Hematology Tables (CS II Exam) PDF

Hematology  Hematologic System Biopsy Site of Bone Marrow Biopsy The iliac crest in the pelvic bone is a common site for a bone marrow aspiration for biopsy Erythrocytes Erythropoietin The hormone erythropoietin, originating...

Hematology  Hematologic System Biopsy Site of Bone Marrow Biopsy The iliac crest in the pelvic bone is a common site for a bone marrow aspiration for biopsy Erythrocytes Erythropoietin The hormone erythropoietin, originating from the kidney, stimulates erythrocyte production in the red bone marrow in response to tissue hypoxia, or insufficient oxygen available to cells Megaloblastic Anemia Folate and vitamin B12 deficiency are the classical causes of megaloblastic anemia The term megaloblastic refers to the appearance of hematopoietic precursor cells in the marrow This megaloblastic change affects not only erythroblasts but other rapidly dividing cells as well, including ○ Maturing granulocytes ○ Megakaryocytes ○ Enterocytes Macrocytosis A descriptive term for red blood cell (RBC) size larger than the normal range. It may be caused by ○ Abnormalities of RBC production in the bone marrow 1001L ○ Altered RBC membrane composition ○ Increase in the percentage of reticulocytes, which are larger than mature RBCs. Microcytosis 80ft A descriptive term for red blood cell (RBC) size smaller than the normal range Heme Heme provides the red color associated with hemoglobin Oxyhemoglobin Arterialblood Oxyhemoglobin has a bright red color, which distinguishes arterial blood from venous blood Deoxygenated hemoglobin Deoxygenated hemoglobin (deoxyhemoglobin or reduced hemoglobin) is dark or bluish red in color and is found in venous blood venousblood Carbon Dioxide Only a small proportion of the carbon dioxide (CO2) in blood is carried by hemoglobin (carbaminohemoglobin) attached to nitrogen in an amino acid group at a different site from that for oxygen Most carbon dioxide is transported in blood as bicarbonate ion (in the buffer pair) Carbon Monoxide Oxygen can easily be displaced from hemoglobin by carbon monoxide, which binds fromñÉm agio tightly to the iron, thus causing a fatal hypoxia (deficit of oxygen) detatches oz binge Carbon monoxide poisoning can be recognized by the bright cherry-red color in the lips fatalhypoxia and face Globin Globin is broken down into amino acids, which can be recycled in the amino acid pool, and the iron can be returned to the bone marrow and liver to be reused in the synthesis acids iron amino of more hemoglobin Excess iron Excess iron can be stored as ferritin or hemosiderin in the liver, blood, and other body tissues Hemochromatosis Hemochromatosis, otherwise known as iron overload, results in large amounts of hemosiderin accumulating in the liver, heart, and other organs, causing serious organ damage organ damage Complete blood count Components A complete blood count is the evaluation of cellular components of the blood. It includes Red blood cell (RBC) count RBC indices White blood cell (WBC) count WBC differential Hemoglobin (Hgb) Hematocrit (HCT) Platelet count Other Names Sometimes it is referred to as a hemogram. hemogram Hematocrit Sex Difference Males have a higher hematocrit, average 42% to 52%, than females, 37% to 48%. Elevenated An elevated hematocrit would indicate dehydration (loss of fluid) or excess red blood cells. Low A low hematocrit might result from blood loss or anemia Coagulation Studies  seventies.ieiniigyirik.nontissuefactor aPTT The aPTT assesses the “intrinsic” non-TF (tissue factor)-dependent and common pathways Heparin The aPTT is also very sensitive to the presence of heparin bound to AT and is used to monitor the anticoagulant effects of unfractionated heparin Low-molecular-weight Heparins Low-molecular-weight heparins (a specific purified subset of unfractionated heparin) in INHIBITXA combination with AT preferentially inhibit factor Xa Newer Direct Oral Anticoagulants Newer direct oral anticoagulants (thrombin or factor Xa inhibitors) affect aPTT or PT/INR less reproducibly, and drug-specific anti-Xa assays or the thrombin time may be needed in cases in which there are concerns about under- or over- anticoagulation with these agents. Increased standardized Times Increased standardized times may be indicative of many disorders, including but not limited to Cardiac surgery DIC Abruptio placentae Factor defects Hemodialysis Obstructive jaundice Vitamin K deficiency Presence of circulating anticoagulants Ingestion of certain drugs Decreased Standardized Times Decreased standardized times are indicative of Acute early hemorrhage Extensive cancer PT i tennisoutsideextrinsic play PT assesses the “extrinsic” TF-dependent and common pathways of the classical coagulation cascade and is used clinically to monitor the effects of warfarin Because all vitamin K–dependent factor levels are lowered by warfarin, eventually the iant.fioirtYun.vimxixt aPTT will also become abnormal with high enough doses; but factor VII has the shortest half-life of those factors, so its levels fall first. Because of its critical role in clotting, thrombin is the principal factor whose activity must be reduced to achieve and maintain therapeutic anticoagulation Prothrombin time (PT) is a measurement of the time taken for clot formation after the 1013sec addition of reagent tissue thromboplastin and calcium to citrated plasma In the clotting process, prothrombin converts to thrombin. Adequate vitamin K is necessary for adequate prothrombin production Normal Adult Levels: 10.0 to 13.0 seconds; may vary according to laboratory Increased PT An increase in PT may be indicative of several disorders, including but not limited to Vitamin K deficiency Liver disorders Anticoagulant therapy Prothrombin deficiency Salicylate intoxication DIC SLE Clotting disorders Biliary obstruction CHF Pancreatitis Snakebite Vomiting Toxic shock syndrome Ingestion of certain drugs Decreased PT A reduced PT may be indicative of certain disorders, including but not limited to Deep vein thrombosis MI Peripheral vascular disease Spinal cord injury Pulmonary embolism