Broad subcutaneous emphysema with airway obstruction during robot-assisted partial nephrectomy: A case report and literature review.

Introduction: Subcutaneous emphysema is a relatively common complication in laparoscopic surgery. However, airway obstruction secondary to subcutaneous emphysema is rare. Case presentation: A 63-year-old woman with a 56-mm left renal tumor underwent a robot-assisted partial nephrectomy. The operative time was 155 min, the insufflation time was 108 min, and the estimated blood loss was 70 mL. The pneumoperitoneum pressure was maintained at 12 mmHg, except at 15 mmHg for 19 min during tumor resection. The end-tidal CO2 was <47 mmHg throughout the procedure. Postoperatively, broad subcutaneous emphysema from the thigh to the eyelid was observed. Computed tomography revealed airway obstruction, and extubation was aborted. On postoperative day 1, emphysema around the trachea and neck improved and the intubation tube was successfully removed. Conclusion: Both laryngeal emphysema and physical compression secondary to emphysema can cause airway obstruction. To reduce gas-related complications, the risk of developing subcutaneous emphysema should be properly assessed during robot-assisted laparoscopic surgery.

A discrepancy between prothrombin time and Normotest (Hepaplastintest) results is useful for diagnosis of acquired factor V inhibitors.

Acquired coagulation factor inhibitors are rare. Among them, coagulation factor V (FV) inhibitor is particularly uncommon and presents with variable clinical manifestations. Certain acquired FV inhibitor patients have only mild bleeding or, in select cases, no symptoms at all, leading to spontaneous recovery. Others have life-threatening bleeding that requires medical attention. Thus, a prompt decision regarding diagnosis and clinical intervention is crucial for such patients. In five acquired FV inhibitor cases treated in our facility, each patient had a malignancy as an underlying disease and all unexpectedly showed prolongation of both prothrombin time (PT) and activated partial thromboplastin time (APTT). They all also displayed a discrepancy between PT and Normotest (Hepaplastintest, HPT) results. All but one patient experienced no bleeding at the time of diagnosis and achieved spontaneous recovery in 1-3 weeks. The patient with bleeding symptoms received plasma exchanges and a platelet transfusion. Useful markers in diagnosing the presence of an acquired FV inhibitor were a sudden prolongation of PT and APTT, and a discrepancy between the PT/APTT and HPT assays. Spontaneous recovery can be expected for patients with only minor bleeding.

Aortic Aneurysm-associated Disseminated Intravascular Coagulation that Responded Well to a Switch from Warfarin to Rivaroxaban.

We describe a case in which uncontrolled chronic disseminated intravascular coagulation (DIC) caused by an aortic aneurysm that was exacerbated by chemotherapy for lung cancer, showed dramatic improvement when warfarin, which was being administered for atrial fibrillation, was replaced by rivaroxaban, a direct oral anticoagulant (DOAC). The present case is interesting because a DOAC was effective in treating DIC due to an aortic aneurysm, whereas warfarin, another oral anticoagulant, was ineffective. In controlling DIC, it is important to inhibit activated coagulation factors such as thrombin and activated factor X, rather than the coagulation factors, which act as substrates.

Thrombosis Prediction Based on Reference Ranges of Coagulation-Related Markers in Different Stages of Pregnancy.

INTRODUCTION: Careful monitoring of the hypercoagulable state is required during pregnancy. However, coagulation and fibrinolysis markers are not fully utilized because there are no reference values reflective of coagulation and fibrinolysis dynamics during pregnancy, which differ from the nonpregnant state. METHODS: Changes in antithrombin (AT), fibrinogen (Fbg), prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex (TAT), soluble fibrin (SF), D-dimer (DD), and protein S (PS) were investigated in healthy pregnant women, and reference ranges in the early, mid, late, and end stages of pregnancy were established. RESULTS: The AT was essentially constant throughout pregnancy. The Fbg, F1+2, TAT, and DD increased significantly as pregnancy progressed. In contrast, SF did not show a significant increase throughout the entire pregnancy period. Total PS antigen and total PS activity showed a corresponding decrease from early gestation. When test data in 3 cases in which deep vein thrombosis or intrauterine fetal death occurred during pregnancy were compared to the established reference ranges, all of the cases had multiple markers with values that exceeded the reference ranges. CONCLUSION: Establishing reference ranges for each week could potentially make it possible to evaluate abnormalities of the coagulation and fibrinolysis systems during pregnancy. Of note, SF might be a useful marker that reflects thrombus formation during pregnancy. Larger-scale studies will be required to establish reference ranges for every gestational week.

