Hematology

1. Hematology By Georges Metellus, M.D., M.P.H. American University of Antigua Miami Site

2. Blood Composition and Volume • A. Plasma: Liquid fraction of whole blood (extracellular part) • B. Formed elements: Cellular components suspended in the plasma. • C. Normal volumes of blood: 1. Plasma: 2,6 L 2. Formed elements: 2.4 L 3. Whole Blood: 4 to 6 L average or 7% to 9% of the total body weight. • D. Blood pH: 1. Blood is Alkaline-pH 7.35 to pH 7.45 2. Blood pH decreased toward neutral creates a condition called “acidosis” • E. Blood donation: 1. Approximately 14 million units donated annually 2. Plasma volume expanders (such as Albumin) can maintain blood volume after hemorrhage for only short period. 3. Storage of donated blood limited to 6 weeks.

3. Formed Elements of the Blood • A. Types 1. RBCs (erythrocytes) 2. WBCs (Leukocytes) a. Granular leukocytes-neutrophils, eosinophils, and basophils b. Nongranular leukocytes- lymphocytes and monocytes. 3. Platelets or thrombocytes • B. Number 1. RBCs-4.2 to 6.2 million / mm3 of blood 2. WBCs-5000 to 10,000 /mm3 of blood 3. Platelets-150,000 to 400,000 /mm3 of blood • C. Formation 1. Red bone marrow ( myeloid tissue) forms all blood cells except some lymphocytes and monocytes. 2. Most other cells are formed by lymphatic (lymphoid) tissue in the lymph nodes, thymus, and spleen

4. Erythropoiesis • Definition: Erythropoiesis is the production of red blood cells (RBCs) in the bone marrow and is dependent on the release of erythropoietin from the kidneys A. Erythropoiesis and erythropoietin (EPO) 1. Stimuli for EPO release: Hypoxemia- severe anemia- high altitude. EPO accelerates erythropoiesis in the bone marrow by stimulating the erythroid stem cell to divide and therefore increasing the total number of RBCs resulting in an increase of the O2-carrying capacity of blood. B. Epoeitin alfa: is a form of EPO produced by recombinant DNA technology, is frequently abused by athletes to increase their energy level. It also is used in the treatment of anemia associated with renal failure, chronic disease, and chemotherapy.

5. Extramedullary Hematopoiesis • A.RBC, White Blood Cell (WBC), and platelet production (hematopoiesis) occurs outside the bone marrow (1). common sites include the liver and spleen (2). Extramedullary hematopoiesis causes hepatomegaly and splenomegaly • B. Pathogenesis: (1). Intrinsic bone marrow disease (e.g., myelofibrosis. (2). Accelerated erythropoiesis (e.g., severe hemolysis in sickle cell disease) a) expand the bone marrow cavity b) Produces frontal bossing of the skull and “hair-on-end” appearance on radiographs of the skull

6. Blood Types Blood is identified as a specific “type” by using the ABO and Rh systems of classification. • ABO system: 1. Type A blood:Type A antigens in RBCs; anti-B type antibodies in plasma 2. Type B Blood:Type B antigens in RBCs; anti-A type antibodies in plasma. 3. Type AB blood: Type A and type B antigens in RBCs; no anti-A or anti-B antibodies in plasma 4. Type O blood: no type A or type B antigens in RBCs; both anti-A and anti-B antibodies are present in plasma; called universal donor blood

7. Blood Types (con’t) • Rh System: 1. Rh-positive blood: Rh factor antigen present in RBCs 2. Rh-negative: no Rh factor present in RBCs; no anti-Rh antibodies present naturally in plasma; anti-Rh antibodies, however, appear in the plasma of Rh-negative persons if Rh-positive RBCs have been introduced into their bodies 3. Erythroblastosis fetalis: may occur when Rh-negative mother carries a second Rh-positive fetus; caused by mother’s Rh antibodies reacting with baby’s Rh-positive cells.