Ingestion of certain drugs International normalized ratio (INR) International normalized ratio (INR) is the standardized result used with treatment of anticoagulation therapy. Critical value: 1.0 to 1.4 seconds Bleeding time The Ivy method The Ivy method is done by placing a blood pressure cuff on the arm, inflating it to 40 mm Hg, and using a lancet or scalpel to make an incision on the underside of the forearm CGminutes The incision is to be shallow at 1 mm depth and about 10 mm long. Filter paper is used to “wick” the blood from the cut every 30 seconds until bleeding has ceased. Normal time at most laboratories is less than 9 minutes. Increased bleeding time Increased bleeding times are indicative of several disorders, including but not limited to Thrombocytopenia DIC Aplastic anemia Platelet dysfunction Vascular disease Leukemias Liver disorders Aspirin ingestion Ingestion of certain drugs Decreased bleeding time Decreased bleeding time is clinically insignificant Fibrinogen X Production inliver Fibrinogen is produced in the liver by hepatocytes Abnormalities Abnormalities of fibrinogen production may be congenital or acquired and, in general, involve either decreased production of a normal molecule (afibrinogenemia and hypofibrinogenemia) or production of an abnormal molecule (dysfibrinogenemia) Degradation Fibrinogen (or fibrin) degradation products (FDPs) are fragments released following plasmin-mediated degradation of fibrinogen or fibrin The d-dimer is a specific fragment formed only upon degradation of cross-linked fibrin Cross-Linked Fibrin Cross-linked fibrin is the endpoint of the coagulation cascade Fibrinolysis Fibrinolysis is the enzymatic breakdown of fibrin in blood clots The fibrinolytic system serves to limit the formation of thrombi and to facilitate healing or recanalization of a vessel with a thrombotic occlusion Primary fibrinolysis Secondary fibrinolysis A normal body process The breakdown of clots due to Medicine Disorder Other cause Fibrin Degradation Products (FDP) Fibrin Degradation Products (FDP) that occur are very heterogeneous and include products derived from ○ Fibrin ○ Soluble complexes ○ Degradation products from fibrinogen ○ From non stabilized fibrin One of the specific FDPs is fragment D Dimers of this fragment (d-dimer) are detected only upon degradation of cross-linked fibrin (indicating active coagulation and fibrinolysis) The presence FDP of in plasma can provide important information for the diagnosis of hemostatic disorders Elevated FDP An abnormal fibrinolytic and/or fibrinogenolytic activity shown by high levels of FDP in plasma can be found in clinical states, such as ○ Eclampsia ○ Carcinoma (promyelocytic leukemia) ○ Cardiac disorders ○ Renal disorders ○ Hepatic disorders ○ Fibrinolysis ○ Pulmonary embolism ○ Deep vein thrombosis (DVT) ○ Following surgery or trauma, and after lytic therapy Increased FDPs are seen in primary fibrinolysis as well as during fibrin clot breakdown Elevated FDP levels are not specific for DIC and increased FDP levels are often seen in ○ Primary fibrinolysis ○ Severe liver disease, including Alcoholic cirrhosis Eclampsia During acute thrombotic RBC Indices Components These are mathematical ratios of three tests (Hgb, Hct, RBC count) Testing For These RBC tests are valuable for identifying various forms of anemia and polycythemia MCV and MCH Mean cell volume (MCV) and mean cell Hgb (MCH) indices: compare the Hct volume and the Hgb value with the total RBC count, respectively MCV By comparing the patient’s MCV with the reference range, the general size of the RBCs can be determined If the MCV is less than 80 μm, for example, the RBCs are microcytic; if the MCV is greater than 100 μm, the RBCs are macrocytic pi e ge2733 MCH The MCH indicates the concentration of Hgb compared with the average size of the RBCs hemoglobin (27 – 33 pg/cell) MCHC hemoglobinamtinsample Mean (average) cell Hgb concentration (MCHC): This ratio is commonly calculated in the ambulatory care setting because Hgb and Hct are both CLIA-waived tests If the patient’s values fall below the reference range, the RBCs contain less Hgb than normal 3236 (32 – 36 g/dL) WBC Differential Count Type of study A differential count uses a stained blood smear Percentage The percentage of each WBC type is compared with the reference values shown in the columns for neonates, infants, children, men, and women Components The appearance of the RBCs and platelets is also observed and described in the report Red Blood Cell Distribution Width Measuring An RDW blood test measures how varied your red blood cells are in size and volume Range When it comes to your red blood cells, size matters. Healthy red blood cells are 628.2 about the same size, ranging from 6.2 to 8.2 micrometers Abnormalities Having red blood cells that are vastly different sizes from each other (high variation) may be a sign of anemia Reticulocytes Components These are young RBCs, which still contain some nuclear remnants Range The average number of reticulocytes found in peripheral blood is approximately 1%. A percentage higher than 3% indicates that the individual is actively producing new RBCs because of a loss of RBCs, such as when hemorrhaging occurs Maturuatity As the reticulocytes continue to mature, they shed their remaining intracellular nuclear material while retaining millions of hemoglobin (Hgb) molecules Haptoglobin hindsight 40200 Overview Hp is a hemoglobin-binding protein synthesized in the liver and released into the circulation free (40 – 200 mg/dL) Function The main function of Hp is to bind free Hgb released from lysed erythrocytes and thus prevent the iron within hemoglobin from reacting with molecular oxygen to produce the free radical superoxide Any free hemoglobin released from RBC breakdown complexes with Hp and is then cleared by the reticuloendothelial system Decrease Any decrease in the plasma Hp concentration occurs when the daily hemoglobin turnover is doubled, irrespective of whether the hemolysis is extravascular or intravascular Hp is more rapidly depleted in intravascular hemolysis. However, congenital