THE RED BLOOD CELL: STRUCTURE AND FUNCTION

Blood:Ave 70 kg 5 L of bld (7% by vol)

Erythrocytes - Morphology

Bi-concave disk Benefits:

Flexible Maximum surface/volume ratio

Size uniform Water 65% Hemoglobin 35% No:

Nucleus Cell organelles

Erythrocytes - Basic function

Create & maintain an environment for physical integrity & functionality of Hgb

Erythropoiesis (Kinetics)

Substances necessary for RBC production:

Metals (iron, cobalt, manganese) Vitamins (B12, B6, C, E, folate, riboflavin, pantothenic, thiamine) Amino acids

Regulatory substances: Erythropoietin Thyroid hormones Androgens

Erythroid hyperplasia of BM in anemia

WHO Criteria Anemia Diagnosis

Hgb 130 g/L (Adult M), 120 g/L (Adult F)

Lower limits of normal, at sea level, in adult M&F

110 g/L: 6 mons to 6 y/o 120 g/L: 6 y/o to 14 y/o 110 g/L: Pregnant women

Classification of Anemia

Based on rate of progression: Acute Chronic

Based on severity: Mild Moderate Severe Very severe

Based on BM cellularity: Hyper-cellular Hypo-cellular

Classification of Anemia

Based on etiology: Impaired erythrocyte production Increase destruction Blood loss

Based on RBC morphology (MCV & MCH) Microcytic Hypochromic Macrocytic Normocytic Normochromic

PATHOPHYSIOLOGIC CLASSIFICATION OF ANEMIA

1. Impaired production 2. Increased destruction (Hemolytic) 3. Blood loss

PATHOPHYSIOLOGIC
Classification Example

Reduced production

Increased destruction

Deficiency of hematinics

Hemolytic anemia

Iron deficiency
Folate & B12 deficiency ACD

Intrinsic causes

Membrane defects Enzymopathy Hemoglobinopathy Immune reactions Microangiopathic Parasitic

Dyserythropoiesis

MDS
Sideroblastic a

Extrinsic causes

Marrow infiltration Failure of production

Aplastic anemia Pure red cell aplasia

Hypersplenism

Bleeding

IMPAIRED PRODUCTION (1) STEM CELL PROLIFERATION/ DIFFERENTIATION

APLASTIC ANEMIA PURE RED CELL APLASIA ENDOCRINE DEF (PITUITARY, THYROID, ADRENAL, TESTIS)

Anemia due to failure of production: Aplastic anemia

Causes Of Aplastic Anemia

Idiopathic (70 % or >)

Acquired/ Secondary:

Inherited/ Primary

Drugs

Fanconi anemia Familial aplastic anemia Dyskeratosis congenita Diamond Blackfan Syndrome Dubowitz syndrome Amegakaryocytic thrombocytopenia

6 mecaptopurine Methotrexate Cyclophosphamide Chloramphenicol NSAIDS

Chemicals: insecticides Toxins (benzene, CCl4 Irradiation Infection: Viral hepatitis; HIV; IM; CMV, EBV Pregnancy PNH MDS

Aplastic anemia

CAUSES

DAMAGE TO STEM CELL

REPEATED INFECTION; FREQUENT SICK DAY

DEPRESSION OR CESSATION OF ACTIVITY OF ALL BLOOD PRODUCING ELEMENT

BLEEDING TENDENCY AEB ECCHYMOSIS, PURPURA, PETICHIAE, BLEEDING FROM NOSE, MOUTH, VAGINA, RECTUM

LEUKOPENIA THROMBOCYTOPENIA DECREASE IN FORMATION OF RBC

PANCYTOPENIA

PALLOR OF SKIN & MUCOUS MEMBRANE, CYANOSIS

APLASTIC ANEMIA

Aplastic Anemia: Clinical Features

Anemia: pallor, easy fatigability, weakness, loss of appetite Thrombocytopenia: petechiae, easy bruising, severe nosebleeds, bleeding into GIT & renal tract Leukopenia: increased susceptibility to infections & oral ulcer

