Leonard M. Miller School of Medicine
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This 14 page Class Notes was uploaded by Hanyao Foong on Saturday February 7, 2015. The Class Notes belongs to 1001 at Leonard M. Miller School of Medicine taught by in Winter2015. Since its upload, it has received 90 views.
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Date Created: 02/07/15
Hematology Lecture WI Dr Whitcomb 30 January 2012 The Topic of This Lecture ls Peripheral Blood Cells gt Peripheral blood smears use a Wright stain with RBCs 5106pL WBCs 5103pL and platelets 2105pL o Platelets lack nuclei They39re just circulating fragments of cellular cytoplasm that help in hemostasis They maintain integrity of small blood vessels by repairing sites of damage with plugs 0 An increased count of any of these is termed cytosis When decreased it39s penia The exceptions to this are anemia low RBCs and neutrophilia high granulocytes Thrombocytopenia 9 excess bleeding Leukopenia 9 increased risk of infections gt Leukocytes WBCs are lymphocytes monocytes and granulocytes neutrophils eosinophils amp basophils o Neutrophils PMNs have segmented nuclei They only circulate for a few days Before they segment they have a cigarshaped nucleus These immature cells are quotbandsquot 0 Eosinophils have two nuclei and abundant cytoplasm Basophils are chock full of granules Eosinophil counts are increased in intracellular parasitic infections and allergic responses 0 Monocytes are the largest leukocytes They become macrophages and phagocytize stuff 0 Lymphocytes are comprised almost entirely of nuclei They circulate for months to years 0 The differential is the percentage of each type of leukocyte within the WBC count For absolute counts multiple the WBC diff 100 Think of how we de ne neutropenia gt Peripheral blood cells are derived from hemat0poietic precursors in the medullarv tissue of cancellous bone 0 Red marrow is found throughout bones in children and the epiphyses of long adult bones Adults also have hematopoiesis in central bones ribs vertebra and the pelvic girdle A histologic section will show precursor cells and fat within bony trabeculae o The most immature cell type is a myeloblast They eventually differentiate and mature Progranulocytes myelocytes and metamyelocytes shouldn39t be seen in peripheral blood gt Erythrocytes undergo a series of mitoses such that those in the peripheral blood of adults lack nuclei 0 Nucleated RBCs should ONLY be seen in the peripheral blood of newborns It39s a red ag in adults gt Blood disorders are characterized by alterations in production from bone marrow or removal Hematology Lecture WI Dr Beardface 30 January 2012 The Topic of This Lecture ls Hematopoiesis gt Bone marrow smears show developing cells They39re best obtained from the posterior ilium or sternum 0 Additionally megakaryocytes are seen Each one is a precursor to thousands of platelets 0 An examination involves both a bone marrow aspirate smear and a bone core biopsy gt On a biopsy there should be roughly half fat cells and half hematopoietic cells 0 Active areas of bone marrow are hypercellular less fat Hypocellular areas are mostly fat 0 Biopsies may also reveal granulomas if there s Tb or metastases of cancers gt As WBCs and RBCs develop they divide Example each myeloblast generates multiple promyelocytes 0 There39s an ampli cation of numbers throughout maturation Few basts 9 lots of leukocytes 0 Stem cells may become either myeloid or lymphoid with the latter producing only lymphocytes Myeloid cells may become granulocytes macrophages erythrocytes or platelets 0 Stem cells are selfrenewing For each mitosis one cell is committed the other remains totipotent Daughter cells are clones of their parents having retained the stem cell genome o All hematopoietic stem cells HSCs have the protein CD34 allowing for idenU cann o Hematopoiesis is appropriate after a hemorrhage increase in altitude infection COPD etc gt jAKs are a type of tvrosine kinase They undergo autophosphorylation when a ligand binds to the receptor o If erythropoietin Epo binds to a stem cell at a jAK it starts the pathway for RBC production 0 Activated jAKs promote and activate STATs transcription factors that translocate to the nucleus Phosphorylated STATs increase transcription of selected genes for hematopoiesis o A mutation in IAK2 leads to inappropriate production of RBCs due to constitutive activation All of the