Author + information
- Yasumi Uchida, MD⁎ (, )
- Yasuto Uchida, MD,
- Takeshi Sakurai, MD,
- Masahito Kanai, MD,
- Seiichiro Shirai, MD,
- Toshihiro Morita, MD,
- Yuko Maezawa, MD and
- Yoshiro Maezawa, MD
- ↵⁎Japan Foundation for Cardiovascular Research, 2-30-17, Narashinodai, Funabashi, 274-0063 Japan
The exact role of fibrin, which is transparent and almost invisible, in coronary thrombus formation and accordingly in the genesis of acute coronary syndrome (ACS) remains unknown. This is because there are no clinically available methods with which to visualize fibrin.
If fibrin can be visualized in vivo, its roles in the initiation and growth of coronary thrombus, and accordingly, in the mechanisms of ACS can be objectively evaluated.
The authors developed a dye-staining angioscopic method that enables visualization of fibrin in vivo (1). The present dye-staining angioscopic study was therefore performed to visualize fibrin in the coronary artery and to examine the roles of fibrin in the genesis of ACS.
From April 1, 1999, to March 31, 2008, 111 successive patients with ACS (37 women and 74 men; age 61.0 ± 4.0 years; 27 with unstable angina (UA), 23 with non–ST-segment elevation myocardial infarction [NSTEMI], and 61 with ST-segment elevation myocardial infarction) underwent conventional coronary angioscopy followed by dye-staining coronary angioscopy at Toho University Sakura Hospital and Funabashi-Futawa Hospital after obtaining approval of the Institutional Review Boards and informed consent from the patients.
After observation by angiography and conventional angioscopy, 1 ml of 2.5% Evans blue dye (EB), which stains fibrin blue but not blood corpuscles (1), was injected into the artery through the flush channel of the angioscope to stain the thrombus, and then the thrombus was observed. Next, the angioscope was advanced distally to observe the changes behind the thrombus. Subsequently, the angioscope was repositioned by an aspiration catheter to aspirate the thrombus. The details are described elsewhere (1). The aspirated thrombus was stained by phosphotungstic acid hematoxylin stain for fibrin staining and by von Willebrand factor immunostain for platelet staining.
In 8 of 111 patients (5 with UA and 3 with NSTEMI), the thrombus was not observed, and a large residual lumen was observed by conventional angioscopy in the angiographic obstructed culprit coronary segment. The residual lumen was stained blue with EB, indicating that the residual lumen was occupied by a transparent fibrin thrombus. No other thrombi were detectable behind the thrombus.
The aspirated thrombus was transparent, jelly-like, and light blue due to previous EB staining. Microscopic examination revealed that the thrombus was composed of a loose fibrin network without platelets or other blood corpuscles (Fig. 1).
It is generally considered that fibrin networks trap blood corpuscles to form a thrombus. The findings in this study indicate that fibrin does not necessarily bind to the blood corpuscles and that it can form a globular thrombus and obstruct the coronary lumen, leading to ACS. Such a phenomenon has not been described previously.
The possible mechanisms for this fibrin thrombus formation are as follows: 1) very early stage of thrombus formation in which fibrin was formed but platelets were not activated to attach to the fibrin (2); and 2) a specific type of fibrin that had no affinity to platelets or other blood corpuscles was formed. Although the reason why this type of thrombus was confined to UA + NSTEMI patients remains unclear, such a thrombus may, however, be a determinant mechanism of UA + NSTEMI.
- American College of Cardiology Foundation