Acute ST-segment elevation myocardial infarction with EDTA-dependent pseudothrombocytopenia: a case report and literature review

doi:10.21203/rs.3.rs-3418191/v1

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Case Report

Acute ST-segment elevation myocardial infarction with EDTA-dependent pseudothrombocytopenia: a case report and literature review

https://doi.org/10.21203/rs.3.rs-3418191/v1

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Background:Acute ST-segment elevation myocardial infarction (STEMI) has a rapid onset and high mortality which should be diagnosed quickly after admission and given reperfusion treatment as soon as possible. Meanwhile, antiplatelet and anticoagulant therapy play an important role in the treatment of acute myocardial infarction. Pseudothrombocytopenia has been rarely reported. This paper reports a STEMI patient with delayed reperfusion treatment due to EDTA-dependent pseudothrombocytopenia, and provides suggestions on how to identify EDTA-dependent pseudothrombocytopenia, so as to avoid the wrong withdrawal of antiplatelet drugs and the delay of reperfusion treatment in patients with acute myocardial infarction complicated with pseudothrombocytopenia.

Case presentation: An 82-year-old male patient with a medical history of hypertension was admitted to the emergency department (ED) complaining of worsening chest discomfort. ST-segment elevation was noted in the leads V1-V4 and T-wave height tip on the electrocardiogram (ECG) in the ED. The cardiac biomarkers tests at ED revealed that his high-sensitivity troponin level (cTnI) was 0.25ng/L (reference interval:＜0.01ng/mL), and the serum creatine kinase-MB(CK-MB) level was 17.22ng/mL (reference interval:＜5ng/mL), and myoglobin level was 126.02ng/mL (reference interval:＜50ng/mL). Unexpectedly, his initial platelet count with a standard EDTA tube was 18 × 10⁹ /L, and he did not receive reperfusion therapy and any fibrinolytic drug or heparin because of thrombocytopenia. Echocardiogram demonstrated regional hypokinesia of left ventricle. She received bone marrow puncture and platelet antibody examination. Subsequently, platelet clumps were seen in bone marrow blood smears and platelet antibody tests were negative. Blood collection in the heparin tube reveals an accurate platelet count of 166×10⁹/L.However,it was been a week after his admission, he refused the operation and was discharged with the medication after his condition improved.

Conclusions: Thrombocytopenia will bring risks and challenges to the reperfusion treatment of acute ST-segment elevation myocardial infarction. Clinician should be alert to EDTA-dependent pseudothrombocytopenia especially complicated with myocardial infarction. Seeking possible evidence of pseudothrombocytopenia is in favor of early diagnosis which may prevent unnecessary examination as well as over-treatment and especially mismanagement of patients in potentially life-threatening clinical conditions

Acute ST-segment elevation myocardial infarction

Pseudothrombocytopenia (PTCP)

Pseudothrombocytopenia is a phenomenon in which platelet clumps are caused by some reasons, leading to a decrease in the number of platelets detected by an automated analyzer ^[1]. Notably, the factors causing pseudothrombocytopenia are varieties of anticoagulants^[2], cryoagglutinin, drugs^[3], etc. Among these factors, ethylenediaminetetra-acetic acid (EDTA) is widely used as anticoagulant in laboratory medicine, EDTA-dependent pseudothrombocytopenia (EDTA-PTCP) is the most reported. In contrast to serious and potential life-threatening causes of thrombocytopenia^[4], EDTA-PTCP is solely an in vitro effect without any clinical relevance^[5]. Additionally, it is a benign laboratory condition that does not increase bleeding, stroke, transfusion requirements, or the need for repeat revascularization^[3]. However, any delay resulting from this condition may be seriously hazardous in some conditions. For example, a low platelet count may alter the decision of heparin and thrombolytic administration, which is essential to management during acute coronary syndromes^[6].

In this report, we describe a patient with EDTA-PTCP who could not receive reperfusion therapy, anticoagulants, and antiplatelets during acute myocardial infarction because of the low platelet counts reported by an automated analyzer.