excessive RBCs carry the jAK2 mutation de ning polycythemia vera gt Chronic myelogenous leukemia CML is due to a fusion gene of bcr abl generated by t922 0 As in the jAK2 mutation every excessive clonal granulocyte will carry the abnormal gene I don39t have any notes for Temple39s lecture on hemoglobinopathies It was only 15 minutes long anyway Hematology Lecture w Drs Whitcomb amp Temple 31 January 2012 The Topic of This Lecture ls Hemolytic Anemias gt Hematocrit HCT is the proportion of blood occupied by RBCs It39s 45 for men and 40 for women 0 If the RBCs are lysed hemoglobin Hb can be quantitated It should be 15 men or 13 women The general rule of thumb for an H and H is that HCT is 3x the Hb gt Flow cytometry pushes cells in a single le line They variously scatter light allowing for cell counts gt RBCs typically live for about 120 days They are removed by histiocytes in splenic quotcords of Bilrothquot o The rate of production must match the rate of removal we replace about 1 of our RBCs daily gt When RBCs are removed at a rate beyond what marrow can compensate for there39s hemolytic anemia 0 Sections of bone marrow with show erythroid hyperplasia with excessive erythroid precursors 0 Still the anemia from decreased RBC lifespans is not as severe as it would be without marrow gt Reticulocytes are slightly immature RBCs which contain residual rRNA strands 0 These can be counted using a special stain A reticulocvte count assesses bone marrow resoonse o In anemia an ideal reticulocyte count is 3 It must be corrected for based on the extent of anemia Corrected count HCT45 reticulocyte count Divide that by 2 if there39s polychromasia gt Hemolytic anemias may be from intrinsic RBC abnormalities something39s wrong with the RBCs o Intrinsic causes are defects in the membrane enzymes or hemoglobin itself 0 Morphology of RBCs can assist in diagnoses Spherocytes are from a membranooathv anlqrin They are slightly smaller and lack central pallor One cause is hereditary spherocytosis These abnormal RBCs spend more time in the spleen decreasing their I espans 0 Thus hereditary spherocytosis can be treated with a W Elliptocytes are slightly larger than normal RBCs They retain central pallor They39re from another membranopathy that39s caused by a defect in em Both hereditary membranopathies they re AD are identi ed by an osmotic fragility test 0 In G6PDD an XLR enzymopathy bluepurple inclusions Heinz bodies are seen on a special stain These are precipitates of oxidized hemodlobin that induce splenic cell removal bite cells 0 Sickle cell anemia thalassemia and malariaBabesia are all hemoglobinopathies o Poikilocytosis is the presence of abnormallv shaped RBCs spherocytes schistocytes etc gt Extrinsic causes of hemolytic anemia are immune disorders microangiopathy TI39P infections malaria o In autoimmune hemolytic anemia Ig antibodies bind to RBCs and turn them into Spherocytes Histiocytes interact with the Fc portion of antibodies and remove or damage the RBCs The direct Coombs test can identify the antibodies by using antihuman globulin It is onlv a suooestive test for diagnoses some RBCs carry antibodies for no reason Drugs can induce hemolysis penicillin type II methyldopa type II and guinidine type III Patients who have had multiple transfusions may develop alloimmunity to the transfused blood Cold agglutinin disease is an lgMmediated autoimmune hemolysis seen at body temps of 2831 C Mnemonic M Montana Maryland Massachusettsall cold G Georgia is warm Fetal Rh incompatibility occurs when blood from an Rh fetus mixes with an Rh mother s blood This is avoided by taking RhoGAM antiD globulin against fetal Rh Schistocytes are irregularly shaped and have sharp points some may even be triangular Mechanical fragmentation can be from 39I39I39P DIC calci c aortic stenosis severe burns Bhemoglobin must remain within cells as the iron ions are targets for oxidative damage 0 0 Also free hemoolobin basses readilv into urine as it does in hemolytic anemia RBCs lack nuclei but use glycolysis to generate ATP and NAD to maintain glycolytic potential In states of hemolysis bilirubin levels rise jaundice There may also be increased LDH or solenomeoalv Hematologv Lecture w Drs Whitcomb 63 Temple 31 Januarv 2012 The Topic of This Lecture ls Microcytic Anemias Anisocytosis is a variation in RBC size measured by the RBC distribution width RDW O O 0 Average RBC size is described as the mean corpuscular