Histopathologically TMA-like distribution of multiple organ thromboses following the initial dose of the BNT162b2 mRNA vaccine (Comirnaty, Pfizer/BioNTech): an autopsy case report

Abstract

Background: Coronavirus disease 2019 (COVID-19) has spread worldwide. Vaccination is now recommended as one of the effective countermeasures to control the pandemic or prevent the worsening of symptoms. However, its adverse effects have been attracting attention. Here, we report an autopsy case of multiple thromboses after receiving the first dose of the BNT162b2 mRNA vaccine (Comirnaty, Pfizer/BioNTech) in an elderly woman.

Case presentation: A 72-year-old woman with a history of diffuse large B-cell lymphoma in the stomach and hyperthyroidism received the first dose of the BNT162b2 mRNA vaccine and died 2 days later. The autopsy revealed multiple microthrombi in the heart, brain, liver, kidneys, and adrenal glands. The thrombi were CD61 and CD42b positive and were located in the blood vessels primarily in the pericardial aspect of the myocardium and subcapsular region of the adrenal glands; their diameters were approximately 5-40 μm. Macroscopically, a characteristic myocardial haemorrhage was observed, and the histopathology of the characteristic thrombus distribution, which differed from that of haemolytic uraemic syndrome and disseminated intravascular coagulation, suggested that the underlying pathophysiology may have been similar to that of thrombotic microangiopathy (TMA).

Conclusion: This is the first report on a post-mortem case of multiple thromboses after the BNT162b2 mRNA vaccine. The component thrombus and characteristic distribution of the thrombi were similar to those of TMA, which differs completely from haemolytic uraemic syndrome or disseminated intravascular coagulation, after vaccination. Although rare, it is important to consider that fatal adverse reactions may occur after vaccination and that it is vital to conduct careful follow-up.

Keywords: BNT162b2; Coronavirus disease 2019; SARS-CoV-2; Thrombosis; Thrombotic microangiopathy; Vaccination.

Fig. 1

Macroscopic and microscopic findings of the heart. a: Macroscopic haemorrhage in the posterior pericardium in situ at the autopsy. b: Gross findings of the heart after fixation. The cut surface of the heart after fixation shows black-red discoloration (arrowhead) in the entire circumference of the pericardium and pericardium-side myocardium. c: Scanning magnifications of the heart with haematoxylin-eosin (HE) staining. d: Schematic illustration of the microscopic pathology. The red dots indicate the microscopic haemorrhage, the blue rectangle indicates the thrombus, and the green arc indicates the contraction band necrosis. LV; left ventricle, IVS; interventricular septum, RV; right ventricle. e and f: Low- and high-power views of the haemorrhage in the cardiomyocytes. The haemorrhages were found in the pericardium and pericardium-side myocardium, which is compatible with the discolouration in macroscopic observation. Scale bars indicate 100 μm (e, f)

Fig. 2

Immunohistochemistry of microthrombi in the heart. Microvascular hyaline thrombus stained with a: HE staining. b: anti-CD42b. c: anti-CD61. d: anti-vWF. e: Periodic acid Schiff staining. f: Phosphotungstic acid haematoxylin staining. Scale bars indicate 50 μm (a-f)