Hematology and Oncology Flashcards
Erythrocyte
Carries O2 to tissues and CO2 to lungs. Anucleate and biconcave, with large surface area-to-volume ratio for rapid gas exchange. There lifespan is 120 days. Source of energy is glucose (90% used in glycolysis, 10% used in HMP shunt). Membrane contains Cl-/HCO3- antiporter, which allows RBCs to export HCO3- and transport CO2 from the periphery to the lungs for elimination. Eryth=red; cyte=cell.
Erythrocytosis
polycythemia; an increase hematocrit
Anisocytosis
varying sizes of RBCs
Poikilocytosis
varying shapes of RBCs.
Reticulocyte
an immature RBC; reflects erythroid proliferation.
Thrombocyte
Platelet. Involved in primary hemostasis. Small cytoplasmic fragment derived from megakaryocytes. Life span of 8-10 days. When activated by endothelial injury, aggregates with other platelets and interacts with fibrinogen to form platelets and interacts with fibrinogen to form platelet plug. Contains dense granules (ADP and Ca) and alpha granules (vWF and fibrinogen). Approximately 1/3 of platelet pool is stored in the spleen. Thrombocytopenia or a decrease in platelet function results in petechiae. vWF receptor binds GpIb. Fibrinogen receptor binds GpIIb/IIIa.
Leukocyte
Divided into granulocytes (neutrophil, eosinophil, basophil) and mononuclear cells (monocytes, lymphocytes). Responsible for defense against infections. Normally 4,000-10,000 cells/mm3.
WBC differential
Neutrophils: 54-62%. Lymphocytes: 25-33%. Monocytes: 3-7%. Eosinophils: 1-3%. Basophils: 0-0.75%.
Neutrophil
Acute inflammatory response cell. Increased in bacterial infections. Phagocytic. Multilobed nucleus. Specific granules contain SLP, collagenase, lysozyme, and lactoferrin. Azurophilic granules (lysosomes) contain proteinases, acid phosphatase, myeloperoxidase, and beta-glucuronidase. Hypersegmented polys (5 or more lobes) are seen in vitamin B12/ folate deficiency. An increase in band cells (immature neutrophils) reflect states of increased myeloid proliferation (bacterial infections, CML). Important neutrophil chemotactic agents: C5a, IL-8, LTB4, Kallikerin, platelet-activating factor.
Monocyte
Differentiates into macrophages in tissues. Large, kidney shaped nucleus. Extensive frosted glass cytoplasm. Mono=one (nucleus); cyte=cell.
Macrophage
Phagocytoses bacteria, cellular debris, and senescent RBCs. Long life is tissues. Macrophages differentiate from circulating blood monocytes. Activated by gamma-interferon. Can function as antigen-presenting cell vis MHC II. Important component of granuloma formation (eg TB, sarcoidosis). Lipid A from bacterial LPS binds CD14 on macrophages to initiate septic shock.
Eosinophil
Defends against helminthic injections (major basic protein). Bilobate nucleus. Pack with large eosinophilic granules of uniform size. Highly phagocytic for antigen-antibody complexes. Produces histaminase and major basic protein (MBP, a helminthotoxin).
Causes of eosinophilia
Neoplasia, Asthma, Allergic processes, Chronic adrenal insufficiency, Parasites (invasive) NAACP.
Basophil
Mediates allergic reaction. Densely basophilic granules contain heparin (anticoagulant) and histamine (vasodilator). Leukotrienes synthesized and released on demand. Basophilic is when stained with basic stains. Basophilia is uncommon, but can be a sign of myeloproliferative disease, particularly CML.
Mast cell
Mediates allergic reactions in local tissues. Mast cells contain basophilic granules and originate from the same precursor as basophils but are not the same cell type. Can bind the Fc portion of IgE to membrane. IgE cross-links upon antigen binding, causing degranulation, which releases histamine, heparin, and eosinophil chemotactic factors. Involved in type I hypersensitivity reactions. Cromolyn sodium prevents mast cell degranulation (used for asthma prophylaxis).
Dendritic cell
Highly phagocytic APC. Functions as link between innate and adaptive immune systems. Expresses MHC class II Fc receptors on surface. Called Langerhans cell in the skin.