volume MCV It should be 80100 fL Mean corpuscular hemoglobin MCH is the average Hb in each RBC Hb10RBC normal 2530 Do If MCV is lt 80 and MCH lt 25 it39s a microcytic hypochromic anemia from a lack of Hb production If both are normal it39s normocytic And if MCV is gt 100 it39s macrocytic anemia gt The most common microcytic hypochromic anemia in the world is iron de ciency o It is identi ed by low serum Fe3 increased total ironbinding capacity TIBC and decreased ferritin Normally iron is stored in histiocytes with ferritin and it stains blue on bone marrow biopsy 0 That39s not so in iron de ciency anemia but bioosies aren39t needed for diagnosis TIBC is increased because transferrin levels are HIGH a key aspect of this anemia 0 Iron uptake is tightly regulated by the absorption rate At best it can be doubled We lose about 1 mo of iron per day in the skin and GI tract It s recycled from RBCs Dietary iron is absorbed in the proximal GI and only in acidic environments parietal cells 0 Iron is moved throughout the body by being bound to transferrin 0 Children are often iron de cient due to rapid growth inadequate diet or parasites hookworm In the elderly iron de ciency necessitates evaluation of the GI tract for malignancy 0 Iron de ciency anemia is treated with iron pills but they can cause black tarry stools and GI upset For rapid resolution of iron de ciency a parenteral shot of iron works very well gt Other causes are thalassemia anemia of chronic disease and hemoglobin E especially in SE Asia 0 In these diseases serum Fe3 is low but total ironbinding capacity is normal and ferritin is high Additionally there is plenty of iron in the bone marrow if it39s looked at 0 Recall from Temple39s lecture that a2thalassemia and mild Bthalassemia lookjust like iron de ciency Major Bthalassemia yields marked anisocytosis erythroid hyperplasia and iron OVERLOAD The body cannot excrete excess transfused iron so chelation may be necessary 0 Hemoglobin E involves a mutated Bglobin chain It looks similar to Bthalassemia Like sickle cell it39s just a point mutation For the boards know that it39s Glu 26Lys o Anemia of chronic disease is a cytokinemediated process that drives iron in blood into macrophages This is adaptive on the shortterm as it starves bacteria But over time it39s a problem Erythrocyte production eventually decreases and serum transferrin becomes LOW Hematologv Lecture w Drs Whitcomb 63 Temple 31 Januarv 2012 The Topic of This Lecture ls Macrocytic Anemias gt Macrocytic RBCs are usually oval with a normal color no polychromasia and normal central pallor o The only two causes we care about are folic acid de ciency and vitamin BlZ de ciency o In both of these the bone marrow paradoxically shows erythroid hyperplasia The developing erythroid cells are large and do not have condensed chromatin This is described as megaloblastic dyserythropoiesis the erythropoiesis is ineffective O o This and other myelodysplastic syndromes may be precursors to w However the reticulocyte count is low as many of the precursors yse before maturation This lysis results in markedly increased LDH levels LDH is lactate dehydrogenase In contrast to iron de ciency anemia a bone marrow biopsy is part of the workup for macrocytosis These de ciencies affect other cell lines noted as hypersegmented neutrophils and pancytopenia Megakaryocytes are also affected so there may be thrombocvt0penia too Macrocytic anemia is due to impaired DNA synthesis so chemotherapy can induce it lack of purines Folic acid de ciency is associated with acohoism or just a poor diet Reserves are fairly small 0 Folic acid is absorbed in the upper GI tract in the same places as iron It is treated orally with a pill and it is not associated with any neuropathy Conversely vitamin 312 de ciency takes years to develop due to vast stores It s not associated with diet 0 O 312 de ciency typically presents as a more severe anemia than foic acid de ciency Vitamin 312 requires intrinsic factor produced by gastric parietal cells in order to be absorbed Pernicious anemia describes a lack of intrinsic factor due to an autoimmune process It is absorbed in the terminal ileum so it has to pass by a whole lot of bacteria As such SIBO can cause BlZ de ciency as can the sh tapeworm DiphyIobothrium It causes neuropathy of the posterior columns vibration and proprioception and lateral ST tracts There may also be a loss of papillae most readin noticed