Acquired hemolytic anaemia

Dr. Fatma Al-Qahtani

Immune haemolytic anaemias

A – Auto immune .H.A Are caused by AB production by the

body against its own red cells. C/BY apositive (DAT) / Coomb’s test. Divided into 1) warm 37c 2) cold 4 c

Warm type Cold type

Idiopathic IdiopathicSecondary SecondarySLE,CLL,LYMPHOMAS Infection – MP,IMDrugs Lymphoma PCH,syphilis

Warm AIHA

• IgG alone or with complement and take up by RE macrophages

• More in spleen • Spherocytosis prominent• DAT is positive • Bind at 37c

Cold AIHA• The AB monoclonal ICHS , lymphoproliferative

disorder Polyclonal infection IM, MP• Usually IgM• Bind to red cell at 4c • Mild jaundice and splenomegaly• Spherocytosis is less marked

B.B. Alloimmune hemolytic Alloimmune hemolytic anemiasanemias

1.1. Hemolytic transfusion reactionsHemolytic transfusion reactions

2.2. Hemolytic disease of the newbornHemolytic disease of the newborn

3.3. Allograft associatedAllograft associated

C.C. Drug-induced immune Drug-induced immune hemolytic hemolytic anemiaanemia

1.1. Drug absorption mechanismDrug absorption mechanism

2.2. Membrane modification mechanismMembrane modification mechanism

3.3. Immune complex mechanismImmune complex mechanism

Coombs TestCoombs TestAntiglobulin TestAntiglobulin Test

RBCRBC

Red cell withRed cell withbound antibody tobound antibody tomembrane antigenmembrane antigen

++

Anti-immunoglobulinAnti-immunoglobulin

Coombs TestCoombs TestAntiglobulin TestAntiglobulin Test

RBCRBC RBCRBC

AgglutinationAgglutination

Non-Immune Hemolytic AnemiasNon-Immune Hemolytic Anemias

Hemolytic anaemias due to mechanisms or Hemolytic anaemias due to mechanisms or agentsagents

other than antibodies +/or complement e.g.:other than antibodies +/or complement e.g.:• Mechanical (traumatic) (fragmentation) Mechanical (traumatic) (fragmentation) • ToxinsToxins• Infections Infections • Splenomegaly (hypersplenism)Splenomegaly (hypersplenism)• Burn (physical)Burn (physical)• Renal failure and liver failureRenal failure and liver failure• ChemicalChemical

Non-Immune Acquired Hemolytic AnemiaNon-Immune Acquired Hemolytic Anemia

Cause

• Infections

Examples

• Malaria• Babesiosis• Bartonella• Meningococcal sepsis• Pneumococcal sepsis• Gram-negative sepsis• Clostridium perfringens

Mechanisms

• Intracellular organisms

• Microangiopathic hemolysis • Enzymatic toxins

Cont…

Non-Immune Acquired Hemolytic AnemiaNon-Immune Acquired Hemolytic Anemia

Cause

• Chemical & physical agents

• Mechanical lysis

• Acquired membrane disorder

Examples

• Drugs• Industrial/domestic substance• Burns• Drowning• Diffuse intravascular coagulation• Vasculitis• Cardiac prostheses• Liver disease• Paroxysmal nocturnal hemoglobinuria

Mechanisms

• Oxidative hemolysis• Membrane damage• Osmotic lysis

• Microangiopathic hemolytic anemia • “Foreign surface” hemolysis• Lipid abnormalities• Somatic mutation

Mechanical (Traumatic) Mechanical (Traumatic) (Fragmentation)(Fragmentation)

This is due to direct trauma (stress) to the This is due to direct trauma (stress) to the RBCs causing fragmentation of the RBCs & RBCs causing fragmentation of the RBCs & intra-vascular hemolysis. The fragmented intra-vascular hemolysis. The fragmented cells can be seen on peripheral blood smears cells can be seen on peripheral blood smears & are called (schistocytes).& are called (schistocytes).Types:Types:

1)1) Cardiac – most commonCardiac – most commonDue to:Due to:

1.1. Prosthetic valvesProsthetic valves2.2. PatchesPatches3.3. Valvular diseasse e.g., stenosisValvular diseasse e.g., stenosis

Cont…

Mechanical (Traumatic) (Fragmentation)

(cont…)

2.2. Microangiopathic:Microangiopathic: mechanical hemolysis mechanical hemolysis due to contact between the RBCs & the due to contact between the RBCs & the abnormal intema of thrombosed, narrowed, abnormal intema of thrombosed, narrowed, necrotic small vessels or fibrin strand necrotic small vessels or fibrin strand formation.formation.Caused by many diseases e.g., DIC Caused by many diseases e.g., DIC (disseminated intravascular coagulation), (disseminated intravascular coagulation), malignant hypertension, disseminated malignant hypertension, disseminated malignancies especially mucin secreting malignancies especially mucin secreting adenocarcinomas, TTP (thrombocytopenic adenocarcinomas, TTP (thrombocytopenic purpura), hemolytic uremic syndrome (HUS).purpura), hemolytic uremic syndrome (HUS).

Causes of Microangiopathic Hemolytic Causes of Microangiopathic Hemolytic AnemiaAnemia

Disease

• Hemolytic uraemic syndrome of childhood• Hemolytic uraemic syndrome with bacterial infection (especially Esch. coli 0157)• Thrombotic thrombocytopenic purpura• Renal cortical necrosis• Acute glomerular nephritis• Pre-eclampsia

Microangiopathy

• Endothelial cell swelling, microthrombi in renal vessels• Endotoxaemia, microthrombi in renal arteries

• Platelet plugs, microaneurysms, arteriolitis.• Necrotizing arteritis.