Lymphocyte
Refers to B cells, T cells, and NK cells. B cells and T cells mediate adaptive immunity. NK cells are part of the innate immune response. Round, densely staining nucleus with small amount of pale cytoplasm.
B cell
Part of the humoral immune response. Originates from stem cells in bone marrow and matures in marrow. Migrates to peripheral lymphoid tissue (follicles of lymph nodes, white pulp of spleen, unencapsulated lymphoid tissue). When antigen is encountered, B cells differentiate into plasma cells (which produce antibodies) and memory cells. Can functions as an APC via MHC II. They have CD19, CD21, CD20. B=Bone marrow
T cell
Mediates cellular immune response. Originates from stem cells in the bone marrow, but matures in the thymus. T cells differentiate into cytotoxic T cells (express CD8, recognize MHC I), helper T cells (express CD4, recognize MHC II), and regulatory T cells. CD28 (co-stimulatory signal) necessary for T-cell activation. The majority of circulating lymphocytes are T cells (80%). T is for Thymus. CD4+ helper T cells are the primary target of HIV. MHCxCD=8 (eg MHC 2 x CD4=8, and MHC 1 x CD8=8).
Plasma cell
Produces large amounts of antibody specific to a particular antigen. Clock-face chromatin distribution, abundant RER, and well-developed Golgi apparatus. Multiple myeloma is a plasma cell cancer.
Group A blood
Group A antigens on RBC surface. Antibodies are IgM anti-B. If a patient receive B or AB, they have a hemolytic reaction.
Group B blood
Group B antigens on RBC surface. Antibodies are IgM anti-A. If a patient receive A or AB, they have a hemolytic reaction.
Group AB blood
Group A and B antigens on RBC surface. There are no antibodies. They are universal recipients of RBCs. If a patient receive B or AB, they have a hemolytic reaction.
Group O blood
No group antigens. They are universal donor of RBCs. Antibodies are IgM anti-B and anti-A. If a patient receive any non O blood, they have a hemolytic reaction.
Rh positive blood
There are Rh (D) antigens and no anti-D antibody.
Rh negative blood
There are no Rh (D) antigens. There are IgG anti-D. Rh negative mothers need to be treated with Rh (D) immunoglobulin after each pregnancy to prevent anti-D IgG formation.
Hemolytic disease of the newborn
IgM does not cross the placenta but IgG does cross placenta. Rh negative mothers exposed to fetal Rh positive blood (often during delivery) may make anti-D IgG. In subsequent pregnancies, anti-D IgG crosses the placenta causes hemolytic disease of the newborn (erythroblastosis fetalis) in the next fetus that is Rh positive. Prevented by administration of RhoGAM to Rh negative pregnant women during the third trimester, which prevents maternal anti-Rh IgG production. Rh negative mothers have anti-D IgG only if previously exposed to Rh positive blood.
Intrinsic coagulation pathway
The intrinsic pathway begins with Factor XII (Hageman factor), which is activated by subendothelial collagen. Factor XII activates factor XI, which activates IX. Factor IX requires Ca and VIII. Factor IX also activates factor X, the beginning of the combined pathway.
Extrinsic coagulation pathway
The extrinsic pathway begins with Factor VII (requires Ca), which is activated by tissue factor (aka Factor III or thromboplastin). Factor VII also activates factor X, the beginning of the combined pathway.
Combined coagulation pathway
The intrinsic and extrinsic pathway converge with the activation of Factor X. The common pathways begins with Factor X, and ends with the formation of fibrin polymers. Factor X requires Ca and V as cofactors and activates prothrombin to thrombin, which cleaves fibrinogen to form fibrin.
Fibrinolysis
Fibrinolysis is the dissolution of a clot. The clot releases the enzyme plasminogen activator (tPA), which activates plasminogen to plasmin. Plasmin lyses fibrinogen and fibrin, dissolving the clot slowly. tPA is inhibited by aminocaproic acid. It is activated by alteplase, reteplase, steptokinase, and tenecteplase.
Anticoagulants that target factor X
Includes LMWH (greatest efficacy), heparin, direct Xa inhibitors (apixaban, rivaroxaban), fondaparinux.
