Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) can occasionally trigger thrombotic microangiopathy (TMA). Cytomegalovirus (CMV) may be reactivated during intensive immunosuppressive therapy for AAV and cause TMA. Therefore, we aimed to evaluate the clinical features of and the association between vascular endothelial injury markers and TMA due to CMV in patients with AAV. A 61-year-old female was diagnosed with AAV and severe kidney injury. Immunosuppressive therapy gradually improved her symptoms and laboratory findings. However, 2 weeks after induction therapy initiation, she exhibited altered consciousness, a significant decrease in platelet count, and hemolytic anemia, resulting in a TMA diagnosis. Plasma exchange did not improve TMA findings and routine screening test revealed CMV infection. Ganciclovir injection improved the infection and TMA findings. Consequently, we diagnosed her with CMV-induced TMA. Both AAV and CMV may induce severe vascular endothelial injury, potentially leading to TMA development. CMV-induced TMA should be considered when TMA develops during induction therapy against AAV. Moreover, of the three serum markers of vascular injury-serum sulfatides, soluble thrombomodulin, and pentraxin 3-serum sulfatides may be associated with the development of TMA, and a high level of soluble thrombomodulin may be associated with the development of CMV viremia during the clinical course of AAV.

We herein present a case involving an 86-year-old man with abdominal aortic aneurysm complicated by symptomatic disseminated intravascular coagulation (DIC). The patient received preoperative treatment for DIC using recombinant human soluble thrombomodulin (rTM) followed by open surgical repair of the aneurysm. The patient\'s coagulopathy cleared quickly after the start of rTM, and the intraoperative and postoperative course went smoothly. The patient was followed without anticoagulant medication, and there was no recurrence of DIC during 14 months of follow-up. The preoperative administration of rTM can be a useful choice to assist safe treatment of aortic aneurysm complicated by aneurysm-related DIC.

Hemophagocytic lymphohistiocytosis (HLH) is a fatal disease characterized by a highly inflammatory state due to the abnormal activation of T lymphocytes and macrophages. Miliary tuberculosis (MTB) is a rare cause of HLH and its clinical appearances occasionally resembles that of intravascular lymphoma (IVL). A 76-year-old woman presented with persistent fever and fatigue. Abnormal laboratory findings showing thrombocytopenia (13,000/μL), hypofibrinogenemia (101 mg/dL), hyperferritinemia (2,312 ng/mL), and markedly elevated soluble interleukin-2 receptor (sIL-2R) level (32,200 U/mL), in addition, hemophagocytosis in the bone marrow (BM) smear, were suggestive of IVL-associated HLH. The pathology of the BM biopsy specimen showed granuloma with non-caseous necrosis, and culture tests using sputum, gastric fluid, urine, and peripheral and bone marrow blood revealed the presence of Mycobacterium tuberculosis, leading to the final diagnosis of MTB-associated HLH. Anti-TB medications and corticosteroids were administered, but thrombocytopenia, hypofibrinogenemia, and hyperferritinemia persisted. Concomitant use of recombinant thrombomodulin (rTM) enabled regression of clinical status. In this case, BM biopsy served as the diagnosis of MTB-associated HLH, although IVL-associated HLH is initially suspected by an extremely high level of sIL-2R. Furthermore, this case report informs that using rTM could improve the outcomes of MTB-associated HLH.

A young man repeatedly found a right atrial mass with severe wheezing and extreme dyspnea. His condition was critical and complicated. The process of correct diagnosis was full of twists and turns. Finally, he got better and was discharged from the hospital after anticoagulation therapy, which suggested that correct clinical thinking and decision are particularly important in the process of diagnosis and treatment.

Disseminated intravascular coagulation (DIC) is a common and morbid complication of streptococcal toxic shock syndrome (STSS). Because DIC with STSS progresses rapidly, prompt and proper care is critical. The present report describes the case of a 10-year-old boy who survived STSS with DIC without sequelae after treatment with combination anticoagulant therapy of recombinant human soluble thrombomodulin (rhTM) and danaparoid. RhTM and antithrombin-III were administered on day 1. RhTM administration was continued. Despite this, on day 2, his general condition remained poor, his fever persisted and his DIC score increased from an initial 5 points upon admission to 9 points. Therefore, danaparoid was additionally administered from day 2 onwards. The patient recovered without serious complications. Combination anticoagulant therapy of rhTM and danaparoid for DIC in a child with STSS was effective and safe. Therefore, this combination therapy could be used as an option for managing high-risk, rapidly progressing disease states, which predispose to morbid sequelae and death, such as DIC with STSS. RhTM and danaparoid therapy may reduce the risk of serious complications, such as organ failure, and improve the prognosis not only in STSS but also in other conditions with infection and DIC concurrence, such as sepsis.

