Blood clots can lead to life-threatening illnesses such as strokes, heart attacks or pulmonary embolisms. Until now, immune cells such as neutrophils and monocytes were primarily considered to be contributory causes of such thromboses. However, the new study shows that these cells can also play a healing role - provided they are in the right ‘mood’.
A look inside the clot - for the first time with precise and comprehensive resolution at single cell level
For their investigations, the researchers used thrombi that were removed from stroke patients as part of a mechanical thrombectomy. This procedure for reopening occluded brain vessels enabled rare access to fresh thrombus material during the acute phase of the disease. In addition, blood samples from the same patients were analysed to compare the immune cell composition in the thrombus with that in the blood.
Thrombi can form in all vascular areas of the body. The researchers chose cerebral arteries for this study because they are easily accessible in everyday clinical practice and the material taken can be standardised and processed gently - an important factor in being able to reliably examine sensitive cell types such as neutrophils.
Using state-of-the-art single-cell technologies such as single-cell RNA sequencing and CITE-seq, the immune cells involved could be characterised with unprecedented resolution. In addition, mouse models and in-vitro experiments were used to functionally confirm the observed mechanisms.
The discovery: Immune cells help to dissolve thrombi
The researchers discovered that certain monocytes - so-called non-classical monocytes - attract neutrophils, which in the low-oxygen environment of the thrombus convert into a form that produces blood clot-dissolving enzymes, in particular the urokinase receptor (PLAUR). The authors call this process ‘immunothrombolysis’.
‘Our results show that immune cells not only cause damage, but can also help to dissolve thrombi again,’ says Dr Kami Pekayvaz, first author of the study and Clinician Scientist at the Medical Clinic I of the LMU Klinikum. ‘This finding opens up completely new therapeutic possibilities.’
New approaches in thrombosis treatment
What is particularly interesting is that if a certain signalling pathway in the neutrophils is artificially activated - the so-called HIF1a signalling pathway - the cells develop increased thrombus-dissolving properties. When the mechanism was blocked, the thrombi dissolved significantly less easily in affected mice.
‘Although current drugs for thrombolysis work quickly, they increase the risk of dangerous bleeding,’ explains Prof Konstantin Stark, last author of the study and Senior Consultant at the LMU Medical Centre's Department of Medicine I. ‘If it is possible to control the body's own immune defence in a targeted manner so that it dissolves thrombi, this could be a gentler form of treatment.’
A new image of the blood clot
The study provides a highly detailed map of immune cell activity in the thrombus - both in humans and in animal models. It shows that thrombi can change dynamically after their formation and that immunologically driven healing processes also take place. In the long term, the findings could help to develop new therapies for the treatment of thrombosis that avoid dangerous bleeding side effects.
Contact:
Dr. Kami Pekayvaz, Medical Clinic I, LMU Hospital Munich, kami.pekayvaz[at]med.uni-muenchen.de
Prof. Dr. Konstantin Stark, Medical Clinic I, LMU Hospital Munich, konstantin.stark[at]med.uni-muenchen.de
Publication:
Pekayvaz K. et al., Immunothrombolytic monocyte-neutrophil axes dominate the single-cell landscape of human thrombosis and correlate with thrombus resolution. Immunity, May 2025