Anticoagulants that target factor II (thrombin)
Includes heparin (greatest efficacy), LMWH (dalteparin, enoxaparin), direct thrombin inhibitors (argatroban, bivalirudin, dabigatran).
Kinin cascade
Kallikrein converts HMWK to bradykinin, which causes an increase in vasodilation, permeability, and pain. HMWK also activates XII, the first step of the intrinsic coagulation pathway.
Vitamin K as a procoagulation cascade components
Oxidized vitamin K get converted to reduced vitamin K by epoxide reductase. Vitamin K acts as a cofactor for factors II, VII, IX, X, C, S. Warfarin inhibits the enzyme vitamin K epoxide reductase. Neonates lack enteric bacteria, which produce vitamin K. A vitamin K deficiency decreases synthesis of factors II, VII, IX, C, protein C, and protein S. vWF carries/ protects VIII.
Protein C
Protein C is activated by thrombin-thrombomodulin complex from endothelial cells, which cleaves and inactivates V and VIII with protein S as a cofactor. Factor V Leiden mutation produces a factor V resistant to inhibition by activated protein C.
tPA
tPA converts plasminogen to plasmin, which causes fibrinolysis by cleaving the fibrin mesh and destruction of coagulation factors.
Antithrombin
It inhibits activated forms of factors II, VII, IX, X, XI, XII. Heparin enhances the activity of antithrombin. The principal targets of antithrombin include thrombin and factor X.
Platelet plug formation (primary hemostasis)
Endothelial damage leads to a transient vasoconstriction via neural stimulation reflex and endothelin (released from damaged cell). vWF binds to exposed collagen. vWF is from Weibel-Palade bodies of endothelial cells and alpha-granules of platelets. Platelets bind vWH via GP1b receptor at the site of injury only, causing platelets to undergo conformational change. Platelets release ADP and Ca (necessary for coagulation cascade) and TXA2 (a derivative of platelet cyclooxygenase. ADP helps platelet adhere to endothelium. ADP binds to a receptor, which induces GpIIb/GpIIIa expression at platelet surface. Fibrinogen binds GPIIb/GpIIIa receptors and links platelets. Temporary plug stops bleeding but it is unstable and can easily be dislodged.
Pro-platelet aggregation factors
TXA2 (released by platelets, aspirin inhibits cyclooxygenase), decreased blood flow, and increased platelet aggregation.
Anti- platelet aggregation factors
PGI2 and NO (released by endothelial cells), increased blood flow, decreased platelet aggregation.
Drugs that inhibit ADP-induced expression of GpIIb/GpIIIa
Clopidogrel, prasugrel, and ticlopidine
Drugs that inhibit GpIIb/GpIIIa directly
Abciximab, eptifibatide, and tirofiban
Drugs that activate vWF to bind GpIb
Ristocetin. Failure of agglutination with ristocetin assay occurs in von Willebrand disease and Bernard-Soulier syndrome.
Acanthocyte
A spur cell, a form of red blood cell that has a spiked cell membrane, due to abnormal thorny projections. It is associated with liver disease, abetalipoproteinemia. Acantho=spiny.
Basophilic stippling
Erythrocytes display small dots at the periphery. It is associated with lead poisoning.
Degamacyte
A bite cell. It is associated with G6PD deficiency
Elliptocyte
It is associated with hereditary elliptocytosis.
Macro-ovalocyte
An enlarged, oval-shaped erythrocytes (red blood cells). It is associated with megaloblastic anemia (also hypersegmented PMNs) and marrow failure.
Ringed sideroblast
An abnormal sideroblast with many iron granules in its mitochondria, found in a ring around the nucleus; seen in sideroblastic anemia.
Schistocyte
A helmet cell. It is associated with DIC, thrombotic thrombocytopenic purpura (TTP) and hemolytic-uremic syndrome (HUS), HELLP syndrome (Hemolysis. Elevated Liver enzymes. Low Platelet count.), mechanical hemolysis (eg heart valve prosthesis).
Spherocyte
Sphere-shaped RBC, associated with hereditary spherocytosis, drug-and infection-induced hemolytic anemia.
