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Patients with essential thrombocythemia (ET) often experience bleeding associated with acquired von Willebrand syndrome (AVWS) when the platelet count is markedly increased.We investigated whether von Willebrand factor (VWF) degradation is enhanced in patients with ET.Seventy patients with ET underwent VWF multimer (VWFM) analysis and measurement of VWF-related parameters. We calculated the VWFM index, defined as the ratio of intensities of a patient's molecular weight-categorized VWFMs, and those of a healthy subject's, using densitometric analysis. VWF degradation product (DP) was measured via ELISA using a monoclonal antibody that specifically recognizes Y1605 at the C-terminal boundary, which is exposed following ADAMTS13-mediated cleavage of the Y1605-M1606 bond of the VWF A2 domain.Patients with higher platelet counts had a significantly reduced high molecular weight (HMW)-VWFM index and an increased VWF-DP:VWF antigen (Ag) ratio compared to those with lower platelet counts. On multivariate analysis, the VWF-DP/VWF:Ag ratio was an independent predictor of the HMW-VWFM index. Patients who underwent cytoreductive therapy had a significantly higher HMW-VWFM index and lower VWF-DP/VWF:Ag ratio than those who did not. Among individual patients, there was also a significant increase in the HMW-VWFM index and a decrease in the VWF-DP/VWF:Ag ratio after cytoreductive therapy compared to pre-therapy values.In patients with ET, an increased platelet count is associated with enhanced cleavage of VWF at the Y1605-M1606 bond, primarily by ADAMTS13, leading to AVWS. Cytoreductive therapy reduces the platelet count, prevents excessive VWF cleavage, and improves VWFM distributions.

Background We compared the prognostic value of plasma high mobility group box 1 protein (HMGB1) and histone H3 levels with the International Society on Thrombosis and Haemostasis (ISTH) disseminated intravascular coagulation (DIC) scores for 28-day in-hospital mortality in patients with DIC caused by various underlying diseases. Methods We conducted a multicenter prospective cohort study including two hematology departments, four emergency departments, and one general medicine department in Japan, between August 2017 and July 2021. We included patients diagnosed with DIC by the ISTH DIC scoring system. Results Overall, 104 patients were included: 50 with hematopoietic disorders, 41 with infections, and 13 with the other diseases. The 28-day in-hospital mortality rate was 21%. The receiver operator characteristic (ROC) curve showed that a DIC score of 6 points, plasma HMGB1 level of 8 ng/mL, and plasma histone H3 level of 2 ng/mL were the optimal cutoff points. The odds ratios of more than these optimal cutoff points of the DIC score, plasma HMGB1, and histone H3 levels were 1.58 (95% confidence interval [CI]: 0.60 to 4.17, p = 0.36), 5.47 (95% CI: 1.70 to 17.6, p = 0.004), and 9.07 (95% CI: 2.00 to 41.3, p = 0.004), respectively. The area under the ROC curve of HMGB1 (0.74, 95% CI: 0.63 to 0.85) was better than that of the ISTH DIC scores (0.55, 95% CI: 0.43 to 0.67, p = 0.03), whereas that of histone H3 was not (0.71, 95% CI: 0.60 to 0.82, p = 0.07). Calibration and net reclassification plots of HMGB1 identified some high-risk patients, whereas the ISTH DIC scores and histone H3 did not. The category-free net reclassification improvement of HMGB1 was 0.45 (95% CI: 0.01 to 0.90, p = 0.04) and that of histone H3 was 0.37 (95% CI: − 0.05 to 0.78, p = 0.08). Conclusions Plasma HMGB1 levels have a prognostic value for mortality in patients with DIC. This finding may help physicians develop treatment strategies.

