One case was a maintenance dialysis patient, and the other two had membranous nephropathy, which is caused by immune complex formation in the glomerulus. antibodies reduce the activity of coagulation factors, leading to a bleeding tendency. Most autoantibodies are to factor VIII (F8), referred to as acquired hemophilia A, and occur at a frequency of 1 1:100 million people. In Japan, the incidence of acquired factor V inhibitors (AFVIs) has been reported as 1:50 relative to acquired hemophilia A (1). Case Statement A 72-year-old man with end-stage renal disease (resulting from nephrosclerosis) was admitted to our hospital with fatigue, abdominal pain, and tarry stools in the middle of September. His medical history included chronic atrial fibrillation (AF), congestive heart failure with massive aortic regurgitation (AR), and peptic ulcer disease. Hypericin He was taking the following chronic medications: warfarin, carvedilol, amlodipine, olmesartan, febuxostat, furosemide, and lansoprazole. A physical examination at the time of admission revealed pale-colored conjunctivae and epigastric tenderness. The laboratory findings on admission are summarized in Table 1. In brief, the eosinophil count was markedly increased (52.1%), and the hemoglobin level was reduced (9.7 g/dL). The prothrombin time-international normalized ratio (PT-INR) was increased to 7.27, but the D-dimer value (0.45 g/mL) was within the normal range. A chest X-ray showed cardiomegaly, with a cardiothoracic ratio of 66% (Fig. 1). A computed tomography (CT) scan of his stomach showed bilateral renal atrophy and a mass, 38 mm in diameter, in the right kidney (Fig. 2). Table 1. Laboratory Findings on Admission. em Peripheral blood /em em Blood chemistry /em em Immuno-serological findings /em WBC 5,600 /LTP 7.9 g/dLIgG 3,049 mg/dL(neutro) 33.3 %Alb 3.49 g/dLIgA 409 mg/dL(lym) 8.3 %T-bil 0.53 mg/dLIgM 83 mg/dL(mono) 4.7 %AST 13 IU/LIgE 2,840 IU/mL(eosino) 52.1 %ALT 12 IU/LIgG4 142 mg/dLRBC 323 104/LLDH 260 IU/LCH50 33.3 IU/mLHb 9.7 g/dLALP 215 IU/LC3 63 mg/dLHt 30.1 %-GTP 25 IU/LC4 13.4 mg/dLPlt 10.8 104/LCh-E 163 IU/LANA 40 em Coagulation test /em Ferritin 233 ng/mLds-DNA IgG2.8 PT(S) 84.6 secBUN 79 mg/dLMPO-ANCA 1.0 IU/mLPT(%)9.0 %Cr 7.1 mg/dLPR3-ANCA 1.0IU/mLPT-INR7.27 Na 136 mEq/Lanti-GBM Ab 2.0 IU/mLAPTT (day6) 98.5 secK 4.8 mEq/Lanti-SS-A Ab 7.0 IU/mLFib 462 mg/dLCl 110 mEq/Lanti-SS-B Ab 7.0 IU/mLFDP 4.1 ng/mLCa 8.2 mg/dLRF 3 IU/mLD-dimer 0.45 g/mLIP 4.1 mg/dLanti-CCP Ab 0.6 IU/mL em Tumor marker /em UA 6.0 mg/dLsIL-2R 5,780 IU/mLCEA 3.3 ng/mLCK 48 IU/LHBs Ag (-)CA19-9 19.8 IU/mLCRP 0.81 mg/dLHCV Ab (-)PSA 0.407 ng/mLT-spot (-) Open in a separate window Open in a separate window Figure 1. A chest X-ray on admission showed cardiomegaly, with a cardiothoracic ratio of 66%. Open in a separate window Physique 2. Abdominal computed tomography on admission exposing bilateral renal atrophy and a mass, 38 mm in diameter, in the right kidney. The patient’s clinical course is usually illustrated in Fig. 3. In the beginning, warfarin toxicity was suspected. Thus, the warfarin was halted, and vitamin K was administered intravenously, with Mouse monoclonal to CD95 a subsequent temporary improvement in his PT values. Although upper and lower gastrointestinal tract endoscopy was performed, no obvious source of bleeding was recognized. However, on Day 14 of admission, a CT scan of the chest showed bilateral massive infiltrative shadows in the right middle and lower lobes of the lung, suggesting an alveolar hemorrhage. On Day 15, the PT-INR value had increased to 5.76, and the activated partial thromboplastin time (APTT) was markedly prolonged ( 180 s). His findings for lupus anticoagulant diluted Russell’s viper venom time (dRVVT) were positive ( 1.33, normal range: 0-1.3 s), and his level of anti-2-glycoprotein 1 (aB2GP1) Hypericin IgG antibody was 3.2 U/mL (normal range: 3 U/mL) and anti-cardiolipin (aCL) IgG antibody was 38 U/mL (normal range: 10 U/mL). A plasma cross-mixing test was then performed and revealed no factor deficiency, but suggested a delayed-type inhibitor pattern (Fig. 4). We suspected acquired hemophilia and carried out tests to detect the coagulation factor activity and inhibitor presence (Table 2). The activity of factor V (FV) was quite low ( 3%). The specific inhibitor for FV was present, with a titer of 6 Bethesda models/mL (BU/mL). Thus, prednisolone was initiated, starting at a dose of 60 mg/day (1.0 mg/kg/day). The patient’s eosinophilia soon improved. The findings from his coagulation studies improved markedly, but his renal failure progressed with oliguria, and he ultimately required chronic hemodialysis. Open in a separate window Physique 3. Clinical course. Horizontal Hypericin axis: hospital days, APTT: activated partial thromboplastin time (s), PT-INR: international normalized ratio of prothrombin time, Hb: hemoglobin (g/dL), Vit K: Vitamin K (Menatetrenone), PSL: prednisolone (mg/day), FFP: New Hypericin frozen plasma, RCC-LR: reddish cells concentrates-leukocytes reduced Open in a separate window Physique 4. Cross-mixing test. Plasma from the patient and normal were mixed at numerous rations after incubation for 2 h at 37?C..