Hematology New PDF

"You Make Mistakes, Mistakes Don't Make You" Maxwell Maltz # HEMATOLOGY ## Components of Whole Blood - Whole blood is composed of plasma and formed elements. - Plasma is comprised of water (91%), proteins (7%), and other solutes (2%). - Proteins are further categorized into: - Albumin...

"You Make Mistakes, Mistakes Don't Make You" Maxwell Maltz # HEMATOLOGY ## Components of Whole Blood - Whole blood is composed of plasma and formed elements. - Plasma is comprised of water (91%), proteins (7%), and other solutes (2%). - Proteins are further categorized into: - Albumins (57%) - Globulins (38%) - Fibrinogen (4%) - Prothrombin (1%) - Other solutes include: - Ions - Nutrients - Waste products - Gases - Regulatory substances - Formed elements are composed of: - Platelets (<1%) - Leukocytes (<1%) - Neutrophils (65-75%) - Lymphocytes (20-25%) - Monocytes (3-8%) - Eosinophils (2-5%) - Basophils (0.5-1%) - Erythrocytes (>99%) ### The Process of Erythropoiesis - Erythropoiesis is the process of making red blood cells. This process is triggered by low oxygen levels in the blood. - The kidneys detect and respond to low oxygen levels, a state known as hypoxia, by releasing a hormone called erythropoietin (EPO). - EPO travels to the bone marrow, where it stimulates the production of red blood cells. - The red blood cells are released into the bloodstream, where they carry oxygen to the tissues. - If the kidneys are not functioning properly, they may not be able to produce enough EPO, which can lead to anemia. ### The Components of Red Blood Cells - Red blood cells (RBCs) contain hemoglobin, which is responsible for carrying oxygen to the tissues. - Hemoglobin is composed of heme and globin. - Heme is a molecule that contains iron and a porphyrin ring. - Globin is a protein that binds to heme. - Each hemoglobin molecule can bind to four oxygen molecules. That makes heme critical for oxygen transport in the blood. ### The Process of Hemolysis - Hemolysis is the breakdown of red blood cells. - Hemolysis typically occurs in the spleen and liver, where old and damaged red blood cells are removed from circulation. - During hemolysis, hemoglobin is broken down into heme and globin. - Heme is further broken down into iron and bilirubin. - Iron is recycled back to the bone marrow, where it is used to make new red blood cells. - Bilirubin is transported bound to serum albumin, conjugated with glucuronic acid in the liver, and excreted into bile. ### The Importance of Iron - Iron is an essential mineral that is necessary for the production of hemoglobin. - Iron is transported in the blood bound to a protein called transferrin. - Iron for hemoglobin synthesis is stored in the liver, as ferritin. ## The Process of Hemostasis - Hemostasis is the process of stopping bleeding. This process involves a combination of platelets, clotting factors, and a cascade of protein interactions resulting in fibrin formation. - The primary hemostatic response involves the formation of a platelet plug. - When a blood vessel is damaged, platelets adhere to the exposed collagen. - This adhesion triggers the platelets to release chemicals that cause them to aggregate, forming a platelet plug. - The secondary hemostatic response involves the coagulation cascade. - This cascade of enzymatic reactions leads to the formation of a fibrin clot. - The fibrin clot strengthens and stabilizes the platelet plug, stopping the bleeding. - Fibrinolysis is the breakdown of the fibrin clot. This process is necessary to remove the clot once the bleeding has stopped and to repair the damaged blood vessel. ### The Coagulation Cascade - The coagulation cascade involves a series of clotting factors that work together to form a fibrin clot. - The coagulation cascade can be activated by either the intrinsic pathway or the extrinsic pathway. - The intrinsic pathway is activated by contact with collagen or other substances that are present in the blood. - The extrinsic pathway is activated by tissue factor, which is released from damaged tissue cells. - Both the intrinsic and extrinsic pathways converge on a common pathway that leads to the activation of thrombin, a key enzyme in the coagulation cascade. - Thrombin converts fibrinogen, a soluble protein in the blood, into fibrin, an insoluble protein that forms the fibrin clot. - Heparin and warfarin are medications that block coagulation, while thrombolysis is an important process for dissolving clots once it is no longer needed to stop bleeding. ### The Breakdown of Clots - Plasmin is a protein that breaks down fibrin clots. It is activated by a trigger like t-PA, or u-PA. - u-PA is found within the blood vessel wall and released on damage. - t-PA is a protein that is found in tissues and is given intravenously as a medication to dissolve blood clots. # Anemia - Anemia is defined as a reduced ability of the blood to deliver oxygen to tissues, leading to a deficiency in oxygen. - Anemia is not a disease, but rather the expression of an underlying disorder or disease. - Anemia can be caused by a reduction in the number of red blood cells, a decrease in the amount of hemoglobin, or both. - The severity of anemia can vary from mild to severe. ### Complete Blood Count (CBC) - A complete blood count (CBC) is a commonly ordered blood test that measures the following: - Red blood cell count - Hemoglobin level - Hematocrit - Mean corpuscular volume (MCV) - Mean corpuscular hemoglobin (MCH) - Mean corpuscular hemoglobin concentration (MCHC) - Red cell distribution width (RDW) ### Classification of Anemia by Morphology - Anemia can be classified by the morphology (size and color) of red blood cells: - Size: - **Macrocytic:** Red blood cells are larger than normal - **Microcytic:** Red blood cells are smaller than normal - **Normocytic:** Red blood cells are the normal size. - Color: - **Normochromic:** Red blood cells have a normal amount of hemoglobin and thus have a normal color. - **Hypochromic:** Red blood cells have a reduced amount of hemoglobin, resulting in a paler than normal