For January through May, 2008, I’ve had the pleasure of working with Elaine Keohane, PhD, Clinical Laboratory Science Program Director for the University of Medicine and Dentistry of New Jersey. In addition managing her program, Elaine teaches an online advanced hemostasis course for sixteen graduate Clinical Laboratory Science students. She invited me to assist. We actually used four Fritsma Factor modules for the course, Coagulation Overview Parts 1 and 2 and Cell-based Hemostasis Parts 1 and 2.
Elaine’s graduate students are Clinical Laboratory Scientists, and most have coagulation laboratory experience. One, Stephanie Ford, asked this question:
On page 600 of your chapter 41, Hemorragic Coagulation Disorders, in Rodak BF, Fritsma GA, and Doig K, Hematology Clinical Principles and Applications, 3rd Edition you indicate factor XI is inherited in an autosomal dominant pattern. Hoffman indicates autosomal recessive on page 2088. An e-medicine source just indicates autosomal.
Is it autosomal dominant because symptoms are expressed when the patient is heterozyygous for a factor XI mutation? This would mean only one copy of the abnormal gene is required.
Then, for other autosomal factor deficiencies on the same page, you indicate they are recessive, meaning an individual has to inherit mutations in both copies of the gene in order for the disease to be expressed. Is this correct?
Stephanie (and Elaine):
Thank you for your question. I sometimes think categorizing an inherited disorder as dominant or recessive is artificial. For factor XI deficiency in homozygotes the bleeds are mild, rarely spontaneous, and the penetrance varies according to the number of factor XI platelet surface receptors. Paradoxically, some heterozygotes also display mild but definite bleeding, which is why factor XI inheritance is categorized as dominant. See Seligson U. Factor XI Deficiency. Thromb Haemost 1993;70:68-70.
In contrast to XI, deficiencies of the autosomal factors II, V, VII, and X express bleeding only when homozygous or double heterozygotes.
For factor XIII, there are a few cases of heterozygotes with bleeding, although most heterozygotes are normal, so the deficiency gets labeled as dominant or recessive by various investigators depending on their experience.
When inherited, afibrinogenemia and dysfibrinogenia are recessive, but they are much more often acquired as a result of liver disease than congenital.
I’m using Camire RM, Pollak E. Genetics of Coagulation. In Colman RW,Marder VJ, Clowes AW, George JN, Goldhaber SZ. Hemostasis and Thrombosis Fifth Edition 2006, Lippincott as my key secondary reference. Geo
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