Anemia

flat **Anemias Table** by Megan Gold, CO 2012

↑LDH ↑SGOT ↑RetC-to compensate for hemolysis ↑RDW-fast output old and new cells Hemoglobinuria/plasma – b/c cannot process all. __↑ Indir bili-overloaded system cannot keep up with demand so bili does not get conjugated to glucuronic acid__ __↑Metheme/methemoglobin-b/c broken free heme byproduct__ __↓Haptoglobin-taken out of serum when binds heme to the liver__ ||  || Enterohepatic recirculation of urobilirubin after cleavage of glucuronic acid in gut à elevated levels of direct bili. || ↑LDH ↑SGOT ↑RetC ↑RDW __↑Direct bili (enterohepatic recirculation)__ ||  || -hyperbilirubinemia || Protects against oxidative stress à ↓ G6PD à ↓reduced glutathione à lacks ability to help with oxidative stress à Hgb sticks to spectrin on RBC wall à abnml shape à lysis by spleen -sex-linked rec || Protein in urine (?) __Perif Smear (sometimes see)__ à Microspherocytes Blister cells à cytoskeleton defect Bite cells à same Usually NO morphology Δ || -Folate -Avoid oxidative foods (fava beans) -supportive care || -Jaundice -Splenomegaly -Hyperbili in 1/3rd of neonates -Aplastic crisis -Bilirubin high à stone à cholecystectomy || Spectrin/ankyrin/ band 3 mutations à weak cytoskeleton, spherical shape à splenic entrapment and easy to lyse || Hct-variable Hgb-variable ↑RetC à account for hemolysis ↑indir bili à too much heme to process ↓MCV à making too fast so microcytic Osmotic fragility test à abnml/low Spherocytes on smear || splenectomy || || Variable chronic anemia Extravascular hemolysis Splenomegaly Gallstones Aplastic crisis || Problem à pyruvate problem à ↓ATP production à ↑2,3-BPG and mis-shapen RBCs à splenic destruction || ↑RetC à account for hemolysis NO morphology Δ || -Folate -Spenectomy-s.times -transfusions in severe cases || COLD/INTRAvascular || Dark Urine Acute/Chronic anemia Pallor/Jaundice Splenectomy s.times
 * Disease || Clinical SS || Pathophysiology/Cause || Lab test and reason why || Treatment ||
 * Intravascular Hemolysis || Splenomegaly || Breakdown of hemoglobin in vessels. || ↑free Hgb
 * Extravascular Hemolysis ||  || Ingestion and clearance by macrophages in the Reticulo-endothelial system. Fe stored in ferritin and heme à bili
 * Glucose-6-Phosphate Dehydrogenase || -Intermittent acute hemolytic anemia
 * Hereditary Spherocytosis || -Anemia mild-mod
 * PK-Pyruvate Kinase Deficiency
 * Autoimmune Hemolytic Disorders

