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Anaemia. An aemia – from greek meaning ¨lack of blood¨ Anaemia = less than the normal quantity of hemoglobin in the blood Anaemic syndrome = clinical.

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Prezentace na téma: "Anaemia. An aemia – from greek meaning ¨lack of blood¨ Anaemia = less than the normal quantity of hemoglobin in the blood Anaemic syndrome = clinical."— Transkript prezentace:

1 Anaemia

2 An aemia – from greek meaning ¨lack of blood¨ Anaemia = less than the normal quantity of hemoglobin in the blood Anaemic syndrome = clinical syndrome caused by tissue hypoxia

3 NORMAL VALUES OF RED BLOOD CELLS men women Haemoglobin (Hb) 136 – g/l Haematocrite (HTK) 0,38 – 0,49 0,35 – 0,46 No of erythrocytes (RBC) 4,2 – 5,8 3,8 – 5,2 x10 12 /l Volume of erythrocyte (MCV) 80 – 95 fl Mass of Hb in erythrocyte 26 – 32 pg (MCH) Hb concentration in erythrocyte 0,32 – 0,37 (MCHC)

4 NORMAL VALUES OF RED BLOOD CELLS men women Haemoglobin (Hb) 136 – g/l Haematocrite (HTK) 0,38 – 0,49 0,35 – 0,46 No of erythrocytes (RBC) 4,2 – 5,8 3,8 – 5,2 x10 12 /l Volume of erythrocyte (MCV) 80 – 95 fl Mass of Hb in erythrocyte 26 – 32 pg (MCH) Concentration of Hb in erythrocyte 0,32 – 0,37 (MCHC)

5 Anaemic syndrome - symptoms rom (AS) Tissue hypoxia: pallor, fatigue, weakness, dyspnea Compensation and adaptation: Hypercinetic circulation, palpitations, tinnitus Secondary : Cardiovascular symptoms – decompensation of ischemic heart disease, AP, IM, claudications…

6 Anemický syndrom (AS) Progress and severity of AS depends on : 1. Absolute value of Hb Hgb g/l = most of patients suffer from symptoms 2. Speed of onset 3. Age and overall performance of the patient

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8 IRON PROTOPORFYRIN HAEM + GLOBIN HAEMOGLOBIN DNA – B12,folic acid, EPO

9 ANAEMIA - CLASSIFICATION Morfologic criteria: According to MCV: (80 – 95 fl) microcytic, normocytic, macrocytic According to MCH: (27-32 pg) normochrome, hypochrome According to no of reticulocytes: (0,7 – 2,8 %) anaemia with lowered, normal or incresed no of reticulocytes

10 A.MICROCYTIC ANAEMIA Iron deficiency anaemia Chronic disease anaemia Thalasemia, sideroblastic anaemia B.MACROCYTIC ANAEMIA Megaloblaste anaemia(lack of B12, folic acid, MDS) Macrocytic non-megaloblaste anaemia (usually secondary) C.NORMOCYTIC ANAEMIA Primar impairment of blood marrow: aplastic anaemia, MDS, PNH, myelofibrosis. Secondary impairment of blood marrow :(infiltration, infection, endocrinological and systemic diseases, ACD) D. ANAEMIA WITH RETICULOSIS Haemolytic aneamia corpuscular Haemolytic anaemia extracorpuscular – imunne and non-immune based

11 Pathofysiological classification

12 EPO

13 TSH Fe, Fol, B12 C, E

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17 Pathofysiological classification Proliferation and differentiation disorder Increased destruction of RBC Blood loss Combined etiology

18 IRON PROTOPORFYRIN Iron insufficiency sideroblastic anaemia ACD HEM + GLOBIN thalasemia HEMOGLOBIN DNA – B12, folic acid, EPO

19 Iron defficiency

20 Most frequent cause of anemia ( worldwide – WHO) 80%of all anaemia SA: 10% of fertile women Sideropenia: 35-58% of fertile women

21 Iron defficiency CAVE: influencing not just the blod count! DNA synthesis impairement Tissue fosforylation impairement Purine metabolism impairement Colagen synthesis impairement Granulocyte function impairement Neurotransmiter function impairement

