1. Coagulation Disorders
Corrina Mc Mahon

3. Laboratory investigations
PT: VII, X, V
APTT; XII, XI, IX, VIII
TT; Fibrinogen
D dimers; fibrin breakdown

7. Case 1 4 yr old boy URTI 2 weeks ago Sudden onset bruising/petechiae
PH: Nil
FH: Nil
Physical examination:

8. 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

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

11. 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)

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

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

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

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

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

18. Inheritance of Haemophilia

20. Life Expectancy In Haemophilia

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

22. Intracranial Bleeds At Birth Injury Admission Factor Concentrate
Scanning
Observation
Neurosurgery

23. Forearm Bleed

24. Joint bleed  Synovial inflammation and hyperaemia  Synovial overgrowth and Bone resorption  Further Bleed  Joint Destruction

25. Joint Bleeding

26. Chronic Joint Bleeding

27. 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 yrs. 79% had no joint problems and the rest had no deterioration in joint abnormalities.
Liesner,Khair, Hann, ( BJH Mar 1996)
27 children aged yrs. No. of bleeds/yr pre-prophylaxis-14.5 and post children had evidence of arthropathy which improved on prophylaxis.

28. Prophylaxis The Irish Data (1992-1997)
Bleeds/yr, pre-prophylaxis, (mean 38)
Bleeds/yr, post-prophylaxis, 0-9 (mean 3.5)
Development of inhibitors, 2 - low level (<1Bu) and transient (< 1 year)

29. 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

30. Dose Adjustment
Growth
Break through bleeds

31. Management of Acute Bleeds
Rest
Factor Concentrate
FVIII; 35-50iu/kg
FIX; % (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

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

33. Haemophilia The problems
Bleeding
Destructive arthropathy
Addiction
Infection
Inhibitors

34. 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

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

36. 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