1. Department of Pathology

2. Iowa Anemia Cases Case Analyses by Dr. Schneider Tuesday, October 11, 2011 and Thursday October 13, 2011

3. Case Histories These cases are made available through the courtesy of Dr. Fred R. Dee, University of Iowa School of Medicine.

4. Iowa anemia cases Here are a few hints as you prepare your analysis of each of the Iowa cases

5. Iowa anemia cases Case 201. Two major causes for the anemia are suggested by the clinical information and the blood smear. What further information would be most helpful in making a distinction between the two.

6. Iowa anemia cases Case 202. You should be able to make a specific diagnosis from the information given.

7. Iowa anemia cases Case 203. You should be able to make a specific diagnosis from the information given.

8. Iowa anemia cases Case 207. This is a classic case except for one of the physical findings.

9. Iowa anemia cases Case 210. The history and the blood smear suggest an extremely common entity.

10. Iowa Case 201

11. Hints Case 201 Two major causes for the anemia are suggested by the clinical information and the blood smear. What further information would be most helpful in making a distinction between the two. Two major causes for the anemia are suggested by the clinical information and the blood smear. What further information would be most helpful in making a distinction between the two.

12. Iowa Case 201 The clinical findings of significance are the presence of occult blood in the stools, the history of chronic (rheumatoid?) arthritis, the weight loss, and the recent worsening of symptoms of anemia. The blood smear indicates microcytosis and hypochromia.

13. Iowa Case 201 The diffential diagnosis is iron deficiency anemia (probably due a bleeding GI tract lesion such as colon cancer) vs. anemia of chronic disease. A less likely (but still possible) cause is beta thalassemia minor.

14. Iowa Case 201 The most helpful laboratory data would be serum iron and total iron binding capacity. While serum iron would be reduced in both, the TIBC would be increased in iron deficiency anemia and decreased in the anemia of chronic disease.

15. Iowa Case 201 Serum ferritin determination might also be useful. If ferritin is reduced then the diagnosis of iron deficiency anemia would be strongly supported. If ferritin is normal or elevated, it would be difficult to interpret since ferritin is a phase reactant that rises because of chronic inflammation such as rheumatoid arthritis.

16. Iowa Case 201 If the hematologic diagnosis remains in doubt, bone marrow aspiration and staining with Prussian blue may give a definitive answer. In any event, the finding of blood in the stools is a major finding and the cause must be determined.

17. Iowa Case 201 Hypochromia and microcytosis on blood smear Significance of blood in stools Significance of rheumatoid arthritis Findings in serum iron, TIBC in iron deficiency Findings in serum iron, TIBC in anemia of chronic disease Importance of weight loss

18. Iowa Case 201 Importance of recent exacerbation of symptoms Significance of A2 hemoglobin in evaluation of hypochromic microcytic anemia and expected CBC findings in beta thalassemia minor Evidence of group participation in preparation for case discussion

19. Iowa Case 202

20. Hints Case 202 You should be able to make a specific diagnosis from the information given.

21. Iowa Case 202 The diagnosis is pernicious anemia. This is supported by the history of slowly developing anemia and neurologic symptoms, the decreased vibratory sensation in the lower extremities, and the blood smear which shows oval macrocytosis, diminished platelets, and hypersegmented polys.

22. Iowa Case 202 Ancillary findings are the snow white hair and blue eyes (part of the PA habitus, but of low diagnostic import). Helpful confirmatory procedures will include a bone marrow examination which should reveal megaloblastic hyperplasia, serum cobalamin (which should be very low) and serum folate and erythrocyte folate assays (which should be normal). Ancillary findings are the snow white hair and blue eyes (part of the PA habitus, but of low diagnostic import). Helpful confirmatory procedures will include a bone marrow examination which should reveal megaloblastic hyperplasia, serum cobalamin (which should be very low) and serum folate and erythrocyte folate assays (which should be normal).

