DIC In Patients Research Articles

Nomogram for predicting disseminated intravascular coagulation in heatstroke patients: A 10 years retrospective study.

Disseminated intravascular coagulation (DIC) can lead to multiple organ failure and death in patients with heatstroke. This study aimed to identify independent risk factors of DIC and construct a predictive model for clinical application. This retrospective study included 87 patients with heatstroke who were treated in the intensive care unit of our hospital from May 2012 to October 2022. Patients were divided into those with DIC (n = 23) or without DIC (n = 64). Clinical and hematological factors associated with DIC were identified using a random forest model, least absolute shrinkage and selection operator (LASSO) regression and support vector machine-recursive feature elimination (SVM-RFE). Overlapping factors were used to develop a nomogram model, which was diagnostically validated. Survival at 30 days after admission was compared between patients with or without DIC using Kaplan-Meier analysis. Random forest, LASSO, and SVM-RFE identified a low maximum amplitude, decreased albumin level, high creatinine level, increased total bilirubin, and aspartate transaminase (AST) level as risk factors for DIC. Principal component analysis confirmed that these independent variables differentiated between patients who experienced DIC or not, so they were used to construct a nomogram. The nomogram showed good predictive power, with an area under the receiver operating characteristic curve of 0.976 (95% CI 0.948-1.000) and 0.971 (95% CI, 0.914-0.989) in the internal validation. Decision curve analysis indicated clinical utility for the nomogram. DIC was associated with significantly lower 30 days survival for heatstroke patients. A nomogram incorporating coagulation-related risk factors can predict DIC in patients with heatstroke and may be useful in clinical decision-making.

Leukotriene metabolism and proiflammatory cytokines in Crimean Congo hemorrhagic fever.

Crimean-Congo hemorrhagic fever (CCHF) is an emerging acute viral infection disease, yet its pathophysiology remains largely uncharacterized. Lipid mediators are molecules that play numerous roles in the physiologic and pathophysiologic conditions in certain viral diseases. No previous study evaluated the status of cysteinyl leukotrienes (CYSLT) and 5-lipoxygenase (5-LO) and their relationship with proinflammatory cytokines in CCHF. A total of 90 subjects including 60 CCHF patients and 30 healthy controls were enrolled the study. Serum CYSLT, 5-LO, interleukin-6 (IL-6), and ferritin levels were determined in the study population. Lower median 5-LO level was determined in patients compared to healthy controls (p = 0.0004). Higher ferritin (p < 0.001) and IL-6 (p < 0.001) levels in patients than healthy controls. No statistically significant difference was observed between patients and controls in terms of CYSLT levels. No statistically significant differences were observed between mild, moderate, and severe groups in terms of both 5-LO and CYSLT levels. IL-6 and ferritin levels were higher in severe group compared mild and moderate groups. In conclusion, changes in 5-LO enzyme and increased inflammation are related with the disease molecular mechanism. Higher inflammatory status contributes to the impaired hemostatic balance in CCHF. Thus, treatment strategies to reduce inflammation may help to prevent bleeding and DIC in patients. IL-6 and ferritin can be used to as an additional biomarker in the estmation of the prognosis and diagnosis of the patients.

Retrospective Analysis of D- Dimer and Procalcitonin as the Predictor of DIC in Patients with COVID 19

Background: COVID 19 causes growing numbers of severe diseases with systemic abnormalities like organ dysfunction, thrombosis, and mortality. Disseminated Intravascular Coagulation or DIC is associated with the development of systemic fibrin, which may cause due to increased thrombin expression, concomitant physiological anticoagulant suppression and dysfunctional fibrinolysis. Methods: This study was a retrospective study that was conducted at the department of Clinical Pathology. The study was carried out during the period of September 2021-February, 2022. The total sample size for this study was 50. Result: Most of the respondents 12(24%) were aged from 50-59 years. Most of the respondents 35(70%) were female and 15(30%) were male. D-Dimer findings of most of the patients (44%) were severe. PCT test findings were normal for 34% of the participants, mild for 6%, moderate for 26%, and the remaining 40% had severe PCT levels. Among the 50 cases, both PCT and D-Dimer values were in the normal range for 26% of the participants, while 62% of the participants had raised values (mild, moderate, or severe) in both PCT and D-Dimer tests. Conclusion: From this study, it can be said that levels of D-dimer and PCT are directly linked to the disease severity among the patients with COVID 19.