During the treatment of disseminated intravascular coagulation (DIC) associated with hematopoietic malignancies (particularly, acute leukemia), fatal bleeding, such as cerebral, alveolar, and gastrointestinal hemorrhages at diagnosis or immediately after initiating treatment, determines the patient's prognosis. DIC should always be suspected in such cases, and the diagnosis should be made on the basis of the former Ministry of Health and Welfare DIC diagnostic criteria or the 2017 Japanese Society on Thrombosis and Hemostasis DIC diagnostic criteria. This treatment requires the use of appropriate anticoagulants and replacement therapies. The anticoagulant should be chosen based on the patient's risk of bleeding. Here we present the recent evidence of DIC complicating hematopoietic malignancies with antithrombin agents and recombinant human soluble thrombomodulin. Moreover, prognostic markers during the course of therapy have been reported. The effect of treatment, including withdrawal from DIC, should be carefully assessed. In the future, detailed evidence regarding the tumor subtype, tumor burden, and disease severity will be required to ensure appropriate drug choice for the treatment.

A 70-year-old woman was hospitalized for exacerbation of chronic idiopathic thrombocytopenic purpura (ITP) and disseminated intravascular coagulation (DIC) from old aortic dissection. Initially, we increased the dose of prednisolone for ITP. However, her bleeding tendency caused by DIC worsened despite the rapid recovery of her platelet count, and the required amount of fresh-frozen plasma for transfusion increased. The administration of edoxaban for atrial fibrillation led to the marked improvement of her DIC status without serious adverse events. This case suggests that a direct oral anticoagulant may be an effective treatment for DIC caused by aortic dissection.

INTRODUCTION A criterion for disseminated intravascular coagulation (DIC) that reflects the status of controlled coagulopathy would be useful for determining when to stop treatment. Use of the DIC criteria of the Japanese Society on Thrombosis and Hemostasis (JSTH) for predicting the outcome during recombinant soluble thrombomodulin (thrombomodulin alfa, TM-α) treatment was evaluated. METHODS A retrospective, multicenter survey was conducted in 798 medical facilities in Japan. Of the 4342 patients who underwent TM-α treatment, 193 with infection-associated DIC were investigated. RESULTS The 28-day mortality rate increased with the increase in JSTH DIC scores at the end of TM-α treatment, with a Cramer's coefficient of association of 0.431. A reduced platelet count (odds ratio [OR]: 0.847, P

Background In patients with infectious diseases, disseminated intravascular coagulation (DIC) is often diagnosed without the fibrinogen value. The relationship between hypofibrinogenemia and outcomes of DIC in infectious diseases has thus remained unclear. Methods We analyzed 3204 patients who received with thrombomodulin alfa (TM-α) for DIC and suspected DIC. Hypofibrinogenemia was defined by a fibrinogen level Results Hypofibrinogenemia was observed in 10.3% of patients with infectious diseases. The frequencies of both bleeding and organ failure symptoms, and the scores for organ failure or the DIC diagnostic criteria were significantly higher in infectious disease patients with hypofibrinogenemia, suggesting that in patients with infectious diseases, hypofibrinogenemia is associated with more progressive and severe DIC. Although the 28-day survival rate and the DIC resolution rate were both significantly lower for infectious disease patients with DIC with hypofibrinogenemia than for those without hypofibrinogenemia, this difference was not observed in DIC patients with hematological diseases. Conclusions Hypofibrinogenemia among infectious disease patients with DIC may reflect increased consumption of fibrinogen due to accelerated coagulation reactions, while hypofibrinogenemia among hematological disease patients with DIC may be caused by fibrinogenolysis due to hyperfibrinolysis, and frequently results in bleeding and multiple-organ failure.

