1. A 43-year-old woman presents for the evaluation of bleeding gums. The patient reports that for the past 2 months, her gums have bled more easily when she brushes her teeth. Physical examination reveals palatal petechiae and scattered petechiae over the lower extremities bilaterally.
Which of the following laboratory tests is most likely to identify the abnormality responsible for this patient's bleeding disorder?
❑ A. Prothrombin time (PT) and international normalized ratio (INR)
❑ B. Complete blood count (CBC)
❑ C. Partial thromboplastin time (PTT)
❑ D. A mixing study
Key Concept/Objective: To understand that thrombocytopenia usually presents as petechial bleeding
Bleeding occurs as a consequence of thrombocytopenia, deficiencies of coagulation fac-tors, or both. Thrombocytopenia usually presents as petechial bleeding that is first observed in the lower extremities. Deficiencies in coagulation factor more often cause bleeding into the gastrointestinal tract or joints. Intracranial bleeding, however, can occur with a deficiency of platelets or coagulation factors and can be catastrophic. CBCs are rou-tinely performed in most laboratories through the use of an electronic particle counter, which determines the total white blood cell and platelet counts and calculates the hema-tocrit and hemoglobin from the erythrocyte count and the dimensions of the red cells. For this patient, a CBC would likely disclose a decreased platelet count (thrombocytopenia).
Impaired hepatic synthetic function and vitamin K deficiency would result in prolonga-tion of the PT and INR. Coagulaprolonga-tion factor deficiencies and coagulaprolonga-tion factor inhibitors would result in prolongation of the PTT. A mixing study is obtained to differentiate between a coagulation factor deficiency and a coagulation factor inhibitor by mixing patient plasma with normal plasma in the laboratory. (Answer: B—Complete blood count [CBC])
2. A 53-year-old man presents with fatigue, weight loss, and a petechial rash. A CBC reveals anemia and thrombocytopenia, with a peripheral smear containing 20% blast cells. A bone marrow biopsy is per-formed, revealing acute myelogenous leukemia (AML). The patient is treated with cytarabine and daunorubicin induction chemotherapy.
Which of the following blood cell lineages has the shortest blood half-life and is therefore most likely to become deficient as a result of this patient's chemotherapy treatment?
❑ A. Red blood cells (RBCs)
❑ B. Platelets
❑ C. Megakaryocytes
❑ D. Neutrophils
Key Concept/Objective: To understand differences in the dynamics of erythrocytes, platelets, and leukocytes in the blood
HEMATOLOGY
SECTION 5
There are important differences in the dynamics or kinetics of erythrocytes, platelets, and leukocytes in the blood. For instance, neutrophils have a blood half-life of only 6 to 8 hours; essentially, a new blood population of neutrophils is formed every 24 hours.
Erythrocytes last the longest by far: the normal life span is about 100 days. These differ-ences partially account for why neutrophils and their precursors are the predominant mar-row cells, whereas in the blood, erythrocytes far outnumber neutrophils. Similarly, the short half-life and high turnover rate of neutrophils account for why neutropenia is the most frequent hematologic consequence when bone marrow is damaged by drugs or radi-ation. Transfusion of erythrocytes and platelets is feasible because of their relatively long life span, whereas the short life span of neutrophils has greatly impeded efforts to develop neutrophil transfusion therapy. (Answer: D—Neutrophils)
3. A 54-year-old man presents with fatigue, weakness, and dyspnea on exertion. Physical examination reveals conjunctival pallor, palatal petechiae, and splenomegaly. A CBC reveals profound anemia and thrombocytopenia. A bone marrow biopsy reveals agnogenic myeloid metaplasia (myelofibrosis). The patient’s splenomegaly is attributed to increased production of blood cells in the spleen.
Which of the following terms indicates blood cell production outside the bone marrow in the spleen, liver, and other locations?
❑ A. Adjunctive hematopoiesis
❑ B. Remote hematopoiesis
❑ C. Accessory hematopoiesis
❑ D. Extramedullary hematopoiesis
Key Concept/Objective: To understand the nomenclature of hematopoiesis
Hematopoiesis begins in the fetal yolk sac and later occurs predominantly in the liver and the spleen. Recent studies demonstrate that islands of hematopoiesis develop in these tis-sues from hemangioblasts, which are the common progenitors for both hematopoietic and endothelial cells. These islands then involute as the marrow becomes the primary site for blood cell formation by the seventh month of fetal development. Barring serious damage, such as that which occurs with myelofibrosis or radiation injury, the bone marrow remains the site of blood cell formation throughout the rest of life. In childhood, there is active hematopoiesis in the marrow spaces of the central axial skeleton (i.e., the ribs, ver-tebrae, and pelvis) and the extremities, extending to the wrists, the ankles, and the cal-varia. With normal growth and development, hematopoiesis gradually withdraws from the periphery. This change is reversible, however; distal marrow extension can result from intensive stimulation, as occurs with severe hemolytic anemias, long-term administration of hematopoietic growth factors, and hematologic malignancies. The term medullary hematopoiesis refers to the production of blood cells in the bone marrow; the term extramedullary hematopoiesis indicates blood cell production outside the marrow in the spleen, liver, and other locations. (Answer: D—Extramedullary hematopoiesis)
