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ANEMIA CLINICAL ASPECTS

All anemias: tired, pallor, weak, ears ringing, tachycardia

DISEASE	DISTRIB, AGE/SEX	CAUSES	PARTICULAR SYMPTOMS	TREATMENT	PROGNOSIS
Iron def	Most common cause of anemia	Blood loss (menses, GI) Poor diet Excess demand (preg, infant, teen) Malabsorption (Stomach disease, sprue)	Pica syndrome, Angular stomatitits, glossitis, Achlorhydria, mucosal atrophy Koionychia	Vitamins Ferrous sulfate (FeSo4) 300 mg/day	Side effects of vitamins: GI problems
Megaloblastic (B12 defic)		↓intake B12 ↓Absorption (lack of IF = Pernicious); lack of TC-II; blind loop Drugs (Anti-cancer agents) ↑demand (pregnancy, hemolysis) Inborn error of metabolism	50 % have abnormal EEG: Neurological disorders: taste, smell, vision changes Slight jaundice	B12 injections
Megaloblastic (Folate defic)		↓intake folate ↓Absorption (ciliac sprue) Drugs (Anti-cancer agents) ↑demand (pregnancy, hemolysis) Inborn error of metabolism	Slight jaundice Spina Bifida	Folate supplements
Anemia of Chronic Ds	2^nd most common cause of anemia	Infections, RA, TB, tumors, kidney/liver disease Trauma/surgery	Slow onset: N/V, Diarrhea, constipation	Fix the cause;	First 5-10 days: ↑retics 4-5 months à normal
Sideroblastic	Elderly	Alcoholism Drugs (TB, chloramphenicol) Hereditary	Sore tongue epithelium		10% à AML =preleukemic
True Porphyria		Genetic defect in heme	Photosensitivity Dermatitis Reddish urine
Precurser Syndrome		Genetic defect in heme Drugs, lead intoxication	Neurological and endocrine disorders
DISEASE	DISTRIB AGE/SEX	CAUSES	PARTICULAR SYMPTOMS	TREATMENT	PROGNOSIS
Hgb Varients in general		Hereditary structural defect in globin Hetero or homozygous Usually single aa substitution	If aa defect is in the internal, hydrophobic area of Hgb, can go from Fe+2 to Fe+3 (met-Hgb)		Hetero parents: 25% chance of affected child
Sickle Cell Trait: Hgb SA	8% US blacks 30% Africans	Hereditary heterozygous	Protected from maleria	Need more iron
Sickle Cell Disease: Hgb SS		Hereditary homozygous	Hypoxia à Sickle crisis Poor growth, splenic infarcts, gall stones, kidney problems, stroke	Need more iron Butyrate to ↑HgbF
HgbC		Hereditary homo or heterozygous	Gold bar crystals (post-spenectomy) Target Cells	Need more iron
Thalessemia (In general)	β high incidence: Mediterranean, India, SE Asia	Hereditary regulatory defect (↓ aa chains) in globin Heterozygous, usually ↓β chain	Extravascular hemolysis (spleen)	Need more iron; Transfusion Iron chelating drugs	How much ↓Hgb “ “ imbalance α β HgbF compensate Severity of anemia, effectiveness of Tx
Cooley’s or Mediterranean Homozygous β Thalessemia		Not enough β chains à Excess α chains à Heinz Bodies à Hemolysis	Hemosiderosis from iron in blood transfusions	Blood transfusion Iron chelating drugs BMT, SC	Not too serious Iron overload
Heterozygous β Thalessemia			asymptomatic		No problems
α Thalessemia
Hemolytic Anemias Mebrane: Hereditary Spherocytosis Anemia (HSA)	Most common membrane defect anemia	Herediary 75% Auto Dominant 25% Auto Recessive (spectin defic)	Shows up right away with jaundice Gallstones in older population; Intermittent disfunction anemia from infections. Intra and extravasc hemolysis	Need splenectomy; Need iron and folate for lifetime.	Infections can cause crisis
Hereditary Elliptocytosis	Not as common	Auto Dom (spectin defic)			Mild-severe; Can compensate
PNH	Elderly with anemia	Blood pH becomes acidic during sleep à RBCs lyse	Hemolysis and thrombosis Red urine in morning; Recurrent intravascular hemolysis Chronic hemosideruria	Need more iron	Pre-leukemia à AML
HDN				Rhogam to Rh neg mother
DISEASE	DISTRIB AGE/SEX	CAUSES	PARTICULAR SYMPTOMS	TREATMENT	PROGNOSIS
Hemolytic Anemias: Metabolic: G6PD def	Most common hemolytic anemia world-wide M>F	Hereditary enzyme deficiency X-linked Drugs worsen: Quinine Sulfa Aspirin Vit K Fava Bean	Infection à exposure to oxidants à hemolysis Fe+2 à Fe +3	Need more iron
GdA	Most common variant of G6PD 10% Blacks		RBC die in 13 days Infection à exposure to oxidants à hemolysis Fe+2 à Fe +3
GdMed	2^nd most common variant Sardinanans, Jews, Italians		RBC half life < 13 days; Infection à exposure to oxidants à hemolysis Fe+2 à Fe +3
Gd Canton	Asians		Infection à exposure to oxidants à hemolysis Fe+2 à Fe +3
Pyruvate Kinase def		Hereditary enzyme deficiency Auto Recessive Only homozygous	Hemolysis	Need more iron

