Von Willebrand factor (VWF)–cleaving protease (ADAMTS13) cleaves ultralarge VWF (ULVWF) secreted from endothelium and by which is regulating its physiologic function. An imbalance between ULVWF secretion and ADAMTS13 level occurs in sepsis and may cause multiple organ dysfunction. We evaluated the association between the VWF-propeptide (VWF-pp)/ADAMTS13 ratio and disease severity in patients with severe sepsis or septic shock. In 27 patients with severe sepsis or septic shock and platelet count less than 120 000/μL, we measured plasma VWF, VWF-pp, and ADAMTS13 levels on hospital days 1, 3, 5, and 7. The VWF-pp/ADAMTS13 ratio was increased greater than 12-fold in patients with severe sepsis or septic shock on day 1 and remained markedly high on days 3, 5, and 7 compared with normal control subjects. The VWF-pp/ADAMTS13 ratio significantly correlated with Acute Physiology and Chronic Health Evaluation II score on days 1 and 5; Sepsis-related Organ Failure Assessment score on days 1, 3, and 5; maximum Sepsis-related Organ Failure Assessment score and tumor necrosis factor α level on days 1, 3, 5, and 7; and creatinine level on days 1, 5, and 7. Patients with greater than stage 1 acute kidney injury had significantly higher VWF-pp/ADAMTS13 ratio than patients without acute kidney injury. In summary, the VWF-pp/ADAMTS13 ratio was associated with disease severity in patients with severe sepsis or septic shock and may help identify patients at risk for multiple organ dysfunction by detecting severe imbalance between ULVWF secretion and ADAMTS13 level.

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare autoimmune disorder caused by neutralizing anti-ADAMTS13 autoantibodies. In Caucasians, human leukocyte antigen (HLA) allele DRB1*11 was a predisposing factor for iTTP, while DRB1*04 was a protective factor. However, the role of HLA in Asians is unclear. In this study, we analyzed 10 HLA loci using next-generation sequencing (NGS) in 52 Japanese patients with iTTP, and the allele frequency in the iTTP group was compared to that in a Japanese control group. We identified the following HLA alleles as predisposing factors for iTTP in the Japanese population: DRB1*08:03 (odds ratio [OR]: 3.06, corrected P-values [Pc]=0.005), DRB3/4/5*blank (OR: 2.3, Pc=0.007), DQA1*01:03 (OR: 2.25, Pc=0.006), and DQB1*06:01 (OR: 2.41, Pc=0.003). The estimated haplotype consisting of these 4 alleles was significantly more frequent in the iTTP group than in the control group (30.8% vs. 6.0%, Pc<0.001). DRB1*15:01 and DRB5*01:01 were weak protective factors for iTTP (OR 0.23, Pc=0.076; and OR 0.23, Pc=0.034, respectively). On the other hand, DRB1*11 and DRB1*04 were not associated with iTTP in Japanese. These findings indicated that predisposing and protective factors for iTTP differ between Japanese and Caucasians. HLA-DR molecules encoded by DRB1*08:03 and DRB1*11:01 have different peptide-binding motifs, but interestingly, were capable of binding to the shared ADAMTS13 peptide in an in silico prediction model.

We modified the dispatch protocol for cardiopulmonary resuscitation (CPR) using results of a retrospective analysis that identified descriptions by laypersons of possible patterns of agonal respiration. The purpose of this study was to assess the effectiveness of this modified protocol by comparing the frequency of dispatch instructions for CPR and bystander CPR before and after protocol implementation. We also identified descriptions of abnormal breathing patterns among ‘Not in cardiac arrest (CA)’ unresponsive cases. This study was conducted prospectively using the population-based registry of out-of-hospital cardiac arrests (OHCAs). For 8 months we implemented this modified protocol in cooperation with 4 fire departments that cover regions with a total population of 840,000. There were 478 and 427 OHCAs before and after implementation, respectively. Among them, 69 and 71 layperson-witnessed OHCAs for pre- and post-implementation, respectively, were analyzed. Dispatchers provided CPR instructions more frequently after protocol implementation than before (55/71 [77.5 %] vs. 41/69 [59.4 %], p < 0.05). Based on breathing patterns described by emergency callers, dispatchers assessed 143 ‘Not in CA’ unresponsive cases and provided CPR instruction for 45 cases. Sensitivity and specificity of this protocol was 93 % and 50 %, respectively. This modified protocol based on abnormal breathing described by laypersons significantly increased CPR instructions. Considering high sensitivity and low specificity for abnormal breathing to identify CA and the low risk of chest compression for ‘Not in CA’ cases, our study suggested that dispatchers can provide CPR instruction assertively and safely for those unresponsive individuals with various abnormal breathing patterns.