22 Iron distribution in the organism

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25 Iron metabolism Food contents: 15-20mg/den Absorption: 1-2mg (duodenum, upper part of jejunum) Loss (epitel desqvamation) 1-2mg Pregnancy: overall loss: mg Supply in the organism: mg

26 Hepcidine Acute phase reactant Source: hepatic cells, heart, Iron stimulates Hepcidine Hepcidine inhibits iron absorption in the intestine, iron release from macrophages and iron transport via placenta ACD, hereditary hemochromatosis

27 Iron defficiency Insufficient intake - malnutrition Absorption impairement – maldigestion, malabsorption Increased loss Lowered intake

28 Insufficient intake Malnutrition Imbalanced diet Vegetarians - Meat: 25-30% of iron is absorbed - Vegetables: 5% of iron is absorbed

29 Iron absorption from various foods (%) Rice Spinach Beans Corn Lettuce Wheat Soya Ferritin Veal liver Fish meat Haemoglo bin Veal meat

30 Iron absorption from various foods (%) Rice Spinach Beans Corn Lettuce Wheat Soya beans Ferritin Veal liver Fish meat Haemoglobi n Veal meat

31 Resection of stomach – 65% patients Achlorhydria Coeliakia M. Crohn Infection H. Pylori with gastritis Absorption disorder

32 Loss GIT (h. hernia, gastritis, ulcerous disease, tumours, intestinal inflammmatory diseases, hemorhoids, parasites, diverticulitis…) Respiratory tractus Urogenital tract Menses = cca 3mg Fe / den NSAIDs, hemodialysis, blood testing, self - harming

33 Increased need Gravidity Brest-feeding Growth

34 Symptoms Anemic syndrome Cefalea, paresthesia, fatigue Tongue burning, angulitis Odyno-, dysfagia Sy Kelly-Patterson Brittle hair, nails (Pica, pagofagia)

35 Physical examination Pallor – skin, mucous membrane Blue sclerae Ulcers/ angulitis Smooth tongue Straight/(spoon-shaped) nails Achlorhydria, atrophic gastritis

36 Laboratory findings RDW: high Trombocytosis (over 50% of patients) BM –staining for iron - lack of Fe in siderophages - sideroblasts lower then 10%

37 Laboratory findings MCV under 80fl MCH under 25ug MCHC – late symptom Transferrin -increased S-ferritin <20ug/l Transferrin satur. – under15 % (N: 20-40%) VKFe (TIBC): increased S-sTfR > 8g/l

38 Fe TIBC satTRF ferritin TRF receptor _______________________________________________ Iron insuf.      Chronic disease associated anaemia   N N N (ACD) Thalasemia N or  N or  N or  N or   DIFFERENTIAL DIAGNOSIS OF IRON INSUFFICIENCY (mikrocytic anaemia)

39 CAVE Ferritine Acute phase reactant Nespecific tumorous marker Level increases with age (75ug/l in old people = ? = iron defficiency)

40 Iron defficiency Prelatent Latent Manifest - SA

41 Typical patient with IDA 1.Woman 20-45y, fatigue, sleepiness, ear buzzing, hairloss, brittle nails, hyper- polymenorhea or normal menses. 2. Man 50y or older, dysfagia, weightloss, treated with ASA for ICD, blood in stools or urine.

42 Treatment of IDA = Treatment of the cause of iron loss + iron supply

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44 Ferrotherapy mg Fe / day Until enough supply is formed (ferritin 50ug/l) Use on an empty stomach CAVE: polyphenols, milk, egg yolk Dyspepsia Parenteral forms (CAVE: anaphylaxis; x new forms are safer - karboxymaltose)

45 Ferinject (Vifor, Francie) inj. Fe3+ karboxymaltóza 100mg, 500mg

46 P.o. iron treatment control -Reticulocyte crisis D Increase of haemoglobin -Normalisation of MCV a RDW -Iron supply forming Ineffective treatment: 1.Diagnosis checking :BM examination, GIT examination aso…. Cave self-harming 2.Switch to i.v. therapy

