Blood, Blood Groups and Hemostasis - Ajman University PDF

BLOOD, BLOOD GROUPS AND HEMOSTASIS Integrated Biological Sciences – II DDS108 Dr. Jayaraj Ajman University 14-Jan-25 1 ...

BLOOD, BLOOD GROUPS AND HEMOSTASIS Integrated Biological Sciences – II DDS108 Dr. Jayaraj Ajman University 14-Jan-25 1  LEARNING OUTCOMES ▪ Name the different types of blood cell ▪ State the functions of blood ▪ Briefly discuss composition of plasma ▪ Describe the structure of hemoglobin and enumerate its properties ▪ Describe the structure and function of each types of WBC ▪ Describe the ABO system of blood groups ▪ State Landsteiner law ▪ Describe the Rh system of blood groups ▪ Explain the procedure and importance of cross-matching of blood ▪ Describe the consequences of mismatched blood transfusion ▪ Describe about Haemolytic disease of the newborn Ajman University 14-Jan-25 2  LEARNING OUTCOMES ▪ Describe the structure and functions of platelets ▪ Describe importance of normal platelet count in hemostasis ▪ Define hemostasis ▪ State the mechanism of primary hemostasis ▪ With the help of flow chart explain the mechanism of blood coagulation Ajman University 14-Jan-25 3  Blood ❑ Blood ▪ Is a connective tissue ▪ Composed of blood plasma ▪ Dissolves and suspends various cells and cell fragments ▪ Denser and more viscous than water ▪ Slightly sticky ▪ Temperature - 38oC ▪ pH - 7.35 to 7.45 ▪ Color of blood High oxygen content - bright red Low oxygen content - dark red Ajman University 14-Jan-25 4  Components of Blood Blood plasma Contains dissolved substances - 55% Formed elements Cells and cell fragments - 45% o Red blood cells (RBCs) o White blood cells (WBCs) o Platelets Ajman University 14-Jan-25 5  Hematocrit ❑ Haematocrit (Packed Cell Volume, (PCV)) ▪ Proportion or percentage of blood made up of cells RBCs Buffy coat – WBCs and platelets ▪ Normal: 0.42 - 0.47 ▪ Generally greater in men than in women ▪ PCV increases in Polycythemia ▪ PCV decreases in Dehydration Anemia Dengue fever Cirrhosis of liver Pregnancy Ajman University 14-Jan-25 6  Blood Plasma ❑ Blood Plasma A straw-colored liquid Non-protein nitrogenous substances ▪ Water - 91.5% Urea ▪ Solutes - 8.5% solutes Uric acid Organic molecules Creatine Plasma proteins (7%) Creatinine Sugar, fats, enzymes, hormones Inorganic molecules Extracellular: Na+, Ca2+, Cl-, HCO3- Intracellular :K+, Mg2+, Cu2+, Fe2+, Fe3+, PO4- Ajman University 14-Jan-25 7  Plasma Proteins Albumin Maintains colloidal osmotic pressure Transport proteins for steroid hormones and for fatty acids Buffering action Maintain viscosity Globulins Immunoglobulins help attack viruses and bacteria Alpha and beta globulins transport iron, lipids, and fat-soluble vitamins Buffering action Fibrinogen Plays essential role in blood clotting Ajman University 14-Jan-25 8  Formed Elements Red blood cells White blood cells ❖Granular leukocytes Neutrophils Eosinophils Basophils ❖Agranular leukocytes Lymphocytes Monocytes Platelets Ajman University 14-Jan-25 9  Functions of Blood Transportation ▪ Respiratory Transports oxygen from the lungs to the cells Carbon dioxide from the body cells to the lungs ▪ Nutritive Carries nutrients from the gastrointestinal tract to body cells ▪ Excretory Transports waste products to various organs for elimination from the body Ajman University 14-Jan-25 10  Functions of Blood Regulation ▪ Maintain homeostasis Regulate water, pH, electrolytes to normal limits ▪ Regulate of body temperature Adjust body temperature through the heat absorbing and coolant properties of the water ▪ Maintain osmotic pressure Through interactions of dissolved ions and proteins Fluid exchange between blood and tissues ▪ Reservoir and transport hormones Ajman University 14-Jan-25 11  Functions of Blood Protection ▪ Blood clot Protects against excessive loss of blood after an injury ▪ Immune function WBCs protect against disease by carrying on phagocytosis Antibodies, interferons, and complement help to protect against disease