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 FBC: Hb 11g/dl; WCC 8x10^/l; Platelets <10x10^9/l PT 14 sec ; APTT 33 sec; Fibrinogen 2.0g/l Treatment options: Nil; IVIg; Steroids Outcome: 90% recovery; 10% chronic

Congenital Thrombocytopenia Dysfunctional platelets Bernard Soulier Grey platelet syndrome Wiskott-Aldrich syndrome Normal Platelet function May-Hegglin TAR

Case 2 Newborn infant Intracranial Haemorrhage No dysmorphic features 1st child No liver/spleen palpable FBC Hb 18.5g/dl WCC 10 x x 109/l /l Platelets 10 x 109/l /l Coagulation screen PT 15 sec. (13-16) APTT 41 sec (28-36)

Differential diagnosis Infection DIC Immune Thrombocytopenia Alloimmune Isoimmune Congenital Thrombocytopenia TAR syndrome Wiscott Aldrich Syndrome Von Willebrands disease Type 2B A-V malformations

Alloimmune Thrombocytopenia Incidence 1:1000-5000 births IgG antibodies HPA1a 80% HPA5b 15% 50% occur in 1st pregnancy Bleeding can be in utero or after birth Treatment Platelets IVIg ?Steroids

Isoimmune Thrombocytopenia Maternal anti-platelet IgG Placental Passage Thrombocytopenia nadir ~5days post-partum History & examination of mother Treatment IvIg ± steroids

Disseminated Intravascular Coagulopathy Infection Symptoms and Signs Petechiae Bruising Bleeding Laboratory results Anaemia Thrombocytopenia ↑PT/ ↑APTT/↓Fibrinogen/ ↑d dimers

Haemophila Inherited Bleeding Disorder Factor VIII/FIX deficiency X-Linked Inheritance Carrier XX may have low levels Spontaneous mutation

Inheritance of Haemophilia

Life Expectancy In Haemophilia

Bleeding problems in Haemophilia Factor Level Type of Bleed <1% Spontaneous/severe 2%-5% Mild trauma/ occasionally spontaneous >5% Trauma/Surgery

Intracranial Bleeds At Birth Injury Admission Factor Concentrate Scanning Observation Neurosurgery

Forearm Bleed

Joint bleed  Synovial inflammation and hyperaemia  Synovial overgrowth and Bone resorption  Further Bleed  Joint 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 (<1Bu) and transient (< 1 year)

Prophylaxis Factor VIII T½ = 8 hours Frequency – three times/week Dose – 20-40iu/kg Factor IX T½ = 18 hours Frequency – twice/week Dose – 50iu/kg

Dose Adjustment Growth Break through bleeds

Management of Acute Bleeds Rest Factor Concentrate FVIII; 35-50iu/kg FIX; 70-100% (7-10iu/ml) Wt x desired rise x 1.25 Continuous infusion FVIII 50iu/kg bolus; infusion 4iu/kg/hr FIX 100% bolus; infusion 6-8iu/kg/hr

Mild Factor VIII Deficiency DDAVP 0.3mcg/kg/30 min Antifibrinolytic therapy

Haemophilia The problems Bleeding Destructive arthropathy Addiction Infection Inhibitors

Inhibitors Anti-FVIII Antibodies - IgG Incidence: 10-20% High responding or lowlevel/transient  Familial incidence (x6) Majority <10yrs Occur within first 25 treatment days  Bleeding

Management of Inhibitors Acute Bleeding episodes FVIIa Immune Tolerance High Dose 200-300iu/kg/d x 1-3 yrs Cyclophosphamide/FVIII/IVIg 50iu/kg/d x 1->12m 25iu/kg/d x 1->12m

Von Willebrands Disease Autosomal Inheritance Abnormal VWF S/S: easy bruising, mucosal bleeds, heavy periods Treatment: antifibrinolytic agents DDAVP Plasma derived factor (Fanhdi) Lab Investigations FVIIIc VWF:Ag VWF:RCF Bleeding time VWF Multimers