It sometimes seems that those writing questions for Boards, whether Written, Oral, or Pain, desire to make this process progressively more difficult, and way beyond what they themselves encountered and with all due respect.
An example of this is a keyword I was working upon this morning, namely activated protein C. To me, at least, it seems a bit esoteric for a Board exam--a definite, "How Many Nits on a Gnat's Nut. . ." First a question, then some summarized content.
Activated protein C (APC) is which of the following:
Activated protein C
1. Activated protein C (APC) inhibits factors V and VIII in the coagulation cascade and in this way inhibits the conversion of prothrombin to thrombin which in turn inhibits the conversion of fibrinogen to fibrin and thus inhibits clot formation. Therefore, since the conversion of thrombin leads to fibrin and clot formation, also known as thrombosis, APC could be described as being anti-thrombotic.
2. Fibrin is formed clot, resulting from fibrinogen activation, through the clotting pathway.
a. Fibrinolysis is the breakdown of clot, and it results from the conversion of the fibrinolytic enzyme plasminogen being converted to plasmin. “Fibrinolysis” is the breakdown of clot therefore the term “anti-fibrinolytic” refers to the preservation of clot.
3. Patients with severe sepsis have systemic inflammation resulting in coagulation abnormalities that range from thrombosis to DIC; initially there is often thrombosis and this ultimately leads to low factors, low platelets, and low fibrinogen—DIC.
4. One, of many, pathophysiologic factors involved with sepsis might be low APC levels, leading to the initial thrombosis mentioned. Indeed, recognition of sepsis caused micro-thrombosis and the presence of low levels of circulating APC led questions about the possible need for APC supplementation in sepsis.
a. Because of the crucial role that protein C plays as an anticoagulant, those with either deficiencies in protein C, or some kind of resistance to APC, suffer from a significantly increased risk of forming dangerous blood clots (thrombosis). On the other hand, medical research into protein C's clinical and pharmacological effects has demonstrated that patients with severe sepsis, ischemic stroke and other serious medical conditions may benefit from treatment with recombinant human activated protein C (rhAPC) in the form of drotrecogin alfa-activated (branded Xigris by Eli Lilly and Company). However, studies since have questioned the drug's overall benefit, and its use is now controversial, given the risk of serious bleeding associated with treatment. However, it should be noted, another reference through MD Consult stated: “Recombinant human APC is the first pharmacological drug that has demonstrated efficacy in the treatment of severe sepsis.” A third source states: “APC is recommended in the setting of severe sepsis with reasonable life expectancy beyond sepsis. The cost is high and use remains controversial. A new randomized placebo controlled trial is currently under way.”
5. As can be imagined, the most severe adverse effect of APC is serious bleeding, hemorrhage, as would be expected due to its anticoagulant effect.
6. In summary, APC is a naturally occurring anticoagulant that inactivates factors Va and VIIa and prevents the generation of thrombin (and is therefore anti-thrombotic). Best answer C.
(Reference: MD Consult)
I hope this was helpful and, as you know, I'm with General George Smith Patton: "The highest honor I have ever attained is having my named linked to yours in these great events." Passing Boards is a Great Event, and it's fun being on your team. Thanks, Niels F. Jensen, M.D.