Increase of salt dependence of halophilic nucleoside diphosphate kinase caused by a single amino acid substitution.

Nucleoside diphosphate kinase (HsNDK) from an extremely halophilic archaea, Halobacterium salinarum, is composed of a homo hexamer, assembled as a trimer of basic dimeric units. It requires >2 M NaCl for refolding, although it does not require NaCl for stability or enzymatic activity below 30 °C. A HisN111L mutant with an N-terminal extension sequence containing hexa-His tag, in which Asn111 was replaced with Leu, was designed to be less stable between basic dimeric units. This mutant can lose between 6 and 12 hydrogen bonds between basic dimeric units in the hexamer structure. The HisN111L mutant had enhanced salt requirements for enzymatic activity and refolding even though the secondary structure of the HisN111L mutant was confirmed to be similar to the control, HisNDK, in low and high salt solutions using circular dichroism. We reported previously that G114R and D148C mutants, which had enhanced interactions between basic dimeric units, showed facilitated refolding and stabilization in low salt solution. The results of this study help to elucidate the process for engineering industrial enzymes by controlling subunit-subunit interactions through mutations.

Two case reports of inherited antithrombin deficiency: a novel frameshift mutation and a large deletion including all seven exons detected using two methods.

An inherited antithrombin deficiency is an autosomal dominant thrombotic disorder. We identified two pedigrees of inherited type I antithrombin deficiency and two responsible mutations in each. A novel 21-22delAA appeared to have caused a frameshift with a premature termination at amino acid +63 in one patient and a large deletion including all seven exons was identified by multiplex ligation-dependent probe amplification in the other. Some asymptomatic relatives of the second patient had the same mutation. The present findings support the value of using more than one method of gene analysis and of studying the families of probands with inherited thrombotic disorders.

[Two cases of acquired hemophilia A in elderly patients].

Acquired hemophilia A is a rare bleeding diathesis caused by autoantibodies against clotting factor VIII. The incidence of acquired hemophilia A increases with age. We report two cases of acquired hemophilia A in elderly patients and their clinical characteristics. Case 1: A 66-year-old man was referred to our hospital with massive subcutaneous and intramuscular hemorrhage. Prolonged APTT, low factor VIII activity and factor VIII inhibitor with high titer (42 BU/ml ) were observed, confirming the diagnosis of acquired hemophilia A. His hemorrhages disappeared soon after 50 mg/day oral prednisolone was administered. Although early steroid withdrawal lead to repeated prolongation of APTT, the addition of 20 mg/day oral prednisolone successfully decreased the inhibitor titer. The underlying disease was not identified. Case 2: An 85-year-old man with advanced gastric cancer was referred to our division because of severe bleeding. His factor VIII inhibitor titer was 64 BU/ml . Activated prothrombin complex concentrates were used to control the bleeding. Initially, he did not seem to respond to 20 mg/day oral prednisolone, but a further 12 weeks of 20 mg/day prednisolone finally achieved normalization of his hemostatic parameters. Subsequently, he successfully underwent surgery for cancer. The responses to immunosuppressive therapy were very different in the two cases, probably because of the difference in the underlying diseases. The immunosuppressive therapy of acquired hemophilia A should be strictly tailored to the patient's characteristics to minimize treatment-related adverse effects.

Expression of annexin II in experimental abdominal aortic aneurysms.