Dacrocyte
Teardrop cell, associated with bone marrow infiltration (eg myelofibrosis). RBC sheds a tear because its mechanically squeezed out of its home in the bone marrow.
Target cell
It is associated HbC disease, Asplenia, Liver disease, and Thalassemia. (HALT, said the hunter to his target)
Heinz bodies
RBC with inclusions within red blood cells composed of denatured hemoglobin. Oxidation of Hb-SH groups to S-S causes Hb precipitation (Heinz body), with subsequent phagocytic damage to RBC membrane creating bite cells. It is associated with G6PD deficiency; Heinz body-like inclusions seen in alpha thalassemia.
Howell-Jolly bodies
Basophilic nuclear remnants found in RBCs. They are normally removed by splenic macrophages. They are seen in patients with functional hyposplenia or asplenia.
Microcytic anemia
Iron deficiency (late), anemia of chronic disease (late), thalassemias, lead poisoning, siderblastic anemia (late).
Nonhemolytic normocytic anemia
anemia of chronic disease, aplastic anemia, chronic kidney disease, iron deficiency (early).
Hemolytic normocytic anemia
Intrinsic causes include RBC membrane defect (hereditary spherocytosis), RBC enzyme deficiency (G6PD and pyruvate kinase), HbC defect, paroxysomal nocturnal hemoglobinuria, sickle cell anemia. Extrinsic causes include autoimmune, microangiopathic, macroangiopathic, and infections.
Megaloblastic macrocytic anemia
Folate deficiency, B12 deficiency, orotic aciduria
Non-megaloblastic macrocytic anemia
Liver disease, alcoholism, reticulocytosis.
Iron deficiency anemia
Microcytic, hypochromic anemia. A decrease in iron can occur due to chronic bleeding (eg GI loss, menorrhagia), malnurtion/absorption disorders, or an increase in demand (pregnancy), which causes there to be a decrease in the final step of heme synthesis. Findings include a decrease in iron, an increase in TIBC, a decrease in ferritin. Patients will have fatigue, conjunctival pallor, spoon nails (koilonychia). There will be microcytosis and hypochromia (central pallor). It may manifest as Plummer-Vinson syndrome.
Plummer-Vinson syndrome
It occurs due to iron deficiency anemia. It manifest as a triad of iron deficiency anemia, esophageal webs, and atrophic glossitis.
alpha-thalassemia
Microcytic, hypochromic anemia. The defect is a deletion of the alpha globin gene, which leads to a decrease in alpha globin synthesis. A cis deletion (αα/–) is prevalent in the Asian populations; trans deletion (α-/α-) prevalent in African populations. 1-2 allele deletion is less clinically severe anemia.
Hb Barts
4 alpha deletions. There is no alpha globin. Excess gamma-globin forms gamma four (Hb Barts). It is incompatible with life and leads to hydrops fetalis.
Hb H disease
This is 3 alpha deletion. There is very little alpha globin. Excess beta globin forms beta-4 (HbH).
Beta-thalassemia
Microcytic, hypochromic anemia. There are point mutations in the splice sites and promoter sequences, which leads to a decrease in beta-globin synthesis. There is high prevalence in mediterranean populations
Beta-thallassemia minor
Heterozygote in the beta gene. The beta chain is underproduced. It usually asymptomatic. It is diagnosed with an increase in HbA2 (above 3.5%) on electrophoresis.
Beta-thallassemia major
Homozygote in the beta gene. The beta chain is absent leading to severe anemia, requiring blood transfusions, which can lead to secondary hemochromatosis. On blood smear, there are anisocytosis, poikilocytosis, target cells, microcytosis, and schistocytes. Marrow expansion also occurs leading to skeletal deformities (crew cut on skull x-ray and chimunk facies). Extramedullary hematopoiesis, which leads to hepatosplenomegaly. This causes an increase risk of parvovirus B19-induced aplastic crisis. Major thallassemia also causes an increase in HbF (alpha2, gamma2). HbF is protective in the infant and disease becomes symptomatic only after 6 months.
Hb S/ Beta-thalassemia heterozygote
It causes mild to moderate sickle cell disease depending on amount of beta-globin production.
