Basic Hematology

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<ul><li><p>Basic Hematology (Biology and Physiology of Blood) </p><p>Fadel Muhammad Garishah </p><p>Diponegoro University School of Medicine In alia:on Dr. Kariadi General Hospital </p><p>Semarang, CJ, Republic of Indonesia </p></li><li><p>Component of blood </p><p>Blood is the term for the liquid substance within vascular system. It consisted of plasma (55%), leukocytes and platelet (</p></li><li><p>Cellular basis of red blood cells </p></li><li><p>Hemoglobin structure </p></li><li><p>erythropoiesis </p><p>Erythropoiesis is a sequence involving proliferaFon and dierenFaFon of commiHed red marrow cells through the erythroblast and normoblast stages to the reFculocytes that are released into the bloodstream, and nally become erythrocytes. </p></li><li><p>RegulaFon of erythrocyte </p><p>89</p><p>Plate4.1</p><p>Compo</p><p>sition</p><p>andFu</p><p>nction</p><p>ofBloo</p><p>d</p><p>b</p><p>a</p><p>PO2</p><p>PO2</p><p>PO2</p><p>PO2Still good</p><p> MCHC (mean Hb conc. in RBCs)</p><p> Hb conc. = (g/LRBC) Hct</p><p> MCV (mean volume of one RBC)</p><p> Hct = (L/RBC) red cell count</p><p> MCH (mean Hb mass/RBC)</p><p> Hb conc. = (g/RBC) red cell count</p><p>Normal:320 360g/L</p><p>Normal:80100 fl</p><p>Normal:27 32 pg</p><p>Centrifugation</p><p>Hemoglobin concentration(g/LBLOOD)</p><p>Erythropoietin</p><p>Hemolysis</p><p>Erythropoietin</p><p>Kidney</p><p>Bone marrow</p><p>High altitude, etc.</p><p>2 Hemolysis</p><p>1 Hypoxia</p><p>Bone marrowLymph nodesSpleenLiver, etc.</p><p>Spleen</p><p>Blood</p><p>Bone marrow</p><p>Test</p><p>RBC formation</p><p>Phagocytosisby</p><p>macrophages in:</p><p>Sinus</p><p>Too old</p><p>Pulpalarteriole</p><p>Life span:120 days</p><p>Red cell count (RCC)(quantity/LBLOOD)</p><p>Hematocrit (Hct)= b/a(LRBC/LBlood)</p><p>Blood sample</p><p>Erythrocytes</p><p>Spenicpulp</p><p>Break-down</p><p>B. Life cycle of red blood cellsA. Regulation of RBC production</p><p>C. Erythrocyte parameters MCH, MCV and MCHC</p><p>Despopoulos, Color Atlas of Physiology 2003 ThiemeAll rights reserved. Usage subject to terms and conditions of license.</p><p>89</p><p>Plate4.1</p><p>Compo</p><p>sition</p><p>andFu</p><p>nction</p><p>ofBloo</p><p>d</p><p>b</p><p>a</p><p>PO2</p><p>PO2</p><p>PO2</p><p>PO2Still good</p><p> MCHC (mean Hb conc. in RBCs)</p><p> Hb conc. = (g/LRBC) Hct</p><p> MCV (mean volume of one RBC)</p><p> Hct = (L/RBC) red cell count</p><p> MCH (mean Hb mass/RBC)</p><p> Hb conc. = (g/RBC) red cell count</p><p>Normal:320 360g/L</p><p>Normal:80100fl</p><p>Normal:27 32 pg</p><p>Centrifugation</p><p>Hemoglobin concentration(g/LBLOOD)</p><p>Erythropoietin</p><p>Hemolysis</p><p>Erythropoietin</p><p>Kidney</p><p>Bone marrow</p><p>High altitude, etc.