Annexin II is a receptor of tissue-type plasminogen activator (t-PA). We have previously identified annexin II by immunolocalization in human atherosclerotic abdominal aortic aneurysms (AAAs). To investigate possible interactions between annexin II and AAA development, we examined annexin II mRNA and protein expression in a rat model of experimental AAA. AAAs were induced in rats by transient aortic infusion of elastase. The rats were divided into three groups: a saline-treated control group, a group with 15-min elastase infusion, and a group with 30-min elastase infusion. The 15-min elastase-infused group had smaller aneurysms and more preserved media than the 30-min elastase-infused group. Immunohistochemistry showed that annexin II expression was increased in the thickened intima and media of AAA rats as compared with the media of control rats. Furthermore, annexin II was colocalized with macrophages and smooth muscle cells. Quantitative real-time polymerase chain reaction showed that annexin II mRNA levels were up-regulated only in the smaller aneurysm group compared with the control group. In contrast, t-PA mRNA levels were increased in both the 15- and 30-min elastase-infused groups as compared with the control group. These results demonstrate various levels of annexin II expression within the aortic wall of rats with experimental AAAs. It has been suggested that alteration of fibrinolytic activity regulated by annexin II within the aortic wall may be associated with aneurysm formation.

Increased macrophage colony-stimulating factor levels in patients with Graves' disease.

Previous studies have found markedly elevated serum concentrations of proinflammatory cytokines in patients with Graves' disease (GD). We investigated the role of macrophage colony-stimulating factor (M-CSF) in GD. We assayed concentrations of M-CSF in sera from 32 patients with GD (25 untreated; 7 receiving thiamazole therapy). We also studied 32 age-matched healthy subjects as controls. Relationships between serum M-CSF and both thyroid state and serum lipids were examined. Moreover, to examine the effect of thyroid hormone alone on serum M-CSF, T3 was administered orally to normal subjects. Serum concentrations of M-CSF in GD patients who were hyperthyroid were significantly increased compared with GD patients who were euthyroid (P < 0.05) and control subjects (P < 0.0001). Serum M-CSF concentrations correlated closely with T3 levels in patients (r = 0.51, P < 0.005). Serial measurement of five individual patients revealed that serum concentrations of M-CSF were significantly decreased (P < 0.05), reaching normal control values upon attainment of euthyroidism. Furthermore, oral T3 administered to 15 volunteers for 7 days produced significant increases in serum levels of M-CSF (P < 0.05). The close correlation between serum M-CSF and serum thyroid hormone levels suggests that high circulating levels of thyroid hormones may directly or indirectly potentiate the production of M-CSF in patients with GD.

Expression of annexin II in human atherosclerotic abdominal aortic aneurysms.

BACKGROUND: Annexin II is a receptor for tissue-type plasminogen activator (t-PA) that converts plasminogen to plasmin. Although the fibrinolytic system is known to play an important role in the pathogenesis of abdominal aortic aneurysms (AAAs), the relationship between annexin II and AAA development is unknown. Therefore, we examined annexin II localization in the wall of human atherosclerotic AAAs. METHODS AND RESULTS: Specimens from 13 patients undergoing elective repair of an AAA were taken. Annexin II expression was evaluated by immunohistochemical analysis. Immunostaining results were semiquantitatively analyzed using histology scores and WinROOF software based on staining intensity. The expression of annexin II was increased and the histology score was higher in the shoulder region of the atheromatous plaque than in the atheroma and fibrous plaque regions. Annexin II appeared to have greater expression and the histology score was higher in regions where the media was preserved. Furthermore, there was a significant inverse correlation between AAA size and histology score in the fibrous plaque region. CONCLUSIONS: The present work demonstrates various levels of annexin II expression within the aneurysm wall. Therefore, we suggest that alteration of annexin II expression within the aortic wall may be associated with the development of an aneurysm.

[The positive rate of lupus anticoagulant according to the each understanding disease in our hospital].

