3Bleeding disorders What are the possibilities What questions have good yieldWhat are screening testsWhat Lab tests are worrisome and what is the risk
4Clinical Approach When did it start ? Dental history Spontanous bruisingBleeding at surgeryBleeding into jointsMenstrual bleedingEpistaxisOne site only? Where ? When ?
5High yield questions Family history Pattern of bleeding - where Difficult to stop orRe-bleedsDrug historyAlcohol intakeCo Morbid disease
6Physical Examination in Bleeding Disorders Check sites of bleedingIs it local or generalized ?what are the manifestations, petichiae, ecchymoses, hematoma ?Are there vessel wall abnormalities, telangectasia, “palpable purpura, perifollicular hemorrhages” ?Are there signs of a connective disease processAre There signs of a systemic diseaseThe type of bleeding should give a good clue as to which part of hemostasis is affected as well as the severity
7Laboratory testingHistory and physicalType of tests guided by clinical featuresScreening testsFurther testsDefinitive tests
9Screening Tests INR Extrinsic pathway PTT (activated partial thromboplastin time)intrinsic pathwayThrombin timefinal pathwayPlatelet countBleeding time – PFA (not useful)
10Laboratory tests further testing INRPTTTT thrombin timeFactor assaysTests of fibrinolysisplatelet countBleeding timeplatelet function testsSpecial tests
11Inerpretation of tests If isolated abnormality likely a single defecteg PTT - possible hemophilia, vWdIf unexplained do mixing test for inhibitorIF more than one abnormality then more complexeg. INR and PTT - vitamin K- Coumadineg. PTT,TT heparineg INR , PTT, TT, PlateletsDIC or liver disease
17Reversing INR wityh vitamin K Depends on clinical scenarioComplete reversalPartial reversal (too high INR)IV or oral forms preferedFor complete reversal 5-10 mg IV q12h for 2 doses will reverse completely in hours.1-2 mg will decrease INR to therapeuticLevel within hrs
19Current practiceSent as 2 vials in a 50 cc mini bag to infuse at 3c/min
20Case 2You 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 bruisesBlood sent off to lab.The lab calls at 6:00 Pm with a “critical” platelet count of 10What is likely diagnosisWhat to do ?
21ITP Immune thromboctopenic purpura What is needed for diagnosisBone marrow examinationAnti platelet antibodiesWhen isolated and very low ITP is most likely diagnosisCould be a part of another disease but not likely (SLE , inf mono)Does it require hospitalization ?
22ITP continued If mucosal bleeding platelets are less than 6 Needs actionSteroidsIVIGAnti DWhat about splenectomyNew treatmentsRituximabTPO agonists
23Case3A 48 year old woman appears in emerg with jaundice of 3 weeks durationExam – jaundice - some RUQ pain an palpationBlood testsCBC Hgb 125, WBC Plat 345INR 2.6 ptt 42What is likely diagnosisWhat to Do ?
24Vitamin K deficiency Obstructive jaundice Malabsorption of Vit K dependent factorsOlder people at riskPost surgery at riskTreatmentOral or IV Vitamin K
25Case 4 A 54 year old male comes to emerg feeling unwell. Exam Mild jaundice, some telangectasis on skinMod ascites.CBC - Hgb 110 WBC plat 68INR 1.6 Ptt 41 TT 25What is likely diagnosis ?
26Hepatic dysfunction - Cirrhosis Liver makes and degradesCoagulation is affected by decreased production and impaired degradation of activated factorsChronic DICSplenomegalyTrearment only if bleedingLiver transplant
27Case 5 18 year old male scheduled for tonsillectomy History of easy bleedingExam normal no bruisesCBC normalINR 1.1 PTT 45What is likely diagnosis ?How to diagnose ?
28HemophiliaX linked bleeding disorders characterized by spontaneous development of large hematomes in deep tissues.May lead to joint bleeding, or into other closed structuresJoint cavity bleeding leads to deformed jointsbleeding may be spontaneous or asssociated with mild or moderate injury
29Hemophilia types Hemophilia A Hemophilia B absent or decreased factor VIIIHemophilia Black of factor IXsimilar in symptoms to Hemophilia AHemophilia A is 10 times more common than hemophilia B
30Genetics of Factor VIII Single chain polypeptideProduced mainly in Liverremember linked to VWfGene deletion - no factor VIIIPoint mutation - abnormal factor VIIIBase deletion - Abnormal Factor VIIICoded on X chromosome -therefore only males affected (transmitted by female carriers)
31Hemophilia types Subclassified by level of factors Levels correspond to clinical symptomsMild % factor activityModerate 1-5% activitySevere <1% activity
32Hemophilia - Clinical Picture Mild- do not develop spontaneous bleeding, but do bleed after injury or surgeryMany patients have sever diseaseJoint Bleeding results in severe disabilityhemarthroseschronic arthritismuscle bleedsSocial, economic,psychological problems
33Case 6 17 year old girl with mennorhagia History of easy bruising Possible history of easy bruisingCBC normalINR 1.1 PTT 32 (2 sec prolonged)What is diagnosisHow to diagnose ?Treatment ?
34Von Willebrand’s Disease Most frequent inherited bleeding disorder1% - 1/100 of western populationless severe than hemophiliaDisease results from a decrease or absence of Von Willebrand factor for platelet adhesionAffects primary hemostasis
35Von Willebrand’s Disease and Factor VIII VW factor produced in megakaryocytes and endothelial cellsCoded on chromosome 12Autosomal dominant inheritanceLarge molecule, and multimericMonomers undergoglycolisation and multimerization before secretionDifferent multimer size = disease
36Von Willebrand’s Disease and Factor VW is carrier for factor VIIIFactor VIII-VWf complexFactor VIII protein carried in circulation as complex with VWfReacts with platelet via GP IbTherefore can be problems with platelets and factor VIII
37Clinical features of Von Willebrand’s Disease Generally mild bleeding - often unrecognized until surgery or injuryepistaxis, menorrhagia, easy bruising, dental and post operative bleedingCan be severe in certain typesRequires accurate diagnosisRequires specific treatment
38VW -types Type I Type II Type III most frequent, quantitave defect (decreased VWf )Type IIqualitative defect (abnormal VWf )Type IIIsevere, rare, (absence of VWf )
39How to diagnose Von Willebrands disease Clinical historyFactor VIII levelBleeding timeMeasure VWf and perform aggregation testsDo gel electrophoresis for multimers
40Anti platelet agents ASA Not likely to create problems Safer to give if there for cardiovascular reasonsClopidogrelIf elective stop before.Minimum 3 daysMore than 5 days likely unnecessary