Coagulation DisordersCorrina Mc Mahon

Laboratory investigationsPT: VII, X, V

APTT; XII, XI, IX, VIII

TT; Fibrinogen

D dimers; fibrin breakdown

Case 14 yr old boyURTI 2 weeks agoSudden onset bruising/petechiaePH: NilFH: NilPhysical examination:

InvestigationsFBC: Hb 11g/dl; WCC 8x10^/l; Platelets

Congenital ThrombocytopeniaDysfunctional plateletsBernard SoulierGrey platelet syndromeWiskott-Aldrich syndrome

Normal Platelet functionMay-HegglinTAR

Case 2Newborn infantIntracranial HaemorrhageNo dysmorphic features1st childNo liver/spleen palpableFBCHb 18.5g/dlWCC 10 x x 109/l /lPlatelets 10 x 109/l /l

Coagulation screenPT 15 sec. (13-16)APTT 41 sec (28-36)

Differential diagnosisInfectionDICImmune ThrombocytopeniaAlloimmuneIsoimmuneCongenital ThrombocytopeniaTAR syndromeWiscott Aldrich SyndromeVon Willebrands diseaseType 2BA-V malformations

Alloimmune ThrombocytopeniaIncidence 1:1000-5000 birthsIgG antibodiesHPA1a 80% HPA5b 15%50% occur in 1st pregnancyBleeding can be in utero or after birth

TreatmentPlateletsIVIg?Steroids

Isoimmune Thrombocytopenia Maternal anti-platelet IgGPlacental PassageThrombocytopenia nadir ~5days post-partumHistory & examination of motherTreatmentIvIg steroids

Disseminated Intravascular CoagulopathyInfection

Symptoms and SignsPetechiaeBruisingBleeding

Laboratory resultsAnaemiaThrombocytopeniaPT/ APTT/Fibrinogen/ d dimers

HaemophilaInherited Bleeding Disorder

Factor VIII/FIX deficiency

X-Linked InheritanceCarrier XX may have low levels

Spontaneous mutation

Inheritance of Haemophilia

Life Expectancy In Haemophilia

Bleeding problems in HaemophiliaFactor LevelType of Bleed5%Trauma/Surgery

Intracranial BleedsAt BirthInjury

AdmissionFactor ConcentrateScanningObservationNeurosurgery

Forearm Bleed

Joint bleedSynovial inflammation and hyperaemiaSynovial overgrowth and Bone resorptionFurther BleedJoint Destruction

Joint Bleeding

Chronic Joint Bleeding

The role of prophylaxis in the prevention of joint injury

Lofqvist, Nilsson et al ( Journal Int. Medicine May 1997): 34 patients aged 7-22yrs. Age at commencement of prophylaxis - 1-4.5yrs. 79% had no joint problems and the rest had no deterioration in joint abnormalities.

Liesner,Khair, Hann, ( BJH Mar 1996)27 children aged 1.3-15.9yrs. No. of bleeds/yr pre-prophylaxis-14.5 and post - 1.5. 20 children had evidence of arthropathy which improved on prophylaxis.

Prophylaxis The Irish Data (1992-1997)

Bleeds/yr, pre-prophylaxis, 9.5-106 (mean 38)

Bleeds/yr, post-prophylaxis, 0-9 (mean 3.5)

Development of inhibitors, 2 - low level (

ProphylaxisFactor VIII

T = 8 hoursFrequency three times/weekDose 20-40iu/kgFactor IX

T = 18 hoursFrequency twice/weekDose 50iu/kg

Dose AdjustmentGrowth

Break through bleeds

Management of Acute BleedsRest

Factor ConcentrateFVIII; 35-50iu/kgFIX; 70-100% (7-10iu/ml)Wt x desired rise x 1.25Continuous infusionFVIII50iu/kg bolus; infusion 4iu/kg/hrFIX100% bolus; infusion 6-8iu/kg/hr

Mild Factor VIII DeficiencyFactor VIII

DDAVP0.3mcg/kg/30 min

Antifibrinolytic therapy

Haemophilia The problems

BleedingDestructive arthropathyAddictionInfectionInhibitors

InhibitorsAnti-FVIII Antibodies - IgGIncidence: 10-20%High responding or lowlevel/transient Familial incidence (x6)Majority

Management of InhibitorsAcute Bleeding episodesFVIIa

Immune ToleranceHigh Dose 200-300iu/kg/d x 1-3 yrsCyclophosphamide/FVIII/IVIg50iu/kg/d x 1->12m25iu/kg/d x 1->12m

Von Willebrands DiseaseAutosomal InheritanceAbnormal VWFS/S: easy bruising, mucosal bleeds, heavy periodsTreatment: antifibrinolytic agentsDDAVPPlasma derived factor (Fanhdi)Lab Investigations

FVIIIcVWF:AgVWF:RCFBleeding timeVWF Multimers