Hematology AND DIC [keywords]
- 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 Jul 5.:1-12.
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.
- OC-16 - Neutrophil extracellular traps and tissue factor-bearing microvesicles: a liaison dangereuse causing overt DIC in cancer patients? [Journal Article]
- Thromb Res 2016 Apr.:S174-5.
Overt disseminated intravascular coagulation (DIC) is a systemic process characterized by excessive coagulation activation and fibrinolysis that may occur in cancer patients. The underlying pathomechanisms are still poorly understood. Recent experimental studies found an important role for the interaction between procoagulant neutrophil extracellular traps (NETs) and tissue factor (TF) in the pathogenesis of thrombosis.To investigate whether NETs and TF-bearing microvesicles (MVs) play a central role in cancer-related overt DIC.Twenty-eight cancer patients with overt DIC (ISTH score ≥5, 14 females, median age: 62 years [range: 21-80], 13 with solid tumors, 15 with acute leukemia) and 28 matched healthy controls were included. NET formation parameters (plasma DNA and nucleosomes), MVassociated TF activity, and routine coagulation parameters were determined at study inclusion. In 11 patients with acute myeloid leukemia (AML), follow-up measurements were also performed.Plasma DNA, nucleosomes, and MV-TF activity were highly elevated in patients with cancer-related DIC compared to healthy individuals (all p-values<0.001). Strong correlations were found between plasma DNA and nucleosomes (Spearman correlation-coefficient: r=0.68), nucleosomes and MV-TF activity (r=0.62), and DNA and MV-TF activity (r=0.57). In multivariate regression, altered routine coagulation parameters were highly associated with NET parameters and MV-TF activity. In detail, a doubling in plasma DNA was associated with a 7.6% decrease in fibrinogen (p=0.012), a 15.3% decrease in platelet count (p=0.002), a 3.9% decrease in prothrombin time (p=0.014), and a 41.0% increase in D-dimer (p<0.001). A 10% increase in nucleosomes was associated with a 3.1% decrease in fibrinogen (p<0.001), a 5.0% decrease in platelet count (p<0.001), a 1.0% decrease in prothrombin time (p<0.009), and a 112.7% increase in D-dimer (p<0.001). A 10% increase in MV-TF activity was associated with a 4.9% decrease in fibrinogen (p<0.001), a 7.1% decrease in platelet count (p<0.001), a 1.3% decrease in prothrombin time (p<0.001), and a 15.5% increase in D-dimer (p<0.001). After initiation of chemotherapy in AML patients, NET parameters and MV-TF activity decreased significantly (nucleosomes: 3.3-fold decrease and normalization after 1 week; DNA: 1.2-fold decrease after 1 week and 1.5-fold decrease after 1 month; MV-TF activity: 10-fold decease after 1 week and normalization after 1 month) (Figure 1), and routine coagulation parameters improved.Our results add to experimental studies that have investigated the interaction between NETs and TF. Taken together, evidence indicates the presence of a liaison dangereuse between NETs and TF-bearing MVs, which could be the underlying cause of cancer-related overt DIC.
- OC-10 - Disseminated intravascular coagulation at diagnosis strongly predicts both arterial and venous thrombosis in acute myeloid leukemia patients. [Journal Article]
- Thromb Res 2016 Apr.:S172.
Acute myeloid leukemia (AML) is associated with a slightly increased risk of VTE with an incidence of 1.7-8.9%, but only limited data are available. The mechanism of the occurrence of thrombosis in hematological disorders is still unresolved. Disseminated intravascular coagulation (DIC) is associated with VTE and bleeding in acute promyelocytic leukemia and acute lymphoblastic leukemia. Although DIC has also been reported in AML, no data exist on the relationship between DIC and VTE in AML patients.We hypothesized that the presence of DIC at diagnosis of AML may contribute to the risk of both venous and arterial thrombosis in AML. Therefore we studied a large cohort of adult patients with newly diagnosed AML aged <65 years by measuring DIC parameters at diagnosis prior to treatment and assessing the occurrence of both venous and arterial thrombosis during follow up. The findings of this study were validated in a second large cohort of patient with newly diagnosed AML aged >60 years.In a prospective study we analysed markers of DIC and their association with the occurrence of thrombosis during follow up in a cohort of 272 young AML patients (aged 18-65) and a validation cohort of 132 elderly AML patients (aged >60) patients that were all treated with intensive chemotherapy. DIC parameters (fibrinogen, D-dimer, alpha-2-antiplasmin, antitrombin, prothrombin time and platelets) were measured at presentation with AML before start of induction chemotherapy. The DIC score according to the International Society of Thrombosis and Haemostasis DIC scoring systemwas calculated of all patients.The prevalence of thrombosis was 8.7% (4.7% venous, 4.0% arterial) in young patients 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) in the cohort of young AML patients. These results were confirmed in our validation cohort of elderly AML patients. (HR 11.08 (3.23-38.06)). Of all DIC parameters D-dimer levels are most predictive for thrombosis with a HR of 12.3 (3.39-42.64) in the cohort of young AML patients and a HR of 7.82 (1.95-31.38) in the elderly cohort for a D-dimer >4.0 mg/L.It is concluded that both venous and arterial thrombosis occurs in around 10% of AML patients treated with intensive chemotherapy, which can be predicted by the presence of DIC, or individual DIC parameters at time of AML diagnosis.
