Review And Insights Into The Bleeding Mechanism Incited By Antithrombotic Therapy: Mechanistic Nuances Of Dual Pro-Hemorrhagic Substrate Incorporating Drug-Induced Microvascular Leakage

In patients with atrial fibrillation antithrombotic prophylaxis for stroke is associated with an increased risk of bleeding. Cerebrovascular risk-benefit ratio for oral anticoagulation therapies continues to be debated. Macro and/or microhematomas as well as visible or cryptic ones may appear unexpectedly in any anatomic region. The diagnostic and prognostic value of subcutaneous hematomas (petechia, ecchymosis, bruise) potentially predisposing intracerebral micro- or macrobleeding might be reconsidered. Hypothetically, subcutaneous hemorrhagic events are "transparent" signs and reflect the coexistence of remote vulnerable sites that are potential bleeding sources. Obviously vigilance is needed for early signs of drug-related petechiae evaluation to determine whether it is a local/superficial subtlety or a systemic problem. Any bleeding complication, regardless of its scale and anatomical location, might be treated as a worrisome clinical symptom requiring subtle correction of antithrombotic regimen. The focus of this article is to review the current knowledge of drug-related hemorrhage with special emphasis on underlying mechanisms and links between the visible bleeding (predominantly subcutaneous) and remote (such as cerebral) hemorrhagic sources. To mitigate inappropriate therapy, we should consider new conceptual insights and more individualized approaches to achieve an optimal balance of efficacy and safety. We hypothesize that bleeding complications occur as a result of two factors - impact of antithrombotic drugs and related detrimental effect on microvascular network. Most likely the microvasculature undergoes pro-hemorrhagic medication stress leading to unfavorable vascular wall "fenestration" with ensuing consequences. If so, it suggests the presence of dual substrate responsible for hemorrhagic events.