HAEMOLYTIC ANAEMIA HAEMOLYTIC ANAEMIA Dairion Gatot, Soegiarto Ganie, Savita Handayani. Divisi Hematologi & Onkologi Medik Departemen Ilmu Penyakit Dalam FK-USU/RS H.Adam Malik Medan 2009

Hb 9 g%transfusion Hb 4 g% HEMOLYTIC ? HEMOLYTIC ? No sign of bleeding WHENBYTHEN

Used Drug or traditional medicine Hb decreased no sign of bleeding no sign of bleeding Hemolytic ?

Anemia + icterus (mild) Infection Hemolytic ?

Definition Any situation in which there is a reduction in RBC life-span due to increase RBC destruction. Failure of compensatory marrow response results in anemia. Predominant site of RBC destruction is red pulp of the spleen.Any situation in which there is a reduction in RBC life-span due to increase RBC destruction. Failure of compensatory marrow response results in anemia. Predominant site of RBC destruction is red pulp of the spleen.

Normositic normochromic anemia Normositic normochromic anemia Diagnostic: –MCV fL and –MCH > 27 pg or MCHC ³ 30 g/dL Cause : –Distribution failure. –Lack of production, –Rate of RBC destruction  reduced red-cell life span

OTHER HAEMOLYTIC ANAEMIAS Parasites Hypersplenism Microangiopathic haemolysis Hereditary spherocytosis Paroxysmal noctural haemoglobinuria Enzyme deficiencies Drug or toxin Haemoglobinopathies AUTO IMMUNO HAEMOLYTIC ANAEMIA Erythroblastosis foetalis Transfusion reaction Collagen vascular disease OTHER Renal disease Infection Malnutrition Aplastic anaemia Radiation MYELOPHTHISIC Tumor Myelofibrosis Infection Leukaemia BLOOD LOSS ANAEMIA REPLACEMENT OF NORMAL MARROW ELEMENTS DECREASED CELLULARITY HYPERCELLULAR ERYTHROID HYPERPLASIA POSITIVE NEGATIVE INCREASEDREDUCED NORMOCYTIC ANAEMIA INTERPRETATION LABORATORY TEST PERIPHERAL SMEAR RETICULOCYTE COUNT BLOOD IN STOOL OR OTHER SOURCE OF BLEEDING IDENTIFIED ANTIHUMAN GLOBULIN (COOMBS’TEST) BONE MARROW AND BONE MARROW BIOPSY DIAGNOSIS

Classification of Hemolytic anemias I. Red cell abnormality (Intracorpuscular factors) A. Hereditary 1. Membrane defect (spherocytosis, elliptocytosis) 2. Metabolic defect (Glucoze-6-Phosphate-Dehydrogenaze (G6PD) deficiency, Pyruvate kinase (PK) deficiency) 3. Hemoglobinopathies (unstable hemoglobins, thalassemias, sickle cell anemia ) B. Acquired 1. Membrane abnormality-paroxysmal nocturnal hemoglobinuria (PNH)

II. Extracorpuscular factors A. Immune hemolytic anemias 1. Autoimmune hemolytic anemia - caused by warm-reactive antibodies - caused by cold-reactive antibodies 2. Transfusion of incompatible blood B. Nonimmune hemolytic anemias 1. Chemicals 2. Bacterial infections, parasitic infections (malaria), venons 3. Hemolysis due to physical trauma - hemolytic - uremic syndrome (HUS) - thrombotic thrombocytopenic purpura (TTP) - prosthetic heart valves 4. Hypersplenism

Mechanisms of hemolysis: - Intravascular - Extravascular - Intravascular - Extravascular

Intravascular hemolysis (1): - red cells destruction occurs in vascular space - clinical states associated with Intravascular hemolysis: acute hemolytic transfusion reactions severe and extensive burns paroxysmal nocturnal hemoglobinuria severe microangiopathic hemolysis physical trauma bacterial infections and parasitic infections (sepsis)

Inravascular hemolysis (2): - laboratory signs of intravascular hemolysis: indirect hyperbilirubinemia erythroid hyperplasia hemoglobinemia methemoalbuminemia hemoglobinuria absence or reduced of free serum haptoglobin hemosiderinuria Inravascular hemolysis (2): - laboratory signs of intravascular hemolysis: indirect hyperbilirubinemia erythroid hyperplasia hemoglobinemia methemoalbuminemia hemoglobinuria absence or reduced of free serum haptoglobin hemosiderinuria

Extravascular hemolysis (1) - red cells destruction occurs in reticuloendothelial system - clinical states associated with extravascular hemolysis : autoimmune hemolysis delayed hemolytic transfusion reactions hemoglobinopathies hereditary spherocytosis hypersplenism hemolysis with liver disease

Extravascular hemolysis (2): Laboratory signs of extravascular hemolysis: indirect hyperbilirubinemia increased excretion of bilirubin by bile erythroid hyperplasia hemosiderosis Extravascular hemolysis (2): Laboratory signs of extravascular hemolysis: indirect hyperbilirubinemia increased excretion of bilirubin by bile erythroid hyperplasia hemosiderosis