The macroenzyme form of aspartate aminotransferase (macro-AST) is formed by the binding of AST with immunoglobulins. Macro-AST excretion from serum is prolonged because of its high molecular weight, leading to increased AST activities. Because of the difficulty in detecting macro-AST through routine laboratory tests, affected patients often undergo repeated examinations, with associated anxiety. We report a case in which macro-AST was detected by assaying the patient’s serum after refrigeration at 4ºC for 3 days. The sample showed progressive loss of AST activity compared with that frozen in the refrigerator, indicating the presence of macro-AST, which was confirmed as a complex with IgG-κ. The cold storage method was validated using many samples obtained from several patients. Use of this simple method to detect macro-AST may avoid unnecessary examinations and patient anxiety even at primary care facilities.

Recent clinical studies have shown that the interruption of platelet function appears to be effective for treatment of coronary occlusive diseases. For this purpose, a Fab fragment of humanized anti-platelet glycoprotein (GP) IIb/IIIa monoclonal antibody (YM 337) that exhibited an in vivo antithrombotic effect without prolongation of bleeding time in monkeys was previously characterized. In this study, the effect of YM 337 under physiological flow conditions with high or low shear rate was evaluated. The antiplatelet effects of YM 337 under varying wall shear rates were examined with the whole blood flow system. This technique allows real time visualization of the formation of fluorescence-labeled platelet thrombi on a collagen surface in a parallel plate flow chamber mounted on an epifluorescence microscope. The process of thrombus growth was also recorded in video tape and subjected to computer-assisted image analysis. We found that YM 337 displayed a high shear-preferential antiplatelet effect, while ReoPro, a control anti-GP IIb/IIIa antibody, did not show such shear dependency. The present findings therefore suggest that YM 337 might be a useful antiplatelet agent which can block pathological thrombotic events occurring under high shear, such as in coronary occlusive diseases.

Giant cell arteritis (GCA) is a chronic vasculitis that primarily affects the elderly, and can cause visual impairment, requiring prompt diagnosis and treatment. The global impact of the coronavirus disease 2019 (COVID-19) pandemic has been substantial. Although vaccination programs have been a key defense strategy, concerns have arisen regarding post-vaccination immune-mediated disorders and related risks. We present a case of GCA after COVID-19 vaccination with 2 years of follow-up. A 69-year-old woman experienced fever, headaches, and local muscle pain two days after receiving the COVID-19 vaccine. Elevated inflammatory markers were observed, and positron emission tomography (PET) revealed abnormal uptake in the major arteries, including the aorta and subclavian and iliac arteries. Temporal artery biopsy confirmed the diagnosis of GCA. Treatment consisted of pulse therapy with methylprednisolone, followed by prednisolone (PSL) and tocilizumab. Immediately after the initiation of treatment, the fever and headaches disappeared, and the inflammation markers normalized. The PSL dosage was gradually reduced, and one year later, a PET scan showed that the inflammation had resolved. After two years, the PSL dosage was reduced to 3 mg. Fourteen reported cases of GCA after COVID-19 vaccination was reviewed to reveal a diverse clinical picture and treatment response. The time from onset of symptoms to GCA diagnosis varied from two weeks to four months, highlighting the challenge of early detection. The effectiveness of treatment varied, but was generally effective similarly to that of conventional GCA. This report emphasizes the need for clinical vigilance and encourages further data collection in post-vaccination GCA cases.