Hemolysis Mechanisms & Consequences

Anemia

A reduction in the hemoglobin content of blood, resulting from a decrease in red blood cell (RBC) count, hemoglobin concentration, or hematocrit below the reference interval for healthy individuals of the same demographic.

Microcytic Anemia

Anemia characterized by a Mean Cell Volume (MCV) less than 80 fL, indicating smaller red blood cells.

Normocytic Anemia

Anemia with a normal Mean Cell Volume (MCV).

Macrocytic Anemia

Anemia with a Mean Cell Volume (MCV) greater than 100 fL, indicating larger red blood cells.

Reticulocyte Count

A count reflecting bone marrow response to anemia, with high counts suggesting excessive red blood cell loss and low counts indicating inadequate production.

Absolute Reticulocyte Count

Obtained by multiplying the percentage of reticulocytes by the red blood cell count, providing a clearer picture of bone marrow response to anemia.

Peripheral Blood Film

A tool for diagnosing anemia, allowing visual assessment of red blood cell morphology, identification of abnormalities, and verification of automated results.

Sickle Cells

Elongated red blood cells seen in sickle cell anemia, leading to vaso-occlusive crises.

Spherocytes

Small, spherical red blood cells associated with hereditary spherocytosis.

Schistocytes

Fragmented red blood cells resulting from mechanical destruction, often seen in conditions like disseminated intravascular coagulation (DIC).

Oval Macrocytes

Large, oval-shaped red blood cells found in megaloblastic anemia.

Microcytes

Small red blood cells (less than 6 mm in diameter) typically associated with iron deficiency anemia or thalassemia.

Macrocytes

Large red blood cells (greater than 8 mm in diameter) often seen in megaloblastic anemia and chronic liver disease.

Hypochromic RBCs

Red blood cells showing increased central pallor, associated with iron deficiency anemia.

Normochromic RBCs

Red blood cells with normal color and hemoglobin content, found in healthy individuals.

Howell-Jolly Bodies

Nuclear remnants seen in patients with splenic dysfunction or after splenectomy.

Basophilic Stippling

Presence of ribosomal RNA, observed in lead poisoning and certain types of anemia.

Malarial Parasites

Inclusions indicating malaria infection.

Fatigue

A common symptom of anemia due to decreased oxygen delivery to tissues.

Pallor

A physical finding of anemia, noticeable in conjunctivae, skin, and nail beds, more pronounced in moderate to severe cases.

Tachycardia

Increased heart rate as the body compensates for low oxygen levels in anemia.

Hypotension

Possible in severe anemia due to inadequate blood volume.

Complete Blood Count (CBC)

Laboratory test showing low hemoglobin, hematocrit, and RBC count in anemia.

Analysis

Critical evaluation involving comparing lab results with clinical findings to differentiate between types of anemia and considering underlying pathophysiology for appropriate management.

Pathophysiology

Understanding mechanisms like decreased RBC production, increased destruction, or blood loss.

Integrate Data

Combine lab findings with symptoms for a comprehensive assessment.

Morphological Insights

Examining RBC size, shape, color, and inclusions for diagnostic clues.

Inclusions

Abnormal substances in RBCs indicating various pathological conditions.

Shape Changes

Variations indicating specific hematologic disorders like sickle cells or spherocytes.

Volume Changes

Measured through MCV, indicating microcytic or macrocytic conditions.

Color Changes

Reflects conditions like iron deficiency or hereditary spherocytosis.

Quantitative Red Cell Disorders

Distinguishing findings of iron deficiency, chronic inflammation, sideroblastic anemia, and iron overload.

Serum Iron

Measures the amount of iron bound to transferrin in the blood, indicating iron availability for erythropoiesis.

Total Iron-binding Capacity (TIBC)

Measures blood's capacity to bind iron with transferrin. Elevated in iron deficiency anemia and low in anemia of chronic inflammation.

Ferritin

Protein storing iron in the body. Reflects total stored iron levels, with low levels in iron deficiency and high levels in overload or inflammation.

Free Erythrocyte Protoporphyrin (FEP)

Indicates protoporphyrin levels in RBCs not converted to hemoglobin due to insufficient iron. Elevated in iron deficiency.

Soluble Transferrin Receptor (sTfR)

Levels increase in response to iron deficiency, indicating increased transferrin receptor expression to capture more iron.

Thomas Plot

Analyzes the curve shift to differentiate iron deficiency anemia (leftward shift) and anemia of chronic inflammation (rightward shift).

Iron Deficiency Anemia

Occurs when the body lacks iron for hemoglobin production, leading to oxygen-carrying issues in the blood.