Ajman University 14-Jan-25 12  Red Blood Cells ❑ Red blood cells or erythrocytes ▪ Are biconcave discs ▪ Diameter of 7–8 µm ▪ Contain hemoglobin molecules ▪ Lack a nucleus and other organelles ▪ Life span -120 days ▪ Normal RBC count in million/µL of blood Adult male - 5.4 Adult female - 4.8 ▪ Lack mitochondria and generate ATP by anaerobic mechanisms, so do not consume any of the oxygen Ajman University 14-Jan-25 13  Red Blood Cells Importance of biconcave shape ▪ Allows for flexibility and shape change while squeezing through capillaries ▪ Increases the surface area for diffusion of gases while decreasing the distance through which gases have to diffuse ▪ Variations in the shape and dimensions of RBCs are useful in the differential diagnosis of anemias Ajman University 14-Jan-25 14  Hemoglobin Molecules ❑ Hemoglobin molecules (Hb) ▪ Each RBC contains about 280 million Hb ▪ Hb consists of a protein called globin ▪ Globin composed of four polypeptide chains Two alpha and two beta chains ▪ A ring like nonprotein pigment called a heme ▪ Heme is bound to each of the four chains ▪ At the center of each heme ring is an iron ▪ Men ion (Fe2+) 14 – 17 Hb in g/100 ml of blood ▪ Fe2+ combine reversibly with one O2 ▪ Women ▪ Each hemoglobin molecule binds four O2 11 -14 Hb in g/100 ml of blood Ajman University 14-Jan-25 15  Fate of Red Blood Cells ▪ Life span in blood stream is 60-120 days ▪ Old RBCs become rigid and fragile ▪ And their hemoglobin begins to degenerate ▪ Dying erythrocytes are engulfed by macrophages ▪ And/or lysed mainly extra vascularly in the reticuloendothelial system( Liver ,Spleen and Bone marrow) Ajman University 14-Jan-25 16  Fate of Red Blood Cells Hb Metabolism ▪ Heme is degraded to a yellow pigment called bilirubin ▪ The liver secretes bilirubin into the intestines as bile ▪ The intestines metabolize it and it leaves the body in feces, as a pigment called stercobilin Urine- excreted as Urobilin ▪ Globin is metabolized into amino acids and is released into the circulation Ajman University 14-Jan-25 17  Hemopoiesis ❑ Hemopoiesis ▪ is the process by which the develop of the formed elements of blood Before birth First occurs in the yolk sac Later in the liver, spleen, thymus, and lymph nodes Last three months - Red bone marrow After birth Red bone marrow Ajman University 14-Jan-25 18  Hemopoiesis ❑ Red bone marrow cells ▪ Are derived from mesenchyme ▪ And are called pluripotent stem cells ▪ Develop into different types of cells In newborns All bone marrow is red In adulthood ▪ Red bone marrow in the long bones becomes inactive ▪ And is replaced by yellow bone marrow ▪ Rate of blood cell formation decreases Ajman University 14-Jan-25 19  Hemopoiesis ▪ Pluripotent stem produce two types of stem cells Myeloid stem cells give rise to Red blood cells Platelets Monocytes Neutrophils Eosinophils Basophils Lymphoid stem cells give rise to Lymphocytes Ajman University 14-Jan-25 20  Erythropoiesis ❑ Erythropoiesis ▪ Synthesize hemoglobin Production of RBCs ▪ Ejects its nucleus and becomes a ▪ Starts in the red bone marrow reticulocyte ▪ Precursor cell called a proerythroblast ▪ Reticulocytes develop into RBCS ▪ Proerythroblast divides several times 1 to 2 days after their release Ajman University 14-Jan-25 21  Factors Affecting Erythropoiesis Erythropoietin Hormones Vitamins Growth hormone Vitamin B12 and Folic acid Thyroid hormones Pyridoxine Cortisol Vitamin C Testosterone Riboflavin and Pantothenic acid Adrenocorticotropic hormone Minerals Proteins Iron Globin synthesis of hemoglobin Copper Cobalt Ajman University 14-Jan-25 22  White Blood Cells ❑ Types of WBCs or leukocytes 5000–10,000 cells per µL of blood Granular Leukocytes ▪ After staining, ▪ Displays conspicuous granules with distinctive coloration and recognized under a light microscope Agranular Leukocytes ▪ The granules are not visible under a light microscope because of their small size and poor staining qualities Ajman University 14-Jan-25 23  