as a depapillated tongue n pernicious anemia there39s achlorhydria increasing the risk for gastric carcinomas Administration of parental 312 not oral causes an immediate response in the bone marrow Still it ll take about a week for precursor cells to mature and get into blood Hematology Lecture WI Dr Temple 1 February 2012 The Topic of This Lecture ls Clinical Approach to Anemia gt The rst step when working up anemia is to determine if the reticulocyte count is approDriatelv elevated O 0 If the corrected count is gt 3 it39s hemolytic anemia Remember HCT45 reticulocyte count System signs of hemolysis are iaundice and Splenomedalv Labs show elevated LDH nonspeci c A peripheral smear will reveal spherocytes which typically signify hemolysis Haptoglobin exists to pick up free hemoglobin usually from the spleen and deliver it to the liver Since haptoglobin is degraded after each use stores will be rapidly depleted Immunemediated hemolysis is suggested but not diagnosed by a positive direct Coombs test Again nonimmune causes are defects in membranes enzymes or hemoglobin itself ln sickle cell there s also vasoocclusion of small vessels dactylitis and r infections Thalassemia is partly a hemolytic condition due to hemoglobin H HbH four 3 subunits Microangiopathic hemolysis fragmentation is seen in DIC 39ITP severe HTN aortic stenosis Drowning in fresh water induces hypotonicity so RBCs lyse as they pass through lungs gt If the reticulocyte count is low the MCV differentiates micro normo and macrocytic anemias gt The only macrocytic anemias are folic acid de ciency and 312 de ciency though drugs caninduceit O 0 Drugs that affect folic acid metabolism are MTX 6MP AZT TMP phenytoin and more It s really anything that impairs DNA synthesis and generates a megaloblastic dysplasia BlZ de ciency causes neuropathy due to a buildup of methylmalonic acid which damages myelin Both de ciencies cause hyperhomocysteinuria as homocysteine can39t be converted to methionine In fact the most common cause of excess homocysteine in the blood is a folate de ciency Homocysteine can damage endothelial cells promoting thrombosis Additionally hypersegmented neutrophils are pathognomonic for these de ciencies To de nitively diagnose BlZ de ciency recall the Schilling test or look for 1 methylmalonic acid gt Microcytic anemias are all hypochromic Again the most common cause is iron de ciency anemia O O 0 Iron de ciency anemia must be differentiated from thalassemia or anemia of chronic disease They look the same microscopically Iron studies provide the diagnosis In iron de ciency serum iron is low TIBC is high saturation is low and ferritin is low In anemia of chronic disease serum iron is low TIBC and saturation are low and ferritin is high The liver produces hepcidin which prevents release of iron to transferrin It39s trapped ln thalassemia all of the iron studies are normal There is no treatment available O cxthalassemia affects SE Asians and blacks Bthalassemia is blacks Greeks and Italians Hb electrophoresis is normal in d2thal but shows HbH in d3thal In Bthal there39s less HbA 2128 and more HbA2 2126 and HbF Sideroblastic anemias are interesting in that they are disorders if iron overload A lack of heme svnthesis leads to iron accumulation within mitochondria Bone marrow aspirates show dark blue granules around nuclei ringed sideroblasts The most common cause is alcoholism as EtOH decouples oxidative metabolism Patients who are taking isoniazid for tuberculosis can develop pyridoxine 36 de ciency Lastly lead poisoning denatures ferrochelatase and aminolevulinic acid ALA dehvdrase Ex kids that eat paint folks who paint pottery guys who work with batteries Sx abdominal cholic encephalopathy peripheral neuropathy Fanconi syndrome Dx A bone marrow biopsy is not needed Just get serum lead levels gt Normocytic anemias are usually a lot harder to identify than those previously discussed 0 Aplastic anemia is de ned by clonal cells that generate severe hypoplasia in the bone marrow This results in pancvtooenia A bone marrow biopsy is required for diagnosis Some drugs can induce anemia such as a patient with G6PDD who takes Bactrim TMPSMX Renal failure causes anemia due to a lack of ervthroboietin production though the liver makes some Myelo brosis is de ned by aberrant meoakarvocvtes that lay down too much brous tissue Leukemia lymphoma myeloma metastases toxins and radiation are all causes as well Cytoplasmic