An 82-year-old male patient with a medical history of hypertension was admitted to the emergency department (ED) complaining of worsening chest discomfort over the previous 12 hours, which started 3 days ago. The patient was on medical treatment with amlodipine. He denied any history of serious bleeding problems except for the nosebleeds accidentally and has never had a physical examination. In the emergency department (ED), his temperature was 36.5℃, blood pressure was 163/96mmHg, respiratory rate was 20 per minute, heart rate was 66/minute, and his oxygen saturation on pulse oximeter was 100% on room air. ST-segment elevation was noted in the leads V1-V4 and T-wave height tip on the electrocardiogram (ECG) in the ED(Fig. 1a). The cardiac biomarkers tests at ED revealed that his high-sensitivity troponin level (cTnI) was 0.25ng/mL (reference interval:<0.01ng/mL), and the serum creatine kinase-MB(CK-MB) level was 17.22ng/mL (reference interval:<5ng/mL), and myoglobin level was 126.02ng/mL (reference interval:<50ng/mL). Three hundred mg of acetylsalicylic acid (ASA) and 300 mg of clopidogrel were administered in the ED, and there were no findings of petechia or ecchymosis. Furthermore, the patient was hospitalized with the diagnosis of hyperacute ST-segment elevation myocardial infarction. A coronary angiography was planned. However, his initial platelet count with a standard EDTA tube was 18 × 10⁹ /L, and he did not receive reperfusion therapy and any fibrinolytic drug or heparin because of thrombocytopenia. Echocardiogram was performed in the cardiovascular care unit (CCU), showing regional hypokinesia of left ventricle with a reduced ejection fraction (EF) of 39%. Dynamic changes of blood biomarkers and arterial blood platetet results were summarized in Table 1. Dynamic changes of ECG were submitted in Fig. 1.After the hematology consultation, bone marrow aspiration and platelet antibody were recommended as well as platelet transfusion. But platelet counts did not increase significantly after transfusion of two therapeutic doses platelets. Meanwhile, the patient complained of chest tightness again accompanied with ECG dynamic changes(Fig. 1d), which was relieved by nitroglycerin effectively. Subsequently, platelet clumps were seen in bone marrow blood smears(Fig. 2) and platelet antibody tests were negative. Blood collection in the heparin tube was sent for inspection, which reveals an accurate platelet count of 166×10⁹/L. Pseudothrombocytopenia (PTCP) was finally diagnosed, and the patient started receiving heparin, aspirin, and clopidogrel. His chest pain nearly diminished, and the onset of the initial chest pain was more than 48 hours. Thus, he did not receive any fibrinolytic drug treatment and reperfusion therapy. The maintenance treatment consisted of 100 mg ASA, 75 mg clopidogrel, 10 mg rosuvastatin, 11.875 mg metoprolol, 100 mg sacubitril valsartan sodium, 10 mg dapagliflozin, 10mg spironolactone, 10mg furosemide and 40 mg pantoprazole. The patient was advised to accomplish coronary angiography and percutaneous coronary intervention one week following acute myocardial infarction. However, he refused the operation and was discharged with the aforementioned medication after his condition improved.

Anticoagulants and antiplatelets are essential in treating acute coronary syndrome (ACS). Coronary angiography (CAG) is a common diagnostic test to evaluate patients for coronary artery disease (CAD). Normally, patients undergoing angiogram receive antiplatelets and anticoagulants pre-catheterization. However, in thrombocytopenic patients, these treatments are a problem^[7]. Thrombocytopenia is classified as severe when the count is < 50x10⁹/L. Patients with platelet count < 50× 10⁹/L have a high bleeding risk after percutaneous coronary intervention (PCI), and when the platelet count drops to < 30×10⁹/L, antiplatelets and anticoagulants should be stopped^[8]. Other guidelines recommend that avoiding antiplatelet and anticoagulant treatment should be restricted to patients with severe thrombocytopenia (i.e., a platelet count < 25x10⁹/L)^[9–11].