Neutrophil Neutrophil (Polymorphonuclear leukocytes) 60–70% of all WBCs Diameter 10–12 µm Cytoplasm has very fine, pale lilac granules Nucleus has 2–5 lobes connected by thin chromatin strands ✓ Functions Phagocytosis Destruction of bacteria with lysozyme, defensins and strong oxidants (Superoxide anion, hydrogen peroxide and hypochlorite anion) Ajman University 14-Jan-25 24  Eosinophil Eosinophil 2–4% of all WBCs Diameter 10–12 µm Large red-orange granules fill the cytoplasm Nucleus has 2 lobes connected by a thick chromatin strand Granules usually do not obscure the nucleus ✓ Functions Combat the effects of histamine in allergic reactions Phagocytize antigen–antibody complexes Destroy certain parasitic worms Ajman University 14-Jan-25 25  Basophil Basophil 0.5–1% of all WBCs Diameter 8–10 µm Large cytoplasmic granules appear deep blue-purple Granules commonly obscure the nucleus Nucleus has 2 lobes ✓ Functions Liberate heparin, histamine, and serotonin in allergic reactions That intensify the overall inflammatory response Ajman University 14-Jan-25 26  Monocytes Monocytes 3–8% of all WBCs Diameter 12–20 µm Nucleus is kidney shaped or horseshoe shaped Cytoplasm is blue-gray and has a foamy appearance Fine azurophilic granules (Lysosomes) ✓ Functions Phagocytosis Ajman University 14-Jan-25 27  Macrophages ❑ Macrophages ▪ The blood transports monocytes from the blood into the tissues ▪ In tissues differentiate into macrophages Fixed macrophages Reside in a particular tissue ▪ Examples are Alveolar macrophages - Lungs Kupffer cells - Liver Neuroglia - Brain Wandering macrophages Roam in the tissues and gather at sites of infection or inflammation Ajman University 14-Jan-25 28  Lymphocytes Lymphocyte 20–25% of all WBCs Diameter 6–9 µm (Small), 10–14 µm (Large) Cytoplasm stains sky blue and forms a rim around the nucleus Nucleus is round or slightly indented ✓ Functions Mediate immune responses, including antigen–antibody reactions T lymphocytes (T cells) Attack invading viruses, cancer cells and transplanted tissue B lymphocytes (B cells) Develop into plasma cells, which secrete antibodies Natural killer (NK) cells Attack infectious microbes and tumor cells Ajman University 14-Jan-25 29  Clinical Connections Leukocytosis leukopenia ▪ An increase in the number of ▪ An abnormally low level of WBCs WBCs above 10,000/µL below 5000/µL Infections Anaphylactic shock Allergy Cirrhosis of liver Common cold Disorders of spleen Tuberculosis Pernicious anemia Glandular fever Typhoid Ajman University 14-Jan-25 30  Clinical Connections ❑ Anemia Is a condition in which the oxygen-carrying capacity of blood is reduced Ajman University 14-Jan-25 31  Clinical Connections Iron deficiency anemia Inadequate absorption of iron or excessive loss of iron Megaloblastic anemia Inadequate intake of vitamin B12 or folic acid Pernicious anemia Inability of the stomach to produce intrinsic factor (Required for B12 absorption) Hemorrhagic anemia Excessive loss of RBCs through bleeding Hemolytic anemia Rupture RBC plasma membranes prematurely Ajman University 14-Jan-25 32  Clinical Connections Thalassemia Deficient synthesis of hemoglobin RBCs are small (microcytic), Pale (hypochromic) Aplastic anemia Destruction of red bone marrow Exposure to toxic chemicals (benzene), radiation or autoimmune disorder. Sickle-Cell Disease Contain Hb-S, an abnormal kind of hemoglobin RBCs become a sickle shape and rupture easily Leukemia Refers to a group of red bone marrow cancers In which abnormal white blood cells multiply uncontrollably Ajman University 14-Jan-25 33  ▪ A 43 old woman presented with a one year history of increasingly heavy but painless periods. The period lasts 8 days. Flooding and clots occur on days 1 and 2. Laboratory investigations revealed a normal range of Haemoglobin and ferritin. Pelvic ultrasound showed a slightly enlarged uterus, but no intrauterine pathology. ▪ Which ONE of the following anaemia is most likely to be developed in this patient? 