Robbins Essential Pathology Hematopoietic and Lymphoid Systems PDF
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This document is a section from a medical textbook on pathology, focusing on the hematopoietic and lymphoid systems. It covers topics such as red blood cell disorders and anemias. The detailed nature of the text suggests it's suitable primarily for advanced students or researchers in the medical field.
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9 Hematopoietic and Lymphoid Systems O U T L I N E Red Blood Cell Disorders, 137 Non-Hodgkin Lymphomas and Chronic Lymphoid Leukemias, 151 Anemias, 137 Hodgkin Lymphoma, 156 Hemolytic Anemias, 137 Plasma Cell Neoplasms and Related Entities, 157 Underproduction Anemias, 143 Histiocytic Neoplasms, 158 White Blood Cell Disorders, 146 Bleeding Disorders, 158 Nonneoplastic Disorders of White Cells, 146 Thrombocytopenia, 159 Leukopenia, 146 Coagulation Disorders, 160 Reactive Leukocytosis, 146 Disorders of Spleen and Thymus, 162 Neoplastic Proliferations of White Cells, 147 Splenomegaly, 162 Acute Leukemias, 148 Disorders of the Thymus, 162 Myelodysplastic Syndromes, 150 Thymic Follicular Hyperplasia, 162 Myeloproliferative Neoplasms, 150 Thymoma, 162 he emaopoec and ympod sysems are afeced by a wde spec- o ssues. Oer clncal consequences o anema are deermned by s rum o dseases, wc can be subdvded based on weer ey pr- severy, rapdy o onse, and underlyng paogenc mecansm, and marly afec red cells, we cells, or e emosac sysem (plaeles wll be dscussed under e specc enes a ollow. and coagulaon acors). We wll organze our dscusson accordngly, recognzng a dsorders a prmarly afec one componen o e Hemolytic Anemias emaolympod sysem oten secondary mpac oers. In addon, Hemo ly tic a nemia s a re a d iv ers e g ro u p of di s o r d e r s that h av e we w brely dscuss dsorders o e speen and (because o er nk as a co mmo n fea ture a ccel era t ed re d cell d e s t r u c t i o n ( h e m o l y s i s ) o ceran mmunoogc dsorders) dsorders o e ymus. he red ce e span s sorened beow s norma 120 days, eadng o anema and aendan ssue ypoxa. Oxygen-sensng ces n e kdney respond by ncreasng e producon o er y- ropoen, smuang e proeraon o marrow er yrod ee- RED BLOOD CELL DISORDERS mens and ncreasng red ce producon. hus, yperpasa o marrow er yrod precursors and ncreased numbers o newy reeased ANEMIAS red ces (retcuocytes) n e bood are amarks o emoyc anemas. Anemia, one of the most common disorders of humans, is a state of red Pathogeness. Mos emoyc anemas are caused by nrnsc red ce cell deciency that lowers the oxygen-carrying capacity of the blood. deecs or damage nduced by exrnsc acors a ncrease red ce Anema may resu rom bood oss, ncreased red ce desrucon desrucon by pagocyes, parcuary n e speen. B ecause e red (emoyss), or decreased red ce producon. Hemoyc anemas can ces are removed rom e crcuaon by pagocyes, s s reerred be urer subcassed based on weer ey are caused by deecs o as extravascuar emoyss. Fndngs a are reavey specc or a are nrnsc or exrnsc o e red cell. hese mecansms provde exravascular emolyss nclude e ollowng: one bass or cassyng anemas (Tabe 9.1). Hyperbrubnema and jaundce, due o degradaon o emoglo- bn n macropages Clncal Features. Careu assessmen o red ce morpoog y and Spenomegay due o “work yperplasa” o pagocyes n e spleen red ce ndces eps o narrow e dagnosc possbes. he mean Brubn-rc gastones (pgmen sones), because blrubn s a ce voume (MCV; e average voume per red ce) dsnguses e breakdown produc o emoglobn, and an