Aplastic Anemia: Clinical Features

Hepatosplenomegaly & LAD do not occur (presence suggest underlying leukemia) Hyperplastic gingivitis Special features Skin: Hyperpigmentation (caf au-lait spots, erythematous rash) Head: Microcephaly, micro-ophthalmia Mouth: cleft lip, leukoplakia General: small stature

Treatment

IMPAIRED PRODUCTION (2) RBC-BLAST PROLIF / DIFF

MEGALOBLASTIC ANEMIA (DNA SYNTHESIS) VIT. B12 DEFICIENCY FOLIC ACID DEFICIENCY HYPOCHROMIC ANEMIA (HEMOGLOBIN SYNTHESIS) HEME: IDA; SIDEROBLASTIC ANEMIA GLOBIN: THALASSEMIAS MULTIPLE MECHANISMS ACD (INFLAMMATORY, INFECTIOUS, NEOPLASTIC) RDA MYELOPHTHISIC ANEMIA (BM INFILTRATION) REFRACTORY ANEMIA W/ CELLULAR BM PROTEIN MALNUTRITION

Megaloblastic Anemia

Impaired DNA synthesis (Asynchronous Hematopoiesis)

B12 = co-factor Folate = transfer single carbon groups

Cells primarily affected: Blood cells, GI epithelial cells Megaloblastosis in BM

Causes of Megaloblastic anemia

Cobalamin deficiency due to Inadequate intake (vegans)

Causes of Megaloblastic anemia

Cobalamin deficiency Malabsorption

Gastric achlorydia Partial / total gastrectomy Drugs that block acid secretion Pernicious anemia

Causes of Megaloblastic anemia

Malabsorption

Terminal ileal disease:

Sprue Enteritis Resection Tumors

Competition of cobalamin:

Fish tapeworm, blind loop syndrome

Causes of megaloblastic anemia

Folic acid deficiency

Inadequate intake: unbalanced diet (alcoholics, teenagers, some infants) Increased requirements

Pregnancy Infancy Malignancy Increased hematopoiesis (chronic hemolytic anemias) Chronic exfoliative skin disorders Hemodialysis

Malabsorption Impaired metabolism

Other causes of Megaloblastic Anemia

Drugs that impair DNA metabolism

Purine antagonists: 6 mercaptopurine, azthioprine Pyrimidine antagonists: 5FU, cytosine arabinoside, others Others: procarbazine, hydroxyurea, zidovudine Hereditary orotic aciduria Lesch Nyhan syndrome
Refractory megaloblastic anemia DiGuglielmos syndrome Congenital dyserythropoietic anemia

Metabolic disorders (rare)

Megaloblastic anemia of unknown etiology

VIT. B12 DEF.

vs FOLIC A. DEF. Clinical

DIET:

VEGANS: DECREASE GENERAL:DECREASE

NORMAL DECREASE

In animal products Unaffected by cooking Need 1-2 ugrams daily

In leafy green veggies, liver, yeast Destroyed by cooking Need 100-200 ugrams daily

VIT. B12 DEF.

vs

FOLIC A. DEF.

CELL TURNOVER

DECREASE
DECREASE DECREASE

DECREASE
DECREASE NO EFFECT

GASTRIC SX

PANCREATIC INSUFFICIENCY

VIT. B12 DEF. PERNICIOUS A

IF DEF (CHRONIC GASTRITIS) ANTI PARIETAL CELL Ab & ANTI IF Ab

FOLIC A. DEF. Absent

Present

S/ S: SPASTIC ATAXIA

Present

Absent

Diagnosis Vit B12 Def

vs Folic A. Def

Morphology Serum B12

Morphology Serum folate

Neurologic findings

Red cell folate

Demyelination of spinal cord, cerebral cortex

Megaloblastic A LAB Dx:

NEUTRO/ THROMBOCYTOPENIA PBS: MACROOVALOCYTES; B. STIPPLINGS; HJ BODIES; MACROPOLYCYTES (HYPERSEG. PMN) INC SERUM BILIRUBIN Inc LDH INC. SERUM Fe; DEC. TIBC

Bone Marrow DYSERYTHROPOIESIS MEGALOBLASTS GIANT METAMYELOCYTES INEFFECTIVE ERYTHROPOIESIS

VIT. B12 DEF. vs FOLIC A. DEF. LAB DX:

URINARY

MMA

INCREASE

NORMAL

FIGLU

NORMAL

INCREASE

GASTRIC ANALYSIS

HISTAMINE FAST ACHLORYDRIA

NONE

Schillings Test

NONE

Megaloblastic Anemia Other Labs:

IF Ab test:

Specific for PA but only 50% sensitive Sensitive (90%) but not specific

Parietal cell Ab test:

FIGLU test: Liver disease Genetic def of glutamate formimino-transferase Urinary excretion of formimino-glutamic acid (intermediate metabolite in histidine catabolism) His to glu acid w/ the formimino group being transferred to tetrahydrofolic acid Homocysteine Folate def.

SCHILLING TEST

Step 1: Non radioactive B12 given (binds all available transcobalamin in PB): Prevents any reabsorbed radioactive B12 from binding to transcobalamin RB12 Forced to be excreted into the urine Step 2: RB12 p.o. Step 3: 24h urine to test for % RB12 reabsorbed Result: No RB12 in 24h urine confirms BI2 def

SCHILLING TEST Interpretation

If corrected w/ IF + oral radioactive B12:

Pernicious a
Bacterial overgrowth

If corrected after antibiotic tx:

If corrected w/ pancreatic extract + oral radioactive B12:

Chronic pancreatitis

Clinical Manifestations:

Anemia w/ slight icteresia GI: glossitis, smooth, beefy red tongue, malabsorption Neurologic:

Subacute degeneration of CNS: disturbances of mentation Peripheral neuropathy: numbness, weakness, ataxia, paresthesia

Treatment B12 & Folate Deficiencies

B12

IM B12 supplementation for life

Folate

Daily folate supplement (1mg/day)

Myelophthisic Anemia

BM Replacement BM failure: Mets Ca (MC) Destruction by nonneoplastic process (Fibrosis, Infection) PBS: Pancytopenia, immature circulating cells

Breast Cancer Replacing BM

Erythrocytes: Normal mature RBC

Biconcave disc Approximatly 8 um in dia 2.5 um thick at the periphery 1.0 um thick at center Contains 27- 34 pg (1012 g) of hgb (about 95% of dry wt of RBC)

INCREASED DESTRUCTION (1) INTRINSIC

HEREDITARY CELL MEMBRANE DEFECT SPHEROCYTOSIS ELLIPTOCYTOSIS STOMATOCYTOSIS PAROXYSMAL NOCTURNAL HEMOGLOBINURIA ENZYMOPATHIES GLUCOSE 6 PHOSPHATE DEHYDROGENASE DEFICIENCY PYRUVATE KINASE DEFICIENCY HEMOGLOBINOPATHIES SICKLE CELL ANEMIA HEMOGLOBIN C DISEASE HEMOGLOBIN E PORPHYRIAS

INCREASED DESTRUCTION (2) EXTRINSIC

ANTIBODY: AIHA (IgG) COLD REACTING (IgM) DRUG INDUCED

MECHANICAL: PROSTHETIC HEART VALVE MAHA BURNS OTHERS: HYPERSPLEENISM OXIDIZING AGENTS VENOM (SNAKE, INSECT)

INFECTION: BACTEREMIA PARASITEMIA MALARIA BARTONELLOSIS

General Clinical Features of Hemolytic Anemias

Splenomegaly generally present Increased incidence of pigmented gallstones Dark urine (tea-colored or red), jaundice, scleral icterus Chronic ankle ulcers Aplastic crises asso w/ Parvovirus B19 Increased requirement for folate