47 Thalassemia

48 IRON PROTOPORFYRIN Fe insufficiency sideroblastic anemia ACD HEM + GLOBIN thalasemia HEMOGLOBIN DNA – B12, folic acid

49 Thalassemia + thalasemia, 0thalasemia Fetus: - Hb F α2 γ2 Adult - Hgb A: α2 β2 - Hgb A2: α2 δ2 - Hgb F: α2 γ2

50 Thalassemia α –thalasemia = α disorder β – thalasemia = β disorder

51 α - Thalassemia (Normal genotype: α α / α α) - α/ α α = silent carrier - α/- α, - - / α α = carrier ( mikrocytosis, erythrocytosis): = Thalassemia minor - - / - α = HbH (β4) (splenomegalia, mikrocytosis, bones) - - / - - = hydrops fetalis, sy Hb Bart´s (γ4)

52 β - Thalassemia More severe then α–thalassemia β – thalasemia minor ( β+/ β, β0/ β) Mikrocytosis, anaemia, erythrocytosis β – thalasemia intermedia ( β+/ β+, β0/ β+) β – thalasemia major ( β0/ β0, β+/ β+) Severe anemia, anisopoikilocytosis, affected ERY, HbF, hepatosplenomegalia,bone deformities,permanent transfusion therapy, Fe overload, Tx, splenectomia, HU

53 BETA THALASEMIA Pathogenesis:Pathogenesis:  chains formation impairement  increased synthesis of  and   chains formation impairement  increased synthesis of  and  Alpha chains overdose –low solubility, precipitation, agregates deform cell membranesAlpha chains overdose –low solubility, precipitation, agregates deform cell membranes Hb – easy autooxidation, lower stability  release ofHb – easy autooxidation, lower stability  release of Fe  cell destruction by peroxidative lipid cleavage. Fe  cell destruction by peroxidative lipid cleavage. Inefective erythropoiesis, large numbers of erytrocytes decline as soon as the BM + peripheral hemolysis + shortened lifespanInefective erythropoiesis, large numbers of erytrocytes decline as soon as the BM + peripheral hemolysis + shortened lifespan Significant compensatory erythropoiesis hyperplasia Significant compensatory erythropoiesis hyperplasia  corticalis usuration  bone deformities, fractures, extramedular corticalis usuration  bone deformities, fractures, extramedular hemopoiesis hemopoiesis Relative Fe defficiency in BM because of hyperplasticRelative Fe defficiency in BM because of hyperplastic erythropoiesis, at the same time increased Fe supply (coming from destroyed ery in monocyte- macrophage system)  increased Fe resorption in the intestine  Fe overload of the organism (together with Fe coming from transfusions). erythropoiesis, at the same time increased Fe supply (coming from destroyed ery in monocyte- macrophage system)  increased Fe resorption in the intestine  Fe overload of the organism (together with Fe coming from transfusions).

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56 MEGALOBLAST IC AN AEMIA Lack of B12 of folic acid: 1. Pernicious anaemia - B12 absorption in the distal intestine disorder due to lack of intrinsic factor (produced by parietal cells of gastric mucosa) 2. D ihydrofol a t redu c t ase inhibitors (MTX, ARA-C)

57 MEGALOBLAST IC AN AEMIA - CAUSES Insufficient intake of B12 of folic Absorption impairement : a) lack of intrinsic factor, intrinsic factor b) celiakia, Crohn disease, intestinal resection, diverticules, strictures,parasites c) resorption inhibitors (fenylhydantoin,PAS,pyrimidin, neomycin) d) sele c tiv e malabsorp tion B12 with proteinuria Transport disorders because of lack of transkobalamin I. a nd II. Increased demand (gravidit y, growth, anaemia with hyperplasia of erythropoiesis Increased loss ( hepatic laesions, bleeding ) dihydrofol at redu ctase inhibitors (MTX,pyrimethamin) pyrimidin antagonists (ARA-C) / purin antagonists (6-MP)

58 Megaloblastic anaemia Blood count– macrocytes (↑MCV, ↑MCH,normal MCHC), ↓RTC, megalocytes, megaloblasts, leukocytosis with left shift, thrombocytopenia. Bone marrow– hyperplasia of erytropoiesis, megaloblasts, granulocyte macrocytosis, mgkc. polyploidia dif.dg. MDS (cytogenetics, cytochemistry) biochemistry – ↓ B12, ↓folic acid, ↑direct and indirect bilirubin, intrinsic factor antibodies, antibodies against parietal cells, normal iron supplies

