APPROACH TO A PATIENT APPROACH TO A PATIENT WITH HEMOLYTIC WITH HEMOLYTIC

ANEMIAANEMIA

ByByDr. Ramlah HasanDr. Ramlah Hasan

H.O MU-IIH.O MU-II

DefinitionDefinition

Hemolytic are a group of disorders characterised Hemolytic are a group of disorders characterised by shortened survival of RBCs in circulation .by shortened survival of RBCs in circulation .

An introductionAn introduction Consequences of hemolysisConsequences of hemolysis

Shortening of red cells survival does not always cause Shortening of red cells survival does not always cause anemia as there is a compensatory increase in red cell anemia as there is a compensatory increase in red cell

production by the bone marrow.If the red cell loss can be production by the bone marrow.If the red cell loss can be contained within the marrowcontained within the marrow’’s capacity for increased s capacity for increased

output,then a hemolytic state can exist without anemia output,then a hemolytic state can exist without anemia (compensated hemolytic disease). (compensated hemolytic disease). The bone marrow can The bone marrow can

increase its output by 6 to 8 times by increasing the increase its output by 6 to 8 times by increasing the proportion of cells committed to erythropoiesis proportion of cells committed to erythropoiesis (erythroid (erythroid

hyperplasia)hyperplasia) and by expanding the volume of active and by expanding the volume of active marrow.marrow. In addition, immature cells In addition, immature cells (reticulocytes)(reticulocytes) are are

released prematurly. released prematurly.

Sites ofSites of hemolysishemolysis

Extra vascular hemolysisExtra vascular hemolysis In most hemolytic conditions red cell In most hemolytic conditions red cell

destruction is extra vascular. The red destruction is extra vascular. The red Cells are removed from the circulation by Cells are removed from the circulation by

macrophages in the reticuloendothelial macrophages in the reticuloendothelial system, particularly the spleen.system, particularly the spleen.

Sites of Hemolysis (contd.)Sites of Hemolysis (contd.) Intra vascular HemolysisIntra vascular Hemolysis

When red cells are rapidly destroyed within When red cells are rapidly destroyed within the circulation Hb is liberated. This is initially the circulation Hb is liberated. This is initially

bound to plasma haptoglobin but these soon bound to plasma haptoglobin but these soon become saturated. Excess free plasma Hb is become saturated. Excess free plasma Hb is

filtered by the glomerulus and enters the urine, filtered by the glomerulus and enters the urine, although small amounts are reabsorbed by the although small amounts are reabsorbed by the

renal tubules. In the renal tubular cells Hb is renal tubules. In the renal tubular cells Hb is broken down and becomes deposited in the broken down and becomes deposited in the

cells as haemosiderin.cells as haemosiderin.

Classification of Hemolytic Classification of Hemolytic AnemiasAnemias

Intra corpuscularIntra corpuscular HereditaryHereditary

Membrane DefectsMembrane DefectsHereditary SpherocytosisHereditary SpherocytosisHereditary ElliptocytosisHereditary Elliptocytosis

Enzyme DeficiencyEnzyme Deficiency G6PD DeficiencyG6PD Deficiency

Pyruvate Kinase DeficiencyPyruvate Kinase Deficiency HaemoglobinopathiesHaemoglobinopathies

Sickle Cells AnemiaSickle Cells Anemia Unstable HaemoglobinsUnstable Haemoglobins

AcquiredAcquired Paroxysmal Nocturnal HaemoglobinuriaParoxysmal Nocturnal Haemoglobinuria

Classification of Hemolytic Classification of Hemolytic AnemiasAnemias

Extra corpuscularExtra corpuscular Autoimmune Hemolytic AnemiasAutoimmune Hemolytic Anemias

Associated with warm antibodiesAssociated with warm antibodies Associated with cold antibodiesAssociated with cold antibodies

Isoimmune Hemolytic AnemiasIsoimmune Hemolytic Anemias Drug induced Hemolytic AnemiasDrug induced Hemolytic Anemias

InfectionsInfections Plasmodiam, ClostridiumPlasmodiam, Clostridium

Microangiopathic Hemolytic AnemiasMicroangiopathic Hemolytic Anemias HypersplenismHypersplenism

Clinical ApproachClinical Approach HistoryHistory

ExaminationExamination InvestigationInvestigation

TreatmentTreatment

HistoryHistory AgeAge

Hemolytic anemia can occur at any age. Hemolytic anemia can occur at any age. Hereditary disorders usually are evident early in life. Hereditary disorders usually are evident early in life.

