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Fibrinogen deficiency, but not plasminogen deficiency, increases mortality synergistically in combination with sickle hemoglobin SAD in transgenic mice
- Source :
- American Journal of Hematology. 82:1044-1048
- Publication Year :
- 2007
- Publisher :
- Wiley, 2007.
-
Abstract
- Patients with sickle cell disease exhibit both acute and chronic activation of the coagulation and fibrinolytic systems. To test the relationship between sickle cell pathology and activation of the hemostatic system, mice with targeted deletions of plasminogen (Plg) or fibrinogen (Fib) were crossed with transgenic mice expressing Hb SAD [β6Glu-Val (HbS), β23Val-Ile (HbAntilles), and β121Glu-Gln (HbD-Punjab)]. Fibrinogen deficiency dramatically reduced the survival of mice with Hb SAD to a much greater degree than mice with normal hemoglobin. The combination of Hb SAD and fibrinogen deficiency had a greater effect on mortality than that obtained by adding the mortality risks of each defect alone. The deleterious effect of the combination of Hb SAD and fibrinogen deficiency on mortality was accelerated by hypoxia. The excess mortality associated with plasminogen deficiency was identical in SAD and control mice. The adverse effect of fibrinogen deficiency on mortality in SAD mice is not consistent with the simple hypothesis that fibrin deposition is uniformly deleterious in the context of vaso-occlusive sickle cell disease. Rather, our findings suggest that the contribution of fibrinogen to tissue repair may in some contexts limit sickle cell disease pathophysiology. Am. J. Hematol., 2007. © 2007 Wiley-Liss, Inc.
- Subjects :
- Genetically modified mouse
medicine.medical_specialty
Genotype
Hemoglobin, Sickle
Cell
Mice, Transgenic
Anemia, Sickle Cell
Biology
Fibrinogen
Mice
Internal medicine
medicine
Animals
Hematology
Plasminogen
Hypoxia (medical)
medicine.disease
Survival Analysis
Sickle cell anemia
Pathophysiology
medicine.anatomical_structure
Immunology
Hemoglobin
medicine.symptom
Gene Deletion
medicine.drug
Subjects
Details
- ISSN :
- 10968652 and 03618609
- Volume :
- 82
- Database :
- OpenAIRE
- Journal :
- American Journal of Hematology
- Accession number :
- edsair.doi.dedup.....7023b54d956b1e200bbd8a6cf2277877