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60 Proteins binding VITAMIN B12 Intrinsic factor B12 absorption in ileum, binding to specific receptor (cubilin) Secerned by parietal gastric cells In case of lack leads to B12 malabsorption TRANSCOBALAMIN I Binds B12 in plasma,binds to B12 in stomach before binding to intrinsic factor, produced by neutrofiles and cells with exocrine secretion, his lack leads to low serum B12 levels TRANSCOBALAMIN II Enables B12 absorption by cells, receptor on all type of cells, produced by endotelial cells, fibroblasts, ileum cells.., his lack leads to severe B12 deficiency in cells

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62 Pernicious anaemia

63 Megaloblastic anaemia Diferential dg.: atrofic gastritis / sprue/ inflamations, parasites/ medication/ liver laesionsatrofic gastritis / sprue/ inflamations, parasites/ medication/ liver laesions DNA synthesis impairement due to abnormal cell clone– MDSDNA synthesis impairement due to abnormal cell clone– MDS (bone marrow biopsy, (bone marrow biopsy, cytogenetics, cytochemistry, B12) cytogenetics, cytochemistry, B12)

64 Treatment Substitution - vitamin B – 1000 μg/d - maintainance dose 1 x za 6 – 8weeks all life long reticulocyte crisis : 5.-7.d of treatment rise of reticulocyte count up to 10-30%. need of iron metabolism parameters, regular GSK and colonoscopy

65 Autoimmune disease Smooth tongue surface, vitiligo, grey hair Not just anaemia, but pancytopenia Parenteral substitution of B12 Reticulocyte crisis GSK á 1-2years

66 Anaemia with increased no of reticulocytes HEMOLYTIC ANAEMIA - corpuscular - estracorspuscular bleeding - acute

67 CORPUSCULAR HEMOLYTIC ANAEMIA MEMBRANE DEFECTS ENZYMOPATIA HEMOGLOBINOPATIA

68 NON-IMMUNE ACQUIRED HEMOLYTIC ANAEMIA MECHANICAL AND PHYSICAL CAUSES heart valve impairement hemoglobinuria microangiopatic hemolytic anemia widespread burns METABOLIC CAUSES liver disease, alcoholism hypofosfatemia hereditary abetalipoproteinemia malnutrition Cu overload Wilsonś disease CHEMICAL SUBSTANCES oxidative agents, snake venon INFECTIONS Direct ery infection – malaria septicemia ( clostridium perfringens aj. ) leptospira, borelia

69 Corpuscular Haemolytic anaemias PathogenesisPathogenesis Lack of and defects in membrane proteins (ankyrin, spectrin, etc.)Lack of and defects in membrane proteins (ankyrin, spectrin, etc.)  Decreasesd size of ery surface – spherocyteDecreasesd size of ery surface – spherocyte increased cell membrane permeability ( Na ) increased cell membrane permeability ( Na )  Increased need for eneregy -Increased need for eneregy - - (Na pump) increased rigidity and loss of flexibility - (Na pump) increased rigidity and loss of flexibility  passge through spleen sinusoid more difficult  passge through spleen sinusoid more difficult  loss of membrane parts – microspherocyte loss of membrane parts – microspherocyte cell deth in the spleen  cell deth in the spleen  EXTRAVASCULAR HAEMOLYSIS EXTRAVASCULAR HAEMOLYSIS

