coagulation disorders
DESCRIPTION
Coagulation Disorders. Corrina Mc Mahon. Laboratory investigations. PT : VII, X, V APTT ; XII, XI, IX, VIII TT ; Fibrinogen D dimers ; fibrin breakdown. Case 1. 4 yr old boy URTI 2 weeks ago Sudden onset bruising/petechiae PH: Nil FH: Nil Physical examination:. Investigations. - PowerPoint PPT PresentationTRANSCRIPT
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