MLT 251 - Anemia of Destruction/Loss OBJs

Recall the reticulocyte count expected in blood loss versus blood destruction anemias.

In cases of blood loss anemia, the reticulocyte count is typically elevated as the body attempts to compensate for the loss. Conversely, in blood destruction anemia, the reticulocyte count may also be elevated but can vary depending on the underlying cause of hemolysis.

List the two types of blood loss anemias, indicate possible causes and the red cell morphology expected in each case.

The two types of blood loss anemia are acute and chronic. Acute blood loss often leads to normocytic red cells, while chronic blood loss typically results in microcytic red cells due to iron deficiency.

Discuss normal erythrocyte destruction and the mechanisms and physiology of extravascular hemolysis and intravascular hemolysis.

Normal erythrocyte destruction involves the breakdown of old or damaged red blood cells, primarily in the spleen and liver. Extravascular hemolysis occurs outside the blood vessels, where macrophages engulf red blood cells, while intravascular hemolysis happens within the blood vessels, often due to trauma, infection, or autoimmune reactions.

Describe tests results for intravascular and extravascular hemolysis.

Tests for intravascular hemolysis typically show elevated lactate dehydrogenase (LDH), decreased haptoglobin, and increased free hemoglobin in plasma. In contrast, extravascular hemolysis is characterized by increased bilirubin and reticulocyte count, with normal haptoglobin levels.

State the usual morphological classification in hemolytic anemias.

Hemolytic anemias are usually classified as normocytic, microcytic, or macrocytic based on red blood cell size, with normocytic anemia often seen in acute cases, microcytic anemia in chronic conditions, and macrocytic anemia associated with certain deficiencies.

Define the terms 'extrinsic' and 'intrinsic' as they relate to defects in the red cells; list several examples of each.

Extrinsic refers to factors outside the red blood cells causing hemolysis, such as autoimmune disorders or infections, while intrinsic pertains to inherent defects within the red blood cells themselves, such as hereditary spherocytosis or sickle cell disease.

Recall the mechanism, RBC morphology, and prognosis of inherited membrane defects such as Hereditary Spherocytosis and Hereditary Ovalocytosis.

Inherited membrane defects like Hereditary Spherocytosis and Hereditary Ovalocytosis lead to red blood cell membrane instability, resulting in spherocytes and ovalocytes respectively. These conditions often result in splenic destruction of the abnormal cells, leading to hemolytic anemia, with a generally favorable prognosis when managed properly.

Discuss the influence on red cell survival of the following enzyme deficiencies: G-6-PD, pyruvate kinase.

Enzyme deficiencies like G-6-PD and pyruvate kinase lead to increased oxidative stress and reduced ATP production, respectively, resulting in decreased red blood cell survival and hemolysis.

Identify in which population groups G-6-PD and pyruvate kinase deficiencies are most often seen.

G-6-PD deficiency is most common in African, Mediterranean, and Asian populations, while pyruvate kinase deficiency is often identified in the Ashkenazi Jewish population.

State which of the inherited anemias is most common in the U.S. and indicate the usual population.

Sickle Cell Anemia; primarily affects African Americans.

Correlate red cell shape with indices in Hereditary Spherocytosis.

Hereditary Spherocytosis is characterized by spherical red blood cells, leading to increased mean corpuscular hemoglobin concentration (MCHC) and decreased red cell deformability, resulting in hemolysis.

List several other reasons for observing spherocytes on the peripheral blood smear.

These may include autoimmune hemolytic anemia, hemolysis due to mechanical damage, and blood transfusions.

Correlate MCHC values with the presence of spherocytes.

Higher MCHC values indicate increased spherocyte presence, often associated with conditions like Hereditary Spherocytosis and autoimmune hemolytic anemia.

Differentiate elevated MCHC due to spherocytes from cold agglutinins.

Elevated MCHC due to spherocytes is typically associated with hereditary spherocytosis, whereas cold agglutinins lead to increased MCHC by causing red cell clumping at low temperatures, affecting overall red cell morphology.

Recall expected osmotic fragility results in Hereditary Spherocytosis and Hereditary Ovalocytosis.

In Hereditary Spherocytosis, osmotic fragility is typically increased, leading to hemolysis in hypotonic solutions, while in Hereditary Ovalocytosis, it remains normal or only mildly increased.

Briefly explain the pathology that leads to red cell hemolysis in each of the following and state the usual morphological classification if anemia results: Paroxysmal Cold Hemoglobinuria (PCH), Paroxysmal Nocturnal Hemoglobinuria (PNH), Hemoglobinopathies, Thalassemias, Microangiopathic Hemolytic Anemia (MAHA), Acquired Hemolytic Anemia, Autoimmune Hemolytic Anemia (AHA) and Hemolytic Disease of the Newborn (HDN).

These conditions result in red cell destruction through various mechanisms: PCH involves antibody-mediated hemolysis triggered by cold exposure; PNH is caused by a genetic defect in red cell membrane proteins leading to complement-mediated lysis; hemoglobinopathies and thalassemias result from abnormal hemoglobin synthesis; MAHA is characterized by microangiopathic damage to red cells; acquired hemolytic anemia involves extrinsic factors destroying red blood cells; AHA involves autoantibodies against red cell antigens; HDN arises from maternal-fetal blood group incompatibility. Each can lead to normocytic or microcytic anemia depending on the severity and type.

Compare and contrast hereditary spherocytosis from immune hemolytic spherocytic anemia.

Hereditary spherocytosis is an inherited condition characterized by a defect in red cell membrane proteins, leading to increased osmotic fragility and hemolysis, while immune hemolytic spherocytic anemia results from autoantibodies targeting red blood cells, causing similar morphological changes. Both conditions manifest with spherocytes but differ in their underlying causes and pathophysiology.

Identify hemolytic anemias in which a positive DAT result may be observed and explain why it occurs.

A positive Direct Antiglobulin Test (DAT) may be observed in autoimmune hemolytic anemia, where antibodies are directed against red cell antigens, and in hemolytic disease of the newborn (HDN), where maternal antibodies cross the placenta and attach to fetal red blood cells. It indicates the presence of antibodies or complement proteins bound to the red blood cell surface.

Give examples of Microangiopathic Hemolytic Anemia (MAHA) and briefly describe each. Categorize as to their morphological classification each of the anemias of destruction.

Examples of Microangiopathic Hemolytic Anemia (MAHA) include Thrombotic Thrombocytopenic Purpura (TTP), characterized by microvascular thrombi leading to hemolysis and thrombocytopenia; Hemolytic Uremic Syndrome (HUS), which involves kidney damage and similar pathogenic mechanisms; and Disseminated Intravascular Coagulation (DIC), caused by systemic activation of coagulation leading to hemolysis. MAHA typically presents as microcytic or normocytic anemia due to red cell fragmentation.

Summarize the most characteristic findings for each of the anemias studied in this lesson.

This lesson covers various types of anemias, highlighting key findings such as increased reticulocytes in hemolytic anemias, microangiopathic changes in MAHA, and hereditary spherocytosis characterized by spherocytes on blood smear.