Hemophilia talk

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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 swellingBrought to A&E

    *

  • Case 1 clinical suspicionNon-accidental injury (NAI)Police report made

  • Case 1 contdHb 4.5 g/dLAPTT x 3 >100 secRx: PRBCs + FFP transfused

  • Case 1 factor assaySample sent over to haemostasis labWithin 1 hourFVIII
  • Do not mistake haemophilia for non-accidental injury (NAI)

    *

  • Bleeding 2 typesImmediate bleedingDefects in primary haemostasisVascular abnormality

    Delayed bleedingDefects in secondary haemostasis

  • Case 1 Day 2 of life following SVDBleeding in haemophilia is delayed

  • Prompt AccurateStep 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

    Posterior fossa tumour*

  • Case 2 contdPlanned 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 laterFVIII < 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 contdPT 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

    This hospital can only do FVIII and FIX levels*

  • Case 3 contdBleeding 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 contdSuspected inhibitor; switched to PCCUnable to do inhibitor assaySample sent to reference laboratoryFVIII 3% No inhibitor detectedvWF Ag < 1%Diagnosis: severe type 3 vWD

    Diagnosis: severe type 3 vWDvWF

  • Learn about haemophiliaGenetic risk & Carrier statusInhibitor riskStep 3: Counseling

  • Case 1 Family history Mom:2 daughters (10 and 6 years old)6 younger siblingsNo f/h of haemophilia

  • Case 1 Family tree

    ?NMIIIIII6 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 disorderD: Explain about haemophilia

  • Haemophilia Hereditary bleeding disorderX-linkedLack a clotting factorfactor VIII (HA) or factor IX (HB)Blood fails to clotBleeds spontaneously in severe disease20% present at birth

    *

  • XHXCarrier WomanHealthy ManCarrier GirlHealthy GirlHaemophilic BoyHealthy BoyXHXXXXXHYXYYInheritance 50%50%

    *Carrier mother has a 50% chance of having a daughter who will be a carrier and a 50% chance of having a son who is a haemophilia ie. 25% chance of passing on the gene with each pregnancy.

  • Classification of Haemophilia

    Severity Factor level %Bleeding Severe < 1Spontaneous 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

    *No aspirin or NSAIDs

  • Haemarrthrosis right elbowHaemarrthrosis the hallmark of haemophilia

    *

  • Bleeding in haemophiliaHaemarrthrosisBegin approx age 1 yearSpontaneousMay be preceded by tinglingBlood 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 haemophiliaMuscle bleedsOften, 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 contdM: 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
  • Genetic testingIndex patient (NM)Intron 22 inversion by PCRIf negativeIntron 1 inversionIf both negativeDNA 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 HaemorrhageFactor 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)Factor level (%)

    0257510050

    036241224489660

    VIIIIX

    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 motionStrengthProprioception, balance and coordination

  • Case 1 Prevention of bleeds Started prophylaxis age 10 months at 50 IU/kg once a weekAfter 4 months, difficulty with venous accessPort-a-cath inserted on 11/10/11; age 14 months

  • Prophylaxis is the Rx of choice Many studiesProphylaxis 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

    2 RCTs- the other Italian study Gringeri: 21 prophy; 19 OD; Jt damage 29% prophy; 74% OD at 6 years*

  • Case 1 Prophylaxis Factor VIII replacement for port-a-cath insertion100% bolus50% 8hrly D1- D250% 12hrly D3- D5Followed by prophylaxis 25 iu/kg 3x/wk

    Medic alert

  • Prophylaxis doseLow dose (Utrecht)15 30 IU/kg

    High dose (Malmo)25 40 IU/kg

    3x/ week for HA 2x/ week for HB Principle: to convert a severe haemophilia to

    a moderate haemophiliaPetrini P, Haemophilia 2004A Srivastava, Haemophilia 2012

  • Starting prophylaxis Primary prophylaxis before any joint bleedsAge 1 2 yearsPrimary prophylaxis after 1 or 2 joint bleedsDamage 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 - 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 youThe end

    **

    Posterior fossa tumour*This hospital can only do FVIII and FIX levels*Diagnosis: severe type 3 vWDvWF