SCIENTIFIC LETTER

Dual antiplatelet therapy is a key element in the pharmacological treatment of coronary heart disease. It consists in the combination of aspirin (ASA) and a P2Y12 platelet inhibitor. This therapy reduces is­chemic and stent thrombosis risk, but on the other hand, it increases bleeding risk. The combination of drugs and treatment duration is still today under constant debate. Scores such as the PRECISE DAPT score, the PARIS risk score, or the DAPT score are tools that are used in medical practice as a guide for decision making, although they do not include platelet count. On the other hand, the ARC-HBR (Academic Research Consortium for High Bleeding Risk) score includes as a criterion moderate to severe thrombocy­topenia (platelet count less than 100 000/mm3), which implies a risk of bleeding greater than or equal to 4% in 1 year, and that can sometimes be the greatest limi­tation of dual antiplatelet therapy. Patients with se­vere thrombocytopenia are usually excluded from the research studies giving origin to these scores, so deci­sions in this regard are subject to the experience of the treating medical team.

We present the case of a 52-year-old male patient, with a diagnosis of acute lymphocytic leukemia (ALL) associated with synchronous clear cell renal carcino­ma and a history of acute myocardial infarction (AMI) in 2016, which required angioplasty with a bare metal stent (BMS) in the right coronary artery (RCA). He had an ongoing hospitalization for severe pancytope­nia due to his oncohematological disease. Admission laboratory tests revealed hematocrit 22%, hemo­globin 7.9 g/dL, platelet count 25 000/mm3, leukocytes 1190/mm3, and unremarkable results for the remain­ing tests. He was asymptomatic for angina or anginal equivalents with an electrocardiogram (ECG) without pathological findings.

Prior to targeted treatment, a myocardial perfu­sion test with pharmacological stress was requested.

 At a dose of 30 mcg/kg/min of dobutamine, severe and extensive ischemia was evident in the middle and api­cal anterior, basal, and middle anteroseptal, basal and middle inferoseptal and inferoapical segments, com­patible with the territory of the left anterior descend­ing (LAD) artery. Results showed summed stress score (SSS) 28, summed rest score (SRS) 4, and summed differential score (SDS) 24, with dilation of the left ventricle (LV), radiotracer uptake in the right ventri­cle (RV) and drop in left ventricular ejection fraction (LVEF) after stress (45% to 32%).

A coronary angiography (CA) was performed with prior platelet infusion, which revealed LAD artery subocclusion and severe in-stent restenosis of the RCA. The case was discussed in an interdisciplinary meeting with Hematology given the high ischemic risk that would have prevented him from receiving onco-specific treatment, as well as facing its eventual complications (infectious, hemorrhagic, among oth­ers). As a consequence, revascularization was decid­ed. Percutaneous transluminal coronary angioplasty (PTCA) was performed with insertion of a BMS in the LAD artery, without subsequent antiplatelet therapy given the very high hemorrhagic risk. The patient developed infectious and oncological complications, so he was transferred to the general ward. On the seventh day after stent placement and with 44 000 platelets/mm3, ASA treatment at a dose of 100 mg per day was initiated. The rest of the hospitalization pro­gressed without cardiovascular events, and without bleeding episodes up to discharge 26 days after admis­sion. Five months after hospitalization, he continues antiplatelet therapy only with ASA, without present­ing any intercurrences.

The case presented here raises a controversy that exceeds the guidelines present in the literature. Platelets in myelodysplastic syndromes often have abnormal concentrations or are dysfunctional, withhigh bleeding risk, even with platelet values over 100 000/mm3. As in other hematological processes, (1) there are no recommendations on antiplatelet treat­ment for patients with severe thrombocytopenia due to myelodysplastic syndrome, who suffer an acute cor­onary syndrome or stable coronary disease.

In this type of patients, an angiographic study should be considered as a first measure since this pro­cedure already presents a great challenge. The Euro­pean cardio-oncology guideline is clear on preventive measures to reduce the risk of bleeding including, among other, platelet transfusion if they are below 20 000/mm3, radial access, careful hemostasis, and low doses of heparin, between 30-50 IU/kg, (2) all actions that were carried out in our patient.

Regarding double antiplatelet therapy, expert agree­ments suggest starting it with platelet values above 30 000/mm3, as well as opting for a type of stent that al­lows shortening its duration. (3) The European cardio-oncology guideline recommends using aspirin starting at 10 000 platelets/mm3, and clopidogrel at 30 000 platelets/mm3 (there are experts who recommend cut-off values of 30 000 and 50 000 platelets/mm3, respective­ly). (2) Our patient had less than 30 000 platelets/mm3. In this sense, we have not found any similar reported case of severe thrombocytopenia.

The greatest evidence regarding thrombocyto­penia and antiplatelet scenarios is provided by con­tradictory opinion articles. On the one hand, in pa­tients with chronic coronary syndrome (CCS), they suggest stopping antiplatelet therapy and avoiding angioplasty if there is a platelet count of less than 50 000/mm3. This consideration was considered in the discussion regarding our patient, but it could not be respected. (4) In patients with platelets be­tween 50 000 and 100 000/mm3, monotherapy with clopidogrel and proton pump inhibitor (PPI) is sug­gested, based on randomized studies, which mostly used second-generation drug-eluting stents (DES). Finally, in patients with CCS, symptomatic despite triple antianginal therapy, PTCA is reasonable when evaluating the risk-benefit ratio. If carried out, the suggestion is second-generation DES rather than BMS, and subsequent double antiplatelet therapy with ASA and clopidogrel for one month, and then continuing with clopidogrel as monotherapy, associ­ated with PPI. The indication for second-generation DES arises from the evidence that demonstrates a lower rate of early stent thrombosis compared with BMS, considering dual antiplatelet therapy with the usual recommendations (duration and composition), a situation that is far from the scenario presented in our case, and that, in fact, would not be advisable to follow given the high ischemic risk that would arise if one did not comply with conventional treatment. (4)

On this issue, evidence has shown that DES reduc­es early restenosis and ischemia associated with the index lesion, when compared with BMS, but has failedto demonstrate superiority with respect to late throm­bosis. (5,6) Therefore, BMS are reserved for patients who cannot receive double antiplatelet therapy for more than a month given the risk of bleeding, (6) and, as in our patient, in scenarios in which the standard double antiplatelet therapy cannot be administered. This type of stent presents the challenge of the risk of thrombosis during the first month, but once this period is over, the risk of late thrombosis would be re­duced and thus the need for dual antiplatelet therapy, making simple antiplatelet treatment a more reason­able goal in these cases.

In conclusion, the evidence is scarce and divergent, so we sustain that the behavior to be adopted should be individualized, and of multidisciplinary decision, until more studies are developed.

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