Impact of thrombophilic gene mutations and graft-versus-host disease on thromboembolic complications after allogeneic hematopoietic stem-cell transplantation

Pihusch, Markus and Lohse, P. and Reitberger, J. and Hiller, E. and Andreesen, Reinhard and Kolb, H. J. and Holler, Ernst and Pinhusch, Rudolf (2004) Impact of thrombophilic gene mutations and graft-versus-host disease on thromboembolic complications after allogeneic hematopoietic stem-cell transplantation. TRANSPLANTATION, 78 (6). pp. 911-918. ISSN 0041-1337,

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Abstract

Background. Hemostatic events in patients undergoing allogeneic hematopoietic stem-cell transplantation (HSCT) increase the morbidity and mortality in this cohort. Little is known about the impact of graft-versus-host disease (GvHD) or of thrombophilic gene mutations/polymorphisms on these complications. Study Design. Eighty-nine allogeneic stem-cell recipients and their donors were evaluated prospectively for the presence of the factor V G1691A mutation, the prothrombin G20210A mutation, the 5,10-methylenetetrahydrofolate-reductase (MTHFR) C677T mutation, the glycoprotein Ilia pI(a1/a2) polymorphism, the fibrinogen-beta-chain 455G/A polymorphism, the plasminogen activator inhibitor-1 -675 4G/5G polymorphism, and the angiotensin-converting enzyme intron 16 I/D polymorphism. These mutations/polymorphisms and GvHD parameters were correlated to hemostatic and toxic complications after transplantation. The data were compared with those of 128 healthy controls. Results. The PAI-1 4G/4G polymorphism increases the risk for catheter thrombosis after HSCT 5.7-fold (32.2% vs. 71.4%, P<0.05). In patients with hepatic veno-occlusive disease, the frequency of the PAI-1 4G allele is also increased (83.3% vs. 55.1%, NS). Thrombophilic mutations/polymorphisms in donors do not influence complications in the corresponding recipients. The MTHFR TT genotype does not modify severity and duration of mucositis and aplasia in patients receiving methotrexate prophylaxis. Patients with chronic GvHD have a higher risk of thromboembolism (12.9% vs. 1.7%, P<0.05). Conclusion. Thrombophilic gene mutations have only a moderate influence on hemostatic complications in patients undergoing HSCT. This may be because of the overwhelming immunologic impact of GvHD on hemostasis in the allogeneic transplantation setting.

Item Type: Article
Uncontrolled Keywords: BONE-MARROW-TRANSPLANTATION; HEPATIC VENOOCCLUSIVE DISEASE; TUMOR-NECROSIS-FACTOR; PLASMINOGEN-ACTIVATOR INHIBITOR-1; MYOCARDIAL-INFARCTION; 4G/5G POLYMORPHISM; VEIN-THROMBOSIS; REDUCTASE GENE; RISK; METHOTREXATE; hematopoietic stem-cell transplantation; thrombophilic gene mutation; hemostatic complication
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie)
Depositing User: Dr. Gernot Deinzer
Date Deposited: 28 Jun 2021 11:40
Last Modified: 28 Jun 2021 11:40
URI: https://pred.uni-regensburg.de/id/eprint/37182

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