Coagulation DisordersCoagulation Disorders

Corrina Mc MahonCorrina Mc Mahon

Laboratory investigationsLaboratory investigations

PTPT: VII, X, V: VII, X, V

APTTAPTT; XII, XI, IX, VIII; XII, XI, IX, VIII

TTTT; Fibrinogen; Fibrinogen

D dimersD dimers; fibrin breakdown; fibrin breakdown

Case 1Case 1

4 yr old boy4 yr old boy URTI 2 weeks agoURTI 2 weeks ago Sudden onset Sudden onset

bruising/petechiaebruising/petechiae PH: NilPH: Nil FH: NilFH: Nil Physical examination:Physical examination:

InvestigationsInvestigations

FBCFBC: : Hb 11g/dl; WCC 8x10^/l; Platelets <10x10^9/lHb 11g/dl; WCC 8x10^/l; Platelets <10x10^9/l

PTPT 14 sec ; 14 sec ; APTTAPTT 33 sec; 33 sec; FibrinogenFibrinogen 2.0g/l 2.0g/l Treatment optionsTreatment options: Nil; IVIg; Steroids: Nil; IVIg; Steroids OutcomeOutcome: 90% recovery; 10% chronic: 90% recovery; 10% chronic

Congenital ThrombocytopeniaCongenital Thrombocytopenia

Dysfunctional plateletsDysfunctional platelets Bernard SoulierBernard Soulier Grey platelet syndromeGrey platelet syndrome Wiskott-Aldrich syndromeWiskott-Aldrich syndrome

Normal Platelet functionNormal Platelet function May-HegglinMay-Hegglin TARTAR

Case 2Case 2

Newborn infantNewborn infant Intracranial Intracranial

HaemorrhageHaemorrhage No dysmorphic No dysmorphic

featuresfeatures 11stst child child No liver/spleen No liver/spleen

palpablepalpable

FBCFBC

Hb 18.5g/dlHb 18.5g/dl

WCC 10 x x 10WCC 10 x x 1099/l /l/l /l

Platelets 10 x 10Platelets 10 x 1099/l /l/l /l

Coagulation screenCoagulation screen

PT 15 sec. (13-16)PT 15 sec. (13-16)

APTT 41 sec (28-36)APTT 41 sec (28-36)

Differential diagnosisDifferential diagnosis

InfectionInfection DICDIC Immune ThrombocytopeniaImmune Thrombocytopenia

AlloimmuneAlloimmune IsoimmuneIsoimmune

Congenital ThrombocytopeniaCongenital Thrombocytopenia TAR syndromeTAR syndrome Wiscott Aldrich SyndromeWiscott Aldrich Syndrome

Von Willebrands diseaseVon Willebrands disease Type 2BType 2B

A-V malformationsA-V malformations

Alloimmune ThrombocytopeniaAlloimmune Thrombocytopenia

Incidence 1:1000-5000 birthsIncidence 1:1000-5000 births IgG antibodiesIgG antibodies

HPA1a 80% HPA1a 80% HPA5b 15%HPA5b 15%

50% occur in 150% occur in 1stst pregnancy pregnancy Bleeding can be in utero or after birthBleeding can be in utero or after birth

TreatmentTreatment PlateletsPlatelets IVIgIVIg ?Steroids?Steroids

Isoimmune Thrombocytopenia Isoimmune Thrombocytopenia

Maternal anti-platelet IgGMaternal anti-platelet IgGPlacental PassagePlacental PassageThrombocytopenia nadir ~5days post-Thrombocytopenia nadir ~5days post-

partumpartumHistory & examination of motherHistory & examination of motherTreatmentTreatment

IvIg IvIg ± steroids± steroids

Disseminated Intravascular CoagulopathyDisseminated Intravascular Coagulopathy

InfectionInfection

Symptoms and SignsSymptoms and Signs PetechiaePetechiae BruisingBruising BleedingBleeding

Laboratory resultsLaboratory results AnaemiaAnaemia ThrombocytopeniaThrombocytopenia ↑↑PT/ ↑APTT/↓Fibrinogen/ ↑d dimersPT/ ↑APTT/↓Fibrinogen/ ↑d dimers

HaemophilaHaemophila

Inherited Bleeding DisorderInherited Bleeding Disorder

Factor VIII/FIX deficiencyFactor VIII/FIX deficiency

X-Linked InheritanceX-Linked InheritanceCarrier XX may have low levelsCarrier XX may have low levels

Spontaneous mutationSpontaneous mutation

Inheritance of HaemophiliaInheritance of Haemophilia

Life Expectancy In HaemophiliaLife Expectancy In Haemophilia

Bleeding problems in HaemophiliaBleeding problems in Haemophilia

Factor LevelFactor Level Type of BleedType of Bleed

<1%<1% Spontaneous/severeSpontaneous/severe

2%-5%2%-5% Mild trauma/ Mild trauma/ occasionally occasionally spontaneousspontaneous

>5%>5% Trauma/SurgeryTrauma/Surgery

Intracranial BleedsIntracranial Bleeds

At BirthAt Birth InjuryInjury

AdmissionAdmission Factor ConcentrateFactor Concentrate ScanningScanning ObservationObservation NeurosurgeryNeurosurgery