Sites of Red Cell Destruction

Extravascular Hemolysis Macrophages in spleen, liver & BM remove damaged or Ab-coated RBCs

Intravascular Hemolysis RBCs rupture w/in vasculature hemoglobinemia

Evidence for Increased Red Cell Destruction

PBS:

Elevated reticulocyte count May be associated with high MCV Circulating NRBCs may be present
Erythroid hyperplasia Reduced M/E ratio Deforming changes in the skull and long bones (frontal bossing)

BM:

Bone:

Evidence for Increased Red Cell Destruction

Biochemical consequences of hemolysis in general

Elevated LDH Elevated B1 jaundice, scleral icterus Lower serum haptoglobin Hemoglobinemia Hemoglobinuria Hemosiderinuria
Schistocytes Spherocytes Bite/blister cells

Morphologic evidence of red cell damage

Reduced red cell life-span

Classification by Etiology

Congenital

Defects in membrane skeleton proteins Defects in enzymes involved in energy production Hemoglobin defects (hemoglobinopathies)

Acquired

Immune-mediated Non-immune-mediated

Areas of RBC metabolism crucial for RBC survival & function

RBC membrane RBC metabolic pathways Hemoglobin structure & function

RBC MEMBRANE: Hereditary Membrane Dse.

Hereditary Spherocytosis Hereditary Ovalocytosis / Elliptocytosis Hereditary Stomatocytosis

RBC MEMBRANE: 3 Major Structural Proteins

Semi-permeable bilayer of lipids (including cholesterol) & proteins Inc surface area: Deformable to pass through microvessels & permeable to H2O & electrolytes Major protein is spectrin
Cytoskeletal Proteins: Maintain RBC Shape, Strength, Flexibility

Hereditary Spherocytosis

AD MC versus AR - More Severe MC in N. European ancestry (AD 1: 5000) Waxing / waning anemia, jaundice Splenomegaly, pigmented gallstones, ankle ulcers

Hereditary Spherocytosis

Defects may be in: Actin - Spectrin - Band 3 complex Spectrin - 4.1 -Glycophorin complex Connection between bilayer & spectrin

Hereditary Spherocytosis

Mutation of Ankyrin Gene (Most Common Defect)

Abnormal Ankyrin Protein

Deficiency of Spectrin Assembly

Hereditary Spherocytosis

Vertical stabilization defect of PL bilayer Spectrin PL bilayer separates Lipid microvesicles pinched off dec surface area (dec MCV) spherocytosis

Hereditary Spherocytosis Lab Dx:

inc LDH, inc B1 inc EOFT Normal MCH w/ an inc MCHC Coombs Test - Negative Inc Autohemolysis Test corrected by glucose

PBS: Mod Anemia; Spherocytes; Reticulocytosis (polychromatophilia) BM - Erythroid Hyperplasia

Hereditary Spherocytosis Tx:

Folate replacement Splenectomy

Case

14 mon old African-American child presents w/ mild anemia; Hx / PDx obtained & when reviewed showed these cells What are they?

Hereditary elliptocytosis Mechanism

Defects in horizontal junctions: Between a- & b- spectrin dimers or spectrin, actin & band 4.1 Structural abnormality of spectrin or def of RBC membrane protein 4.1 RBC cytoskeleton loose structural strength & lateral integrity

Hereditary elliptocytosis Clinical

AD Most patients asymptomatic

No anemia No splenomegaly Mild hemolysis (spleenectomy corrects hemolysis, but not the RBC membrane defect) # of elliptocytes does not correlate w/ severity of hemolysis

Hereditary elliptocytosis Lab Dx

PBS: large #s of elliptocytes &/or ovalocytes EOFT is usually normal Reticulocytes mild inc (<5%) Haptoglobin levels low

Hereditary pyropoikilocytosis

Rare AR Hallmarks: Severe hemolysis, bizarre poikilocytosis & RBC fragmentation Structural abnormality of spectrin, RBCs fragment when heated (45C) vs. Normal RBCs fragment at 49C