ahaptoglobinemia is seen in 2% of the Caucasian population and concentrations may also be lowered in megaloblastic anemia (because of ineffective erythropoiesis) and in liver disease Increase Haptoglobin is an acute phase protein, with its concentration rising in Many inflammatory conditions In pregnancy During use of oral contraceptives Corticosteroids Peripheral Smear Components The hematologist scans stained blood smears to identify the distribution of the five types of leukocytes on the basis of their ○ Staining characteristics ○ Shapes ○ Sizes This procedure is called a differential count Types of Cells Leukocyte Type Appearance Fxn (Table credit to Sabrina) Segmented Neutrophil Fine lavender or pink granules, Most prevalent WBC; first to segmented nucleus respond to tissue damage, 1 perform phagocytosis Only survives 4 days Banded Neutrophil Bed-shaped nucleus Immature neutrophil; increase in bacterial infections “Shift to the left” in the pattern of leukocytes being seen. Small Lymphocyte Dense circular nucleus, scant 2nd Most Prevalent WBC blue cytoplasm Monocyte Largest WBC; large, lacy Can enter tissue to become nucleus macrophages; act as 2 phagocytes when tissue damage occurs Eosinophils Large Red Granules Increased by allergic reactions & parasitic infections (like histamine) Basophil Large dark-blue or black Migrate from blood to become granules mast cells that release  histamine & heparin Monitoring Heparin Montorting Laboratory monitoring is widely recommended to measure the anticoagulant effect of unfractionated heparin and to adjust the dose to maintain levels in the target therapeutic range aPTT The most widely used laboratory assay for monitoring unfractionated heparin therapy is controlvalue the activated partial thromboplastin time (aPTT) 1.5-2.5 A fixed therapeutic range for the aPTT of 1.5 to 2.5 times the control value has become widely accepted, but the evidence supporting this range is weak and the clinical validity of using the aPTT for predicting thrombotic or bleeding events is questionable The aPTT test is also affected by numerous preanalytic and analytic variables that are unrelated to the anticoagulant effect of unfractionated heparin, further eroding its potential value for monitoring unfractionated heparin treatment Unfractionated heparin dose appears to be more important than the aPTT in predicting clinical efficacy Despite serious limitations, the reliance on the aPTT is likely to continue because of its ready availability and familiarity of clinicians with the test The focus of clinicians who manage unfractionated heparin therapy should be to ensure that an adequate starting dose of unfractionated heparin is used and that the aPTT method is standardized However, currently available unfractionated heparin assays are much more expensive than the aPTT, are not widely available, and their validity has not been adequately assessed in clinical outcome studies Normal aPTT 25-35 sec A normal partial thromboplastin time (PTT) is between 25 and 35 seconds Prolonged aPTT A prolonged PTT could indicate a number of conditions: Hemophilia Deficiencies in clotting factors VIII, IX, or XI Liver disease Vitamin K deficiency Certain types of leukemia, autoimmune diseases Shortened aPTT A shortened PTT could indicate an increased risk of thrombosis Monitoring Warfarin Function of Warfarin Warfarin inhibits the synthesis of clotting factors II, VII, IX, and X, as well as the naturally occurring endogenous anticoagulant proteins C and S The anticoagulant and antithrombotic activity of warfarin depend on the clearance of functional clotting factors from the systemic circulation once the drug is administered The earliest changes in INR are typically seen 24 to 36 hours after administration of the dose The antithrombotic effect of warfarin is not present until approximately the fifth day of therapy, which is dependent on the clearance of prothrombin Warfarin, a vitamin K antagonist, is an oral anticoagulant indicated for the prevention and treatment of venous thrombosis and its extension, and the prevention and treatment of the thromboembolic complications associated with atrial fibrillation Warfarin has also been used to prevent recurrent transient ischemic attacks and to reduce the risk of recurrent myocardial infarction, but data supporting these indications are inconclusive at this time INR The safety and efficacy of warfarin therapy are dependent on maintaining the INR within the target range for the indication When a patient is started on an oral anticoagulant, INR monitoring should be performed daily until the INR is within the therapeutic range for at least 2 consecutive days Unexpected fluctuation Unexpected fluctuations in the INR in an otherwise stable patient could be due to ○ A change in diet ○ Poor compliance ○ Undisclosed drug use ○ Alcohol consumption ○ Self-medication Lab error should also be considered for unexpected values Normal Range The normal range for a prothrombin time (PT) test is 11 to 13.5 seconds Recommended therapeutic range for oral anticoagulant therapy Treatment of venous thrombosis 2.0–3.0 Treatment of pulmonary embolism 2.0–3.0 Prophylaxis of venous thrombosis (high-risk surgery) 2.0–3.0 Prevention of systemic embolism 2.0–3.0 Tissue heart valves 2.0–3.0 AMI (to prevent systemic embolism) 2.0–3.0 Valvular heart disease 2.0–3.0 Atrial fibrillation 2.0–3.0 Bileaflet mechanical valve in aortic position 2.0-3.0 Mechanical prosthetic valves (high risk) 2.5–3.5 Systemic recurrent emboli 2.5–3.5 Thrombocytes Components Thrombocytes are not cells; rather, they are very small, irregularly shaped, non- nucleated fragments from large megakaryocytes Function Platelets stick to damaged tissue as well as to each other to form a platelet plug that seals small breaks in blood vessels, or they can adhere to rough surfaces and foreign material a clotting Aspirin The common drug acetylsalicylic acid (ASA), or aspirin, reduces this adhesion and can lead to an increased bleeding tendency. Thrombocytes can also initiate the coagulation process. bleeding Blood Dyscrasias Anemias Low hemoglobins