Lead poisoning anemia
Microcytic, hypochromic anemia. Lead inhibits the ferrochelatase and ALA dehydrogenase, leading to a decrease in heme synthesis and an increase in RBC protoporphyrin. It also inhibits rRNA degradation, causing RBCs to retain aggregates of rRNA, causing basophilic stippling. There is high risk in old houses with chipped paint. LEAD: Lead Lines gingiva (burton lines) and on metaphyses of long bones on x-ray. Encephalopathy and Erythrocyte basophilic stippling. Abdominal colic and sideroblastic Anemia. Drops- wrist and foot drop. Dimercaprol and EDTA are 1st line of treatment. Succimer used for chelation for kids. (It SUCks to be kid who eats lead).
Sideroblastic anemia
Microcytic, hypochromic anemia. Due to a defect in heme synthesis. Inheritable causes include X-linked defect in delta-ALA synthase gene. Other causes include myelodysplastic syndromes (aquired) and reversible (alcohol is most common; also vitamin B6 deficiency, copper deficiency, isoniazid). Ringed sideroblasts (with iron-laden, Prussian blue-stained mitochondria) are seen in bone marrow. Other findings include an increase in iron, normal/ decrease in TIBC, increase in ferritin. Treatment includes pryidoxine (B6, cofactor for delta-ALA synthase).
Megaloblastic anemia
Macrocytic anemia. It occurs due to impaired DNA synthesis, leading to maturation of nucleus of precursor cells in bone marrow delayed relative to maturation in cytoplasm. Findings include RBC macrocytosis, hypersegmented neutrophils, and glossitis.
Folate deficiency
Megaloblastic macrocytic anemia. Causes include malnutrition (eg alcoholics), malabsorption, drugs (eg methotrexate, trimethoprim, phenytoin), and increase requirement (eg hemolytic anemia and pregnancy). Findings include an increase in homocysteine and normal methylmalonic acid. There are no neurologic symptoms (vs B12 deficiency).
B12 (cobalamin) deficiency
Megaloblastic macrocytic anemia. Causes include insufficiency intake (eg veganism), malabsorption (eg Crohn disease), pernicious anemia, Diphyllobothrium latum (fish tapeworm), gastrectomy. Findings include an increase in homocysteine and methylmalonic acid. Neurologic symptoms include subacute combined degeneration (due to involvement of B12 in fatty acid pathways and myelin synthesis), which affects the spinocerebellar tract, lateral corticospinal tract, and dorsal column dysfunction.
Orotic aciduria
Megaloblastic macrocytic anemia. Inability to convert orotic acid to UMP (de novo pyrimidine synthesis pathway) due to a defect in UMP synthase. It is autosomal recessive. It presents in children as failure to thrive, developmental delay, and megaloblastic anemia refractory to folate and B12. There is no hyperammonemia (vs ornithine transcarbamylase deficiency, which has an increase orotic acid with hyperammonemia). Findings include orotic acid in urine. Treatment includes uridine monophosphate to bypass mutated enzyme.
Nonmegaloblastic macrocytic anemias
Macrocytic anemia in which DNA synthesis is unimpaired. Causes includes alcoholism, liver disease, hypothyroidism, and reticulocytosis. Findings include, RBC macrocytosis without hypersegmented neutrophils.
Normocytic normochromic anemia
Normocytic, bormochromic anemias are classified as nonhemolytic or hemolytic. The hemolytic anemias are further classified according to the cause of the hemolysis (intrinsic vs extrinsic to the RBC) and by location of the hemolysis (intravascular vs extravascular).
Intravascular hemolysis
Normocytic normochromic anemia. Findings include a decrease in haptoglobin, an increase in LDH, schistocytes, and reticulocytes on blood smear. Characteristic include hemoglobinuria, hemosiderinuria, and urobilinogen in urine. Notable causes include mechanical hemolysis (eg prosthetic valve), paroxysmal nocturnal hemoglobinuria, microangiopathic hemolytic anemias.
Extravascular hemolysis
Normocytic normochromic anemia. Macrophages in spleen clear RBCs. Findings include spherocytes in peripheral smear, an increase in LDH, no hemoglobinuria. hemosiderinuria, an increase in unconjugated bilirubin, which can cause jaundice.