Case

Membrane permeability defect in stomatocytosis

Biochemical changes that can cause shape change in RBC

Accumulation of cholesterol causes increased membrane

Decreased spectrin causes decreased membrane

Target cell Acanthocyte

Spherocyte Bite cell

RBC Metabolic Pathways

Essential for O2 transport & maintaining physical characteristics of RBC

EMP

Generates 90% - 95% of energy needs thru Glucose 2 ATP Maintained by PK

PK Def affects Na-K ATPase pump & Ca-Mg ATPase pump affected

Case

5 y/o African-American boy recently presented w/ fever. Prescribed Bactrim for presumed otitis media. Brought back in by mom due to increased fatigue & PBS showed

HMP

Metabolizes 5-10% of glucose Generates glutathione G6PD is rate-limiting enzyme

G6PD also produces NADPH (keeps glutathione reduced) Glutathione protects via break down of H2O2 H2O +O G-6PD def denatures Hgb

G6PD Pathophysiology

Actual def not due to absence of enzyme, but defective protein folding protein w/ decrease half-life later stages of RBCs life (> 20 days), functional levels of enzyme decline

G6PD Types
Mediterranean type: Association Fava bean ingestion African American type: In response to oxidative states (infections)

Degree of Hemolysis

More severe because all RBCs have dec G6PD activity due to dec synthesis & stability

Intermittent since older RBCs have dec levels of G6PD

G6PD Def: Clin Dx

X-linked common in African Americans & Mediteraneans > 400 Variants Acute self-limited IV hemolytic a Jaundice in 1st 24 hrs of life (pathologic jaundice) Asymptomatic Unless Oxidative Stress (Therapeutic Drugs, Fava Beans)

G-6-PD def Clinical

> 200 M people (Mediterranean, West African, Mid-East & SEA) due to chronic hemolysis Blacks often have an episodic variant in w/c oxidant cmpds (antimalarials, sulfonamides, or infections) cause hemolysis Women heterozygotes (half the normal amount of RBC) G6PD show increased resistance to P falciparum

G6PD Deficiency Lab Dx

Heinz body prep PBS: Bite cells & blister cells G6PD level: May be normal in acute setting (selective rx of older RBCs w/ lower baseline G6PD levels

G-6-PD def: Stressors of G6PD System

Antimalarials Sulfonamides Nitrofurans Phenacetin Synthetic vit K Naphthalene (moth balls) Fava beans Infection Diabetic ketoacidosis

Tx:

Get rid of offending oxidant stress (drug, infection)

Red cell metabolic pathways

Methhemoglobin Reductase Pathway: Maintains iron in Fe2 state In the absence of methgb reductase methgb accumulates

Red cell metabolic pathways

Leubering-Rapaport shunt Allows RBC to regulate O2 transport during conditions of hypoxia or acid-base imbalance Permits accumulation of 2,3-DPG essential for maintaining normal O2 tension

Hb-O2 Dissociation Curve

Sigmoid Shape F8 Histidine & Porpyrin Ring Alpha-Beta Dimer Cooperative Binding

OxyHgb Dissociation Curve

Breakdown of the RBC

Toward the end of 120 day life span, 1% of RBCs per day

Membrane becomes less flexible Concentration of cellular hemoglobin increases Enzyme activity (esp glycolysis) diminishes

Erthrocyte Destruction

Extravascular Hemolysis (major- 90% via RES) Intravascular Hemolysis (minor- 5-10%)

INCREASED DESTRUCTION (1) INTRINSIC

HEREDITARY CELL MEMBRANE DEFECT SPHEROCYTOSIS ELLIPTOCYTOSIS STOMATOCYTOSIS PAROXYSMAL NOCTURNAL HEMOGLOBINURIA ENZYMOPATHIES GLUCOSE 6 PHOSPHATE DEHYDROGENASE DEFICIENCY PYRUVATE KINASE DEFICIENCY HEMOGLOBINOPATHIES SICKLE CELL ANEMIA HEMOGLOBIN C DISEASE HEMOGLOBIN E PORPHYRIAS

