Write short notes on:
a) Recombinant activated protein C (drotrecogin alpha)
b) Recombinant coagulation Factor VIIa
a) Recombinant activated protein C (drotrecogin alpha)
a) endogenous human protein, a component of natural anti-coagulant system b) Recombinant version shown to improve survival in septic shock in a RCT. c) Indications for use:septic shoe2 system failure, APACHE II> 25
d) Possible mechanisms: Sepsis decreases APC levels and therefore
administration increases levels, Improved microcirculation through alteration
of coagulation, Anti-inflammatory and antiapoptotic e) Side effects:Bleeding
f) Controversies: Not proven in immunocompromised patients, increases mortality in paediatric population
g) Expensive
b) Recombinant coagulation Factor VIIa
a) Novel agent for control of intractable hemorrhage
b) Evidence base: hemophilia, trauma, post cardiac bypass, intracranial hemorhage
c) Mechanism: Causes a thrombin burst which in tum converts fibrinogen to fibrin to form a clot
d) Complications:DVT risk
e) Expensive
Following the shameful worldwide withdrawal of Drotrecogin Alpha, it seems unlikely that the candidates would ever be expected to "write short notes" on it in the ultra-pragmatic CICM fellowship exam. Thus, I will leave the discussion of its merits and demerits to the historians. Moreover, given the changing nature of the fellowship exam (trending further towards easy-to-mark data interpretation questions and tabulated comparisons), it is unlikely the candidates will ever be asked to write short notes on any topic whatsoever.
Recombinant Factor VIIa remains a possibly examinable topic. One might someday be expected to tabulate its advantages and limitations, or to critically evaluate its use.
Thus:
Rationale
Advantages
Disadvantages
Guidelines for practice
Boffard, Kenneth David, et al. "Recombinant factor VIIa as adjunctive therapy for bleeding control in severely injured trauma patients: two parallel randomized, placebo-controlled, double-blind clinical trials." Journal of Trauma-Injury Infection and Critical Care 59.1 (2005): 8-18.
O’Connell, Kathryn A., et al. "Thromboembolic adverse events after use of recombinant human coagulation factor VIIa." Jama 295.3 (2006): 293-298.
Levi, Marcel, Marjolein Peters, and Harry R. Büller. "Efficacy and safety of recombinant factor VIIa for treatment of severe bleeding: a systematic review."Critical care medicine 33.4 (2005): 883-890.
Yank, Veronica, et al. "Systematic review: benefits and harms of in-hospital use of recombinant factor VIIa for off-label indications." Annals of Internal Medicine154.8 (2011): 529-540.
Willis, Cameron David, Peter A. Cameron, and L. E. Phillips. "Clinical guidelines and off‐license recombinant activated factor VII: content, use, and association with patient outcomes." Journal of Thrombosis and Haemostasis7.12 (2009): 2016-2022.
Vincent, Jean-Louis, et al. "Recommendations on the use of recombinant activated factor VII as an adjunctive treatment for massive bleeding–a European perspective." Critical Care 10.4 (2006): R120.
Martinowitz, U., M. Michaelson, and Israeli Multidisciplinary rFVIIa Task Force. "Guidelines for the use of recombinant activated factor VII (rFVIIa) in uncontrolled bleeding: a report by the Israeli Multidisciplinary rFVIIa Task Force." Journal of Thrombosis and Haemostasis 3.4 (2005): 640-648.
Payen, J-F., et al. "Reduced mortality by meeting guideline criteria before using recombinant activated factor VII in severe trauma patients with massive bleeding." BJA: British Journal of Anaesthesia 117.4 (2016): 470-476.