Supplemental material, sj-doc-1-cath-10.1177_10760296211054094 for Clinical Features of Disseminated Intravascular Coagulation According to the French-American-British Classification in Patients With Acute Leukemia and Thrombomodulin Alfa Treatment���A Cohort Study Using a Postmarketing Surveillance Database by Seki Yoshinobu, Goichi Honda and Noriaki Kawano, Toshimasa Uchiyama, Kazuo Kawasugi, Seiji Madoiwa, Naoki Takezako, Ikezoe Takayuki, Hideo Wada in Clinical and Applied Thrombosis/Hemostasis

Introduction In patients with infectious diseases, disseminated intravascular coagulation (DIC) is often diagnosed without the fibrinogen value and the relationship between hypofibrinogenemia and the outcomes of infectious DIC has remained unclear.Materials and Methods We analyzed 3204 patients who received with thrombomodulin alfa (TM-α) for with DIC and suspected DIC. Hypofibrinogenemia was defined by a fibrinogen level of Results Hypofibrinogenemia was observed in 10.3% of patients with infectious diseases. The frequencies of both bleeding and organ failure symptoms, and the scores for organ failure or the DIC diagnostic criteria were significantly high in infectious disease patients with hypofibrinogenemia, suggesting that in patients with infectious diseases, hypofibrinogenemia is associated with more progressive and severe DIC. Although the 28-day survival rate and the DIC resolution rate were both significantly lower in infectious disease patients with DIC with hypofibrinogenemia than in those without hypofibrinogenemia, this difference was not observed in DIC patients with hematological diseases.Conclusion In infectious disease patients with DIC, hypofibrinogenemia may reflect from the increased consumption of fibrinogen due to an accelerated coagulating reaction, while that in hematological disease patients DIC may be caused by fibrinogenolysis due to hyperfibrinolysis, and frequently results in bleeding and multiple-organ failure.

The frequency of severe antithrombin deficiency (SAD) was examined in the hematopoietic disorder-, infectious-, and basic-types of the disseminated intravascular coagulation (DIC). A posthoc analysis of 3008 DIC patients (infectious-type, 1794; hematological disorder-type, 813; and basic-type, 401) from post-marketing surveillance data of thrombomodulin alfa was performed. The clinical features of patients and outcomes were compared between patients with and without SAD, using an antithrombin cutoff value of 50%. Patients with SAD accounted for 40.4% of infectious-type DIC, 8.0% of hematopoietic disorder-type DIC, and 26.7% of basic-type DIC. There was no significant difference in thrombin–antithrombin complex levels between patients with and without SAD. The decreased fibrinogen level and differences in clinical features were significantly greater but the increases in fibrinolytic markers were significantly lower in patients with SAD than in those without. The 28-day survival rate was significantly lower in patients with SAD than in those without. Severe antithrombin deficiency was observed in all types of DIC, including hematopoietic disorders. Both hypofibrinolysis and hypercoagulability in patients with SAD may cause multiple organ failure and poor outcomes.

Myeloid sarcoma is an extramedullary tumor composed of immature myeloid cells and occurs in various extramedullary sites. We report a 48-year-old man diagnosed with myeloid sarcoma in the epididymis. He was admitted to our hospital due to a painless right intrascrotal mass. Magnetic resonance imaging showed a 30 mm tumor in the right epididymis, and we subsequently performed right high orchiectomy. The pathological diagnosis was myeloid sarcoma. Bone marrow aspiration and biopsy revealed no hematological disease, and cytogenetic analysis in the bone marrow showed normal karyotype. He was diagnosed with isolated myeloid sarcoma in the epididymis. Six months after the operation, myeloid sarcoma recurred in the para aorta and left sub-diaphragm. Bone marrow examination revealed myelodysplastic syndrome, and cytogenetic analysis showed 46, XY. We performed surgical resection of the recurrent mass, and cytogenetic analysis showed 47, XY, +21. He was diagnosed with recurrent MS with adult-onset trisomy 21. Although the effect of trisomy 21 on prognosis is unknown, the patient is currently undergoing systemic chemotherapy with maintained remission.