- Acute promyelocytic leukemia presenting as a paraspinal mass. [Journal Article]
- J Community Support Oncol 2016 Mar; 14(3):126-9.
Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia (AML) that is characterized by a balanced translocation between chromosomes 15 and 17 [t(15;17)], which results in the fusion of the promyelocytic leukemia (PML) and retinoic acid receptor α (RARA) genes. Historically, APL was a fatal disease because of the high relapse rates with cytotoxic chemotherapy alone and a significant bleeding risk secondary to disseminated intravascular coagulation (DIC). However, APL is now one of the most curable hematological malignancies because of molecularly targeted therapies. With the advent of all-trans retinoic acid (ATRA) containing chemotherapy regimens, rates of complete remission and long-term, disease-free survival have improved dramatically. More recently, regimens incorporating both ATRA and arsenic trioxide (ATO) have allowed a substantial number of patients to be treated with little or no additional cytotoxic chemotherapy.
- Antifibrinolytics (lysine analogues) for the prevention of bleeding in people with haematological disorders. [Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't, Review]
- Cochrane Database Syst Rev 2016.:CD009733.
People with haematological disorders are frequently at risk of severe or life-threatening bleeding as a result of thrombocytopenia (reduced platelet count). This is despite the routine use of prophylactic platelet transfusions to prevent bleeding once the platelet count falls below a certain threshold. Platelet transfusions are not without risk and adverse events may be life-threatening. A possible adjunct to prophylactic platelet transfusions is the use of antifibrinolytics, specifically the lysine analogues tranexamic acid (TXA) and epsilon aminocaproic acid (EACA). This is an update of a Cochrane review first published in 2013.To determine the efficacy and safety of antifibrinolytics (lysine analogues) in preventing bleeding in people with haematological disorders.We searched for randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (The Cochrane Library 2016, Issue 3), MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1937), the Transfusion Evidence Library (from 1950) and ongoing trial databases to 07 March 2016.We included RCTs involving participants with haematological disorders, who would routinely require prophylactic platelet transfusions to prevent bleeding. We only included trials involving the use of the lysine analogues TXA and EACA.Two review authors independently screened all electronically-derived citations and abstracts of papers, identified by the review search strategy, for relevancy. Two review authors independently assessed the full text of all potentially relevant trials for eligibility, completed the data extraction and assessed the studies for risk of bias using The Cochrane Collaboration's 'Risk of bias' tool. We requested missing data from one author but the data were no longer available. The outcomes are reported narratively: we performed no meta-analyses because of the heterogeneity of the available data.We identified three new studies in this update of the review. In total seven studies were eligible for inclusion, three were ongoing RCTs and four were completed studies. The four completed studies were included in the original review and the three ongoing studies were included in this update. We did not identify any RCTs that compared TXA with EACA.Of the four completed studies, one cross-over TXA study (eight participants) was excluded from the outcome analysis because it had very flawed study methodology. Data from the other three studies were all at unclear risk of bias due to lack of reporting of study methodology.Three studies (two TXA (12 to 56 participants), one EACA (18 participants) reported in four articles (published 1983 to 1995) were included in the narrative review. All three studies compared the drug with placebo. All three studies included adults with acute leukaemia receiving chemotherapy. One study (12 participants) only included participants with acute promyelocytic leukaemia. None of the studies included children. One of the three studies reported funding sources and this study was funded by a charity.We are uncertain whether antifibrinolytics reduce the risk of bleeding (three studies; 86 participants; very low-quality evidence). Only one study reported the number of bleeding events per participant and there was no difference in the number of bleeding events seen during induction or consolidation chemotherapy between TXA and placebo (induction; 38 participants; mean difference (MD) 1.70 bleeding events, 95% confidence interval (CI) -0.37 to 3.77: consolidation; 18 participants; MD -1.50 bleeding events, 95% CI -3.25 to 0.25; very low-quality evidence). The two other studies suggested bleeding was reduced in the antifibrinolytic study arm, but this was statistically significant in only one of these two studies.Two studies reported thromboembolism and no events occurred (68 participants, very low-quality evidence).All three studies reported a reduction in platelet transfusion usage (three studies, 86 participants; very low-quality evidence), but this was reported in different ways and no meta-analysis could be performed. No trials reported the number of platelet transfusions per participant. Only one study reported the number of platelet components per participant and there was a reduction in the number of platelet components per participant during consolidation chemotherapy but not during induction chemotherapy (consolidation; 18 participants; MD -5.60 platelet units, 95% CI -9.02 to -2.18: induction; 38 participants, MD -1.00 platelet units, 95% CI -9.11 to 7.11; very low-quality evidence).Only one study reported adverse events of TXA as an outcome measure and none occurred. One study stated side effects of EACA were minimal but no further information was provided (two studies, 74 participants, very low-quality evidence).None of the studies reported on the following pre-specified outcomes: overall mortality, adverse events of transfusion, disseminated intravascular coagulation (DIC) or quality of life (QoL).Our results indicate that the evidence available for the use of antifibrinolytics in haematology patients is very limited. The trials were too small to assess whether or not antifibrinolytics decrease bleeding. No trials reported the number of platelet transfusions per participant. The trials were too small to assess whether or not antifibrinolytics increased the risk of thromboembolic events or other adverse events. There are three ongoing RCTs (1276 participants) due to be completed in 2017 and 2020.