Diagnosis of human immunodeficiency virus associated disseminated intravascular coagulation.

Disseminated intravascular Coagulation (DIC) is a thrombotic microangiopathy which may complicate a number of severe disease processes including sepsis. Development of microvascular thromboses results in consumption of coagulation factors and platelets and ultimate bleeding. Patients with HIV infection (PWH) often present with baseline dysregulation of the coagulation system which may increase severity and derangement of DIC presentation. Previously, we have shown that HIV is a significant risk factor for development of DIC. We conducted a retrospective record review of all DIC screens submitted to our tertiary coagulation laboratory in Johannesburg, South Africa, over a one year period and compared the laboratory presentation of DIC in PWH with presentation of DIC in patients without HIV infection. Over the year, 246 patients fulfilled the International Society of Thrombosis and Haemostasis (ISTH) diagnostic criteria for DIC- 108 were confirmed HIV-infected and 77 were confirmed uninfected. PWH and DIC presented at a significantly earlier age (41 vs 46 years respectively, p<0.02). The prothrombin time was significantly more prolonged (30.1s vs 26.s), the d-dimer levels were substantially higher (5.89mg/L vs 4.52mg/L) and the fibrinogen (3.92g/L vs 1.73g/L) and platelet levels (64.8 vs 114.8x109/l) were significantly lower in PWH. PWH also showed significant synthetic liver dysfunction and higher background inflammation. PWH who fulfil the diagnostic criteria for DIC show significantly more dysregulation of the haemostatic system. This may reflect baseline abnormalities including endothelial dysfunction in the context of inflammation and liver dysfunction.

Management of Disseminated Intravascular Coagulation in Acute Leukemias.

Disseminated intravascular coagulation (DIC) is characterized by the intravascular activation of coagulation with loss of localization arising from different causes, and is diagnosed using scoring systems which rely upon the presence of an underlying disorder compatible with DIC alongside hemostatic derangements such as low platelet count, prolonged prothrombin time, and elevated fibrinogen degradation products. DIC is common in patients with acute leukemia, with prevalence ranging from 17 to 100% in acute promyelocytic leukemia (APL) and 8.5 to 25% in acute lymphoblastic leukemia (ALL) and non-APL acute myeloid leukemia (AML). The pathophysiology is complex and varies between the leukemia subtypes, and is not fully reflected by the laboratory markers currently used to classify DIC. Similarly, the clinical consequence of DIC in acute leukemia also varies across the types of leukemia. DIC is primarily associated with bleeding in APL, while thrombosis is the dominant phenotype in ALL and non-APL AML. The cornerstone of managing DIC is the treatment of the underlying disease, as exemplified by the important role of early administration of all-trans retinoic acid in APL. Other aspects of management focus on supportive care aimed at minimizing the risk of bleeding, via transfusion of blood products. The use of blood products is more liberal in APL, due to the hemorrhagic phenotype and unacceptably high rates of early hemorrhagic death. This review will focus on the pathophysiology, risk factors, clinical implications, and the management of DIC in patients across the spectrum of acute leukemias.

Coagulopathy: A Vicious Indicator of COVID-19

COVID-19 is routinely associated with coagulopathy and complications associated with thrombosis. However, the difference between the coagulopathy, which is associated with COVID-19 and the coagulopathy, which is due to different causes, is that the "COVID-19 associated coagulopathy" shows raised levels of D-Dimer and that of fibrinogen. However, it shows quite some abnormalities in the levels of prothrombin time and also in the platelet count. "Venous thromboembolism" and arterial thrombosis is frequently seen in COVID-19 associated coagulopathy as opposed to "disseminated intravascular coagulopathy". Patients suffering from COVID-19 have many have multiple factors in common for thromboembolism which is associated with "Adult respiratory distress syndrome" from different etiologies like generalized inflammation and being unambulatory. “Cytokine storm" is the hallmark of COVID-19 associated coagulopathy which is distinguished by high levels of IL-6,1, tumour necrosis factor and other cytokines. The clinical features of COVID-19 associated coagulopathy overlap that of some syndromes like antiphospholipid syndrome and thrombotic microangiopathy. Studies have shown that patients diagnosed with disseminated intravascular coagulation have a poor prognosis compared to the one's that don't get diagnosed with DIC. The advancement of the condition from coagulopathy in the vasculature of the lungs to DIC in patients who have tested positive for COVID-19 shows that the patient’s dysfunction associated with coagulation has evolved from local to generalized state. Investigating the coagulopathies will help in understanding the mechanism of COVID-19 associated coagulopathy.

