Case Report Blood Purif DOI: 10.1159/000510554

Received: April 17, 2020 Accepted: July 28, 2020 Published online: September 30, 2020

Early Selective C-Reactive Protein Apheresis in a Patient with Acute ST Segment Elevation Myocardial Reinfarction Maja Milosevic a Bela Balint a, b Srdjan Boskovic a, c Milovan Bojic a Aleksandra Nikolic a, c Petar Otasevic a, c  

 

 

 

 

 

aDedinje

Cardiovascular Institute, Belgrade, Serbia; bDepartment of Medical Sciences, Serbian Academy of Sciences and Arts, Belgrade, Serbia; cBelgrade University School of Medicine, Belgrade, Serbia

Abstract The patient was admitted for urgent coronary angiography following an acute anterior ST segment elevation myocardial reinfarction (STEMI) caused by acute stent thrombosis. A stent had been implanted 10 days prior to the reinfarction for an acute anterior STEMI. However, the patient had stopped taking ticagrelor post-discharge. Primary percutaneous coronary intervention of the left anterior descending artery was performed. Subsequently, due to a high C-reactive protein (CRP) level, 3 CRP apheresis sessions were performed, with the first session starting 12 h after the onset of symptoms. A significant drop in CRP was noted after each apheresis. The post-procedural course was uneventful. © 2020 S. Karger AG, Basel

Introduction

C-reactive protein (CRP) is the classical acute-phase protein that mediates secondary damage of the myocardial cells during acute myocardial infarction by activating [email protected] www.karger.com/bpu

© 2020 S. Karger AG, Basel

the complement system and opsonizing biological particles for macrophages [1, 2]. It has been shown that elevated CRP levels correlate with poor outcome after ST segment elevation myocardial infarction (STEMI) [3, 4]; therefore, lately, therapeutic CRP apheresis has been extensively studied [5–7]. It has been shown that CRP apheresis reduces not only CRP levels but also levels of other plasma proteins, such as γ-globulin and fibrinogen [6]. However, whether performing therapeutic CRP apheresis immediately after STEMI has any long-term beneficial effects remains unclear. Case Report

A 54-year-old male with typical cardiac chest pain occurring two and a half hours before admission and with ECG signs of anterior STEMI was admitted for urgent coronary angiography. The patient’s history revealed that 10 days prior to admission he had suffered an acute anterior STEMI treated by primary percutaneous coronary intervention of the left anterior descending artery (LAD) with stent implantation. It was discovered that he had stopped taking ticagrelor following discharge. Coronary angiography revealed in-stent occlusion of the proximal LAD, and successful thromboaspiration and balloon angioplasty of the LAD were performed. FolPetar Otasevic Department of Cardiology, Dedinje Cardiovascular Institute Milana Tepica 1 Belgrade 11000 (Serbia) potasevic @ yahoo.com

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Keywords Apheresis · C-reactive protein · Cardiovascular disease · Post-procedural course · ST segment elevation myocardial reinfarction

■ Before apheresis ■ After apheresis

50

30

43.7

20

0

after apheresis. PCI, percutaneous coronary intervention; CRP, C-reactive protein.

lowing the procedure, the patient was hemodynamically stable. After obtaining informed consent, early CRP apheresis was performed consisting of 3 sessions starting 12, 24, and 48 h after the onset of symptoms. These procedures were performed according to the study protocol, which was approved by the hospital committee on human research. The study will include approximately thirty subjects to test the feasibility, efficacy, and safety of early CRP apheresis following acute myocardial infarction. During 3 consecutive days, therapeutic plasma exchange procedures by the Spectra Optia centrifugal device (Terumo-BCT, Lakewood, CO, USA) were performed for plasma separation. Additionally, the ADAsorb secondary device with the PentraSorb CRP “regenerative adsorber” was used for CRP depletion from separated/treated plasma, and the treated plasma (total 18,000 mL) was replaced by an equal volume of CRP-depleted autologous plasma [8]. Blood was anticoagulated by Acid-Citrate-Dextrose formula A solution (ACD-A; USP; with 2.2% citrate concentration), ratio = 1:12. The selective therapeutic plasma exchange duration and volume of processed blood (single treatment) were 270 ± 12 min and 15,050 ± 218 mL, respectively. The volume of treated plasma was up to 6,000 mL in all procedures. No adverse events were noted. Plasma CRP apheresis resulted in a significant drop in CRP values as shown in Figure 1. As previously mentioned, CRP apheresis also has the effect of reducing immunoglobulin and fibrinogen plas2

