HEMOPHILIA B * “Christmas Disease” * Deficient Factor Ix * Lab Findings Normal PT, TT and Fibrinogen Assay * Prolonged: PTT * Factor IX assay: if with normal PTT ( PTT reagent may be insensitive to factor IX deficiencies at the level of 30 units/dL) * Treatment: F IX concentrate 4pHEMOPHILIA C * “Rosenthal Syndrome” + "E XI Deficiency” Kt Ashkenazi jews * Lab Findings: * Normal PT * Prolonged PTT Other Factors Deficiency + Factor V deficiency + Prolonged Bleeding Tine due to diminished platelet function ‘proores:vmarT? Tad PET + Treatment: Platelet Concentrate + Factor Vil deficiency, + moderate to severe antonichemortage + halite of factor Vi 6 hours = longed WHAT? BOTOther Factors Deficiency + Factor X deficiency ichemorrhage J PCC * Factor XIII woth * stored in platelets, monocytes placenta, prostate, and uteru * a2-antiplasmin and PAI-I deficiency * bleeding THROMBOTIC DISORDERS PRIMARY TH R | “eageee DISORDERS ISche wig — taue $ 2 ANY \n corrgt dying uh PRIMARY THROMBOTIC DISORDERSSE CONDARY THROMBOTIC DISORDERS Lupus Anticoagulant and ~ Autos antibodies against platelets phospholipid Antibodies Post-operative Status ~ due to release of Tissue Factor during surgery Malignancy ~ causes release of thromboplastic substances by neoplastic cells = v car EV (|| —- << SECONDARY THROMBOTIC DISORDERS Lupus Pregnancy Placenta has rich Tissue Factor which enhances thrombosis during pregnancy - Increase levels of FV and F Vill Estrogen/Oral Contraceptives - increase risk of venous thrombosis and renal arten SECONDARY THROMBOTIC DISORDERS y thrombosis Morbid Obesity - causes decrease AT levels and increase PAI-1 Hyperhomocysteinemla ~ causes arterial and venous t - maybe due to decrease in localize hromboembolism d activation in Protein C pathwayON NTATI INSTRUNEY ASSAYS o LAB! studies coagulation ND PROCESSING * Non traumatic Venipuncture * Use of Plastic/Silicone aes fube - activates, intrinsic pathway * Ratio of Blood to, Anticoagulant et n Tsing ome * Specimen Processing: processed * Recommendation within ¢haser SAMPLE COLLECTION, HANDLING 7 4 er collection, PTT, 24 hours itr - * Temperature: performed at 37 degc, i 1 FV and Vill- breakdown at temp > 37 * FMiland XI- activated a cold temp Activated Partial Thromboplas Time “is 3 Screening tests for Fx, x1, Pre-K, HMWK, x, Vil x, ¥ and! {Intrinsic Pathway) * Monitor unfractionated Heparin therapy Reagents: Platelet Phosphilipd Substitute + activator (Kaolin/celite/sica/ellagie acid) 0.025M Calcium Chloride .Actiy, an Time ated Partial Thro, Principle: Adding toc Hated poor plasy 7 incubate to a Kc WW cc activation, Add f i low cont, ctor a i Measure time "quired for cio eu ee ot formation” , i ic me 7 re Reference Range: 23.9. 35 Os | Prolonged: Factor Defici ficiencies Aquired ci (25-30%) culating inhi factor ting inhibitor: Heparin Lupus Inhibitor and Ab toa Activated Partial Thromboplastin Time Sources of Error Improper sample collection, preparation and patient eas longed: Inadequate sample, large clot in the tube, Feaarinated Heparin (WV), Hct > 50% and lipemic/iteric sample (optical method) Falsely Shortened: Hemolysis, smell clot and plasma containing platelets Activated Partial Thromboplastin Time Sources of Error Incorrect reagent t preparation: Incorrect dilution, water impurities o| improper storage Instrumentation: Changes in t sample np, light source and bubbles in theProthrombin Time + screening F Vil, X, V, !!and! (Extrinsic and Common pathways) monitors anticoagulant therapy (Warfarin/Co ‘Antagonist yumadin) Vitamin K bee tum chlroride Thromboplasti Prothrombin Time .n source (TF) + 0.025M Calcit to Citrated Principle: Add formation. + platelet poor plasma; measure the time required for clot fe