A 66-year-old man with hypertension was diagnosed with chronic myelogenous leukemia in 1996. Treatment was started with hydroxycarbamide and imatinib 400 mg in 1996 + 6, which was increased to 600 mg. Although he achieved a complete cytogenic response in 1996 + 9, he could not continue imatinib because of edema; the regimen was changed to nilotinib 800 mg in 1996 + 13. After he achieved a molecular response better than 4.5 in 1996 + 19, he was referred to our hospital. His urinalysis had shown urine protein since 1996 + 13, and his creatinine level increased in 1996 + 16. Renal biopsy, performed in 1996 + 20, revealed abdominal distention and massive ascites. After the nilotinib dosage was reduced to 400 mg, liver biopsy, also performed in 1996 + 20, revealed hypertrophy of renal small blood vessels and endothelial cells of the hepatic artery and loss of endothelial cells of the renal glomeruli, portal vein, and hepatic sinusoids. Both renal and liver biopsies revealed marked pathological vascular damage. The patient took oral imatinib for approximately 3.5 years and nilotinib for 11 years. Pathological findings indicated a tendency for thrombosis, which could induce vascular occlusive disease. Accumulation of cases, such as the present case, is needed to further analyze the pathophysiological processes.

Background Although disseminated intravascular coagulation (DIC) is life-threatening, any organ failure associated with DIC resolution and outcomes have been unclear. Patients and methods A total of 2795 DIC patients (infection: 1990, hematological malignancy: 805) were analyzed in the post-marketing surveillance of thrombomodulin alpha (TM-α). The background factors of sequential organ failure assessment (SOFA) and antithrombin (AT) were investigated in DIC with infectious disease for their association with DIC resolution and outcome using κ statistics, indicating DIC resolution and survival or DIC non-resolution and non-survival. The same analyses were performed for total bilirubin, creatinine, lactate dehydrogenase, and underlying disease in DIC with hematological malignancy. Results In DIC with infectious disease, higher SOFA score severity was closely correlated with lower overall survival in both the DIC resolution and non-resolution groups, but AT activity was not. κ coefficients were 0.234, 0.295, and 0.311 for the SOFA score 0–6, 7–12, and 13–24 groups, respectively. In DIC with hematological malignancy, κ coefficients of total bilirubin were 0.251 and 0.434, and those of creatinine were 0.283 and 0.437 in the normal and abnormal groups, respectively, showing better concordance in the abnormal group than in the normal. Other factors had poor concordance. Conclusion In DIC with infectious disease, DIC resolution is an important therapeutic target in patients who have higher SOFA score severity. In DIC with hematological malignancy, DIC resolution is similarly important in patients with abnormality of bilirubin and/or creatinine. Trial registration The clinical characteristics and treatment outcomes of patients with DIC treated with TM-α between May 2008 and April 2010 were retrospectively analyzed by subgroup analysis of the post-marketing surveillance data.

We report a 70-year-old woman diagnosed with unicentric Castleman’s disease with a contrast well-enhanced retroperitoneal tumor of 25 mm in diameter that located between the aorta and inferior vena cava. The imaging finding did not suggest any specific features, and no other lesion was detected. Laboratory examinations indicating malignant lymphoma such as soluble interleukin-2 were all negative. We resected the retroperitoneal tumor laparoscopically, and histopathological examination revealed hyaline vascular type Castleman’s disease. Although complete resection of hyaline vascular type unicentric Castleman’s disease results in a good prognosis, a late relapse has been reported and long-term follow-up is warranted.