Forearm BleedForearm Bleed

Joint bleedJoint bleed

Synovial inflammation and hyperaemiaSynovial inflammation and hyperaemia

Synovial overgrowth and Bone resorptionSynovial overgrowth and Bone resorption

Further BleedFurther Bleed

Joint DestructionJoint Destruction

Joint BleedingJoint Bleeding

Chronic Joint BleedingChronic Joint Bleeding

The role of prophylaxis in the prevention The role of prophylaxis in the prevention of joint injuryof joint injury

Lofqvist, Nilsson Lofqvist, Nilsson et alet al ( ( Journal Int. Medicine May 1997)Journal Int. Medicine May 1997): :

34 patients aged 7-22yrs. Age at commencement of 34 patients aged 7-22yrs. Age at commencement of prophylaxis - 1-4.5yrs. 79% had no joint problems and prophylaxis - 1-4.5yrs. 79% had no joint problems and the rest had no deterioration in joint abnormalities.the rest had no deterioration in joint abnormalities.

Liesner,Khair, Hann, ( Liesner,Khair, Hann, ( BJH Mar 1996)BJH Mar 1996)

27 children aged 1.3-15.9yrs. No. of bleeds/yr pre-27 children aged 1.3-15.9yrs. No. of bleeds/yr pre-prophylaxis-14.5 and post - 1.5. 20 children had prophylaxis-14.5 and post - 1.5. 20 children had evidence of arthropathy which improved on prophylaxis.evidence of arthropathy which improved on prophylaxis.

Prophylaxis Prophylaxis The Irish Data (1992-1997)The Irish Data (1992-1997)

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

Bleeds/yr, post-prophylaxis, 0-9 (mean Bleeds/yr, post-prophylaxis, 0-9 (mean 3.53.5))

Development of inhibitors, 2 - low level (<1Bu) and Development of inhibitors, 2 - low level (<1Bu) and transient (< 1 year) transient (< 1 year)

ProphylaxisProphylaxis

Factor VIIIFactor VIII

TT½ = 8 hours½ = 8 hours Frequency – three Frequency – three

times/weektimes/week Dose – 20-40iu/kgDose – 20-40iu/kg

Factor IXFactor IX

TT½ = 18 hours½ = 18 hours Frequency – Frequency –

twice/weektwice/week Dose – 50iu/kgDose – 50iu/kg

Dose AdjustmentDose Adjustment

GrowthGrowth

Break through bleedsBreak through bleeds

Management of Acute BleedsManagement of Acute Bleeds

RestRest

Factor ConcentrateFactor Concentrate FVIII; 35-50iu/kgFVIII; 35-50iu/kg FIX; 70-100% (7-10iu/ml)FIX; 70-100% (7-10iu/ml)

Wt x desired rise x 1.25Wt x desired rise x 1.25 Continuous infusionContinuous infusion

FVIIIFVIII50iu/kg bolus; infusion 4iu/kg/hr50iu/kg bolus; infusion 4iu/kg/hr

FIXFIX100% bolus; infusion 6-8iu/kg/hr100% bolus; infusion 6-8iu/kg/hr

Mild Factor VIII DeficiencyMild Factor VIII Deficiency

Factor VIIIFactor VIII

DDAVPDDAVP 0.3mcg/kg/30 min0.3mcg/kg/30 min

Antifibrinolytic therapyAntifibrinolytic therapy

Haemophilia Haemophilia The problemsThe problems

BleedingBleedingDestructive arthropathyDestructive arthropathyAddictionAddiction InfectionInfection InhibitorsInhibitors

InhibitorsInhibitors

Anti-FVIII Antibodies - IgGAnti-FVIII Antibodies - IgG Incidence: 10-20%Incidence: 10-20% High responding or lowlevel/transientHigh responding or lowlevel/transient Familial incidence (x6)Familial incidence (x6) Majority <10yrsMajority <10yrs Occur within first 25 treatment daysOccur within first 25 treatment days BleedingBleeding

Management of InhibitorsManagement of Inhibitors

Acute Bleeding episodesAcute Bleeding episodes FVIIaFVIIa

Immune ToleranceImmune Tolerance High Dose 200-300iu/kg/d x 1-3 yrsHigh Dose 200-300iu/kg/d x 1-3 yrs Cyclophosphamide/FVIII/IVIgCyclophosphamide/FVIII/IVIg 50iu/kg/d x 1->12m50iu/kg/d x 1->12m 25iu/kg/d x 1->12m25iu/kg/d x 1->12m

Von Willebrands DiseaseVon Willebrands Disease

Autosomal InheritanceAutosomal Inheritance Abnormal VWFAbnormal VWF S/S: easy bruising, S/S: easy bruising,

mucosal bleeds, mucosal bleeds, heavy periodsheavy periods

Treatment:Treatment: antifibrinolytic agentsantifibrinolytic agents DDAVPDDAVP Plasma derived factor Plasma derived factor

(Fanhdi)(Fanhdi)

Lab InvestigationsLab Investigations

FVIIIcFVIIIc VWF:AgVWF:Ag VWF:RCFVWF:RCF Bleeding timeBleeding time VWF MultimersVWF Multimers