Phospholipase A(2) activates hemostasis
1Department of Clinical Chemistry, University Hospital Giessen & Marburg, Germany.
Drug Target Insights
|September 9, 2011
Summary
Phospholipases A(2) (PLA(2)) enzymes activate blood coagulation, leading to pathological disseminated intravascular coagulation (PDIC). Early diagnosis by screening patients for plasmatic thrombin activity is crucial for life-threatening conditions.
Area of Science:
- Biochemistry
- Hematology
- Enzymology
Background:
- Phospholipases A(2) (PLA(2)) are enzymes that degrade cell membrane phospholipids.
- PLA(2) activity can initiate the kallikrein-mediated contact phase of coagulation.
- Elevated PLA(2) levels are observed in conditions like trauma, pancreatitis, and sepsis.
Purpose of the Study:
- To investigate the effect of PLA(2) on thrombin generation in human blood.
- To quantify thrombin generation in recalcified plasma after exposure to PLA(2).
Main Methods:
- Citrated whole blood was incubated with bovine pancreatic or snake PLA(2), LPS, or zymosan A.
- Plasma was recalcified and thrombin generation was measured using a chromogenic assay.
- Arginine was used to stop the coagulation reaction and depolymerize fibrin.
Main Results:
- PLA(2) induced dose-dependent thrombin generation, comparable to LPS and zymosan A.
- Thrombin generation was proportional to PLA(2) concentration up to 60 ng/ml.
- High PLA(2) concentrations (10 μg/ml) also induced significant thrombin generation, unlike in control plasma.
Conclusions:
- Elevated plasmatic PLA(2) activates the hemostasis system, potentially causing pathological disseminated intravascular coagulation (PDIC).
- Screening for plasmatic thrombin activity is recommended for early diagnosis of these critical conditions.
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