Anemia of chronic disease
Nonhemolytic, normocytic anemia. Inflammation leads to an increase in hepcidin, which is released by the liver and binds ferroportin on intestinal mucosal cells and macrophages, thus inhibiting iron transport. The increase in hepcidin causes a decrease in release of iron from macrophages. It is associated with conditions like SLEm rheumatoid arthritis, neoplastic disorders, and chronic kidney disease. Findings include a decrease in iron and TIBC and an increase in ferritin. It can become microcytic anemia. Treatment includes EPO in chronic kidney disease only.
Aplastic anemia
Normocytic normochromic anemia. It is caused by failure or destruction of myeloid stem cells due to: radiation and drugs (benzene, chloramphenicol, alkylating agents, antimetabolites); viral agents (parvocirus B19, EBV, HIV, HCV), Faconi anemia (DNA repair defect); idiopathic (immune mediated, primary stem cell defect), may follow acute hepatitis. Pancytopenia is characterized by severe anemia, leukopenia, and thrombocytopenia. There is normal cell morphology, but hypocellular bone marrow with fatty infiltration (dry bone marrow tap). Symptoms include malaise, pallor, purpura, mucosal bleeding, petechiae, and infection. Treatment includes withdrawal of offending agent, immunosuppressive regimens (eg antit-hymocyte globulin, cyclosporine), bone marrow allograft, RBC/platelet transfusion, bone marrow stimulation (eg GM-CSF).
Hereditary spherocytosis
Extravascular hemolytic normocytic intrinsic anemia. It occurs due to a defect in proteins interacting with RBC membrane skeleton and plasma membrane (eg ankyrin, band 3, protein 4.2, spectrin). This results in small round RBCs with less surface area and no central pallor (resulting in an increase in MCHC and red cell distribution width), which causes premature removal by spleen. Findings includes splenomegaly, aplastic crisis (eg due to parvovirus B19 infection). Labs include a positive osmotic fragility test and a normal to decrease in MCV. with an abundance of cells. Treatment includes splenectomy.
G6PD deficiency
Extravascular and intravascular intrinsic hemolytic normocytic anemia. It is the most common enzymatic disorder of RBCs. It is x-linked recessive. A defect in G6PD leads to a decrease in glutathione, which makes RBCs more susceptible to oxidant stress. Hemolytic anemia occurs following oxidant stress (eg sulfa drugs, antimalarials, infections, fava beans). Clinical findings include back pain, hemoglobinuria a few days after oxidant stress. A blood smear shows RBCs with heinz bodies and bite cells. “Stress makes me eat bites of fava beans with Heinz ketchup.
Pyruvate kinase deficiency
Extravascular intrinsic hemolytic normocytic anemia. It is autosomal recessive. A defect in pyruvate kinase, which catalyzes the transfer of a phosphate group from phosphoenolpyruvate (PEP) to ADP, yielding one molecule of pyruvate and one molecule of ATP, decreases ATP, causing RBCs to be rigid. It presents as hemolytic anemia in a newborn.
HbC defect
Extravascular intrinsic hemolytic normocytic anemia. Occurs due to a glutamic acid to lysine mutation in beta-globlin. Patients with HbSC (one of each mutant gene) have milder disease than HbSS.
Paroxysomal nocturnal hemoglobinuria
Intravascular intrinsic hemolytic normocytic anemia. An increase in complement-mediated RBC lysis due to an impairment in the synthesis of GPI anchor for decay-accelerating factor that protects RBC membrane from complement. This is due to an acquired mutation in a hematopoietic stem cell. There are also an increase incidence of acute leukemias. There is a triad of negative coombs hemolytic anemia, pancytopenia, and venous thrombosis. Labs show negative CD55/59 RBCs on flow cytometry. Treatment includes eculizumab (terminal complement inhibitor).