1. Hemorrhagic anemia 2. Iron deficiency anemia 3. Hemolytic anemia 4. Pernicious anemia Ajman University 14-Jan-25 34  Blood Types ▪ Human blood cells antigens 30 commonly occurring and hundreds of rare antigens Which can cause antigen-antibody reactions Most of the antigens are weak Important to study inheritance of genes and crime detection ▪ Antibodies (agglutinins) Present in the plasma ▪ Antigens (agglutinogen) Present on the surfaces of the RBCs Antigens cause blood transfusion reactions o O-A-B system antigens o Rh system antigens Ajman University 14-Jan-25 35  Agglutinogens ▪ Agglutinogen found on the surfaces of the RBCs Agglutinogen Blood ▪ Four major O-A-B blood types Type Presence/absence of type A & B agglutinogens on RBCs None O ▪ Neither A nor B agglutinogen— Blood type O A A ▪ Only A agglutinogen is present — Blood type A B B ▪ Only B agglutinogen is present — Blood type B ▪ Both A and B agglutinogens are present — Blood type AB A&B AB Ajman University 14-Jan-25 36  Genetic Determination of the Agglutinogens Agglutinog Genotype Blood ▪ Two genes determine the O-A-B blood type ens type/Phen (Antigen) otype ▪ Type O gene– No agglutinogen on the RBCs None OO O ▪ Type A & B genes – Agglutinogens on the RBCs A OA, AA A B OB, BB B A&B AB AB Ajman University 14-Jan-25 37  Agglutinins ▪ Absent of A agglutinogen in the RBCs — anti-A agglutinins (Agglutinin α) develop ▪ Absent of B agglutinogen in the RBCs — anti-B agglutinins (Agglutinin β) develop ▪ No agglutinogens in the RBCs — anti-A and anti-B agglutinins develop ▪ α- and ß-agglutinins are IgM type of immunoglobulins Blood Agglutinogen- Agglutinin- Plasma Type RBC (Antigen) (Antibody) Type A B AB O Type A A ß -Agglutinin (Anti-B agglutinins) Type B B α -Agglutinin (Anti-A agglutinins) Type AB AB None Type O O α- and ß- agglutinins Ajman University 14-Jan-25 38  Origin of Agglutinins in the Plasma ▪ Immediately after birth Zero agglutinins in the plasma ▪ 2 to 8 months after birth Begins to produce agglutinins ▪ 8 to 10 years old Reaches maximum titer ▪ Remaining years of life Gradually declines ▪ The agglutinins are gamma globulins Most of them are IgM and IgG ▪ α- & ß-agglutinins are IgM type of immunoglobulins Ajman University 14-Jan-25 39  Landsteiner’s Law ▪ When a particular antigen is present on the RBCs, the plasma does not contain the corresponding antibody RBC have antigen A, plasma would not have α agglutinin ▪ If an antigen is absent, the plasma always contains the corresponding antibody Group A blood has β agglutinin, Group O blood has both α and β agglutinins Ajman University 14-Jan-25 40  O-A-B Blood Types Ajman University 14-Jan-25 41  Rh Blood Types ▪ Rh blood type system is important when transfusing blood ❑ Difference between O-A-B and Rh system O-A-B system Plasma agglutinins responsible for causing transfusion reactions Develop agglutinins spontaneously Rh system Development of spontaneous agglutinins never occur Prior exposure to Rh antigen cause significant transfusion reactions ▪ Three types of Rh antigens (Rh factor) — C,D, E ▪ D antigen is widely prevalent in the population Presence of type D antigen — Rh+ (90% in population) Absence of type D antigen — Rh- (10% in population) Ajman University 14-Jan-25 42  Genetic Determination of Rh factor ▪ Rh + individual may have DD or Dd genotype Ajman University 14-Jan-25 43  Formation of Anti-Rh Agglutinins ▪ Rh antibodies appear in blood: Rh- person transfused Rh+ blood Rh- female gives birth to a Rh+ baby — father is Rh+ When Rh factor are injected into a Rh- person Anti-Rh agglutinins develop about 2 to 4 months later A delayed transfusion reaction occurs (usually mild) Subsequent transfusion of Rh+ blood into the same person Transfusion reaction is greatly enhanced Cause immediate and severe transfusion reaction Ajman University 14-Jan-25 44  Erythroblastosis Fetalis ▪ Hemolytic disease of the newborn is a disease of the fetus and newborn child ▪ Characterized by agglutination and