Haemolytic anemia , hematologia resumida .pptx

Anemias

1. Introduction to haemolytic anaemias Block 4.1 2024 Dr. Ismênia Todo

2. Hemolysi s refers to the premature destruction or shortening of the half-life of erythrocytes ( normal 120 days ). Anemia produced by hemolysis stimulates: the secretion of the erythropoietin hormone (kidney), which gives rise to an increase in number of erythroid precursors in the marrow and prominente reticulocytosis in the peripheric blood; accumulation of Hb degradation products, released by breakdown red cells. extra- medullary hematopoiesis , in severe anemia, which appears in the liver, spleen and lymph nodes.

3. Frequency : 5% of all anemias. Mortality : The overall incidence is low . Race : There are disorders that cause hemolysis in special groups : The sickle cell anemia in africans , arabics and south of India, G-6-PD deficiency in africans , afro- americans and mediterraneans . Sex: are not specifics . Age : Hemolytic anemia can occur at any age . E tiological classification : Intracorpuscular : intrinsic defect of the erythrocyte , be it genetic, hereditary or acquired. Extracorpuscular : secondary lesion, by external agents , of a normal erythrocyte. HAEMOLYTIC ANAEMIA

4. Physiopathological classification Extravascular : constitutes an exacerbation of the normal physiological elimination of red blood cells in the SMF that leads to splenomegaly . It is generally due to alterations that rend red cells less deformable. Anemia, splenomegaly , jaundice. Intravascular : rupture of the red blood cell ( lysis ) or fragmentation inside the vascular system. It is due to mechanical injury, complement fixation, intracellular parasite, exogenous toxic factor . Anemia, hemoglobinemia , hemoglobinuria , hemosiderinuria , jaundice. Almost all haemolyses are mixed.

5. Clinical classification : Acute : Brusque onset, striking clinical pattern and severe alteration of biomedical parameters. Chronic : more overlapped . Genetic clasification Hereditary Acquired Hereditary are evident in early life and AIHA is more likely to occur in middle age and older individuals.

6. The clinical and biological expressiveness depends on the intensity and speed of onset of the hemolysis . In the acute form : fever , dizziness , abdominal pain , jaundice or /and pallor , asthenia , tachycardia and sometimes hemoglobinuria. The dark urine caused by hemoglobinuria should not be confused with other pigments: bilirubin , drugs, myoglobin ... ( ≠ coluria). If hemolysis takes place following the intake of a medicine: G6PD deficit etiology must be suspected if the patient is young… CLINICAL

7. DIAGNOSIS Haemogram: They are normally normocytic-normochromic or discreet macrocytosis at the expense of the size of the recticulocytes, with Hb . Recticulocyte count (+++): Reticulocytes are of the so-called class or type I (globulose), larger and with a bluish tone (polychromatic macrocyte) with basophilic stippling as an expression of their high RNA content (immature RBC ).

8. Morphological blood examination : The examination of the blood smear makes it possible to confirm haemogram alterations, besides viewing alterations in the form of the red blood cells : poikilocytosis , anisocytosis , target cells, sickle cells... Biological hemolysis indicators : Bilirubinemia ( indirect ) ++ Plasma LDH (+++) Haptoglobin (---) Erythrocyte half-life (--- ) MCV bigger ( macrocytical anemia) DIAGNOSIS

9. Bilirubinemia It is caused by the catabolism of haemoglobin, always at the expense of the unconjugated fraction. Consequently it is NOT eliminated in urine (Not coluria) but its accumulation in the skin leads to jaundice. Excess serum bilirubin leads to fecal urobiline and gallstones from heme pigment. BIOLOGICAL HEMOLYSIS INDICATORS Plasma LDH This enzyme is found in high concentrations in the erythrocyte (and other cells), whereby it increases in plasma when there is hemolysis … or fast celular growing…( can be a tumoral marker …) It is rather unspecific because it increases with any cell lysis (AMI, myopathy, neoplasm, renal failure, myelofibrosis..). Inefficacious erythropoiesis also produces an ↑ in LDH (megaloblastic anaemia due to intramedullary abortion..etc.).

10. alfa 2 glycoprotein synthesized in the liver that binds to free haemoglobin, forming a complex that is eliminated through the liver. When there is haemolysis, its plasma rate falls and even becomes undetectable. The fall in haptoglobin lasts ± 48 hours after haemolysis, since its synthesis increases and the haptoglobinemia is normalised, although the hemolytic state may persist… It is one of the earliest detectors of hemolysis . Haptoglobin BIOLOGICAL HEMOLYSIS INDICATORS Half-life of red blood cells and other markers It is determined by labelling the red blood cells with radioactive Cr 51 → they are reinjected into the blood stream and residual radioactivity is determined every 2- 3 days. This is only carried out in exceptional circumstances. In cases of recent intravascular haemolysis, the Free Hb of plasma is partly oxidised and gives rise to Metahemoglobinemia (MHA). It persists in the blood stream for several weeks after the hemolytic episode (it gives the plasma a brown colour). is observed only in the chronic intravascular hemolysis → the urine elimination of small amounts of Hb → it is reabsorbed in the renal tubule → the tubular cells, on desquamation, can be recognised by Fe staining. Hemosiderinuria does not appear until 2-3 weeks after the hemolysis ( = chronic detector ). Hemosiderinuria is found in Paroxysmal Nocturnal Hemoglobinuria and in Malaria… Hemosiderine

