Hemolysis and Hemolysis and Hemolytic Hemolytic AnemiasAnemias

Dr. SabirDr. Sabir

Hemolytic Anemias-Hemolytic Anemias-IntroductionIntroduction

• DefinitionDefinition: a group of : a group of disorders characterized by disorders characterized by decreased red cell lifespan.decreased red cell lifespan.

• Normal red cell lifespan is Normal red cell lifespan is 120d.120d.

• The patient may not always be The patient may not always be anemic, anemic, depending on the depending on the degree of marrow degree of marrow compensation.compensation.

General Clinical General Clinical FeaturesFeatures

• Splenomegaly Splenomegaly is generally is generally presentpresent

• Increased incidence of Increased incidence of pigmented gallstones.pigmented gallstones.

• Dark urine (tea-colored or red)Dark urine (tea-colored or red)• Patients may have chronic Patients may have chronic

ankle ulcersankle ulcers..• Aplastic crisesAplastic crises associated with associated with

Parvovirus B19, Parvovirus B19, may occurmay occur• Increased Increased requirement forrequirement for

folatefolate

Hemolytic Anemias - Hemolytic Anemias - Classification SchemesClassification Schemes

•Classification by Classification by sites of sites of red cell destructionred cell destruction

•Classification as Classification as acquiredacquired vs vs congenitalcongenital

•Classification by Classification by mechanismmechanism of red cell of red cell damagedamage

Hemolytic Anemias - Hemolytic Anemias - Sites of Red Cell Sites of Red Cell

DestructionDestruction• Extravascular Hemolysis -Extravascular Hemolysis -

– Macrophages in spleen, liver, Macrophages in spleen, liver, and marrow remove damaged and marrow remove damaged or antibody-coated red cellsor antibody-coated red cells

• Intravascular HemolysisIntravascular Hemolysis– Red cells rupture within the Red cells rupture within the

vasculature, releasing free vasculature, releasing free hemoglobin into the circulationhemoglobin into the circulation

Laboratory Evidence for Laboratory Evidence for Presence of HemolysisPresence of Hemolysis

• Evidence for Evidence for increased increased red cell productionred cell production

• Evidence for Evidence for increased increased red cell destructionred cell destruction

Evidence for Evidence for increased red cell increased red cell

productionproduction• In the blood: In the blood:

– Elevated reticulocyte countElevated reticulocyte count– Circulating Circulating NRBCsNRBCs may be may be

presentpresent• In the bone marrow: In the bone marrow:

– erythroid hyperplasiaerythroid hyperplasia – reduced M/E (myeloid/erythroid) reduced M/E (myeloid/erythroid)

ratioratio• In the bone: In the bone:

– Deformities in the skull and long Deformities in the skull and long bones (“bones (“frontal bossingfrontal bossing”)”)

PolychromatopPolychromatophilic cell hilic cell on on Wright-Giemsa Wright-Giemsa stainingstaining

ReticulocytReticulocyteses(supravital (supravital staining)staining)

Erythroid HyperplasiaErythroid Hyperplasia

• Expansion of the erythroid lineage.Expansion of the erythroid lineage.• Arrow is pointing to red cell precursor.Arrow is pointing to red cell precursor.• Myeloid:erythroid ratio is normally Myeloid:erythroid ratio is normally

3:1. The slide above has ratio of 1:103:1. The slide above has ratio of 1:10. .

Frontal BossingFrontal Bossing

Results from Results from increased increased erythropoietic erythropoietic activity and activity and marrow space marrow space expansionexpansion

Evidence for Evidence for Increased Red Cell Increased Red Cell

DestructionDestruction• Biochemical consequences of Biochemical consequences of

hemolysis in generalhemolysis in general• Morphologic evidence of red cell Morphologic evidence of red cell

damagedamage– seen on peripheral smearseen on peripheral smear

• Reduced red cell life-spanReduced red cell life-span– Measurement of red cell survival no Measurement of red cell survival no

longer routinely done.longer routinely done.

