Use of recombinant factor VIIa for post-operative haemorrhage in a patient with Glanzmann's thrombasthenia and human leucocyte antigen antibodies

Recombinant factor VIIa is licensed for the treatment of patients with inherited or acquired haemophilia with inhibitors to coagulation, but has also been used to treat bleeding conditions without inhibitors to coagulation proteins, such as hereditary factor VII (FVII) deficiency, factor XI (FXI) deficiency, inherited platelet disorders and von Willebrand disease (Hedner, 1998). The haemostatic effect of the agent may be by activating coagulation on the surface of platelets. Even when only a small number of activated platelets are present, activation of factor X (FX) by FVIIa may produce enough thrombin for local fibrin production at bleeding sites (Monroe et al, 1997).

Glanzmann's thrombasthenia is a rare inherited platelet function disorder with abnormalities of the membrane glycoprotein (GP) IIb/IIIa receptor. Clinical manifestations include mucosal and post-operative bleeding (d'Oiron et al, 2000). Transfusion of platelets may promote haemostasis, but repeated transfusions may stimulate anti-human leucocyte antigen (HLA) and anti-GP IIb/IIIa immunization and cause platelet refractoriness. Factor VIIa may be a useful haemostatic option in such cases.

Three cases have recently been reported of Glanzmann's thrombasthenia with anti-GPIIb/IIIa antibodies treated preoperatively with factor VIIa (d'Oiron et al, 2000). There was no surgical bleeding in any of the patients, although one had a thromboembolic complication. There has also been a case of Glanzmann's thrombasthenia with anti-HLA antibodies in which HLA-matched platelets and FVIIa were successfully used during major surgery (Wielenga et al, 1998). In this case, HLA-matched platelets alone had not been sufficient to prevent bleeding complications during previous dental treatment. In both these reports, all patients also received tranexamic acid.

We have treated a patient with Glanzmann's thrombasthenia and anti-HLA alloantibodies with FVIIa for post-operative haemorrhage. The 33-year-old woman with type I Glanzmann's thrombasthenia underwent elective lumbar discectomy. She had documented anti-HLA antibodies but no anti-GPIIb/IIIa antibodies. Previous epistaxes and traumatic bleeding had responded well to HLA-matched platelets with tranexamic acid. Immediately prior to and following surgery she received HLA-matched platelets without tranexamic acid. Twenty minutes after surgery she had a brisk 250 ml haemorrhage from the surgical wound which persisted despite application of a pressure dressing. A single bolus of 4·8 mg (60 μg/kg) of recombinant factor VIIa was given while awaiting further HLA-matched platelets. Bleeding stopped 15 min following this without further platelet transfusions. No further factor VIIa was administered.

This and other recent cases suggest that emergency haemostasis can be achieved with FVIIa (d'Oiron et al, 2000) for a platelet refractory state secondary to anti-HLA or anti-GP IIb/IIIa alloantibodies in patients with Glanzmann's thrombasthenia. This occurred in our case without additional treatment with tranexamic acid. The level of risk of thromboembolism associated with FVIIa is unknown. The thrombosis reported in the patient with Glanzmann's thrombasthenia by d'Oiron et al (2000) may have been related to a higher VIIa dose, prolonged treatment duration and concurrent anti-fibrinolytic therapy.