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Increased platelet aggregation due to plasma-aggregating activity. Identification of the responsible factors
Abstract:
Platelet-poor plasmas (PPPs) from 52 out of 71 patients affected by different diseases and selected for increased amounts of circulating platelet aggregates, incubated at 37 degrees C for 30 min with control platelet-rich plasma (PRP; cross-matching test) induced the formation of platelet aggregates, stimulated the production of malondialdehyde and enhanced ADP-induced aggregation. 31 control PPPs were consistently negative at cross-matching test. Gel chromatography of plasmas on agarose 4% allowed the identification of four different fractions (A, B, C, D) provided with aggregating activity. Fraction A eluted at the void volume was to be identified with the von Willebrand factor, whereas B, C and D fractions, eluted at the same elution volumes as activated factor X were mainly composed of factor X (fraction B) and activated factor X (fractions C and D). Thrombin activity was absent in all the fractions provided with aggregating activity. Also, from control PPPs negative at cross-matching tests, the same fractions could be obtained, although of 5--10 times lower aggregating potency, thus explaining the negative cross-matching tests. These findings stress the role of some extraplatelet factors related to hypercoagulability in platelet hyperaggregability.
Insights
Patient plasma with platelet aggregates can trigger platelet aggregation and related responses. These effects are linked to specific plasma fractions, suggesting a role for hypercoagulability in platelet hyperaggregability.
Area of Science:
- Hematology
- Biochemistry
- Pathophysiology
Background:
- Platelet hyperaggregability is a concern in various diseases.
- Circulating platelet aggregates in patient plasma may indicate underlying issues.
Purpose of the Study:
- To investigate the role of plasma factors in platelet hyperaggregability.
- To identify specific plasma components responsible for inducing platelet aggregation.
Main Methods:
- Cross-matching tests using patient platelet-poor plasma (PPP) and control platelet-rich plasma (PRP).
- Incubation of plasma at 37°C and assessment of platelet aggregation, malondialdehyde production, and ADP-induced aggregation.
- Gel chromatography on agarose 4% to isolate and characterize plasma fractions.
Main Results:
- Patient PPPs induced platelet aggregation, malondialdehyde production, and enhanced ADP-induced aggregation in control PRP.
- Gel chromatography identified four fractions (A, B, C, D) with aggregating activity.
- Fraction A contained von Willebrand factor; fractions B, C, and D contained factor X and activated factor X. Thrombin activity was absent.
- Control PPPs showed similar fractions but with significantly lower potency.
Conclusions:
- Extraplatelet factors associated with hypercoagulability play a significant role in platelet hyperaggregability.
- Specific plasma fractions, including von Willebrand factor and activated factor X, contribute to platelet activation.
- These findings highlight the link between coagulation system abnormalities and platelet function disorders.