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The Effect of Temperature and pH on the Activity of Factor VIIa: Implications for the Efficacy of High-Dose Factor VIIa in Hypothermic and Acidotic Patients
Abstract
BACKGROUND: Recombinant coagulation factor VIIa (FVIIa) is approved for treating hemophiliacs with inhibitors. High-dose FVIIa has also been used off-label to manage hemorrhage in trauma and surgical patients, many of whom also develop hypothermia and acidosis. METHODS: We examined the activity of FVIIa on phospholipid vesicles in the presence and absence of tissue factor (TF) and on platelets as a function of temperature and pH. RESULTS: FVIIa activity on phospholipids and platelets was not reduced at 33 degrees C compared with 37 degrees C. The activity of FVIIa/TF was reduced by 20% at 33 degrees C compared with 37 degrees C. A pH decrease from 7.4 to 7.0 reduced the activity of FVIIa by over 90% and FVIIa/TF by over 60%. CONCLUSION: FVIIa should be effective in enhancing hemostasis in hypothermic patients. However, because the activity of FVIIa is so dramatically affected by pH, its efficacy may be reduced in acidotic patients.
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Citations
Cited by
The Coagulopathy of Trauma: A Review of Mechanisms
Hess, J. R., Brohi, K., Dutton, R. P., Hauser, C. J., Holcomb, J. B., Kluger, Y., Mackway-Jones, K., Parr, M. J., Rizoli, S. B., Yukioka, T., et al. (2008) · Journal of Trauma: Injury, Infection & Critical Care · doi:10.1097/ta.0b013e3181877a9c · Cited by 933
Management of severe perioperative bleeding: Guidelines from the European Society of Anaesthesiology
Kozek-Langenecker, S. A., Afshari, A., Albaladejo, P., Santullano, C. A. A., De Robertis, E., Filipescu, D. C., Fries, D., Görlinger, K., Haas, T., Imberger, G., et al. (2013) · European Journal of Anaesthesiology · doi:10.1097/eja.0b013e32835f4d5b · Cited by 909
Management of bleeding following major trauma: a European guideline
Spahn, D. R., Cerny, V., Coats, T. J., Duranteau, J., Fernández-Mondéjar, E., Gordini, G., Stahel, P. F., Hunt, B. J., Komadina, R., Neugebauer, E., et al. (2007) · Critical Care · doi:10.1186/cc5686 · Cited by 437
Noninfectious Serious Hazards of Transfusion
Hendrickson, J. E., & Hillyer, C. D. (2009) · Anesthesia & Analgesia · doi:10.1213/ane.0b013e3181930a6e · Cited by 419
Schöchl, H., Frietsch, T., Pavelka, M., & Jámbor, C. (2009) · Journal of Trauma: Injury, Infection & Critical Care · doi:10.1097/ta.0b013e31818b2483 · Cited by 393
Metadata
- Authors
- Meng, Z. H., Wolberg, A. S., Monroe, D. M., & Hoffman, M.
- Venue
- The Journal of Trauma: Injury, Infection, and Critical Care
- Published
- 2003-11
- Volume
- 55
- Issue
- 5
- Pages
- 886-891
- ISSN
- 0022-5282 (ISSN-L)
- OpenAlex
- W2048378282
- Cited by
- 475
- References
- 0
- FWCI
- 13.56
- Type
- journal article
- Language
- en
- Open access
- closed
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- Meng, Z. H., Wolberg, A. S., Monroe, D. M., & Hoffman, M. (2003). The Effect of Temperature and pH on the Activity of Factor VIIa: Implications for the Efficacy of High-Dose Factor VIIa in Hypothermic and Acidotic Patients. The Journal of Trauma: Injury, Infection, and Critical Care. https://doi.org/10.1097/01.ta.0000066184.20808.a5
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