Biochemical Biochemical consequences of consequences of

hemolysis in generalhemolysis in general

• Elevated Elevated LDH levelsLDH levels• Elevated Elevated unconjugated unconjugated

bilirubinbilirubin– Only clinically significant if liver Only clinically significant if liver

function is abnormalfunction is abnormal– Only begins to rise when red Only begins to rise when red

cell life span is 50 days or lesscell life span is 50 days or less

Biochemical Biochemical Consequences of Consequences of

IntravascularIntravascular Hemolysis Hemolysis

•Reduced serum Reduced serum haptoglobinhaptoglobin

•Hemoglobinemia Hemoglobinemia - red plasma- red plasma

•Hemoglobinuria Hemoglobinuria - red urine- red urine•Hemosiderinuria Hemosiderinuria - stain for - stain for

iron inside cells in urineiron inside cells in urine

Hemolytic Anemias - Hemolytic Anemias - Classification by Classification by

EtiologyEtiology• CongenitalCongenital

– Defects in membrane skeleton Defects in membrane skeleton proteinsproteins

– Defects in enzymes involved in Defects in enzymes involved in energy productionenergy production

– Hemoglobin defectsHemoglobin defects• AcquiredAcquired

– Immune-mediatedImmune-mediated– Non-immune-mediatedNon-immune-mediated

Congenital Hemolytic Congenital Hemolytic Anemias-Anemias-

Membrane DefectsMembrane Defects•Hereditary spherocytosisHereditary spherocytosis

is the most common is the most common defect leading to anemia, defect leading to anemia, affecting 1/5000 affecting 1/5000 EuropeansEuropeans

•OtherOther– Hereditary elliptocytosisHereditary elliptocytosis

•Usually no anemiaUsually no anemia•Autosomal dominant, affecting Autosomal dominant, affecting

1/2500 Europeans1/2500 Europeans

– Hereditary pyropoikilocytosisHereditary pyropoikilocytosis

Hereditary Hereditary SpherocytosisSpherocytosis

• Defect is in Defect is in proteins of the proteins of the membrane membrane skeleton, usually skeleton, usually spectrin spectrin oror ankyrin ankyrin

• Lipid microvesicles Lipid microvesicles are pinched off in are pinched off in the spleen and the spleen and other RE organs, other RE organs, causing causing decreased decreased MCVMCV and and spherocyticspherocytic change.change.

Hereditary Hereditary SpherocytosisSpherocytosis

• Autosomal DominantAutosomal Dominant trait trait• Patients develop hemolysis and Patients develop hemolysis and

abdominal pain with even trivial abdominal pain with even trivial infectious illnessesinfectious illnesses

• Diagnose by Diagnose by Osmotic FragilityOsmotic Fragility• Aplastic crises with Parvovirus Aplastic crises with Parvovirus

B19B19• Treatment: Treatment:

– Folate supplementationFolate supplementation– SplenectomySplenectomy will stop will stop

hemolysis, but spherocytes will hemolysis, but spherocytes will persist.persist.

HEREDITARY HEREDITARY SPHEROCYTOSISSPHEROCYTOSIS

Osmotic FragilityOsmotic Fragility

0

20

40

60

80

100

0.3 0.4 0.5 0.6

NaCl (% of normal saline)

% H

emo

lysi

s

Normal HS

Osmotic FragilityOsmotic Fragility

NormalNormal

AbnormaAbnormal-l-HS cells HS cells lyse more lyse more readily at readily at low ionic low ionic strength strength

Congenital Congenital Hemolytic AnemiasHemolytic Anemias

Enzyme DefectsEnzyme Defects

Red Cell Enzyme DefectsRed Cell Enzyme Defects• RBCs require constant energy to RBCs require constant energy to

maintain biconcave disc shape and maintain biconcave disc shape and hemoglobin in reduced form.hemoglobin in reduced form.

• Without adequate energy, red cells Without adequate energy, red cells lyse and/or deform.lyse and/or deform.

• Energy from glucose is derived from Energy from glucose is derived from metabolism via anaerobic glycolysis metabolism via anaerobic glycolysis (Embden-Myerhof pathway). There (Embden-Myerhof pathway). There is an alternate aerobic pathway is an alternate aerobic pathway (pentose-phosphate shunt) which (pentose-phosphate shunt) which starts with G-6-P. starts with G-6-P. Rate-limiting Rate-limiting enzyme in this pathway is G6PDenzyme in this pathway is G6PD

RBC Metabolism RBC Metabolism Simplified Simplified

GlucoseGlucoseAnaerobic glycolysisAnaerobic glycolysis

Aerobic metabolismAerobic metabolism

Glucose-6-PGlucose-6-P

G6PDG6PD

• Detoxification of Detoxification of metabolites of oxidative metabolites of oxidative stressstress

• Elimination of Elimination of methemoglobinmethemoglobin

F-6-PF-6-P

G6PD DeficiencyG6PD DeficiencyPathophysiologyPathophysiology

• Low G6PD activity results in low Low G6PD activity results in low levels of NADPH and reduced levels of NADPH and reduced glutathione, which are required to glutathione, which are required to protect hemoglobin from oxidative protect hemoglobin from oxidative damage.damage.