23. Iowa Case 202 Also, useful should be the demonstration of anti-intrinsic factor antibodies.

24. Iowa Case 202 Oval macrocytes, hypersegmented poly, paucity of platelets Neurologic symptoms Impaired vibratory sensation Diagnosis of pernicious anemia Likelihood of megalobastic hyperplasia in bone marrow Likelihood of anti-intrinsic factor antibodies

25. Iowa Case 202 Likelihood of reduced serum cobalamin and normal serum and RBC folate Evidence of group participation in preparation for case discussion

26. Iowa Case 203

27. Hints Case 203 You should be able to make a specific diagnosis from the information given.

28. Iowa Case 203 The diagnosis is hereditary spherocytosis. The diagnosis is supported by the history of both jaundice and splenic abnormalities in the mother and daughter and the finding of spherocytes and polychromatophilia on the blood smear.

29. Iowa Case 203 Important ancillary evidence will include an elevated reticulocyte count, increase in unconjugated serum bilirubin and lack of bilirubin pigment in the urine, a negative direct Coombs test and increased erythrocyte osmotic fragility.

30. Iowa Case 203 Microspherocytes and polychromatophilic erythrocytes on blood smear Family history with autosomal dominant pattern of inheritance Splenomegaly in patient and history of splenectomy in mother Likelihood of increased reticulocyte count

31. Iowa Case 203 Likelihood of increased unconjugated bilirbuin in serum Likelihood of negative urinary bilirubin Importance of increased osmotic fragility Importance of negative direct Coombs test Evidence of group participation in preparation for case discussion

32. Iowa Case 207

33. Hints Case 207 This is a classic case except for one of the physical findings.

34. Iowa Case 207 The diagnosis is almost certainly homozygous hemoglobin C disease as evidenced by the blood smear showing target cells and hemoglobin crystals in an African-American.

35. Iowa Case 207 This condition is usually manifest by splenomegaly and mild hemolytic anemia, and in this instance the absence of splenomegaly is atypical. The complaints of joint pains and abdominal pain are probably entirely unrelated to the hematologic findings. This condition is usually manifest by splenomegaly and mild hemolytic anemia, and in this instance the absence of splenomegaly is atypical. The complaints of joint pains and abdominal pain are probably entirely unrelated to the hematologic findings.

36. Iowa Case 207 The diagnosis is almost certainly homozygous hemoglobin C disease as evidenced by the blood smear showing target cells and hemoglobin crystals in an African-American.

37. Iowa Case 207 Target cells and hemoglobin crystals on peripheral smear African lineage Diagnosis is homozygous hemoglobin C Absence of splenomegaly is atypical finding Absence of causes or findings of other forms of anemia

38. Iowa Case 207 Confirm diagnosis by hemoglobin electrophoresis Probable slight increase in reticulocyte count Complaints probably unrelated to hematologic diagnosis Evidence of group participation in preparation for case discussion

39. Iowa Case 210

40. Hints Case 210 The history and the blood smear suggest an extremely common entity.

41. Iowa Case 210 This is the case of an older African-American man who was well until recently with no prior history of anemia. While under treatment with sulfonamides, he has developed rapidly increasing weakness (acute anemia?). The blood smear shows "blister cells" which are equivalent to bite cells and typical of G6PD deficiency. This is the case of an older African-American man who was well until recently with no prior history of anemia. While under treatment with sulfonamides, he has developed rapidly increasing weakness (acute anemia?). The blood smear shows "blister cells" which are equivalent to bite cells and typical of G6PD deficiency.

42. Iowa Case 210 Smear shows blister cells, which are equivalent of bite cells (difficult finding for students who have not seen this before) African lineage History of two sulfonamides, sulfisoxizole and gantrisin Male sex Dark urine recently (hemoglobinuria)

43. Iowa Case 210 Absence of causes or findings of other forms of anemia Most likely diagnosis, by far, is G6PD deficiency with hemolytic episode due to sulfisoxizole and/or gantrisin. Propensity affects about 10% of African American men. Evidence of group participation in preparation for case discussion Bonus because blood smear is unfamiliar