Fibrinolysis - Medical Notes

78 Fibrinolysis ❖ Protein C I@"Vitamin K dependent serine PRIMARY SECONDARY (DIC) protease...

78 Fibrinolysis ❖ Protein C I@"Vitamin K dependent serine PRIMARY SECONDARY (DIC) protease I@" Activated by Platelet Count N t thrombomodulin on the endothelial cell Red Cell N RBC Fragments I@" Requires Protein S cofactor Morphology I@" Inactivates Factors V and VIII PT and APTT Abnormal Abnormal ❖ Protein S I@" Vitamin K dependent FOP + + I@" Co-factor for Protein C 0-0imer - + I@" Bound and free state I@" Only free protein S is c. Liver Disease ( depending on functionaJ so measure total seve1·ity or stage) and free ❖ Deficiency of Factors I, II, V, c. Factor V Leiden VII, IX and X ❖ Mutant Factor V ❖ Factor VII deficiency most ❖ Resists the action of Protein C/S pro.n ounced ❖ Activated Protein C Resistance ❖ t clearance of plasminogen Test d. Antiphospholipid syndrome activators ❖.+- FDP due to fibrin(ogen)olysis ❖ Any of three classes of d. Disseminated Intravascu]ar antibodies Coagulation (DlC) I@" Anticardiolipin antibodies ❖ Secondary to sepsis, obstetric I@" Lupus anticoagulant I@" Specific antibodies (e.g. complications, Ebola virus infection beta-2-glycoprotein) ❖ Thrombotic occlusion of micro- e. Prothrombin mutation circulation ❖ Mutation at position 20210 ❖ RBC fragments ❖ First described in 1996 ❖ Consumption of platelets and ❖ 1-2% of general population are Factors I, V, VIII heterozygotes ❖ High levels of FDP and D-dimer ❖ Results in.+- thrombin formation ❖.+- risk of thrombotic event Thrombotic Diseases 1. Arterial Events - platelet driven ( arthlerosclerosis, prosthetic heart devices) 2. Venous Events a. Blood flow problems ( superficial or Characteristi.cs of deep vein thrombosis) Protein C aad S b. Clot inhibitor deficiency (about 20%) ❖ Antithrombin ( formerly ATIII) I@" Principle antagonist of active coagulation proteases I@" Produced in the liver I@" Activated by heparan sulfate on the endothelial cell and by heparin as therapeutic AHect of LA on APl'T drug  79 Anticoagulant Therapy 3. Parenteral anticoagulants a. Heparin (unfractionated) 1. Platelet inhibitors ❖ Inhibits the active serine a. Aspirin- destroys cyclo-oxygenase to protease factors via Anti- inhibit r elease reaction thromhin ❖Affected platelets are inhibited ❖ Usually monitored with the permanently until replaced APTT using a heparin response b. Clopidogre1 (Plavix™)- Blocks the curve ADP recptor (P2Yl2) and is also ❖ Can also h e monitored using permanent until platelet is r eplaced anti-Xa assay c. Glycoprotein IIb/lIIa receptor b. Low Molecular Weight H eparin inhibitors (Ahciximah, (LMWH) Eptifibatide,Tirofiban)- not ! Targets Factor Xa permanent ❖ Yields a more predictable 2. Oral plasma protein anticoagu]ants response tha11 unfractionated a. Wafarin- prevents production of heparin functional Factors II, VII, IX and ❖ Does not usually require X by inhibiting Vitamin K. monitoring but if needed, ❖ requires monitoring using monitor with the anti factor Xa PT/INR assay. b. Thrombin inhibitor (Dabigatran)- requires no monitoring c. Factor Xa inhibitors (Rivaroxaban and Apixaban)- generally require no monitoring COAGULATION SAMPLE QUESTIONS I. If one pertorms an APTT on a patient on 4. A 22 year old female was seen in the high-dose warfarin therapy, we would emergency room with evidence of expect that the result would be: bleeding following a spider bite. A. Normal because warfarin effects the PT only Laboratory results show B. ,t. because of fibrinogen split Blood smear: Schistocytes products Platelet count: S0,000/mm3 C. l because of factor VII deficiency D. + because of other multiple factor PT: 20 secs APTT: 60 secs deficiencies d-dimer: positive 2. Abnormal PFA results and giant platelets The most likely diagnosis is best describe A. Allergic r eaction A. Bernard-Soulier syndrome B. Primary fihrinolysis B. Glanzmann thrombasthenia C. Secondary fihrinolysis C. von Willebrand disease D. Vitamin K deficiency D. Wiskott-Aldrich syndrome 5. A 4 year old male has a prolonged APTT of 3. A 7 year old male child is a candidate for 53 seconds. Mixing with normal plasma at ear tube surgery because of repeated ear a ratio of I to I yields an APTT of SO infections but he has a persistent seconds. Which of the following is most prolonged Prothrombin Time. The APTT is likely? normal. Which condition is most likely? A. Systemic 1upus erythematosu s A. Congenital factor VII deficiency B. Inhibitor or other anticoagulant B. Vitamin K deficiency C. Hemophilia B C. Hemophilia A D. Hemophilia A D. Factor V Leiden