Anemia of Bone Marrow Failure and Systemic Disorder Result of an absolute failure of the bone marrow to replace erythrocytes

that are normally destroyed after 120 days or those that are prematurely destroyed such as hemolysis. Epidemiology: Low before the age of 1 Increases until the age of 50 highest !arrow aplasia is2 5" more fre#uent in far east than in the west. $econdary%!isc causes of altered &ematopoesis: $ystemic diseases of the Renal ' Endocrine system. results in absolute or secondary decrease in erythroid precursor E() is usually decreased or null but has some erythropoeitic stimulatory effect. *one marrow is functionally normal. (rimary defect of the *one !arrow itself: Part 1. Aplastic Anemia anemia with peripheral blood pancytopenia the boone marrow is se+erely hypoplastic or aplastic with mar,ed neutropenia and thrombocytopenia fran, aplastic anemia milder form of aplastic anemia. secondary to drug into"ication &allmar, of -plastic -nemia that differentiates it from the rest of anemia: .o splenomegaly. !echanisms that underlies defect in all -plastic -nemia that results to failure of hematopoetic stem cell growth/ resulting in hypoplastic marrow and pancytopenia. 1. 0eficiency in the number of bone marrow stem cells. 2. Immune suppression of stem cells. 1. 0efect in the stem cells themsel+es. 2unresponsi+e to differentiation and mitotic stimuli3. 4. 0amage to bone marrow microen+ironment. 0amages 0.- and ultimately to apoptosis. sol+ed by bone marrow transplant. (rimary 5lassification of -plastic -nemia: 1. 5ongenital or &ereditary 6anconi7s -nemia (ancytopenic disorder with hypoplastic to aplastic *!. Rare inherited form of aplastic anemia. Inheritance appears to be autosomal recessi+e. !ore than 100 cases e"ist. 8here are 11 different subtypes of 6anconi7s -nemia Inherited through autosomal recessi+e mode 9# and 20# with e"ception to 6- * subtype which is : lin,ed. 6re#uent chromatin brea,s/ gaps/ rearrangements/ reduplications and e"changes. !ales are affected by the disease. 6emales are carriers. 5linical (resentation: (rominent congenital abnormalities include !icroencephaly 2-bnormally small brain3.

*rown s,in pigmentation 5af; -u Lait spots. $hort $tature !alformation of the thumbs Internal $trabismus 25rossed eyed3 !alfromation of the ,idney <enital &ypoplasia &ypogonadism !ental Retardation (* abnormatities don7t manifest til 5 10 y%o (*6 with pancytopenia/ anemia. *oth anisocytosis and poi,ilcytosis are seen. !ar,ed increase in &b E$R ' )smotic 6ragilitiy Increases=simply might be a reflection of the anemia. (atient is normocellular if diagnosed early but will e+entually become aplastic. 5ytogenetics test shows multiple chromosomal abnormalities including ring chromosome dislocations/ dicentric forms and spontaneous brea,s. In contrast with late manifestations in the appearance of aplasia. 5hromosomal abnormalities can be demonstrated by birth in blood cells/ fibroblasts and tissues. 8reatment: -ndrogen theraphy > 5orticosteroids stimulates erythropoeisis 0eath is secondary to hemorrhage or infection but rarely as a reasult of se+ere anemia. Recombinant granulocyte colony stimulating factor 5$6 < helps with neutropenia but ineffecti+e in stimulating erythro and thrombotic cell. *! 8ransplantation is possible but bec of widespread chromosomal damage in all body 8ransplantation with an &L- identical sibling 25ryopreser+ed umbilical cord blood3 tissues. It lea+es patients +ulnerable to maglignant disease. 8ranslocations in abnormal genes predispose these patients to de+elop -!L 6amily members 2including carriers3 has increased rin de+elopling leu,emia bec of the hereditary abnormal gene. 2. 0iopathic -plastic -nemia no ,nown participating factors. 1. Idiopathic 40 ?0@ in A$- and 90@ in Bapan. $econdary -plastic -nemia: 1. 5hemicals 5hloramphenicol highly associated with marrow aplasia. *ut is transient. 5 40fold ris, in ppl who are e"posed to the drug. 5haracteriCed by +auolated cells in the *! especially among erythroid series. *enCene and deri+ates. 8rinitrotoluene (urine and pyrimidines 2-nti !etabolites3 &ydantoins $ulfonamides <old (reparations. Insecticides such as 5hlordane/ 5horophenothane 20083 ' <amma benCene he"acholirde 2Lindane3.