The low hemoglobin level may result from declining production of the protein, a decrease in the number of erythrocytes, or a combination of these factors Classification Anemias may be classified by typical cell characteristics such as size and shape (morphology) or by etiology—for example, the hemolytic anemias. Sequence of events The oxygen deficit leads to a sequence of events: 1. Less energy is produced in all cells; cell metabolism and reproduction are diminished 2. Compensation mechanisms to improve the oxygen supply include tachycardia and peripheral vasoconstriction 3. These changes lead to the general signs of anemia, which include ○ Fatigue (excessive tiredness) ○ Pallor (pale face) ○ Dyspnea (increased effort to breathe) ○ Tachycardia (rapid heart rate) 4. Decreased regeneration of epithelial cells causes the digestive tract to become inflamed and ulcerated, leading to ○ Stomatitis inflamed ○ Cracked lips ○ Dysphagia the hair and skin may show degenerative changes 5. Severe anemia may lead to angina (chest pain) during stressful situations if the oxygen supply to the heart is sufficiently reduced. Chronic severe anemia may cause congestive heart failure Iron Deficiency Anemia Physiology Insufficient iron impedes the synthesis of hemoglobin, thereby reducing the amount of oxygen transported in the blood Type of anemia This results in microcytic (small cell), hypochromic (less color) erythrocytes owing microcytic 80117 to a low concentration of hemoglobin in each cell Lab components Because iron deficiency anemia is frequently a sign of an underlying problem, it is important to determine the specific cause of the deficit. There is also a reduction in stored iron, as indicated by Decreased serum ferritin Decreased hemosiderin Decreased iron-containing histiocytes in the bone marrow Causes An iron deficit can occur for many reasons: Dietary intake of iron-containing vegetables or meat may be below the minimum baddietchronicbleeding requirement, particularly during the adolescent growth spurt or during pregnancy and breastfeeding, when needs increase Chronic blood loss from a ○ Bleeding ulcer ○ Hemorrhoids ○ Cancer ○ Excessive menstrual flow is a common cause of iron deficiency Continuous blood loss, even small amounts of blood, means that less iron is recycled to maintain an adequate production of hemoglobin Lab results Laboratory tests demonstrate low values for ○ Hemoglobin ○ Hematocrit everythinglow ○ Mean corpuscular volume ○ Mean corpuscular hemoglobin ○ Serum ferritin ○ Serum iron ○ Transferrin saturation Microscopic On microscopic examination the erythrocytes appear hypochromic and microcytic Pernicious Anemia–Vitamin B12 Deficiency (Megaloblastic Anemia) Characteristics Megaloblastic anemias, are characterized by Very large Immature Nucleated erythrocytes Causes (vitamins) This type of anemia usually results from a deficit of folic acid (vitamin B9) or vitamin B12 (cyanocobalamin) folatelowB12 Vitamin deficiencies usually develop gradually There is an increased interest in the folic acid deficiency that may occur during the first 2 months of pregnancy, resulting in an increased risk of spina bifida and other spinal abnormalities in the child The prototype of megaloblastic anemia is pernicious anemia, a vitamin B12 deficiency. Pernicious anemia is the common form of megaloblastic anemia that is caused by the malabsorption of vitamin B12 owing to a lack of intrinsic factor (IF) produced in the glands of the gastric mucosa Intrinsic factor must bind with vitamin B12 to enable absorption of the vitamin in the lower ileum An additional problem occurs with the atrophy of the mucosa because the parietal cells can no longer produce hydrochloric acid, resulting in a low level or absence of acid in the gastric secretions referred to as achlorhydria Achlorhydria interferes with the early digestion of protein in the stomach and with the absorption of iron; thus, an iron deficiency anemia may be present as well A deficit of vitamin B12 leads to impaired maturation of erythrocytes owing to interference with DNA synthesis Lab Values The RBCs are very large (megaloblasts or macrocytes) and contain. These large erythrocytes are destroyed prematurely, resulting in a low erythrocyte count, or anemia macrocytic 100 4 Hemoglobin in the RBCs is normal and is capable of transporting oxygen. Often the maturation of granulocytes is also affected, resulting in development of abnormally large hypersegmented neutrophils Thrombocyte levels may be low. In addition, lack of vitamin B12 is a direct cause of demyelination of the peripheral nerves and eventually of the spinal cord. Loss of NORMAL Hemoglobin myelin interferes with conduction of nerve impulses and may be irreversible. Sensory fibers are affected first, followed by motor fibers The bone marrow is hyperactive, with increased numbers of megaloblasts. Granulocytes are hypersegmented and are decreased in number The vitamin B12 level in the serum is below normal. In the Schilling test, an oral dose of radioactive vitamin B12 is used to measure absorption Treatment Oral supplements are recommended as prophylaxis for pregnant women and vegetarians. Vitamin B12 is administered by injection as replacement therapy for people with pernicious anemia. Prompt diagnosis and treatment of pernicious anemia prevents cardiac stress and neurologic damage Aplastic Anemiabone marrow Characteristics not working It results from impairment or failure of bone marrow, leading to loss of stem cells and pancytopenia, the decreased numbers of erythrocytes, leukocytes, and platelets in the PancytopeniaLow everything blood These deficits lead to many serious complications. In addition, the bone marrow exhibits reduced cell components and increased fatty tissue Causes Aplastic anemia may be a temporary or permanent condition depending on the cause: In approximately half the cases, the patients are middle-aged, and the cause is unknown idiopathic or idiopathic (primary type) chemicals Myelotoxins, such as radiation, industrial chemicals (eg, benzene), and drugs (chloramphenicol, gold salts, phenylbutazone, phenytoin, and