ncreased rsk o cole- mcrocyc (ow MCV), normocyc (norma MCV), and macrocyc cyss secondar y o ble duc obsrucon (g MCV) anemas, wc ypcay ave dsnc causes (Tabe 9.2). In soaed anema, perpera bood ess usuay suice o esabs e Intravascuar emoyss s caused by njures a are so severe a cause. Wen anema occurs n concer w rombocyopena and/or red cells burs wn e crculaon. hese may be caused by mecan- granuocyopena, a marrow dsorder (e.g., apasa or nlraon by a ca orces (e.g., urbuen bood low) or bocemca or pysca agens neoplasm) s lkely and a bone marrow examnaon s oten warraned. a damage e red ce membrane. Fndngs a dsngus nravas- Paor, ague, and assude are common o a orms o anema. I e cuar emoyss rom exravascuar emoyss ncude: onse s sow, e dec n oxygen-carryng capacy s parally compen- Hemogobnema and emogobnura. Hemogobn reeased no saed or by adapve ncreases n plasma volume, cardac oupu, resp- e crcuaon passes no e urnar y space and s oxdzed o raory rae, and oer meabolc canges a ncrease oxygen delvery meemogobun, eadng o browns dscooraon o e urne. 137 138 CHAPTER 9 Hematopoietic and Lymphoid Systems Table 9.1 Classification of Anemia According to Underlying Mechanism Blood Loss Acute Trauma Chronic Gastrointestinal tract lesions, gynecologic disturbances Increased Destruction (Hemolytic Anemias) Intrinsic (Intracorpuscular) Abnormalities Hereditary Membrane abnormalities (e.g., hereditary spherocytosis) Enzyme deficiencies (e.g., glucose-6-phosphate dehydrogenase) Disorders of hemoglobin synthesis Structurally abnormal globin synthesis (hemoglobinopathies): sickle cell anemia Deficient globin synthesis: thalassemia syndromes Acquired Membrane defect: paroxysmal nocturnal hemoglobinuria (rare) Extrinsic (Extracorpuscular) Abnormalities Antibody-mediated Nonautoantibodies: transfusion reactions, hemolytic disease of the fetus and newborn Autoantibodies Mechanical trauma to red cells Microangiopathic hemolytic anemias (e.g., disseminated intravascular coagulation) Defective cardiac valves Infections: malaria Impaired Red Cell Production Disturbed proliferation and differentiation of stem cells: aplastic anemia Disturbed proliferation and maturation of erythroblasts Defective DNA synthesis: vitamin B and folic acid deficiency (megaloblastic anemias) 12 Anemia of renal failure (erythropoietin deficiency) Anemia of chronic inflammation (iron sequestration, relative erythropoietin deficiency) Marrow replacement: primary hematopoietic neoplasms (acute leukemia, myelodysplastic syndromes) Marrow infiltration (myelophthisic anemia): metastatic neoplasms, granulomatous disease Table 9.2 Microcytic, Normocytic, and Macrocytic Anemias Microcytic Anemia (Causes and Characteristic Laboratory Findings) Iron deficiency Low serum iron, low serum ferritin, high serum transferrin Thalassemia High serum iron, high serum ferritin, normal serum transferrin Normocytic Anemia (Causes and Characteristic Findings) Anemia of chronic inflammation Elevated red cell sedimentation rate, low serum iron, high serum ferritin, normal or low serum transferrin Anemia of renal failure Elevated creatinine and blood urea nitrogen Hereditary spherocytosis Evidence of hemolysis, spherocytic red cells Immunohemolytic anemia Evidence of hemolysis, spherocytic red cells, direct Coombs test positive Mechanical destruction of red cells Evidence of hemolysis, red cell fragments (schistocytes) in peripheral blood Sickle cell anemia Evidence of hemolysis, sickled red cells in peripheral blood Anemia of marrow infiltration Teardrop-shaped