• Fibrinoid necrosis

Cont…

Causes of Microangiopathic Hemolytic Causes of Microangiopathic Hemolytic AnemiaAnemia

(cont…)(cont…) DiseaseDisease

• VasculitisVasculitis• Polyarteritis nodosaPolyarteritis nodosa• Wegener’s granulomatosisWegener’s granulomatosis• Systemic lupusSystemic lupus

• Homograft rejectionHomograft rejection

• Meningococcal sepsisMeningococcal sepsis

• CarcinomatosisCarcinomatosis

• Primary pulmonary hypertensionPrimary pulmonary hypertension• Cavernous haemangioma (Kasabach-Cavernous haemangioma (Kasabach- Merritt Syndrome)Merritt Syndrome)

MicroangiopathyMicroangiopathy

• ArteritisArteritis

• Microthrombi in transplanted organMicrothrombi in transplanted organ

• Endotoxaemia, diffuse intravascularEndotoxaemia, diffuse intravascular coagulationcoagulation• Abnormal tumour vessels,Abnormal tumour vessels, intravascular coagulation – local orintravascular coagulation – local or diffusediffuse• Abnormal vasculatureAbnormal vasculature• Local vascular changes andLocal vascular changes and thrombosisthrombosis

Mechanical (Traumatic) (Fragmentation)

(cont…)

Causes intravascular hemolysis Causes intravascular hemolysis • HemoglobinureaHemoglobinurea• HemoglobinemiaHemoglobinemia• Low haptoglobinLow haptoglobin• Fragmented RBCs (schistocytes) Fragmented RBCs (schistocytes)

on peripheral blood filmon peripheral blood film• HemosidrinureaHemosidrinurea

• Clostidium Perfringens:Clostidium Perfringens:– Due to action of lipase and Due to action of lipase and

proteinase enzymes proteinase enzymes produced by the organism. produced by the organism.

• Meningococcal:Meningococcal:– Due to DIC Due to DIC

• Malaria due to:Malaria due to:– Direct invasion causing intravascular Direct invasion causing intravascular

lysis &/or extravascular lysis.lysis &/or extravascular lysis.– Immune complex formation.Immune complex formation.– Splenomegaly. Splenomegaly.

• Black water fever:Black water fever:– Is an example of severe intravascular Is an example of severe intravascular

hemolysis due to falciparum sp. hemolysis due to falciparum sp.

• Chemical:Chemical:– e.g., some toxins e.g., spider venom, snake e.g., some toxins e.g., spider venom, snake

venom, bacterial toxins, arsenic (As), (Cu).venom, bacterial toxins, arsenic (As), (Cu).• Physical:Physical:

– Burn: characterized by the presence of Burn: characterized by the presence of many spherocytes in the peripheral blood.many spherocytes in the peripheral blood.

• SplenomegalySplenomegaly• Renal failure and liver failureRenal failure and liver failure

Due to change in the metabolic structure of Due to change in the metabolic structure of the RBCs,the RBCs,

Hemolytic Uremic Syndrome

Acquired-disorder affecting mainly infants andAcquired-disorder affecting mainly infants andchildren. children.

Characterized by:Characterized by:• Intravascular hemolysisIntravascular hemolysis• Renal failureRenal failure• ThrombocytopeniaThrombocytopenia

Classification

Sporadic:Sporadic:– Occuring denovo with no preceeding disease. Believed to be Occuring denovo with no preceeding disease. Believed to be

due to an inherited defect in vascular hemostasis.due to an inherited defect in vascular hemostasis. Epidemic, typical form:Epidemic, typical form:

– Following a systemic illness of fever, diarrhea and vomiting. Following a systemic illness of fever, diarrhea and vomiting. In many cases, no organisms are identified. However, in In many cases, no organisms are identified. However, in some cultures are positive e.g., for E. coli.some cultures are positive e.g., for E. coli.

Mechanisms:Mechanisms:– Endothelial swelling & disruption resulting in platelet Endothelial swelling & disruption resulting in platelet

deposition on the vessel wall.deposition on the vessel wall.

Clinical FeaturesClinical Features

• Jaundice, hemoglobinuria, Jaundice, hemoglobinuria, proteinuria.proteinuria.

• Hypertension, uremia, oliguria.Hypertension, uremia, oliguria.• Anemia, thrombocytopenia Anemia, thrombocytopenia

purpura.purpura.• CNS – unusual: convulsion, comaCNS – unusual: convulsion, coma

Laboratory FindingsLaboratory Findings(Cont…)

Chemistry:Chemistry:– Elevated ureaElevated urea– Elevated creatinine Elevated creatinine – Elevated bilirubinElevated bilirubin– Proteinuria + hemoglobinuria Proteinuria + hemoglobinuria

Coagulation:Coagulation:– Prolonged PT, PTT but not alwaysProlonged PT, PTT but not always

Laboratory Findings

Blood film:Blood film:– Fragmentation of RBCsFragmentation of RBCs– ThrombocytopeniaThrombocytopenia– Polychromasia Polychromasia

CBC:CBC:– AnemiaAnemia– Thrombocytopenia: usually <50,000Thrombocytopenia: usually <50,000

Bone marrow:Bone marrow:– Hypercellular with increased erythropoiesis + increased Hypercellular with increased erythropoiesis + increased

megakaryopoiesismegakaryopoiesis

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