We investigated positive rate of lupus anticoagulant (LA) according to the each understanding disease in our hospital. 596 cases (F/M 477/149, 7-87 y.o.) were examined from 2003 to 2004 years. LA tests were performed using 2 methods such as kaolin clotting time (KCT) mixing test and dilute Russell's viper venom time (dRVVT). The LA tests were most frequently ordered in dermatology, and the most common purpose of LA test was the check of existence of antiphospholipid (aPL) in patients with collagen diseases. The LA positive rate was the highest in patients with SLE among the collagen diseases, and in patients with cerebral infarction among the thrombotic diseases. The LA positive rate exceeded 40% in ITP and livedo reticularis. Moreover, LA positive rate was 16% in preoperative tests of the orthopedic patients without any physical diseases. Thus, it was suggested that there were considerable numbers of the asymptomatic LA positive persons. The LA positive cases based on KCT only accounted for about 60% of all the LA positive cases. Among the thrombotic patients, there were not the DVT/PE patients with only KCT positive. On the other hands, the KCT positive rate was higher than the dRVVT positive rate in patients with cerebral infarction. There were not dRVVT single positive cases in patients with recurrent abortion and ITP, but KCT single positive case accounted for about 90%. From these results, it is suggested that there is a difference in KCT and dRVVT about detecting aPL, and that care should be taken to interpret the LA test.

No interplay between the pathways mediating coagulation and inflammation in tissue factor-induced disseminated intravascular coagulation in rats.

OBJECTIVE: Previous reports have suggested an interplay between the pathways mediating coagulation and inflammation in endotoxemia and sepsis. The present study was designed to examine whether cross-signaling between the pathways mediating coagulation and inflammation occurs, as suggested by the pattern of cytokine production observed following tissue-factor (TF)-induced disseminated intravascular coagulation (DIC). DESIGN: Prospective, comparative, experimental study. SETTING: Laboratory at a university hospital. SUBJECTS: Male Wistar rats, aged 6-7 wks, and weighing 160-170 g. INTERVENTIONS: Male Wistar rats were administered TF (3.75 units/kg every 4 hrs), TF, and tranexamic acid (TA; 50 mg/kg every 4.5 hrs) or lipopolysaccharide (30 mg/kg every 4 hrs) via the tail vein, and blood was sampled at 0, 4, 8 and 12 hrs. MEASUREMENTS AND MAIN RESULTS: Subsequent alterations in thrombin-antithrombin complex and fibrinogen levels, as well as platelet counts, indicated that the severity of both types of experimental DIC (TF-induced and lipopolysaccharide-induced) was similar with respect to hemostatic activation and development of consumption coagulopathy. In lipopolysaccharide-induced DIC, a sharp increase in plasma tumor necrosis factor levels was observed at 4 hrs, after which a sharp decline was noted. Plasma levels of interleukin-6 were markedly increased at 4 hrs, after which a sustained elevation was observed for the duration of the experimental period (tumor necrosis factor, 1270 +/- 280, 180 +/- 40, and 120 +/- 30 pg/mL at 4, 8 and 12 hrs, respectively; interleukin-6, 5810 +/- 1320, 4850 +/- 730, and 5230 +/- 1280 pg/mL at 4, 8 and 12 hrs, respectively). On the other hand, tumor necrosis factor and interleukin-6 were not detected following TF-induced DIC (0 +/- 0 at 4, 8, and 12 hrs for both tumor necrosis factor and interleukin-6). In the TF+TA group, significant increases in tumor necrosis factor and interleukin-6 were observed, compared with the TF group. CONCLUSIONS: There is no overt interplay between the pathways mediating coagulation and inflammation in TF-induced DIC, as observed in lipopolysaccharide-induced DIC.

Immunoglobulin preparations attenuate organ dysfunction and hemostatic abnormality by suppressing the production of cytokines in lipopolysaccharide-induced disseminated intravascular coagulation in rats.