The Japan Society for Oriental Medicine makes a compilation of structured abstracts of randomized controlled trials (RCTs) of Kampo medicines available on its Evidence Reports of Kampo Treatment (EKAT) website. Using EKAT, we conducted a systematic review and meta-analysis on the efficacy of using daikenchuto ( https://mpdb.nibiohn.go.jp/stork ) for bowel dysfunction after surgery for gastrointestinal cancer. The primary outcomes were the time to first postoperative flatus and the time to first postoperative bowel movement (BM). We found nine relevant RCTs. The mean differences between the daikenchuto group and control group (daikenchuto was not administered) were − 0.43 (95% CI: − 0.77 to − 0.09) days for the time to first postoperative flatus, − 0.29 (95% CI: − 0.59 to 0.01) days for the time to first postoperative BM, and − 0.95 (95% CI: − 1.70 to − 0.21) days for the length of postoperative hospital stay, and the risk ratio of the incidence of intestinal obstruction was 0.60 (95% CI: 0.35–1.03). The time to first postoperative flatus and the length of postoperative hospital stay were significantly shorter in the daikenchuto group than those in the control group (P = 0.01). However, only double-blind studies were evaluated; the results turned to be non-significant. As a result of meta-analysis by all retrieved according to the registered protocol, daikenchuto was efficacious in improving postoperative bowel dysfunction in patients with gastrointestinal cancers. However, limiting to articles with description of COI and blindness, significance disappeared.

To improve the prognosis of patients with hematological malignancies, close attention should be paid to major hemorrhage in the clinical management of patients with disseminated intravascular coagulation (DIC) associated with hematological malignancies, especially from diagnosis to induction therapy. Cerebral, alveolar, and GI tract hemorrhages may cause a life-threatening event. Therefore, DIC should always be suspected, and careful observation for hemorrhage and hemostatic examination should be performed. The diagnostic criteria for DIC according to the Japanese Ministry of Health and Welfare and the Japanese Society on Thrombosis and Hemostasis (2017) are useful resources for the diagnosis of DIC associated with hematological malignancies. Following diagnosis, treatment for DIC should be initiated as soon as possible, and the risk of hemorrhage should be considered when choosing the anticoagulant. Sufficient amount of fresh frozen plasma or platelet concentrates should be used if necessary. Recombinant human soluble thrombomodulin has promising potential for use as a drug for the treatment of DIC associated with hematological malignancies that can manage a wide range of pathologic processes such as hypercoagulable states, inflammation, excessive fibrinolysis, and easy hemorrhage caused by endothelial cell damage.

In the original publication of this article, Tables 2, 3 and 4 were published incorrectly. The corrected tables 2, 3 and 4 are given in the following pages.

We focused on the level of reduction of Wilms' tumor gene 1 (WT1) mRNA in bone marrow as minimal residual disease during chemotherapies in adult acute myeloid leukemia (AML) patients. Forty-eight patients were enrolled in this study. Log levels of reduction of WT1 mRNA transcript after induction therapy compared with those at diagnosis were associated with disease-free survival (DFS) (P=0.0066) and overall survival (OS) (P=0.0074) in patients who achieved complete remission. Also log levels of reduction of WT1 mRNA transcript after final consolidation therapy compared with those at diagnosis were associated with DFS (P=0.015) and OS (P=0.012). By multivariate analysis, log levels of reduction of WT1 mRNA transcript after induction therapy and after final consolidation therapy compared with those at diagnosis were extracted as risk factors for outcome. Our results suggest that early and deep reduction of tumor burden may be important for the outcome of AML patients. In addition, it may be useful for the decision to proceed with allogeneic SCT as post-remission therapy.

In paroxysmal nocturnal hemoglobinuria (PNH), various symptoms due to intravascular hemolysis exert a negative impact on patients’ quality of life (QOL). To determine clinical factors related with improvements in QOL in PNH patients treated, we analyzed changes in QOL scales in PNH patients treated with eculizumab based on data collected from post-marketing surveillance in Japan. Summary statistics were obtained using figures from QOL scoring systems and laboratory values, and evaluated by t test. One-year administration of eculizumab improved the most QOL items in comparison with the baseline. In particular, significant improvement of EORTC QLQ-C30 was observed in fatigue, dyspnea, physical function, and global health status. Canonical correlation analysis revealed a high correlation between QOL and laboratory values. Changes in serum lactate dehydrogenase (LDH) and hemoglobin showed strong correlations with QOL improvement. Quality of life improvement was independent of patients’ baseline characteristics of co-occurrence of bone marrow failure (BMF), or the degree of LDH. In this analysis, we found that the degree of QOL improvement was independent of the baseline LDH before eculizumab treatment and of co-occurrence of BMF. Paroxysmal nocturnal hemoglobinuria patients who have not received eculizumab treatment due to mild hemolysis may benefit from eculizumab treatment.