red cells, nucleated red cells, early white cell progenitors in periph- eral blood (leukoerythrocytosis) Malaria, babesiosis Evidence of hemolysis, organisms seen within red cells G6PD deficiency Evidence of hemolysis, red cells with “bites” Macrocytic Anemia (Causes and Characteristic Laboratory Findings) Folate, Vitamin B deficiency Macroovalocytic red cells, hypersegmented neutrophils, megaloblastic marrow 12 progenitors Myelodysplastic syndromes Dysplastic marrow progenitors and peripheral blood elements Aplastic anemia Pancytopenia Liver disease, alcoholism Target red cells in peripheral blood smears CHAPTER 9 Hematopoietic and Lymphoid Systems 139 Hemosdernura and oss of ron. Hemogobn absorbed by rena rom e spl e n c ve nous c rc u l a on , re su l ng n e x r av as c u l ar ubuar ces s processed no emosdern and os wen rena ces e moly s s. Spl e ne c omy mprove s e ane m a , bu no e u nd e rly - soug no e urne. ng ge ne c d e e c , e nc e spe ro c y e s re ma n n e bl o o d. Laboraory ndngs sared by nravascular and exravascular emo- lyc anemas nclude retcuocytoss (ncreased mmaure red cells, called Clncal Features. he dagnoss depends on e amy sor y, e reculocyes, n e perperal blood), eevated serum actate deydro- evdence o exravascuar emoyss, e presence o sperocyes n genase (an enzyme released rom lysed red cells), and decreased serum perpera smears, and oer ess. Foowng spenecomy, paens eves of aptogobn (a plasma proen a bnds ree emoglobn). ave an exceen prognoss bu are a rsk or sepss w encapsuaed Hemolyc anemas are less common an underproducon ane- bacera due o e oss o spenc uncon. hey aso are prone o apas- mas (dscussed laer), bu several are o paogenc neres and mer c crses durng necons by par vovrus B19, wc necs and ks consderaon. er yrod progenors n e marrow. hs necon s rapdy ceared by e mmune sysem and as no consequences n norma ndvduas, Hereditary Spherocytosis bu eads o rapdy worsenng anema n HS and oer emoyc Hereditary spherocytosis is caused by inherited defects in red cell anema paens n wom e red ce a-e s markedy decreased. membrane skeleton proteins that lead to membrane loss and the Sickle Cell Anemia formation of spherocytes that lose deformability. Sickle cell anemia, a prototypical hemoglobinopathy, is an autoso- Pathog e ne s s. T e n e r anc e o e re d ar y spe ro c y o s s (HS) s mal recessive disorder caused by a single amino acid substitution usu a l ly auo s oma l d om n an. In p e r pe r a l bl o o d s me ars , spe ro - in β-globin that creates sickle hemoglobin. c y e s l a ck c e n r a l p a l l or (F g. 9. 1). T e c el ls c an no p ass rou g Scke ce anema s e mos common ama emoyc anema. In e nar row sl - l ke op e n ng s a s e p ar ae e spl e n c re d pu lp pars o Arca, e gene requency approaces 30%, appareny because o a proecve efec o sckle emoglobn (HbS) agans malara n eerozy- goes. In e Uned Saes, approxmaely 8% o paens o Arcan descen are eerozygous HbS carrers and abou 1 n 600 as sckle cell anema. Pathogeness. Sckle cell anema s caused by a muaon n -globn a leads o e polymerzaon o sckle emoglobn (HbS) no long, sf cans wen s deoxygenaed. As a resul, e cell assumes an elongaed sckle sape bu reurns o s normal sape wen oxygen- aed (Fg. 9.2). he mos mporan varabe a deermnes weer HbS-conanng red ces undergo sckng s e nraceuar concen- raon o oer emogobns. In eerozygoes, approxmaey 60% o emogobn s norma HbA, wc neracs ony weaky w deoxy- genaed HbS and reards HbS poymerzaon; as a resu, eerozygoes w HbS are generay asympomac (ey are sad o ave e