• In the absence of adequate reducing In the absence of adequate reducing ability (provided by G6PD), oxidizing ability (provided by G6PD), oxidizing agents convert hemoglobin to agents convert hemoglobin to methemoglobin, then denature it, methemoglobin, then denature it, causing it to precipitate as causing it to precipitate as Heinz Heinz bodiesbodies..

• The spleen pinches off the Heinz The spleen pinches off the Heinz body and the overlying membrane, body and the overlying membrane, leaving a leaving a “bite cell”“bite cell” or or “blister cell”“blister cell”

G6PDG6PD• Two normal forms of enzyme. Most Two normal forms of enzyme. Most

prevalent type is prevalent type is BB. 20% of healthy . 20% of healthy Africans have type Africans have type AA..

• Deficiency is Deficiency is X-linkedX-linked..• In Africans with G6PD deficiency, In Africans with G6PD deficiency,

mutant protein is mutant protein is A-,A-, which is which is unstable and loses activity as the unstable and loses activity as the red cell ages( 5-15% of normal red cell ages( 5-15% of normal activity). activity).

• Mediterranean variant has baseline Mediterranean variant has baseline low activity(1-3%activity).low activity(1-3%activity).

• In US, 10-14% of AA men affectedIn US, 10-14% of AA men affected• In ME, deficiency can be seen in In ME, deficiency can be seen in

women, since prevalence is high women, since prevalence is high enough.enough.

G6PD Deficiency G6PD Deficiency Agents to avoidAgents to avoid

Blister Blister cellcell

– PrimaquinePrimaquine– AspirinAspirin– Quinolones(ciprQuinolones(cipr

o)o)– Sulfa drugsSulfa drugs– DapsoneDapsone– Vitamin KVitamin K– Fava Fava

beans(favism)beans(favism)– Naphtha Naphtha

compounds compounds (mothballs) (mothballs)

FavismFavism

• Hemolysis after hours/days Hemolysis after hours/days of ingestion of fava beansof ingestion of fava beans

• Beans contain oxidants vicine Beans contain oxidants vicine & convicine>free & convicine>free radicals>oxidise glutathioneradicals>oxidise glutathione

• Shock may develop-may beShock may develop-may be fatalfatal

G6PD DeficiencyG6PD DeficiencyClinical FeaturesClinical Features

• Typically, hemolysis is triggered by Typically, hemolysis is triggered by drugs or infections.drugs or infections.

• Anemia is maximal 7-10 d after Anemia is maximal 7-10 d after exposure.exposure.

• Urine becomes dark associated with Urine becomes dark associated with low back & abd pain low back & abd pain

• Individuals with A- begin to Individuals with A- begin to compensate for the anemia by making compensate for the anemia by making reticulocytes, despite continuation of reticulocytes, despite continuation of drug.drug.

• Immediately after a hemolytic Immediately after a hemolytic episode, episode, G6PD levels in pts with A- G6PD levels in pts with A- may be normalmay be normal, since the mature cells , since the mature cells have been lysed, and only younger have been lysed, and only younger cells with normal G6PD levels, are cells with normal G6PD levels, are presentpresent

• Wait for 6 wk after hemolysis to do Wait for 6 wk after hemolysis to do enzyme assayenzyme assay

TreatmentTreatment

• Avoid oxidant drugsAvoid oxidant drugs• Transfuse in severe casesTransfuse in severe cases• IV fluids to maintain good IV fluids to maintain good

urine outputurine output• Splenectomy in severe Splenectomy in severe

recurrent hemolysisrecurrent hemolysis• Folic acid supplementsFolic acid supplements

Congenital Hemolytic Congenital Hemolytic AnemiasAnemias

HemoglobinopathiesHemoglobinopathies• Structural Hemoglobin Structural Hemoglobin

DefectsDefects– Hemoglobin SHemoglobin S– Hemoglobin CHemoglobin C

• ThalassemiasThalassemias– Alpha thalassemiaAlpha thalassemia– Beta thalassemiaBeta thalassemia