8. Blood Plasma Liquid fraction of whole blood minus formed elements. • Composition: Water containing many dissolved substances including: a. Foods, salts b. about 3% of total 02 transported in blood c. About 5% of total CO2. d. Most abundant solutes dissolved in plasma are plasma proteins (1) Albumins (4) Fibrinogen (2) Globulins (5) Prothrombin • Serum: Plasma minus clotting factors (a) Serum is liquid remaining after whole blood clots (b) Serum contains antibodies

9. Mechanism of Blood Disease A. Most blood diseases result from failure of myeloid and lymphatic tissues (1).Causes include toxic chemicals, radiation, inherited defects, nutritional deficiencies and cancers, including leukemia. B. Aspiration biopsy cytology (ABC) permits examination of blood-forming tissues to assist in diagnosis of blood diseases. C. Bone marrow, cord blood, and hematopoietic stem cell transplants may be used to replace diseased or destroyed blood-forming tissues

10. Red Blood Cells(Erythrocytes) A. Characteristics: 1. Biconcave disk shape( thin center and thicker edges) results in large cellular surface area. 2.Tough and flexible plasma membrane deforms easily allowing RBC to pass through small diameter capillaries 3.Absence of nucleus and cytoplasmic organelle limits life span to about 120 days but provides more cellular space for red pigment called hemoglobin 4.Named according to size: normocytes ( normal size about 7 to 9 um in diameter); microcytic (small size); macrocytic (large size) 5.Named according to hemoglobin content of cell: normochromic (normal Hb content); hypochromic (low Hb content); Hyperchromic (high Hb content)

11. Red Blood Cells B. General Functions I.Transport of respiratory gases ( O2 and CO2) a)Combined with hemoglobin (1) Oxyhemoglobin (Hb+O2) (2) Carbaminohemoglobin (Hb+CO2) b)CO2 inside the RBC as bicarbonate II.Important role in homeostasis of acid-base balance

12. Red Blood Cell Disorders • Polycythemia (overproduction of RBCs) 1.Cause is generally cancerous transformation of red bone marrow 2.Dramatic increase in RBC numbers- often in excess of 10 million/mm3 of blood; hematocrit may reach 60% 3.Signs and symptoms include: a. Increased blood viscosity or thickness b. Slow blood flow and coagulation problems c. Frequent hemorrhages d. Distension of blood vessels and hypertension 4.Treatment may include: a. Blood removal b. Irradiation and chemotherapy to suppress RBC production

13. Red Blood Cell Disorders(low oxygen carrying capacity of blood) B. ANEMIA: 1. Caused by low numbers or abnormal RBCs or by low levels or defective types of hemoglobin (Normal Hb levels: 12-14 g/100 ml of blood-Low Hb level: below 9g/100 ml of blood, classified as anemia) 2. Majority of clinical signs of anemia related to low tissue oxygen levels a) Fatigue; skin pallor b) Weakness; faintness; headache c) compensation results in increased heart and respiratory rates.

14. Red Blood Cell Disorders ANEMIA (continuation) 3. Types: a) Hemorrhagic anemia (1) Acute- blood loss is immediate (for example, surgery or trauma) or chronic-Blood loss occurs over time (for example, ulcers or cancer) b) Aplastic anemia (1)Characterized by low RBC numbers and destruction of bone marrow (2) Often caused by toxic chemicals, irradiation, or certain drugs c) Deficiency anemias caused by inadequate supply of some substance needed for RBC or hemoglobin production I. Pernicious Anemia (1) caused by Vitamin B12 deficiency (2) Genetic-related autoimmune disease (3) decrease RBC, WBC, and platelet numbers

15. Red Blood Cell Disorders Anemia (cont’) • Deficiency anemias: Pernicious anemia(cont’) (4) RBCs are macrocytic (5) Classic symptoms of anemia coupled with CNS impairment (6) Treatment is repeated vitamin B12 injections.

16. Red Blood Cell Disorders Deficiency Anemias (cont’ II. Iron Deficiency anemia (1) Caused by deficiency or inability to absorb iron needed for Hb synthesis (dietary iron deficiency is common worldwide). Bleeding is the most common cause: a) Newborn and children: bleeding Merckel diverticulum b) bleeding peptic ulcer in males < 50 years or older c) menorrhagia in females < 50 years of age d) GI bleeding (polyp, colorectal cancer) in both males and females older than 50 years of age. (2) RBCs are microcytic and hypochromic (3) Hematocrit is decreased (4) Treatment is oral administration of iron compounds

17. Red Blood Cell Disorder(Anemia Continuation) • Hemolytic anemia: caused by decreased RBC life span or increase RBC rate of destruction. • Symptoms: in addition to the regular symptoms of anemia, the following are characteristics of Hemolytic anemia. 1. Jaundice 2. Swelling of spleen , gallstone formation 3. Tissue iron deposits (Symptoms are related to the retention of RBC breakdown products).