AIHA is more likely to occur in middle-aged and older AIHA is more likely to occur in middle-aged and older individuals.individuals.

SexSexMost cases of hemolytic anemia are not specific to any Most cases of hemolytic anemia are not specific to any

gender. gender. Autoimmune hemolytic anemia (AIHA) is slightly Autoimmune hemolytic anemia (AIHA) is slightly

more more likely to occur in females than in males. likely to occur in females than in males. G-6-PD deficiency is an X-linked recessive disorder. G-6-PD deficiency is an X-linked recessive disorder.

Males usually are affected, and females are carriers Males usually are affected, and females are carriers

History (contd.)History (contd.) SymptomsSymptoms

Pallor, Fatigue, Worsening of preexisting, angina, Pallor, Fatigue, Worsening of preexisting, angina, Palpitation, Postural dizzinessPalpitation, Postural dizziness

Mottled or Numb fingers or toesMottled or Numb fingers or toes Pigment gall stonePigment gall stone

Reddish Brown first morning urineReddish Brown first morning urine Symptoms due to splenomegaly like dragging Symptoms due to splenomegaly like dragging

sensation in abdomensensation in abdomen Acute painful episode include the bones Acute painful episode include the bones

(especially the back and long bones) and the chest.(especially the back and long bones) and the chest.

History (contd.)History (contd.) Family HistoryFamily History

Positive Medical History for Associated Positive Medical History for Associated DiseasesDiseases

Drug HsitoryDrug Hsitory AnalgesicsAnalgesics

Anti-malarialsAnti-malarials Anti-bacterialsAnti-bacterials

ExaminationExamination PallorPallor

JaundiceJaundice TachycardiaTachycardia

Flow murmursFlow murmurs Signs of congestive cardiac failure Signs of congestive cardiac failure

Poorly healing ulcers over lower tibiaPoorly healing ulcers over lower tibia SplenomegalySplenomegaly CholelithiasisCholelithiasis

InvestigationsInvestigations Blood Complete PictureBlood Complete Picture

Hb Hb or N or N TLCTLC PLTPLT

Red Cell IndicesRed Cell Indices MCVMCV

MCHCMCHC ReticulocytosisReticulocytosis

Bone Marrow ExaminationBone Marrow Examination Erythroid HyperplasiaErythroid Hyperplasia

Serum LevelsSerum Levels BilirubinBilirubin

The level of unconjugated bilirubin never exceeds 4 to 5 mg/dl.The level of unconjugated bilirubin never exceeds 4 to 5 mg/dl. HaptoglobinHaptoglobin

Plasma HaemoglobinPlasma Haemoglobin Lactate DehydrogenaseLactate Dehydrogenase

Positive Urinary HaemosiderinPositive Urinary Haemosiderin

Peripheral Blood FilmPeripheral Blood Film

Blood Film

SpherocytesNo spherocytes Fragmentation

DCT+ DCT-

Autoimmunehemolysis

Hereditaryspherocytosis

Malaria, Clostridum

Hereditary enzymopathies

Microangiopathic ,Traumatic

Hereditary SpherocytosisHereditary Spherocytosis

Sickle Cell AnemiaSickle Cell Anemia

Other InvestigationsOther Investigations Osmotic fragility testOsmotic fragility test

Specific enzymatic assaysSpecific enzymatic assays Hb electrophoresisHb electrophoresis

Evaluation of HemolysisEvaluation of HemolysisExtra vascularExtra vascularIntra vascularIntra vascular

Plasma Or SerumPlasma Or SerumBilirubinBilirubin UnconjugatedUnconjugatedUnconjugatedUnconjugatedHaptoglobinHaptoglobin, Absent, AbsentAbsentAbsentPlasma HbPlasma HbN - N - Lactate DehydrogenaseLactate Dehydrogenase ))variable)variable) (variable)(variable)UrineUrineBilirubinBilirubin0000HemosiderinHemosiderin00++HaemoglobinHaemoglobin00+ in severe cases+ in severe cases

TreatmentTreatment More than 200 types of hemolytic anemia exist, and each type More than 200 types of hemolytic anemia exist, and each type

requires specific treatment. Therefore, only the aspects of medical requires specific treatment. Therefore, only the aspects of medical care relevant to most cases of hemolytic anemia are discussed. care relevant to most cases of hemolytic anemia are discussed.