Acquired Hemolytic Acquired Hemolytic AnemiasAnemias

Immune-Mediated Immune-Mediated HemolysisHemolysis

PathophysiologyPathophysiology• RBCs react with RBCs react with

autoAb±complement> autoAb±complement> premature destruction of premature destruction of RBCs by RE systemRBCs by RE system

• RBCs opsonized by IgG, RBCs opsonized by IgG, recognized by Fc receptors recognized by Fc receptors on RES macrophages on RES macrophages >phagocytosis>phagocytosis

• If phagocytosis is incomplete If phagocytosis is incomplete > spherocytosis, but usually > spherocytosis, but usually it is complete if complement it is complete if complement is involvedis involved

Immune hemolytic anemias -Immune hemolytic anemias -ClassificationClassification

• AutoimmuneAutoimmune– Warm antibody-mediatedWarm antibody-mediated– Cold antibody-mediatedCold antibody-mediated– Paroxysmal Cold Paroxysmal Cold

Hemoglobinuria Hemoglobinuria • Drug-related hemolysis Drug-related hemolysis • Hemolytic transfusion Hemolytic transfusion

reactionsreactions• Hemolytic disease of the Hemolytic disease of the

newbornnewborn• Paroxysmal Nocturnal Paroxysmal Nocturnal

HemoglobinuriaHemoglobinuria

Auto-Immune Hemolytic Auto-Immune Hemolytic AnemiasAnemias

• Antibodies causing hemolysis can Antibodies causing hemolysis can be broken down into 2 general be broken down into 2 general categories: warm and cold.categories: warm and cold.

• Warm antibodies react with RBCs Warm antibodies react with RBCs best at best at 37°37° and typically and typically do notdo not agglutinate red cellsagglutinate red cells

• Cold antibodies typically react Cold antibodies typically react best at best at <32°<32° and do cause and do cause RBC RBC agglutinationagglutination

• The hallmark of this disease is a The hallmark of this disease is a positive Coomb’s testpositive Coomb’s test

Coomb’s TestCoomb’s Test

• The The Direct Coomb’sDirect Coomb’s = = DATDAT (Direct Antiglobulin Test) - (Direct Antiglobulin Test) - tests for IgG or C3 tests for IgG or C3 DIRECTLY DIRECTLY ON THE RED CELLSON THE RED CELLS. .

• The The Indirect Coomb’sIndirect Coomb’s - tests - tests for IgG or C3 for IgG or C3 in the serumin the serum which react with generic which react with generic normal red cells. This is also normal red cells. This is also known as the known as the antibody antibody screenscreen in blood-banking. in blood-banking.

Patient’s RBCs Patient’s RBCs coated with IgG or coated with IgG or C3C3

Direct Coomb’s TestDirect Coomb’s Test

Antibodies to Antibodies to human IgG/C3 human IgG/C3 (Coomb’s (Coomb’s reagent)reagent)

AgglutinatiAgglutinationin the onin the test tube test tube

Indirect Coomb’s TestIndirect Coomb’s Test

AgglutinatiAgglutinationin the onin the test tubetest tube

Patient serum Patient serum containing anti RBC containing anti RBC AbsAbs

Normal RBCs and Normal RBCs and Coomb’s reagentCoomb’s reagent

Warm-Antibody Hemolytic Warm-Antibody Hemolytic AnemiasAnemias

• Idiopathic ( most of cases)Idiopathic ( most of cases)• 2º to lymphoid malignancies (CLL, NHL)2º to lymphoid malignancies (CLL, NHL)• 2º to autoimmune dis. Eg: SLE2º to autoimmune dis. Eg: SLE• Age: usually pts > 50 yrAge: usually pts > 50 yr• Clinically: highly variable: from Clinically: highly variable: from

asymptomatic-severely anemicasymptomatic-severely anemic• Mild jaundice commonMild jaundice common• Splenomegaly usualSplenomegaly usual

Spherocyte FormationSpherocyte Formation

Progressive loss of membrane, loss Progressive loss of membrane, loss of surface area, more spherocytic of surface area, more spherocytic shapeshape

Warm-Antibody Hemolytic Warm-Antibody Hemolytic AnemiasAnemiasDiagnosisDiagnosis

• SpherocytosisSpherocytosis• ReticulocytosisReticulocytosis• Coomb’s +veCoomb’s +ve• LDH îLDH î• Serum haptoglobin lowSerum haptoglobin low• Investigate for underlying Investigate for underlying

causecause

Warm Autoimmune Hemolytic Warm Autoimmune Hemolytic Anemia - spherocytesAnemia - spherocytes

Warm-Antibody Hemolytic Warm-Antibody Hemolytic Anemias TreatmentAnemias Treatment

• Patients may require red cell Patients may require red cell transfusions, if they are transfusions, if they are symptomatic with their symptomatic with their anemiaanemia

• However,However, immunosuppression is the immunosuppression is the mainstay of therapymainstay of therapy..