</p><p>2 Hemolysis</p><p>1 Hypoxia</p><p>Bone marrowLymph nodesSpleenLiver, etc.</p><p>Spleen</p><p>Blood</p><p>Bone marrow</p><p>Test</p><p>RBC formation</p><p>Phagocytosisby</p><p>macrophages in:</p><p>Sinus</p><p>Too old</p><p>Pulpalarteriole</p><p>Life span:120 days</p><p>Red cell count (RCC)(quantity/LBLOOD)</p><p>Hematocrit (Hct)= b/a(LRBC/LBlood)</p><p>Blood sample</p><p>Erythrocytes</p><p>Spenicpulp</p><p>Break-down</p><p>B. Life cycle of red blood cellsA. Regulation of RBC production</p><p>C. Erythrocyte parameters MCH, MCV and MCHC</p><p>Despopoulos, Color Atlas of Physiology 2003 ThiemeAll rights reserved. Usage subject to terms and conditions of license.</p></li><li><p>Life cycle of erythrocytes </p><p>89</p><p>Plate4.1</p><p>Compo</p><p>sition</p><p>andFu</p><p>nction</p><p>ofBloo</p><p>d</p><p>b</p><p>a</p><p>PO2</p><p>PO2</p><p>PO2</p><p>PO2Still good</p><p> MCHC (mean Hb conc. in RBCs)</p><p> Hb conc. = (g/LRBC) Hct</p><p> MCV (mean volume of one RBC)</p><p> Hct = (L/RBC) red cell count</p><p> MCH (mean Hb mass/RBC)</p><p> Hb conc. = (g/RBC) red cell count</p><p>Normal:320 360g/L</p><p>Normal:80100 fl</p><p>Normal:27 32 pg</p><p>Centrifugation</p><p>Hemoglobin concentration(g/LBLOOD)</p><p>Erythropoietin</p><p>Hemolysis</p><p>Erythropoietin</p><p>Kidney</p><p>Bone marrow</p><p>High altitude, etc.</p><p>2 Hemolysis</p><p>1 Hypoxia</p><p>Bone marrowLymph nodesSpleenLiver, etc.</p><p>Spleen</p><p>Blood</p><p>Bone marrow</p><p>Test</p><p>RBC formation</p><p>Phagocytosisby</p><p>macrophages in:</p><p>Sinus</p><p>Too old</p><p>Pulpalarteriole</p><p>Life span:120 days</p><p>Red cell count (RCC)(quantity/LBLOOD)</p><p>Hematocrit (Hct)= b/a(LRBC/LBlood)</p><p>Blood sample</p><p>Erythrocytes</p><p>Spenicpulp</p><p>Break-down</p><p>B. Life cycle of red blood cellsA. Regulation of RBC production</p><p>C. Erythrocyte parameters MCH, MCV and MCHC</p><p>Despopoulos, Color Atlas of Physiology 2003 ThiemeAll rights reserved. Usage subject to terms and conditions of license.</p></li><li><p>Clinically related erythrocytes parameter </p><p>89</p><p>Plate4.1</p><p>Compo</p><p>sition</p><p>andFu</p><p>nction</p><p>ofBloo</p><p>d</p><p>b</p><p>a</p><p>PO2</p><p>PO2</p><p>PO2</p><p>PO2Still good</p><p> MCHC (mean Hb conc. in RBCs)</p><p> Hb conc. = (g/LRBC) Hct</p><p> MCV (mean volume of one RBC)</p><p> Hct = (L/RBC) red cell count</p><p> MCH (mean Hb mass/RBC)</p><p> Hb conc. = (g/RBC) red cell count</p><p>Normal:320 360g/L</p><p>Normal:80100 fl</p><p>Normal:27 32 pg</p><p>Centrifugation</p><p>Hemoglobin concentration(g/LBLOOD)</p><p>Erythropoietin</p><p>Hemolysis</p><p>Erythropoietin</p><p>Kidney</p><p>Bone marrow</p><p>High altitude, etc.</p><p>2 Hemolysis</p><p>1 Hypoxia</p><p>Bone marrowLymph nodesSpleenLiver, etc.