Cammaert, Timothy

Decaestecker, Karel

Devreese, Katrien

Rottey, Sylvie

Sundahl, Nora

Ghent University Academic Bibliography

LETTER TO THE EDITORA patient with acquired factor X deficiency and metastatictransitional cell carcinoma of the bladder: is there a linkbetween metastasis and factor deficiency in solid tumors?T. Cammaert1 & K. Decaestecker2 & N. Sundahl3 & S. Rottey4 & K. M. J. Devreese1Received: 12 October 2017 /Accepted: 4 November 2017 /Published online: 13 November 2017# Springer-Verlag GmbH Germany, part of Springer Nature 2017Dear Editor,Acquired deficiency of factor X (FX) is commonly foundduring antivitamin K therapy in prevention of thrombosis oras a consequence of liver disease [1]. Less frequently, it hasbeen observed as an isolated deficiency in a number of diseasestates. It has been associated with amyloidosis and hemato-logic malignancies [2], and few non amyloid-related caseshave been reported. Association with solid tumors is rare[3–5]. We would like to present a patient with a transitionalcell carcinoma who developed a FX deficiency.A 67-year-old man was diagnosed with a localized transi-tional cell carcinoma of the bladder. Hewas first admitted to ourhospital in January 2014 for a second-opinion consultation.Transurethral resection of the bladder took place and neoadju-vant chemotherapy was administered at our hospital, followedby a cystectomy. During follow-up, suspicious lesions werenoticed on medical imaging and a lung biopsy was carriedout. Pathological examination revealed a metastasis of the tran-sitional cell carcinoma. The patient subsequently received ste-reotactic body radiotherapy to all lung lesions yet had progres-sive disease 6 months later. He was then enrolled in a clinicaltrial (NCT02826564) in which he received pembrolizumab(Keytruda) and stereotactic body radiation therapy to one lunglesion according to the study protocol [6].During follow-up, prothrombin time (PT), activated partialthromboplastin time (aPTT), and fibrinogen concentration weremeasured to assess his blood’s clotting status. First measure-ments were within reference ranges, but after the lung metasta-ses were noticed and prior to administration of pembrolizumab,a prolongation of the PT (20s; reference ranges 11.5–14.5 s) andaPTT (51 s; reference ranges 28.9–38.1 s) was detected (Fig. 1).In the laboratory diagnostic workup, mixing patient’s plas-ma with normal pooled plasma showed correction of aPTT(37.6 s) and PT (14.2 s). Clotting factor activities for the ex-trinsic factors were determined by a one-stage clotting assay ina 1:10 sample predilution. Factor II, V, and VII levels werewithin normal ranges with 105, 71, and 98% activity but FXactivity was 21% (factor reference ranges 70–120%). Testingwas repeated in higher predilutions of 1:40 and 1:100, withoutincrease of FX activity (20%). These findings were confirmed3 weeks later.In FX deficiencies, FX activity correlates relatively wellwith bleeding and may be provoked by levels lower than10% [1, 7]. If no active bleeding is diagnosed, as in our patient,careful monitoring and treatment of the underlying disease aresufficient. If bleeding occurs, it can be treated with prothrom-bin complex concentrate or plasma, keeping the target FXlevel above 20% of the normal reference population [7].* T. CammaertTimothy.cammaert@uzgent.beK. Decaesteckerkarel.decaestecker@uzgent.beN. Sundahlnora.sundahl@uzgent.beS. Rotteysylvie.rottey@uzgent.beK. M. J. DevreeseKatrien.devreese@uzgent.be1 Coagulation Laboratory, Ghent University Hospital, De Pintelaan,185 (2P8), B-9000 Ghent, Belgium2 Department of Urology, University Hospital Ghent, De Pintelaan185, 9000 Ghent, Belgium3 Department of Radiation-Oncology and Experimental CancerResearch, University Hospital Ghent, De Pintelaan 185,9000 Ghent, Belgium4 Department of Medical Oncology, University Hospital Ghent, DePintelaan 185, 9000 Ghent, BelgiumAnn Hematol (2018) 97:545–546https://doi.org/10.1007/s00277-017-3172-xThis is, to our knowledge, the first case of an acquired defi-ciency of FX associated with an urothelial carcinoma. We sug-gest that there might be a link with metastasis of solid tumors[4, 5], as the FX deficiency occurred simultaneously with thepresence of metastases, in accordance with the previously pub-lished articles discussing this deficiency in solid tumors withmetastasis. This theory is consistent with the status quo of thelab results and progressive lesions on medical imaging.Compliance with ethical standardsConflict of interest The authors declare that they have no conflict ofinterest.References1. Uprichard J, Perry DJ (2002) Factor X deficiency. Blood Rev 16(2):97–110 Review2. Furie B, Greene E, Furie B (1977) Syndrome of acquired factor Xdeficiency and systemic amyloidosis in vivo studies of the metabolicfate of factor X. N Engl J Med 297(2):81–853. Coucke L, Trenson S, Deeren D, Van haute I, Devreese K (2013)Life-threatening bleeding tendency provoked by an acquired isolatedfactor X deficiency associated with respiratory infection. AnnHematol 92(10):1437–14384. Korte W, Flury R (1992) Acquired factor X deficiency and dissem-inated intravascular coagulation in a case of metastasizing carcinomaof the stomach and its course under chemotherapy. Ann Hematol 64:152–1545. Stefanini M, Wiggishoff CC (1966) Stuart factor (factor X) deficien-cy associated with renal and adrenal cortical insufficiency. AnnIntern Med 64:1285–12916. Sundahl N, De Wolf K, Rottey S, Decaestecker K, De MaeseneerD, Meireson A et al (2017) A phase I/II trial of fixed-dose ste-reotactic body radiotherapy with sequential or concurrentpembrolizumab in metastatic urothelial carcinoma: evaluationof safety and clinical and immunologic response. J Transl Med15(1):1507. Henson K, Files J, Morrison F (1989) Transient acquired factorX deficiency: report of the use of activated clotting concentrateto control a life-threatening hemorrhage. Am J Med 87(5):583–585010203040506005101520254224013993803593383172961630-1aPTT(s)PT(s)Time in days, compared to date of metastac diagnosisRoune coagulaon parametersPT (s)aPTT (s)Fig. 1 aPTT and PT results546 Ann Hematol (2018) 97:545–546

A patient with acquired factor X deficiency and metastatic transitional cell carcinoma of the bladder : is there a link between metastasis and factor deficiency in solid tumors?

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A patient with acquired factor X deficiency and metastatic transitional cell carcinoma of the bladder : is there a link between metastasis and factor deficiency in solid tumors?

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