What is Hemolysis
- Premature destruction of dead cells.
- Causes hereditary and acquired disorders.
-Hemolysis occurs at two sites:
Intravascular
-Hemolysis occurs within systemic
circulation.
-Hemoglobin is released into plasma.
-Hemoglobin is lost through kidneys or
catabolized in the liver.
Extravascular
-Trapping of red cells in spleen or liver
sinuses.
-Lyses of trapped red cells.
-Release of lysed hemoglobin and
catabolism within the sequestering organ.
Classification of Hereditary
Hemolytic Anemia
•Based on side effect:
- Metabolic defect
- Membrane defect
- Hemoglobin defect
A) Metabolic defect:
-Defect in hexose monophosphate shunt:
G-6-PD deficiency.
-Defects of glycolysis; pyrovate kinase def.,
glucose phosphate isomerase def.
-Defects in red cell nucleotide metabolism:
pyramidine-5-nucleotidase def.
B) Membrane defect:
-Heriditary spherocytosis
-Heriditary elliptocytosis
-Hereditary pyropoikilocytosis
C) Hemoglobin defect:
-Thalassemias
-Sickle cell anemia
-Hemoglobin C disease
-Hemoglobin E disease
-Unstable hemoglobin
Laboratory Findings
•Chemistry
Hyperbilirubinemia, predominantly unconjugated bilirubin
due to breakdown of heme ring by reticuloendothelial cells
in the liver.
elevated LDH: released from destroyed cells.
Hemoglobinemia: free hemoglobin level increases in
hemolysis esp. intravascular hemolysis: levels of 10-20
mg/dl gives plasma amber color and 50-100 gm/dl reddish
color.
Hemoglobinuria: red-brown color of urine due to free
hemoglobin and methamoglobin.
Decreased Heptaglobin level: it is a alpha-2-globin produced
in the liver. It binds free hemoglobin thus level is reduced in
hemolysis.
Hemosidrinuria: it reflects extensive hemolysis for a
prolonged period of time. When hemoglobin is filtered by
nephron, proximal tubular cells metabolize hemoglobin and
iron accumulate in the cells. Cells then exfoliate in the urine
and iron can be detected by Prussian blue reaction.
Drug-Induced Acute Hemolysis
•Drugs that have been linked to G6PD:
•Primaquine (an antimalarial)
•Sulphonamide antibiotics
•Sulphones (e.g. dapsone, used against leprosy)
•Other sulphur-containing drugs: glibenclamide (an anti-diabetic drug)
•Nitrofurantoin (an antibiotic often used for urinary tract infections)
•Vitamin K analogues
•Several others
•Henna can cause a hemolytic crisis in G6PD deficient infants
Acquired hemolytic anaemia
Immune haemolytic anaemias
Are caused by AB production by the body
against its own red cells.
Divided into 1) warm 37c
2) cold 4 c
Warm AIHA
•IgG alone ,Bind at 37c
Cold AIHA
•Usually IgM
•Bind to red cell at 4c
Coombs TestCoombs Test
Antiglobulin TestAntiglobulin Test
RBCRBC
Red cell withRed cell with
bound antibody tobound antibody to
membrane antigenmembrane antigen
++
Anti-immunoglobulinAnti-immunoglobulin
Coombs TestCoombs Test
Antiglobulin TestAntiglobulin Test
RBCRBC RBCRBC
AgglutinationAgglutination
Non-Immune Hemolytic AnemiasNon-Immune Hemolytic Anemias
Hemolytic anaemias due to mechanisms or agentsHemolytic anaemias due to mechanisms or agents
other than antibodies +/or complement e.g.:other than antibodies +/or complement e.g.:
•Mechanical (traumatic)Mechanical (traumatic)
•ToxinsToxins
•Infections Infections
•Splenomegaly (hypersplenism)Splenomegaly (hypersplenism)
•Burn (physical)Burn (physical)
•Renal failure and liver failureRenal failure and liver failure
•ChemicalChemical
Mechanical (Traumatic) Mechanical (Traumatic)
(Fragmentation)(Fragmentation)
This is due to direct trauma (stress) to the RBCs This is due to direct trauma (stress) to the RBCs
causing fragmentation of the RBCs & intra-causing fragmentation of the RBCs & intra-
vascular hemolysis. The fragmented cells can be vascular hemolysis. The fragmented cells can be
seen on peripheral blood smears & are called seen on peripheral blood smears & are called
(schistocytes).(schistocytes).
Due to:Due to:
1.1.Prosthetic valvesProsthetic valves
2.2. PatchesPatches
3.3. Valvular diseasse e.g., stenosisValvular diseasse e.g., stenosis
Cont…
Mechanical (Traumatic)
(Fragmentation)
(cont…)
1.1.Microangiopathic:Microangiopathic:mechanical hemolysis due to mechanical hemolysis due to
contact between the RBCs & the abnormal intema contact between the RBCs & the abnormal intema
of thrombosed, narrowed, necrotic small vessels or of thrombosed, narrowed, necrotic small vessels or
fibrin strand formation.fibrin strand formation.
Caused by many diseases e.g., DIC (disseminated Caused by many diseases e.g., DIC (disseminated
intravascular coagulation), malignant hypertension, intravascular coagulation), malignant hypertension,
disseminated malignancies especially mucin disseminated malignancies especially mucin
secreting adenocarcinomas, TTP secreting adenocarcinomas, TTP
(thrombocytopenic purpura), hemolytic uremic (thrombocytopenic purpura), hemolytic uremic
syndrome (HUS).syndrome (HUS).