Referance range: 10.0-14.0s ; standardizing the PT result worldwide: not dependent on thromboplastin reagent/instrument used = Use to monitor warfarin/coumarin therapy -2.0-3.0 for thromboplastin reagent, this Aumber is provided by the rgt manufacturer Prothrombin Time Principle: add + to Citrated Platelet poor plasma; measure the time required for clot f or 7 e ti clot formati In. Referance range: 10.0- 14.05 ces not dependent on thrombe past ng the PT aa Ise to Monitor warfarin/coumarin t! ~2.0-3.0 Sey aM sib vit number is provided by the rgt man fer {hromboplastin reagent, this oplastin reagent/instrument used herapy ine ua il PT ormProthrombin Time Prolonged: Factor Deficiencies in Extrinsic/Common Pathway Sources or Error he tube, Prolonged; Inade: uate sample, large clot Pa a” contahmeen ee rade Het > 50% and lipemic/icteric sarnol (optical method) Falsely shrotened: Small clot in tube REPTILASE TIME Occassionaly useq to confirm Dysfibrogenemia * mimics Thrombin Time tests but it Uses (Atroxin)venom from as reagent * NV: 10.0-15.05 Reptilase/Thrombin , Fibronogen ee, Fr Thrombin Time Principle it tal at 5 National j it AN units/ml cleaves fibtinopeptides Aand 8 f; ores g eth Olma detectable fibrin Polymer. Testis done 37 dee rnogen NV: 15-205 Prolonged: Decreseg Fibrinogen level / Impaired Fibrinog onMIXING STUDIES longed * performed when the PT/PTT is pro! ’ ect . i differentiate a factor deficiency from a circulating inhibitor * patient’s plasma is mixed with normal pooled plasma ans tests are repeated Shortened: indicates factor deficiency i Partial/no correction: circulating inhibitor Fibrinogen Assay * quantitative tests for Fibrinogen level Reagent: Principle: Thror mbin + Undiluted patient’ irombin Clo} mbin + ung 's plasma, measurement of ting Time is obtained, EEE Factor Assay * USE to confitm sus * MEasures the ability of 3 Obtained with plasms ke * Reported in factor Pected factor deficiency Patient's plasma t, }own to have fact activity percent OPELIC,| 0 Correct the PT/PTT result tor deficient5.0M Urea Clot Solubility Test *“Duckert’s Test” * screening test for F XIll deficiency Prolonged: Unstable clot that forms in F xill deficiency dissolvesinS.0M Urea _ pa Gay astral Normal: Factor X lla-stabilized clot remains intact 4 Urea for atleast 24hours efi : Sed snap “Hlup 2 100s Pathway result $s MMhibitae; reagent io S Prolong l® activat Activated Clotting Time +» whole blood placed in glass tube contain ee Jetermined time it taks tO in an ai eo to monitor high + POCT, omst often use during CABG EVALUATIO N TE FIBRINOLYTic sveTon FDP (Fibrin Degradation Product) latex particles mixed with pati Coated with anti lent’s Serum. OGY aint fibronogen and are Result: (+) macrosco, products Pi¢ #8elutination particles = presence of d Indication: it ndication: DIC and primary fibrinogenolysis ma~ latex Particle ; Presence o “linked D-pj has been lysed ff) Result: bic, Pulmonay ibrinolysis Normal Resuit: Chromogenic intbstrate assay tees the natura) irzIMatic process Whereby 'sminogen is Converted toactie Plasmin whic Cleaves jts Substrate’ fibrinogen Reagent, ( activatorWHOLE BLOOD CLOT LYsIs TIME * test for increased fibrinolysis Normal: Intact clot for approx, 48 hours at 37 deg C Abnormal: Clot lysis < 48 hours ( excessive fibrinolysis activity) EUGLOBULIN LYSIS TIME * screening test to measure fibrinolytic activity - protein made of plasminogen, plsmin, fibrinogen and plasminogen activator procedure: The fraction is precipitated w/ 1% acetic acid and resuspended Borate solution. The Suglobulins are clotted by the wadition of thrombin. Clot is cubated and the time of lysis is reported, Normal: lysis time # 1-2 hours Abnormal: Lysis time < 1-2 hours