color. ### Macrocytic Anemia - Macrocytic anemia is characterized by the presence of larger than normal red blood cells. - Macrocytic anemia is most often caused by a deficiency of vitamin B12 or folate. - Symptoms of macrocytic anemia include fatigue, weakness, and a pale complexion. In some cases, neurological symptoms such as numbness and tingling may occur. - Treatment for macrocytic anemia typically involves replacing the deficient nutrient. - In cases of B12 deficiency, injections of vitamin B12 are often required for treatment. - In cases of folate deficiency, oral supplements of folate are typically prescribed. - Macrocytic anemia may also be caused by other conditions such as liver disease, hypothyroidism, and certain medications. #### Pernicious Anemia - Pernicious anemia is a type of macrocytic anemia that is caused by a deficiency of vitamin B12. - Pernicious anemia is an autoimmune disorder that results in the destruction of parietal cells in the stomach. - The parietal cells are responsible for producing intrinsic factor, a protein that is essential for the absorption of vitamin B12 from the diet. #### Folate Deficiency - Folate deficiency is another common cause of macrocytic anemia. - Folate is a B vitamin that is essential for DNA synthesis. - Folate is absorbed in the upper small intestine and is not dependent on intrinsic factor or other factors. - A deficiency of folate can occur due to a lack of folate in the diet, poor absorption of folate, or increased requirements for folate such as during pregnancy. - Symptoms of folate deficiency are similar to those of B12 deficiency but neurological symptoms are usually absent. - Treatment typically involves taking oral folate supplements. ### Microcytic Anemia - Microcytic anemia is characterized by the presence of smaller than normal red blood cells. - Microcytic anemia is most often caused by a deficiency of iron. The iron deficiency causes decreased hemoglobin production and leads to the production of small, pale red blood cells. - Other causes of microcytic anemia include certain genetic disorders, such as thalassemia, and chronic disease states such as chronic inflammation and chronic kidney disease. - Symptoms of iron deficiency anemia include fatigue, weakness, pale skin, shortness of breath, and brittle, thin nails. - Treatment for iron deficiency anemia typically involves taking oral iron supplements. #### Iron Deficiency Anemia - Iron deficiency anemia is the most common type of anemia worldwide. - Iron deficiency anemia can occur due to a lack of iron in the diet, poor absorption of iron, or blood loss. - Treatment for iron deficiency anemia involves addressing the underlying cause and supplementing with oral iron. ### Normocytic Anemia - Normocytic anemia is characterized by the presence of red blood cells that are normal in size. - Normocytic anemia can be caused by a variety of conditions, including: - Hemolysis: destruction of red blood cells - Bone marrow suppression: decreased production of red blood cells - Anemia of chronic disease: a condition that can occur with long-term inflammation # Platelet Dysfunction and Coagulopathy - Platelet dysfunction is a condition in which platelets do not function properly. - Coagulopathy is a disorder of the coagulation system, leading to either an increased or decreased ability to form a clot. ## Platelet Dysfunction - Platelet dysfunction can be congenital (present at birth) or acquired. - Platelet dysfunction can cause excessive bleeding. - One example of inherited platelet dysfunction is von Willebrand disease. - von Willebrand disease is an autosomal dominant disorder characterized by defective platelet adhesion and/or prolonged bleeding time. It is the most common inherited bleeding disorder. ## Coagulation Cascade Dysfunction - Coagulation cascade dysfunction is a condition in which the coagulation system does not function properly. - A deficiency of clotting factors can lead to excessive bleeding. - This can be due to: - Vitamin K deficiency (necessary for the synthesis of many of the clotting factors), - Liver disease (liver produces clotting factors), - Defective absorption of clotting factors, - Medications such as warfarin (Coumadin) and heparin. - Examples of coagulation cascade dysfunction include hemophilia. #### Hemophilia - Hemophilia is a group of inherited bleeding disorders that are caused by a deficiency of clotting factors. - Hemophilia A is the most common type of hemophilia and is caused by a deficiency of factor VIII. - Hemophilia B is caused by a deficiency of factor IX. - Hemophilia is an X-linked recessive disorder, meaning that more men are affected than women. ## Disseminated Intravascular Coagulation (DIC) - DIC is a serious condition that is characterized by widespread blood clotting and bleeding simultaneously. - This condition is often triggered by a serious underlying medical condition such as sepsis, trauma, cancer, or pregnancy. - DIC is a complex disorder that can be fatal. - Often it results from an overwhelming activation of the coagulation cascade. - This leads to the formation of small clots throughout the bloodstream. The small clots can block blood vessels, causing tissue damage and organ failure. # Anemia Workup - Case Study A 56 year old male patient presents to the clinic with a 6 month history of anemia. His hemoglobin is 9.6 g/dL. To assess for the cause of his anemia, it is important to assess key features of his presentation and obtain a complete history and physical exam. - It is important to obtain demographic information such as age, sex, and race. - It is important to determine the duration and severity of the patient's symptoms. - Laboratory investigation should be performed including: - A complete blood count (CBC), including white blood cell count, red blood cell count, and platelets - A reticulocyte count - A review of peripheral blood smear - Iron studies including serum iron, ferritin, and transferrin levels - Levels of vitamin B12 and folate - Treatment will be determined based on the diagnosis.