Blood Purif DOI: 10.1159/000510554

31.8%

64.1

57.6

23.5

10

Fig. 1. Absolute and relative CRP reduction

58.0%

59.2%

40

24

12

29.8

26.9

Time after PCI, h

48

ma levels. However, our article focused only on reduction of CRP levels. We plan to include these other parameters in future research. Discussion

Our study shows that early apheresis reduces CRP values up to 59.2%, which is similar to the CAMI-1 trial, in addition to the study by Ries et al. [5, 6]. As shown, CRP reduction following the third CRP apheresis was lower despite the same “apheresis parameters” being used. We speculate that it is possible due to “alteration” in CRP synthesis kinetics/ dynamics and/or inferior adsorber regeneration efficacy. Increase in CRP concentration starts about 6–12 h after the onset of ischemia and peaks within 48 h. Therefore, it may express its maximum damaging effect early in the course of the disease [7]. Consequently, it has been suggested that CRP levels should be decreased as early as possible [7]. This is the reasoning behind the first CRP apheresis being performed in our patient only 12 h after the onset of symptoms. Comparatively, the average time of CRP apheresis in the CAMI-1 trial was 24 h after the onset of symptoms [5]. The CAMI-1 study also excluded patients with previous STEMI [5]. In conclusion, early CRP apheresis is feasible in patients with acute myocardial reinfarction and could lead to significant CRP reduction with no adverse events. Whether this may translate to a mitigated inflammatory response and therefore a reduction in infarction size needs further investigation. Milosevic/Balint/Boskovic/Bojic/Nikolic/ Otasevic

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CRP concentration, mg/L

60

Color version available online

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Funding Sources

Statement of Ethics The study protocol was approved by the institute’s committee on human research. Written informed consent for performing CRP apheresis and publication of data and images in the form of a case report was obtained from the patient.

Conflict of Interest Statement Maja Milosevic, Bela Balint, Milovan Bojic, and Aleksandra Nikolic have no disclosures. Srdjan Boskovic served as a consultant and received honoraria from Astra Zeneca, Novartis, and SanofiAventis. Petar Otasevic served as a consultant and received honoraria from Astra Zeneca, Bayer, Merck, Novartis, and SanofiAventis. The authors have no conflicts of interest to declare.

No funding to declare.

Author Contributions Maja Milosevic wrote the paper and analyzed the clinical details. Bela Balint wrote the paragraph on plasma apheresis, collected laboratory data, and critically reviewed the manuscript. Srdjan Boskovic designed the protocol and wrote the paragraph on percutaneous coronary intervention. Milovan Bojic critically reviewed the manuscript. Aleksandra Nikolic critically reviewed the manuscript. Petar Otasevic designed the protocol and critically reviewed the manuscript.

References

Early Selective C-Reactive Protein Apheresis

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Blood Purif DOI: 10.1159/000510554

  6 Ries W, Heigl F, Garlichs C, Sheriff A, Torzewski J. Selective C-reactive protein-apheresis in patients. Ther Apher Dial. 2019 Dec;23(6): 570–4.   7 Sheriff A, Schindler R, Vogt B, Abdel-Aty H, Unger JK, Bock C, et al. Selective apheresis of C-reactive protein: a new therapeutic option in myocardial infarction. J Clin Apher. 2015 Feb;30(1):15–21.   8 Boljevic D, Nikolic А, Rusovic С, Lakcevic Ј, Bojic М, Balint B. A promising innovative treatment for ST-elevation myocardial infarction: the use of C-reactive protein selective apheresis: case report. Blood Purif. 2020 Feb: 1–5.

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  1 Volanakis JE, Kaplan MH. Interaction of Creactive protein complexes with the complement system. II. Consumption of guinea pig complement by CRP complexes: requirement for human C1q. J Immunol. 1974 Jul; 113(1): 9–17.   2 Mortensen RF, Duszkiewicz JA. Mediation of CRP-dependent phagocytosis through mouse macrophage Fc-receptors. J Immunol. 1977 Nov;119(5):1611–6.   3 Seropian IM, Toldo S, Van Tassell BW, Abbate A. Anti-inflammatory strategies for ventricular remodeling following ST-segment elevation acute myocardial infarction. J Am Coll Cardiol. 2014 Apr;63(16):1593–603.