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Acquired factor V inhibitor (AFVI) results from the formation of autoantibodies to coagulation factor V (FV), and the clinical phenotype can range from asymptomatic laboratory abnormalities to life-threatening bleeds. We describe a 74-year-old man who developed AFVI along with a massive subcutaneous hematoma. He was initially treated with prednisolone (PSL), but AFVI recurred when the dose was reduced after a short period. We subsequently increased the PSL dose and added cyclophosphamide (CY), which resulted in a complete response. We then gradually tapered PSL and stopped CY, and the patient has since remained free of recurrent AFVI symptoms. We monitored FV activity, antigen concentrations, and inhibitor titers of this patient throughout the clinical course. The ratio of FV activity to antigen concentration was low at diagnosis and gradually increased along with the patient's improvement. This ratio might be a useful parameter for evaluating the effects of immunosuppressive therapy in patients with AFVI. [ABSTRACT FROM AUTHOR]

Lactic acidosis is a rare but serious side effect in individuals receiving nucleoside reverse transcriptase inhibitors. An underweight woman with HIV was admitted to our hospital because of nausea and diffuse myalgia. Her antiretroviral regimen had been changed to tenofovir disoproxil fumarate (TDF)/emtricitabine and darunavir/cobicistat 3 months prior, after which her renal function had gradually declined. After admission, she was diagnosed with lactic acidosis, and a liver biopsy suggested mitochondrial damage. Her plasma tenofovir levels were elevated at the onset of lactic acidosis. We hypothesise that the patient's low body weight, combined with the addition of cobicistat, induced renal dysfunction and led to elevated plasma tenofovir concentrations, resulting in mitochondrial damage and lactic acidosis. Careful monitoring of renal function and lactic acidosis is required during use of TDF-containing regimens for underweight HIV patients, particularly when combined with cobicistat., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Neuropsychiatric symptoms comprise one of the five classic symptoms of autoimmune thrombotic thrombocytopenic purpura (aTTP). Although aTTP is typically transient, it is sometimes complicated by cerebral infarction with residual disability. This report presents the case of an 87-year-old man previously admitted to a different hospital with fever and transient consciousness loss. After receiving platelet transfusion with diagnosis of Evans syndrome, he was transferred to our hospital with worsening consciousness disturbance. He was subsequently diagnosed with aTTP with a PLASMIC score of 6 points, ADAMTS13 activity of less than 0.5%, and its inhibitor of 7.4 BU/ml. Platelet count and consciousness were rapidly improved with plasmapheresis and steroids, but motor aphasia emerged. MRI showed multiple cerebral infarctions, including a large infarction in the left frontal lobe. Thus, unfractionated heparin was administered. When his platelet count dropped once again on the 20th day, rituximab was added. The treatment eventually proved to be successful, and his aTTP remained in remission one year after the onset. Treatment for cerebral infarctions was switched to DOAC, and rehabilitation was continued. However, his ADL has not yet recovered. Advances in aTTP treatment have cured many similar cases. Thus, rituximab is now considered a treatment option for refractory cases. However, ischemic organ damage in acute phase and sequelae are observed. Therefore, early diagnosis and novel therapy are required.

Acquired thrombotic thrombocytopenic purpura (aTTP) is caused by a deficiency of ADAMTS13 activity due to neutralizing auto-autoantibodies (inhibitors) against ADAMTS13. Patients with aTTP show a rapid and fatal clinical course, unless an effective therapeutic intervention such as plasma exchange therapy (PEX) is performed. There is, however, a small population of patients who show a smoldering clinical course, for which no effective treatment strategy has yet been established. We herein report a 77-year-old man, who had repeated episodes of cerebral infarction and persistent thrombocytopenia over several months, but was not correctly diagnosed as having aTTP at a local hospital. However, sudden progression to an unconsciousness state together with thrombocytopenia prompted his physician to make a clinical diagnosis of aTTP, and the patient was then referred to our hospital, where the diagnosis of aTTP was confirmed by analyzing ADAMTS13. An improvement of his clinical signs was achieved with PEX and steroid therapy, but the latter had to be discontinued due to the development of grade 3 liver dysfunction. Despite discontinuation of steroid therapy, his clinical condition remained stable, but with a persistently low level of ADAMTS13 activity associated with the presence of low-titer inhibitors. Our experience may raise awareness of the diagnosis and treatment of aTTP with a smoldering clinical course.