70 Hereditary spherocytosis Autosomal dominant ( rarely recesiive) disease with variable gene expressivity  variable clinical symptoms (phenotype)Autosomal dominant ( rarely recesiive) disease with variable gene expressivity  variable clinical symptoms (phenotype) ( anemia with ićterus, splenomegaly, hemolytic crisis ). ( anemia with ićterus, splenomegaly, hemolytic crisis ). Diagnostics:Diagnostics: Anemia + s reticulocytosis + spherocytes in blood smear, Hyperplůasti erythropoiesis in bone marrow, increased level of both direct and indirect bilirubin, serum Fe a feritin not increasedAnemia + s reticulocytosis + spherocytes in blood smear, Hyperplůasti erythropoiesis in bone marrow, increased level of both direct and indirect bilirubin, serum Fe a feritin not increased Osmotic resistance of erythrocytes decreasedOsmotic resistance of erythrocytes decreased Autohemolýza ( upravuje se po podání glukózy i ATP ) increasedAutohemolýza ( upravuje se po podání glukózy i ATP ) increased PINK testPINK test Dif dg.: other corpuscular anemias (HE, etc.)Dif dg.: other corpuscular anemias (HE, etc.) imunne hemolytic anemias imunne hemolytic anemias non-immune extracorpuscular hemolytic anemias non-immune extracorpuscular hemolytic anemias paroxysmal nocturnal hemoglobinuria paroxysmal nocturnal hemoglobinuria sometimes MDS sometimes MDS Léčba: splenectomyLéčba: splenectomy

71 ERYTROCYTE ENZYMOPATHY Defects in enzymes of anaerobe glykolysisDefects in enzymes of anaerobe glykolysis pyruvát kinázy defficiency (PKD) – chronic: haemolytick anemia, with little effect of splnectomia Defect in enzymes of pentos cycleDefect in enzymes of pentos cycle glucose-6-phosphate dehydrogenase defficiency increased sensitivity to oxydazing agents – chronic haemolysis or haemolytic crisis– anemia with Heinz bodies

72 ANAEROBE GLYKOLYSIS

73 GLUCOSE-6-PHOSPHATE DEHYDROGENASE defficiency Results in: lack of NADPH …. Increased sensitivity to oxydating agentsResults in: lack of NADPH …. Increased sensitivity to oxydating agents Gene for G6PDH: X – chromosome, wide physiologic variability of the enzymeGene for G6PDH: X – chromosome, wide physiologic variability of the enzyme Mutation: mostly point mutation in 1 or to bases  Mutation: mostly point mutation in 1 or to bases  decreased enzyme production, production of the enzyme with decreased decreased enzyme production, production of the enzyme with decreased activity or production of the enzyme with decreased afinty to the substrate or activity or production of the enzyme with decreased afinty to the substrate or with decreased stability with decreased stability Wide variability in clinical symptoms : Wide variability in clinical symptoms : Silent carrier severe haemolytic crisis, neonatal icterus Silent carrier severe haemolytic crisis, neonatal icterus Diagnostics:Diagnostics: G-6-PD activity analysisG-6-PD activity analysis Activity to substrate analysis, mobility in ELFO, stabilityActivity to substrate analysis, mobility in ELFO, stability Molecular geneticsMolecular genetics Other: GSH stability test, Heinz body formation testOther: GSH stability test, Heinz body formation test Th:Th: Prevention of exposure to oxydative agents (medication: antimalarics, sulfonamides,. Food: vicia fava etc.), splenectomy, stem cell transplantPrevention of exposure to oxydative agents (medication: antimalarics, sulfonamides,. Food: vicia fava etc.), splenectomy, stem cell transplant

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76 HEMOGLOBINOPATHIES Abnormal Hb with mostly one aminoacid (AA) substitution in the globion chaineAbnormal Hb with mostly one aminoacid (AA) substitution in the globion chaine a/ sicle cell anemia – HbS a/ sicle cell anemia – HbS b/ Hb C, Hb D, Hb E – chronic haemolytic anemias often in combination with Hb S or  thal b/ Hb C, Hb D, Hb E – chronic haemolytic anemias often in combination with Hb S or  thal c/ instable haemoglobin diseases c/ instable haemoglobin diseases hydrofobe AA  decreased binding activity of Hb or impaired secondary structure of Hb hydrofobe AA  decreased binding activity of Hb or impaired secondary structure of Hb and contacts between subunits and contacts between subunits chronic hemolytic anemia with Heinz bodies( denaturation of nestable Hb ) chronic hemolytic anemia with Heinz bodies( denaturation of nestable Hb ) d/ methemglobinemia d/ methemglobinemia Fe3+ stabilisation due to histidine tyrosine in proximity of hem group results in cynosis Fe3+ stabilisation due to histidine tyrosine in proximity of hem group results in cynosis e/ hemoglobine with increased oxygen affinity e/ hemoglobine with increased oxygen affinity tissue hypoxia, cyanosis, polycythaemia in blood count. tissue hypoxia, cyanosis, polycythaemia in blood count. Diagnostika:Diagnostika: elfo Hb elfo Hb identifikace abnormálního Hb tryptickým štěpením identifikace abnormálního Hb tryptickým štěpením isopropanol test, Heinz body tests, isopropanol test, Heinz body tests, methemoglobine tests, afinity to O2 tests methemoglobine tests, afinity to O2 tests molekular genetics, DNA analysis molekular genetics, DNA analysis