-spirin innocent drug which may cause aplastic anemia. 2. Radiations Radiation damages the stem cells or the hematopoetic microen+ironment the hematopoetic tissues that supports de+eloping hematopoietic cells. -ffects cell to cell interactions/ resulting to decrease in the growth response of the cells in bm. *ut the damage is li,ely irre+ersible. Indi+iduals e"posed to long term low dose radiation li,e patients in radiotheraphy/ radioacti+e isotope administration or 40 folds. Radiologist 20 folds ris, or wor,ers in an unsafe nuclear power plants. 1. -bnormal Immune !echanisms -utomimmune mechanisms directly by lymphocytes or by some humoral factor. so before bm transfusion/ these patients were gi+en cyclosphosphamide immunosuppresant. In some cases whre lymphocytes suppresses growth of normal marrow. (atients has been gi+en -8< 2-nti 8hymocyte globulin3. &uman .atural Diller 5ell 2&.D3 are responsible for lymphocyte mediated aplasia. *ut not fully understood yet. In Eitro inhibition of E() resulted to an abnormal composition of 8 cell subsets 2e"cess of acti+ated 8ac> 81> and 811> lymphocytes3. Engraftment of *! sol+ed the problem. &umoral Inhibitors of stem cell growth was reported as either idiopathic or associated with systemic lupus erythematosus/ #uinidine or cryoglobulinemia. 4. !I$5 Etiologies: Rare occasional infection precdes the syndrome in .on -/ */ 5 ' < &epatitis 2&epatitis by un,nown &ep $train3/ !Iliary 8*/ *rucellosis and parasitic infestations/ E*E/ 5!E/ 8ype *19 &(E !ay be transient due to the +irus or by the administered antibiotics (aro"ysmal .octurnal &emoglobinuria 2(.&3 F but con+ersely/ 5 10@ of ppl with aplastic anemia de+elop (.&. -nd 1 5@ actually ha+e leu,emia and some progresses to acute leu,emia. lue,emic cells releases one or more factors that suppress hematopoeisis causing hypoplastic marrow and pancytopenic peripheral blood. )n a rare occasion/ aplasia occurred during pregnancy with reco+ery after gi+ing birth. 5linical (resentation: (allor Gea,ness Easy 6atigability Hdue to decrease o"ygen capacity in the body. 0ecresed neutrophils e"poses patients to bacterial infections but not +iral. &emorrhage may be seen due to thrombocytopenia. .ormal $pleen=no more cells to destroy. 5).<E.I8-L RE0 *L))0 5ELL REL-8E0 0I$)R0ER

8elomeres shortens e+ery cell cycle/ its fundamental to normal senescent cell/ tissues and organisms. Insufficiency causes end replication shortens afeter e+ery cell di+ision. In congenital hematologic disorders/ they are associated with inherited mutations in telomere repair and protection genes. Part2. Pure Red Cell Aplasia (PRCA Ac!uired Rare condition that may be inherited or ac#uired. 0e+elops secondary to benign thymomas 28hymus <land tumors3. 20@ of these patients ha+e remission of (R5-. $ome patients ha+e -.-/ $pi,es on E($ and some &ypogammaglobulinemia. )thers: 0rugs/ 5hemical ' Infections ' the aplastic crisis of hemolytic anemia self limited and re#uired no theraphy/ only tranfusion=high degree of anemia. 0iamond *lac,fan -nemia Inherited form of (R5-. (R5- is either idiopathic or autoimmune mechanism. Idiopathic: 8hese patients has increased E() -utoimmune type: $ome patients ha+e an I< inhibitor of erythroid precursors. &as little or no E(). 5linical 6indings: E"treme (allor constant finding. $plenomegaly/ &epatomegaly or both is conse#uence of &emosiderosis due to multiple transfuion from treatment. 8reatment: Red 5ell transfuion $earch and cure thymoma Immunosuppressi+e theraphy -dnrogen theraphy stimulate E(). 0iamond *lac,fan -nemia 25ongenital (ure Red 5ell -plasia3 5ongenital hypoplastic -nemia. Rare disorder. .ot fully studied. )nly 200 5ases reported 5ongenital mutations in R($19 and other ribosomal proteins. Ap to ?? mutations has been described to date 0efined as .ormal (*6 but with mar,ed decrease in marrow erythroblast. 56A E were insensiti+e to E() stimulation. Lymphocytes were able to inhibit erythropoeisis of *!. Htherefore concluedes immunologic etiology. <rowth Retardation esp bones )steoporosis -bnormal thumb (allor present at birth 6ailure of secondary se"ual maturity -nemia and hemorisderosis interferes with li+er function and endocrine maturation. H&allmar, is that these patients do not dmonstrate Renal abnormalities. <enetics: It is un,nown if the anemia is congenital or inherited.