4. A 35-year-old woman with advanced HIV disease complicated by anemia is seen for routine follow-up.
The patient is started on erythropoeitin to decrease the severity of her anemia and to provide sympto-matic improvement.
Which of the following laboratory findings is the most easily monitored immediate effect of erythro-poietin therapy?
❑ A. An increase in the reticulocyte count
❑ B. An increase in the mean corpuscular volume
❑ C. An increase in the hemoglobin level
❑ D. An increase in the mean corpuscular hemoglobin level
Key Concept/Objective: To understand that an increase in the reticulocyte count is the most easi-ly monitored immediate effect of erythropoietin therapy
Erythropoietin is a glycosylated protein that modulates erythropoiesis by affecting several steps in red cell development. The peritubular interstitial cells located in the inner cortex and outer medulla of the kidney are the primary sites for erythropoietin production.
Erythropoietin can be administered intravenously or subcutaneously for the treatment of anemia caused by inadequate endogenous production of erythropoietin. Treatment is maximally effective when the marrow has a generous supply of iron and other nutrients, such as cobalamin and folic acid. For patients with renal failure, who have very low ery-thropoietin levels, the starting dosage is 50 to 100 units subcutaneously three times a week.
The most easily monitored immediate effect of increased endogenous or exogenous ery-thropoietin is an increase in the blood reticulocyte count. Normally, as red cell precursors mature, the cells extrude their nucleus at the normal blast stage. The resulting reticulo-cytes, identified by the supravital stain of their residual ribosomes, persist for about 3 days in the marrow and 1 day in the blood. Erythropoietin shortens the transit time through the marrow, leading to an increase in the number and proportion of blood reticulocytes within a few days. In some conditions, particularly chronic inflammatory diseases, the effectiveness of erythropoietin can be predicted from measurement of the serum erythro-poietin level by immunoassay. It may be cost-effective to measure the level before initiat-ing treatment in patients with anemia attributable to suppressed erythropoietin produc-tion, such as patients with HIV infecproduc-tion, cancer, and chronic inflammatory diseases.
Several studies have shown that erythropoietin treatment decreases the severity of anemia and improves the quality of life for these patients. In patients with anemia caused by can-cer and cancan-cer chemotherapy, current guidelines recommend erythropoietin treatment if the hemoglobin level is less than 10 g/dl. (Answer: A—An increase in the reticulocyte count)
5. A 55-year-old man with type 1 diabetes undergoes dialysis three times a week for end-stage renal disease.
You recently started him on erythropoietin injections for chronic anemia (hematocrit, 25%).
Which of the following is the best test to determine whether this patient will respond to the erythro-poietin treatment?
❑ A. Erythropoietin level
❑ B. Hematocrit
❑ C. Creatinine level
❑ D. Reticulocyte count
❑ E. Blood urea nitrogen
Key Concept/Objective: To understand the site of production, effect, and therapeutic monitoring of erythropoietin
In many renal diseases, the kidneys fail to produce sufficient amounts of erythropoietin.
Replacement of endogenous erythropoietin stimulates red cell precursors in the bone mar-row to mature more quickly. If the patient has normal bone marmar-row, an elevated reticulo-cyte count should be seen several days after initiation of therapy. (Answer: D—Reticuloreticulo-cyte count)
6. A 34-year-old woman undergoes chemotherapy for advanced-stage breast cancer. As expected, she devel-ops pancytopenia.
Which cell line would you expect to be the last to recover in this patient?
❑ A. Eosinophils
❑ B. Platelets
❑ C. Basophils
❑ D. Monocytes
❑ E. RBCs
Key Concept/Objective: To understand the time needed for cell-line recovery after bone marrow damage
The proliferation and maturation of platelets take longer than those of either red blood cells (7 to 10 days) or white blood cells (10 to 14 days) and thus are the slowest to recover from an acute bone marrow injury, such as occurs with chemotherapy. (Answer: B—Platelets)
For more information, see Dale DC: 5 Hematology: I Approach to Hematologic Disorders.
ACP Medicine Online (www.acpmedicine.com). Dale DC, Federman DD, Eds. WebMD Inc., New York, June 2003