Warm-Antibody Hemolytic Warm-Antibody Hemolytic Anemias Immunosuppressive Anemias Immunosuppressive

TreatmentTreatment• First line is First line is corticosteroids corticosteroids

( prednisone 1mg/kg/d tapering after ( prednisone 1mg/kg/d tapering after response)response)

• If steroids fail to work, or if patient If steroids fail to work, or if patient relapses after steroid taper, relapses after steroid taper, splenectomysplenectomy may be necessary. IVIg may be necessary. IVIg can be used as adjunctive therapy.can be used as adjunctive therapy.

• Immunosuppressives such as Immunosuppressives such as cyclophosphamide or azathioprine cyclophosphamide or azathioprine may be required as third-line may be required as third-line therapy. Rituximab has been used therapy. Rituximab has been used successfully.successfully.

• Regular folic acidRegular folic acid

Cold Agglutinin DiseaseCold Agglutinin Disease• Pathogenic antibodies are usually Pathogenic antibodies are usually

IgMIgM, which bind to red cells in the , which bind to red cells in the cooler extremities, then fix cooler extremities, then fix complement. When red cells complement. When red cells return to the warmer torso, IgM return to the warmer torso, IgM falls off.falls off.

• Complement-coated red cells can Complement-coated red cells can be lysed directly within the vessel be lysed directly within the vessel (intravascular hemolysis).(intravascular hemolysis).

• Alternatively, complement-coated Alternatively, complement-coated red cells can be engulfed by red cells can be engulfed by complement receptors on complement receptors on macrophages within the liver macrophages within the liver (extravascular hemolysis)(extravascular hemolysis)

Cold Agglutinin DiseaseCold Agglutinin Disease• In the cold, IgM can In the cold, IgM can

lead to red cell lead to red cell agglutinationagglutination

• Red cells clumps Red cells clumps cannot pass cannot pass through through microvasculature, microvasculature, leading to cyanosis leading to cyanosis and ischemia in and ischemia in extremities.extremities.

• Smear shows RBC Smear shows RBC agglutination.agglutination.

Digital ischemia from Digital ischemia from cold-agglutinin diseasecold-agglutinin disease

Cold Agglutinin DiseaseCold Agglutinin DiseaseClinical featuresClinical features

• Can be associated with infection Can be associated with infection with either with either Mycoplasma or Mycoplasma or MononucleosisMononucleosis, ,

• Can also be idiopathic or associated Can also be idiopathic or associated with a with a lymphoproliferative diseaselymphoproliferative disease..

• Treatment is to keep patient Treatment is to keep patient (especially the extremities) warm. (especially the extremities) warm. Blood and IV fluids should be Blood and IV fluids should be warmed.warmed.

• Immunosuppression with oral Immunosuppression with oral chemotherapy may be required.chemotherapy may be required.

• Steroids and splenectomy are Steroids and splenectomy are usually ineffective.usually ineffective.

Paroxysmal Nocturnal Paroxysmal Nocturnal HemoglobinuriaHemoglobinuria

• An An acquiredacquired disease in which an disease in which an abnormal stem cell clone gives rise to abnormal stem cell clone gives rise to abnormal RBCs, WBCs, and platelets all abnormal RBCs, WBCs, and platelets all missing proteins which are attached to missing proteins which are attached to the cell surface by a the cell surface by a GPI (glycero-GPI (glycero-phosphatidylinositol) anchorphosphatidylinositol) anchor..

• Among these proteins are Among these proteins are CD55CD55 and and CD59CD59, which protect red cells from , which protect red cells from complement-mediated lysis.complement-mediated lysis.

• Diagnose by Diagnose by flow cytometryflow cytometry for CD55 for CD55 and CD59.and CD59.

• Former diagnostic test was Former diagnostic test was Ham’s testHam’s test - - looking for abnormal sensitivity to looking for abnormal sensitivity to addition of acidified serum. PNH cells addition of acidified serum. PNH cells lyse at a higher pH than normal red lyse at a higher pH than normal red cells.cells.