General statements have been published regarding the clinical laboratory tests for thrombosis and hemostasis to be used by hematologists who do not specialize in this field. Screening tests for bleeding are bleeding time, capillary fragility test, platelet count, prothrombin time, activated partial thromboplastin time (APTT), fibrinogen, fibrin/fibrinogen degradation products (FDP), and the cross mixing test conducted by measuring APTT. Screening tests for thrombosis and related factors include measurements of FDP, D-dimer, and thrombin-antithrombin complex. To assess thrombotic factors, we should measure antithrombin (AT), protein C, protein S, antiphospholipid antibody, and heparin induced thrombocytopenia antibody. If a congenital thrombotic factor abnormality is suspected, the clinician should examine activities of AT, protein C, protein S, plasminogen, and fibrinogen. Antigen levels of each parameter are also examined, if warranted. The cross mixing test conducted by measuring APTT is useful for differentiating between deficiencies and inhibitor presence.

We evaluated the diagnostic criteria for disseminated intravascular coagulation (DIC), which was published by the Japanese Society of Thrombosis and Hemostasis (JSTH), in 232 patients with suspected DIC without hematopoietic injury or infection. The diagnoses of the patients were as follows: DIC (n = 116), pre-DIC (n = 54), and non-DIC (n = 63). The efficacy of the diagnostic criteria for DIC was evaluated using a receiver operating characteristic analysis. The area under the curve and odds ratio for the global coagulation test (GCT) scores in the diagnosis of “DIC” were high, whereas those for the diagnosis of “DIC and pre-DIC” were low, suggesting that the addition of a reduced platelet count (RPC), antithrombin (AT), and soluble fibrin (SF)/thrombin AT (TAT) complex was required to diagnose DIC and pre-DIC. When the GCT score with the RPC, AT, and TAT/SF values was used, the cutoff DIC score for the diagnosis of DIC or DIC and pre-DIC was 6 points. For predicting the outcome, a scoring system that used the GCT result was useful, but the addition of RPC, AT, or SF/TAT was not. The modified diagnostic criteria of JSTH, which included the GCT score and the RPC, AT, and TAT/SF values, were useful for diagnosing both DIC and pre-DIC.

An 80-year-old man was diagnosed with disseminated intravascular coagulation (DIC) and thrombotic microangiopathy (TMA) associated with mucin-producing gastric cancer with bone marrow metastasis. He died suddenly on the third day of hospitalization before chemotherapy. Microscopic autopsy findings revealed fibrin thrombi by phosphotungstic acid hematoxylin (PTAH) staining of the renal glomeruli, and platelet thrombi by von Willebrand Factor (Factor VIII Antigen) staining of the microvessels of the bleeding intestine. Tumor cells were negative for both stains. Staining of endothelial cells (EC) of the small vessels with thrombomodulin (TM) stain revealed destruction of EC structure. This patient was thought to have had systemic dissemination of solid tumor cells associated with DIC and TMA, the clinical course of which is extremely aggressive. Different types of thrombi were observed in different organs, such as the kidneys and small intestine, which supported the co-occurrence of DIC and TMA by microscopic pathological findings. These findings provide pathological evidence for the pathology of the concurrent development of DIC and TMA and show differences in the types of thrombi according to the blood vessel localization. Furthermore, the findings were highly suggestive of the mechanisms causing organ dysfunction, such as renal dysfunction, and gastrointestinal bleeding.

