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A red blood cell survives 90 to 120 days (on average) in the circulation,
therefore about 1% of human red blood cells break down each day. The spleen (part of the reticulo-endothelial system) is the main organ which removes old and damaged RBCs from the circulation. In health the breakdown and removal of RBCs from the circulation is matched by the production of new RBCs in the bone marrow. When the rate of breakdown increases, the body compensates by producing more RBCs, but if compensation is inadequate clinical problems can appear. Breakdown of RBCs can exceed the rate that the body can make RBCs and so anemia can develop. The breakdown products of hemoglobin will accumulate in the blood causing jaundice and be excreted in the urine causing the urine to become dark brown in colour.
HEMOLYTIC ANEMIA
Hemolytic anemia = reduced red-cell life span
*Genetic conditions of RBC membrane **Hereditary spherocytosis **Hereditary elliptocytosis *Genetic conditions of RBC metabolism (enzyme defects) **Glucose-6-phosphate dehydrogenase deficiency (G6PD or favism) **Pyruvate kinase deficiency *Genetic conditions of hemoglobin **Sickle cell anemia **Thalassaemia
*Autoimmune hemolytic anemia **Warm antibody autoimmune hemolytic anemia **Cold antibody autoimmune hemolytic anemia
***Idiopathic ***Systemic lupus erythematosus (SLE) ***Evans' syndrome (antiplatelet antibodies and hemolytic antibodies) ***Idiopathic cold hemagglutinin syndrome ***Infectious mononucleosis and mycoplasma ( atypical) pneumonia ***Paroxysmal cold hemoglobinuria (rare)
***Rh disease (Rh D) ***ABO hemolytic disease of the newborn ***Anti-Kell hemolytic disease of the newborn ***Rhesus c hemolytic disease of the newborn ***Other blood group incompatibility (RhC, Rhe, RhE, Kidd antigen system, Duffy antigen, MN, P and others)
compatible blood type) *Drug induced immune mediated hemolytic anemia **Penicillin (high dose) **Methyldopa
negative)
*Drugs (i.e., some drugs and other ingested substances lead to hemolysis by direct action on RBCs) *Toxins (e.g., snake venom) *Trauma **Mechanical (heart valves, extensive vascular surgery, microvascular disease) *Microangiopathic hemolytic anemia (a specific subtype with causes such as TTP, HUS, DIC and HELLP syndrome) *Infections **Malaria **Babesiosis **Septicaemia *Membrane disorders **Paroxysmal nocturnal hemoglobinuria (rare acquired clonal disorder of red blood cell surface proteins) **Liver disease *Hypersplenism
Mechanisms of hemolysis:
- intravascular - extravascular
Extravascular hemolysis :
- 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 - laboratory signs of extravascular hemolysis: tests for hemolysis
Hemolytic anemia
Crises: hemolytic aplastic
Differential diagnosis
* ''Ineffective hematopoiesis'' is sometimes misdiagnosed as hemolysis. ** Clinically these conditions may share many features of hemolysis ** Red cell breakdown occurs before a fully developed red cell is released into the circulation. ** Examples: myelodysplastic syndrome, megaloblastic anemia.
Therapy
Compensated hemolysis observation (clinical evaluation) and folic acid at an oral dose 1mg/day Decompensated hemolysis (definitive therapy depends on the cause): *Symptomatic treatment -blood transfusion: if there is marked anemia. *In immune-related hemolytic anemia: steroid therapy , immunosupressive agents, immunoglobulins *Sometimes splenectomy can be helpful where extravascular heamolysis is predominant (ie most of the red blood cells are being removed by the spleen). Folic acid Hemochromatosis chelatic agents (Desferal)
3. PNH laboratory features: - pancytopenia - chronic urinary iron loss - serum iron concentration decreased - hemoglobinuria - hemosiderinuria - positive Hams test (acid hemolysis test) - positive sugar-water test - specific immunophenotype of erytrocytes (CD59, CD55) 4. Treatment: - washed RBC transfusion - iron therapy - allogenic bone marrow transplantation (streoids may reduce transfusion requirements; splenectomy very questionable benefit)
IN HOMOZYGOTES 1. Clinical complications due to severe hemolytic anaemia - slowed growth and development in children - bilirubins stones - aplastic crisis - congestive heart failure from chronic anemias and cardiac overload compensation 2. Consequences of vaso-occlusion of the microcirculations (tissue ischemia and infarction) - infarction of spleen, brain, marrow, kidney, lung, aseptic necrosis, central nervous system and ophtalmic vascular lesions
Thalasemias
The regions in which thalasemia occure are contiguous
with regions endemic for malaria (protection against malaria) Thalasemia result from gene (located on chromosomes 11 and 16) deletion, abnormalities in transcription and translation and instability of the mRNA directing globin synthesis or of the globin itself. Result: imbalanced synthesis of normal globin chain. The unpaired chain accumulates in the developing erythroid precursor cell, and toxicity results ineffective erythropoiesis, hemolysis and anemia of variable degree.
synthesized Clinical futures: sever anemia that appears in the first year of life; jaundice, hepatosplenomegaly (secondary neutropenia and thrombocytopenia), skin pigmentation and chronic leg ulceration, expansions of the erythroid marrow with secondary body changes (including retarded growth, bossing of skull, expanded maxilla, widened diploe, gross skeletal deformities, spontaneous fractures, dental problem), increased susceptibility to infection, symptoms of iron overloading