BACKGROUND: Administration of recombinant human soluble thrombomodulin (rTM) is often used in Japan to treat septic disseminated intravascular coagulation (DIC). Thrombin-activatable fibrinolysis inhibitor (TAFI) is a fibrinolysis inhibitor activated by the thrombin-thrombomodulin complex, however, it is unknown whether circulating activated TAFI is increased after rTM administration in patients with DIC. Furthermore, the relationship between TAFI activation and the prognosis of septic DIC is not defined yet.
METHODS: We report a series of 8 patient\'s TAFI activation with septic DIC treated by rTM. We sought to investigate the effect of rTM on TAFI activation and the association of plasma activated TAFI (TAFIa/ai) levels with the prognosis of septic DIC. Using plasma samples from clinical studies conducted from May 2016-March 2017 on eight patients with septic DIC at Kagoshima University Hospital, we measured plasma levels of total TAFI, TAFIa/ai, thrombin-antithrombin complex (TAT), prothrombin fragment 1 + 2 (F1 + 2), soluble fibrin (SF), antithrombin (AT), protein C (PC), protein S (PS), and plasminogen activator inhibitor-1 (PAI-1) before and after intravenous rTM administration. Then, we evaluated the relationship of these marker levels to prognosis. The thrombin-rTM complex activated TAFI in vitro in plasma from a healthy volunteer. However, TAFIa/ai levels did not significantly increase over baseline in the septic DIC patients after intravenous rTM administration. Baseline TAFIa/ai levels in non-survivors were significantly higher than those in survivors.
CONCLUSIONS: Plasma TAFIa/ai did not increase with rTM administration. Elevated baseline TAFIa/ai concentration may be a negative prognostic indicator in septic DIC. Larger studies are needed to confirm the in vivo effect of rTM on TAFI activation.

We report the case of a 36‒year‒old man who was treated with S‒1 plus oxaliplatin(SOX)therapy for gastric cancer with disseminated intravascular coagulation(DIC). The patient visited our hospital for the treatment of an unresectable type 4 advanced gastric cancer. He had respiratory distress at the first visit. A chest CT scan revealed ground‒glass shadows as well as interstitial and septal thickening diffusely located in both the lungs, which suggested cancerous lymphangiopathy. Moreover, based on blood test results, DIC was diagnosed. After the administration of SOX in combination with recombinant human soluble thrombomodulin, the patient recovered from DIC, and the values of the tumor markers(CEA and CA19‒9) were normalized. After more than 14 months post treatment, the patient has survived without relapse. There are several reports that chemotherapy for gastric cancer is effective for DIC; however, there are no reports on regimens using oxaliplatin. Regimens using this drug may improve the prognosis of gastric cancer complicated by disseminated myelocarcinomatosis and DIC.

BACKGROUND: Chronic disseminated intravascular coagulation (DIC) associated with thoracic aortic aneurysm is characterized by enhanced fibrinolysis and is thought to be stable in the compensated/asymptomatic stage, with few bleeding symptoms. However, DIC can lead to decompensated/hemorrhagic stage disseminated intravascular coagulation, resulting in severe bleeding diathesis, and there is currently no established strategy for treatment of DIC in aortic aneurysms.
METHODS: A 77-year-old woman underwent angiography and cardiac catheterization, before descending aortic replacement surgery. She developed DIC in postprocedure week 2 with extensive, uncontrollable massive subcutaneous hemorrhage.
METHODS: Her acute-phase DIC score was 7 points, and the risk of mortality within 30 days after surgery according to the JapanSCORE was estimated to be 33.6%.
METHODS: Therapy was a combination of recombinant human soluble thrombomodulin (rhTM) and an aortic stent-graft treatment.
RESULTS: Short-term improvements were seen in both DIC and bleeding diathesis. The thoracic aortic aneurysm with severe DIC was eventually corrected by administration of rhTM.
CONCLUSIONS: We report the use of rhTM as an effective, novel anticoagulant drug with anti-inflammatory activity for treating DIC with suppressed fibrinolysis, which is typically associated with sepsis. In patients with a high hemorrhagic diathesis, in whom preoperative control of DIC cannot be achieved with conventional anticoagulation and radical surgical repair cannot be performed, a combination of rhTM and endovascular therapy may be a powerful new treatment option.

Vibration induced white fingers (VWF) is one form of secondary Raynaud\'s phenomenon (RP).
Vibration exposed workers with RP and vibration exposed controls without RP participated. Blood samples were collected before and after cold challenge exposure (COP). The concentration of von Willebrand factor (vonWf), thrombomodulin (TM), serotonin (SER), endothelin-1 (ET1 ), calcitonin gene-related peptide, or thromboxane A2 was calculated. The diagnostic usefulness of the substances for ruling in the diagnosis of Raynaud\'s was evaluated.
The cases showed a significant lower concentration of vonWf before and after COP, a significant increase of ET1  and a decrease of TM after COP. The diagnostic usefulness of vonWf showed a likelihood of defining a true case by 35%.
vonWf, TM, SER, or ET1 are suggested biomarkers for VWF. Diagnostic evaluation of vonWf showed a likelihood of defining a true case by 35% in the diagnosis of RP related to vibration.

Thrombomodulin functions as an anticoagulant through thrombin binding and protein C activation. We herein report the first case of hereditary functional thrombomodulin deficiency presenting with recurrent subcutaneous hemorrhage and old cerebral infarction. The patient had a homozygous substitution of glycine by aspartate at amino acid residue 412 (Gly412Asp) in the thrombin-binding domain of the thrombomodulin gene (designated thrombomodulin-Nagasaki). In vitro assays using a recombinant thrombomodulin with the same mutation as the patient showed a total lack of thrombin binding and activation of protein C and thrombin-activatable fibrinolysis inhibitor (TAFI). Marked clinical and laboratory improvement was obtained with recombinant human soluble thrombomodulin therapy.