Transfusion therapyTransfusion therapy Avoid transfusions unless absolutely necessary, but they may be essential for Avoid transfusions unless absolutely necessary, but they may be essential for

patients with angina or severely compromised cardiopulmonary status. patients with angina or severely compromised cardiopulmonary status. Administer packed RBC slowly to avoid cardiac stress. Administer packed RBC slowly to avoid cardiac stress.

In AIHA, type matching and crossmatching may be difficult. Use the least In AIHA, type matching and crossmatching may be difficult. Use the least incompatible blood if transfusions are indicated. The risk of acute hemolysis of incompatible blood if transfusions are indicated. The risk of acute hemolysis of

transfused blood is high, but the degree is dependent on the rate of infusion. transfused blood is high, but the degree is dependent on the rate of infusion. Slowly transfuse by administering half units of packed red cells to prevent rapid Slowly transfuse by administering half units of packed red cells to prevent rapid

destruction of transfused blood.destruction of transfused blood. Discontinuing medicationsDiscontinuing medications

Discontinue penicillin and other agents that can cause immune hemolysis and Discontinue penicillin and other agents that can cause immune hemolysis and oxidant medication such as sulfa drugs oxidant medication such as sulfa drugs

Treatment (contd.)Treatment (contd.) Administer folic acid because active hemolysis may consume folate Administer folic acid because active hemolysis may consume folate

and cause megaloblastosis. and cause megaloblastosis. Corticosteroids are indicated in AIHA. Corticosteroids are indicated in AIHA.

IV immunoglobulin G (IgG) has been used for patients with AIHA, IV immunoglobulin G (IgG) has been used for patients with AIHA, but only a few patients have responded, and the response has been but only a few patients have responded, and the response has been

transient. transient. Iron therapyIron therapy

This is indicated for patients with severe intravascular hemolysis This is indicated for patients with severe intravascular hemolysis in which persistent hemoglobinuria has caused substantial iron in which persistent hemoglobinuria has caused substantial iron

loss. loss. Before iron is administered, document the iron deficiency by Before iron is administered, document the iron deficiency by

serum iron studies and, possibly, by assessing iron stores in bone serum iron studies and, possibly, by assessing iron stores in bone marrow aspirates. marrow aspirates.

Because iron stores increase in hemolysis, iron administration Because iron stores increase in hemolysis, iron administration generally is contraindicated in hemolytic disorders, particularly generally is contraindicated in hemolytic disorders, particularly

those that require chronic transfusion support.those that require chronic transfusion support.

Treatment (contd.)Treatment (contd.) Surgical Care: Surgical Care:

Splenectomy may be the first choice of treatment in Splenectomy may be the first choice of treatment in some types of hemolytic anemia such as hereditary some types of hemolytic anemia such as hereditary

spherocytosis.spherocytosis. In other cases, it is recommended when other measures, In other cases, it is recommended when other measures,

such as in AIHA, have failed.such as in AIHA, have failed. Splenectomy usually is not recommended in hemolytic Splenectomy usually is not recommended in hemolytic

disorders such as cold agglutinin hemolytic anemia.disorders such as cold agglutinin hemolytic anemia. Immunize against infections with encapsulated organisms, Immunize against infections with encapsulated organisms,

such as such as Haemophilus influenzaeHaemophilus influenzae and and Streptococcus Streptococcus pneumoniae,pneumoniae, as far in advance of the procedure as possible. as far in advance of the procedure as possible.

Points to RememberPoints to Remember Peripheral smear is the most

important initial investigation and Coombs test with anti-IgG and anti-complement in diagnosing hemolytic

anemia.