proteins from Tb HIV etc can suppress hematopoiesis gt I included a lot of stuff because not covered by Dr Temple because it s found in both First Aid and Goljan s Rapid Review Pathology l m of the opinion it should be learned now and not in April or May Hematology Lecture WI Dr Temple 1 February 2012 The Topic of This Lecture ls Inherited Immunode ciencies gt Patients who are born without humoral immunity Bcells tend to get sinobulmonarv infections 0 Most are caused by pyogenic organisms like S pneumoniae S aureus and H in uenzae 0 These patients mount normal acute resbonses to viruses but they can39t manufacture memorv cells So they can get recurrent infections from things like measles VZV etc gt Those who lack Tcells are predisposed to disseminated viral infections EBV VZV HSV and CMV 0 They also get more fungal infections starting with mucocutaneous C albicans gt More severe systemic infections like PCP are seen in combined immunode ciencv B and T cells gt DiGeorge syndrome 22q11 deletion is an autosomal dominant inherited Tcell disorder 0 The parathyroid glands don39t develop properly hypercalcemia and there are cardiac issues ToF gt Isolated lgA de ciency leads to respiratory infections and carries risk for transfusion alloimmunity 0 Also for some reason there s a greatly increased risk of autoimmune conditions gt Common variable immunode ciency CVID is the most common primary immunode ciency seen in adults 0 Bcells are not fully developed so the body responds by overproducing them The result is a polyclonal hyperplasia in lymph nodes Lymphoma would be monoclonal gt Severe combined immunode ciency SCID is seen in kids There are autosomal and XIinked forms Hematology Lecture w Drs Whitcomb amp Temple 2 February 2012 The Topic of This Lecture ls Myeoproiferative Disorders gt All myeloproliferative disorders involve clonal proliferation of mveloid cells which differentiate and mature 0 Cells of various maturities are seen in peripheral blood The bone marrow is always hvnercellular The fancy term for what39s seen on bone marrow aspirates is panmyeloid hyperplasia o The genetic defect in these is within pluripotent stem cells so all cells show the same mutations o Splenomedalv is also a common abnormality of nonbone marrow tissue seen in these disorders The splenomegaly is due to extramedullary hematopoiesis gt In chronic myelogenous leukemia CMLthere39s marked leukocvtosis with immature dranulocvte precursors 0 Bone marrow aspirates reveal marked hvpercellularitv The blood and bone marrow look very similar 0 CML is due to a famous chromosomal abnormality t922 the Philadelphia chromosome The fusion gene of bcrablyields a protein that increases proliferation in CD34 cells These cells have reduced adhesion to bronectin and reduced chemotaxis to SDFlcxCXCL12 They have increased growth factorindependent survival as well 0 These patients are typically asvmptomatic for decades until the spleen burns out When it does become symptomatic the treatment of choice is imatinib Gleevec Without treatment CML terminates as an acute leukemia which is fatal gt While CML is clonal proliferation of granulocytes polycythemia vera is proliferation of clonal ervthroid cells 0 Hb levels are gt 185 gdL men or gt 165 gdL women Notably ervthroooietin levels are LOW There is no discernable cause such as COPD righttoleft shunt or living at high altitude Nucleated RBCs are a common nding as is iron de ciency from excessive erythropoiesis 0 Recall from the rst day of lectures that a mutated jAKZ gene is often seen in polycythemia vera o The treatments for this are cyclophosphamide and hydroxyurea Phlebotomy controls symptoms gt Similarly essential thrombocythemia is proliferation of clonal meoakarvocvtes which yield platelets 0 But an abundance of megakaryocytes is not diaonostic It s seen in all myeloproliferative disorders 0 In this disorder platelets are gt 600000uL and tend to be large but Hb levels are not elevated Just as Epo is suppressed in polycythemia vera thrombopoietin is suppressed in this There is no bcr abgene though there may be a mutated MK 0 Against common sense hemorrhaoe is iust as common as thrombosis The platelets are quotlazyquot gt Chronic idiopathic myelo brosis involves excessive brous stromal tissue within medullary bone 0 The brous tissue contains meoakarvocvtes and presumably thev re promoting the brosis 0 In contrast to other disorders peripheral blood shows marked