Acquired hemophilia A (AHA) is a rare coagulation disorder caused by autoantibodies against coagulation factor VIII (FVIII). We report herein a very rare case of AHA complicated by immune thrombocytopenia (ITP). A 30-year-old woman was hospitalized with severe thrombocytopenia. Her platelet count was 5,000/μl on admission, at which time APTT was normal. ITP was diagnosed and she was treated with γ-globulin, platelet transfusion, and prednisolone at 1 mg/kg/day. She was discharged after platelet count normalization and prednisolone was tapered to 5 mg/day. During the prednisolone tapering, purpura appeared on both thighs and in the left inguinal region, and APTT was found to be prolonged. She was referred to our hospital for examination of APTT prolongation. FVIII activity was markedly decreased to 7.7% and the FVIII inhibitor was positive (1.5 BU/ml), based on which AHA was diagnosed. We carefully followed this patient without intensification of immunosuppressive therapy for 7 weeks, but her platelet count decreased from 150,000/μl to 70,000/μl and the FVIII inhibitor increased to 4 BU/ml. We therefore increased prednisolone to 30 mg/day, after which her platelet count increased and complete remission of AHA was achieved by day 42. In addition, we examined the relationship of the FVIII inhibitor and FVIII binding antibody in this case.

Acquired thrombotic thrombocytopenic purpura (TTP) is caused by autoantibodies against ADAMTS13. TTP patients run a rapidly fatal course unless immediate plasma exchange (PEX) is initiated upon diagnosis. Herein, we report a 72-year-old man with TTP, which developed after he underwent artificial blood vessel replacement surgery for an abdominal aneurysm with impending rupture. In the perioperative period, the patient received several platelet transfusions for severe thrombocytopenia (minimum platelet count: 0.6×10(4)/μl). Thereafter, he was admitted to our department for rapidly progressing coma with multiple cerebral infarctions, and was transferred to the ICU. Based on the tentative diagnosis of TTP, we immediately began PEX and steroid pulse therapy. The diagnosis was confirmed thereafter by markedly reduced ADAMTS13 activity (<0.5%) and his being positive for the ADAMTS13 inhibitor. We performed PEX for five consecutive days and administered high-dose prednisolone (PSL). On the second hospital day (HD), his platelet count rose along with improvement of his consciousness level. The ADAMTS13 inhibitor was not detected on the 10th HD. TTP did not relapse and his general condition improved despite tapering of PSL. In this case, by closely monitoring ADAMTS13-related parameters and minimizing the number of plasma exchanges, the patient was able to achieve a remission without the use of boosting inhibitors.

A 40-year-old man was diagnosed with Langerhans cell histiocytosis (LCH) in October 2010. His LCH was refractory to conventional chemotherapy, and thus worsened to Langerhans cell sarcoma (LCS) in May 2011. Although we repeated combination chemotherapies, new infiltration of the liver and bone marrow, as well as primary lesions of the bone, lymph nodes, and skin, appeared. These intensive chemotherapies caused candida liver abscesses, invasive aspergillosis, disseminated varicella zoster virus infection and bacterial sepsis. We administered bendamustine for chemotherapy, which resulted in a partial response (PR) with no severe adverse events. Because of pancytopenia caused by secondary myelodysplastic syndrome, we stopped the bendamustine chemotherapy after two courses. PR was maintained for 4 months. We plan to perform allogeneic hematopoietic stem cell transplantation from a sibling donor after a conditioning regimen. Optimal therapy for adult LCH, which is a rare and treatment-resistant disease, has yet to be established. Bendamustine is a potential chemotherapeutic agent for standard treatment of LCS.

A 45-year-old woman with acute myelogenous leukemia developed platelet transfusion refractoriness (PTR) after the engraftment of an allogeneic peripheral blood stem cell transplantation (PBSCT) from her multiparous sister, which was attributed to HLA antibodies that could not be detected in the patient's serum before transplantation. She achieved neutrophil engraftment by day 18 and megakaryocytopoiesis and complete donor chimerism was confirmed in the bone marrow on day 21. IgG-class HLA antibodies were detected in her serum on day 24 after PBSCT; however, on day 15, no HLA antibodies were detected. The specificity of the antibodies that emerged in the patient closely resembled that of the antibodies found in the donor. The donor had probably been immunized during pregnancy by their partner's HLA-antigens expressed by the fetus. Consequently, transplanted donor-derived cells provoked HLA antibodies in the recipient early after PBSCT, and those HLA antibodies induced PTR. The presence of HLA antibodies should be examined at least in pregnant female donors whose recipients developed PTR attributable to HLA antibodies after SCT.