</p><p>Spleen</p><p>Blood</p><p>Bone marrow</p><p>Test</p><p>RBC formation</p><p>Phagocytosisby</p><p>macrophages in:</p><p>Sinus</p><p>Too old</p><p>Pulpalarteriole</p><p>Life span:120 days</p><p>Red cell count (RCC)(quantity/LBLOOD)</p><p>Hematocrit (Hct)= b/a(LRBC/LBlood)</p><p>Blood sample</p><p>Erythrocytes</p><p>Spenicpulp</p><p>Break-down</p><p>B. Life cycle of red blood cellsA. Regulation of RBC production</p><p>C. Erythrocyte parameters MCH, MCV and MCHC</p><p>Despopoulos, Color Atlas of Physiology 2003 ThiemeAll rights reserved. Usage subject to terms and conditions of license.</p></li><li><p>Iron intake and metabolism </p><p>91</p><p>Plate4.2</p><p>Iron</p><p>Metab</p><p>olism</p><p>andErythrop</p><p>oiesis</p><p>Fe</p><p>FeFe</p><p>7mg</p><p>1 mg</p><p>HCI</p><p>Fe</p><p>Fe</p><p>Fe</p><p>FeIII FeIII</p><p>FeIII</p><p>Fe2+ FeIII</p><p>Fe2+</p><p>H+</p><p>Fe stores</p><p>Systemicblood</p><p>LiverBone</p><p>marrow</p><p>Hemo-siderin</p><p>FerritinHeme</p><p>Hb</p><p>Erythrocytes</p><p>Hemo-pexin</p><p>Hapto-globin</p><p>Ferritin</p><p>Hemo-siderin</p><p>Transferrin</p><p>Macrophagesin spleen, liver and</p><p>bone marrow (extravascular)</p><p>Already in bone marrow</p><p>Liver</p><p>Ileum</p><p>Vitamin B120.001mg/day</p><p>Folic acid0.05mg/day</p><p>Other organs</p><p>Stores</p><p>Bone marrow</p><p>NADP NADPH +H+</p><p>Dihydrofolatereductase</p><p>Folateregeneration</p><p>Thymidylatesynthase</p><p>7,8-dihydro-</p><p>folate</p><p>Tetrahydro-folate</p><p>N5-tetra-hydrofolate</p><p>Deoxy-uridylate</p><p>Deoxy-thymidylate</p><p>ErythroblastDNA synthesis</p><p>ErythropoiesisStomach</p><p>Erythrocytes</p><p>Stomach</p><p>Liver</p><p>Fe absorption:3 15 % ofFe intake</p><p>Normal Fe intake: 1020 mg/day 510 mg/day</p><p>Intrinsicfactor</p><p>Methyl-cobalamin</p><p>Lum</p><p>en</p><p>Ferritin</p><p>Bloo</p><p>d</p><p>Lyso-some</p><p>Cellturnover</p><p>Mucosaltransferrin</p><p>Apo-</p><p>tran</p><p>sfer</p><p>rinHeme-FeII</p><p>Mucosal cells(duodenum)</p><p>Tran</p><p>s-fe</p><p>rrin</p><p>Non-absorbed Fe in feces:Normally 8597% of intake</p><p>Heme</p><p>FR</p><p>FeIII</p><p>2 Fe absorption</p><p>3 Fe storage and Fe recycling</p><p>1 Iron intakeA. Iron intake and metabolism</p><p>B. Folic acid and vitamin B12 (cobalamins)</p><p>Despopoulos, Color Atlas of Physiology 2003 ThiemeAll rights reserved. Usage subject to terms and conditions of license.