Clinical Hematology Lecture Notes PDF

Clinical Hematology Lecture N1 Liza Akhvlediani  Hematology refers to the study of the numbers and morphology of the cellular elements of the blood—the RBCs (erythrocytes), WBCs (leukocytes), and platelets (thrombocytes)—and the use of these results in the...

Clinical Hematology Lecture N1 Liza Akhvlediani  Hematology refers to the study of the numbers and morphology of the cellular elements of the blood—the RBCs (erythrocytes), WBCs (leukocytes), and platelets (thrombocytes)—and the use of these results in the diagnosis and monitoring of disease The rare pluripotent hemopoietic stem cells divide slowly, maintain their own population, and give rise to two major cell lineages of progenitor cells: the myeloid and lymphoid stem cells. The myeloid lineage includes precursor cells (blasts) for erythropoiesis, thrombopoiesis, granulopoiesis, and monocytopoiesis, all in the bone marrow. The lymphoid lineage forms B and T lymphocytes and related cells called natural killer cells, with the later differentiative stages occurring in lymphoid organs. Erythropoietin (EPO), colony stimulating factors (CSF), cytokines and growth factors promote growth and Products and Functions of the Blood Cells Erythrocytes Erythrocytes (red blood cells), which are anucleate, are packed with the O2-carrying protein hemoglobin. Under normal conditions, these corpuscles never leave the circulatory system.Most mammalian erythrocytes are biconcave disks without nuclei. When suspended in an isotonic medium, human erythrocytes are 7.5 micro m in diameter, 2.6 micro m thick at the rim, and 0.8micro m thick in the center. The biconcave shape provides erythrocytes with a large surface-to-volume ratio, thus facilitating gas exchange. Three RBC measurements are routinely done: Packed cell volume (PCV), the proportion of whole blood volume occupied by RBCs; Hemoglobin (Hgb) concentration of whole lysed blood;  RBC count, the number of RBCs per unit volume of whole blood; Although these are separate estimations, they are in effect three ways to measure the same thing, and it is incorrect to attempt to interpret them as separate variables. Inasmuch as they do vary in relation to each other, they allow calculation of two further meaningful parameters: Mean Corpuscular Volume (MCV) Mean Corpuscular Hemoglobin Concentration (MCHC) APPROACH TO ANEMIA IN THE ADULT Anemia is the clinical state of low red cell mass and one of the most commonly encountered laboratory findings and clinical disorders in hematology Is defined as a reduction in the RBC mass MECHANISMS OF ANEMIA Three broad categories of anemia are  Blood loss anemia  Hypoproliferative anemia Hemolytic anemia Blood loss may occur acutely or chronically. When blood is lost acutely through hemorrhage, it may take several hours before a decline in hemoglobin concentration is observed because of the time required for restoration of the plasma volume and equilibration. Several days may elapse before an appropriate reticulocytosis is noted. Chronic blood loss ultimately leads to hypoproliferative anemia because of iron deficiency SYSTEMIC APPROACH TO ANEMIA The correct diagnosis of anemia can often be determined by combining a thorough history and physical examination with review of the CBC, concentrating particularly on the MCV and RDW, along with review of the reticulocyte count and the peripheral blood smear  History and Physical Examination Fatigue often accompanies anemia, but it is very nonspecific and may be related to systemic illness A history of diabetes mellitus can be associated with significantly impaired renal production of erythropoietin even in the setting of only a mildly elevated creatinine level. Certain medications may be associated with BM depression or, alternatively, the development of autoimmune hemolytic anemia, all pharmacologic agents, prescribed and over the counter, including alternative medicines, should be reviewed Occupational history is occasionally relevant, as in the case of individuals, such as welders, who might have been exposed to lead or other potentially BM toxic agents Social history can be important. A history of intravenous drug use might suggest the possibility of virally transmitted diseases, such as HIV, which may be associated with anemia Dietary history is also very important, particularly in young and elderly individuals with anemia A family history of anemia is highly relevant in the evaluation of children with anemia. However, it is also relevant in adults because certain congenital anemias, such as milder forms of sickle β+ thalassemia and hereditary spherocytosis, occasionally first become clinically apparent in adulthood More Specific Findings Angular cheilitis (cracking at the edges of the lips) and koilonychia (spooning of the nails) may accompany iron- deficiency anemia Splenomegaly may be present in patients with anemia arising from a wide variety of different causes When present early in life, it is suggestive of a congenital hemolytic anemia, such as