scke ce ra). Fea emogobn (HbF) aso neracs weaky w HbS; s expans wy newborns w scke ce anema are asympomac un e HbF eves a a 5 o 6 mons o age. Fig. 9.1 Hereditary spherocytosis: peripheral blood smear. Note the Sckng o red ces n paens w scke ce anema as wo major anisocytosis and several hyperchromic spherocytes. Howell-Jolly bod- consequences: (1) cronc emoyc anema and (2) epsodc pan cr- ies (small nuclear remnants) are also present in the red cells of this ses assocaed w scemc ssue damage (Fg. 9.3). Hemoyss sems asplenic patient. (Courtesy of Dr. Robert W. McKenna, Department of rom repeaed sckng, wc damages e red ce membrane, evenuay Pathology, University of Texas Southwestern Medical School, Dallas.) A B Fig. 9.2 Sickle cell anemia: peripheral blood smear. (A) Low magnification shows sickle cells, anisocytosis, poi- kilocytosis, and target cells. (B) Higher magnification shows an irreversibly sickled cell in the center. (Courtesy of Dr. Robert W. McKenna, Department of Pathology, University of Texas Southwestern Medical School, Dallas.) 140 CHAPTER 9 Hematopoietic and Lymphoid Systems condon. Adu emogobn, or HbA, s a eramer composed o wo α cans and wo cans. he α cans are encoded by wo α-gobn G G A T genes yng n andem on cromosome 16, wereas e cans are Point C C G G encoded by a snge -gobn gene ocaed on cromosome 11. Muc T mutation A o e varaon n α- and -aassemas s due o e nerance o C C dferen combnaons o muaed alleles (Table 9.3). β-aassema. here are wo ypes o aees, dsngused by dferen 0 sngle-base muaons: (1) alleles, wc produce no -globn and HbA HbS + (2) alleles, wc produce reduced amouns o -globn. Persons nerng one abnormal allele ave -alassema mnor (also known 0 + as -alassema ra). Mos people nerng any wo and alleles RBC ave -alassema major, bu occasonally persons nerng a leas + one allele ave a mlder dsease ermed -alassema nermeda. Deoxygenation he deecve syness o -gobn conrbues o anema n Irreversibly wo ways: (1) e nadequae ormaon o HbA resus n mcro- sickled 2+ + cell cyc, poory emogobnzed red ces and (2) e excess unpared Ca K , H O 2 α-gobn cans orm oxc precpaes a damage e membranes Hemolysis o er yrod precursors, mos o wc de by apoposs (Fg. 9.4) Extensive (nefecve er yropoess). he red ces a are produced ave membrane damage membrane damage, eadng o emoyss. Facors reeased rom Oxygenation er yrod progenors ndrecy ncrease e absorpon o dear y ron, eadng o ron overoad (dscussed aer). Additional Reversibly cycles of α-aassema. α-haassema s caused by deeon o one or more o sickled Deoxygenation, deoxygenation e α-gobn genes; dsease severy s proporona o e number o cell prolonged α-gobn genes a are deeed (see Tabe 9.3). Excess -gobn and transit times Microvascular γ-gobn cans orm reavey sabe and γ eramers known as 4 4 occlusion HbH and Hb Bars, respecvey, wc cause ess membrane damage Cell with dehydration an ree α-gobn cans. Inefecve eryropoess and emolyss and membrane damage are less pronounced n HbH dsease an n -alassema. However, Fig. 9.3 Pathophysiology of sickle cell disease. HbA, hemoglobin A; bo HbH and Hb Bars delver oxygen neiceny o ssues. HbS, sickled hemoglobin; RBC, red blood cell. Morphology. In -aassema mnor and α-aassema ra, producng rreversby scked ces a are rapdy removed rom e cr- abnormaes are conned o e perperal blood. Red cells are small cuaon. Pan crses are caused by ocazed obsrucon o e mcrovas- (mcrocyc) and pale (ypocromc) bu normal n sape. -alassema cuaure by scked red ces. hese obsrucons are argey conned o major red cells sow marked