Treatment of patients with rare bleeding disorders in the Netherlands: real-life data from the RBiN study
Patients with rare inherited bleeding disorders (RBDs) exhibit a wide variety of hemorrhagic symptoms. Prolonged bleeding after invasive procedures is common. Adequate perioperative therapy captured in a treatment plan can reduce the risk of bleeding complications during and after invasive procedures.
The Rare Bleeding Disorders in the Netherlands (RBiN) study is a multicenter cross-sectional study of patients from all six Dutch Haemophilia Treatment Centers (HTC) diagnosed with a RBD. Individualized treatment plans were extracted from patient files. All patients with a history of tooth extraction or surgery were questioned about the procedure, use of prophylaxis and bleeding complications.
Two-hundred sixty-three patients were included in the RBiN study of which 16% did not have a treatment plan. Based on the existing treatment plans, tranexamic acid was used frequently for mild/mucosal bleeding. Moreover, tranexamic acid was described for most patients with a fibrinolytic disorder as monotherapy for major or life-threatening bleeding (86% and 75% respectively). Factor concentrates with or without tranexamic acid were frequently advised for life-threatening bleeds in patients with fibrinogen, FVII and FXIII deficiency (70%, 68% and 86% respectively). Treatment plans of patients with FX and FXI deficiency were highly heterogeneous. FX-deficient patients were treated with factor concentrates, plasma or prothrombin complex concentrate, and FXI-deficient patients with either plasma, factor concentrates, tranexamic acid or any combination.
In our RBiN cohort, 308 dental procedures and 408 surgical procedures were performed. Bleeding was reported in 132 dental procedures (43%) and 157 operations (39%). Omission of any prophylactic treatment resulted in bleeding complications in 50% of the dental procedures and 53% of the surgical procedures. Patients remained symptom-free in 65% of the dental procedures performed with tranexamic acid and 76% of the dental procedures performed with replacement therapy. No bleeding events were reported in the majority of surgical procedures carried out with tranexamic acid or replacement therapy (respectively 75% and 84%).
Most surgical procedures performed without prophylaxis in patients with FXI deficiency were complicated by bleeding, irrespective of FXI level (FXI<26%: 60% versus FXI 26-50%: 59%). Prophylaxis with replacement therapy resulted in less bleeding complications in both patient categories (FXI<26%: 12% versus FXI 26-50%: 15%).
We found a large heterogeneity in treatment plans of patients with RBDs between the six Dutch HTC, even in case of life-threatening bleeding. The variability was most pronounced in patients with FX or FXI deficiency. Bleeding complications after dental and surgical procedures were frequently reported. Proper prophylactic therapy reduced the bleeding risk significantly. The decision to use preprocedural prophylaxis cannot be solely made on individual coagulation factor level, but should also take into account the individual bleeding history.