thalassemia, sickle cell disease, or hereditary spherocytosis When found for the first time later in life, splenomegaly may indicate an acquired disorder, such as autoimmune hemolytic anemia, lymphoproliferative disease, or a myeloproliferative disease such as myelofibrosis Anemia itself may lead to the presence of systolic cardiac murmurs, the finding of an increased cardiac murmur in an anemic patient with a prosthetic aortic valve and new microangiopathic change on peripheral smear may indicate that investigation into the possibility of perivalvular leak or prosthetic dysfunction is in order Because neurologic manifestations can accompany or even predate the anemia associated with vitamin B12 deficiency, findings such as loss of vibration or position sense in the extremities may be relevant Reticulocyte Count As a marker of RBC production, the reticulocyte count provides essential information in directing the initial investigation of anemia. Modern flow cytometers accurately determine the reticulocyte count using fluorescent probes that bind to the residual ribonucleic acid present in newly released RBCs.These measurements are useful, accurate, and reflect the state of erythropoiesis. However, when significant numbers of nucleated RBCs or nuclear debris are present in the peripheral blood, this diagnostic accuracy declines, and manual counting methods are generally preferable When the reticulocyte count is reported as a percentage, it needs to be adjusted for the total number of RBCs present. This correction can be made by multiplying the reticulocyte count by the patient’s hematocrit divided by an age- and sex-appropriate normal hematocrit. No such correction is necessary when the reticulocyte count is reported as an absolute number or when it is converted to an absolute number by multiplying the percentage by the RBC number (in RBC/μL). In the absence of anemia, the normal absolute reticulocyte count is between 25,000 and 75,000/μL. In the presence of anemia, an absolute reticulocyte count of less than 75,000/μL is indicative of a hypoproliferative process, and an absolute reticulocyte count of greater than 100,000/μL is indicative of hemolysis or an appropriate erythropoietic response to blood loss. Reticulocyte counts between 75,000 and 100,000/μL require interpretation in the context of other available clinical data, including the severity of anemia present. Mean Corpuscular Volume and Red Blood Cell Distribution Width From the Complete Blood Count Automated cell counters provide a wealth of information regarding the size, shape, and hemoglobin content of RBCs. The two parameters most useful in classifying anemia are the MCV and the RDW MCV is reported in femtoliters (fL) and reflects average cell size RDW is often reported in percent and represents the standard deviation of RBC volume divided by the mean volume. It reflects the variation in cell size in the population of RBCs These two parameters are useful because relatively reproducible changes in the MCV and RDW are associated with certain types of anemia The MCV and RDW can significantly narrow the differential diagnosis, particularly when combined with the reticulocyte count Examination of the Peripheral Blood Smear Despite the development and availability of more sophisticated diagnostic testing, review of a well-made peripheral blood smear remains one of the most informative and rewarding diagnostic procedures It offers the chance to confirm the findings of the automated CBC count, which can be inaccurate in the presence of nucleated RBCs or rouleaux formation Review of the blood smear also allows for evaluation of other cell lineages, which might suggest a primary BM or infiltrative disease. For example, the finding of hypersegmented neutrophils suggests a megaloblastic process, and this morphologic abnormality can be seen in the blood smear before there are significant changes in the hemoglobin or MCV Only the blood smear reveals the unique morphologic changes occurring with several of the various hemolytic disorders Bone Marrow Examination Bone marrow aspiration and biopsy permit evaluation of cellular morphology and BM architecture Diagnostic uncertainty in the setting of hypoproliferative anemia is an indication for BM biopsy. Hematologic disorders such as myelodysplasia, leukemia, lymphoma, or myeloma may be identified. Myelodysplasia in the marrow classically includes megaloblastic change and nuclear budding in maturing erythroblasts, as well as morphologic abnormalities in other lineages, such as hypolobated megakaryocytes and hypogranulation of the myeloid lineage. A variety of infiltrative (myelophthisic) processes may be observed. These include malignancies such as small-cell lung, breast, and prostate cancers, which frequently can appear in advanced stages with BM involvement. Alternatively, granulomas may be present, suggesting the possible presence of mycobacterial disease. In children, disseminated neuroblastoma and rhabdomyosarcoma occasionally can appear as a myelophthisic anemia