mcrocyoss, ypocroma, ansocyoss ssues n wc blood low s suggs, suc as e speen, e marrow, (varaon n cell sze), and pokocyoss (varaon n cell sape). and nlamed ssues, were e rans me o red ces roug capar- Nucleaed red cells (normoblass) also are seen n e perperal blood. es exceeds e me requred or sckng o ces oowng deoxygenaon. -haassema nermeda and HbH dsease sow eaures beween ese wo exremes. In -aassema major, yperpasc eryrod Clncal Features. In scke ce dsease, rreversby scked ces can be progenors ll e marrow, nvade e bony corex, mpar bone grow, seen n perpera bood smears. In eerozygoes, sckng s nduced and produce skeleal deormes. Exrameduary emaopoess resuls nvro by exposng ces o ypoxc condons. he presence o HbS s n promnen splenomegaly, epaomegaly, and lympadenopay. conrmed by emoglobn elecroporess. HbH dsease and -alassema nermeda are assocaed w a lesser Obsrucon o blood low n e speen eads o spenc auonarc- degree o splenomegaly, eryrod yperplasa, and grow reardaon. on, markedy ncreasng e rsk or sepss w encapsuaed bacera. Addona compcaons ncude e-reaenng sckng crses o e Clncal Features. he dagnoss s based on e amy sor y, perp- ung (acue ces syndrome) oowng pumonar y necons; sroke; era bood ndngs, and laboraor y ess. Hemoglobn elecroporess and rena damage a may ead o bndness. Hydroxyurea rases can deec abnormal emoglobns suc as HbH, as well as HbA , a 2 HbF eves and as annlammaor y efecs, bo o wc decrease mnor emoglobn a s oten ncreased n -aassema Cnca e ncdence o pan crses. eaures var y wdey : Thalassemias β-aassema ra and α-aassema ra paens are ypcay Thalassemias are inherited disorders caused by mutations in glo- asympomac and ave md mcrocyc anema. bin genes that result in decreased synthesis of α- or β-globin. The β-aassema major maness posnaay wen HbF syness dmn- associated anemia results from reduced hemoglobin synthesis and ses. Increased numbers o red ce precursors consume nurens, hemolysis due to an imbalance in globin chain synthesis. causng grow reardaon and cacexa. Survva no aduood s haassema s common n Mederranean, Arcan, and Asan regons possbe w ransusons and reamen w an ron ceaor, wc n wc maara s endemc; e assocaed muaons may proec prevens ron overoad and assocaed cardac dysuncon. Hemaopo- agans acparum maara. ec sem ce ranspanaon a an eary age s e reamen o coce. HbH dsease and β-aassema nermeda are no as severe as Pathogeness. A dverse coecon o α-gobn and -gobn muaons -aassema major. Anema s moderae and paens usuay do causes severe orms o aassema, wc s an auosoma codomnan no requre ransusons. CHAPTER 9 Hematopoietic and Lymphoid Systems 141 Table 9.3 Clinical and Genetic Classification of Thalassemias Clinical Syndrome Genotype Clinical Features Molecular Genetics -Thalassemias -Thalassemia major Homozygous -thalassemia Severe anemia; regular blood transfusions Mainly point mutations that lead 0 0 + + 0 + ( / , / , / ) required to defects in the transcription, 0 + + + 0 + splicing, or translation of -glo- -Thalassemia inter- Variable ( / , / , /, /) Severe anemia, but regular blood transfusions bin mRNA media not required -Thalassemia minor Heterozygous -thalassemia Asymptomatic with mild or absent anemia; 0 + ( /, /) red cell abnormalities seen α-Thalassemias Silent carrier −/ α, α/α Asymptomatic; no red cell abnormality Mainly gene deletions α-Thalassemia trait −/−, α/α (Asian) Asymptomatic, like -thalassemia minor −/α, −/α (black African, Asian) HbH disease −/−, −/ α Severe; resembles -thalassemia intermedia Hydrops fetalis −/−, −/− Lethal in utero without