18. Red Blood Cell disordersAnemia (cont’) Hemolytic Anemia (cont’) • Examples of hemolytic anemia: A. Sickle Cell anemia: (a) Genetic disease resulting in formation of abnormal hemoglobin (HbS); primary found in black people (1 in every 600 African American newborns) (b) RBCs become fragile and assume sickled shape when blood oxygen levels decrease (c) Mild sickle cell trait-result of one defective gene. (d) More severe sickle cell disease-result of two defective genes.

19. Red Blood Cell DisordersAnemia (cont’) Examples of hemolytic Anemia (cont’) • Thalassemia: group of inherited hemolytic anemias (autosomal recessive disorder) occurring primarily in people of mediterranean descent, southeast Asians and in African Americans. (a) decrease in alpha-globin chain synthesis on chromosome 16 due to gene deletion (alpha-thalassemia) or beta-globin chain synthesis on chromosome 11 (beta-thalassemia) (b) RBCs microcytic and short lived (c) Present as mild thalassemia trait and severe thalassemia major (d) Hb levels often fall below 7g/100ml of blood in thalassemia major (e) Classic symptoms of anemia coupled with skeletal deformities and swelling of spleen and liver (f) Marrow and stem cell transplantation needed for long-term treatment.

20. Red Blood cell DisordersAnemia (cont’) Type Of Hemolytic anemia: (cont’) 3. Erythroblastosis fetalis: (a) Caused by blood ABO or Rh factor incompatibility during pregnancy between developing baby and mother. (b) Maternal antibodies against “foreign” fetal RBCs or Rh factor can cross placenta, enter the fetal circulation, and destroy the unborn baby’s red cell. (c) Symptoms in developing fetus related to decline in RBC numbers and Hb levels; Jaundice, intravascular coagulation, and heart and lung damage are common (d) Treatment may include in utero blood transfusion and premature delivery of the baby. (e) Prevention of Rh factor incompatibility now possible by administration of RhoGAM to Rh negative mothers.

21. White Blood Cells(Leukocytes) • General function is protection of body from microorganisms by phagocytosis or antibody formation • WBC Count: Normal range is 5,000 to 10,000/mm3 1. Leukopenia: total numbers below 5,000 /mm3 of blood. (infrequent but may occur with malfunction of blood-forming tissues or diseases affecting immune system, such AIDS) 2. Leukocytosis: total WBC numbers over 10,000/mm3 of blood (a) Frequent finding in bacterial infections (b) classic sign in blood cancers (leukemia) 3. Differential WBC count : component test in CBC; measures proportions of each type of WBC in blood sample

22. White Blood Cells(Leukocyte) Types and functions • Granulocytes:Neutrophils; eosinophils; basophils (a). Neutrophils (1). Most numerous type of Phagocyte (2). Numbers increase in Bacterial infections (b). Eosinophils (1). Weak phagocyte (2). Active against parasites and parasitic worms (3). Involved in allergic reactions (c). Basophils: (1). Related to mast cells in tissue spaces (2). Both mast cells and basophils secrete histamine (related to inflammation) (3). Basophils also secrete heparin (an anti-coagulant)

23. White Blood Cells(Leukocytes) B. Agranulocytes:Monocytes in peripheral blood (macrophage in tissues); Lymphocytes: “B lymphocytes” (plasma cells) and “T lymphocytes” a. Monocytes (1) largest leukocyte (2) Aggressive phagocyte: capable of engulfing larger bacteria and cancer cells (3) Develop into much larger cells called macrophages after leaving blood to enter tissues spaces b. Lymphocytes (1)B lymphocytes involved in Immunity against disease by secretion of antibodies (2)Mature B lymphocyte called plasma cells (3)T Lymphocytes involved in direct attack on bacteria or cancer cells (not antibody production)

24. White Blood Cell Disorders WBC Cancers: may be originated from B and T lymphocyte precursor or their descendent cell types (lymphoid neoplasms), or from malignant transformation of precursor cells of granulocytic WBCs, monocytes, RBCs, and platelets. • Multiple Myeloma: 1. Cancer of B limphocytes called plasma cells 2. Most deadly blood cancer in people over age of 65. 3. Causes bone marrow dysfunction and production of defective antibodies 4. Characterized by recurrent infections and anemia and destruction and fracture of bones 5. treatment includes chemotherapy, drug, antibody therapy, and marrow and stem cell transplantation

