past 3 months. A stool sample is positive for occult blood. On colonoscopy, biopsy results reveal Crohn’s disease. She has surgery to remove part of her colon and terminal ileum. She is transfused with 2 units of RBC’s. 2 weeks later she c/o fatigue. Labs are shown. Which of the following is the most likely to produce these findings? A) Hemolytic anemia B) Aplastic anemia C) Chronic blood loss D) Anemia of chronic disease E) Bone marrow metastases F) Vitamin B12 deficiency Hb 10.6 Hct 31.6 Platelet count 378 RBC count 2.69 MCV 118 Retic count 0.3%

Answer B) Aplastic anemia C) Chronic blood loss A) Hemolytic anemia B) Aplastic anemia C) Chronic blood loss D) Anemia of chronic disease E) Bone marrow metastases F) Vitamin B12 deficiency High MCV indicated macrocytosis. B12 is absorbed in the terminal ileum and removal causes B12 deficiency.

A 22 year old woman has experienced malaise and sore throat for 2 weeks. She has a temp of 37.8C and her pharynx is erythematous. Monospot test is positive. The direct and indirect Coombs test results are positive at 4C, but not at 37C. Which of the following substances on the surfaces of the RBC’s accounts for these findings? A) Ig E B) IgG C) Histamine E) Complement C3b and IgM F) Fibronectin

Answer A) Ig E B) IgG C) Histamine E) Complement C3b F) Fibronectin The patient has cold agglutinin disease (cold antibody hemolytic anemia), with IgM antibodies that bind to the RBC’s at low temperature and fix complement. With a rise in temp. the IgM leaves the cell, and the C3b remains attached to the RBC membrane. This is an extravascular hemolysis.

A 3 y/o boy of Italian ancestry is brought to the physician because he has a poor appetitie and is underweight for his age and height. PE shows hepatosplenomegaly. Hb is 6, and peripheral blood smear shows hypochromic, microcytic RBC’s. Total serum Fe is normal and retic count is 10%. A radiograph of ths skull shows maxillfacial deformities and an expanded marrow space. Which of the following is the most likely principle cause of the child’s illness? A) Reduced synthesis of Hb F B) Imbalance in production of alpha and beta globin chains C) Sequestration of iron in reticuloendothelial cells D) Increased fragility of RBC membrane E) Relative deficiency of vitamin B12

Answer A) Reduced synthesis of Hb F B) Imbalance in production of alpha and beta globin chains C) Sequestration of iron in reticuloendothelial cells D) Increased fragility of RBC membrane E) Relative deficiency of vitamin B12 The patient has beta thal major. There is a severe reduction in synthesis of beta globin chains with normal production of alpha chains. The alpha chains form aggregates that precipitate and cause cell death. This results in inefective erythropoiesis and iron overload (hemochromatosis). Patients have infiltrative cardiomyopathy, hepatic cirrhosis, and bronze diabetes. EPO stimulates the bone marrow causing BM expansion. Hepatosplenomegaly occurs with extramedullary hematopoiesis.

A 12 y/o boy has a h/o episodes of severe abdominal pain and back pain since early childhood. On PE, he is afebrile. Labs show Hb 11.2, platelets 194, and WBC 9020. Peripheral blood smear is shown. Hb electrophoresis shows 1% HbA2, 6%Hb F, and 93%Hb S. Hydroxyurea is started. Which of the following is the most likely mechanism of this drug? A) Increase in production of Hb A B) Increase in oxygen affinity for Hb C) Stimulation of RBC production D) Increase in production of HbF E) Decrease in overall globin synthesis

Answer A) Increase in production of Hb A B) Increase in oxygen affinity for Hb C) Stimulation of RBC production D) Increase in production of HbF E) Decrease in overall globin synthesis The crescent shaped RBC’s are characteristic of Hb SS. Sickled cells can undergo hemolysis and cause microvascular occlusions causing pain crises (acute chest syndrome, splenic infarction). Howell jolly bodies are result of autosplenectomy. Hydroxyurea can increase the HbF concentration, which interferes with the polymerization of Hb S.

Resources to Use Robbins Review of Pathology questions http://library.med.utah.edu/WebPath/webpath.html