antineoplastic drugs) may Medpication damage the bone marrow Viruses, particularly hepatitis C, may cause aplastic anemia. Autoimmune disease such as systemic lupus erythematosus (SLE) may affect the bone LSE marrow. Genetic abnormalities such as myelodysplastic syndrome or Fanconi anemia may also affect bone marrow function Testing Blood counts indicate pancytopenia. A bone marrow biopsy may be required to confirm the cause of the pancytopenia. The erythrocytes are often normal in appearance (normocytic) Hemolytic Anemias destructionofRBC Characteristics These result from excessive destruction of RBCs, or hemolysis, leading to a low erythrocyte count and low total hemoglobin fasterthan replaced Causes They have many causes, including genetic defects affecting structure, immune reactions, changes in blood chemistry, the presence of toxins in the blood, infections such as malaria, transfusion reactions, and blood incompatibility in the neonate (erythroblastosis fetalis) Sickle Cell Anemia Hb Hemoglobin S It is representative of a large number of similar hemoglobinopathies In this anemia, an inherited characteristic leads to the formation of abnormal hemoglobin, hemoglobin S (HbS)  In HbS, one amino acid in the pair of beta-globin chains has been changed from the normal glutamic acid to valine Sickling When this altered hemoglobin is deoxygenated, it crystallizes and changes the shape of instead of120 the RBC from a disc to a crescent or “sickle” shape live20days The cell membrane is damaged, leading to hemolysis, and the cells have a much shorter life span than normal, perhaps only 20 days, instead of the normal 120 days Initially the sickling may be reversible when increased oxygen is available, but after several episodes, the damage to the RBC is irreversible and hemolysis occurs A major problem resulting from the sickling process is the obstruction of the small blood vessels by the elongated and rigid RBCs, resulting in thrombus formation and repeated multiple infarctions, or areas of tissue necrosis, throughout the body A serious crisis may occur in individuals with lung infection or dehydration when basic oxygen levels are reduced. During a sickling crisis, many larger blood vessels may be involved, and multiple infarctions occur throughout the body, affecting the brain, bones, or organs Demographics The gene for HbS is recessive and is common in individuals from Africa and the Middle East It is estimated that 1 in 12 African Americans have the trait and about 1 in 500 have sickle cell anemia Signs and Symptoms Clinical signs of sickle cell anemia do not appear until the child is about 12 months of age, when fetal hemoglobin (HbF) has been replaced by HbS. The proportion of HbS in the erythrocytes determines the severity of the condition Severe anemia causes ○ Pallor ○ Weakness ○ Tachycardia ○ Dyspnea Hyperbilirubinemia is indicated by jaundice, The high bilirubin concentration in the bile may cause the development of gallstones Vascular occlusions and infarctions lead to periodic painful crises and permanent damage to organs and tissues Such damage may be manifested as ulcers on the legs and feet, areas of necrosis in the bones or kidneys, or seizures or hemiplegia resulting from cerebral infarctions. Pain can be intense In the lungs, occlusions and infection cause acute chest syndrome with pain and fever. It can be diagnosed by x-ray. It is a frequent cause of death Occlusions in the smaller blood vessels of the hands or feet cause hand-foot syndrome. Pain and swelling are often early signs in children. Growth and development are delayed. Late puberty is common. Tooth eruption is late, and hypoplasia is common. Intellectual development is usually impaired. Frequent infections occur because of the decreased defenses when the damaged spleen can no longer adequately filter the blood, the presence of necrotic tissues, and poor healing capabilities Pneumonia is a common cause of death in children Diagnosis Carriers of the defective gene can be detected by a simple blood test (hemoglobin electrophoresis) Prenatal diagnosis can be checked by DNA analysis of the fetal blood In children older than 1 year of age, the diagnosis can be confirmed by the presence of sickled cells in peripheral blood and the presence of HbS Autoimmune Hemolytic Anemia Overview Some antibodies are capable of activating complement and producing brisk intravascular hemolysis Others behave as opsonins, promoting red cell destruction in the spleen Some antibodies react only in a cold environment, some only in warmth. Some coat the red cell and do nothing more These disorders present with the typical manifestations of anemia, with variable rates of onset 1Fsn Warm autoimmune hemolytic Warm autoimmune hemolytic anemia (WAIHA) is mediated by IgG autoantibodies that 37C anemia (WAIHA) optimally bind RBCs at body temperature (37o C) Cold agglutinin hemolytic disease In severe IgM-induced cold autoimmune hemolytic anemia (CAIHA), the skin may (CAIHA) have a livedo reticularis pattern, and there may be acrocyanosis on exposure to cold CAIHA, also called cold agglutinin disease, is mediated by IgM antibodies that bind IgM 10C RBCs at lower temperature ranges When temperature falls a bit below core body temperature, resulting in acrocyanosis IgM antibodies are capable of activating complement Heat Related Diseases However, these antibodies may cause difficulty in the laboratory, where studies are routinely carried out at room temperature, which could be within this thermal amplitude Antibodies with broader thermal amplitude may bind to red cells in the extremities Both WAIHA and CAIHA are often idiopathic conditions. However, a significant number are secondary to another underlying condition, including Lymphoid neoplasms (chronic lymphocytic leukemia) ○ Medication use ○ Systemic autoimmune diseases (systemic lupus erythematosus), immunodeficiency (common variable immunodeficiency) ○ Infection (infectious mononucleosis, HIV, and Mycoplasma pneumoniae) Paroxysmal cold hemoglobinuria Paroxysmal cold hemoglobinuria (PCH), is caused by IgG antibodies that