Paroxysmal Nocturnal Paroxysmal Nocturnal Hemoglobinuria - Clinical featuresHemoglobinuria - Clinical features

• PancytopeniaPancytopenia • Predisposition to thrombosis.Predisposition to thrombosis.

– Both arterial and venousBoth arterial and venous– Associated with Associated with Budd-ChiariBudd-Chiari

syndrome.syndrome.

• May develop during the course of May develop during the course of aplastic anemia, either preceding aplastic anemia, either preceding or after recovery from aplasia.or after recovery from aplasia.

• May develop into acute leukemiaMay develop into acute leukemia• Hemolysis is predominantly Hemolysis is predominantly

nocturnal (when pH usually falls), nocturnal (when pH usually falls), usually mild.usually mild.

Non-Immune Hemolytic Non-Immune Hemolytic AnemiaAnemia

ClassificationClassification• Mechanical trauma to red Mechanical trauma to red

cellscells– Microangiopathic Hemolytic Microangiopathic Hemolytic

AnemiaAnemia– Abnormalities in heart and Abnormalities in heart and

large vesselslarge vessels– March HemoglobinuriaMarch Hemoglobinuria

• InfectionsInfections• Drugs, Chemicals, and Drugs, Chemicals, and

VenomsVenoms

Microangiopathic Hemolytic Microangiopathic Hemolytic AnemiasAnemias

• Shear damage to red cells as the result Shear damage to red cells as the result of endothelial cell activation/damage.of endothelial cell activation/damage.

• Hallmark is presence of Hallmark is presence of schistocytesschistocytes on on the peripheral smear.the peripheral smear.

• Can be caused by the following Can be caused by the following disordersdisorders::

– TTP/HUSTTP/HUS– DIC DIC – Malignant hypertensionMalignant hypertension– Ecclampsia, HELLP syndromeEcclampsia, HELLP syndrome– VasculitisVasculitis– Other, including metastatic cancer, Other, including metastatic cancer,

scleroderma renal crisis, solid organ scleroderma renal crisis, solid organ transplant rejectiontransplant rejection

MAHA - SchistocytesMAHA - Schistocytes

Macroangiopathic Hemolytic Macroangiopathic Hemolytic AnemiasAnemias

• Abnormalities within heart and Abnormalities within heart and large vessels can cause shear large vessels can cause shear damage to RBCs.damage to RBCs.

• Schistocytes Schistocytes • Prior to surgery: AS, ruptured Prior to surgery: AS, ruptured

sinus of valsalva, ruptured sinus of valsalva, ruptured chordae, coarctation, aortic chordae, coarctation, aortic aneurysm and/or dissection.aneurysm and/or dissection.

• After surgery: complement After surgery: complement activation in bypass or dialysis activation in bypass or dialysis tubing, after “patching” tubing, after “patching” operations, after valve operations, after valve replacementreplacement

March HemoglobinuriaMarch Hemoglobinuria

• 1861 - German soldier 1861 - German soldier complained of dark urine after complained of dark urine after strenuous marches.strenuous marches.

• 1964 - 2 track runners noted dark 1964 - 2 track runners noted dark urine after races. Disappeared urine after races. Disappeared after softer shoe insoles used.after softer shoe insoles used.

• Mechanical damage to red cells Mechanical damage to red cells also reported after conga drum also reported after conga drum playing, head beating, and karate playing, head beating, and karate exercises.exercises.

Hemolysis from Hemolysis from InfectionsInfections

• MalariaMalaria• Bartonella bacilliformis Bartonella bacilliformis • Clostridium welchii toxinClostridium welchii toxin

– Hemolysis can be so severe it Hemolysis can be so severe it produces a dissociation b/w produces a dissociation b/w hemoglobin and hematocrithemoglobin and hematocrit

Hemolysis Associated with Hemolysis Associated with Chemical and Physical Chemical and Physical

AgentsAgents• Arsenic, especially arsine gasArsenic, especially arsine gas• Lead Lead • Copper - deliberate ingestion, Copper - deliberate ingestion,

accumulation from dialysis fluid accumulation from dialysis fluid exposed to copper pipes, and exposed to copper pipes, and Wilson’s disease.Wilson’s disease.

• Insect, spider (esp brown Insect, spider (esp brown recluse), snake venomsrecluse), snake venoms

• Heat/burnsHeat/burns