Coagulation Medicine for Primary Practitioners Michael SilveySilvey,, DO Clinical Assistant Professor of Pediatrics Children’s Mercy Hospital/UMKC School of Medicine ©2013 Children's©2013 Children's Mercy. All Mercy. Rights All Reserved. Rights Reserved. 09/13 09/13 Disclosures . I have nothing to disclose 2 ©2013©2013 Children's Children's Mercy. Mercy. All Rights All Rights Reserved. Reserved. 09/13 09/13 Objectives • Review the basic physiology of the coagulation system •Understand the proper evaluation of a patient with a possible bleeding disorder •Accurately interpret specific coagulation laboratory studies •Discuss clinical manifestations/complications of Hemophilia and other common bleeding disorders •Discuss inherited thrombophilias 3 ©2013©2013 Children's Children's Mercy. Mercy. All Rights All Rights Reserved. Reserved. 09/13 09/13 Coagulation System Review * All numbers Fiscal 2012 4 ©2013©2013 Children's Children's Mercy. Mercy. All Rights All Rights Reserved. Reserved. 09/13 09/13 ©2013 Children's Mercy. All Rights Reserved. 09/13 X II VIII/vWF TF VIIa Xa Va IIa TF-Bearing Cell VIIIa TF VIIa VVVaVa IX Platelet IXa X II Xa IXa VIIIa Va IIa Activated Platelet Hoffman M et al. Blood Coagul Fibrinolysis. 1998;9(suppl 1):S61-S65. 6 ©2013©2013 Children's Children's Mercy. Mercy. All Rights All Rights Reserved. Reserved. 09/13 09/13 Extrinsic Pathway Intrinsic Pathway Common Pathway Clot 7 ©2013©2013 Children's Children's Mercy. Mercy. All Rights All Rights Reserved. Reserved. 09/13 09/13 PT Pathway PTT Pathway XV Prothrombin Thrombin Fibrinogen Fibrin 8 ©2013©2013 Children's Children's Mercy. Mercy. All Rights All Rights Reserved. Reserved. 09/13 09/13 The PT pathway PT Pathway •Only one factor Factor VII involved shorter time •Shorter time one less letter XV Prothrombin Thrombin Fibrinogen Fibrin 9 ©2013©2013 Children's Children's Mercy. Mercy. All Rights All Rights Reserved. Reserved. 09/13 09/13 The PTT Pathway Factor XII PTT Pathway Factor XI Factor IX •More factors more letters and longer time Factor VIII V •Remember by thinking the PTT starts at the top X of the clock! (12) Prothrombin Thrombin Fibrinogen Fibrin 10 ©2013©2013 Children's Children's Mercy. Mercy. All Rights All Rights Reserved. Reserved. 09/13 09/13 Elevated PT/PTT . If PT is elevated Factor VII Deficiency is possible . If PTT i s el evat ed dfiideficienc ies o fFf Fac tors XIIXIIXXII, XI, IX, and VIII . If both are elevated deficiencies of Factors X, V, Prothrombin (II), and Fibrinogen (I) 11 ©2013©2013 Children's Children's Mercy. Mercy. All Rights All Rights Reserved. Reserved. 09/13 09/13 Evaluation of a Patient with a possible Bleeding Disorder 12 ©2013©2013 Children's Children's Mercy. Mercy. All Rights All Rights Reserved. Reserved. 09/13 09/13 What causes abnormal bleeding? . Trauma . Factor Deficiencies . Antibodies/Inhibitors . Liver Failure . Thrombocytopenia . Vitamin K Deficiency 13 ©2013©2013 Children's Children's Mercy. Mercy. All Rights All Rights Reserved. Reserved. 09/13 09/13 The bleeding work up . The most sensitive initial test for a bleeding disorder is an accurate history . Can be difficult – Your idea of bleeding is not my idea . If the patient has a negative history, is asymptomaticand there is a negative family history, no other work up is usually necessary 14 ©2013©2013 Children's Children's Mercy. Mercy. All Rights All Rights Reserved. Reserved. 09/13 09/13 Initial General Questions . Has the patient has significant bleeding? . Is there a family history of bleeding? . What type of bleeding does the patient have? 15 ©2013©2013 Children's Children's Mercy. Mercy. All Rights All Rights Reserved. Reserved. 09/13 09/13 Type of Bleeding . Different symptoms may lead you down a different path of why the patient is bleeding – Mucosal bleeding platelet dysfunction – Muscle/Joint Bleeds factor deficiencies 16 ©2013©2013 Children's Children's Mercy. Mercy. All Rights All Rights Reserved. Reserved. 09/13 09/13 Bleeding Questions . Epistaxis . Gingival Bleeding . Menorrhagia . Bruising . Bleeding after dental procedures . Bleeding after surgeries 17 ©2013©2013 Children's Children's Mercy. Mercy. All Rights All Rights Reserved. Reserved. 09/13 09/13 Have to be Specific! . Epistaxis – How long? Which Nare? How did you try to stop it? How often? Any trauma? . Menorrhagia – How manyyy days? How many yp pads/day ? How many heavy/light days? Family History of Menorrhagia? 18 ©2013©2013 Children's Children's Mercy. Mercy. All Rights All Rights Reserved. Reserved. 09/13 09/13 Laboratory Work Up . If patient has a positive bleeding history next need to do screening labs –CBC . thrombocytopenia –PT/PTT – Fibrinogen – PFA-100 19 ©2013©2013 Children's Children's Mercy. Mercy. All Rights All Rights Reserved. Reserved. 