Autoimmune hemolytic anemia caused by warm- reactive antibodies: I. Primary II. Secondary 1. acute - viral infections - drugs (  -Methyldopa, Penicillin, Quinine, Quinidine) 2. chronic - rheumatoid arthritis, systemic lupus erythematosus - lymphoproliferative disorders (chronic lymphocytic leukemia, lymphomas, WaldenstrÖm’s macroglobulinemia) - miscellaneous (thyroid disease, malignancy )

Autoimmune hemolytic anemia caused by cold-reactive antibodies: I. Primary cold agglutinin disease II. Secondary hemolysis: - mycoplasma infections - viral infections - lymphoproliferative disorders III. Paroxysmal cold hemoglobinuria

LABORATORY RBC abnormalities  Sel target : HbC  Fragmented RBC : schistocytes burr cells helmet cells (MAHA) Plasmodium HbCHelmet cellsBurr cellsP. falciparum

LABORATORY 2.BONE MARROW Erythroid hyperplasia: rubrisit predominant Iron stores : negative / or normal

LABORATORY 1.BLOOD FILM Microspherocyte : 1. Autoimmuno haemolytic anaemia (AIHA) 2. Hereditary spherocytosis 3. Haemoglobinopathies : HbC 4. Hipersplenisme MCV N MCH N MCHC AIHA Spherocyte

DIAGNOSIS DIAGNOSIS OF HEMOLYTIC ANAEMIA Basic steps are : 1.Evaluation of clinical information from a review of the history & physical examination 2.Evaluation of the basic blood examination & specialized laboratory examination 3.Bone marrow examination

Laboratory features: 1. Laboratory features - normocytic/macrocytic, hyperchromic anemia - reticulocytosis - increased serum iron - antiglobulin Coombs’ test is positive 2. Blood smear - anisopoikilocytosis, spherocytes - erythroblasts - schistocytes 3. Bone marrow smear - erythroid hyperplasia

Hemolytic anemia - clinical features: - pallor - jaundice - splenomegaly

Diagnosis of hemolytic syndrome: 1. Anemia 2. Reticulocytosis 3. Indirect hyperbilirubinemia Diagnosis of hemolytic syndrome: 1. Anemia 2. Reticulocytosis 3. Indirect hyperbilirubinemia

Autoimmune hemolytic anemia - diagnosis - positive Coombs’ test Autoimmune hemolytic anemia - diagnosis - positive Coombs’ test

Treatment : - steroids - splenectomy - immunosupressive agents - transfusion Treatment : - steroids - splenectomy - immunosupressive agents - transfusion

G-6PD DEFISIENSI

G-6PD deficiency X-linked disorders, heterozygote females only rarely have significant haemolysis Haemolysis cause by infection, acidosis, drugs & toxins Red blood cells membrane oxidation Precipitation of haemoglobin Heinz bodies PB smear bite cells In acute haemolytic episode G-6PD activity maybe normal

Diagnosis Diagnosis : Low level G-6PD concentration Treatment : 1. Avoid of drugs exposure. 2. Transfusion. 3. No spesific treatment. 4. Anti oksidan, ???.

Drug exposure of hemolytic. Asetanilidprimakuin Furazolidonsulfasetamid Biru metilensulfametoksazol Asam nalidixatsulfanilamid Naftalensulfapiridin Nitrofurantoinbiru toluidin Fenazopiridtrinitrotoluen Fenilhidrazinjamu

Hereditary microspherocytosis (1) 1. Pathophysiology - red cell membrane protein defects (spectrin deficiency) resulting cytoskeleton instability 2. Familly history 3. Clinical features - splenomegaly 4. Laboratory features - hemolytic anemia - blood smear-microspherocytes - abnormal osmotic fragility test - positive autohemolysis test - prevention of increased autohemolysis by including glucose in incubation medium 5. Treatment - splenectomy

A : congenital non-spherocytic anaemias B : spherocytosis Osmotic fragility test

Hereditary microspherocytosis (2) 5. Treatment : Splenectomy

Paroxysmal nocturnal hemoglobinuria (PNH). 1. Pathogenesis - an acquired clonal disease, arising from a somatic mutation in a single abnormal stem cell - glycosyl-phosphatidyl- inositol (GPI) anchor abnormality - deficiency of the GPI anchored membrane proteins (delay-accelerating factor =CD55 and a membrane inhibitor of reactive lysis =CD59) - red cells are more sensitive to the lytic effect of complement - intravascular hemolysis 2. Symptoms - passage of dark brown urine in the morning

3. PNH –laboratory features: - pancytopenia - chronic urinary iron loss - serum iron concentration decreased - hemoglobinuria - hemosiderinuria - positive Ham’s test (acid hemolysis test) - positive sugar-water test - specific immunophenotype of erytrocytes (CD59, CD55)

HAMS & SUGAR WATER TEST Paroxymal nocturnal haemoglobinuria (PNH) RBC in PNH are abnormally sensitive to lysis to complement Diagnosis can be made by : 1.Abnormal lysis of RBC by acidic serum (Ham’s tests) 2.Hypotonic medium solution (Sugar water test)

4. Treatment : - washed RBC transfusion - iron therapy - allogenic bone marrow transplantation