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78 SICLE CELL ANEMIA Substitution glutamate valin on 6. position Substitution glutamate valin on 6. position  chain: Hb polymerisation, deformation of erythrocyte, tvaru sickle cell. chain: Hb polymerisation, deformation of erythrocyte, tvaru sickle cell. hemolýza extravscular + intravascular (small vessel obstruction)hemolýza extravscular + intravascular (small vessel obstruction) Autosomal dominant typeAutosomal dominant type homozygotic form – both  chains impairedhomozygotic form – both  chains impaired heterozygotic form – one  chain impairedheterozygotic form – one  chain impaired 25-50% HbS – sickle cell trait 25-50% HbS – sickle cell trait

79 SRPKOVITÁ ANÉMIE Clinicaly:Clinicaly: Hemolytic + aplastic crisis, splenomegaly, Hemolytic + aplastic crisis, splenomegaly, DiagnosticsDiagnostics krevní obraz – anemie s retikulocytozou a krevní obraz – anemie s retikulocytozou a srpkovitými ery srpkovitými ery elfo hemoglobinu – přítomnost Hb S elfo hemoglobinu – přítomnost Hb S identifikace Hb S peptickým štěpením globinu identifikace Hb S peptickým štěpením globinu molekul.genetika – analýza DNA - v prenatální péči molekul.genetika – analýza DNA - v prenatální péči Treatment:Treatment: Crisis prevention, transfusions, SCT Crisis prevention, transfusions, SCT

80 NEIMUNNÍ ZÍSKANÉ HEMOLYTICKÉ ANÉMIE MECHANICKÉ A FYZIKÁLNÍ PŘÍČINY MECHANICKÉ A FYZIKÁLNÍ PŘÍČINY vadná srdeční chlopeň vadná srdeční chlopeň pochodová hemoglobinurie pochodová hemoglobinurie mikroangiopatické hemolytické anémie mikroangiopatické hemolytické anémie rozsáhlé popáleniny rozsáhlé popáleniny METABOLICKÉ PŘÍČINY METABOLICKÉ PŘÍČINY jaterní choroby, alkoholismus jaterní choroby, alkoholismus hypofosfatémie hypofosfatémie hereditární abetalipoproteinemie hereditární abetalipoproteinemie podvýživa podvýživa nadbytek mědi, Wilsonova choroba nadbytek mědi, Wilsonova choroba CHEMICKÉ LÁTKY CHEMICKÉ LÁTKY oxidační činidla, hadí jedy oxidační činidla, hadí jedy INFEKCE INFEKCE přímá infekce erytrocytů: malárie aj. přímá infekce erytrocytů: malárie aj. septikémie ( clostridium perfringens aj. ) septikémie ( clostridium perfringens aj. ) leptospiry, borelie. leptospiry, borelie.

81 MIKROANGIOPATICKÁ HEMOLYTICKÁ ANÉMIE příčina: rozrušení integrity membrány erytrocytu mechanickou příčinou v průsvitu cévy, nejčastěji depozity fibrinu v místě poškození endotelu cévní stěny.příčina: rozrušení integrity membrány erytrocytu mechanickou příčinou v průsvitu cévy, nejčastěji depozity fibrinu v místě poškození endotelu cévní stěny. Vaskulitidy, akutní glomerulonefritis, po SCT, nádory, operace chlopní, AV malformace, léky – ticlopidin, infekce – Shigatoxin. Vaskulitidy, akutní glomerulonefritis, po SCT, nádory, operace chlopní, AV malformace, léky – ticlopidin, infekce – Shigatoxin. fragmentace krvinek – schistocyty – zvýšený zánik ve slezině, při masivní hemolýze – intravaskulární hemolýza při současné aktivaci kaogulačního systému – DIC s tvorbou mikrotrombů v cirkulaci.fragmentace krvinek – schistocyty – zvýšený zánik ve slezině, při masivní hemolýze – intravaskulární hemolýza při současné aktivaci kaogulačního systému – DIC s tvorbou mikrotrombů v cirkulaci. klinický obraz : dán kombinací hemolytické anémie, trombocytopénie a přítomnosti mikrotrombů (CNS, ledviny )klinický obraz : dán kombinací hemolytické anémie, trombocytopénie a přítomnosti mikrotrombů (CNS, ledviny ) HUS, TTP, HELLP v graviditě – hemolýza, poruchy jaterních funkcí, trombocytopenie, DIC. HUS, TTP, HELLP v graviditě – hemolýza, poruchy jaterních funkcí, trombocytopenie, DIC.