25. White Blood cell Disorder Leukemias: Malignant neoplasm of the hemopoietic stem cells characterized by: • 1. diffuse replacement of the bone marrow by neoplastic cells. • 2. Identified as: a. Acute:Acute myelogenous leukemia (AML) and acute lymphocytic leukemia (ALL). Characterized replacement of the bone marrow with very immature cells (called Blast) and a paucity of mature cells. Blast, which are lymphoid in origin are called lymphoblasts. Most other blasts, are referred to as myeloblasts. -Rapid development of symptoms b. Chronic: Chronic myelogenous leukemia (CML) is characterized by the Philadelphia chromosome and chronic lymphocytic Leukemia (CLL) which is a proliferative disorder of mature B cells.-Slow development of symptoms, presence of organomegally with lymphoadenopathy and a very high white cell count. Lymphocytes are small cells. Damaged lymphocytes are plentiful and are referred to as smudge cells

26. White Blood Cell Disorders Chronic Lymphocytic Leukemia (CLL) 1. Average age of onset is 65; rare before age of 30. 2. More common in men than in women 3. Often diagnosed unexpectedly in routine physical exams with discovery of marked B lymphocyte leukocytosis 4. Malignant precursor B lymphocytes are produced in great numbers and spread from the bone marrow to the lymph nodes and other lymphoid tissues. Splenomegaly may occur. 5.Generally mild symptoms include anemia, fatigue, and enlarged-often painless- lymph nodes. In late disease: neutropenia, thrombocytopenia, decreased immunoglobulin production. 6. Most patients live many years following diagnosis 7. Treatment of severe cases involves chemotherapy and irradiation

27. White Blood Cell Disorders Acute lymphocytic leukemia: 1. Primarily a disease of children between 3 and 7 years of age; 80% of children who develop leukemia have this form of the disease. 2. Highly curable in children but less so in adults 3. Onset is sudden: marked by fever, leukocytosis, bone pain, and increases in infections 4. Lymph node, spleen and liver enlargement is common 5. treatment includes chemotherapy (methrotrexate, mercaptopurine, prednisone, vincristine…), irradiation, and bone marrow or stem cell transplantation

28. White Blood Cell Disorders Chronic myeloid leukemia (CML) 1. Account for about 20% of all cases of leukemia 2. Occurs most often in adults between 25 and 60 years of age 3. Caused by cancerous transformation of granulocytic precursor cells in the bone marrow 4. Onset and progression of disease is slow with symptoms of fatigue, weight loss, and weakness 5. Diagnosis often made by discovery of marked granulocyte leukocytosis and extreme spleen enlargement 6. Treatment by new “designer drug” Gleevec or bone marrow transplantation is curative in more than 70% of cases

29. White Blood Cell Disorders Acute myeloid leukemia (AML) 1. Account for 80% of all cases of acute leukemia in adult and 20% of acute leukemia in children 2. Characterized by sudden onset and rapid progression 3. Symptoms include leukocytosis, fatigue, bone and joint pain, spongy bleeding gums, anemia, and recurrent infections 4. Prognosis is poor with only about 50% of children and 30% of adults achieving long-term survival 5. Bone marrow and stem cell transplantation has increased cure rates in selected patients.

30. White Blood Cell disorders Infectious mononucleosis 1. Non cancerous WBC disorder caused by Epstein-Barr virus(herpes virus) present in saliva of infected individuals 2. Highest incidence between 15 and 25 years of age 3. Leukocytosis of atypical lymphocytes with abundant cytoplasm and large nuclei 4. Symptoms include fever, severe fatigue, sore throat, rash, and enlargement of lymph nodes and spleen 5. Generally self-limited and resolves without complications in about 4 to 6 weeks

31. Exercise on Blood Disorders(Case 36 a) • A 62-year-old woman complains of fatigue and numbness of her arms and legs for 1 month. She has a history of hypothyroidism and takes thyroid replacement therapy. A complete blood count (CBC) shows WBCs 4000/mm3 (normal: 4800-10,800), Hb 9g/dL (normal: 12-16), hematocrit(Hct) 27% (normal: 36-46), mean corpuscular volume (MCV) 120 femtoliters (fL) (normal: 80-100), and platelets 150,000/mm3 (normal: 150,000-400,000) A peripheral blood smear showed megaloblastic red blood cells with enlarged erythrocytes with hypersegmented neutrophils. • A. What is the most likely diagnosis? • B. What is the Biochemical basis for this disorder?

