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Hemolytic Anemia
Hemolytic Anemia
Overview
Clinical features of hemolysis Laboratory features of hemolysis Congenital hemolytic anemias
Membrane defects Enzyme defects
Hemolytic AnemiasIntroduction
Definition: a group of disorders characterized by decreased red cell lifespan. Normal red cell lifespan is 120d. Remember that the patient may not always be anemic, depending on the degree of marrow compensation.
Parvovirus B19
Non-encapsulated DNA virus. Infects and lyses RBC precursors in marrow, causing 7-10d cessation of erythropoiesis. Normal individuals have no significant hematologic effect, since RBCs have normal life span. In pts with hemolytic anemias, loss of red cell production causes H/H to plummet dramatically = Aplastic Crisis
Intravascular Hemolysis
Erythroid Hyperplasia
Expansion of the erythroid lineage. Arrow is pointing to red cell precursor. Myeloid:erythroid ratio is normally 3:1. The slide above has ratio of 1:10.
Frontal Bossing
Results from increased erythropoietic activity and marrow space expansion
Only clinically significant if liver function is abnormal Only begins to rise when red cell life span is 50 days or less
Biochemical Consequences of Intravascular Hemolysis Reduced serum haptoglobin Hemoglobinemia Hemoglobinuria Hemosiderinuria
Acquired
Hereditary pyropoikilocytosis
Hereditary Spherocytosis
Defect is in proteins of the membrane skeleton, usually spectrin or ankyrin Lipid microvesicles are pinched off in the spleen and other RE organs, causing decreased MCV and spherocytic change.
Hereditary Spherocytosis
Autosomal Dominant trait Patients can develop increased hemolysis and abdominal pain with even trivial infectious illnesses Diagnose by Osmotic Fragility Aplastic crises with Parvovirus B19 Treatment: Folate supplementation Splenectomy will cause hemolysis to abate, but spherocytes will persist.
Osmotic Fragility
Normal
Abnormal
Low G6PD activity results in low levels of NADPH and reduced glutathione, which are required to protect hemoglobin from oxidative damage. In the absence of adequate reducing ability (provided by G6PD), oxidizing agents convert hemoglobin to methemoglobin, then denature it, causing it to precipitate as Heinz bodies. The spleen pinches off the Heinz body and the overlying membrane, leaving a bite cell or blister cell
G6PD
Two normal forms of enzyme. Most prevalent type is B. 20% of healthy Africans have type A. Deficiency is X-linked. In Africans with G6PD deficiency, mutant protein is A-, which is unstable and loses activity as the red cell ages. Mediterranean variant has baseline low activity. In US, 10-14% of AA men affected In NC, deficiency can be seen in women, since prevalence is high enough.
Blister cell
Typically, hemolysis is triggered by drugs or infections. Anemia is maximal 7-10 d after exposure. Individuals with A- begin to compensate for the anemia by making reticulocytes, despite continuation of drug. Immediately after a hemolytic episode, G6PD levels in pts with A- may be normal, since the mature cells have been lysed, and only younger cells with normal G6PD levels, are present
Thalassemia-like syndromes from decreased synthesis of an abnormal globin chain: Hb E, Hb LePore, Hb Constant Spring
Pathophysiology
Red cells react with antibody, with or without complement fixation, leading to RBC destruction. IgG-coated RBCs interact with Fc receptors on macrophages, leading to complete or partial phagocytosis, with spherocyte formation (extravascular hemolysis). C3-coated red cells interact with C3 receptors on macrophages, with phagocytosis (extravascular hemolysis). Alternatively, complement cascade can be competed, with complement-mediated RBC lysis (intravascular hemolysis).
Coombs Test
The Direct Coombs = DAT (Direct Antiglobulin Test) - tests for IgG or C3 DIRECTLY ON THE RED CELLS. The Indirect Coombs - tests for IgG or C3 in the serum which react with generic normal red cells. This is also known as the antibody screen in blood-banking.
Agglutination
Agglutination
Normal control
Spherocyte Formation
Warm-Antibody Hemolytic Anemias Treatment Patients may require red cell transfusions, if they are symptomatic with their anemia However, immunosuppression is the mainstay of therapy.
True autoimmune
Paroxysmal Nocturnal Hemoglobinuria Clinical features Pancytopenia may be seen. Predisposition to thrombosis.
May develop during the course of aplastic anemia, either preceding aplasia or after recovery from aplasia. May develop into acute leukemia Hemolysis is predominantly nocturnal (when pH usually falls), usually mild.
Both arterial and venous, ae well as clots in odd places. Associated with development of BuddChiari syndrome.
TTP/HUS DIC
Malignant hypertension Ecclampsia, HELLP syndrome Vasculitis Other, including metastatic cancer, scleroderma renal crisis, solid organ transplant rejection
MAHA - Schistocytes
Macroangiopathic Hemolytic Anemias Abnormalities within heart and large vessels can cause shear damage to RBCs. Schistocytes are also seen here Prior to surgery: AS, ruptured sinus of valsalva, ruptured chordae, coarctation, aortic aneurysm and/or dissection. After surgery: complement activation in bypass or dialysis tubing, after patching operations, after valve replacement
March Hemoglobinuria
1861 - German soldier complained of dark urine after strenuous marches. 1964 - 2 track runners noted dark urine after races. Disappeared after softer shoe insoles used. Mechanical damage to red cells also reported after conga drum playing, head beating, and karate exercises.
Arsenic, especially arsine gas Lead - produces some shortening of RBC lifespan, but anemia mainly due to defect in heme synthesis. Copper - deliberate ingestion, accumulation of toxic amounts from dialysis fluid exposed to copper pipes, and Wilsons disease. Insect, spider (esp brown recluse), snake venoms Heat/burns