82 Patofyziologie HUS a diagnostika aktivace endotelu toxin sekrece cytokinů sekrece vWF exprese adhezivních molekul aktivace monocytů zánik endotelií sekrece cytokinů aktivace trombocytů adheze a invaze neutrofilů aktivace neutrofilů elastázy, proteázy, H 2 O 2 adheze trombocytů deskvamace endotelií poškození endotelií trombocytopenie okluze glomerulů MAHA renální selhání

83 MIKROANGIOPATICKÁ HEMOLYTICKÁ ANÉMIE Laboratorní nález:Laboratorní nález: anémie s retikulocytózou, schistocyty, akantocyty, sférocyty, anémie s retikulocytózou, schistocyty, akantocyty, sférocyty, trombocytopenie se známkami DIC, nález multimerů při elfo vWF při TTP, molekulárně genetické vyšetření. trombocytopenie se známkami DIC, nález multimerů při elfo vWF při TTP, molekulárně genetické vyšetření. Zvýšen přímý i nepřímý bilirubin v séru, zvýšení LDH, Zvýšen přímý i nepřímý bilirubin v séru, zvýšení LDH, proteinurie, Hburie, zvýšen volný Hb, kreatinin, urea. proteinurie, Hburie, zvýšen volný Hb, kreatinin, urea. Léčba:Léčba: léčba vyvolávající příčiny, u TTP/HUS plasmaferéza se substitucí čerstvou zmrazenou plasmou, kortikoidy, antikoagulancia, transfuze erytrocytů. léčba vyvolávající příčiny, u TTP/HUS plasmaferéza se substitucí čerstvou zmrazenou plasmou, kortikoidy, antikoagulancia, transfuze erytrocytů.

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85 AUTOIMMUNE HEMOLYTIC ANAEMIA Clasification HEAT antibodies - idiopatic - secondary (lymfoproliferation, other type of tumours, autoimmune diseases, viral infections, immunodefficiency) -drug induced HA COLD antibodies - idiopatic - secondary (lymfoproliferation, viral inf., mykoplasma, autoimmune diseases - paroxysmal cold haemoglobinuria (lues …) MIXED HEAT AND COLD antibodies

86 Pathogenesis of AIHA: Cooperation disorder among supresor T helper T lymphocytes and B lymphocytes responsible for immunity control Dysregulation of this system leads to insufficient supression of antibody formation against own antigens

87 IgG – monomér, Fc část – vazebné místo pro C1q složku komplementu a Fcγ receptor makrofágů. IgM – pentamér, Fc část – vazebné místo pro C1q složku komplementu a Fcγ receptor makrofágů.

88 HEAT ANTIBODIES IgG chara cter – optim al at 37 0 C Catch up of erythrocytes with binded antibody by spleen macrophages EXTRAVAS CULAR HEMOL YSISEXTRAVAS CULAR HEMOL YSIS Activation of complement by high antibody titre INTRAVA CULAR HEMOL YSISINTRAVA CULAR HEMOL YSIS

89 COLD ANTIBODIES IgM chara c ter – optimál at 4 0 C Bound to erytrocyt es in colder acral parts, possibility of complement activation, ery aglutination INTRAVAS CULAR HEMOL YSIS EXTRAVAS CULAR HEMOL YSIS