09/13 09/13 PT/PTT . Already discussed . Helps determine if there are any factor deficiencies . Can have elevated PT/PTT without having a bleeding disorder 20 ©2013©2013 Children's Children's Mercy. Mercy. All Rights All Rights Reserved. Reserved. 09/13 09/13 PFAPFA--100100 . AKA “Closure Time” . Screening test for platelet dysfunction . Blood is passed through coated membranes with high shear stress . Once the membrane is occludedClosure time 21 ©2013©2013 Children's Children's Mercy. Mercy. All Rights All Rights Reserved. Reserved. 09/13 09/13 PFAPFA--100100 . Membranes are coated with Collagen/Epi and Collagen/ADP . If first closure time is elevated, then sample is automatically run in the second cartridge 22 ©2013©2013 Children's Children's Mercy. Mercy. All Rights All Rights Reserved. Reserved. 09/13 09/13 PFAPFA--100100 . If both are elevated, then screening test is positive for possible bleeding disorder . If the first is positive and second is normal, then you have “aspirin-induced platelet defect” – Better way of saying this is drug effect 23 ©2013©2013 Children's Children's Mercy. Mercy. All Rights All Rights Reserved. Reserved. 09/13 09/13 PFAPFA--100100 . Affected by many things – Need to have a certain Hct and plt count – Affected by many drugs (ASA, NSAIDS, antibiotics, cardiac drugs) 24 ©2013©2013 Children's Children's Mercy. Mercy. All Rights All Rights Reserved. Reserved. 09/13 09/13 Abnormal ResultsResults--WhatWhat to do . Prolonged PT or PTT – 1:1 Mixing study . Mix patient plasma with normal plasma 1:1 ratio . Run PT/PTT again immediately and after one hour . If PT/PTT normalizes, this indicates factor deficiency . If/PT/PTT remains elevated, something is inhibiting the reaction 25 ©2013©2013 Children's Children's Mercy. Mercy. All Rights All Rights Reserved. Reserved. 09/13 09/13 Abnormal resultsresults--WhatWhat to do . Abnormal PFA-100 – Both Col/Epi and Col/ADP are increased . Ensure patient has positive bleeding history . If so, refer to us – Col/Epi increased and Col/ADP normal . Most likely drug effect, make sure patient is not taking anything for at least one week prior to test— re-test if deemed necessary in 1-2 weeks 26 ©2013©2013 Children's Children's Mercy. Mercy. All Rights All Rights Reserved. Reserved. 09/13 09/13 When Abnormal Tests are NOT Bleeding disorders . Elevated PTT – ENT wants to do T&A on a 4yo and ran screening labs prior to surgery – Normal CBC, normal PT, normal PFA-100, but PTT slightly prolonged at 41.1 – Called PCP to have it rechecked and was still elevated at 42.3 one week later 27 ©2013©2013 Children's Children's Mercy. Mercy. All Rights All Rights Reserved. Reserved. 09/13 09/13 When Abnormal Tests are NOT Bleeding disorders . Elevated PTT – Mixing Study is needed – Results of Mixing Study shows persistent elevation to 40.5 – Patient has a non-specific inhibitor preventing the test from working 28 ©2013©2013 Children's Children's Mercy. Mercy. All Rights All Rights Reserved. Reserved. 09/13 09/13 When Abnormal Tests are NOT Bleeding disorders . Non-specific inhibitors – Common in pediatric population – Usually after having a viral illness – No effect on in vivo coagulation – Can persist for a few weeks 29 ©2013©2013 Children's Children's Mercy. Mercy. All Rights All Rights Reserved. Reserved. 09/13 09/13 Hemophilia 30 ©2013©2013 Children's Children's Mercy. Mercy. All Rights All Rights Reserved. Reserved. 09/13 09/13 Types of Hemophilia . Hemophilia A – Factor VIII deficiency – Most cases (~80-85%) . Hemophilia B – Factor IX deficiency . Hemophilia C – Factor XI deficiency 31 ©2013©2013 Children's Children's Mercy. Mercy. All Rights All Rights Reserved. Reserved. 09/13 09/13 Hemophilia . X-linked recessive – Except Hemophilia C (autosomal recessive) . Mothers are the carriers . Males usually affected – Can have symptomatic females . Increased PTT – Decreased Factor levels 32 ©2013©2013 Children's Children's Mercy. Mercy. All Rights All Rights Reserved. Reserved. 09/13 09/13 Carrier Mother . One normal gene and one affected gene . Daughter has 50:50 chance of being a carrier . Son has 50:50 chance of having hemophilia 33 ©2013©2013 Children's Children's Mercy. Mercy. All Rights All Rights Reserved. Reserved. 09/13 09/13 Degrees of Hemophilia . Mild Hemophilia (5-50%) – Very minor bleeding with trauma and sometimes does not need to have factor replacement . Moderate Hemophilia (1-5%) – Can have severe bleeding after minor trauma . Severe Hemophilia (<1%) – Severe Spontaneous Bleeding anywhere 34 ©2013©2013 Children's Children's Mercy. Mercy. All Rights All Rights Reserved. Reserved. 09/13 09/13 Signs/Symptoms of Hemophilia . Bleeding after circumcision – Can be VERY severe . Difficult to control mouth bleeding . Frequently swollen joints . MltilMultiple Bru ises . Signs of child abuse 35 ©2013©2013 Children's Children's Mercy. Mercy. All Rights All Rights Reserved. Reserved. 09/13 09/13 Hemarthrosis .