The generation of thrombin–antithromin (AT) complex (TAT) or soluble fibrin (SF) was prospectively compared with prothrombin fragment 1 + 2 (F1 + 2) generation in patients with disseminated intravascular coagulation (DIC). The plasma levels of TAT, SF, and F1 + 2 were significantly higher in the DIC group than in the non-DIC group. The differences in these levels between the DIC group and non-DIC group were significantly related to infections and hematopoietic tumors. There were no significant differences in the TAT/F1 + 2 ratio between DIC and non-DIC patients, but the SF/F1 + 2 ratio was significantly higher in the DIC group than the non-DIC group. The plasma AT activity was significantly higher in patients with DIC with resolution than in those without resolution, and in survivors than in nonsurvivors. These findings suggest that the ratio of TAT/thrombin is constant between the patients with and without DIC but that the ratio of fibrin formation/thrombin might increase in DIC.

Fibrin-related markers (FRMs) such as fibrin and fibrinogen degradation products (FDPs), d-dimer, and soluble fibrin monomer complex (SFMC) were prospectively evaluated in 522 patients using the overt disseminated intravascular coagulation (DIC) diagnostic criteria. The differences in all FRMs between the DIC group and the non-DIC group, and those between the survivors and nonsurvivors were significant in the patients with infections. In an analysis of all patients, DIC score cutoff values of 2 and 3 points for FDP, d-dimer, and SFMC were recommended to be 8.3 and 42.0 μg/mL, 2.4 and 22.0 μg/mL, and 3.4 and 138.0 μg/mL, respectively. In conclusion, the adequate cutoff value is thus considered to be useful for both making a diagnosis of DIC and for predicting the outcome. Fibrin-related markers are therefore thought to be more useful for making a diagnosis of DIC based on infections than based on any other underlying disorders.

This retrospective analysis investigated the prognostic value of monitoring the response to imatinib using peripheral blood (PB) samples and the impact of the response on outcome in 133 patients with chronic myeloid leukemia (CML). We divided the response into 3 categories according to the results of neutrophil (N)-FISH and BCR-ABL transcript levels in PB; more than a 3-log reduction [major molecular response (MMR)], between a 2-log and 3-log reduction or negative with N-FISH [complete cytogenetic response equivalent (CCyRe)], N-FISH positive or less than a 2-log reduction (non-CCyRe). The median follow-up was 5.46 years. At 5 years, the overall survival (OS) rate and progression-free survival (PFS) rate were 94.4 and 92.0%, respectively. The estimated rate of the CCyRe and MMR were 81.7 and 67.1%, respectively. 106 patients achieving the CCyRe had significantly better OS and PFS than 27 patients without achieving the CCyRe. Patients with MMR had significantly better survival free from death, progression, imatinib withdrawal and a loss of the CCyRe, than patients whose response level remained in the CCyRe without achieving MMR until 18 months. Our observation suggests that the response level of the CCyRe on PB serve as a prognostic indicator, and achieving MMR provides stable long-term survival.

Disseminated intravascular coagulation (DIC) sometimes has a poor outcome, and therefore early diagnosis and treatment are required. This study prospectively evaluated the hemostatic abnormalities and the onset of DIC in 613 patients with underlying diseases to identify a useful marker for diagnosing Pre-DIC. Pre-DIC was defined as the condition of patients within a week before the onset of DIC. Initially, 34.4% of patients were diagnosed with DIC, and about 8.5% of the patients without DIC were diagnosed as DIC within a week after registration (pre-DIC). The mortality of DIC, Pre-DIC and "without DIC" was 35.3%, 32.4% and 17.2%, respectively. All hemostatic parameters were significantly worse in "DIC" than "without DIC" and the values of the prothrombin time ratio, platelet count and fibrin monomer complex could classify the three groups; "DIC", "pre-DIC" and "without DIC". No useful marker was identified that provided an adequate cutoff value to differentiate "pre-DIC" from "without DIC". A multivariate analysis identified clinical symptoms that were related to poor outcome. DIC must be treated immediately; there is no specific marker to identify pre-DIC.