are directed at Donald coldsometimes (PCH) the red cell P antigen is The antibody responsible for PCH is called the Donath–Landsteiner antibody. This 196 particular IgG antibody has peculiar tendencies, including the binding of red cells in colder temperatures (in the blood of the extremities) and the activation of complement,  producing intravascular hemolysis Originally described in association with syphilis, the antibody now is more often seen in children with viral infections Mortality can be quite high, up to 30% Drug-induced immune hemolytic anemia arises through several pathophysiologic mechanisms PCH Diagnosis The direct antiglobulin test (DAT), also known as the direct Coombs test, is pivotal for the diagnosis of immune hemolysis Additional laboratory findings include ○ Anemia DATguy Donald is ○ Reticulocytosis ○ Indirect hyperbilirubinemia ○ Decreased haptoglobin a coomb ○ Increased LDH The peripheral blood smear often demonstrates spherocytes, polychromasia, and, in severe cases, nucleated red cells. In cold agglutinin disease, red cell clumping is seen Hemolytic Disease of the Fetus and Newborn (HDFN) Blood-Clotting Disorders Hemophilia A Infectious  Infectious Diseases Bacteremia Overview Replication of bacteria in the blood can contribute to the signs and symptoms of sepsis (fever, tachycardia, leukocytosis, and hypotension) and may lead to dissemination of the organism to other tissues and organs; however, patients can be septic without having demonstrable bacteria in their blood Types Bacteremia is often described as transient, intermittent, or continuous based on the number of positive specimens Transient bacteremia Intermittent bacteremia Continuous bacteremia Occurs when small numbers Usually associated with a Associated with an of a commensal organism sequestered infection intravascular focus of present on a mucosal surface somewhere in the organs or infection. (Ex: gain access to the tissues (an abscess) include endocarditis or an bloodstream infected vascular catheter) Organisms The isolation of certain species may have additional significance; for example, bacteremia caused by S. gallolyticus or Clostridium septicum is often associated with the presence of colon cancer Diagnosis Blood cultures are routinely collected as part of the diagnostic evaluation of patients who present with signs and symptoms of sepsis or disseminated infection To maximize sensitivity and specificity, it is recommended that two to three sets of blood cultures be collected per septic episode Most hospitals use continuous blood culture systems that utilize colorimetric, fluorescent, or manometric methods to detect bacterial growth To identify intermittent bacteremias, the timing of the blood collection is important to maximize the likelihood of finding organisms while they are in the blood Ideally, blood from patients with intermittent bacteremias is collected during the hour before a temperature spike, but this is not practical because the febrile episodes are often not predictable It is common practice for blood to be collected at 30- to 60-minute intervals (if possible) when a febrile patient is suspected of having an intermittent bacteremia A major problem in the interpretation of the blood culture results is incidental contamination of the specimen with the normal bacterial flora from the skin The isolation of recognized pathogens such as ○ S. aureus ○ S. pneumoniae ○ Beta-hemolytic streptococci (S. pyogenes and S. agalactiae) ○ Enterococci, gram-negative rods (aerobic and anaerobic) ○ Yeast from one or more blood cultures is almost always clinically significant In contrast, if only one of the multiple blood culture specimens is positive for an organism found on the skin (coagulase-negative staphylococci or Corynebacterium 2 spp.), the result is likely to reflect contamination during specimen collection rather than it'smycornytoputthatstuffon urskin true septicemia This frequently encountered problem is one reason why at least two blood samples should be collected for blood cultures Although skin-derived bacteria are often thought of as nonpathogenic, it is important to remember that they can cause clinically significant infections, particularly in immunosuppressed patients and in patients with intravascular catheters or prosthetic  devices The isolation of the same skin flora organism in two separately collected specimens increases the probability that it represents a clinically significant bacteremia To avoid the problem of contamination of the blood culture bottles with skin organisms, meticulous preparation of the skin with a bactericidal agent is necessary. Infections Caused by Rickettsia, Ehrlichia, and Related Organisms Detection Rickettsia, Ehrlichia, and Anaplasma are obligate intracellular bacteria that cannot be detected in routine bacterial cultures ticks notdetectable Spread These organisms are transmitted to humans by ticks Rickettsia rickettsii Rickettsia rickettsii, the agent of Rocky Mountain spotted fever (RMSF), is mainly transmitted by the dog tick (Dermacentor variabilis) and infects endothelial cells iiii.it The resulting vascular injury elicits widespread vasculitis, consisting of vasodilation iiiiiuan vermaceai with perivascular edema, and at times complicated by thrombosis and hemorrhage. Erythrocytes extravasating into the dermis form non blanching petechial or purpuric lesions nilis Ehrlichia chaffeensis Ehrlichia chafeensis is transmitted by the lone star tick (Amblyomma americanum) and infects monocytes motikytes Patients present with nonspecific findings including ○ Fever ○ Leukopenia ○ Thrombocytopenia, ○ Elevations of hepatic enzymes Diagnosis None of these agents can be cultured on artificial media callthedogsirser RMSF is usually diagnosed retrospectively with serologic tests Examination of peripheral blood smears in patients with Anaplasma can reveal the presence of organisms within inclusions in neutrophils, but many cases are negative Ehrlichia infects monocytes but is rarely observed in peripheral blood smears. NAAT-based tests of blood and/or serologic tests are the best methods