Hemostatic assessment of combined anticoagulant therapy using warfarin and prothrombin complex concentrates in a case of severe protein C deficiency
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Patients with severe congenital protein (P)C deficiency require long-term anticoagulant management. Recombinant PC concentrates for prophylactic use are not available in Japan; prothrombin complex concentrates (PCC), containing factors (F)II, VII, IX, X, and PC (PPSB-HT®), have been used ‘off-label’ in a few patients. We investigated the combined use of prophylactic PCC and Warfarin (VKA; PT-INR 2.0–2.5) in a severely PC-deficient patient in whom VKA alone did not prevent recurrent purpura. Plasma VKA-dependent factor levels and global PC function (Thrombopath®) were assessed. Plasma activity levels of FII/FVII/FIX/FX post-infusion of PCC (6.3 unit/kg) increased 35/27/27/35 (initial level) to 59/60/38/83 IU/dl, respectively. FVII:C and FIX:C rapidly returned to baseline levels 12–24 h post-infusion, but FII:C and FX:C returned more slowly. PC antigen (< 5%) increased to ~ 15%, followed by return to baseline levels 24 h post-infusion. Global PC function was very low (%PiCi 24%), but improved post-PCC infusion. This potential was slightly detectable even at an undetectable PC level. At day 3, high levels of d-dimer and FDP were observed without thrombotic event, but these improved post-infusion. Although PCC restored VKA-dependent coagulation factors, PC contained in PCC significantly improved global anticoagulation, and was clinically beneficial in this severely deficient patient.
KeywordsPC deficiency PCC Warfarin Vitamin K-dependent clotting factor PC pathway function
We thank Dr. Satoshi Mushiake for providing patient’s lab data, and thank patient’s home doctor for keeping the patient’s condition stable for long term. This work was partly supported by a Grant-in-Aid for Scientific Research (KAKENHI) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) to KN (Grant No. 18K07885) and by a Japan Agency for Medical Research and Development (AMED) to KN (18ek0109210h0002).
KO; performed experiments, interpreted the data, made the figures, and wrote the paper, KN; designed the research, interpreted the data, wrote the paper, edited the manuscript, and approved the final version to be published, KM, TN; performed experiments, NN, SO, performed the genetic analyses and interpreted the data, MS; supervised the studies.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
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