Hematology AND DIC [keywords]
- Shock, acute disseminated intravascular coagulation, and microvascular thrombosis: is 'shock liver' the unrecognized provocateur of ischemic limb necrosis: comment. [JOURNAL ARTICLE]
- J Thromb Haemost 2016 Aug 19.
Disseminated intravascular coagulation (DIC) is an acquired syndrome characterized by the intravascular activation of coagulation with loss of localization arising from different causes. It can originate from, and cause damage to, the microvasculature, which if sufficiently severe, can induce organ dysfunction  This article is protected by copyright. All rights reserved.
- Disseminated intravascular coagulation in paediatrics. [REVIEW, JOURNAL ARTICLE]
- Arch Dis Child 2016 Aug 18.
Disseminated intravascular coagulation (DIC) in paediatrics is associated with significant morbidity and mortality. Although there have been several recent advances in the pathophysiology of DIC, most of these studies were done in adults. Since the haemostatic system is very different in early life and changes dramatically with age, creating a variety of challenges for the clinician, delay in the diagnosis of DIC can happen until overt DIC is evident. In this review article, we report the aetiology, pathophysiology, clinical manifestations, diagnostic tests and a management algorithm to guide paediatricians when treating patients with DIC.
- A phase III clinical trial of a mixture agent of plasma-derived factor VIIa and factor X (MC710) in haemophilia patients with inhibitors. [JOURNAL ARTICLE]
- Haemophilia 2016 Aug 1.
MC710, a 1:10 protein weight ratio mixture of plasma-derived activated factor VII (FVIIa) and factor X (FX), is a novel bypassing agent for haemostasis in haemophilia patients with inhibitors. We evaluated the haemostatic efficacy and safety of one to two administrations of MC710 in 21 joint, muscle, and subcutaneous bleeding episodes in 14 male patients, in a multi-centre, open-label, non-randomized clinical trial.Subjects were intravenously administered one or two doses of 60 or 120 μg kg(-1) MC710 (as FVIIa) once or twice (to a maximum of 180 μg kg(-1) ) over up to five bleeding episodes per subject. The haemostatic efficacy of MC710 was determined for each episode by investigator evaluation, using changes in visual analogue scale (VAS) for pain relief, and/or knee joint or muscle circumference for swelling reduction, and range of motion (ROM) for improvement of joint mobility.In 21 treatments for bleeding episodes, 19 were rated "excellent" or "effective" 8 h after the last treatment. VAS significantly decreased over time, and ROM significantly improved over time compared with the values before treatment. One mild adverse reaction, decreased blood potassium, and two serious adverse events, both knee joint bleeding, were observed within 1 week after first administration, with no significant effect on safety. Furthermore, diagnostic markers did not show any signs of disseminated intravascular coagulation (DIC).These results show that MC710 has sufficient haemostatic efficacy and safety, and can be used as a potential bypassing agent to control bleeding in haemophilia patients with inhibitors.
- Antithrombin supplementation and risk of bleeding in patients with sepsis-associated disseminated intravascular coagulation. [JOURNAL ARTICLE]
- Thromb Res 2016 Jul 27.:46-50.
Although antithrombin is commonly used for the treatment of sepsis-associated disseminated intravascular coagulation (DIC) in Japan, the factors influencing the incidence of bleeding complications have not been sufficiently studied. The purpose of this survey was to identify the factors that predict clinically relevant bleeding in patients receiving antithrombin for DIC.We analyzed data from 1026 sepsis-associated DIC patients with a baseline antithrombin activity ≤70% who underwent antithrombin supplementation at two dosages (1500IU/day or 3000IU/day) for three consecutive days. The patients' demographic characteristics, parameters before and after the treatment, and co-administered anticoagulants were analyzed in relation to the bleeding events.Overall, 55 patients (5.36%) experienced bleeding events (major bleeding: 1.75%). Logistic regression analysis revealed that sustained DIC>7days was significantly associated with bleeding (odds ratio: 2.761, P=0.001). In contrast, the higher dose of antithrombin or the co-administration of recombinant thrombomodulin or heparins were not associated with bleeding events.A higher dose of antithrombin or the concomitant use of other anticoagulants were not associated with bleeding events. On the other hand, sustained DIC lasting more than one week was associated with an increased risk of bleeding in patients with sepsis-associated DIC.
- Pathological findings in a case of bone marrow carcinosis due to gastric cancer complicated by disseminated intravascular coagulation and thrombotic microangiopathy. [JOURNAL ARTICLE]
- Int J Hematol 2016 Jun 29.
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.
- Disseminated intravascular coagulation at diagnosis is a strong predictor for both arterial and venous thrombosis in newly diagnosed acute myeloid leukemia. [JOURNAL ARTICLE]
- Blood 2016 Jun 28.
