Two coagulation factor questions from Madan Verma, MLT:
I was cruising through your website and I have two questions:
Do coagulation factors circulate in blood as activated proteins or they are in a non-active form? Is there a certain proportion of activated and non-active?
Factor VII (activated or native form?) has the shortest half life of six hours. Does this mean in vivo or in vitro? We may add PT on a specimen up to 24 hrs, but, while factor VIII has a half life of 12 hrs, a PTT is allowed to be added on a drawn specimen within only four hours. Why?
Thanks in advance, Madan Verma, MLT
Madan Verma, thank you for your questions. Coagulation factors are inactive until clotting occurs. Most coagulation factors are enzymes called serine proteases, but circulate as zymogens (sometimes called proenzymes). When inactive, they are identified by a Roman numeral alone, such as IX, but when they become activated during coagulation they are given a lower-case a, for example IXa. Factors V and VIII are not serine proteases, but rather cofactors that help to stabilize the active proteases Xa and IXa, respectively, however V and VIII also become activated, and are then renamed Va and VIIIa.
The half-life of a coagulation factor is one of its in vivo characteristics. The half-lives of factors are computed from their behavior when used as therapeutics. For example, provide factor VIII concentrate to a hemophilic who has no anti-VIII inhibitor. Collect a blood specimen shortly after administration and then after 12 hours, and the factor VIII concentration is reduced by approximately 50% in 12 hours. Conversely, when providing factor VII, a Novo Nordisc concentrate called NovoSeven, you would find its activity drops more rapidly.
Once a blood specimen is collected, factor VII, despite its short in vivohalf-life, is stable. Factor VIII is not. If you were to assay a stored specimen hourly for VII and VIII, you would demonstrate the VIII concentration drops by at least 10% within four hours, but the VII activity remains steady. This is why the prothrombin time (PT) can be accurately performed on specimens held up to 24 hours, whereas the partial thromboplastin time (PTT, activated partial thromboplastin time, APTT) must be performed within four hours.
More information is available in our on-line audio lectures, Coagulation Overview Parts 1 and 2.
Thank you for your question, and thank you for visiting the Fritsma Factor. Geo.
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