phagocytosis of the fetus’s RBCs Ajman University 14-Jan-25 45  Erythroblastosis Fetalis ▪ Mother is Rh- and father Rh+ ▪ Baby has inherited the Rh+ antigen from the father ▪ Mother develops anti-Rh agglutinins ▪ Anti-Rh antibodies diffuse through the placental into fetus’s blood ▪ Cause agglutination of the fetus’s blood ▪ Agglutinated RBCs hemolyze and release Hb into the blood ▪ Fetus’s macrophages convert Hb into bilirubin Baby’s skin to become yellow (jaundiced) ▪ First Rh+ child does not develop sufficient anti-Rh agglutinins ▪ 3% of second Rh+ babies exhibit signs of erythroblastosis fetalis ▪ Incidence rises progressively with subsequent pregnancies Ajman University 14-Jan-25 46  Clinical Picture of Erythroblastosis Jaundice Anemia Enlarged liver and spleen Presence of nucleated blastic RBCs - called erythroblastosis fetalis Exhibit permanent mental impairment kernicterus Damage to motor areas of the brain Because of precipitation of bilirubin in the neuronal cells ▪ Fetal death in utero or ▪ The baby dies soon after birth Ajman University 14-Jan-25 47  Treatment & Prevention of the Erythroblastosis ❑ Treatment ▪ Replace the neonate’s blood with Rh- blood ▪ About 400 ml of Rh- blood is infused over a period of 1.5 hrs (repeated) ▪ Neonate’s own Rh+ blood is being removed Mainly to keep the bilirubin level low and prevent kernicterus ▪ A process that requires 6 or more weeks ❑ Prevention ▪ Anti-D antibody (Rh immunoglobulin globin) is administered to the expectant mother starting at 28 to 30 weeks of gestation ▪ Anti-D antibody is administered to Rh- women who deliver Rh+ babies to prevent sensitization of the mothers to the D antigen Ajman University 14-Jan-25 48  Blood Typing ▪ The red blood cells are first separated from the plasma and diluted with saline ▪ Then mix with anti-A agglutinin, anti-B agglutinin and anti-D agglutinin ▪ The mixtures are observed under a microscope Ajman University 14-Jan-25 49  Cross Matching of Blood ▪ Match RBCs of donor with serum of recipient ▪ Match serum of donor with RBCs of recipient Ajman University 14-Jan-25 50  Cross Matching of Blood Major crossmatch ▪ This is the most important cross-match Testing the patient’s serum with donor cells To determine whether the patient has an antibody which may cause a hemolytic transfusion reaction ▪ Minor crossmatch ▪ Testing the patient's cells with donor plasma ▪ To determine whether there is an antibody in the donor’s plasma directed against an antigen on the patient’s cells Ajman University 14-Jan-25 51  Transfusion Reactions ❑ Mismatched Blood Types ▪ Transfusion reaction is occur in the RBCs of the donor blood Agglutination ▪ Rare that the transfused blood causes agglutination of the recipient’s cells Plasma portion of the donor blood becomes diluted by plasma of the recipient ❑ In an emergency ▪ Type O blood (universal donors, preferably O–) will be administered Ajman University 14-Jan-25 52  Agglutination — In Transfusion Reactions ❑ If bloods are mismatched ▪ Agglutinins are mixed with RBCs that contain corresponding agglutinogens ▪ The agglutinins have 2 (IgG type) or 10 (IgM type) binding sites ▪ A single agglutinin can attach to 2 or more RBCs ▪ Causes the RBCs to clump — Agglutination ▪ RBCs either phagocytise by macrophages or physical distruction ▪ Hemolysis of RBCs release Hb Ajman University 14-Jan-25 53  Transfusion Reactions ▪ The Hb released from the RBCs converted by the phagocytes into bilirubin o And excreted in the bile by the liver ▪ If liver function is normal, the bile pigment will be excreted ▪ Jaundice usually not appear in an adult unless more than 400 ml of blood is hemolyzed in less than a day Ajman University 14-Jan-25 54  Transfusion Reactions ▪ One of the most lethal effects of transfusion reactions is kidney failure Powerful renal vasoconstriction Due to release of toxic substances from the haemolyzed blood Circulatory shock Caused by loss of circulating RBCs along with toxic substances Arterial blood