90 Secondary AIHA with heat antibodies AUTOIM MUNE DISEASESAUTOIM MUNE DISEASES syst emic lupus erytematodes, revmatoid art h ritis, s c lerodermi a, ulceros e c olitis, syndrom e of anti ph os ph olipid antibodies HEMATOLOGIC TUMOURS chronic lym ph aden osis, malign lymphomas, rarely a c ute leu cae mi a OTHER TUMOURS c arcinom a, thymom a, Kaposi sarkom a, teratom a INFECTIONSINFECTIONS EBV, HIV-1,2, HCV, vaccination (difteria-pertusis- tetanus) IMUNODEFICIENCYIMUNODEFICIENCY congenital and acquired congenital and acquired hypogamaglobulinemia and dysgamaglobulinemia

91 DRUG-INDUCED HEMOLYTIC ANAEMIA hapten typehapten type imunocomplex typeimunocomplex type De-novo antigen formationDe-novo antigen formation

92 AIHA –laboratory parameters: Blood count:Blood count: makrocytic anaemia with reticulocytosis Biochemistry:Biochemistry:  direct and indirect bilirubin,  urobilinogen in urine Special tests:Special tests: Direct and indirect antiglobuline test (Coombs test) INTRAVASCULAR HEMOLYSIS PROOF:  free Hb in plasma,  levels of haptoglobin and hemopexin in serum, hemoglobinuria

93 DIRECT COOMBS TEST DIRECT COOMBS TEST We add : anti IgG Erytrocytes with bound Ab

94 INDIRECT COOMBS TEST Sérum with free antibodies we add: erythrocytes of particular blood group we add : anti IgG or anti C3b

95 AIHA – diferential diagnosis: CORPUSCULAR HEMOLYTIC ANAEMIACORPUSCULAR HEMOLYTIC ANAEMIA PAROXYSMÁL NIGHT HAEMOGLOBINURIA negative Coombs test, positive special tests (autohemolysis, erytrocyte enzyme tests, elfo Hb, shortened lifespan of autologous, not donor erythrocytes) PAROXYSMÁL NIGHT HAEMOGLOBINURIA negative Coombs test, pancytopenia, CD59 and CD55 antigen defficiency on erythrocytes, CD14 antigen def. on the surface of granulocytes and monocytes GILBERT DISEASE negative hemolysis testsGILBERT DISEASE- negative hemolysis tests NON- IMMUNE HEMOLYTIC ANAEMA NON- IMMUNE HEMOLYTIC ANAEMA microangiopatic hemolytic anemia (schistocytes, kidney and CNS affection), anemia from physical and chemical causes MYELODYSPLASTIC SYNDROME MYELODYSPLASTIC SYNDROME - hemolytic form morfological dysplastic changes,chromosomal aberances,cytochemical changes, clonality.

96 AIHA - treatment: Light form ( Hb > 80 g/l ): PREDNISONE PREDNISONE 1 mg/kg/d 2-3 weeks - in case of good effect decreasing dose every 2-3 days by 10mg until 20 mg/day. - slow reduction of dose (by 5mg in 7-10 days) until 5-10mg every second day. - end of corticooid therapy when repeated direct Coombs test negativity When therapy is ineffective or relaps occurs: combination with CYCLOPHOSPHAMIDE CYCLOPHOSPHAMIDE mg/d or CYCLOSPORINE A CYCLOSPORINE A 3 mg/kg/d.

97 AIHA - treatment: SEVERE form ( Hb < 80 g/l ): PREDNISONE PREDNISONE 1-2 g i.v. daily 5 days, after that in case of good response fast decrese of dose to 1 mg/kg. - combination of corticoids with : CYCLOPHOSPHAMIDE CYCLOPHOSPHAMIDE 200 mg i.v./d i.v. IMMUNOGLOBULINS i.v. IMMUNOGLOBULINS 0,5g /kg/d PLASMAPHERESIS RITUXIMAB RITUXIMAB (anti CD20 monoclonal Ab) Transfusion – together with corticoids, monitored hospitalised patient, not more then 1 TU/day (unless vital indication)

98 Thank you


Stáhnout ppt "Anaemia. An aemia – from greek meaning ¨lack of blood¨ Anaemia = less than the normal quantity of hemoglobin in the blood Anaemic syndrome = clinical."

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