Thrombotic microangiopathy, DIC-syndrome and COVID-19: link with pregnancy prothrombotic state

For last months, humanity has faced a formidable unknown enemy, which is presented as a new coronavirus infection. Despite the fact that the causative agents of new diseases appear at a certain frequency and that the virus SARS-CoV-2 has certain common properties with its predecessors, at the moment we are dealing with a new unknown pathogenesis of the development of severe complications in patients with risk factors. A final understanding of pathological process mechanisms is the goal of the scientific community. Summarizing research data from different countries, it became obvious that in severe cases of viral infection, we are dealing with a combination of the systemic inflammatory response syndrome, disseminated intravascular coagulation and thrombotic microangiopathy (TMA). Thrombotic microangiopathy is represented by a group of different conditions in which thrombocytopenia, hemolytic anemia, and multiple organ failure occur. The article reflects the main types of TMA, pathogenesis and principles of therapy. The main participants in the process are described in detail, including the von Willebrand factor and ADAMTS-13. Based on the knowledge available, as well as new data obtained from patients with COVID-19, we proposed possible models for the implementation of conditions such as sepsis, TMA, and DIC in patients with severe new coronavirus infection. Through a deeper understanding of pathogenesis, it will be possible to develop more effective diagnosis and therapy.

Clinical evaluation of Chinese disseminated intravascular coagulation scoring system (version 2017) in patients with acute promyelocytic leukemia

目的探索2017年版中国DIC诊断积分系统（CDSS）在急性早幼粒细胞白血病（APL）DIC诊断中的适用性。方法回顾性分析2004年1月至2018年2月就诊于中国医学科学院血液病医院并行诱导治疗的220例APL患者病历资料，采用CDSS、国际血栓与止血协会（ISTH）DIC积分系统和日本卫生福利部（JMHW）DIC积分系统分别进行评价及比较分析。结果220例APL患者中，男114例，女106例，中位年龄38.5（12~70）岁，其中低/中危组173例，高危组47例。11例患者诱导治疗期死亡。CDSS、ISTH、JMHW三种标准诊断DIC阳性率分别为62.27%、54.09%、69.09%。CDSS和ISTH诊断DIC的一致率为78.10%，CDSS和JMHW诊断DIC的一致率为88.32%。ROC曲线比较三者互为参照的敏感度及特异度，敏感度JMHW>CDSS>ISTH，特异度ISTH>CDSS>JMHW。CDSS DIC（+）和DIC（−）组患者PT、APTT、纤维蛋白原（FIB）、D-二聚体及纤维蛋白原/纤维蛋白降解产物（FDP）之间差异均有统计学意义（P值均<0.05）；但采用ISTH诊断积分系统时DIC（−）组的D-二聚体水平高于DIC（+）组[26.3（0.6~488.7）mg/L对21.9（1.2~477.1）mg/L，χ2=1.871，P=0.002]；采用JMHW诊断积分系统时DIC（+）与DIC（−）组的APTT差异无统计学意义[27.05（18.0~181.0）s对26.15（18.2~35.5）s，χ2=1.162，P=0.134]。CDSS DIC（+）和DIC（−）组患者的年龄及性别差异无统计学意义（P>0.05）；单因素Logistic回归显示患者起病时WBC、骨髓中异常早幼粒细胞比例对DIC的发生存在影响（P<0.05），而多因素分析显示在CDSS中起病时WBC>3×109/L是DIC发生的独立危险因素（OR=3.525，95%CI 1.875~6.629，P<0.001）。结论2017年版CDSS诊断DIC的敏感度高于ISTH DIC积分系统，特异度优于JMHW DIC积分系统。CDSS较ISTH、JMHW对于DIC相关指标具有较好区分度，适用于中国APL患者的DIC诊断。

