Immune thrombocytopenia (ITP) is an acquired autoimmune disorder characterized by a low platelet count due to platelet destruction and impaired platelet synthesis. The incidence of ITP is estimated to be 2–5 per 100,000 persons in the general population and can present as an isolated primary condition or secondary to other conditions (1).

Unstable angina (UA), acute non-ST-elevation myocardial infarction (NSTEMI), and acute ST-elevation myocardial infarction (STEMI) are the three presentations of acute coronary syndromes (ACS). They are considered cardiac emergencies, requiring prompt interventions, including revascularization with percutaneous coronary intervention (PCI), thrombolytic therapy, or coronary artery bypass graft surgery (CABG). Dual antiplatelet therapy (DAPT) consisting of aspirin and a P2Y12 receptor antagonist is the cornerstone of ACS management, with longstanding endorsements by international guidelines, including the American College of Cardiology Foundation (ACCF), the American Heart Association (AHA), and the European Society of Cardiology (ESC) (2, 3). While DAPT effectively reduces the risks of both stent thrombosis and spontaneous ischemic events, it does so at the cost of an increased bleeding risk (4, 5). The management of antiplatelet therapy in ACS patients with thrombocytopenia, particularly ITP, poses a particular challenge for clinicians, as this population is at a higher risk of both bleeding and, paradoxically, thrombotic events (6). Therefore, long-term clinical outcomes, including bleeding and recurrent ACS, might be difficult to attain in this vulnerable population. Similarly, ITP management with ACS remains difficult as corticosteroids, which are first-line therapy for ITP, are associated with increased bleeding risk when used concurrently with DAPT and pose a concern for myocardial healing when used in the setting of ACS. Moreover, some second-line ITP therapies are associated with an increased risk of thrombosis (1, 7).

To date, the literature guiding clinicians on the management of coronary artery disease (CAD) complicated by ITP remains scarce. Therefore, we conducted a systematic review to summarize the available evidence of ACS management in the setting of ITP to help provide future directions and management strategies for this population cohort.

The evidence of CAD management in the context of ITP is limited, and such clinical presentation remains very challenging to clinicians as a balance between the risk of bleeding and thrombosis needs to be achieved. Thus, we conducted this systematic review following PRISMA guidelines to summarize the available literature on the management and outcomes of CAD complicated by ITP. Our systematic review included a total of 32 CAD cases that were managed by three different approaches in the setting of ITP: 18 cases had PCI, 12 cases underwent CABG, and the remaining 2 cases were managed conservatively. We have demonstrated that irrespective of intervention used, patients had different CAD presentations, including STEMI, NSTEMI, UA, stable CAD, and a low baseline platelet count, and the majority were treated with either corticosteroids alone, IVIG alone, or a combination of corticosteroids and IVIG. In addition, the antithrombotic therapy regimen was variable, especially among those who underwent PCI. Notably, all CAD treatment modalities resulted in favorable clinical outcomes with respect to bleeding and mortality, and the ITP-induced ACS was relatively very low.

We have demonstrated that, irrespective of CAD presentation, mode of intervention, baseline platelet count, and ITP treatment regimen, patients had favorable clinical outcomes with respect to bleeding and mortality, and the event rate of ACS related to ITP medications was very low.

The management of ACS with thrombocytopenia was addressed in a review by McCarthy et al. in 2017 (34). McCarthy et al. suggested the following strategies to minimize the risk of bleeding among patients with thrombocytopenia and ACS: (1) to proceed with PCI only if platelet count was > 50 x 10⁹/L without active bleeding using radial access instead of femoral access and to use drug-eluting stent (DES) over bare-metal stent (BMS) with limiting DAPT duration to 1 month followed by a single antiplatelet P2Y12 inhibitor, preferably clopidogrel and (2) to hold all anti-platelet agents and avoid PCI in cases where the platelet count was <50 × 10⁹/L or there was concurrent active bleeding. Therefore, the dilemma of ACS management with ITP remains unaddressed and requires further guidance, especially with the presumed thrombotic risks of ITP therapies. The first step in the management of newly diagnosed ITP is to determine whether starting pharmacologic therapy is needed or if close observation of the platelet count is enough. According to the latest guideline for ITP management by the American Society of Hematology (ASH), among those with newly diagnosed ITP and a platelet count of >30 × 10⁹/L with asymptomatic or minor bleeding, observation alone might be used, while for those with a platelet count of <30 × 10⁹/L, pharmacological treatment with corticosteroids is indicated (1). Nevertheless, the challenge with the observation approach among patients with CAD, particularly ACS, is that they require antiplatelet and anticoagulation therapies, which might put them at an increased risk of bleeding if the ITP remains untreated (2, 3).

In our systematic review, we found that patients with symptomatic CAD in the setting of active ITP were treated with different ITP regimens, including corticosteroids alone, IVIG alone, and corticosteroids and IVIG together, in addition to no treatment. According to the latest ASH guidelines for ITP management, the first line therapy for newly diagnosed ITP is a short course of corticosteroids of <6 weeks alone with either prednisone 0.5–2.0 mg/kg/day or dexamethasone 40 mg/day for 4 days as the initial corticosteroid. For those with ITP ≥ 3 months and who are either corticosteroid-dependent or corticosteroid-poor responders, the ASH guidelines suggest using second-line therapy, including TPO-RAs, rituximab, or splenectomy, after appropriate immunizations. Nevertheless, ITP management with ACS remains troublesome, as corticosteroids are associated with bleeding when used with antithrombotic agents and are associated with a possible increased risk of myocardial rupture if used in the setting of ACS (1, 7). Furthermore, second-line therapies are associated with an increased risk of thrombosis (2.5% with thrombopoietin receptor agonists, 2.2% with rituximab, and 2.4% with splenectomy) (1, 8).

Despite the important findings from this systematic review, given the limited literature on co-existing CAD and ITP management, it has a few limitations. First, although we have not restricted our inclusion criteria to any study type, only case reports and case series were identified and included. This highlights the complexity and difficulty of conducting research studies on the vulnerable population of ACS with ITP. Second, we limited our literature search to articles published in English, which might have predisposed the systematic review to language bias and the possibility of missing important findings.

In conclusion, the simultaneous presentation of CAD and ITP presents a significant challenge for clinicians to achieve a sensible balance between the prevention of thrombosis and the bleeding risk. Despite the paucity of evidence of CAD management with ITP, our systematic review of symptomatic CAD in the setting of ITP demonstrated that revascularization with either PCI or CABG with the concurrent use of corticosteroids and IVIG, either alone or in combination, for ITP was feasible with a non-negligible risk of bleeding and mortality. This systematic review may provide reassurance and clinical guidance to cardiologists and hematologists on the feasibility of coronary revascularization in ACS while providing adequate treatment for ITP, and the choice of PCI vs. CABG should be decided depending on the coronary anatomy, severity, and urgency of CAD, baseline platelet count, and patients' concurrent medical conditions and risk factors.

The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.

AR, MY, and DP conceptualized the study. AR and KS did the literature search. AR and AA did the literature screening. KS, MN, AA, and WR extracted the data. AR and KS wrote the first draft of the manuscript. DP, MY, MA-K, MM, MA, and HO edited the manuscript. All authors reviewed the final version of the manuscript. All authors contributed to the article and approved the submitted version.