Lauren is a 34 year old woman with a postpartum acquired haemophilia. The presentation and diagnosis of this disorder has been discussed in the previous posts; the management is what concerns us at this point.
The traditional approach to the management of acquired haemophilia is three pronged:
- Identify any underlying cause.
- Manage the bleeding.
- Manage the inhibitor.
It is beyond the remit of this post to discuss the details of each of these aspects, but the essential concepts, with relevant references, are outlined below.
Identify the underlying Cause
The potential underlying causes of acquired haemophilia are listed in the previous post. Identifying any driving cause is essential as it is clearly vital to rectify this where possible to eradicate the inhibitor in the longer term. However no underlying cause is identified in 40%.
Manage The Bleeding
Not all patients present with active bleeding, but during their illness two thirds will require treatment for an acute bleed. Options for treating bleeding are based on the need to overcome the effect of the action of the inhibitor, as standard factor VIII is unlikely to be effective. In some patients with low inhibitor titres it is possible to overwhelm the inhibitor with high doses of standard FVIII, so this is an option, but rarely used.
Porcine Factor VIII is currently being trialed and shows promise; it has been engineered to lack the beta domain against which the neutralising antibodies are directed.
FVIII bypassing agents are the current mainstay of management. Recombinant FVIIa (Novoseven being the UK brand) and activated PCC (FEIBA) both stimulate the coagulation cascade and thus thrombin (and clot) formation without requiring FVIII. The current evidence does not suggest superiority of one to the other, but the practicalities of administration (such as frequency and local stocks) will usually influence selection decisions.In addition rFVIIaIn is often preferred in young patients due to the small risk of exposure to microorganisms from a donor derived product. In some patients one agent may be more effective than other, and it may be necessary to switch agents within a given bleeding episode if adequate response is not achieved.
Manage the Inhibitor
Modification of the defective immune response is the third aspect to managing Acquired Haemophilia. Although about one third of patients in historical case series spontaneously remitted, the risk of significant bleeding is generally felt to outweigh the risks of immunosuppression.
Steroids are first line therapy and are usually started at 1mg/kg prednisolone. Some authorities advocate the addition of cyclophosphamide initially. A response is usually seen within 3-5 weeks but if not the addition of rituximab is generally the second choice. Other immunosuppression can be considered, including ciclosporin, immune tolerance therapy and multiagent therapies.
Whilst postpartum status is known to be a risk factor for acquired haemophilia it remains a rare phenomenon with a handful of case reports only. Points to consider include:
- Primigravidae are most at risk.
- Presentation can occur between 1 month and 1 year from delivery.
- The most common presenting complaint is persistent PV bleeding.
- Bleeding at delivery is extremely rare, however emergency hysterectomy due to persistent postpartum PV bleeding has been reported, usually due to a delay in establishing the diagnosis of acquired haemophilia.
- Recurrence in subsequent pregnancies is not inevitable but neither is it predictable.
- Complete remission in case series was reported at 16 months with no therapy, 12 months with steroids and 8 months with steroid and other immunosuppression.
- Cyclophosphamide should be avoided in such young patients due to the long term risk of secondary malignancy; any other agents should be considered in the context of breastfeeding where applicable.
- Overall survival at two years is reported as 97%.