1. MLAB 1415: Hematology Keri Brophy-Martinez Anemia Part Three

2. RBC Shape Variations Alterations in the shape of the RBC is called poikilocytosis. 2

3. Target Cells (Codocytes) Occur due to an increased red blood cell surface area. Appear as "targets" on peripheral blood smear. Have a pale central area with most of the hemoglobin around the rim of the cell. Are always hypochromic. 3

4. Target Cells (Codocytes) Mechanism in formation is related to excess membrane cholesterol and phospholipid, and to decreased cellular hemoglobin. Osmotic fragility is decreased. 4

5. So what is Osmotic Fragility? It is a test to measure RBC resistance to hemolysis The quicker the hemolysis occurs, the greater the osmotic fragility What affects osmotic fragility? ◦ Surface to volume ratio ◦ Cell membrane permeability

6. Target Cells (Codocytes) Seen in patients with: ◦ Liver disease ◦ Hemoglobin C Disease or Trait ◦ Post-splenectomy ◦ Iron Deficiency Anemia ◦ Any Hemoglobin Abnormality ◦ Can be artifactual 6

7. Spherocytes Have a low surface-to- volume ratio. Smaller than normal red cell; hemoglobin relatively concentrated; and, have no area of central pallor. Shape change is irreversible. 7

8. Spherocytes Several mechanisms for formation, but all involve loss of membrane; aging, antibody coating or genetic defect Is the final stage for red cells before they are sequestered in the spleen. 8

9. Spherocytes Seen in patients with: ◦ Activated complement ◦ Immune Hemolytic Anemia ◦ Hereditary Spherocytosis ◦ Post-Transfusion 9

10. Wait! What is Complement? Complement refers to a complex set of 14 distinct serum proteins that are involved in three separate pathways of activation. Major Functions ◦ Promote the inflammatory response by opsonization which enhances susceptibility of coated cells to phagocytosis. ◦ Alter biological membranes to cause direct cell lysis.

11. Ovalocytes and Elliptocytes Ovalocytes may appear normochromic or hypochromic; normocytic or microcytic. Hemoglobin concentrated at both ends Exact mechanism of formation unknown. 11

12. Ovalocytes and Elliptocytes Ovalocytes associated with: ◦ Myelodysplastic Syndromes ◦ Thalassemias ◦ Megaloblastic Processes Elliptocytes associated with: ◦ Iron Deficiency Anemia ◦ Hereditary Elliptocytosis ◦ Idiopathic Myelofibrosis 12

13. Stomatocytes Red cell of normal size Slit-like central area of pallor Exact mechanism of formation unknown Usually artifactual Increased osmotic fragility 13

14. Stomatocytes Associated with following disorders: ◦ Hereditary Stomatocytosis ◦ Hemolytic, Acute Alcoholism ◦ Rh Null Phenotype 14

15. Sickle Cells (Drepanocytes) Have at least one pointed end. Surface area of cell much greater than normal cell. 15

16. Sickle Cells (Drepanocytes) Low oxygen tension causes hemoglobin to polymerize, forming tubules that line up in bundles to deform cell. Most sickle cells can revert back to normal shape when oxygenated. 16

17. Sickle Cells (Drepanocytes) Associated with the following disorders: ◦ Sickle Cell Anemia ◦ Hemoglobin C Disease 17

18. Acanthocytes Normal or slightly smaller size Possess 3-12 thorny projections of uneven length along periphery of cell membrane. Projections are blunt 18

19. Acanthocytes Specific mechanism of formation unknown. Contain increased cholesterol-to- phospholipid ratio. Surface area increased Susceptible to removal by spleen 19

20. Acanthocytes Possible pathologies include: ◦ Alcohol Intoxication ◦ Pyruvate Kinase Deficiency ◦ Congenital Abetalipoproteinemia ◦ Vitamin E Deficiency ◦ Post-Splenectomy 20

21. Fragmented Cells Includes: ◦ Burr Cells ◦ Helmet Cells ◦ Schistocytes Fragmentation is defined as a loss of a piece of cell membrane that may or may not contain hemoglobin. 21

22. Fragmented Cells Two pathways that lead to fragmentation: ◦ Alteration of normal fluid circulation (vasculitis, malignant hypertension, heart valve replacement). ◦ Intrinsic defects of red cell that make it less deformable (spherocytes and antibody-covered red cells). 22

23. Prominent Morphology Fragmented Cells Possible Pathology Burr CellsRenal diseaseLiver DiseaseBurnsSchistocytes Prosthetic Heart Valve Microangiopat hic Hemolytic Anemia DICTTPHUS Clostridial Infections Helmet Cells G6PD Deficiency Pulmonary Emboli

24. Burr Cells (Echinocytes) Red cells with 10-30 evenly spaced spicules over the surface of the cell. Normocytic and normochromic. In large numbers, are an artifact of sample contamination. 24

25. Burr Cells (Echinocytes) "True" burr cells occur in small numbers in uremia, heart disease, stomach cancer, bleeding peptic ulcers, and in patients with untreated hypothyroidism. Seen in liver disease, renal disease, and burn patients. May occur in any situation that causes change in tonicity of intravascular fluid (dehydration). 25

26. Helmet Cells (Bite Cells) Usually have two projections surrounding an empty area of red cell membrane. Looks as if cell has had a bite taken out of it. Caused by spleenic pitting and impalement of the RBC on fibrin strands 26

27. Helmet Cells (Bite Cells) In conditions where red cells have large inclusion bodies (such as Heinz bodies G6PD deficiency May be seen in patients with pulmonary emboli, and disseminated intravascular coagulation (DIC) 27

28. Schistocytes Extreme cell fragmentation Cell is missing whole pieces of membrane. Causes bizarre shapes of red cells. 28

29. Schistocytes Caused by loss of membrane by mechanical means See in patients with microangiopathic hemolytic anemia, DIC, heart valve surgery, or severe burns. 29

30. Teardrop Cells Appear as pear-shaped cells. Length of tail varies. May be microcytic, normocytic, or macrocytic. Exact formation process unknown. Commonly seen in red cells that contain large inclusion bodies. 30

31. Teardrop Cells Most commonly seen in idiopathic myelofibrosis, thalassemia, and iron deficiency anemia. 31

32. References Harmening, D. M. (2009). Clinical Hematology and Fundamentals of Hemostasis. Philadelphia: F.A Davis. McKenzie, S. B., & Williams, J. L. (2010). Clinical Laboratory Hematology. Upper Saddle River: Pearson Education, Inc. http://www.ezhemeonc.com/index.php/hematolog ical-disorders/ http://www.ezhemeonc.com/index.php/hematolog ical-disorders/ http://www.wiwe.net/irene/lab/chemheme/heme/ microscope/stomatocyte.htm http://www.wiwe.net/irene/lab/chemheme/heme/ microscope/stomatocyte.htm http://home.ccr.cancer.gov/oncology/oncogenomic s/WEBHemOncFiles/Review%20of%20Terms.html