32. Answers to questions on case 36-a • Q.1. Most likely Diagnosis: Pernicious anemia. • Q.2. This patient has a history of thyroid disease and present with findings of megaloblastic anemia with enlarged erythrocytes with hypersegmented neutrophils. The two possibilities are folate and vitamin B12 deficiencies; both of these vitamin deficiencies can lead to defective DNA synthesis, specially thymidine synthesis. Abnormally large red blood cells result from defects in cell maturation and division, whereas RNA synthesis and cytoplasm growth are not affected. Folate deficiency is particularly common in individuals who abuse alcohol. Vitamin B12 stores usually last for several years, but deficiencies may occur in patients with inadequate intrinsic factor, which is needed for vitamin B12 absorption in the ileum. Intrinsic factor is secreted by the parietal cells of the gastric fundus. Vitamin B12 is involved in propionate metabolism. Deficiency of B12 leads to accumulation of methylmalonic acid and propionic acid, which produces demyelination in the spinal cord (that explains abnormal gait, loss of vibratory sensation… etc)

33. Exercise on Blood Disorders(case 37 b) A 48-year-old man who works as an accountant complains of weakness, fatigue, and bleeding from the gums when he brushes his teeth. A CBC shows severe pancytopenia with WBC 1000/mm3 (normal: 4800-10,800), Hgb 8g/dL (normal: 13-17), hematocrit (Hct) 24% (normal: 41-53),MCV 10 fL (normal: 80-100), and platelets 30,000/mm3 (normal:150,000-500,000). A. What is the most likely diagnosis? B. What are the laboratory and clinical findings. C. What are the possible causes of this situation?

34. Answers to Questions on case 37 • Q.1. Most likely diagnosis: Aplastic Anemia (suppression or destruction of the trilineage myeloid stem cells) Characterized by a pancytopenia expressed by anemia, leukopenia, and thrombocytopenia. • Q.2. Laboratory findings: Panhypoplasia of the marrow with associated leukopenia, and thrombocytopenia. Clinical findings include Fever( infection associated with neutropenia) bleeding (thrombocytopenia), fatigue (anemia) • Q.3. Etiology: Drugs(e,g.,chloramphenicol, chemotherapy agents); Infection (papovirus B19, which also produces pure RBC aplasia); Chemical (e.g., benzene), irradiation

35. Exercise on Blood Disorders(Case 38) • A 4-year-old boy is seen by his pediatrician for easy bruising, joint pain, and leg pain; red dots on the skin that do not blanch; and hepatosplenomegaly. The complete blood count reveals an elevated WBC count (50,000/mm3), a low hemoglobin level (anemia), and thrombocytopenia. Examination of the peripheral smear of the blood shows numerous cells with a high nuclear to cytoplasmic ratio, and fine chromatin; the complete blood count shows anemia and thrombocytopenia. A. What is the most likely diagnosis? B. What other investigations need to be done? C. what is the Etiology of this disorder?

36. Answers to questions on case#38 • Q.1. Most likely diagnosis: Acute leukemia, most likely acute lymphoblastic leukemia ( leg and joint pain, fever, enlarged spleen and liver, petechiae. These manifestations usually are due to infiltration of the bone marrow with malignant cells or malignant proliferation cells in the liver and spleen. ALL is more common in children than AML. Children with Down syndrome and those exposed to radiation are at increased risk. )

37. Answers to questions on case #38 (cont’) • Q.2. Additional studies that should be performed are: Bone Marrow examination for differential count of the cells and the morphology of the cells for evaluation. Flow cytometry (for immunophenotypic studies), and Cytogenetic studies (reliable independent indicators of prognosis…) • Q.3. Etiology: The etiology of acute leukemia is unknown, but genetic, environmental and occupational factors are thought to contribute in some cases. Chemotherapeutic agents, especially alkylating agents, increase the risk of developing AML.

38. Comprehension Questions(multiple choice : 36-1) • A 39-year-old woman who presented with increasing fatigue and muscle weakness is found to have a microcytic and hypochromic anemia. What is the most likely cause of her anemia? A. Folate deficiency B. Iron deficiency C. Viral infection D. Vitamin B12 deficiency E. Vitamin C deficiency

39. Answer to case 36-1 • “B” The most common causes of microcytic hypochromic anemia are iron deficiency, anemia of chronic disease, thalassemia, and sideroblastic anemia. Among these conditions, the most common cause of microcytic hypochromic is a deficiency of iron. Causes of iron deficiency include a dietary deficiency of iron, decreased intestinal absorption of iron, increased demand for iron, and chronic blood loss.