OBJECTIVE: We attempted to clarify the effect of immunoglobulin concentrates on the rat lipopolysaccharide (LPS)-induced disseminated intravascular coagulation (DIC) model. DESIGN: Prospective, comparative, experimental study. SETTING: Laboratory at a university hospital. SUBJECTS: Male Wistar rats, aged 6 to 7 wks and weighing 160 to 170 g. INTERVENTIONS: Two kinds of experiments were performed. In the first, experimental DIC was induced by sustained infusion of 30 mg/kg LPS for 4 hrs via the tail vein, and two doses of immunoglobulin (25 or 100 mg/kg/4.5 hrs) were administered to rats 30 mins before infusion of LPS, after which immunoglobulin infusion was continued for a further 4 hrs. In the second, experimental DIC was induced by sustained infusion (5 mg/kg/1 hr) of LPS for 1 hr, and one dose of immunoglobulin (100 mg/kg/4 hrs) was administered to rats after LPS induction. The parameters were estimated at 4 hrs and 8 hrs in the first experiment and at 1, 5, and 10 hrs in the second one. MEASUREMENT AND MAIN RESULTS: Similar results were observed in the two experiments. Consumption coagulopathy and hemostatic activation were attenuated, especially when immunoglobulin was administered before LPS infusion. Plasma levels of creatinine and alanine aminotransferase were significantly depressed by coadministration of immunoglobulin. Marked glomerular fibrin deposition was observed in the LPS-induced DIC model, but this deposition was reduced by immunoglobulin. In the first stage of the experiment, plasma levels of tumor necrosis factor (TNF) and interleukin (IL)-6 were suppressed by coadministration of immunoglobulin. In the second, plasma levels of IL-6 were significantly suppressed by immunoglobulin. CONCLUSION: It was concluded that plasma levels of TNF and IL-6 could be significantly suppressed by immunoglobulin in the LPS-induced DIC model. Moreover, hemostatic abnormality, organ dysfunction, and glomerular fibrin deposition in this model were all ameliorated by immunoglobulin.

Effects of sarpogrelate hydrochloride in a patient with chronic graft-versus-host disease: a case report.

Chronic graft-versus-host disease (cGVHD) is a frequent complication of allogenic bone marrow transplantation. Even with aggressive treatment, cGVHD is associated with a significant degree of morbidity and mortality. cGVHD resembles autoimmune disorder, particularly systemic sclerosis (SSc). Sarpogrelate hydrochloride (SH) is an antagonist of the 5-hydroxytryptamine2A (5HT2A) receptor and has been reported to be effective in the treatment of systemic sclerosis (SSc) patients with Raynaud phenomenon. We used SH to treat a cGVHD patient, and we measured plasma PDGF and total TGF-beta levels. After SH treatment, his plasma PDGF and total TGF-beta levels decreased, and he noticed improvement in his skin pigmentation. In the present case, SH may have improved the skin lesion by inhibiting the synthesis of PDGF and TGF-beta.

Treatment of primary central nervous system lymphoma with induction of complement-dependent cytotoxicity by intraventricular administration of autologous-serum-supplemented rituximab.

We describe an immunocompetent 19-year-old man with CD20-positive primary central nervous system (CNS) lymphoma refractory to chemotherapy and irradiation. After intraventricular administration of rituximab, a chimeric anti-CD20 monoclonal antibody, supplemented with autologous serum, a remarkable response developed to the CNS parenchymal lymphoma. Cytotoxicity assays showed that untreated patient's serum with rituximab, but not that of heat-inactivated patient's serum with rituximab or rituximab alone, induced potent rituximab-mediated cytotoxicity against tumor cells in the patient's cerebrospinal fluid, suggesting induction of complement-dependent cytotoxicity against CNS lymphoma.

Effect of combined therapy of danaparoid sodium and tranexamic acid on chronic disseminated intravascular coagulation associated with abdominal aortic aneurysm.

Chronic disseminated intravascular coagulation (DIC) is a well-known complication of aortic aneurysm. A 63-year-old man with bleeding tendency and a large palpable abdominal aortic aneurysm (AAA) was diagnosed as having fibrinolysis dominant DIC by the excessive activation of both coagulation and fibrinolysis (plasmin -alpha2 plasmin inhibitor complex concentration is usually >4 microg/ml). Although several treatments were tried, DIC could not be controlled until the patient was given combined therapy of danaparoid (1,250 U/12 h, bolus IV) and tranexamic acid (0.5 g x 3/day, oral administration). This therapy may be beneficial when control for bleeding is required without restricting the ambulatory movement of patients by continuous drip.