transfusions HbH, hemoglobin H; mRNA, messenger ribonucleic acid. NORMAL β-THALASSEMIA Reduced β-globin synthesis, Insoluble α-globin aggregate with relative excess of α-globin HbA (α β ) 2 2 HbA Normal erythroblast Abnormal erythroblast α-globin Few abnormal aggregate red cells leave Normal HbA Hypochromic red cell Normal red blood cells Ineffective erythropoiesis Most erythroblasts Extravascular hemolysis die in bone marrow Destruction of aggregate-containing Dietary iron red cells in spleen ANEMIA Increased iron Blood absorption transfusions Tissue hypoxia Reduce Erythropoietin increase Liver Heart Marrow expansion Systemic iron overload (secondary hemochromatosis) Skeletal deformities Fig. 9.4 Pathogenesis of -thalassemia major. Note that aggregates of excess α-globin are not visible on routine blood smears. Blood transfusions constitute a double-edged sword, diminishing the anemia and its attendant complications but also adding to the systemic iron overload. HbA, hemoglobin A. 142 CHAPTER 9 Hematopoietic and Lymphoid Systems Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency anbodes a cross e pacena and cause emoyss o ea red ces. Mos Mutations that cause G6PD deciency decrease the half-life of G6PD cases o emoyc dsease o e eus and newborn occur n pregnances protein, leaving older red cells at risk for oxidant damage and n wc e eus expresses RD angen and e moer s RD angen intravascular hemolysis. negave, or n wc ere s ABO angen ncompaby beween e eus G6PD decency s an X-lnked dsorder a afecs approxmaely and e moer. Generay, e rs angen-ncompable pregnancy does 10% o black males n e Uned Saes. G6PD s an enzyme needed or no produce dsease because e moer does no produce an–red cell IgG e syness o reduced gluaone (GSH), wc parcpaes n e elm- anbodes (e ype a crosses e placena) beore delvery. he rsk rses naon o poenally njurous reacve oxygen speces. he enzyme de- w eac subsequen ncompabe pregnancy owng o memory B ces a cency resuls n cell damage caused by exposure o ree radcals. All cells respond rapdy wen ey are reexposed o angen. IgG-medaed yss o n e body express muaed G6PD, bu e dsorder maness only n red ea red ces eads o progressve anema, ssue scema, nrauerne car- cells because ey lack e capacy o synesze new proens. hus, e dac aure, and perpera edema, and may be aa n severe cases. agng red ces o afeced paens become severely G6PD decen and are R-negave moers are reaed w R mmune gobun parcularly suscepble o oxdan-nduced damage and lyss. (RIg) a 28 weeks and wn 72 ours ater dever y o an R-pos- Hemolyss n G6PD decenc y s epsodc and ollows exposures ve baby. e RIg masks e angenc ses on e ea red ces and a ncrease e producon o oxdans, parcularly acue necons prevens senszaon o R angens. As a resu, AB O ncompaby and exposure o ceran drugs. A caracersc ndng n perperal s now e mos common cause o emoyc dsease o e eus and smears s “be” cells, red cells w severely damaged membranes newborn. ABO ncompaby occurs n approxmaey 20% o 25% a ave porons “ben of ” by macropages removng paces o o pregnances, bu emoyss deveops n ony a sma racon o sub- membrane w assocaed emoglobn precpaes known as Henz sequen pregnances, prmary n ceran group O women wo make bodes, leadng o nravascular emolyss (Supplemenal eFg. 9.1). IgG anbodes dreced agans group A or B angens (or bo) a he emoyss s oten ransen, even w perssen necon or cross e pacena and reac e ea crcuaon. In genera, e dsease drug exposure, because yss o oder ces eaves younger ces w s muc mder an R ncompaby, n par because many ces ger eves