</p></li><li><p>Iron storage and recycling </p><p>91Plate4.2</p><p>Iron</p><p>Metab</p><p>olism</p><p>andErythrop</p><p>oiesis</p><p>Fe</p><p>FeFe</p><p>7 mg</p><p>1 mg</p><p>HCI</p><p>Fe</p><p>Fe</p><p>Fe</p><p>FeIII FeIII</p><p>FeIII</p><p>Fe2+ FeIII</p><p>Fe2+</p><p>H+</p><p>Fe stores</p><p>Systemicblood</p><p>LiverBone</p><p>marrow</p><p>Hemo-siderin</p><p>FerritinHeme</p><p>Hb</p><p>Erythrocytes</p><p>Hemo-pexin</p><p>Hapto-globin</p><p>Ferritin</p><p>Hemo-siderin</p><p>Transferrin</p><p>Macrophagesin spleen, liver and</p><p>bone marrow (extravascular)</p><p>Already in bone marrow</p><p>Liver</p><p>Ileum</p><p>Vitamin B120.001mg/day</p><p>Folic acid0.05mg/day</p><p>Other organs</p><p>Stores</p><p>Bone marrow</p><p>NADP NADPH +H+</p><p>Dihydrofolatereductase</p><p>Folateregeneration</p><p>Thymidylatesynthase</p><p>7,8-dihydro-</p><p>folate</p><p>Tetrahydro-folate</p><p>N5-tetra-hydrofolate</p><p>Deoxy-uridylate</p><p>Deoxy-thymidylate</p><p>ErythroblastDNA synthesis</p><p>ErythropoiesisStomach</p><p>Erythrocytes</p><p>Stomach</p><p>Liver</p><p>Fe absorption:3 15 % ofFe intake</p><p>Normal Fe intake: 1020 mg/day 510 mg/day</p><p>Intrinsicfactor</p><p>Methyl-cobalamin</p><p>Lum</p><p>en</p><p>Ferritin</p><p>Bloo</p><p>d</p><p>Lyso-some</p><p>Cellturnover</p><p>Mucosaltransferrin</p><p>Apo-</p><p>tran</p><p>sfer</p><p>rinHeme-FeII</p><p>Mucosal cells(duodenum)</p><p>Tran</p><p>s-fe</p><p>rrin</p><p>Non-absorbed Fe in feces:Normally 8597% of intake</p><p>Heme</p><p>FR</p><p>FeIII</p><p>2 Fe absorption</p><p>3 Fe storage and Fe recycling</p><p>1 Iron intakeA. Iron intake and metabolism</p><p>B. Folic acid and vitamin B12 (cobalamins)</p><p>Despopoulos, Color Atlas of Physiology 2003 ThiemeAll rights reserved. Usage subject to terms and conditions of license.</p></li><li><p>Folic acid and Cobalamin (B12) metabolism </p><p>91</p><p>Plate4.2</p><p>Iron</p><p>Metab</p><p>olism</p><p>andErythrop</p><p>oiesis</p><p>Fe</p><p>FeFe</p><p>7mg</p><p>1 mg</p><p>HCI</p><p>Fe</p><p>Fe</p><p>Fe</p><p>FeIII FeIII</p><p>FeIII</p><p>Fe2+ FeIII</p><p>Fe2+</p><p>H+</p><p>Fe stores</p><p>Systemicblood</p><p>LiverBone</p><p>marrow</p><p>Hemo-siderin</p><p>FerritinHeme</p><p>Hb</p><p>Erythrocytes</p><p>Hemo-pexin</p><p>Hapto-globin</p><p>Ferritin</p><p>Hemo-siderin</p><p>Transferrin</p><p>Macrophagesin spleen, liver and</p><p>bone marrow (extravascular)</p><p>Already in bone marrow</p><p>Liver</p><p>Ileum</p><p>Vitamin B120.001mg/day</p><p>Folic acid0.05 mg/day</p><p>Other organs</p><p>Stores</p><p>Bone marrow</p><p>NADP NADPH +H+</p><p>Dihydrofolatereductase</p><p>Folateregeneration</p><p>Thymidylatesynthase</p><p>7,8-dihydro-</p><p>folate</p><p>Tetrahydro-folate</p><p>N5-tetra-hydrofolate</p><p>Deoxy-uridylate</p><p>Deoxy-thymidylate</p><p>ErythroblastDNA synthesis</p><p>ErythropoiesisStomach</p><p>Erythrocytes</p><p>Stomach</p><p>Liver</p><p>Fe absorption:3 15 % ofFe intake</p><p>Normal Fe intake: 10 20 mg/day 5 10 mg/day</p><p>Intrinsicfactor</p><p>Methyl-cobalamin</p><p>Lum</p><p>en</p><p>Ferritin</p><p>Bloo</p><p>d</p><p>Lyso-some</p><p>Cellturnover</p><p>Mucosaltransferrin</p><p>Apo-</p><p>tran</p><p>sfer</p><p>rinHeme-FeII</p><p>Mucosal