pressure falls, and renal blood flow and urine output decrease Renal tubular blockage Hb precipitates and blocks the kidney tubules ▪ Renal vasoconstriction, circulatory shock, and renal tubular blockage cause acute renal shutdown Ajman University 14-Jan-25 55  Clinical Connections ▪ When blood is lost, Immediate need is to stop further blood loss And replace the lost volume Blood volume expander ▪ Intravenous therapy that provide the volume for the circulatory system Crystalloids (normal saline) Dextrans Gelatin derivatives Hydroxy ethyl starch Human albumin solutions Ajman University 14-Jan-25 56  Platelets Platelets Under the influence of thrombopoietin Myeloid stem cells develop into megakaryocyte- colony-forming cells That in turn develop into precursor cells called megakaryoblasts Megakaryoblasts transform into megakaryocytes Megakaryocytes splinter into 2000 to 3000 fragments Each fragment is a platelet (thrombocyte) ✓ Stop blood loss from damaged blood vessels by forming a platelet plug ✓ Granules contain chemicals that promote blood clotting Ajman University 14-Jan-25 57  Platelets Platelets 150,000 and 400,000 μL of blood Disc-shaped Diameter 2–4 μm Life span- 5 to 9 days Has many vesicles but no nucleus ▪ Vesicles contain: Clotting factors, ADP, ATP, Ca2+, and serotonin Enzymes that produce thromboxane A2, prostaglandin ✓ Which helps to strengthen the blood clot Hormone Platelet-derived growth factor (PDGF) ✓ Cause proliferation of vascular endothelial cells Ajman University 14-Jan-25 58  Hemostasis ❑ Hemostasis ▪ Sequence of responses that stops bleeding ▪ Three mechanisms reduce blood loss Vascular spasm Platelet plug formation Blood clotting (coagulation) Ajman University 14-Jan-25 59  Vascular Spasm ❑ Vascular spasm When arteries or arterioles are damaged, The smooth muscle in their walls contracts immediately ✓ Reduces blood loss for several minutes to several hours ▪ The spasm is caused by Damage to the smooth muscle Substances released from activated platelets Reflexes initiated by pain receptors Ajman University 14-Jan-25 60  Platelet Plug Formation ❑ Platelet plug formation Platelet adhesion Platelet release reaction Platelet aggregation Platelet adhesion ▪ Platelets contact with collagen fibers and stick to parts of a damaged blood vessel Collagen fibers of the connective tissue underlying the damaged endothelial cells Ajman University 14-Jan-25 61  Platelet Plug Formation Platelet release reaction ▪ Due to adhesion, ▪ The platelets become activated ▪ Platelets extend many projections ▪ Liberate the contents of their vesicles - Platelet release reaction ▪ ADP and thromboxane A2 activate nearby platelets ▪ Serotonin and thromboxane A2 causes vasoconstriction ▪ Decreases blood flow through the injured vessel Ajman University 14-Jan-25 62  Platelet Plug Formation Platelet aggregation ▪ The release of ADP Makes other platelets in the area sticky ▪ Newly recruited and activated platelets Adhere to the originally activated platelets ▪ Gathering of platelets Is called platelet aggregation ▪ Platelet plug Accumulation and attachment of large numbers of platelets to form a mass Ajman University 14-Jan-25 63  Blood Clotting o Serum Blood plasma minus the clotting proteins ❑ Blood clotting (coagulation) ▪ The process of gel formation ▪ is a series of chemical reactions that culminates in formation of fibrin threads ▪ Blood-clotting cascade divided into three stages 1. Extrinsic pathway and the intrinsic pathway lead to the formation of prothrombinase and lead to common pathway 2. Prothrombinase converts prothrombin into thrombin 3. Thrombin converts soluble fibrinogen into insoluble fibrin Ajman University 14-Jan-25 64  Extrinsic Pathway o Tissue factor (TF) or thromboplastin Is a mixture of lipoproteins and phospholipids Released from the surfaces of damaged cells (extrinsic to) Initiates the formation of prothrombinase Extrinsic pathway In the presence of Ca2+ TF activates clotting factor X Factor X combines