Red Blood Cell and Bleeding Disorders

Red Blood Cell and Bleeding Disorders

• Blood cell development begins in the yolk sac (3rd week), liver (4th week), and then bone marrow (4th month)
• At birth, bone marrow is throughout the skeletal structure, with minimal hematopoiesis in the liver
• In adults, approximately 50% of the bone marrow remains active
• Hematopoiesis is the formation of blood cellular components.

Hematopoiesis

• Hematopoiesis occurs in prenatal and postnatal stages.
• Prenatal hematopoiesis occurs in the yolk sac followed by the liver and spleen.
• Postnatal hematopoiesis predominantly occurs in the bone marrow; later in life, the vertebral column, ribs, sternum, pelvic girdle, and proximal femur are involved.
• Graph showing the change of hematopoietic sites through prenatal and postnatal development
• A chart displays normal hemoglobin (Hb) values in adults categorized by gender

Anemia

• Anemia is a reduction below normal limits of total circulating red blood cells (RBCs), leading to decreased oxygen transport.
• Symptoms include weakness, malaise, easy fatigability, dyspnea (shortness of breath), headache, dizziness, and angina
• Physical examination may show pallor, brittle nails, koilonychia (spoon-shaped nails), etc.
• Anemia reduces the oxygen-carrying capacity of the blood, causing tissue hypoxia.
• Diagnosis is typically based on reduced hematocrit and hemoglobin concentration.

Normal Hemoglobin

• HbA (α2β2) comprises approximately 95% of adult hemoglobin.
• HbA1c, HbA2 (α2δ2), and HbF (α2γ2) are other types present in smaller percentages.
• Fetal hemoglobin (HbF) is the major type during the 3rd to 9th fetal month, promoting oxygen delivery to the growing embryo from the placenta
• Gower 1 and 2, and Portland are early embryonic hemoglobins.

Classification of Anemia

• Classification categories, as examples include: Blood loss (acute/chronic), Increased rate of destruction (hemolytic anemia), and Impaired red cell production.
• Categories of hemolytic anemia by cause, either intrinsic or extrinsic

Intravascular Hemolysis

• This process causes free hemoglobin to be present in the blood (hemoglobinemia) and in the urine (hemoglobinuria).
• Causes include mechanical injury (artificial heart valves), complement fixation, intracellular parasites, and exogenous toxic factors

Extravascular Hemolysis

• This process occurs primarily within the spleen, resulting in anemia, splenomegaly, and jaundice.
• Causes include conditions that reduce red blood cell deformability leading to splenic sequestration and phagocytosis by macrophages within the splenic cords

Glucose-6-Phosphate Dehydrogenase Deficiency

• Abnormalities in the hexose monophosphate shunt or glutathione metabolism.
• Reduced ability of red cells to protect themselves against oxidative injuries causing hemolysis.
• Oxidant-induced cross-linking of reactive sulfhydryl groups on globin chains leads to Heinz bodies.
• Bite cells and spherocytes are trapped and removed from the blood by splenic macrophages.
• Exposure to oxidant drugs, fava beans, or infections can trigger hemolysis.

Sickle Cell Anemia

• Inherited hemoglobinopathy caused by a point mutation in the β-globin gene
• Deoxygenated hemoglobin S (HbS) polymerizes, altering red blood cell shape.
• Chronic hemolysis, microvascular occlusion, and ischemic tissue damage are major consequences.
• Symptoms include severe pain crises, especially in bones, and organ damage.
• Factors influencing sickling include HbS concentration, oxygen tension, and intracellular pH.

Thalassemia

• Hereditary diseases caused by mutations affecting α- or β-globin chain synthesis.
• Defective globin synthesis causes hemoglobin deficiency and an excess of either α or β chains.
• Causes include gene deletions or point mutations, resulting in abnormal hemoglobin synthesis.
• The clinical severity ranges, with symptoms varying in intensity
• Patients may require blood transfusions and may develop iron overload complications.

Aplastic Anemia

• A syndrome of primary failure of hematopoiesis, causing pancytopenia (low levels of all blood cell types).
• The bone marrow is hypocellular or shows suppression of hematopoiesis.
• Causes may be intrinsic (stem cell abnormality) or extrinsic (immune system-mediated).
• Treatment often involves transplantation or immunosuppressive therapy.

Acquired Hemolytic Anemias

• Hemolytic anemias occurring in response to antibodies against red blood cells.
• Classified as warm antibody, cold agglutinin, and cold hemolysin types, based on antibodies' temperature-dependent binding to red blood cells
• Different classifications for warm antibody and cold agglutinin immunohemolytic anemia (IHA).
• IHA due to antibodies against red blood cell surface proteins.
• Causes include drug reactions, autoimmune disorders, or lymphoproliferative diseases.
• Treatment includes drug discontinuation, immunosuppressants, or splenectomy.

Anemia Due to Diminished Production

• Deficiency of vitamin B12 or folate, often due to impaired absorption, increased requirement, or impaired utilization of these vitamins.
• Abnormal DNA synthesis in erythroid precursors characterizes megaloblastic anemia, with macrocytic, hyperchromic (large cells with elevated hemoglobin content) red blood cells.
• Impaired absorption of certain vitamins leads to megaloblastic anemia.
• Diagnosis relies on a variety of tests, including blood counts and bone marrow analysis Causes of each deficiency including; vitamin B12 and folate deficiencies

Megaloblastic Anemia

• Caused by deficits in vitamin B12 or folic acid, affecting DNA synthesis in erythroid precursors
• Manifestation: presence of megaloblasts, large red blood cells; also characterized by hypersegmented neutrophils and decreased reticulocyte counts

Polycythemia

• An abnormally high number of circulating red blood cells, often with elevated hemoglobin levels.
• May be relative (hemoconcentration) or absolute (increased red blood cell mass).
• Primary polycythemia vera stems from an intrinsic hematopoiesis abnormality.
• Secondary cases indicate increased erythropoietin secretion due to various factors (e.g., low oxygen levels, lung disease)
• Physical examination may show cyanosis, plethoracy (redness of the skin)
• A range of laboratory tests are utilized to support diagnosis and differentiation.

Bleeding Disorders

• Disorders characterized by defects in blood vessels, platelets, or clotting factors, leading to spontaneous or excessive bleeding

Clotting Factors

Includes inherited disorders (like hemophilia A and B, deficiencies in other clotting factors, and von Willebrand disease) or liver disease related to problems with the clotting cascade.

Immune related bleeding disorders

Includes defects in platelets, von Willebrand factors and clotting factors.

This quiz explores the development of red blood cells, hematopoiesis, and anemia. It covers the stages of blood cell formation from prenatal to postnatal periods, as well as normal hemoglobin values in adults. Test your knowledge on the key concepts related to blood cell disorders.