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 Secondary SLE,CLL,LYMPHOMAS Infection – MP,IM Drugs 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.Alloimmune hemolytic anemias B.Alloimmune hemolytic anemias 1.Hemolytic transfusion reactions 2.Hemolytic disease of the newborn 3.Allograft associated C.Drug-induced immune hemolytic anemia C.Drug-induced immune hemolytic anemia 1.Drug absorption mechanism 2.Membrane modification mechanism 3.Immune complex mechanism

Coombs Test Antiglobulin Test RBC Red cell with bound antibody to membrane antigen + Anti-immunoglobulin

Coombs Test Antiglobulin Test RBCRBC Agglutination

Non-Immune Hemolytic Anemias Hemolytic anaemias due to mechanisms or agents other than antibodies +/or complement e.g.: Mechanical (traumatic) (fragmentation)Mechanical (traumatic) (fragmentation) ToxinsToxins InfectionsInfections Splenomegaly (hypersplenism)Splenomegaly (hypersplenism) Burn (physical)Burn (physical) Renal failure and liver failureRenal failure and liver failure ChemicalChemical

Non-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 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) (Fragmentation) This is due to direct trauma (stress) to the RBCs causing fragmentation of the RBCs & intra-vascular hemolysis. The fragmented cells can be seen on peripheral blood smears & are called (schistocytes). Types: 1)Cardiac – most common Due to: 1.Prosthetic valves 2. Patches 3. Valvular diseasse e.g., stenosis Cont…

Mechanical (Traumatic) (Fragmentation) (cont … ) 2.Microangiopathic:mechanical hemolysis due to contact between the RBCs & the abnormal intema of thrombosed, narrowed, necrotic small vessels or fibrin strand formation. Caused by many diseases e.g., DIC (disseminated intravascular coagulation), malignant hypertension, disseminated malignancies especially mucin secreting adenocarcinomas, TTP (thrombocytopenic purpura), hemolytic uremic syndrome (HUS).

Causes of Microangiopathic Hemolytic Anemia 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 Anemia (cont … ) Disease Disease Vasculitis Vasculitis Polyarteritis nodosa Polyarteritis nodosa Wegener ’ s granulomatosis Wegener ’ s granulomatosis Systemic lupus Systemic lupus Homograft rejection Homograft rejection Meningococcal sepsis Meningococcal sepsis Carcinomatosis Carcinomatosis Primary pulmonary hypertension Primary pulmonary hypertension Cavernous haemangioma (Kasabach- Cavernous haemangioma (Kasabach- Merritt Syndrome) Merritt Syndrome) Microangiopathy Microangiopathy Arteritis Arteritis Microthrombi in transplanted organ Microthrombi in transplanted organ Endotoxaemia, diffuse intravascular Endotoxaemia, diffuse intravascular coagulation coagulation Abnormal tumour vessels, Abnormal tumour vessels, intravascular coagulation – local or intravascular coagulation – local or diffuse diffuse Abnormal vasculature Abnormal vasculature Local vascular changes and Local vascular changes and thrombosis thrombosis

Mechanical (Traumatic) (Fragmentation) (cont … ) Causes intravascular hemolysis HemoglobinureaHemoglobinurea HemoglobinemiaHemoglobinemia Low haptoglobinLow haptoglobin Fragmented RBCs (schistocytes) on peripheral blood filmFragmented RBCs (schistocytes) on peripheral blood film HemosidrinureaHemosidrinurea

Clostidium Perfringens:Clostidium Perfringens: –Due to action of lipase and proteinase enzymes produced by the organism. Meningococcal:Meningococcal: –Due to DIC

Malaria due to:Malaria due to: –Direct invasion causing intravascular lysis &/or extravascular lysis. –Immune complex formation. –Splenomegaly. Black water fever:Black water fever: –Is an example of severe intravascular hemolysis due to falciparum sp.

Chemical:Chemical: –e.g., some toxins e.g., spider venom, snake venom, bacterial toxins, arsenic (As), (Cu). Physical:Physical: –Burn: characterized by the presence of many spherocytes in the peripheral blood. SplenomegalySplenomegaly Renal failure and liver failureRenal failure and liver failure Due to change in the metabolic structure of the RBCs,

Hemolytic Uremic Syndrome Acquired-disorder affecting mainly infants and children. Characterized by: Intravascular hemolysisIntravascular hemolysis Renal failureRenal failure ThrombocytopeniaThrombocytopenia

Classification Sporadic: –Occuring denovo with no preceeding disease. Believed to be due to an inherited defect in vascular hemostasis. Epidemic, typical form: –Following a systemic illness of fever, diarrhea and vomiting. In many cases, no organisms are identified. However, in some cultures are positive e.g., for E. coli. Mechanisms: –Endothelial swelling & disruption resulting in platelet deposition on the vessel wall.

Clinical Features Jaundice, hemoglobinuria, proteinuria.Jaundice, hemoglobinuria, proteinuria. Hypertension, uremia, oliguria.Hypertension, uremia, oliguria. Anemia, thrombocytopenia purpura.Anemia, thrombocytopenia purpura. CNS – unusual: convulsion, comaCNS – unusual: convulsion, coma

Laboratory Findings Laboratory Findings (Cont … ) Chemistry: –Elevated urea –Elevated creatinine –Elevated bilirubin –Proteinuria + hemoglobinuria Coagulation: –Prolonged PT, PTT but not always

Laboratory Findings Blood film: –Fragmentation of RBCs –Thrombocytopenia –Polychromasia CBC: –Anemia –Thrombocytopenia: usually <50,000 Bone marrow: –Hypercellular with increased erythropoiesis + increased megakaryopoiesis

Thank You For Your Attention!