with factor V in the presence of Ca2+ To form the active enzyme prothrombinase Rapid [12 to 15 seconds] Prothrombinase Ajman University 14-Jan-25 65  Intrinsic Pathway Intrinsic pathway triggered by Damaged endothelial cells expose collagen fibers Damaged platelets Damaged platelets release phospholipids ▪ Contact with collagen fibers and platelets ▪ Activates clotting factor XII ▪ Activated factor XII activates clotting factor X In the presence of phospholipids and Ca2+ ▪ Once factor X is activated ▪ Combines with factor V, presence of Ca2+ ▪ Form the active enzyme prothrombinase ▪ Require several minutes Ajman University 14-Jan-25 66  Common Pathway Common Pathway ▪ Prothrombinase and Ca2+ catalyze, Conversion of prothrombin to thrombin ▪ Thrombin, in the presence of Ca2+, Converts fibrinogen (soluble) to fibrin (insoluble) ▪ Thrombin also activates factor XIII, Stabilizes the fibrin threads into a sturdy clot o Factor XIII Present in plasma Also released by platelets trapped in the clot Ajman University 14-Jan-25 67  Positive feedback ❑ Thrombin has two positive feedback effects First positive feedback loop ▪ Factor V accelerates the formation of prothrombinase Prothrombinase accelerates the production thrombin Second positive feedback loop ▪ Thrombin activates platelets Aggregation of platelet and the release of phospholipids Ajman University 14-Jan-25 68  Clot Retraction ▪ Clot plugs the ruptured area of the blood vessel Thus stops blood loss Clot retraction Is the consolidation or tightening of the fibrin clot Fibrin threads contract as platelets pull on them Pulls the edges of the damaged vessel closer together Decrease the risk of further damage ▪ During retraction Some serum can escape But formed elements in blood cannot Ajman University 14-Jan-25 69  Ajman University 14-Jan-25 70  Factor IV - Diet, bones, and platelets Ajman University 14-Jan-25 71  Anticoagulants Natural anticoagulants Synthetic anticoagulants (in vivo) (In vitro) Heparin Heparin Anti-Thrombin III ▪ Ca++ chelating agents: Sodium citrate Thrombomodulin Sodium oxalate EDTA (ethylene diamine Protein C tetra acetic acid) Ajman University 14-Jan-25 72  Clinical Connections ▪ Patients who are at increased risk of forming blood clots may receive anticoagulants Heparin Inactivate thrombin and activated factor X through an antithrombin (AT)- dependent mechanism Administered during hemodialysis and open-heart surgery Warfarin (Coumadin) Acts as an antagonist to vitamin K Blocks synthesis of four clotting factors EDTA (ethylene diamine tetraaceticacid) and CPD (citrate phosphatedextrose) Used to prevent clotting in donated blood (blood banks and laboratories) Substances that remove Ca2+ Ajman University 14-Jan-25 73  Clinical Connections Aspirin Inhibits vasoconstriction and platelet aggregation By blocking synthesis of thromboxane A2 Reduces the chance of thrombus formation Thrombolytic agents Are chemical substances that are injected into the body to dissolve blood clots Activate plasminogen (accelerates fibrinolysis) E.g. Streptokinase, Human tissue plasminogen activator (t-PA) Ajman University 14-Jan-25 74  Clinical Connections Hemophilia Is an inherited deficiency of clotting factors Bleeding may occur spontaneously or after only minor trauma Different types of hemophilia are due to deficiencies of different blood clotting factors Thrombocytopenia Is a condition characterized by abnormally low levels of thrombocytes Is an autoimmune diseases Immune system mistakenly attacks and destroys platelets Ajman University 14-Jan-25 75  A 66-year-old woman had a left-sided deep-vein thrombosis, and oral warfarin dosing was recommended. Warfarin produces anticoagulation by inhibiting the activity of the vitamin K-dependent clotting factors. Which ONE of the following clotting factors is most likely to inhibited in this patient? A Fibrinogen B Christmas factor C Hageman factor D Ionized calcium Ajman University 14-Jan-25 76  Ajman University 14-Jan-25 77