for diagnosing Anaplasma and Ehrlichia infections Disease Etiologic Agent Mechanism of Transmission to Humans Clinical Features Lab Tests Rocky Rickettsia rickettsii Tick vector Higher rate seasonally/specific geographic Serology: increased Mountain areas rash from a vasculitis, fever and a ab titer after exposure. Spotted Fever headache Immunohistochemical tests on tissue (sensitivity @ 70%) Murine typhus Rickettisia typhi Flea feces inoculated into flea bite wound on Seasonal and geographic; rash, fever and Serology: increased human headache ab titer after exposure snit moremurflea  Q fever Coxiella burnetti Inhalation of infected aerosols, ingestion of Acutely, it is usually an asymptomatic or Serology: increased ab titer after exposure contaminated dairy products, or, rarely, by self-limited febrile pneumonia; can become (most common method); PCR of blood cowsimam.is zoonotic tick vector chronic with damage to heart valves and available in reference labs bone Ehrlichiosis Ehrlichia chaffeensis Tick vector From asymptomatic to a severe RMSF-like Serology: increased ab titer after exposure; illness PCR of blood Anaplasmosis Anaplasma phagocytophilium Tick vector Fever, headache, myalgias Serology: increased ab titer after exposure; PCR of blood Fungemia Overview Yeast belonging to the genus Candida are a major cause of hospital-acquired ass bloodstream infections. These organisms are frequently part of the oral and mouth Candida hospital gastrointestinal flora Treatment with broad-spectrum antibiotics that disrupt the normal bacterial flora, the incathetar presence of intravenous catheters, and neutropenia all predispose to the development of candidemia Infectious Agents Cryptococcus neoformans and Histoplasma capsulatum are important causes of fungemia in patients with markedly depressed cell-mediated immunity Although molds such as Aspergillus spp. can cause disseminated infections in immunosuppressed patients, they are rarely detected in the bloodstream Diagnosis Candidemia can usually be detected with routine blood cultures. Specialized techniques (e.g., lysis–centrifugation cultures) are usually required to detect H. capsulatum and may enhance the detection of C. neoformans Parasitic Infections of the Blood WHAT Organism girl Several vector-borne parasites can infect the blood. These include protozoans such as Plasmodium spp. (malaria), Babesia spp., and Trypanosoma spp., and nematodes such as the agents of lymphatic filariasis Illness Plasmodium infections are an important cause of nonspecific febrile illnesses in returning travelers, and Babesia infections are endemic in parts of the United States. Other blood parasites are uncommon in the United States Malaria Overview Malaria is one of the largest causes of mortality and morbidity in the world Organisms There are four species of Plasmodium that cause most cases of human malaria These parasites are transmitted by Anopheles mosquitoes that are widely distributed buzz think plasmo buzz throughout Africa, Asia, and Latin America. The most dangerous of the four species is  Plasmodium falciparum flac bad This organism can achieve very high levels of parasitemia and adheres to capillary endothelium, and this can lead to severe organ damage P. falciparum infection may be fatal within days. P. vivax and P. ovale are morphologically similar and generally cause less severe infection, but unlike P. falciparum, they can establish persistent infection and cause relapses several months after the initial infection P. malariae is the least virulent species and can cause low-level infection that may cause few symptoms, but it can persist for years. P. knowlesi, which infects monkeys, can also cause human infections Diagnosis Currently, the diagnosis of malaria and the identification of the species of Plasmodium responsible for malaria are usually based on the microscopic examination of stained iiestes ipiisoynenstih.is erythrocytes in thick and thin blood films PCR is starting to be used for the diagnosis of malaria and is particularly useful when low levels of parasitemia make it difficult to identify individual species. A rapid Radidalsookwhenno immunodiagnostic test for malaria may also be useful in settings where microscopy is not immediately available microscope Babesiosissame Overview blacklegged tickasLyme Babesia species are protozoa that, like Plasmodium species, infect erythrocytes Proliferation They are delivered to the infected host by the same tick (Ixodes) that transmits the agent of Lyme disease and human granulocytic anaplasmosis In the United States, B. microti is responsible for most cases of human babesiosis ixod.is Babesiosis occurs mainly in the Northeast and upper Midwest in the United States. It affects patients of all ages, but most cases occur during the sixth and seventh decades of life Signs and Symptoms Babesiosis mimics malaria, in that it causes hemolysis, fever, anorexia, and hemoglobinuria visaiinsaaaria The infection from Babesia tends to be self-limited. In most cases, it lasts from weeks to months, following an incubation period of 1 to 6 weeks Mild symptoms, including malaise, fever, and headache, characterize the disease in normal hosts, but asplenic patients often develop severe infections with high levels of parasitemia Screening Transfusion-transmitted babesiosis is a significant concern because blood donors may have blood couldhaveasymptomatic subclinical/asymptomatic infections, and Babesia screening tests are still in the investigational stage donor Diagnosis The laboratory diagnosis rests upon the identification of the Babesia organisms inside erythrocytes in stained thick and thin peripheral blood smears bloodsmearerythrocytes There are a number of morphologic features that differentiate Babesia from Plasmodium. Despite its relative shortcomings, serologic testing for B. microti can be performed The level of parasitemia with Babesia does not always correlate with the severity of symptoms Viral Infections of the Blood Viral Organisms  Organisms Many viruses such as varicella zoster virus (VZV), measles, enteroviruses, and arboviruses (such as West Nile virus) exhibit a viremic phase inblood canmovetootherparts and stream ofbody Organic specific manifestation Cytomegalovirus (CMV), Epstein– Barr virus (EBV), and parvovirus B19 can have a direct effect EBV Bla cmv immunosuppressed on the blood (mononucleosis or anemia) or their presence in blood is associated with opportunistic infections in immunosuppressed patients Infectious Mononucleosis/Epstein–Barr Virus Overview Most cases of mononucleosis are caused by EBV, a member of the herpesvirus family, which infects B lymphocytes and causes them to proliferate rapidly m ultiply This in turn stimulates the proliferation of cytotoxic T cells that control the active infection but do not eradicate the latent state Spread Although infection with EBV is extremely common, the majority of individuals have usually asymptatic asymptomatic infections Symptoms Patients with infectious mononucleosis typically present with fever, sore throat, and typicalvirus enlarged cervical lymph nodes s.fi Cancer In addition to mononucleosis, EBV is associated with two types of human tumor (Burkitt lymphoma and nasopharyngeal carcinoma) and is responsible for lymphoproliferative disorders in patients with severe immunosuppression following organ transplantation or AIDS. oiiiiiigiiiirinon It also causes oral hairy leukoplakia in HIV-infected patients Diagnosis Large, atypical lymphocytes (cytotoxic T cells) are usually present in peripheral blood smears of patients with infectious mononucleosis caused by EBV, but they are also found in many other infections The diagnosis of EBV-associated infectious mononucleosis is usually confirmed by a HF positive serum heterophile antibody test that detects the presence of antibodies that kissingdisease agglutinate horse or cow erythrocytes The heterophile test is often negative in young children or in patients with atypical children be presentations; EBV-specific serologic tests are especially important in establishing the inyoung neg diagnosis in these situations Quantitation of EBV DNA in peripheral blood is important in the diagnosis and it management of EBV-associated lymphoproliferative disease in solid organ and bone marrow transplant recipients immunoc Cytomegalovirus 1euoyjleuk youareFATmega it Overview CMV causes several clinical syndromes. It infects leukocytes, where it remains latent in ma immunocompetent individuals but readily reactivates in immunosuppressed individuals Demographics CMV is a leading cause of opportunistic infections in transplant recipients and AIDS patients s iiiiiiii In transplant recipients, it often presents as a nonspecific febrile illness, but it can also cause more invasive infections including ○ Esophagitis ○ Hepatitis ○ Colitis ○ Pneumonitis canspreadtobabyfrom ○ Retinitis, particularly in severely immunocompromised patients CMV is also the most common congenital viral infection. preggoGama It affects approximately 40,000 infants born each year in the United States Hematogenous spread appears to be responsible for transmission of the virus to the fetus fromboobiemilk Most congenital infections occur when the mother has a primary CMV infection during the pregnancy Neonates can also acquire the infection from maternal breast milk. Approximately 10% of infants congenitally infected with CMV are symptomatic at birth. Signs and Symptoms Common sites of involvement are ○ Liver ○ Spleen don'tJudge guysiam manic ○ Lungs ○ Central nervous system (CNS) Although most congenitally infected infants are asymptomatic at birth, approximately 10% to 15% will develop later problems such as ○ Hearing loss ○ Other neurologic problems. iii In children and young adults, primary CMV infection can cause a mononucleosis-like illness Treatment Because specific antiviral therapy is available for treatment of these infants, rapid detection of CMV infection is necessary Diagnosis The detection of CMV in blood and tissues generally correlates with active disease, whereas detection of CMV in urine is not necessarily diagnostic of active CMV disease, PCR even in immunocompromised patients Quantitative PCR assays of CMV DNA in blood (viral load assays) are more useful than qualitative assays serology High levels of CMV correlate with increased risk of serious opportunistic infections in a variety of organs; however, the interpretation of CMV viral loads depends on the underlying condition (solid organ transplant vs. hematopoietic stem cell transplant vs. AIDS) Congenital CMV infection is established when CMV is isolated from the urine of neonates who are less than 3 weeks of age CMV serology is used to determine whether donors and/or recipients are latently infected with CMV This has important implications for preventing subsequent infections. For example, a seronegative individual who receives a transplant from a seropositive donor has the highest risk of developing CMV infection Parvovirus B19 Overview A small single-stranded DNA virus that is transmitted by respiratory droplets droplets resp Demographics It is a common cause of infection in children in whom it causes a distinctive rash known as I stn diseasePause Anemia ikthatfifth disease. In young adults, it often causes a significant arthropathy joint pausecan'tmove pain An unusual feature of this virus is that it replicates in erythroid precursor cells and causes a temporary cessation of RBC production until the virus is cleared by the immune system In normal hosts this has little, if any, consequence, but in patients who have a chronic hemolytic anemia such as sickle cell disease or hereditary spherocytosis, parvovirus B19  infection causes a transient aplastic crisis in which there is a profound drop in the hematocrit Parvovirus B19 can also cause chronic anemia in immunocompromised patients who are unable to clear the virus. Intrauterine infection of the fetus can cause a severe anemia that leads to congestive failure and hydrops fetalis Diagnosis Acute parvovirus infection can be confirmed by demonstration of IgM antibodies or detection of viral DNA by PCR During a transient aplastic crisis, the reticulocyte count decreases to