Sickle cell anemia
Extravascular intrinsic hemolytic normocytic anemia. HbS point mutation causes a single amino acid replacement in the beta chain (a substitution of glutamic acid with valine). Low O2, high altitude, or acidosis can precipitates sickling, which occurs due to deoxygenated HbS polymerization. This causes anemia and vaso-occlusive disease. Newborns are initially asymptomatic due to high levels of HbF and low levels of HbS. Heterozygotes (sickle cell trait) are resistant to malaria. 8% of Africans Americans carry an HbS allele. Xray will show a crew cut on the skull due to marrow expansion from an increase in erythropoiesis (this is also seen in thalassemia). Complications in sickle cell disease include: aplastic crisis (due to parvovirus B19), autosplenectomy (showing Howell-Jolly bodies with blood smear) that has an increase risk of infection from encapsulated bacteria, splenic infarct/ sequestration crisis, salmonella osteomyelitis, painful crises (a vaso-occlusive event, which can manifest as dactylitis (painful swelling of hands/ feet), acute chest syndrome, avascular necrosis, or stroke), renal papillary necrosis (due to a decrease in PO2 in papilla) and microhematuria (medullary infarcts). Diagnosis is based on hemoglobin electrophoresis. Treatment includes hydroxyurea (which increases HbF) and hydration.
Autoimmune hemolytic anemia
Extrinsic hemolytic normocytic anemia. Includes warm and cold agglutination. Many warm and cold AIDAs are idiopathic in etiology. Autoimmune hemolytic anemias are usually Coombs positive.
Warm agglutinin
Autoimmune hemolytic anemia, IgG mediated. Chronic anemia is seen in SLE and CLL and with certain drugs (eg alpha-methyldopa). Warm weather is Great.
Cold agglutinin
Autoimmune hemolytic anemia, IgM mediated. It is an acute anemia triggered by the cold. It is seen in CLL, Mycoplasma pneumonia infections, and infectious Mononucleosis (cold weather is MMMiserable).
Direct Coombs test
Anti-Ig antibody (Coombs reagent) is added to patients blood. RBCs agglutinate if RBCs are coated with Ig.
Indirect Coombs test
Normal RBCs are added to patient’s serum. If serum has anti-RBC surface Ig, RBCs will aggluntinate when Coombs reagent is added.
Microangiopathic anemia
Extrinsic hemolytic normocytic anemia. RBCs are damaged when they are passing through obstructed or narrowed vessel lumina. It is seen in DIC, TTP/HUS, SLE, and malignant hypertension. Schistocytes (helmet cells) are seen on blood smear due to mechanical destruction of RBCs.
Infections causing anemia
Extrinsic hemolytic normocytic anemia. Malaria or babesia among others can cause an increase destruction of RBCs.
Lab values seen in iron deficient anemia
A decrease in serum iron, an increase in transferrin or TIBC, a decrease in ferritin, and a large decrease in the precent of transferrin saturation (serum iron/ TIBC)
Lab values seen in anemia in chronic disease
A decrease in serum iron, a decrease in transferrin or TIBC, an increase in ferritin, and no change in the precent of transferrin saturation (serum iron/ TIBC)
Lab values seen in anemia due to hemochromatosis
An increase in serum iron, a decrease in transferrin or TIBC, an increase in ferritin, and a large increase in the precent of transferrin saturation (serum iron/ TIBC)
Lab values seen in anemia due to pregnancy or OCP use
No change in serum iron, an increase in transferrin or TIBC, no change in ferritin, and a decrease in the precent of transferrin saturation (serum iron/ TIBC)
Transferrin
Transports iron in blood.
Total iron binding capacity (TIBC)
Indirectly measures transferrin.
Ferritin
It is the primary iron storage protein of body.
Corticoidsteroid effect on blood cells
Corticosteroids cause neutropenia, despite causing eosinophenia and lymphopenia. Corticosteroids decrease activation of neutrophil adhesion molecules, impairing migration out of the vasculature to sites of inflammation. in contrast, corticosteroids sequester eosinophils in lymph nodes and cause apoptosis of lymphocytes.
delta- aminolevulinic acid synthase
The first step in heme synthesis, also the rate limiting step. It catalyzes glycine and succinyl-CoA into delta aminolevulinic acid, with vitamin B6 as a cofactor. It is inhibited by glucose and heme. It is mutated in sideroblastic anemia.
