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Updated: Mar 28, 2026
Procoagulant Platelet Characterization by Measuring Phosphatidylserine Exposure and Microvesicle Release from Human Purified Platelets
Published on: November 29, 2024
Increased phosphatidylserine-exposing microparticles and their originating cells are associated with the coagulation
Zhangxiu He1, Yan Zhang2, Muhua Cao2
1Department of Nephropathy and Hemodialysis, First Hospital, Harbin Medical University, Harbin, China.
Background:
Relatively little information is available about phosphatidylserine positive (PS(+)) microparticles (MPs) and their originating cells in IgA nephropathy (IgAN) despite well-established intraglomerular coagulation. Our objectives were to detect PS exposure on MP membranes and MP-origin cells and to evaluate its role in procoagulant activity (PCA) and fibrin formation and their association with pathological lesions in the disease.
Methods:
Patients with IgAN and healthy controls were studied. Lactadherin was used to quantify PS exposure on MPs and MP-origin cells. PCA of MPs and MP-origin cells was evaluated by clotting time and purified coagulation complex assays. Fibrin production was determined by turbidity. PS exposure, fibrin strands and FVa/Xa binding were observed on MPs/cells using confocal microscopy.
Results:
Using flow cytometry, we found that IgAN patients had high levels of PS(+) MPs derived from lymphocytes, monocytes, neutrophils, platelets, erythrocytes and endothelial cells (ECs). The PS exposure on MP-origin cells also increased in these patients. MPs and MP-origin cells (leukocytes, platelets and erythrocytes) isolated from IgAN patients and ECs cultured with IgAN serum had a significantly shorter median coagulation time (P < 0.001), higher median intrinsic FXa (P < 0.001) and higher thrombin (P < 0.001) generation than controls. These coagulation functional assays were associated with the glomerular lesions. The lesions were also correlated with glomerular fibrin deposition (all P < 0.05). In the presence of patient MPs or their related cells, fibrin formation peaked faster with a higher maximum turbidity when compared with healthy controls. Blocking PS with lactadherin in the IgAN group prolonged coagulation time to control levels, inhibited the PCA up to 80% and markedly reduced fibrin formation. More importantly, we observed that fibrin strands formed on MPs and ECs in the same regions that bound lactadherin, similar to the FVa/Xa costaining.
Conclusions:
We find that high levels of PS(+) MPs and the MP-origin cells are associated with the coagulation process in IgAN, and this may provide a previously unrecognized contribution to intraglomerular coagulation.
Insights
High levels of phosphatidylserine positive (PS(+)) microparticles (MPs) and their originating cells are linked to coagulation in IgA nephropathy (IgAN). This discovery offers new insights into intraglomerular coagulation in IgAN patients.
Area of Science:
- Nephrology
- Hematology
- Immunology
Background:
- IgA nephropathy (IgAN) is associated with intraglomerular coagulation, but the role of phosphatidylserine positive (PS(+)) microparticles (MPs) and their originating cells remains unclear.
- Limited information exists regarding PS exposure on MP membranes and MP-origin cells in IgAN.
Purpose of the Study:
- To detect PS exposure on MP membranes and MP-origin cells in IgAN patients.
- To evaluate the role of PS exposure in procoagulant activity (PCA) and fibrin formation.
- To assess the association between PS exposure, PCA, fibrin formation, and pathological lesions in IgAN.
Main Methods:
- Quantified PS exposure on MPs and MP-origin cells using lactadherin.
- Assessed PCA via clotting time and coagulation complex assays.
- Measured fibrin production using turbidity and observed PS exposure, fibrin strands, and FVa/Xa binding via confocal microscopy.
Main Results:
- IgAN patients exhibited elevated PS(+) MPs from various cell types (lymphocytes, monocytes, neutrophils, platelets, erythrocytes, endothelial cells) and increased PS exposure on MP-origin cells.
- MPs and MP-origin cells from IgAN patients demonstrated significantly enhanced procoagulant activity and thrombin generation compared to controls.
- Blocking PS with lactadherin normalized coagulation time, inhibited PCA, and reduced fibrin formation, indicating PS's critical role.
Conclusions:
- Elevated PS(+) MPs and their originating cells are significantly associated with the coagulation process in IgAN.
- This association suggests a novel contribution of PS(+) MPs and related cells to intraglomerular coagulation in IgAN.
- Targeting PS exposure may offer a therapeutic strategy for managing coagulation abnormalities in IgAN.
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