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Approach to Diagnosis & Management of
Haemophilia
Step 1: Clinical suspicion
Case 1 Baby boyDOB: 30th July 2010SVD, discharged
wellThat night, noted
bruise behind ears and scalp swelling
Brought to A&E
Case 1 – clinical suspicionNon-accidental injury (NAI)Police report made
Case 1 – cont’dHb 4.5 g/dLAPTT x 3 >100 secRx: PRBCs + FFP
transfused
Case 1 – factor assaySample sent over to haemostasis labWithin 1 hour
FVIII <1 % vWF 90%
Δ: Severe haemophilia A
Do not mistake haemophilia for non-accidental injury (NAI)
Bleeding – 2 types1. Immediate bleeding
Defects in primary haemostasisVascular abnormality
2. Delayed bleedingDefects in secondary haemostasis
Case 1 – Day 2 of life following SVD
Bleeding in haemophilia is delayed
Prompt Accurate
Step 2: Laboratory confirmation
Case 22 year old boyc/o sudden onset of
headacheVomiting >10xGCS: 12/15Suspected
posterior fossa tumour
Courtesy of Dr Peter, March 2012
Case 2 – cont’dPlanned for emergency surgeryAPTT 127 (36.9- 45.5) secUnable to do factor assaySample sent over to reference laboratoryChild deteriorated and diedResults came back 10 days later
FVIII < 1%
Case 35 year-old boyAdmitted for upper GI haemorrhageh/o recurrent epistaxis and easy bruisingNo f/h of bleedingHb 4.5 g/dL TW 4.5 Plt 398
Case 3 – cont’dPT 12.o (11.5- 14.4) secAPTT 102.0 (36.9- 45.5) sec4 PRBC & 4 FFP transfused Factor VIII 2.5%Diagnosis: Moderate Haemophilia A
Case 3 – cont’dBleeding stopped with FFP x 3 dosesOGDS: pangastritisSwitched to hemofil M (high purity FVIII)3 days later, re-bledHb fell from 11.o to 5.0 g/dLAPTT 98 sec Mixing studies 48 sec
Case 3 – cont’dSuspected inhibitor; switched to PCCUnable to do inhibitor assaySample sent to reference laboratory
FVIII 3% No inhibitor detectedvWF Ag < 1%
Diagnosis: severe type 3 vWD
Learn about haemophiliaGenetic risk & Carrier status
Inhibitor risk
Step 3: Counseling
Case 1 – Family history Mom:
2 daughters (10 and 6 years old)
6 younger siblings
No f/h of haemophilia
Case 1 – Family tree
?
NM
I
II
III6 yrs
Case 1 – Counseling D: Your son has been diagnosed with
severe haemophilia A. Have you heard about haemophilia?
M: No doctor, but from what I see it must be a serious bleeding disorder
D: Explain about haemophilia
Haemophilia Hereditary bleeding disorderX-linkedLack a clotting factor
factor VIII (HA) or factor IX (HB)Blood fails to clotBleeds spontaneously in severe disease20% present at birth
XH X
Carrier Woman
Healthy Man
Carrier Girl
Healthy Girl
Haemophilic Boy Healthy Boy
XH
X
X X X XHY X Y
Y
Inheritance
50% 50%
Classification of HaemophiliaSeverity Factor
level %Bleeding
Severe < 1 Spontaneous Moderate 2 – 5 After minor
traumaMild 6 – 40 After major
trauma or surgery
Management Replace the factor that is missingVaccinations are not contraindicated but
must be given S/CLearn about haemophilia and inhibitor riskLearn to recognise bleedsNeed to report trauma or bleeding
Bruises or haematomas?