Venous thromboembolism (VTE) is a common complication in patients with cancer but only limited data are available in AML. In a prospective study in a cohort of 272 adult patients (aged 18-65) and an independent validation cohort of 132 elderly adults (aged > 60) with newly diagnosed AML we assessed markers of disseminated intravascular coagulation (DIC) (fibrinogen, D-dimer, alpha-2-antiplasmin, antitrombin, Prothrombin time and platelet count), the DIC score according the International Society of Thrombosis and Haemostasis and their associations with the occurrence of venous and arterial thrombosis during follow up. The prevalence of thrombosis was 8.7% (4.7% venous, 4.0% arterial) in the younger adults over a median follow up of 478 days and 10.4% (4.4% venous, 5.9% arterial) in elderly patients. Most thrombotic events (66%) occurred before start of the second course of chemotherapy. The calculated DIC score significantly predicted venous and arterial thrombosis with a Hazard Ratio (HR) for a high DIC score (≥5) of 4.79 (1.71-13.45). These results were confirmed in the validation cohort of elderly AML patients (HR 11.08 (3.23-38.06)). Among all DIC parameters, D-dimer levels are most predictive for thrombosis with a HR of 12.3 (3.39-42.64) in the first cohort and a HR of 7.82 (1.95-31.38) in validation cohort for a D-dimer >4 mg/L vs ≤ 4 mg/L. It is concluded that venous and arterial thrombosis may develop in around 10% of AML patients treated with intensive chemotherapy, which to a large extent can be predicted by the presence of DIC at time of AML diagnosis.
- Efficacy and safety of anticoagulant therapy in three specific populations with sepsis: a meta-analysis of randomized controlled trials: comment. [JOURNAL ARTICLE]
- J Thromb Haemost 2016 Jun 22.
The guidance for the diagnosis and treatment of disseminated intravascular coagulation (DIC) from the Scientific Standardization (SSC) Committee on DIC of the International Society on Thrombosis Haemostasis (ISTH)  did not recommend anticoagulant therapy, such as antithrombin (AT), activated protein C, and thrombomodulin. Although many clinical trials have found little evidence supporting the effectiveness and safety of anticoagulant therapy against severe sepsis, several studies have suggested that certain anticoagulant therapies may reduce mortality in patients with sepsis-induced DIC [2, 3]. Therefore, we read the recent article by Umemura Y et al. with great interest . They conducted separate meta-analyses of randomized controlled trials for anticoagulant therapy in three different populations: an overall population with sepsis; the population with sepsis-induced coagulopathy; and the population with sepsis-induced DIC. This article is protected by copyright. All rights reserved.
- Disseminated intravascular coagulation - new pathophysiological concepts and impact on management. [Journal Article]
- Expert Rev Hematol 2016 Aug; 9(8):803-14.
Disseminated intravascular coagulation (DIC) is an intermediary mechanism of disease which develops secondary to many causes including sepsis, trauma and malignancies. This review attempts to summarise the new pathophysiological developments and the impact they have on the current and future management of DIC.Several publications detailing the pathophysiology of DIC and the clinical management were identified using a pubmed search. Expert commentary: In recent years, on the initiatives of the international society of thrombosis and haemostasis, important advances have been made on the diagnostic aspect of DIC. In addition, several researchers have focused on the pathophysiology of the condition which is likely to provide better diagnostic markers and targeted therapy. However, some confusion still exists in the definition and management of DIC since various specialists understands the mechanisms involved in DIC from different perspectives.
- An Evaluation of the Modified Diagnostic Criteria for DIC Established by the Japanese Society of Thrombosis and Hemostasis. [JOURNAL ARTICLE]
- Clin Appl Thromb Hemost 2016 Jun 14.
We evaluated the modified diagnostic criteria for disseminated intravascular coagulation (DIC), which was published by the Japanese Society of Thrombosis and Hemostasis (JSTH) in 108 patients with suspected infectious DIC.The diagnoses of the patients were as follows: DIC (n = 63), pre-DIC (n = 22), and non-DIC (n = 45). The efficacy of the diagnostic criteria for DIC was evaluated using a receiver-operating characteristic analysis.Although the area under the curve for global coagulation test (GCT) scores in the diagnosis of "DIC" was high that for the diagnosis of "DIC and pre-DIC" was low, suggesting that the addition of antithrombin (AT), soluble fibrin (SF)/thrombin-AT complex (TAT), and reduced platelet count (PLT) values was required to diagnose "DIC and pre-DIC." Using GCT score with the AT, SF/TAT, and reduced PLT values, the cutoff value of the DIC score for the diagnosis of "DIC and pre-DIC" was 5 points.The modified JSTH's diagnostic criteria for DIC, which used the GCT score and the reduced PLT, AT, and TAT/SF values, were useful for diagnosing "DIC and pre-DIC."
- [Fulminant visceral disseminated varicella-zoster virus infection without skin involvement in a patient with autoimmune hemolytic anemia on prednisolone therapy]. [English Abstract, Journal Article]
- Rinsho Ketsueki 2016 Apr; 57(4):467-71.
An 80-year-old man with autoimmune hemolytic anemia (AIHA) received immunosuppressive therapy with prednisolone (1 mg/kg). One month later, his hemoglobin level had normalized, and the prednisolone dose was tapered. The next day, he complained of acute and progressive back pain. He was admitted to our hospital for further examination approximately 24 h after the pain had started. Computed tomography revealed only localized pneumonia. However, he showed signs of severe disseminated intravascular coagulation (DIC), liver dysfunction, and respiratory failure. Empiric broad-spectrum antibacterial therapy was started with a presumptive diagnosis of severe bacterial infection. However, his condition rapidly deteriorated, and he died 17 h after admission. Varicella-zoster virus (VZV) was detected by quantitative PCR in the peripheral blood sample and by immunohistochemistry in all organs except for the brain at autopsy. Visceral VZV infection is a severe disease with a high mortality rate. Although appropriate diagnosis and treatment is crucial, in cases without the characteristic skin rash the diagnosis is difficult. The possibility of visceral VZV infection should be taken into consideration when administering prednisolone to patients with AIHA.