Common denominator in HAs is an increase in erythrocyte destruction primarily by the trapping of cells in sinuses of the spleen or liver and producing a decrease in normal lifespan of the red blood cell.
The inability of bone marrow activity to compensate for increased red blood cell destruction resulted in anemia.
Most anemias have a hemolytic component.
Hemolysis is especially evident in megaloblastic anemias, thalassemias, and dyserythropoietic syndromes.
Causes of hemolysis are divided by various categories: disorders inherent to the red cell structure, conditions resulting in mechanical injury to the erythrocytes, immune mediated disease, infections, and toxic effects.
Disorders inherent to red cell structure include enzymopathy, membranopathy, and hemoglobinopathy and usually develop early in life.
Hemolysis associated with mechanical injury include march hemoglobinuria, aortic stenosis, and mechanical prosthetic heart valves, and microangiopathic hemolytic anemia.
The Causes of hemolytic anemias can be grouped into two main categories related to the location of the hemolysis.
Extravascular hemolysis is characterized by premature phagocytosis of red look cells by macrophages in the spleen and other reticuloendothelial tissues due to immune mediated destruction, hypersplenism, abnormal red cell deformability, or hemoglobinopathies.
Intravascular hemolysis occurs by direct mechanical red blood cell trauma, toxins, a microangiopathic process, or a complement mediated immunity crisis.
Hemolytic destruction of the erythrocyte involves alteration in the red cell membrane.
Hemolytic anemia is are divided into inherited hemolytic disorders or acquired hemolytic disorders.
Hemolytic anemias that are inherited are referred to as intrinsic hemolytic anemias and those that are acquired is referred to as extrinsic hemolytic anemia.
Hemolytic anemia’s can also be divided into intravascular and extravascular types referring to the site of destruction of the red blood cells, within the circulating blood or outside of it, respectively.
Inherited hemolytic disorders may affect the basic membrane structure, erythrocytic enzymes, or the hemoglobin molecules within the red blood cell.
The erythrocytes membrane proteins are important in the pathophysiology of hemolytic anemia.
As a consequence is severe intravascular hemolysis, a large amount of free hemoglobin is released into the circulation, after which the hemoglobin is bound and cleared by haptoglobin.
The presence of a low haptoglobin level and hemoglobinuria favors a diagnosis of intravascular hemolysis.
Structural proteins forming the erythrocyte skeleton are alpha and beta spectrin, actin, and protein 4.
Mutations in the genes that code for major membrane proteins can alter the functions of the proteins , compromise the integrity of the red blood cell membrane, and contribute to abnormal erythrocyte morphology.
Gene alterations of the skeletal and integral proteins in the red cell membrane are associated with hereditary hemolytic anemias.
Inherited abnormalities of the skeletal protein network of the red cell membrane produce decrease membrane stability, flexibility and deviations from the normal discoid shape.
Examination of the peripheral blood smear helps identify the cause of hemolytic anemia.
The presence of sickle cells and elliptocytes suggest an hereditary process.
Sphercutes suggest the presence of Hereditary spherocytosis or antibody mediated causes of hemolytic anemia such as drug induced hemolytic anemia or an auto immune disease.
The presence of schistocytes, red cell fragments, are the result of intravascular destruction that can occur from mechanical trauma such as mechanical heart valves mechanical circulatory support of ventricular assist devices, or dialysis or non-traumatic causes such as thrombotic microangiopathy.
Mechanical trauma induced hemolytic anemia can be associated with prosthetic valves, occurring in the presence of a mechanical heart valve with paravalvular regurgitation.
Prosthetic heart valve hemolysis can occur as a result of high shear stress with turbulent flow precipitated by foreign material, valve failure degeneration or a para valvular leak.
Paravalvular leaks are the most common cause of hemolysis among patients with a prosthetic valve and they are caused by an incomplete seal between the valve and the adjacent cardiac tissue, resulting in abnormal retrograde blood flow around the circumference of the valve.
Drug induced hemolytic anemias are usually mediated by immunologic mechanisms, and more than 150 drugs have been implicated.
Two types of drug induced hemolytic anemias exist: drug dependent subtype where auto antibodies are produced in response to a neo antigen formed by the binding of a drug to a cell surface structure; and a drug independent subtype, with the offending drug induces an auto immune response that persists even in the absence of the drug.
Historically methyldopa in large doses of penicillin were the most frequent causes of drug induced hemolytic anemia.
Today most cases are caused by ceftriaxone and other cephalosporins, pippericillin, and nonsteroidal anti-inflammatory drugs.
