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
1
st
child
No liver/spleen
palpable
FBC
Hb 18.5g/dl
WCC 10 x x 10
9
/l /l
Platelets 10 x 10
9
/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 1
st
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

T = 8 hours
Frequency three
times/week
Dose 20-40iu/kg
Factor IX

T = 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
Factor VIII

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