11. Hereditary haemolytic anemias Membranopathies Protein defects of the erythrocyte membrane that produce alterations of form → Poikilocytosis Enzymopathies G6PD deficiency Hemolysis Pyruvate kinase (PK) deficiency enzymopathic Hemoglobinopathies Abnormal Hb ( structural haemoglobinopathies ) Reduction of normal Hb ( Thalassemias ) Persistence of foetal Hb Acquired hemolytic anemias Non- immune Immune HAEMOLYTIC ANEMIA CLASSIFICATION

12. 1. BY NON-IMMUNE MECHANISM Hemolytic anaemias by germs or parasites Mechanical Hemolytic Anaemias Hypersplenism Hemolytic anaemias by natural agents Hemolytic anaemias by toxic or oxidising agents Metabolic or endocrine anaemias

13. Anaemia is a very frequent and often serious complication of P. falciparum malaria in early chilhood. The pathogenesis is multifactorial: obligatory destruction of red cells containing parasites; also accelerated destruction of non-parasited red cells; dyserythropoiesis with a maturation arrest at the normoblast stage in bone marrow. Haemolysis is extra- and intravascular. Blackwater fever refers to severe acute intravascular haemolysis with haemoglobinemia, haemoglobinuria. Malarial anaemia responds very well to effective antimalarial treatment but there is a lag period of 4-5 days before reticulocytosis occurs. Reticulocyte counts are usually low in the acute phase of the disease. ANAEMIA AND MALARIA: hemolytic anemia by non- immune mechanism (h emolytic anaemia by parasite)

14. The spleen is one of the organs belonging to the SMF. It eliminates the blood cells that have completed their vital physiological cycle (“culling” function). It also eliminate defective or bad performed cells (“pitting” function). When the spleen size increases ( splenomegaly ), its culling and pitting functions also increase. Hypersplenism is the result of a splenomegaly caused by multiple causes, that leads to → anaemia and/or leukopenia and/or thrombopenia and bone marrow functioning normal. HYPERSPLENISM

15. 2. BY IMMUNE MECHANISM AUTOIMMUNE HEMOLYTYC ANAEMIAS Hemolytic disease of the newborn Post-transfusional hemolytic anaemias Paroxysmal Nocturnal Hemoglobinuria Drug-induced immune hemolytic anaemias Hapten mechanism Neoantigen mechanism Autoimmune mechanism

16. It is attributed to a functional alteration of the immune system that generates antibodies against own antigens located in the erythrocyte membrane. The hemolytic process always occurs in the erythrocyte membrane which, on becoming damaged, induces its premature elimination. The destruction of erythrocytes is through the action of Autoantibodies and/or of the Complement or other immunogenic medicinal product-type agents. The elimination of defective red blood cells may be carried out in the vascular tree by the action of the antibodies (intravascular) or they are withdrawn from the blood stream as they pass through the cells of the SMF organs (extravascular). In 50% of the cases it accompanies autoimmune or lymphoproliferative base diseases, viral infections, Mycoplasma, etc . (HOT AIHA) AUTOIMMUNE HEMOLYTIC ANAEMIA (AIHA).

17. The antierythrocyte autoantibodies of these diseases fall into three generic types : Cold agglutinins , almost always IgM , clump RBCs at cold temperature , they provoke an intravascular hemolysis . Hot agglutinins : Ig G Donath-Landsteiner f ixe RBCs in the cold and activate when the cells are warmed to 37°C IgG warm autoantibodies bind to erythrocytes at 37°C but fail to aglutinate the cells They are incomplete antigens and cannot produce the lysis of the erythrocyte by themselves, but rather “ sensitise ” it ( opsonization ) for extravascular destruction by SMF. The Coombs Test (direct or indirect) tends to be . When the red blood cell bound with the IgG comes into contact with a serum that has a specific antiglobulin against IgG (Coombs serum), agglutination of the red blood cell takes place  Coombs test + .

18. Haemolysis arises when there are antibodies against the membrane of the red blood cells of a donor with an incompatible blood group. Post-transfusional Hemolytic Reaction Hemolytic Disease of the Newborn In this haemolysis, it is the mother's antibodies that attack the erythrocyte membrane of the newborn's red blood cell during pregnancy. It produces intense hemolysis in the 2 nd pregnancy of the same incompatibility characteristics. These antibodies target the Rh and ABO blood group. Medicinal products which, through a complex process, activate the immune system against the red blood cell . Drug-induced Immune Hemolytic Anaemia

19. It is produced by a defect of the red blood cell membrane secondary to an acquired genetic mutation of the X chromosome. Despite its name, PNH is rare, chronic (non-nocturnal) and intermittent (non-paroxysmal). The main clinical symptom is the hemolytic anaemia precipitated by triggering events (infections, surgery, trauma…etc.). It may also course with other cytopenias (leukopenia and thrombopenia) as an expression of a medullary hypoplasia due to alterations of the “stem cell”. Diagnosis: Hemolytic anaemia, Hemosiderinuria, Hemoglobinuria. PAROXYSMAL NOCTURNAL HEMOGLOBINURIA (PNH)

20. Thank you for your attention.

21. Bibliografy Harrison’s “ Principles of Internal Medicine “, 17 th edition Hoffman , Benz and others , “ Hematology , Basic Principles and Practice ”, 3 rd edition , 2000 Linch , Yates , Watts “ Hematology ”, Churchill Livingstone , 1996 Robbins and Contran , “ Pathologic Bases of Disease ”, 8 th edition .