Usefulness of Serum Procalcitonin as a Predictive Marker of Sepsis and DIC in Patients with Non-perforated Appendicitis

Usefulness of Serum Procalcitonin as a Predictive Marker of Sepsis and DIC in Patients with Non-perforated Appendicitis

Increased Levels of Histone In Human Plasma In Septic Patients with DIC.

AbstractAbstract 1422Sepsis is a life-threatening condition that is characterized by a whole-body inflammatory state (called a systemic inflammatory response syndrome, SIRS). Histones are essential for packing DNA into the cell nucleus and also play role in regulating gene expression but the new study (Jun Xu et al, Nature Medicine 15. 1318, 2009) have shown histones released into blood stream at the onset of sepsis can have devastating effects (endothelial damage and organ failure etc). However, about extracellular histones in the plasma from human, they have shown only one patient's data. Therefore, we measured extracellular hisotones in the plasma from septic patients with DIC (n=20). Also, we investigated extracellular hisotones in the plasma from septic patients without DIC (n=5). Extracellular histones in the plasma from human were examined by western blot analysis for histone H3 (H3).The thrombin antithrombin complexes (TAT) levels were higher in septic patients with DIC as reported by others. We detected high levels of extracellular hisotones (H3) in the plasma of all septic patients with DIC by western blotting. However, we did not find any extracellular histones (H3) in the plasma of fiver septic patients without DIC by western blotting. Moreover, high-mobility group box 1 (HMGB1) concentrations in the human plasma were determined using ELISA kit (Shino-Test, Japan). Plasma levels of HMBG1 were negative for four cases in 20 septic patients with DIC. Also, Plasma levels of HMBG1 were negative in septic patients without DIC.These results suggest that assess of extracellular hisotones in the plasma may be helpful in the making the diagnosis in septic patients with DIC. It appears that extracellular hisotones in the plasma may contribute to develop DIC in patients with sepsis. Disclosures:No relevant conflicts of interest to declare.

Mechanisms of Platelet Activation by Antithymocyte Globulin (ATG).

We have previously shown that polyclonal rabbit ATG from Fresenius (ATG-F) can induce non-overt DIC in patients undergoing hematopoietic stem cell transplantation (HSCT) [Weber et al. 2003]. The compensated state of the coagulopathy suggested that the severe drop in platelet counts (>60%) observed in patients with normal pretreatment levels was not solely due to thrombin generation and platelet consumption. We thus further investigated the mechanisms of ATG-F-induced thrombocytopenia, hypothesizing that ATG-F had direct platelet-stimulating activity. Using an indirect flow cytometric binding assay we found that, compared to control IgG, ATG-F dose-dependently (1–100 μg/ml) bound to the surface of resting and TRAP-activated platelets, showing an up to 50fold increase in MFI at 50–100 μg/ml. In a washed platelet system, in which baseline positivity for CD62P was generally <15%, ATG-F alone had no effect on platelet aggregation. However, when platelets were primed with low concentrations of ADP (1–2 μM) or epinephrine (0.5 μM), ATG-F induced strong and stable aggregation of up to 80–100% in a dose-dependent manner (25–100 μg/ml), whereas control IgG did not. The priming effect of ADP was dependent on both P2Y1 and P2Y12 as evidenced by respective ADP receptor antagonists. Preincubation of platelets with inhibitory CD32 mAb completely abolished ATG-F-induced platelet aggregation, suggesting that clustering of, and signalling through, FcγRIIA was crucial for this platelet response. Similarly, ATG-F-derived F(ab′)2 had no effect on ADP-triggered platelet aggregation. Furthermore, preliminary studies indicated that responsiveness of platelet donors to ATG-F was associated with the FcγRIIA-R/R131 polymorphism, which has previously been shown to confer increased in vitro platelet responsiveness to heparin/PF4 antibodies from patients with HIT. In a 14C-serotonin release assay, in which prolonged incubation at 370C under shaking conditions increases baseline platelet activation and ensures constant platelet-platelet contacts, ATG-F (100 μg/ml), but not control IgG, induced strong FcγRIIA-dependent dense-granule release of up to 80%. In contrast, using diluted platelet-rich plasma under static conditions, ATG-F had only minor effects on platelet activation, increasing CD62P+ platelets from 2±1 to 15±5% (n=5). In a cohort of 16 consecutive HSCT patients receiving ATG-F, two patients were identified with normal pretreatment platelet counts and soluble CD62P (sCD62P) plasma levels of >51 ng/ml (mean+2SD of 23 controls). In these patients, an ATG-F-induced drop in platelet count to 38 and 19% of baseline was associated with a 1.7 and 2.2fold increase in sCD62P, respectively, indicating further platelet activation. In summary, strong binding of ATG-F to resting platelets may accelerate their clearance by the reticulo-endothelial system, thus contributing to the pathophysiology of thrombocytopenia. While ATG-F alone had negligible effects on resting platelets, it significantly enhanced activation of prestimulated platelets. Patients with normal-to-high platelet counts and evidence of in vivo platelet activation may especially be prone to this potentially hazardous side effect.

