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Coagulation-Anticoagulation Balance and Imbalance of Haemostatic System Slide 2 Hemophilia A Deficiencies in factor IX Deficiency in vitamin K von Willebrand disease Antithrombin deficiency VIII Clinical Significances of Hemostasis Bleeding Disorders Thromboembolism Slide 3 Role of Vitamin K Inactive prozymogen Carboxylated prozymogens Vitamin K-dependent carboxylase (Clotting factors II, VII, IX, X, protein C and S) Slide 4 1.Concepts: Disseminated Intravascular Coagulation (DIC), Shwartzman reaction 2.Conditions and predisposing factor 3.Mechanism of DIC 4.Clinical and laboratory findings 5.Prevention and treatment principle Contents Slide 5 Disseminated Intravascular Coagulation (DIC) Disseminated Intravascular Coagulation (DIC) Slide 6 A disorder of widespread micro- vascular thrombosis caused by activation of coagulation with or without bleeding caused by secondary fibrinolytic activation.micro- vascular thrombosis bleeding Definition Slide 7 Slide 8 Meningococcemia on the calves Slide 9 Meningococcemia associated purpura Slide 10 A 23-year woman, induced abortion, delivered one dead fetus. Case Presentation 14 hrs after parturition, convulsion and obnubilation developed. Large ecchymosis on extremities and abdomen. After parturition, profluvium sanguis from vagina constantly. BP: undetectable; platelet: 7,000; BT: 1 min; CT: 1min; PT: 18 sec; Fib:1.1g/L; 3P test (+) Slide 11 Infections (most common): Acute DIC: Bacteria and their toxins, fungi, viruses, rickettsiae; Chronic DIC: Any chronic infection (eg, tuberculosis, abscesses, osteomyelitis) Malignancy: Acute DIC: Acute promyelocytic leukemia, acute monocytic leukemia, disseminated prostatic carcinoma Chronic DIC: Lung, breast, gastrointestinal malignancy Obstetrical complications: Acute DIC: Abruption placenta, abortions (especially therapeutic abortions), amniotic fluid embolism, hemorrhagic shock Chronic DIC: Dead fetus syndrome Trauma: Acute DIC: Massive tissue destruction, brain damage Vascular disease: Acute DIC: Brain infarction or hemorrhage Chronic DIC: Aortic aneurysm, giant hemangioma Venoms: Acute DIC: Snake, spider (rare) Others: Acute DIC: Heparin-induced thrombocytopenia with thrombosis (HITT), purpura in newborns (homozygous protein C deficiency) Conditions Causing DIC Syndromes Slide 12 DIC Predisposing Factors Impaired clearance system: Liver, mononuclear phagocyte Shwartzman reaction; Hypercoagulable state: e.g., pregnancy; Disorder of microcirculation: e.g., giant hemangioma. Slide 13 Excessive clotting Infection Cancer Childbirth, dead fetus, or surgery Severe head injury Poisonous snake Clotting factors and platelets are depleted Excessive bleeding occurs Endothelial damage; tissue damage; director activation of factor X, damage of blood cells Hypercoagulable stage Hypocoagulable stage Secondary fibrinolytic stage Slide 14 Roel of Endothelial Cell Slide 15 Scanning electron micrograph of moderately active platelet Pseudopods Slide 16 Slide 17 IntrinsicExtrinsic The Cascade theory of Coagulation The Cascade theory of Coagulation Slide 18 Anticoagulation System Macrophage, endothelial cell, etc Serine-containing enzyme inhibitorsSerine-containing enzyme inhibitors; Protein C system; Protein C system; Tissue factor pathway inhibitor; Fibrinolytic systemFibrinolytic system, etc Molecules Cells Slide 19 Antithrombin III is the most important a2-macroglobulin heparin cofactor II a1-antitrypsin Controls at Thromblin Level Others: Slide 20 Protein S Activated Protein C Degradation of Va, VIIIa Protein C Thrombin Thrombomodulin Resistance to activated protein C in patients with thromboembolism Slide 21 tPA: tissue plasminogen activator; PAI-1: plasminogen activator inhibitor; AP: antiplasmin Slide 22 VEC Heparin+ATIII TFPI PC, PS, TM FDPS Plasmin tPA,uPA TFPI: tissue factor pathway inhibitor; PC: protein C; PS: protein S; TM: thrombodulin; ATIII: antithrombin III; tPA:tissue plasminogen activator; uPA:urokinase; FDPS: fibrin degradation products; plasminogen activator-inhibitors type 1 (PAI-1); VEC: vascular endothelial cell. PAI Slide 23 1.Bleeding at multiple sites (Ecchymoses of skin, mucous membranes; Visceral hemorrhage)at multiple sites 2.Organ dysfunction (Waterhouse-Friderichsen syndrome; Sheehans syndrome) 3.Shock 4.Hemolytic anemia (microangiopathic hemolytic anemia) Clinical findings Clinical and Laboratory Findings in DIC Slide 24 Integumentary system: Widespread hemorrhage and vascular lesions, Oozing from puncture sites, incision, mucous membranes, irregular-shaped cyanotic patches Central nervous system: Subarachnoid hemorrhage, altered state of consciousness Gastrointestinal system: Occult bleeding to massive gastrointestinal bleeding; abdominal distention; malaise, weakness Pulmanary system Renal system: hematuria, oliguria, renal failure Slide 25 1.Coagulation abnormalities: prolonged prothrombin time, activated partial thromboplastin time, thrombin time; decreased fibrinogen levels; increased levels of FDP (eg, 3P test, D-dimer) 3P test 2.Platelet count decreased as a rule but may be falling from a higher level yet still be normal 3.SchistocyteSchistocyte Laboratory abnormalities Slide 26 Plasma Protamin Paracoagulation Test (3Ptest) Protamin FDP+Fibrin FDP+Protamin Fibrin Aggregation Slide 27 Schistocyte Slide 28 1. Avoid delay 2. Treat vigorously (eg, shock, sepsis, obstetrical problems) Treat the underlying disease Treatment Principles Slide 29 Blood components as needed Fresh frozen plasma Platelet transfusions Anticoagulants after bleeding risk is corrected Manage the DIC Slide 30 Summary Slide 31 Thank you