8o 0ifferentiate 0iamond *lac,fan to 6anconi -nemias: (p 14I Part " Myelopt#isic Anemia Ghen a normal bone marrow myeloid cells are replaced by a metastatic tumor 2space occupying lesion3 and is replaced by fats. 6ound in patients with carcinoma. 5lassified as anemia of chronic inflammation -nemia correlates with patient7s tumor burden Hthe greater the tumor load/ the more se+ere the anemia is. !etastatic carcinoma when healthy bm was replaced by abnormal cells. 0amage in the marrow stroma by in+asion of abnormal cells. .on malignant 5onditions that can in+ade the bm are: !iliary 8* and <ranulomas In !yelopthisic/ .R*5 is present with immature leu,ocytes in (*. this is not associated by anemia. *ut with the space occupying lesion of the *!. $tippled (olychromatophilic R*5s may also be present. -s well as bands/ metamyelocytes and myelocytes Rare than immature rbcs. Leu,oerythroblastosis is often found is patients with far ad+anced stage of the disease with gra+e prognosis. <ranulocyte reading is inappropriate due to presence of infection in patients with immunosuppresed !yelpthicis anemia that causes the increase in G*5s. 0ifferential diagnosis: 5arcinomas that are li,ely to metastasiCe the *! are: *reast/ prostate/ lungs 2small cell or oat cell types3/ .euroblastoma in children/ -drenal corte"/ thyroid/ ,idney/ <I tract/ <eneto urinary tract and malignant melanoma. *iospy is the best method to +iew o+erall marrow structure. 8reatment 0epends on the underlying cause of the myelopthisic anemia. -.E!I- )6 $J$8E!I5 0I$)R0ER$: -. -nemia of 5hronic Renal 0isease 6ound in 5hronic Renal failure patients. *A. and Area is high. 0ue to accumulation of waste products in the plama and failure in E() production. (atients needs to be stimulated with E() to pre+ent anemia. -bnormal buff and helmet cell fragments may be seen at (*. 8reatment: 8ransfusion 0ialysis -llotransplantation of Didneys Recombinant E() *. -nemia of Endocrine 0isorders &ormones stimulate erythropoeisis by e"erting direct effect on *! stem cells. -nd a stimulatory effect on E().

-nemia here is usually mild/ with the marrow showing only decreased erythroid production. &ypothryoidism )"ygen re#uirements are influence by numbers of factors including thyroid. Lower metabolic rate decreases )C. &ypothyroidism patients are a bit anemic. Li,ely to occur in males than females 5ombination anemias are not uncommon/ I0- and pernicious might be present (ernicious and &ypothyroidism is thought to be autoimmune disorders. *ec 8hyroid antibodies tend to be high on patients with pernicious anemia. - significant no of patients with pernicious anemia has autoantibody for stomach gastric mucosa.=can also cause I0-/ due to malabsorptionK 8reatment: 8hyro"in &ypopituitarism (ituitary gland controls the thyroid/ gonads and adrenals. -nemia is caused by reduced metabolic demands. Easopressin from &ypothalamus stimulates E() 8he &ypothalamus acts on the (ituitary with in turn releases a number of hormones. (ituitary is its end gland that secretes the hormones. <rowth &ormone/ 8hyro"ine and prolactin also stimulates Erythropoeisis. 2independent of E()3. 8reatment: 5oc,tail of hormone drugs. -drenal -bnormalities: &ypoadrenalis -ddison 0isease &yperadrenalism=5ushings disease. 5ortisol produced in -drenal <lands 5ortisol has significant effects on circulating lymphocytes and eosinophils. -drenal hormones also ha+e effect on R*5 but not fully understood. -ddison7s mar,ed by decreased cortisolL anemia with granulocytopenia and lymphocytosis. 5ushings7 mar,ed by increased cortisolL normal to high rbc/ but rarely results to polycythemic. &ypogonadism Retarded growth and se"ual de+elopment secondary to deficiency of the testosterone. 8estosterone deficiency causes erythrocyte +alues to fall within female range. 8reatment: -ndrogen hormone 5. -nemia of (regnancy (regnancy increases demand for Iron. I0- is the common anemia during pregnancy. 8hough less li,ely/ folate anemia is also possible.

-nemias de+elops during the 12 14th w, of pregnancy. )r also through time of deli+ery. 0uring pregnancy (lasma +olume increases=so anemia might be caused by dilution. E"cessi+e loss of blood during the time of deli+ery 2450!L a+erage3 se+eres anemia. 8hrombocytopenia absent radius syndrome.KKK