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Thrombin generation capacity of prothrombin complex concentrate in an in vitro dilutional model
Oliver Grottke1, Rolf Rossaint, Yvonne Henskens
1Department of Anesthesiology, RWTH Aachen University Hospital, Aachen, Germany.
Insights
Prothrombin complex concentrates (PCCs) vary in composition, impacting their effectiveness in treating trauma-induced coagulopathy. Low-heparin PCCs restore blood clotting, while heparin-containing PCCs have anticoagulant effects, necessitating further clinical investigation.
Area of Science:
- Hematology
- Pharmacology
- Critical Care Medicine
Background:
- Prothrombin complex concentrates (PCCs) are used for trauma-induced coagulopathy but may increase risks like thromboembolism due to imbalanced pro- and anticoagulants.
- PCC compositions vary significantly between manufacturers, necessitating a detailed assessment of their hemostatic effects.
Purpose of the Study:
- To evaluate the procoagulant potential and thrombin generation of five different PCCs using an in vitro dilutional model.
- To compare the effects of varying heparin and antithrombin levels in PCCs on blood coagulation parameters.
Main Methods:
- Assessed vitamin K-dependent factors, heparin, and antithrombin in five commercial PCCs.
- Used classical coagulation assays, thrombin generation assay, and thromboelastometry on diluted whole blood (20-80%) from healthy donors.
- Investigated PCC effects on prothrombin time (PT), activated partial thromboplastin time (aPTT), and Ex-tem thromboelastometry.
Main Results:
- PCCs showed similar levels of clotting factors but widely different heparin and antithrombin concentrations.
- In vitro blood dilution prolonged PT/aPTT and reduced thrombin generation and clot strength.
- PCCs with low or no heparin normalized clotting in diluted blood, while heparin-containing PCCs exhibited anticoagulant effects.
- Thrombin generation assay proved most sensitive for assessing PCC effects.
Conclusions:
- Most commercially available PCCs exhibit an imbalance between procoagulant and anticoagulant components.
- Differences in thrombin generation among PCCs warrant further investigation to understand their clinical significance in managing trauma-induced coagulopathy.
Background:
The use of PCC for the treatment of trauma-induced coagulopathy potentially increase the risk of thromboembolism and disseminated intravascular coagulation, which is addressed to an imbalance of both pro- and anticoagulants. As PCCs differ in composition, we used an in vitro dilutional approach to assess the overall thrombin generation of five different PCCs through various laboratory assays.
Methods:
The vitamin K-dependent coagulation factors, heparin, and antithrombin were assessed in five commercially available PCCs. The procoagulant potential of the PCCs was assessed in plasma and whole blood from 4 healthy donors by means of classical coagulation assays, thrombin generation assay and thromboelastometry. In order to reflect coagulopathy, whole blood was diluted to 80, 60, 40, and 20% with Ringer's lactate solution.
Results:
The five different PCCs were characterised by comparable levels of factors II, VII, IX and X (all around 20-30 IU/mL), whereas the heparin (0 to 17.6 IU/mL) and antithrombin (0.06 to 1.29 IU/mL) levels were remarkably different between manufactures. In vitro dilution of blood induced a prolongation of the PT and aPTT, and attenuation of thrombin generation and ExTem induced thromboelastometry. Overall, non- or low-heparin containing PCCs restored the in vitro dilutional coagulopathy, whereas PCCs containing heparin have an anticoagulant effect. The thrombin generation assay showed to be the most sensitive method for assessment of PCC effects.
Conclusions:
This study shows that most available PCCs are not balanced regarding their pro- and anticoagulants. The effect of measured differences in thrombin generation among different PCCs requires further investigations to elaborate the clinical meaning of this finding in the treatment of trauma induced coagulopathy.