anisocvtosis and poikilocytosis We see nucleated RBCs oddlyshaped platelets and teardrop RBCs There39s pancytopenia 0 Though splenomegaly is seen in all myeloproliferative neoplasias it39s CRAZY in myelo brosis In early stages the platelet count is normaltohigh It gets lower as the spleen enlarges o Myelo brosis is treated with supportive care and blood transfusions not chemotherapy Hematology Lecture w Drs Whitcomb amp Temple 2 February 2012 The Topic of This Lecture ls Lymphoproiferative Disorders gt Recall that lymphoid cells differentiate early on and mature in the thymus and peripheral lymphoid tissues 0 In nodes Bcells are found in lymphoid follicles while Tcells hang out in the parafollicular cortex Mature but slightly different Bcells are seen in the marginal zone and mantle 0 Transforming events that produce neoplasms can occur at anv point in the maturation process Lymphocytes stimulated by antigens are transformed to larger more cytoplasmic cells There39s a different lymphoma for every single type of Bcell and Tcell gt Proliferation of lymphoid tissue results in lymphadenopathy It can be reactive painful or neoplastic o The key to diagnosing a malignant lymphoma is the presence of monoclonal cells 0 Clonality is assessed by chromatography looking at the number of DNA rearrangements A single wellde ned band rather than a smear signi es monoclonal cells neoplasm gt The type of lymphoid cell is assessed by particular markers Bcells are CD20 while T cells are CD3 gt NonHodgkin lymphomas are either lowgrade or highgrade which determines aggressiveness of therapy 0 Diffuse large Bcell lymphomas are the most common usually not always involving germinal Bcells These are all treated as highgrade though some types of them are able to m 0 Small lymphocytes mantle cells marginal zone etc progress more slowly and are lowgrade o Follicular lymphomas are phenotypically identical to follicular Bcells The cells are called centrocytes This lowgrade lymphoma is not quite as common as diffuse large Bcell lymphoma 0 The goal of chemotherapy for these is just management not a cure Most involve a t1418 abnormality which results in deregulation of BcIZ an inhibitor of bax Overexpression of Bcl2 leads to decreased aDODtosis in the clonal population 0 Burkitt lymphoma is caused by t 14 t2 or t 22 Any of those yield deregulation of myc This is extremely aggressive with a doubling time of 24 hours That39s nuts 0 The histologic subtype is the key to predicting outcome moreso than staging gt Hodgkin lymphoma is another neoplasm of follicular Bcells but there are actually lots of reactive cells 0 That must be contrasted with nonHodgkin lymphomas which mostly contain neoplastic cells 0 There are abnormal large polyploid Bcells with eosinophilic nucleoli Reed Sternberg cells EBV can contribute to Hodgkin lymphoma by transforming Bcells and inhibiting apoptosis ReedSternberg cells move from one lymph node to the next rather than through the blood 0 So it39s important to ascertain that the spread is continuous 0 It presents just like nonHodgkin lymphoma but the presence of polyclonal cells is very important It s harder to assess the effectiveness of therapy due to the rarity of monoclonal cells Staging is immensely important for predicting outcome but even stage IV can be cured Extranodal sites for lymphoma include the GI tract MALT in stomach lungs nasopharynx and skin 0 Marginal zone Bcell lymphomas are particularly associated with the GI tract and H pylori Malignant lymphomas can metastasize and in ltrate bone marrow which is key for cancer staging Dr Temple Comparecontrast Hodgkin lymphoma readily cured and nonHodgkin lymphoma 0 0 Know about chronic lymphocytic leukemia CLL Know about large cell lymphomas 40 of all lymphomas which have quotB symptomsquot fever night sweats weight loss and are fairly susceptible to chemotherapy 50 cure rate Know about follicular lymphoma 2nCI most common lowgrade not curable but manageable Know about Burkitt lymphoma which is extremely aggressive its 24 hour doubling time is the most rapidly dividing malignancy in humans Know about hairy cell leukemia if only for its historical aspects awesome new treatment 2CDA Know about HTLVl associated lymphoma Know about MALT lymphoma in the GI tract Hematology Lecture w Drs Whitcomb amp Temple 3 February 2012 The Topic of This Lecture ls Acute Leukemia gt The presence of immature cell precursors basts in the peripheral