40. Comprehension Questions(Multiple choice: 36-2) • Which one of the following autoantibodies is most likely to be present in a patient with pernicious anemia? A. Anticentromere antibodies B. Antigliadin antibodies C. Anti-intrinsic factor antibodies D. Antimitochondrial antibodies E. Anti-smooth muscle antibodies

41. Answer to question on case 36-2 • “C” In contrast to iron deficiency, which causes a microcytic hypochromic anemia, vitamin B12 deficiency produces a macrocytic anemia. The most common cause of Vitamin B12 deficiency in adults is pernicious anemia which is an autoimmune disease characterized by the formation of autoantibodies against intrinsic factor and parietal cells of the stomach. A gastric biopsy from an individual with pernicious anemia will show chronic inflammation with atrophy (chronic atrophic gastritis).

42. Comprehension Questions(Multiple choice: 36-3) • A 61-year-old woman with pancytopenia, mild jaundice, and peripheral neuropathy is found to have decrease serum levels of vitamin B12. Which of the abnormal cell morphologies listed below is most likely to be present in a smear made from her peripheral blood? A. Hypersegmented PMNs B. Large granular lymphocytes C. Oval microcytes D. Pelger-Huet neutrophils E. Plasmocytoid lymphocytes

43. Answer to question on case 36-3 • “A” The two most common causes of megaloblastic anemia are deficiencies of Vitamin B12 or folate. These deficiencies decrease the synthesis of DNA, which results in nuclear-cytoplasmic asynchrony in maturation, which is the hallmark of megaloblastic anemias. This abnormal maturation will produce characteristic histologic changes in the cells in the peripheral blood, including oval macrocytes and hypersegmented PMNs, which are neutrophils with more than five lobes to their nuclei.

44. Comprehension Questions(Multiple choice: 37-1) • A 35-year-old woman with a history of Hepatitis C infection presents with increasing fatigue. Physical examination finds pallor of the skin and conjunctiva and multiple petechial hemorrhages on the skin. No hepatomegaly or splenomegaly is present. A complete blood cell count finds pancytopenia. Which of the following bone marrow findings is most consistent with a diagnosis of aplastic anemia? A. Absolute erythroid hyperplasia B. General lymphoid hyperplasia C. Relative marrow hypoplasia D. relative erythroid aplasia E. relative granulocytic hypoplasia

45. Answer to Question on case 37-1 • “C” Aplastic anemia is characterized by marked hypoplasia of all the cells in the bone marrow. The decrease in the erythroid, granulocytic, and megakaryocytic cell lines in the bone marrow will decrease all cell lines(pancytopenia) in the peripheral blood.

46. Comprehensive Questions(multiple choice: 37-2) • A 66-year-old man presents with signs and symptoms of anemia. Examination of his peripheral blood smear reveals the abnormal presence of nucleated red blood cells and myelocytes. What is the best diagnosis? A. Aplastic anemia B. Digeorge syndrome C. fanconi anemia D. myelophthisic anemia E. Potter syndrome

47. Answer to question on case 37-2 • “D” The term myelophthisic anemia refers to anemia caused by a space-occupying lesion within the bone marrow. Causes of myelophthisic anemia include metastases to the bone marrow, granulomas, and fibrosis (myelofibrosis). With myelophthisis anemia, the peripheral blood smear will show both immature RBCs (nucleated red blood cells) and immature WBCs (myelocyte). This abnormality of the peripheral blood also is known as leukoerythroblastosis.

48. Comprehension Question(Multiple choice: 37-3) • Which one of the laboratory tests listed below would best differentiate hypersplenism from aplastic anemia as being the cause of peripheral pancytopenia? A. Direct Coombs test B. Ham test C. Metabisulfite test D. reticulocyte test E. sugar water test

49. Answer to question on case 37-3 • “D” Hypersplenism can cause destruction of red blood cells, white blood cells, and platelets within the spleen by the splenic macrophage. With hypersplenism, the bone marrow will be hypercellular and the peripheral reticulocyte count will be elevated. This is in contrast to aplastic anemia, in which the bone marrow will be hypocellular and the reticulocyte count will be low.

50. Bleeding Disorders Abnormal hemostasis: • Hemostasis requires a dynamic balance between factors that promote clot formation and factors that promote anticoagulation. • The tendency to bleed or to clot can be inherited or acquired • The type of bleeding problems you encounter in the outpatient setting are likely to be quite different from the bleeding problems you might see in hospitalized patients