A 92-year-old woman with history of hypertension, heart failure, atrial fibrillation, pulmonary embolism, and erysipelas, treated with warfarin, presented with extensive hematomas in the context of a recent leg infection treated with amoxicillin + clavulanic acid, followed by ceftriaxone and clindamycin. An INR of eight prompted warfarin discontinuation and vitamin K substitution (2 mg). In the absence of clinical or biological improvement, prothrombin complex concentrate was administered, without further efficiency.Biological hemostasis tests were as follows: PT of 10%, INR of 8, APTT >180 seconds, normal fibrinogen (3.7 g/L). A normal thrombin time (17 seconds) eliminated a possible heparin contamination. D-dimers were increased (4 µg/mL), but in the absence of increased fibrin monomers (4 µg/mL), the hypothesis of DIC was excluded, and D-dimer increase was attributed to intratissular fibrinolysis (hematomas). All common pathway factors being dramatically decreased (1 to 2%), as were all other coagulation factors (Table 1), a common pathway inhibitor was suspected.A titration of factor II, V, and X inhibitors performed according to a one-stage Bethesda method indicated the positivity for an inhibitor directed against each of these three factors (respectively, 6.9, 496, and 38 Bethesda units), FV being by far the highest. This result suggested the presence of an antibody directed against one of these factors, probably factor V (highest titration), leading to an artifactual underestimation of all coagulation factors by one-stage assay and to an overestimation of inhibitor titrations. Accordingly, factors VIII, IX, XI, and XII were also dramatically decreased (<1% for all plasma dilutions).In the hypothesis of an antibody with antiphospholipid activity, as is frequently the case for factor II inhibitors, especially in the context of "Lupus Anticoagulant Hypoprothrombinemia Syndrome" (LAHS), a dRVVT test was performed. A 1/40 dilution of the plasma (hence, of the inhibitor) was necessary to achieve interpretable coagulation times. In these conditions, adding excess of phospholipids ("dRVVT confirm test") did not correct the coagulation time (dRVVT normalized ratio <0.85), thus excluding an antiphospholipid
AbstractWe report a very high factor V inhibitor affecting the measurement of all coagulation factors besides fibrinogen, all these factors being dramatically decreased. This inhibitor could be linked to antibiotic use. The patient died of massive hemorrhage before a plasma exchange could be initiated.
K E Y W O R D Scoagulation factors, factor inhibitor, factor V inhibitor