LABORATORY FINDINGS IN ANEMIA

DISEASE	Mechanism	Iron	RBC SIZE: MCV	Hgb MCHC	RBC SHAPE	Hct	OTHER
Iron def	Nutritional: Maturation defect Fe loss>Fe abs	↓serum iron ↓ferritin	micro	hypo		↓	Lose iron stores first Then lose serum iron
Megaloblastic (B12 defic)	DNA syn defect From ↓B12	↑serum iron ↑ferritin	Macro	normo	Oval; Howell-Jolly	Normal	Erythroid hyperplasic BM, ineffective ↓ reticulocyte count ↓Platelets and PMNs, hyperseg Schillings Test part II positive ELISA for B12
Megaloblastic (Folate defic)	DNA syn defect From ↓Folate	↑serum iron ↑ferritin	Macro	normo		Normal	Erythroid hyperplasic BM, ineffective ↓ reticulocyte count ELISA for folate
Chronic Ds	Can’t mobilize Fe from BM store: In mac:IL-1 and lactoferrin increases Fe binding, TNF inhibits erythroipoiesis.	↓TIBC ↓serum iron ↑ferritin	Normo	Normo to hypo		↓Drops to 25-35	↑Serum Fe binding TICB Retics norm-increased Iron stores normal
Sideroblastic	Enzyme problem; Fe not put on heme ring properly, Fe accum in mito of precursors	↑Serum Fe ↑ferritin	Micro	Hypo	Oval; Siderosm		Erythroid hyperplasic BM Ineffective erythroipoiesis ↓retic count
True Porphyria	Block in latter steps of heme synthesis; Iron not inserted in heme ring; excess production of rings.
Precurser Syndrome	Excess production of precursors in earlier steps of heme syn (PBG, ALA)
DISEASE	Mechanism	Diagnostic	RBC SIZE: MCV	Hgb MCHC	RBC SHAPE	Hct	OTHER
Hgb Varients in general	Structural globin defect Single aa substitution or deletion on globin Usually on β chain	Electrophoresis to ID type
Sickle Cell Trait: Hgb SA	α α βA βS 6 glutamic acid à valine	Na metabisulfite + phosphate à ppt of Hgb; Electrophoresis to ID type		Less soluble, ppts out	Sickle		ID by electrophoresis
Sickle Cell Disease: Hgb SS	α α βS βS			↑HgbF	Sickle		↑Reticulocytes BM: Prussian Blue stain Tactoids force RC into sickle in ↓O2
HgbC	α α βS βC 6 glutamic acid à lysine				Target Gold bar Finger
Thalassemia In general	α α βS βThal Defect in Hgb ↓ BM iron stores		Micro	Hypo	Heinz Target Howell J Sphero’s		Erythroid hyperplasic BM Ineffective erythroipoiesis ↑reticulocytes, Polychromasia
Cooley’s or Mediterranean Homozygous β Thalassemia	β0 β0 or β+ β+		Micro	Hypo	Heinz		Heniz Bodies (supravital stain)
Heterozygous β Thalessemia	βA β0 or βA β+		Micro	Hypo	Target cells
α Thalessemia	α -- α α						silent carrier
α Thalessemia	-- -- α α				Target cells		Basophilic stippling
α Thalessemia	-- α -- α						Excess β chains
α Thalessemia	β β β β						Hgb H Disease, can still survive
α Thalessemia	γ γ γ γ no α chains			No HgbF			Bart’s Hgb gamma 4; skeletal changes, Hepatomegaly, still live normal span
α Thalessemia	-- -- -- --			No Hgb			Hydrops Fetalis; dies at birth. Asian, blacks, Mediterranean
DISEASE	Mechanism	Iron	RBC SIZE: MCV	Hgb MCHC	RBC SHAPE	Hct	OTHER
Hemolytic Anemias Mebrane: Hereditary Spherocytosis Anemia (HSA)					Spherocytes		Erythroid hyperplasic BM Ineffective erythroipoiesis Polychromasia, ↑ retics
Hereditary Elliptocytosis					Elliptocytes
PNH	RBCs lack CD55 (delayed accelerated factor)	Prussian Blue Stain or Ab fluorescence
HDN	Hgb F: α α γ γ	Kleinhaure-Betke method					Rh neg mother: ghost cells.
Hemolytic Anemias: Metabolic: G6PD def					Heinz Bodies
GdA
GdMed
Gd Canton
Pyruvate Kinase def	Deficiency in ATP				No Heinz Bodies