INCREASED DESTRUCTION (2) EXTRINSIC

ANTIBODY: AIHA (IgG) COLD REACTING (IgM) DRUG INDUCED

MECHANICAL: PROSTHETIC HEART VALVE MAHA BURNS OTHERS: HYPERSPLEENISM OXIDIZING AGENTS VENOM (SNAKE, INSECT)

INFECTION: BACTEREMIA PARASITEMIA MALARIA BARTONELLOSIS

Paroxysmal Nocturnal Hemoglobinuria

Rare, acquired, chronic S/s:

Complications: Aplastic anemia Leukemia Venous thrombosis

Recurrent abdominal pain, vomiting, headaches, eye pain, thrombophlebitis Breathlessness at night Episodic Hgb in urine, Hemosiderinuria

Clinical

IV & EV hemolysis, classically at night (due slight acidosis during sleep; C components more active in pH

And in exercise (lactic acidosis), causes activation of complement

PNH: Pathophysiology

Acquired Somatic mutation in PIG-A gene Clonal cell disorder (affects all cell lines) Dec Glycosyl Phosphatidyl Inositol (GPI)linked proteins, esp Decay Accelerating Factor

DAF binds GPIs on RBC surface to breakdown C components from lysing cell (specifically C3 convertase) DAF inhibition = inc C activity

PNH

Mutation of Stem Cells - No Anchor Protein (Chronic Hemolysis) + SERUM C vs RBC, WBC, PLATELETS INC C3 FIXATION INC MAC
C C ComplementInduced Lysis (Intravascular - Hgb in Urine)

PNH: Lab Dx

PANCYTOPENIA DEC. NAP

SUCROSE HEMOLYSIS T (SCREEN) > 10%= PNH 5-10%= MEGA. A; AIHA

Flow cytometry: CD 59 negative (a product of the PIG-A gene)

ACIDIFIED SERUM TEST/ HAMS (CONFIRM) 10- 15% HEMOLYSIS

INCREASED DESTRUCTION (2) EXTRINSIC

ANTIBODY: AIHA (IgG) COLD REACTING (IgM) DRUG INDUCED

MECHANICAL: PROSTHETIC HEART VALVE MAHA BURNS OTHERS: HYPERSPLEENISM OXIDIZING AGENTS VENOM (SNAKE, INSECT)

INFECTION: BACTEREMIA PARASITEMIA MALARIA BARTONELLOSIS

HA: Others

Antibody Mediated (Spherocytes) VS Mechanical Trauma (Schistocytes)

Heart Valves, Microthrombi, Fibrin Strands in Vessels (DIC, TTP, HUS)

Coombs (+) w/ Spherocytes Immune & Autoimmune HA

Immune Hemolytic Anemias

Ab Mediated: RBC Destruction Caused By Ab to RBC Surface Ag Phagocytosis in Spleen More Common w/ Aging 2 Types - Warm & Cold Autoimmune HA

Immune Hemolytic Anemias

Warm Ab Type (IgG, 37o C): IgG + RBC Surface Ags Primary: Idiopathic (60%) Secondary: Leukemia, Lymphoma, SLE, Drugs Spherocytes - Spleen Removes Membrane Protein from Ab Coated RBCs Positive DCT

Cold Ab Type (IgM, <30o C) Usually Not Clinically Significant Acute: Mycoplasma pneumoniae IM (Mild Transient Anemia) Chronic: Idiopathic, Lymphoma

Coombs (+) w/ Spherocytes Autoimmune hemolytic a

Warm AIHA: Abrupt onset IgG Anti-Rh, e, C, c, LW, U Jaundice Splenomegaly SLE, CLL, Lymphoma Drugs: methyl-dopa, mefenamic acid, cimetidine, cefazolin

Cold AIHA: Insidious onset IgM, complement Anti-I, I, P (PCH) Cold agglutinin titer Absent jaundice Mycoplasma Virus

Warm-Antibody Hemolytic Anemias Treatment

Immunosuppressive Treatment

Corticosteroids (i.e. prednisone) Splenectomy may be necessary Immunosuppressives such as cyclophosphamide (Cytoxan) or azathioprine (Immuran) may be required as third-line therapy.

