Impact of Anticoagulation in Acquired Hemophilia a

Background

Acquired Hemophilia A (AHA) is a rare autoimmune disorder that occurs due to the development of autoantibodies against factor VIII which leads to inhibition of the coagulation cascade and results in a propensity for hemorrhage. The estimated incidence is approximately 1.5 per million per year. It carries an exceptionally high morbidity and mortality rate, with severe or life-threatening hemorrhagic events occurring in 70-90% of cases, with 5-10% of these cases resulting in mortality. Several underlying conditions are associated with AHA, including autoimmune disorders, obstetrical and oncologic disease, and various medications, such as direct oral anticoagulants (DOACs) and antiplatelet therapy (APT), both of whose usage has increased significantly over the past decade.

Objectives

We aimed to evaluate whether patients prescribed an antiplatelet or anticoagulant at the time of diagnosis of AHA experienced more severe bleeding and worse clinical outcomes compared to those with AHA not prescribed an antiplatelet or anticoagulant.

Methods

This is a single-center retrospective study examining 16 individuals with AHA from April 2013 to April 2023. These individuals were categorized by the presence or absence of a prescribed anticoagulant and then further divided into class of anticoagulant (APT, DOAC or other oral anticoagulant (OAC), or exposure to both). Primary end points included the number of blood product transfusions received, hospital length of stay (LOS), need for intervention or procedure, and degree of hemoglobin (Hgb) drop from baseline. Continuous variables were compared using t-test or Wilcoxon rank-sum test while categorical variables were compared using the chi-square test or Fisher's exact test.

Results

Of the 16 individuals in our cohort, 9 were without prior exposure to anticoagulation or antiplatelet agents before the diagnosis of AHA while 7 were prescribed either an anticoagulant, antiplatelet agent, or both. Of those taking one of these classes of medications, 2 were prescribed OACs, 3 were prescribed APTs, and 2 were prescribed both classes. The mean baseline Hgb was similar in both groups, 12.84 for the non-exposed group and 12.92 for the exposed group, while mean Hgb at diagnosis was 9.55 and 8.81 for the non-exposed group and exposed group respectively (p-value 0.638). Median factor VIII titer inhibitors at diagnosis were 3.30 and 38.10 (p-value 0.124) for non-exposed and exposed groups, respectively. Mean hospitalization rates for non-exposed individuals versus exposed individuals were 5.0 and 7.0 (p-value 2.00) with a mean hospital LOS of 10.20 and 12.57 days (p-value 0.624) in the non-exposed and exposed group, respectively. The mean number of packed red blood cell (pRBC) transfusions needed during the index hospitalization was 1.6 and 3.0 (p-value 0.333) in the non-exposed group and exposed group respectively while the mean number of platelet transfusions were 4 and 6 in the non-exposed and exposed groups respectively. There was a statistically significant increase in intramuscular bleeding with a mean of 1.0 and 5.0 (p-value 0.035) in the non-exposed and exposed groups respectively. In each group there was only one individual who required procedural intervention. There was one death due to hemorrhage which occurred in the exposed group (p-value 0.467).

Conclusions

The increased rates of intramuscular bleeding in patients exposed to prior anticoagulation was statistically significant. Intramuscular hemorrhage is associated with increased morbidity due to the risk for compartment syndrome requiring surgical intervention. Our data demonstrates a trend towards the need for a longer hospitalization and more pRBC transfusions in individuals with prior exposure though notably, there is not an apparent increased trend for an increased rate of platelet transfusions. There is also a trend towards significance for higher factor VIII titer inhibitor levels in patients on anticoagulation at the time of diagnosis. While this study is limited in power by the sample size, there are no comparable studies to date examining the impact of anticoagulation on individuals with AHA. With the increasing rates of anticoagulation therapy, further investigation is needed on the impact of therapeutic anticoagulant or antiplatelet use prior to the diagnosis of AHA and subsequent clinical outcomes.