o G6PD a are ressan o oxdan sress. oer an red ces express A and B angens and us adsorb some o e ranserred anbodes. ere s no efecve meod o prevenng emolyc dsease resulng rom AB O ncompably. Immunohemolytic Anemia Immunohemolytic anemia is caused by antibodies that bind to Mechanical Trauma to Red Cells antigens found on red cell membranes. e paogenc anbodes may arse sponaneousy or be nduced Inravascular emolyss o red cells due o er exposure o abnormal by exogenous agens suc as drugs or cemcas. Immunoemoyc mecancal orces occurs n wo sengs. anema s cassed on e bass o (1) e naure o e anbody and Traumatc emoyss due o deecve cardac valve proseses, (2) e presence o predsposng condons (summarzed n Table 9.4). wc may sear red cells (e blender efec), or an acvy resul- hus, e anema may be prmary (dopac) or secondary o oer ds- ng n repeaed pyscal poundng o one or more body pars (e.g., orders o e mmune sysem. In mos nsances, e bound anbodes maraon racng, bongo drummng, karae). ac as opsonns and e emoyss s exravascuar. he drec Coombs Mcroangopatc emoytc anema occurs wen small vessels es deecs anbodes and/or compemen on red ces and s ereore become narrowed by romb. Mos requenly, s s due o ds- posve. Dependng on e cause and e severy o e emoyss, rea- semnaed nravascular coagulaon (DIC) (descrbed laer), n men may nvove mmunosuppresson, remova o suspeced rggers, or wc vessels are narrowed by e nravascular deposon o brn, reamen o underyng condons. and romboc rombocyopenc purpura and emolyc-uremc syndrome, n wc vessels are narrowed by plaele-rc romb. Hemolytic Disease of the Fetus and Newborn he cnca sgncance o mcroangopac emolyss s a This disorder results from an antibody-induced hemolytic anemia oten ndcaes a serous underyng condon. caused by blood group incompatibility between the mother and Mecancay ragmened red ces (scsocyes) are easy recog- the fetus. nzed n perpera bood smears, were ey ake on e appearance o burr ces, eme ces, and range ces (Fg. 9.5). Pathogeness. Red ce ncompaby occurs wen e eus ners red Malaria ce angenc deermnans rom e aer a are oregn o e moer. Fea red ces oten ener e maerna crcuaon durng e as rmeser o It is estimated that malaria affects 500 million and kills more than pregnancy or durng cdbr (eomaerna beed), senszng e moer 400,000 people per year, making it one of the most widespread o paerna red ce angens and eadng o e producon o an–red ce afictions of humans. Maara s ransmed by e be o Anopees mosquoes and s Table 9.4 Classification of Immunohemolytic Anemias endemc n Asa and Arca; due o wdespread je rave, cases are seen wordwde. O e ve causave Pasmodum speces, Pasmodum fa- o Warm Antibody Type (active at 37 C) cparum s e mos mporan because causes a serous dsorder w Primary (idiopathic) a g aaly rae. Secondary : B-cell neoplasms (e.g., chronic lymphocytic leukemia), autoimmune disorders (e.g., systemic lupus erythematosus), Pathogeness. Wen mosquoes eed on umans, sporozoe orms are drugs (e.g., α-methyldopa, penicillin, quinidine) nroduced a nec lver cells, were ey mulply as merozoes and Cold Antibody Type (active at temperatures lower than core are en released o nec red cells (Fg. 9.6). Inraer yrocyc para- body temperature) ses eer connue asexual reproducon as ropozoes or gve rse Acute: Mycoplasma infection, infectious mononucleosis o gameocyes a are capable o necng e nex ungr y mosquo. Chronic: idiopathic, B-cell lymphoid neoplasms (e.g., lymphoplasma- he asexua pase s compee wen e ropozoes gve rse o new cytic lymphoma) merozoes, wc escape by ysng e red ces.