blood de nes an acute leukemia o The clonal proliferation disblaces hematoboietic cells in marrow gt 20 of cells in a marrow aspirate o This is contrasted with CML in which the marrow has granulocytes of all maturation stages CML eventually progresses into an aggressive acute leukemia This is a blast cr5s o Blast cells are identi ed in blood as being CD34 and TdT Morphology and markers separate types For lineage Bcells are CD20 Tcells are CD3 and myeloid cells are CD33 gt Acute myeloid leukemia AML varies in the ratio of granulocytes to monocytes so there are subclasses 0 One subtype M3APML has a t1517 which affects the retinoic acid receptor geneRARaL Abnormal progranulocytes can be induced to mature by Vitamin A alltrans retinoic acid PMLRARu is a fusion gene that is repressed unless concentrations of retinoic acid are high This subtype almost always presents with DIC due a rapid increase in progranulocytes DIC presents with widespread hemorrhage epistaxis bruising and renal failure 0 Auer rods are rare but pathodnomonic for AML They39re comprised of fused lysosomes o FLT3 is an RTK expressed by hematopoietic stem cells Mutations are common in AML gt Acute lymphoblastic leukemia ALL is differentiated as either Bcell or Tcell type wav more common 0 Bcell ALL has cells that are CALLACD10 and TdT Tcell ALL has only TdT o The prognosis is better in younger patients and those that have a t11221 abnormality t1922 which also causes CML is a sign of verv poor prodnosis in ALL gt The goal for treatment is to wipe out the abnormal stem cells in bone marrow with a blast of chemotherapy 0 Obviously this results in neutropenia and susceptibility to infections gt AML tends to affect patients aged 1539 while ALL affects kids under 15 most common neoplasm of kids 0 CML hits people 4059 and CLL is most commonly seen in patients over 60 AGE IS IMPORTANT Hematologv Lecture w Drs Whitcomb 63 Temple 3 Februarv 2012 The Topic of This Lecture ls Plasma Cell Disorders gt Chronic lymphocytic leukemia CLL is the most common leukemia of adults There39s absolute lymphocytosis o A peripheral blood smear will show smudge cells There are monoclonal cells in the marrow o Nontender IvmphadenODathv is common as is hvoooammadlobulinemia and normocytic anemia The lack of lgG makes sense because abnormal Bcells cannot mature into plasma cells o CLL is innocuous except for diminished humoral immunity leading to more bacterial infections Hairy cell leukemia is identi ed by cytoplasmic projections that are seen with a TRAP stain o It presents with splenomegaly and pancytopenia low WBC There is NO lymphadenopathy The hairy cells are rarely seen in the peripheral blood but numerous in the bone marrow 0 Total remission is induced by pentostatin or 2CDA which are purine analogs with few side effects Adult Tcell leukemia is associated with HTLVl leading to monoclonal proliferation of CD4 helper T cells o The nuclei look like ower petals ATL is seen in the Caribbean and southern Japan 0 The disease develops due to activation of m which suppresses p53 Lymphoblasts release osteoclastactivating factor 9 bone lvtic lesions and hypercalcemia Multiple myeloma is identi ed as an accumulation of monoclonal plasma cells in the bone marrow o Rouleaux formations RBCs stacked like poker chips are seen in the peripheral blood 0 Amyloid builds up in tissue as sheets of light chains which can induce nephrotic syndrome Renal failure is due to amyloid deposition urate nephropathy and direct tubular damage 0 There is an M spike of lgGK The light chains Bence Jones protein are excreted in urine It doesn39t have to be lgGK Cases of lgA and pure light chain myeloma exist too 0 There39s bone pain and fracture risk from punchedout lvtic lesions in the vertebra or axial bones There39s often anemia hypercalcemia hyperviscosity neuropathy and infections 0 Levels of BZmicroglobulin are elevated in multiple myeloma correlating with poor prognosis If there39s an M spike but no symptoms it39s monoclonal gammopathy of uncertain signi cance MGUS 0 About 1 of people with MGUS progress into multiple myeloma each year Lymphoplasmacytic lymphoma is also called Waldenstrom39s macroglobulinemia It s a paraprotein disorder 0 In contrast to multiple myeloma the M spike is of lgM There39s also generalized lymphadenopathy There are no lvtic lesions The worry is instead about hvperviscositv syndrome
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