Management of haemophilic patients with inhibitors in major orthopaedic surgery by immunadsorption, substitution of factor VIII and recombinant factor VIIa (NovoSeven^®): a single centre experience

Abstract

Inhibitors of factor VIII or FIX in haemophilic patients are a common and serious complication associated with an increased risk of life-threatening bleeding during elective surgery. Substitution therapy fails to be effective, therefore an alternative treatment is needed. We have performed six major elective orthopaedic interventions in four patients with haemophilia A and inhibitors. A preoperative immunadsorbant therapy with Therasorb to eliminate inhibitors was successful in four cases, but during FVIII substitution inhibitors increased on day 4 to day 6 after surgery, leading to decreasing FVIII levels. Therefore, therapy was changed to recombinant FVIIa (rFVIIa; NovoSeven). Two interventions had to be covered with sole rFVIIa therapy as immunadsorbant therapy failed to be effective in one case and the need for acute intervention did not allow pretreatment in the other. We did not see increased bleeding during or after surgery when compared to our experience with non-inhibitor haemophilic patients. In conclusion, a preoperative decrease of inhibitors from immunadsorbant therapy, perioperative substitution of FVIII and changing treatment to rFVIIa when inhibitors are increased, is a safe and economic therapy for guaranteeing haemostasis in major elective orthopaedic surgery. On the contrary, sole therapy with rFVIIa allows immediate surgical intervention without a long hospital stay prior to surgery and a need for laboratory monitoring of inhibitor titres and FVIII levels. Our findings support data previously published.

Major surgery in a severe haemophilia A patient with high titre inhibitor: use of the thrombin generation test in the therapeutic decision

“…Recently, Habermann et al . [19] reported results of four major orthopaedic interventions in haemophilia A patients with inhibitor, using preoperative immunoadsorption, FVIII substitution and rFVIIa when inhibitors increased. They concluded that this combined protocol was effective and safe guaranteeing sufficient haemostasis.…”

Health economics of treating haemophilia A with inhibitors

“…The availability of effective alternative haemostatic agents such as rFVIIa and the development of clinical protocols such as preoperative immunoadsorbant therapy and continuous infusion of rFVIIa [28–30] has meant that surgical interventions such as joint replacement have become a clinical option for all haemophilia patients regardless of their inhibitor status [27,31]. However, orthopaedic surgery for haemophilia A patients without inhibitors is an expensive procedure [32–34] and there remains the perception that such procedures for patients with inhibitors are extremely high cost and clinically unpredictable.…”

Short-course use of recombinant factor VIIa in a haemophilia patient with inhibitor undergoing cataract surgeries

“…Among these treatment options, rFVIIa represents a major therapeutic advance in the management of haemophilia patients with factor VIII or factor IX inhibitors. Also, in haemophiliacs with previous history of inhibitor who do not test positive at the time of surgery rFVIIa can be used safely to avoid inhibitor recurrence and refractoriness to FVIII or FIX concentrates [2]. Beside this usage, rFVIIa has been reported to be safe and effective in controlling bleeding in nonhaemophilic patients such as Glanzmann's thrombastenia [3], Bernard-Soulier syndrome [4], thrombocytopenia [5], liver disease [6], intracranial haemorrhage [7] and traumatic bleeding [8].…”