Latent Iron Deficiency

State with low stored iron levels but no anemia symptoms yet, maintaining normal RBC production.

Anemia of Chronic Inflammation

Anemia in chronic diseases where inflammation disrupts iron metabolism, limiting iron availability for erythropoiesis.

Sideroblastic Anemia

Characterized by ringed sideroblasts in bone marrow failing to incorporate iron into hemoglobin, either hereditary or acquired.

Iron Overload Conditions

Lead to excessive iron accumulation in the body, potentially damaging organs, caused by various dysfunctions in iron metabolism.

Megaloblastosis

Presence of large abnormal erythroid precursors due to halted cell division from deficiencies of vitamin B12 and folate.

Red Blood Cell Morphology

In megaloblastic anemia, includes oval macrocytes, possible teardrop cells, RBC fragments, and hypersegmented neutrophils.

White Blood Cell Morphology

Shows hypersegmented neutrophils due to impaired DNA synthesis in megaloblastic anemia.

Bone Marrow Findings

In megaloblastic anemia, ineffective hematopoiesis leads to decreased reticulocyte levels, with possible presence of increased megakaryocytes.

Bilirubin and Lactate Dehydrogenase (LDH)

Elevated in megaloblastic anemia due to increased breakdown of ineffective RBCs, reflecting cell destruction.

Inherited Aplastic Anemia

Caused by genetic defects affecting hematopoietic stem cells, leading to bone marrow failure and reduced cell production.

Transient Erythroblastopenia of Childhood

Temporary condition with a sudden halt in RBC production, often self-resolving.

Diamond-Blackfan Anemia

Characterized by pure red cell aplasia and congenital abnormalities, leading to severe anemia.

Congenital Dyserythropoietic Anemia

Inherited disorder with ineffective erythropoiesis, resulting in abnormal RBC morphology and anemia.

Hematopoietic Stem Cells

Cells affected by genetic defects leading to bone marrow failure and reduced cell production

Pancytopenia

Symptoms include fatigue, pallor, bruising, and increased infection susceptibility

Hypocellularity

Bone marrow biopsy shows decreased hematopoietic stem cells

Sideroblastic Anemias

Anemias with unique bone marrow findings despite adequate iron stores

Red Cell Distribution Width (RDW)

Marker indicating variability in RBC size, elevated in iron deficiency anemia

Pathogenesis

The development process of various anemias, influenced by factors like iron intake, inflammation, and lead exposure

Lead Poisoning

Causes sideroblastic anemia by inhibiting heme synthesis enzymes and interfering with erythroid maturation

Hemochromatosis

Excessive iron accumulation in tissues due to genetic mutations disrupting iron absorption regulation

Erythropoietic Porphyrias

Anemia type with specific etiology, CBC picture, diagnostic metabolites, and clinical presentation

Erythropoietic porphyrias

Disorders from heme synthesis pathway impairments, affecting protoporphyrin production.

Enzyme deficiencies

Key etiology in erythropoietic porphyrias, like uroporphyrinogen III synthase and ferrochelatase.

Protoporphyrin

Accumulates in erythrocytes and hepatocytes in erythropoietic porphyrias.

CBC picture

Shows mild microcytic, hypochromic anemia in erythropoietic porphyrias.

Diagnostic metabolites

Include elevated protoporphyrin and uroporphyrin levels in blood, urine, and feces.

Porphobilinogen

Increased in urine in erythropoietic porphyrias, aiding in diagnosis.

Photosensitivity

Common symptom in erythropoietic porphyrias, exacerbated by sunlight.

Thymidine nucleotides

Essential for DNA replication, dependent on vitamin B12 and folate.

5-methyl THF

Active form of folate, conversion to THF impaired in vitamin B12 deficiency.

Tetrahydrofolate

Critical for DNA synthesis, affected by vitamin B12 deficiency.

dUMP

Methylated to dTMP in folate metabolism, hindered in folate deficiency.

Megaloblastic features

Result from ineffective DNA synthesis, seen in megaloblastosis.

Nuclear-cytoplasmic asynchrony

Occurs in megaloblastosis, where nucleus maturation lags behind cytoplasm.

Autoimmune responses

In acquired aplastic anemia, immune system targets and destroys stem cells.

Fanconi Anemia

An inherited aplastic anemia linked to DNA repair gene mutations.

Telomere shortening

Seen in Dyskeratosis Congenita, leads to stem cell senescence.

Fragmentation hemolysis

RBC lysis in bloodstream due to mechanical forces, leading to catabolic products.

Haptoglobin

Binds hemoglobin dimers released from lysed RBCs in fragmentation hemolysis.

Free heme

Breaks down into iron and protoporphyrin, converted to bilirubin after RBC lysis.