Inhibitors to factor XI (FXI) can develop following exposure to plasma products in 33% of patients with severe FXI deficiency who are homozygous for the type II nonsense mutation prevalent in Jews (

Salomon et al. Blood 2003;101:4783
). Hemostasis in five such patients was previously achieved during surgery by infusion of recombinant factor VIIa (rFVIIa) and tranexamic acid, but two patients experienced arterial thrombosis following surgery (
Schulman et al. Hemophilia 2006; 12:223
). Conceivably, the rather high dose of rFVIIa used was responsible for the thrombotic events in these patients. In a previous in vitro study, we showed that low concentrations of rFVIIa can correct thrombin generation in plasma of patients with severe FXI deficiency and an inhibitor to FXI (
Livnat et al. J Thromb Hemost 2006; 4:192
). In the present study we addressed the question whether low doses of rFVIIa and use of tranexamic would be hemostatically effective and less thrombogenic during and after major surgery in patients with severe FXI deficiency in whom plasma derivatives could not be used. Three patients (two with FXI inhibitor and one with severe IgA deficiency) underwent major surgery managed by a single low dose infusion of rFVIIa and administration of tranexamic acid 1 G q.i.d for 7 days (Table). In patient 1 the infusion was given immediately prior to surgery and in patients 2 and 3 at the end of surgery. Hemostasis was achieved in all patients and no thrombosis occurred.

No.Sex/ageFXI (U/dL)FXI inhibitor (B.U)OperationSingle dose rVIIa (uG/Kg)Adverse events
* IgA deficiency 
1 M/62 < 0.01 5.0 Laparoscopic cholecystectomy 30 None 
2 M/61 < 0.01 5.0 Transuretheral prostatectomy 16 None 
3 M/63 0.02 0* Parathyroidectomy 15 None 
No.Sex/ageFXI (U/dL)FXI inhibitor (B.U)OperationSingle dose rVIIa (uG/Kg)Adverse events
* IgA deficiency 
1 M/62 < 0.01 5.0 Laparoscopic cholecystectomy 30 None 
2 M/61 < 0.01 5.0 Transuretheral prostatectomy 16 None 
3 M/63 0.02 0* Parathyroidectomy 15 None 
View Large

These observations suggest that a single infusion of low dose rFVIIa and use of tranexamic acid can be a safe modality of treatment in patients with severe FXI deficiency who cannot receive blood products. Furthermore, the protocol outlined here may be used to avoid inhibitor formation in patients with extremely severe FXI deficiency who undergo surgery.

Topics:
factor xi deficiency, iga deficiency, infusion procedures, recombinant coagulation factor viia, surgery specialty, surgical procedures, operative, tranexamic acid, hemostasis procedures, adverse event, arterial thrombosis

Disclosures: No relevant conflicts of interest to declare.

Author notes

Corresponding author

2008, The American Society of Hematology
2008
Sign in via your Institution