Risk for Major Bleeding in Patients with Severe Factor XI Deficiency Treated with Aspirin and Clopidogrel

Introduction

Israel contains within it a unique variety of groups predisposed to autosomal recessive diseases secondary to the history of segregated religious communities. Indicated groups include Ashkenazi Jews and Israeli Arabs. Factor XI deficiency is one of the conditions that can be included in this group of diseases. It is reported to have a prevalence of 8-13.4% within the Ashkenazi Jewish community. Due to the risk for bleeding and delayed coagulation as a result of a deficient Factor XI, it has been suggested to avoid use of Aspirin and Clopidogrel in patients with severe deficiency. However, cardiovascular interventions mandate use of anti-aggregation therapy. We investigated the risk for major bleeding events in patients with severe factor XI deficiency treated with Aspirin and Clopidogrel.

Methods

This is an observational, historical cohort study performed using the electronic data base of Clalit Health organization, largest HMO in Israel. The objective of this study is to determine the incidence of major bleeding in patients with severe Factor XI deficiency (activity ≤ 15%). The study was approved by a centralized IRB committee. In the population of subjects with severe factor XI deficiency we identified subjects treated with Aspirin alone (n=126), Clopidogrel alone (n=38), and subjects treated with both simultaneously (n=21). Individuals were followed retrospectively, during the time on anti-aggregation treatment, for the occurrence of bleeding episodes classified according to bleeding severity; life threatening bleeding, severe bleeding (needed blood transfusion), and minor bleeding

Results

One hundred and eighty five subjects with severe factor XI deficiency were treated with anti-aggregation therapy. Most of the patients treated with Aspirin (68%) followed by Plavix (21%) and both (11%). Among patients treated with aspirin 4.7% (6/126) had life threatening bleeding and 2.3% (3/126) had minor bleeding. Among patients treated with Clopidogrel 2.6% (1/38) had life threatening bleeding, 2.6% (1/38) had severe bleeding, and 2.6% (1/38) had minor bleeding. Among patients treated with Aspirin and Plavix 4.7% (1/21) had life threatening bleeding following a trauma but no other bleeding was observed.

Discussion

Use of Aspirin and/or clopidogrel in patients with severe factor XI deficiency is associated with overall low risk for major bleeding. The use of Clopidogrel doesn't seem to add significantly to the risk of bleeding in this unique population.