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Significance of platelet and monocyte activation for therapeutic immunoglobulin-induced thromboembolism.
Thromb Res. 2014 Feb; 133(2):244-53.TR

Abstract

OBJECTIVES

Thromboembolic events (TEE) in patients receiving infusions of intravenous immunoglobulin (IVIG) products have recently been associated with contaminating factor XIa. We studied whether platelet and monocyte activation could also be involved.

METHODS

Twenty IVIG samples from five manufacturers were tested for the induction of visible whole blood clot formation. A selection of TEE-associated and not associated lots was further analyzed for effects on thromboelastometry, platelet activation and adhesion, as well as monocyte tissue factor surface expression. Pure factor XIa was included for comparison. Western blotting was applied to analyze anti-CD154-reactive proteins in IVIG.

RESULTS

In whole blood, IVIG enhanced macroscopic clotting additively with factor XIa. In monocytes, all IVIG products induced the FcγRII-dependent tissue factor expression to a similar extent, which was not affected by addition of factor XIa. Testing platelet aggregation, IVIG strengthened the ADP and TRAP-6-elicited response. Furthermore, IVIG increased platelet-monocyte adhesion and annexin V binding to platelet microvesicles, and promoted platelet adhesion to IVIG-coated surfaces. The strongest effects were observed with TEE-associated lots. CD154-related proteins were detected in all IVIG products. CD154-related high molecular weight complexes were particularly found in the TEE-associated IVIG. In platelet aggregation, recombinant soluble CD154 enhanced aggregate formation and stability.

CONCLUSION

Our data demonstrate that IVIG modulate platelet and monocyte activation and can thereby affect the hemostatic balance. These effects are either additive to or independent from factor XIa. CD154-related proteins are assumed to be involved in these interactions, the mechanism of which needs to be elucidated in further studies.

Authors+Show Affiliations

Division of Hematology and Transfusion Medicine, Paul-Ehrlich-Institut, Langen, Germany. Electronic address: Ursula.Salge-Bartels@pei.de.Division of Hematology and Transfusion Medicine, Paul-Ehrlich-Institut, Langen, Germany.Division of Immunology, Paul-Ehrlich-Institut, Langen, Germany.Division of Hematology and Transfusion Medicine, Paul-Ehrlich-Institut, Langen, Germany.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

24342536

Citation

Salge-Bartels, Ursula, et al. "Significance of Platelet and Monocyte Activation for Therapeutic Immunoglobulin-induced Thromboembolism." Thrombosis Research, vol. 133, no. 2, 2014, pp. 244-53.
Salge-Bartels U, Heiden M, Groβ N, et al. Significance of platelet and monocyte activation for therapeutic immunoglobulin-induced thromboembolism. Thromb Res. 2014;133(2):244-53.
Salge-Bartels, U., Heiden, M., Groβ, N., & Seitz, R. (2014). Significance of platelet and monocyte activation for therapeutic immunoglobulin-induced thromboembolism. Thrombosis Research, 133(2), 244-53. https://doi.org/10.1016/j.thromres.2013.11.026
Salge-Bartels U, et al. Significance of Platelet and Monocyte Activation for Therapeutic Immunoglobulin-induced Thromboembolism. Thromb Res. 2014;133(2):244-53. PubMed PMID: 24342536.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Significance of platelet and monocyte activation for therapeutic immunoglobulin-induced thromboembolism. AU - Salge-Bartels,Ursula, AU - Heiden,Margarethe, AU - Groβ,Nannette, AU - Seitz,Rainer, Y1 - 2013/12/03/ PY - 2013/06/28/received PY - 2013/11/04/revised PY - 2013/11/26/accepted PY - 2013/12/18/entrez PY - 2013/12/18/pubmed PY - 2014/9/16/medline KW - ADP KW - BSA KW - CD40 Ligand KW - CT KW - Coagulation factor XI KW - ECL KW - FIIa KW - FITC KW - FXIa KW - HBS KW - HSA KW - Hepes-buffered saline KW - IVIG KW - Intravenous immunoglobulins (IVIG) KW - LPS KW - MAPK KW - MCF KW - MFI KW - MNC KW - Mean fluorescence intensity KW - PE KW - TEE KW - TF KW - TRAP-6 KW - Thromboelastometry KW - Thromboembolic events KW - Thromboplastin KW - WB KW - Western blot KW - adenosine diphosphate KW - bovine serum albumin KW - clotting time KW - coagulation factor XIa KW - enhanced chemiluminescence KW - fluorescein isothiocyanate KW - human serum albumin KW - intravenous immunoglobulin KW - lipopolysaccharide KW - maximum clot firmness KW - mitogen-activated protein kinase KW - mononuclear cells KW - phycoerythrin KW - recombinant soluble human CD154 KW - rshCD154 KW - thrombin KW - thrombin receptor activating peptide KW - thromboembolic events KW - tissue factor SP - 244 EP - 53 JF - Thrombosis research JO - Thromb Res VL - 133 IS - 2 N2 - OBJECTIVES: Thromboembolic events (TEE) in patients receiving infusions of intravenous immunoglobulin (IVIG) products have recently been associated with contaminating factor XIa. We studied whether platelet and monocyte activation could also be involved. METHODS: Twenty IVIG samples from five manufacturers were tested for the induction of visible whole blood clot formation. A selection of TEE-associated and not associated lots was further analyzed for effects on thromboelastometry, platelet activation and adhesion, as well as monocyte tissue factor surface expression. Pure factor XIa was included for comparison. Western blotting was applied to analyze anti-CD154-reactive proteins in IVIG. RESULTS: In whole blood, IVIG enhanced macroscopic clotting additively with factor XIa. In monocytes, all IVIG products induced the FcγRII-dependent tissue factor expression to a similar extent, which was not affected by addition of factor XIa. Testing platelet aggregation, IVIG strengthened the ADP and TRAP-6-elicited response. Furthermore, IVIG increased platelet-monocyte adhesion and annexin V binding to platelet microvesicles, and promoted platelet adhesion to IVIG-coated surfaces. The strongest effects were observed with TEE-associated lots. CD154-related proteins were detected in all IVIG products. CD154-related high molecular weight complexes were particularly found in the TEE-associated IVIG. In platelet aggregation, recombinant soluble CD154 enhanced aggregate formation and stability. CONCLUSION: Our data demonstrate that IVIG modulate platelet and monocyte activation and can thereby affect the hemostatic balance. These effects are either additive to or independent from factor XIa. CD154-related proteins are assumed to be involved in these interactions, the mechanism of which needs to be elucidated in further studies. SN - 1879-2472 UR - https://www.unboundmedicine.com/medline/citation/24342536/Significance_of_platelet_and_monocyte_activation_for_therapeutic_immunoglobulin_induced_thromboembolism_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0049-3848(13)00562-8 DB - PRIME DP - Unbound Medicine ER -