Predicting Thrombotic Events in Rheumatoid Arthritis by Using Bleeding Time: Look at the Platelet

Abstract

Background: Rheumatoid Arthritis (RA) is associated with an elevated risk of thrombosis, which contributes to increased major adverse cardiovascular events and mortality in individuals with RA aged over 50, as compared to the general population. This increased thrombotic risk is thought to be due to systemic inflammation leading to platelet dysfunction. Additionally, certain RA treatments have been associated with an increased risk of clot formation. We proposed the hypothesis that a shortened bleeding time measurement could serve as an identifying marker for individuals at risk of clotting events. The bleeding time assesses platelet function. Aspirin can reverse the short bleeding time and may prevent the incidence of thrombosis. Methods: Sequential RA patients over age 50 (n=246) at one center had bleeding time testing at the initial visit and 2 weeks after beginning a medication known to affect coagulation. These were estrogen, rofecoxib, celecoxib, naproxen, ibuprofen, aspirin, tofacitinib, baricitinib, upadacitinib, filgotinib, and anti-coagulants. Results: The RA control group had a bleeding time of 3.7 + 0.4 minutes. This is a shorter bleeding time than expected in the normal population, where bleeding time is 4 to 7 minutes. The RA patients who developed MACE or thrombotic events had shorter bleeding time at 2.3 + 0.4 minutes, significantly shorter than the RA control group, p<0.001. A shorter bleeding time was demonstrated with COX-2 agents, rofecoxib and celecoxib at less than 2.5 minutes, and JAK agents had short bleeding time from 1.5 to 2.3 minutes, all significantly lower than the control p<0.002. Adding daily 81 mg low dose aspirin to JAK reversed the bleeding time to the control values. A bleeding time measured at less than 3 minutes was associated with higher incident rates of thrombotic events and MACE. Conclusion: These findings suggest that bleeding time less than 3 minutes may serve as a clinically relevant marker for assessing thrombotic risk in RA patients. Further research with larger cohorts is warranted to validate and expand upon these observations, potentially paving the way for the incorporation of bleeding time testing into the clinical management of RA patients to optimize thrombotic risk assessment and preventive strategies.