Avoid aspirin/ NSAIDsSuperficial cuts – OKPlatelets – primary haemostasis
IM injections must be avoided
Haemarrthrosis right elbow
Haemarrthrosis – the hallmark of haemophilia
Bleeding in haemophilia1. Haemarrthrosis
Begin approx age 1 yearSpontaneousMay be preceded by ‘tingling’Blood fills joint cavityRise in pressure is excruciatingly painfulPressure eventually stops the bleedingBlood damages cartilageJoint becomes prone to recurrent bleeds
Target joint
Joint damage
Bleeding in haemophilia2. Muscle bleeds
Often, apparently spontaneousMay result from exertionBlood fills muscle capsule or compartmentCompartment syndrome may resultPressure eventually stops the bleedingPsoas bleed is a typical example
Psoas bleed
Muscle contractures
Case 1 – Counseling cont’dM: Does that mean I am a carrier?D: Possible but in 30% it may be a
spontaneous mutationM: How do I know if I am a carrier?
Ratio <0.7FVIII 82%vWF antigen 81%Ratio: 1.0
Genetic testingIndex patient (NM)
Intron 22 inversion by PCRIf negative
Intron 1 inversionIf both negative
DNA sequencingOnce mutation detected, screen mom
Case 1 – Result NM- T1468X mutationMom- normalSo mom is not a carrierNot at risk of having another child with
haemophiliaNo need to screen daughters and sisters
Rx of acute bleedsPrevention of bleeds – Prophylaxis
Physiotherapy
Step 4: Treatment
Case 1 – Intracranial Haemorrhage
Factor replacementD1 – D2: 100% D3 – D4: 80% D5 – D9: 50%D11 – D14: 30%
Monitor FVIII levelsD1 – post dose, 6 – 8 h
laterD2, D4, D6 – trough
time (hours)
Fact
or le
vel
(%)
0
25
75
100
50
0 36241224
4896
60VIIIIX
Factor replacement
Factor dosingFormula:
Dose in units = weight in kg x % rise in factor required
K factor
(K factor for FVIII = 2.0 , FIX = 1.0)
Physiotherapy Start exercise once
pain subsidesEarly restoration of
Full range of motion
StrengthProprioception,
balance and coordination
Case 1 – Prevention of bleeds Started prophylaxis age
10 months at 50 IU/kg once a week
After 4 months, difficulty with venous access
Port-a-cath inserted on 11/10/11; age 14 months
Prophylaxis is the Rx of choice Many studies
Prophylaxis prevents joint damageBetter joint scores
* Manco-Johnson Prophylaxis (32 boys) vs. enhanced episodic
therapy (33 boys)93% vs. 55% (normal MRI joints
at 6 years)
Manco-Johnson MJ, NEJM 2007
Case 1 – Prophylaxis Factor VIII replacement
for port-a-cath insertion100% bolus50% 8hrly D1- D250% 12hrly D3- D5
Followed by prophylaxis 25 iu/kg 3x/wk Medic alert
Prophylaxis doseLow dose (Utrecht)
15 – 30 IU/kgHigh dose (Malmo)
25 – 40 IU/kg
3x/ week for HA 2x/ week for HB Principle:
to convert a severe haemophilia to a moderate haemophilia
Petrini P, Haemophilia 2004A Srivastava, Haemophilia 2012
Starting prophylaxis Primary prophylaxis before any joint bleeds
Age 1 – 2 yearsPrimary prophylaxis after 1 or 2 joint bleeds
Damage already done
Explain about inhibitor riskD: There is a 15 – 30% risk
of inhibitor developmentP: What is an inhibitor?D: An inhibitor is an
antibody against the infused factor VIII
P: Why is it important? D: It will render treatment
with FVIII useless
Prophylaxis protects against inhibitor development
Gouw SC et al. Blood 2007;109(6)4648-4654
Self-infusion & DosingRecognising problems
Communicating
Step 5: Caregiver & Patient education
Mom taught to infuse
Starting home therapy
Home therapy
Self-infusion
Home & School Visits
Communicate If any doubtsIf bleeding not
resolvedIn an emergencyIf factors running
lowPlan your travels
Dental check-ups ½ - 1 yearlyPrevention is better
Physiotherapy Know your
exercisesKeep to your
appointments
Approach to Diagnosis & Mx of Haemophilia: 5 steps
Step 1: Clinical suspicionStep 2: Laboratory confirmation – prompt &
accurateStep 3: Counseling & carrier detectionStep 4: Treatment/ Home therapyStep 5: Parent/ Caregiver/ Patient education
Thank you
The end