Cold Agglutinin Disease

IgM antibodies bind to I antigens of RBCs when cold (falls off when warm) Causes agglutination cyanosis & ischemia of extremities Has both intravascular and extravascular hemolytic components

Cold Agglutinin Disease

Primary, or associated w/ Mycoplasma, Mononucleosis, or lymphoproliferative disease

Treat by avoiding cold & folate repletion

Corticosteroid and splenectomies uneffective

Coombs (+) w/ Spherocytes Other immune hemolytic a

Alloantibody hemolytic anemia: Transfusion reaction Feto-maternal incompatibility (Kleihauer-Betke test)

Drug related Hemolytic anemia: Toxic immune complex (drug+Ab+C3)

Quinine, Quinidine, Rifampin, INH, Sulfonamides, Tetracyclin PCN, methicillin, ampicillin

Hapten formation (anti-IgG)

Drug-Induced Immune Hemolysis Three general mechanisms

Innocent bystander

Ab directed at the drug, but it cross reacts w/ RBCs Drug must be present for hemolysis to occur Quinine, Quinidine, Isoniazide

Hapten

Drug binding to RBC Abs that react to this complex Penicillins, Cephalosporins

Drug-Induced Immune Hemolysis Three general mechanisms

True autoimmune

no drug needed in the body any more to produce hemolysis Alpha-methyldopa, L-DOPA, Procainamide

TTP- HUS

TTP - HUS: Thrombocytopenia MAHA Neurologic symptoms & signs Renal failure Fever

Causes: Idiopathic:37% Drug asso:13% Autoimmune dse:13% Sepsis: 9% Pregnancy:7% Bloody diarrhea: 6% Hematopoietic cell transplantation: 4%

DIC

Depletion of clotting factor (in TTP: normal) Thrombocytopenia Bleeding (64%) Renal dysfunction (25%) Hepatic dysfunction (19%) Respiratory dysfunction (16%) Shock (14%) Thromboemboli (7%) CNS involvement (2%) Sepsis, trauma, malignancy

TTP-HUS / DIC

Acanthocytosis: Intrinsic vs

Extrinsic

AR MECHANISM:

ACQUIRED MECHANISM:

ABETALIPOPROTEINE MIA MALABSORPTION; RETINAL & CNS C DEC LCAT/ INC SPHI:LECI DEC SERUM CHOLE.

TERMINAL CIRRHOSIS

LAB DX:

LAB DX:

INC RBC MEMBRANE CHOLE. DEC LCAT

Non-Immune Hemolytic Anemia Classification

Mechanical trauma to red cells

Microangiopathic Hemolytic Anemia Abnormalities in heart and large vessels March Hemoglobinuria

Infections Drugs, Chemicals, and Venoms

Chemical & Physical Agents Causing Hemolysis

Severe Burns Arsenic Copper Insect and spider bites

Infections Causing Hemolysis

Malaria Babesia microti Clostridium welchii

Bartonella bacilliformis

Malaria

Infections
Malaria - Organisms Destroy RBCs Most Common Acquired HA Worldwide Tropical Distribution w/ Variety of Species Parasites Destroy RBCs Cyclical Hemolysis Produces Fever & Chills Splenomegaly - Mononuclear Cells

References

Harmening, D.H., et al., Clinical hematology and fundamental of hemostasis, 3rd Ed, F.A. Davis Company, Philadelphia, 1997.

McKenzie, S.B., et al., Text book of hematology, 2nd Ed, Williams & Wilkins, A Waverly Company, Baltimore,1995.

WAKAS!!!