cells(duodenum)</p><p>Tran</p><p>s-fe</p><p>rrin</p><p>Non-absorbed Fe in feces:Normally 8597% of intake</p><p>Heme</p><p>FR</p><p>FeIII</p><p>2 Fe absorption</p><p>3 Fe storage and Fe recycling</p><p>1 Iron intakeA. Iron intake and metabolism</p><p>B. Folic acid and vitamin B12 (cobalamins)</p><p>Despopoulos, Color Atlas of Physiology 2003 ThiemeAll rights reserved. Usage subject to terms and conditions of license.</p></li><li><p>The blood groups </p><p>101</p><p>Plate4.7</p><p>Bloo</p><p>dGroup</p><p>s</p><p>+</p><p>=</p><p>O</p><p>A</p><p>B</p><p>AB</p><p>O A B AB</p><p>lgE</p><p>5 10 15 20</p><p>21</p><p>Rh+</p><p>Rh+</p><p>Rh+ Rh+</p><p>Rh</p><p>RhRh</p><p>Rh</p><p>Rh+</p><p>(After Kownatzki)</p><p>Days after first antigen exposure</p><p>Compatible</p><p>Incompatible(agglutination)Anti-AAnti-B</p><p>Antig</p><p>en o</p><p>n re</p><p>d bl</p><p>ood </p><p>cells</p><p>Red blood cells</p><p>Antibodies</p><p>Agglutination</p><p>Hemolysis</p><p>Conc</p><p>entr</p><p>atio</p><p>n in</p><p> blo</p><p>od</p><p>Antigen-antibodycomplexes</p><p>Antigen Symptoms</p><p>Freeantibodies</p><p>lgEreceptor</p><p>Antigen</p><p>Histamine, PAF, leukotrienesand other mediators</p><p>Granules</p><p>Mast cell or basophil</p><p>Antibody in serum</p><p>Severe hemolysisin fetus</p><p>Father Mother</p><p>Subsequent Rh+ childrenFirst Rh+ child</p><p>Subsequent mismatched Rh+ transfusion</p><p>Rh+ red cells</p><p>Highanti-Rh+ titer</p><p>Damage</p><p>Rh+ red cells</p><p>Anti-Rh+</p><p>Highanti-Rh+ titer</p><p>Damage</p><p>Anti-Rh+ antibodyBlood</p><p>First mismatched Rh+ transfusion</p><p>A. Anaphylaxis B. Serum sickness</p><p>C. ABO blood group incompatibility</p><p>D. Rh sensitization of mother by child or by Rh-mismatched transfusion</p><p>Despopoulos, Color Atlas of Physiology 2003 ThiemeAll rights reserved. Usage subject to terms and conditions of license.</p></li><li><p>Biology of Rhesus </p><p>101</p><p>Plate4.7</p><p>Bloo</p><p>dGroup</p><p>s</p><p>+</p><p>=</p><p>O</p><p>A</p><p>B</p><p>AB</p><p>O A B AB</p><p>lgE</p><p>5 10 15 20</p><p>21</p><p>Rh+</p><p>Rh+</p><p>Rh+ Rh+</p><p>Rh</p><p>RhRh</p><p>Rh</p><p>Rh+</p><p>(After Kownatzki)</p><p>Days after first antigen exposure</p><p>Compatible</p><p>Incompatible(agglutination)Anti-AAnti-B</p><p>Antig</p><p>en o</p><p>n re</p><p>d bl</p><p>ood </p><p>cells</p><p>Red blood cells</p><p>Antibodies</p><p>Agglutination</p><p>Hemolysis</p><p>Conc</p><p>entr</p><p>atio</p><p>n in</p><p> blo</p><p>od</p><p>Antigen-antibodycomplexes</p><p>Antigen Symptoms</p><p>Freeantibodies</p><p>lgEreceptor</p><p>Antigen</p><p>Histamine, PAF, leukotrienesand other mediators</p><p>Granules</p><p>Mast cell or basophil</p><p>Antibody in