Hemolytic Anemia
Hemolytic anemia's are a diverse group of diseases. Clinically they present on laboratory results with a high lactate dehydrogenase, LDH (must rule out a concurrent heart attack). High reticulocytes, which are red blood cell precursors. Calculation of the reticulocyte production index is useful here. RPI = retics % x (hct /45) x 1/2. Normal RPI = 1, above 2 = adequate marrow response. A high total bilirubin, mainly composed of unconjugated (unprocessed from the liver) (indirect ) bilirubin from lysed blood cells. However, one can have normal bilirubin. A low haptoglobin, and urine hemosiderin if there is any intravascular hemolysis.
Hemolytic anemia can either occur as a congenital or an acquired disorder.
Hereditary spherocytosis is when there is an intracorpuscular membrane defect in a structural protein termed spectrin. This disorder is passed through generations as an autosomal dominant trait. It is the most common type of hereditary hemolytic anemia. Positive family history is therefore seen. The spherocytes, which are the abnormally shaped red blood cells, are very fragile and will lyse prematurely. The test for this is the osmotic fragility test. Treatment is needed is through splenectomy.
Glucose 6 Phosphate deficiency (G6PD) is a X-linked recessive disorder, in which red blood cells (RBC) are susceptible to oxidative damage. These include drugs, such as sulfonamides and antimalarials, infection, fava beans, in addition to numerous others. Blood films may show bite cells and Heinz bodies, which are RBC inclusions. Treatment is only required during there oxidative stresses, as most patients can compensate. The only available treatments is transfusion, and of course, stopping the oxidative stressor (e.g. drug).
There are also numerous other congenital disorders, these include hereditary elliptocytosis, xerocytosis (abnormalities of RBC hydration), sickle cell anemia, thalassemia, hemoglobin Koln (which is a hemoglobin susceptible to oxidative stress), and PK deficiency.
Acquired hemolytic anemias include immune mediated forms.
Autoimmune hemolytic anemia (AIHA), where warm AIHA is removed by spleen, and are mainly IgG antibodies. Cold AIHA are of the immunoglobulin M types, and occur at temperatures of less than 37 celsius. Immunoglobulin M, IgM, is strong in fixing complement, and therefore complement fixing antibodies on the red blood cells leads to intravascular hemolysis. There are numerous etiologies for immune mediated forms of hemolytic anemias. These include idiopathic causes, lymphoproliferative disorders, autoimmune diseases (warm type), infections (cold), such as EBV and mycoplasma. Diagnosis is seeing sperocytes on blood film and a positive direct antibody test (DAT). Treatment is through steroids, splenectomy, and treatment of any underlying disese.
In drug induced forms of hemolytic anemia, these are hapten-induced. The drug binds to the red blood cell (RBC), and antibody binds to cell bound drug, such as with penicillins. Each drug has quite a different method of causing hemolysis. Innocent bystander, a drug-antibody complex binds to RBC and there is c-mediated destruction with quinines. Autoimmune destruction with drug triggers in AIHA, seen with methyldopa.
A transfucion reaction can also cause hemolysis, which is very severe.
The hemolysis is usually acute in nature, but can be delayed in 1/1000, with presentation 5-14 days post transfusion. Extravascular hemolysis due to alloantibodies too weak t be seen by cross matching. The patient presents with anemia, fever, and jaundice.
Microangiopathic Hemolytic Anemia is intravascular hemolysis due to intra-arteriolar fibrin which damages the red bloo cells. This can be seen in; DIC, HUS/TTP, leukemia, malignant hypertension, eclampsia, HELLP, prosthetic valves, infected vascular prosthesis. On blood film, there are Schistocytes, thrombocytopenia +/- other abnormalities associated with DIC, TTP. Main treatment is treat the underlying abnormality
Paroxysmal Nocturnal Hematuri is an acquired intracorpuscular defect in membrane associated proteins which predisposes RBCs to complement-mediated lysis. During, sleep there is mild respiratory acidosis which the patients RBCs are unable to protect against, and hemolysis and hemoglobinuria is seen. Blood in the urine only at night. Patients are also more susceptible to thrombosis. Diagnosis is through a postivie Ham’s test (acid hemolysis test) or sucrose hemolysis. Diagnosis can also be made through Flow cytometry.
Other causes of Acquired Hemolytic Anemias include: Liver disease, hypersplenism, March hemoglobinuria, RBC fragmentation, Hypersplenism, Infection: malaria, babesiosis, clostridial sepsis, and Thermal burns.
Intravascular hemolysis is caused through direct trauma, artificail valves, complement induced lysis, post hypotonic solution, bacterial toxins, microangiopathic (AS, prosthetic valves), PNH, transfusion reaction, hypotonic infusions. In these cases, decreased haptoglobin, hemoglobinuria, and hemosiderinuria can be seen.
Extravascular hemolysis, severely damaged RBCs coated in complement, due to being damaged in the liver. Spleen destroys poorly deformable RBC such as spherocytes. Hemoglobin is initially degraded into bilverdin, which is subsequently reduced to unconjugated bilirubin and released into plasma. Haptoglobin down from mopping up free hemoglobin. All intrinsic RBC defects, also liver spleen problem, infections, DIC, TTP, AIHA, post IvIg can cause.
Blood film looking for spherocytes, RBC fragments, acanthocytes – liver disease, bite cells and Heinz bodies – oxidant induced damage, inclusions: malaria, babesiosis, teardrops, nucleated RBC – marrow involvement – fibrosis or infiltration, elevated LDH (released from lysed cells), Haptoglobin – decreased, but it is also known to be an acute phase reactant. Reticulocyte count to see if the bone marrow is compensating appropriately. Indirect bilirubin, Direct antiglobulin test (Coombs Test). Can also test for cold agglutinins. To confirm intravascular hemolysis: plasma hemoglobin concentration, free hemoblobin in urine, and urine hemosiderin.