IgA RIPA inhibitor in a case of acquired von Willebrand syndrome

Acquired inhibitor of von Willebrand factor-platelet interaction occurring in a 57 year-old female has been partially characterized. She had no personal or familial bleeding tendencies, but presented a subcutaneous hematoma of recent origin. She was diagnosed as having an acquired von Willebrand syndrome because she had low levels of FVIII complex in plasma, with platelet adhesiveness to glassbeads and RIPA decreased. This inhibitor was classified as an IgA immunoglobulin, and had no activity against any component of FVIII complex. The purified IgA by the chromatographic technology interacted with normal platelets to inhibit RIPA. Following 1-deamino-8-D-arginine vasopressin (DDAVP) infusion, she had higher immediate rise in all components of FVIII complex in plasma, with no rapid decline. Plasma von Willebrand factor (vWF) multimers analyzed by 1.5% SDS-AGE technology revealed to be identical with those of normal plasma. These studies suggest that the abnormality of ristocetin-induced vWF-platelet interaction by IgA RIPA inhibitor and the reduction of all vWF multimers (like type IA von Willebrand disease) may have a relationship with the pathogenesis of bleeding diathesis in this case.     

Isoniazid disposition,comparison of isoniazid phenotyping methods in and acetylator distribution of Japanese patients with idiopathic systemic lupus erythematosus and control subjects.

1 Plasma levels of isoniazid (INH) and acetyl INH in plasma were measured with a spectrofluorometric method, and INH and its metabolites (acetyl INH, mono-acetylhydrazine, diacetylhydrazine and free hydrazine) excreted in urine were measured with a gas chromatography-mass spectrometry, respectively, after an oral dose of INH 10 mg/kg in 19 Japanese patients with idiopathic systemic lupus erythematosus (SLE) and in the same number of healthy controls. 2 When phenotyped according to various methods previously reported, 16 to 18 of the SLE and 17 to 19 of the control group were rapid acetylators. Regardless of the phenotyping methods applied, the distribution of acetylator phenotype of SLE patients was not significantly different from the control group or from the data previously reported among normal Japanese population. 3 By phenotyping our subjects with an INH T 1/2 of 110 min or less as rapid acetylators, and more slow acetylators, 3 of SLE patients and 2 of the controls were slow, while the remainder were all rapid. When this antimode was used, the mean apparent kinetic variables of INH and acetyl INH estimated from the plasma concentration-time data and the mean values for the 24-h urinary amount of INH and its metabolites, except for monoacetylhydrazine (P less than 0.05), did not significantly differ between the rapid acetylators of SLE and control groups. 4 The distribution of INH T 1/2, acetyl INH to INH ratios in plasma and urine, values in urine for log10 (diacetylhydrazine to monoacetylhydrazine) and for diacetylhydrazine to INH or acetyl INH was similar between the two groups except for one patient who was definitely classified as a slow acetylator regardless of whichever phenotyping methods were used. The excretory patterns of hydrazine compounds reflect, in general, the inactivating ability of INH in each individual. 5 The data suggest that phenotyping by using plasma samples is, in general, better than by using urine samples. The plasma T 1/2 alone is the most satisfactory criterion. 6 We conclude that neither INH disposition nor phenotype distribution assessed by the reported methods using INH as the test compound are altered in idiopathic SLE, and that a search for racial and/or geographical factor(s) likely to result in autoimmune disease may give a clue to the pathogenesis in addition to further exploration for the possible interrelation between idiopathic SLE and genetic slow acetylation.     

Secondary sclerosing cholangitis with hemobilia induced by pembrolizumab: Case report and review of published work

A 66‐year‐old man was admitted to our department due to cholestatic liver injury. He had received five cycles of pembrolizumab for small‐cell lung cancer. Imaging showed the possibility of sclerosing cholangitis (SC) with hemobilia. Histologically, CD8⁺ T cells had infiltrated the biliary epithelium of the extrahepatic bile duct. We reached the diagnosis of secondary SC induced by pembrolizumab. Although we treated him with high‐dose corticosteroids, laboratory data showed only a moderate response. Clinicians should recognize that immune checkpoint inhibitors can sometimes cause severe and irreversible SC.