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