J. Bormanis/ cg edits

 When did it start ?  Dental history  Spontanous bruising  Bleeding at surgery  Bleeding into joints  Menstrual bleeding  Epistaxis  One site only? Where ? When ?

 Family history  Pattern of bleeding - where  Difficult to stop or  Re-bleeds  Drug history  Alcohol intake  Co Morbid disease

 History and physical  Type of tests guided by clinical features  Screening tests  Further tests  Definitive tests

Blood Coagulation & Tests Thrombin time

 Platelet count  INR Extrinsic pathway  PTT (activated partial thromboplastin time) intrinsic pathway  Thrombin time final pathway  fibrinogen

 Factor assays  Tests of fibrinolysis  platelet function tests  Special tests

 Cirrhosis  Renal dysfunction  Age  Drugs  Right heart failure

 If isolated abnormality likely a single defect  eg PTT - possible hemophilia, vWd  If unexplained do mixing test for inhibitor  IF more than one abnormality then more complex  eg. INR and PTT - vitamin K- Coumadin  eg. PTT,TT heparin  eg INR, PTT, TT, Platelets  DIC or liver disease (Cirrhosis)  New anticoagulants  Dabigatran: TT, PTT  Rivaroxaban: antiXa, PT/INR

INRPTTTTPLATDx > > >60396

 It is Friday at 4:40pm  Lab calls  You are patient is being preped for urgent surgery.  INR 6.5  What to do ?

Why INR’s go out of control

 Warfarin affects factors II,VII,IX and X  These are the vitamin K dependent factors  Can reverse warfarin effect (Vitamin K, prothrombin complex concentrates)

Efficacy of route of administration

 Depends on clinical scenario  Complete reversal  Partial reversal (too high INR)  IV or oral forms prefered  For complete reversal 5-10 mg IV q12h for 2 doses will reverse completely in hours.  1-2 mg will decrease INR to therapeutic  Level within hrs

 You are on call for ENT and are asked to see an 18 year old girl with refractory nosebleed.  The nose is packed and bleeding does not stop.  You notice a few bruises  Blood sent off to lab.  The lab calls at 6:00 Pm with a “critical” platelet count of 10  What is likely diagnosis  What to do ?

 What is needed for diagnosis?  When isolated and very low ITP is most likely diagnosis  Could be a part of another disease but not likely (SLE, inf mono)  Does it require hospitalization ?

 If mucosal bleeding platelets are less than 10  Needs action  Steroids  IVIG  Anti D  splenectomy  Newer treatments  Rituximab  TPO agonists

 A 48 year old woman appears in emerg with jaundice of 3 weeks duration  Exam – jaundice - some RUQ pain an palpation  Blood tests  CBC Hgb 125, WBC 7.6 Plat 345  INR 2.6 ptt 42  What is likely diagnosis  What to Do ?

 Obstructive jaundice  Malabsorption of Vit K dependent factors  Older people at risk  Post surgery at risk  Treatment  Oral or IV Vitamin K

 A 54 year old male comes to office feeling unwell.  Exam  Mild jaundice, some telangectasis on skin  Mod ascites.  CBC - Hgb 110 WBC 2.5 plat 68  INR 1.6 Ptt 41 TT 25  What is likely diagnosis ?

 Liver makes and degrades  Coagulation is affected by decreased production and impaired degradation of activated factors  Chronic DIC  Splenomegaly  Treatment only if bleeding  Liver transplant

 18 year old male scheduled for tonsillectomy  History of easy bleeding  Exam normal no bruises  CBC normal  INR 1.1 PTT 45  What is likely diagnosis ?  How to diagnose ?

 X linked bleeding disorders characterized by spontaneous development of large hematomas in deep tissues.  May lead to joint bleeding, or into other closed structures  Joint cavity bleeding leads to deformed joints  bleeding may be spontaneous or associated with mild or moderate injury

 Hemophilia A  absent or decreased factor VIII  Hemophilia B  lack of factor IX  similar in symptoms to Hemophilia A  Hemophilia A is 10 times more common than hemophilia B

 Single chain polypeptide  Produced mainly in Liver  remember linked to VWf  Gene deletion - no factor VIII  Point mutation - abnormal factor VIII  Base deletion - Abnormal Factor VIII  Coded on X chromosome -therefore only males affected (transmitted by female carriers)

 Subclassified by level of factors  Levels correspond to clinical symptoms  Mild 5-30% factor activity  Moderate1-5% activity  Severe<1% activity

 Mild- do not develop spontaneous bleeding, but do bleed after injury or surgery  Many patients have severe disease  Joint Bleeding results in severe disability  hemarthroses  chronic arthritis  muscle bleeds  Social, economic,psychological problems

 17 year old girl with mennorhagia  History of easy bruising  Possible history of easy bruising  CBC normal  INR 1.1 PTT 32 (2 sec prolonged)  What is diagnosis  How to diagnose ?  Treatment ?

 Most frequent inherited bleeding disorder  1% of western population  less severe than hemophilia  Disease results from a decrease or absence of Von Willebrand factor for platelet adhesion  Affects primary hemostasis

 VW factor produced in megakaryocytes and endothelial cells  Coded on chromosome 12  Autosomal dominant inheritance  Large molecule, and multimeric  Monomers undergoglycolisation and multimerization before secretion  Different multimer size = disease

 VW is carrier for factor VIII  Factor VIII-VWf complex  Factor VIII protein carried in circulation as complex with VWf  Reacts with platelet via GP Ib  Therefore can be problems with platelets and factor VIII

 Generally mild bleeding - often unrecognized until surgery or injury  epistaxis, menorrhagia, easy bruising, dental and post operative bleeding  Can be severe in certain types  Requires accurate diagnosis  Requires specific treatment

 Type I  most frequent, quantitave defect ( decreased VWf )  Type II  qualitative defect ( abnormal VWf )  Type III  severe, rare, ( absence of VWf )

 Clinical history  Factor VIII level  Antigen and activity tests (Ristocetin cofactor activity)  Do gel electrophoresis for multimers

 ASA  Not likelely to create problems  Safer to give if there for cardivascular reasons  Clopidogrel  If elective stop before.  Minimum 3 days  More than 5 days unnecessary

 common  DVT, PE  Splanchnic/portal vein thrombosis  Signs and Symptoms:  Pain, swelling, erythema in an extremity  SOB, CP, tachycardia, hypoxia  Diagnosis  Clinical prediction models: Wells’ score  D-dimer testing  Imaging: US, CTPA, VQ  Underlying risk factors  Thrombophilia: inherited, acquired

 Treatment  Low molecular weight heparin  warfarin*  IV unfractionated heparin  warfarin  HIT (T): to consider if drop in platelet count in patient on a heparin agent  *continue LMWH for first 6 months after diagnosis of cancer associated VTE  New oral anticoagulant agents  Rivaroxaban (Xarelto)  Apixaban (Eliquis)