serum</p><p>Severe hemolysisin fetus</p><p>Father Mother</p><p>Subsequent Rh+ childrenFirst Rh+ child</p><p>Subsequent mismatched Rh+ transfusion</p><p>Rh+ red cells</p><p>Highanti-Rh+ titer</p><p>Damage</p><p>Rh+ red cells</p><p>Anti-Rh+</p><p>Highanti-Rh+ titer</p><p>Damage</p><p>Anti-Rh+ antibodyBlood</p><p>First mismatched Rh+ transfusion</p><p>A. Anaphylaxis B. Serum sickness</p><p>C. ABO blood group incompatibility</p><p>D. Rh sensitization of mother by child or by Rh-mismatched transfusion</p><p>Despopoulos, Color Atlas of Physiology 2003 ThiemeAll rights reserved. Usage subject to terms and conditions of license.</p></li><li><p>Plasmaproteins </p><p>93</p><p>Plate4.3</p><p>Flow</p><p>Prop</p><p>erties</p><p>ofBloo</p><p>d</p><p>IgA 2.25</p><p>IgM 1.15</p><p>IgD 0.03IgE 0.0002</p><p>IgG 11.0g/L</p><p>100</p><p>50</p><p>3 181512963</p><p>IgM</p><p>IgGIgAIgDIgE</p><p>60% 4% 8% 12% 16%1 2 8</p><p>6</p><p>4</p><p>2</p><p>1</p><p>01 5 10 50 100 500 1000</p><p>Na+</p><p>K+1424.3</p><p>2.6 (1.3*)1.0 (0.5**)</p><p>1534.6</p><p>2.8 (1.3)1.0 (0.5)</p><p>1454.4</p><p>2.5 (1.5)0.9 (0.45)</p><p>ca. 12ca. 140</p></li><li><p>Ion composiFon of body uids </p><p>93Plate4.3</p><p>Flow</p><p>Prop</p><p>erties</p><p>ofBloo</p><p>d</p><p>IgA 2.25</p><p>IgM 1.15</p><p>IgD 0.03IgE 0.0002</p><p>IgG 11.0g/L</p><p>100</p><p>50</p><p>3 181512963</p><p>IgM</p><p>IgGIgAIgDIgE</p><p>60% 4% 8% 12 % 16%1 2 8</p><p>6</p><p>4</p><p>2</p><p>1</p><p>01 5 10 50 100 500 1000</p><p>Na+</p><p>K+1424.3</p><p>2.6 (1.3*)1.0 (0.5**)</p><p>1534.6</p><p>2.8 (1.3)1.0 (0.5)</p><p>1454.4</p><p>2.5 (1.5)0.9 (0.45)</p><p>ca. 12ca. 140</p></li><li><p>The immunoglobulin in serum </p><p>93</p><p>Plate4.3</p><p>Flow</p><p>Prop</p><p>erties</p><p>ofBloo</p><p>d</p><p>IgA 2.25</p><p>IgM 1.15</p><p>IgD 0.03IgE 0.0002</p><p>IgG 11.0g/L</p><p>100</p><p>50</p><p>3 181512963</p><p>IgM</p><p>IgGIgAIgDIgE</p><p>60% 4% 8% 12% 16%1 2 8</p><p>6</p><p>4</p><p>2</p><p>1</p><p>01 5 10 50 100 500 1000</p><p>Na+</p><p>K+1424.3</p><p>2.6 (1.3*)1.0 (0.5**)</p><p>1534.6</p><p>2.8 (1.3)1.0 (0.5)</p><p>1454.4</p><p>2.5 (1.5)0.9 (0.45)</p><p>ca. 12ca. 140</p></li><li><p>White blood cells (Leukocytes) </p></li><li><p>The leukocytes </p><p>Leukocytes. (a) Neutrophil. (b) Eosinophil. (c) Basophil. (d) Small lymphocyte. (e) Monocyte. In each case the leukocytes are surrounded by erythrocytes. Note also the three platelets above the lymphocyte in (d). (All 1600) </p></li><li><p>The Leukopoiesis </p><p>Leukocyte formaFon. Leukocytes arise from ancestral stem cells called hemocytoblasts. (ac) Granular leukocytes develop via a sequence involving myeloblasts. (de) Monocytes, like granular leukocytes, are progeny of the myeloid stem cell and diverge from a myeloblast that can become either a