The present report from The Japanese Society of Thrombosis and Hemostasis provides an expert consensus for the treatment of disseminated intravascular coagulation (DIC) in Japan. Disseminated intravascular coagulation (DIC) may be classified as follows: asymptomatic type, marked bleeding type, and organ failure type. Although treatment of DIC is important, adequate treatment differs according to type of DIC. In asymptomatic DIC, low molecular weight heparin (LMWH), synthetic protease inhibitor (SPI), and antithrombin (AT) are recommended, although these drugs have not yet been proved to have a high degree of effectiveness. Unfractionated heparin (UFH) and danaparoid sodium (DS) are sometimes administrated in this type, but their usefulness is not clear. In the marked bleeding type, LMWH, SPI, and AT are recommended although these drugs do not have high quality of evidence. LMWH, UFH, and DS are not recommended in case of life threatening bleeding. In case of severe bleeding, SPI is recommended since it does not cause a worsening of bleeding. Blood transfusions, such as fresh frozen plasma and platelet concentrate, are also required in cases of life threatening bleeding. In the organ failure type, including sepsis, AT has been recommended based on the findings of several clinical trials. DIC is frequently associated with thrombosis and may thus require strong anticoagulant therapy, such as LMWH, UFH, and DS.

Introduction: Vascular endothelial cell damage plays an important role in microvascular thrombogenesis. In vivo administration of cyclosporin A or mitomycin C sometimes results in thrombotic microangiopathy in patients. Materials and methods: The effects of cyclosporin A, mitomycin C and/or prednisolone on the cell cycle in cultured human umbilical vein endothelial cells were investigated to evaluate drug-induced endothelial cell damage and the protective effect of prednisolone on endothelial cells against the damage by cyclosporin A or mitomycin C in vitro. Results: The addition of cyclosporin A to cultures caused proliferation arrest in the G1-phase in a dose-dependent manner, while mitomycin C inhibited DNA synthesis, which resulted in cell cycle arrest and inhibition of BrdUrd incorporation in the S-phase. The administration of prednisolone also caused cell cycle arrest in the G1 by itself, and protected the cells from the damage caused by mitomycin C. The inhibitory effects of cyclosporin A and prednisolone on the cell cycle were reversible, while mitomycin C was not. The highly phosphorylated retinoblastoma protein expressed in human umbilical vein endothelial cells decreased in the presence of mitomycin C. Soluble thrombomodulin levels in the culture supernatant were elevated by the addition of cyclosporin A. Conclusion: These effects of the drugs may cause the cell cycle arrest and the prolonged repair of damaged endothelial cells in patients. D 2004 Elsevier Ltd. All rights reserved.

老人の骨髄異形成症候群 (MDS) の治療では, 薬剤の効果は不十分である。輸血依存性の症例ではさらに治療に苦慮する。加味帰脾湯は血液学分野では特発性血小板減少性紫斑病に有効であったという報告が散見される。その使用目標には貧血も認められるので輸血依存性のMDSへの効果も期待される。そこで老人のMDS患者に加味帰脾湯を投与し, 血液学的所見の推移の検討および全身状態の推移の評価を行った。症例は74歳, 男性, 虚証。8年来のMDSでプレドニゾロン, 後にメテノロンを内服していた。2週に2単位程度の赤血球輸血が必要で, ヘモクロマトーシスを併発し, 食欲不振を呈していた。加味帰脾湯を投与し, 約2ヵ月後, 白血球数と血小板数が増加した。赤血球数は改善しなかった。骨髄所見は殆ど不変であった。食欲および活動性等の全身状態は, 投与6週後より著明に改善した。ヘモクロマトーシス併発の本症例で血液学的効果とは別に食欲不振および全身倦怠感の改善を認めた。今後補剤のより優れた効果として検討してゆく必要性があるものと思われた。