Coagulation Disorders

Corrina Mc Mahon

Laboratory investigations
PT:

VII, X, V

APTT;
TT;
D

XII, XI, IX, VIII

Fibrinogen

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

Congenital Thrombocytopenia

TAR syndrome
Wiscott Aldrich Syndrome

Von Willebrands disease

Alloimmune
Isoimmune

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 postpartum
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
Factor

Bleeding Disorder

VIII/FIX deficiency

X-Linked
Carrier

Inheritance

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%
>5%

Mild trauma/
occasionally
Trauma/Surgery

spontaneous

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 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 preprophylaxis-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

Antifibrinolytic

min

therapy

Haemophilia
The problems
Bleeding
Destructive
Addiction
Infection
Inhibitors

arthropathy

Inhibitors
Anti-FVIII Antibodies
Incidence:

- IgG

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
High

Tolerance

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