SAME FOR EXTRA ↓ || IgG and IgM à activates C5-9 complement à RBC damage by complement || ↑RetC ↑Bili Hemoglobinuria Spherocytes Bite cells __Direct Coombs__ (test for IgG, C3D, C4D-bound to RBC) à **+ Complement** (C3D, C4D) __Indirect Coombs__ (test for IgG and Complement-free in plasma) à WARM/EXTRAvasc. || Dark Urine Acute/Chronic anemia Pallor/Jaundice Splenectomy s.times || IgG only Opsonizing Macrophages and spleen affected so that the lysis is in the spleen and outside the blood system || ↑RetC ↑Bili Hemoglobinuria Spherocytes Bite cells __Direct Coombs__ (test for IgG, C3D, C4D-bound to RBC) à **+ IgG** (sometimes weak complement) __Indirect Coombs__ (test for IgG and Complement-free in plasma) à Pallor Pain with exercise SOB Tachycardia Muscle problems Neurological problems || Dietary Absorption problems Inflammation/Infection à Cytokine production || Microcytic and Hypochromic ↓Hgb-no iron to bind heme ↓Hct-less and smaller RBC’s bc no iron ↓ferritin-iron stores used up ↓RetC-because no iron to make RBC’s ↓serum iron ↑TIBC-bc capacity is increased due to no binding ↑RDW __Perif Smear__ Spherocytes, fragmented cells, target cells || Oral iron salts (150-200 mg tid) IV/IM iron. 1st see serum Fe respond à RetC nmlizes, Hgb nml after 7- 10 days. Continue treatment until ferritin stores returned and MCV and RDW are nml (which will take 100 days or so until abnml RBC’s have been removed) || -Brown-blood due to Fe+3 without change when exposed to O2 -In severe cases à brady, respire depression, convulsions, acidosis. || __Acquired__ -free radicals (NO, H2O2) -Drugs (benzocaine) __Hereditary__ -homozygous def of cytochrome-b-5-reductase (prevents reduction of Fe+3 à Fe+2) -Hemoglobin M (mutation of chains that inhibits reduction of Fe+3) ||  || __Acquired__ Remove drug or chemical causing disease __Hereditary__ Methylene Blue || -Underlying inflammatory disease -Renal insufficiency -Thyroid disorder -Adrenal insufficiency -fever -arthritis -swelling (infections) || Inability to use iron stores and decrease EPO production result from inflammatory cytokines: -TNF/IL-1 à ↓iron mobilization/ EPO production -INFγ/β à inhibits erythropoisis -Hepcidin (induced by cytokines) à ↑ Fe storage, ↓duod abs, block Fe release from macrophages || -Hgb 8-12 -Usually Normocytic/ normochromic à microcytic /mild hypochroma ↓RetC –reticulocytopenia b/c cannot get iron since sequestered due to presence of **hepcidin**. ↑Ferritin-due to increased/sequestration of iron(**DIFF from Iron defic anemia** ) ↓TIBC (**DIFF from IDA** ) ↓Serum Iron (**like IDA** ) ↓Transferrin saturation (**as with IDA** ) ↓EPO for degree of anemia (espec with renal disease. But usually not seen until <40% renal function) || -Treat underlying condition to à ↓cytokines and inflammation -Give iron -Give EPO (especially with renal disease) -Hormone replacement of endocrine disease || -irritability -weakness -wt loss -abdominal pain and vomiting || -Pb inhibits synthesis of protoporphyrin ring à ↓heme || ↓MCV = Microcytic/hypochromic because Pb is preventing production of porphyrin ring ↓RetC-because no heme to make iron so cannot make RBC’s ↑Lead levels 2. Chelation || Microcytic/hypochromic Pappenheimer bodies (ppt iron in mitochondria à ring around nucleus) || B6-s.times works Transfusions Tx of other underlying cause (Cu deficiency, EtOHism, drugs) || CNS changes-cognitive dysfunction and emotional changes Numbness, tingling, loss of fine sensations Proprioception Ataxia CNS changes may be permanent. || Required for synthesis of methionine from homocysteine à precursors for DNA synthesis à effect erythropoisis in BM. So essentially it is a disease of ↓DNA synthesis __Causes__ __-Vegan Diet-rare cause__ __-IF deficient = **Pernicious**__ **__Anemia__** __à__ __(mal-abs of B12)__ __-autoimmune destruction of parietal cells that secrete IF__ __-Loss of ilial receptors-surgery, IBD__ __TcII deficiency__ || ↑MVC = Macrocytic/Normochromic (because increase in size as waiting for DNA to be made-arrest in S phase ↓RBC ↓RetC-because no B12 to make cells ↑RDW à anisocytosis -Nuclear-Cytoplasmic Asynchrony M:E ratio