neutrophil or a monocyte. Only lymphocytes arise via the lymphoid stem cell line. </p></li><li><p>The Thrombopoiesis </p><p>The hemocytoblast gives rise to cells that undergo several mitoFc divisions unaccompanied by cytoplasmic division to produce megakaryocytes. The cytoplasm of the megakaryocyte becomes compartmentalized by membranes, and the plasma membrane then fragments, liberaFng the platelets. (Intermediate stages between the hemocytoblast and megakaryoblast are not illustrated.) </p></li><li><p>Clo]ng factors </p><p>102</p><p>4Bloo</p><p>d</p><p>!</p><p>Hemostasis</p><p>The hemostatic system stops bleeding. Throm-bocytes (platelets), coagulation (or clotting) fac-tors in plasma and vessel walls interact to sealleaks in blood vessels. The damaged vesselconstricts (release of endothelin), and plateletsaggregate at the site of puncture (and attractmore platelets) to seal the leak by a plateletplug. The time required for sealing (ca. 2 to 4min) is called the bleeding time. Subsequently,the coagulation system produces a fibrinmeshwork. Due to covalent cross-linking of fi-brin, it turns to a fibrin clot or thrombus that re-tracts afterwards, thus reinforcing the seal.Later recanalization of the vessel can beachieved by fibrinolysis.</p><p>Platelets (170400 103 per L of blood;half-life !10 days) are small non-nucleatedbodies that are pinched off from megakaryo-cytes in the bone marrow. When an en-dothelial injury occurs, platelets adhere tosubendothelial collagen fibers (!A1) bridgedby von Willebrands factor (vWF), which isformed by endothelial cells and circulates inthe plasma complexed with factor VIII. Glyco-protein complex GP Ib/IX on the platelets arevWF receptors. This adhesion activates plate-lets (!A2). They begin to release substances(!A3), some of which promote platelet adhe-siveness (vWF). Others like serotonin, plate-let-derived growth factor (PDGF) andthromboxane A2 (TXA2) promote vasoconstric-tion. Vasoconstriction and platelet contractionslow the blood flow. Mediators released byplatelets enhance platelet activation and at-tract and activate more platelets: ADP, TXA2,platelet-activating factor (PAF). The shape ofactivated platelets change drastically (!A4).Discoid platelets become spherical and exhibitpseudopodia that intertwine with those ofother platelets. This platelet aggregation(!A5) is further enhanced by thrombin andstabilized by GP IIb/IIIa. Once a plateletchanges its shape, GP IIb/IIIa is expressed onthe platelet surface, leading to fibrinogenbinding and platelet aggregation. GP IIb/IIIaalso increases the adhesiveness of platelets,which makes it easier for them to stick to sub-endothelial fibronectin.</p><p>I Fibrinogen Half-life (h): 96</p><p>II K Prothrombin 72</p><p>III Tissue thrombo