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Fitzgerald and Fletcher Factor Deficiencies

Another brain teaser from Kim Kinney at Clarian in Indianapolis:

Hi George,

I am working on a case study for American Society for Clinical Laboratory Science (ASCLS). We had a patient who came in for a right hip replacement and ended up being < 1% high molecular weight kininogen (HMWK, Fitzgerald factor) and 58% prekallikrein (PK, Fletcher factor), also decreased. We had no previous coagulation data even though she had the left hip replaced seven years prior. Is there an association between HMWK/PK deficiency and thrombosis like there is with XII? I cannot find it in writing in any of my reference books. This lady has since developed DVTs in both legs and is on coumadin and Plavix. Funny though, there is no mention of the HMWK deficiency in her file. As always, thanks for your help. Kim.

Hi, Kim. Your questions always take me a day or two of reference-checking. My favorite for “minor” factor deficiencies is Roberts HR, Escobar MA. “Less common congenital disorders of hemostasis.” In Kitchens CS, Alving BM, Kessler CM. Consultative Hemostasis and Thrombosis, 2nd Edition. Elsevier, St. Louis, 2007.

PK and HMWK are members of the contact factor group, which includes factor XII, and some anecdotes implicate deficiencies of each in venous thromboembolic disease, though never in bleeding disorders. Roberts and Escobar, however, suggest the association may be secondary to anti-phospholipid antibody syndrome (APS). This makes some sense, particularly as lupus anticoagulants may interfere with PTT-based factor assays for the contact factors. In the case you are working on, has the patient been worked up for lupus anticoagulant and APS? This could account for an artifactual reduction of the HMWK and PK not noted in previous hospitalizations and her thrombotic episodes. Geo.

Comments (1)
May 5, 2009 8:27am

Thanks George. This patient actually did have a dRVVT and it
Thanks George. This patient actually did have a dRVVT and it was normal. Also, her mixing study showed very strong correction and none of her PTT factors showed any dilutional effect. I did finally find a blurb in a Coleman reference that there may be some association with thromboembolic disease and that both index cases for PK and HMWK dificiency had DVT/PE. Thanks again.

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