à E predominance ↑Homocysteine levels __↑methylmalonic acid__ __↑ to nml serum folate*__ __↓B-12 levels (s.times predictive)__ __Shillings Test: If abnml then add IF and see if corrects. If normal then not B-12 abs problem__ || B-12 injections Oral replacement ↑doses à abs via mass action Watch for other immune diseases -Rapid response to treatment and slowly resolving CNS indicates accurate dx. || So essentially it is a disease of ↓DNA synthesis __Causes__ __Insufficient dietary intake*1⁰__ __Mal-abs__ __à__ __parasitic infection (disrupts enterohepatic recirc)__ __EtOH consumption excess__ || ↑MVC = Macrocytic/Normochromic (because ↓RBC ↓RetC-because no B12 to make cells ↑RDW à anisocytosis -Nuclear-Cytoplasmic Asynchrony M:E ratio à E predominance ↑Homocysteine levels __↓serum folate__ __↓methylmalonic acid__ || Folate 1mg/d PO/IV/IM Rapid recovery of CBC. || Aplastic crisis - ↓RetC Pain crisis – Acute chest pain, multi-organ failure, priapism, bone infaction. || Sickling cells are actually “sticky” which leads to vessel damage, endothelial remodeling and vessel narrowing. This microvessel damage affects all organs (lungs, retina, kidneys, spleen, CNS) || ↑RetC-to compensate for hemolysis (except during aplastic crisis) ↑WBC/platelets due to BM response ↑RDW-increase production and constantly changing shape of the sickled cell ↓MCV – Microcytosis (Sβ ⁰ /Sβ+) Heme C crystals = red rods in RBC’s (SC disease) ↑Hb Fetal (2-30%) ↑LDH, AST (released from lysed RBC) ↑indirect bilirubin-due to hemolysis ↑Total bilirubin __Perif Smear__ Schistocytes Polychromasia-blue colored cells Anisocytosis (RDW effect) Howell Jolly bodies-occur in pt w/out functional spleen due to injury/occlusion from sickled cells à **splenic sequestration.** || 1. BM transplant w/ HLA matched sibling is 90% 2. Hydroxyurea à ↑Hb F 3. Transfusions – decrease pain crises extend life. || Infant Barts bodies = γ-4 H-bodies in adult || --/-α à limited binding to gamma chain during in-utero development and then β-agglutination during life. || ↓MCV – bc low α chains and agglutination of β-chains which à Barts ↓MCHC-because low levels of heme since less produced || Transfusions s.times || Mild splenomegaly Extramedullary Hematopoiesis à frontal bossing, hair on ends, enlarged mandible etc || Hb E is an unstable globin chain à ↓amount for heme production || ↓MCV = Microcytic ↓MCHC-because low levels of heme Target cells = Mexican hat = Excess of RBC plasma membrane due to ↓in heme content to RBC itself (RBC is not filled up so takes on this shape) || No transfusions || Extramedullary Hematopoiesis 2/3rds have abnml endocrine problems (hypothyroid, gonad problems etc) || 2 severely abnml β-globin chains ↑ Levels of Hb F (10-90%) || ↓MCV = Microcytic ↓MCHC-because low levels of heme since less produced Target cells = Mexican hat = Excess of RBC plasma membrane || ALWAYS transfusions Always chelation tx Hydroxyurea=↑HbF (via increasing gamma chains that can bind with the excess α-chains. ||
 * + complement** ||  ||
 * Autoimmune Hemolytic Disorders
 * + IgG** ||  ||
 * Iron Deficiency || Fatigue
 * Methemoglobinemia || -Cyanosis without accompanying ↓ in arterial PP
 * Anemia of Chronic Disease/Inflammation || -Variable anemia
 * Lead Based Anemia || -Personality changes
 * Basophilic stippling** -aggregates of RNA(also seen with macrocytic anemia of B12 and Folate) || 1. REMOVE source of lead
 * Sideroblastic Anemia || Variable anemia || Impaired production of protoporphyrin ring or incorporation of Fe into heme à accumulation of iron in mitochondria à Ring sideroblasts || ↓MCV =
 * B-12 Deficiency || Slow (months) onset
 * Hypersegmented neutrophils** -classical sign of B12 or folate deficiency.
 * Folate Deficiency || Quick Onset (weeks) || Required for synthesis of methionine from homocysteine à precursors for DNA synthesis à effect erythropoisis in BM.
 * Hypersegmented neutrophils**
 * Sickle Cell Anemia || Chronic Hemolytic Anemia
 * Hb H (Barts) || Mod-severe anemia
 * Hb EE || Mild Anemia
 * Cooley’s β-thal Major || Severe anemia

=Evaluation Flowchart=

=Table (MS Word)= by Megan Gold, CO 2012