An up-to-date overview on haemophilia management – Dr Charles Percy
Haemophilia A and B : Factor VIII and IX deficiency respectively. Both X linked inheritance.
International categorisation: Severe: <1 IU/dL; Moderate: 1-5 IU/dL;Mild: > 5 IU/dL
Variety of mutations known and the type can influence the risk of inhibitor formation.
New mutations for haemophilia arise in up to 50% of patients (no FH previously known).
Important to screen potential carriers of known haemophiliacs.
Pregnancy management: 1 in 5 carriers of haemophilia VIII will have a low factor level. Factor VIII levels usually normalise in last trimester (check before 38 weeks). If low give desmopressin or factor concentrate with labour /C-section.
Where a FH is known: pre-implantation genetic diagnosis (like IVF). Fetal sexing with ffDNA at the end of first trimester. 3rdT amniocentesis to genetically test the fetus and guide delivery risk.
Risk of haemophilia in fetus: aim is to avoid intracranial haemorrhage. Elective C-section is the lowest risk but more risk for the mother (bleeding/thrombosis risk). Emergency c-section is the highest risk. NVD okay. Need to discuss options.
No rotational forceps or vontouse and fetal scalp electrode monitoring or fetal blood sampling at delivery. Intracranial doppler post birth- ideally within 24 hours.
Register baby at a comprehensive care centre.
Prophylaxis: whole of life care moderate/severe – start before 1stbleed or at the latest the first sign of a joint bleed. Trough at least 1IU/dl and no bleeding- ( will change to 3IU/dL in the future).
New joint bleed: Q: when was the last dose? what is usual trough? what is the severity of the bleed? Usually the aim is for: 50-80 IU/dL (Desired rise in factor level x weight (kg) )/2). Rest, ice, compression and elevation and physio as soon as bleed has settled. Subsequently aim for level between 30-50 and monitor for inhibitor. TXA not useful.
ISTH target joint= > 3 bleeds into joints within 6 month periods.
Surgery: aim 30-60 min before to get factor VIII level of 100 IU/dL (check level before and shortly after administration) Start tranexamic acid the night before. Keep trough level for 1stweek around 50 – often needs BD dosing. Once wound healing, trough of 30 and then week 3 can go to usual prophylaxis. DVT thromboprophylaxis is important. Mild haemophilia A – desmopressin (can’t give until primary school age as risk of hyponatraemia and seizures). In adults fluid restrict to 1-1.5L in 24 hours. Document response – pre and post 1 hour and 4 hour.
Annual review -national guidelines for what to check.
Other therapeutic options: 1. Extended half-life factor VIII and IX. 2. Emicizumab – a factor VIII mimic (for congenital factor VIII deficiency and for those with inhibitors).NB can get MAHA with FEIBA. 3. Trials of gene therapy – factor VIII and IX deficiency. 4. Inhibitors of TFPI or activated protein C or antithrombin – trying to downregulate the anti-coagulant pathways to compensate for poor coagulation.
Inhibitor screening: Factor VIII – every 3rdED check for inhibitor up until 20 then every 3-6 months. Once you’ve done 150 ED can check every 6 months, mild haemophiliacs every year. Check before any product change. During any peak incidence e.g surgery. Factor IX – similar screening but at 150 ED with Factor IX can stop screening. Get anaphylaxis and nephrotic syndrome with factor IX inhibitors.