Our patient is an old man with a medical history of hypertension, presenting with similar presentations to ACS. Abnormal ECG changes and elevated cardiac biomarkers in ED led to a diagnosis of ST-elevation MI. Echocardiogram confirmed regional left ventricular wall motion abnormalities, which support the aforementioned diagnosis. Unfortunately, he did not receive reperfusion therapy and any fibrinolytic drug or heparin because that his initial platelet count with a standard EDTA tube was 18 × 10⁹ L − 1. Even more, unnecessary examination as well as over-treatment and especially mismanagement have been adopted.

Ethylenediaminetetra-acetic acid (EDTA) is widely used because of its little influence on various blood cells, but it can occasionally lead to platelet aggregation^[12]. EDTA-dependent pseudothrombocytopenia(EDTA-PTCP)is a laboratory finding defined by in vitro thrombocyte aggregation in blood collected in an ethylenediaminetetraacetic acid (EDTA) collection tube^[13], which occurs due to anti-platelet autoantibodies, usually IgG but also IgM and IgA, recognize platelet antigens on the platelet membrane modified by EDTA^[14], which results in platelet agglutination. Notably, prolonged time intervals between blood draws and assays enhance the occurrence of PTCP^[15]. Therefore, the incidence of EDTA-dependent pseudothrombocytopenia in hospitalized patients is higher than in outpatients and emergency patients^[5]. This phenomenon is more common in critically ill patients, related to autoimmune diseases, tumors, atherosclerosis-related diseases, and liver diseases^[16–18].

PTCP is seen in 0.1% -2% of hospitalized patients^[19]. This proportion is much higher in patients with isolated thrombocytopenia^[20]. More importantly, EDTA-PTCP has been reported in only a few cases. Herein, we only retrospectively reviewed two available case reports of patients with AMI and PTCP^{[11, 21]}. Therefore, it is easy for clinicians to overlook the signs of EDTA-PTCP, resulting in excessive examination and unnecessary platelet transfusions and likely increasing the risk of thrombosis and leading to adverse events. Awareness of such a phenomenon may result in rapid and prompt diagnosis and prevent patient mismanagement in acute myocardial infarction^[21].

Examination of the peripheral blood smears, widely regarded as the gold standard for detecting EDTA-PTCP, should be applied^[22]. Additionally, alternative anticoagulants to EDTA should be reconsidered in samples with clear evidence of PTCP. Usually, blood collection in citrate and heparin tubes will prevent EDTA-induced platelet clumping and reveal an accurate platelet count^[23]. But, occasionally, it is even more complex when occurring with multi-anticoagulants PTCP^[24].

In conclusion, this case illustrates that a low platelet count may occasionally result from a laboratory error. When an automated platelet count falls complicated with myocardial infarction, the principal considerations are thrombocytopenia or pseudothrombocytopenia and heparin-induced thrombocytopenia. Patients with low platelet count who have never had a physical examination and deny any notable bleeding problems in their medical history should be noticed. Thus, other than EDTA, some novel methods must be used to clear the blood counts. Awareness of such a phenomenon may prevent unnecessary examination as well as over-treatment and especially mismanagement of patients in potentially life-threatening clinical conditions

Acknowledgments

The authors thank AiMi Academic Services (www.aimieditor.com) for English language editing and review services.

Ethics approval and consent to participate

Not applicable. Study approval was not necessary as this is a case report andconsent for publication was taken from the patients.

Consent for publication

Written informed consent was obtained from the patient for the publicationof this case report. A copy of the written consent is available for review by

the Editor-in-Chief of this journal.

Availability of data and materials

All data generated or analysed during this study are included in this manuscript and its Additional files

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Table 1 is available in the Supplementary Files section.

No competing interests reported.

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Acute ST-segment elevation myocardial infarction with EDTA-dependent pseudothrombocytopenia: a case report and literature review

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