From Tracy Dixon, Western Australia Department of Health. Hi George, We have a case currently of an elderly man with metastatic melanoma and liver involvment who is giving us a consistently long APTT (PTT) with a silica reagent, often >200 seconds. Prolonged incubation with the silica reagent has shortened this to around 60 seconds. The APTT corrects fully upon 50:50 mix with normal plasma using a 3 minute incubation. Could this be a case of acquired prekallikrein (PK, PKK) defiency? I am currently trying to source some HMWK & PKK deficient plasma to confirm. We also ran ROTEM thromboelastometry which uses ellagic acid for the INTEM channel which gave a markedly long clottiing time (CT). Are you able to suggest any further investigations we may undertake? Thank you and kind regards.
Hello, Tracy, and thank you for this case study, which illustrates the classic PTT response to prekallikrein (Fletcher factor) deficiency. For a description, see Asmis LM, Sulzer I, Furlan M, Lämmle B. Prekallikrein deficiency: the characteristic normalization of the severely prolonged aPTT following increased preincubation time is due to autoactivation of factor XII. Thromb Res. 2002;105:463–70. Please send more about your conclusion that this is an acquired PK deficiency, do you have prior PTT results for comparison? Of course, the combination of metastatic melanoma and liver involvement can lead to a variety of plasma protein imbalances, so there’s not a reason to exclude the possibility. Existing literature documents 75 cases of PK deficiency between 1965 and 2010, all are assumed to be inherited. See Girolami A, Allemand E, Bertozzi I, Candeo N, Marun S, Girolami B. Thrombotic events in patients with congenital prekallikrein deficiency: a critical evaluation of all reported cases. Acta Haematol. 2010;123:210–14.
You can order PK-deficient plasma from Precision BioLogic Inc, however I know of no source for Fitzgerald factor (HMWK) -deficient plasma. You’ve probably already assayed for VIII, IX, XI, and XII deficiency, it would be academically useful to examine these results also based on your patient’s liver involvement. Your ROTEM results are interesting, I suspect few investigators have examined TEM or TEG results in PK deficiency. Again, thank you for this interesting case, and please keep us posted on developments.