We evaluated several molecular markers of hemostasis in 92 patients with hypercoagulable states treated with anticoagulant therapy. In all patients, the average values of the international normalized ratio (INR) were 1.70 +/- 0.50; this increase in INR was not, however, significant in patients under thrombotest (TT) monitoring. There were no thrombotic or severe bleeding complications in these patients during a period of 27 months. Plasma levels of thrombin-antithrombin complex (TAT), plasmin-plasmin inhibitor complex (PPIC), D-dimer, and soluble fibrin monomer (sFM) were slightly increased, suggesting that anticoagulant therapy was not completely effective in our Japanese patients based on the values of the TT. The INR was negatively correlated with TT, protein C, and protein S and particularly with TT between 10 and 80%. The range of TT was not correlated with the plasma level of TAT, PPIC, D-dimer, or sFM, but the range of INR was correlated with the plasma level of TAT, D-dimer, and sFM. The percentage of TAT, D-dimer, and sFM within normal range was significantly lower in patients with high INR. These findings show that INR is better than TT for the monitoring of warfarin therapy and that the therapeutic values of INR during the anticoagulant therapy should be > 1.7 in Japanese patients.
We examined haemostatic abnormalities and thrombotic disorders in 217 patients with malignant lymphoma. Plasma levels of fibrinogen and D-dimer were significantly higher in patients with malignant lymphoma than in healthy subjects. The incidence of severe complications, such as disseminated intravascular coagulation (DIC) and interstitial pneumonia (IP), differed with each clinical stage or histological type, but they occurred frequently in stage IV or natural killer (NK) cell lymphoma. Plasma levels of fibrinogen degradation products (FDP) and D-dimer, leukocyte tissue factor (TF) mRNA and plasma TF antigen were significantly higher in stage IV than in stage I, II or III. Plasma levels of FDP, D-dimer, and leukocyte TF mRNA in NK cell lymphoma were markedly higher than in other types of lymphoma. Immunohistochemical staining of NK cell lymphoma revealed that granulocyte macrophage colony-stimulating factor was positive in tumour cells, whereas von Willebrand factor and TF were positive in vascular endothelial cells of surrounding tissue. Our results suggested that patients with stage IV disease and NK cell lymphoma were in abnormal thrombotic and haemostatic state, and may frequently develop DIC and IP. One of the mechanisms of DIC and IP may involve elevated cytokine production by lymphoma cells, which can stimulate the expression of TF in blood cells or surrounding tissue.
Background: It has been suggested that there is a complex interaction between microbiota and various human diseases. Some bacteria have been reported to be involved in the inception and progression of asthma, and others in the protection against asthma. We know very little about the mechanisms by which bacteria do harm or good with regard to asthma. This study investigated whether bacteria exert differential effects on the functions of eosinophils, major effector cells in airway inflammation in asthma. Methods: Eosinophils were purified from healthy adult volunteers by Percoll density gradient centrifugation and negative immunomagnetic bead selection using anti-CD16 microbeads. Three kinds of heat-killed bacteria that have been implicated in asthma, namely Staphylococcus aureus (SA), Haemophilus influenzae (HI) and a Prevotella sp. (PS), were tested for their effects on the secretion of eosinophil-derived neurotoxin (EDN), the generation of superoxides and the production of cytokines/chemokines. Results: SA, but not HI or PS, induced significant EDN release in a dose-dependent manner. Superoxide generation was significantly enhanced by each of the bacterial species, but most strongly by SA, which induced significantly greater TNF-α production by eosinophils than either HI or PS. Conversely, interleukin 10, an anti-inflammatory cytokine, was more strongly induced by HI and PS than by SA. Conclusions: Bacteria exert differential effects on eosinophils. Based on these results, SA may be involved in the exacerbation of, and HI and PS in the inhibition of, eosinophilic inflammation in asthma.
In 1984, the Scientific and Standardization Committee (formerly ICTH) recommended the use of the International Sensitivity Index and International Normalized Ratio (INI/INR) System for the monitoring of oral anticoagulant therapy. This system was introduced because the sensitivity of thromboplastin reagents used for the measurement of prothrombin time (PT) was widely different and comparison among hospitals employing different reagents was virtually impossible. In this study, we simultaneously measured the plasma from 7 patients with warfarin therapy at 4 different institutions for PT seconds, PT-INR, thrombotest (TT) seconds and TT-INR. The comparison between these laboratories revealed clinically important variances between the 4 laboratories even when PT was converted to PT-INR. Laboratory 1 and laboratory 3 were using the same thromboplastin reagents for the measurement of PT. The PT (seconds) in both laboratories showed similar numbers, but when they converted into INR, the variances were significant (maximum coefficient of variance 10.44). We investigated the reason why these differences occurred and found that the PT seconds (11.40) for normal control at laboratory 3 were somewhat larger than those of other laboratories. If we assume that PT-INR is identical to TT-INR, the estimated PT (second) for normal control at laboratory 3 can be calculated from TT-INR, and was found to be 10.56 ± 0.10 seconds. This was nearly the same as the one that was used at laboratory 1. In conclusion, there still exist some difficulties that must be overcome bfore the ISN/INR system can be used reliably, and we suggest attention be given to the PT seconds used as normal control plasma.
Pseudolymphoma is reactive extranodal lymphocytosis, and it's lymphocytes are so minimally atypical that it is basically benign. The patient was a 68-year-old female with pain in the left back and lower abdomen. Plain CT (computerized tomogram) of the kidney revealed a mass in the left kidney. It had a smooth surface and higher density than parenchyma. Similarly a left orbital mass was revealed by CT. We could not deny the mass to be a malignant tumor, so we took specimens from these lesions by an open biopsy. Histological examination of these specimens showed pseudolymphoma. Pseudolymphoma of the left kidney was reduced in its size by treatment with prednisolone. The patient is continuously followed up to date.