ＩＩＩ．ＤＩＣの病態定義，感染症と非感染症

ＩＩＩ．ＤＩＣの病態定義，感染症と非感染症

Disseminated Intravascular Coagulation in Solid Tumors: Clinical and Pathologic Study

Disseminated intravascular coagulation (DIC) is a well known hemostatic complication of solid tumors. We evaluated the occurrence of DIC in 1117 patients with solid tumors. Of these patients, 76 (6.8%) were diagnosed with DIC. There were a total of 145 bleeding and clotting episodes reported in the 76 patients. Thrombocytopenia, hypofibrinogemia, elevated D-dimer and fibrinogen degradation products were the most common coagulation abnormalities encountered in patients with DIC. In multivariate analysis, older age (p = .0001), male gender (p = .009), advanced malignancies (p = .027), breast cancer (p = .038) and the presence of necrosis in the tumor specimen (p = .004), emerged as independent factors significantly related to the occurrence of DIC in patients with solid tumors. Of the 76 patients, 25 (33%) achieved response to treatment of DIC as defined in the study. Patients with early stage and advanced malignancies who developed DIC had inferior survival when compared with their counterparts without DIC (p = .039 and p = .005, respectively). Taken together, this study indicates that certain clinical and laboratory features are more common in patients with solid tumors who developed DIC. The occurrence of DIC appears to have an independent effect on survival of patients with cancer. Cooperative studies are encouraged to better address the usefulness and optimal prophylactic heparin regimen in patients at risk for DIC.

SYNDROMES OF DISSEMINATED INTRAVASCULAR COAGULATION IN OBSTETRICS, PREGNANCY, AND GYNECOLOGY: Objective Criteria for Diagnosis and Management

This article presents current understanding of the causes, pathophysiology, clinical, and laboratory diagnosis, and management of fulminant and low-grade DIC, as they apply to obstetric, pregnant, and gynecologic patients. General medical complications leading to DIC, which may often be seen in these patients, are also discussed. Considerable attention has been given to interrelationships within the hemostasis system. Only by clearly understanding these pathophysiologic interrelationships can the obstetrician/gynecologist appreciate the divergent and wide spectrum of often confusing clinical and laboratory findings in patients with DIC. Objective clinical and laboratory criteria for diagnosis of DIC have been outlined to eliminate unnecessary confusion and the need to make empiric decisions regarding the diagnosis. Particularly in the obstetric patient, if a condition is observed that is associated with DIC, or if any suspicion of DIC arises from either clinical or laboratory findings, it is imperative to monitor the patient carefully with clinical and laboratory tools to assess any progression to a catastrophic event. In most instances of DIC in obstetric patients, the disease can be ameliorated easily at early stages. Many therapeutic decisions are straightforward, particularly in obstetric and gynecologic patients. For more serious and complicated cases of DIC in these patients, however, efficacy and choices of therapy will remain unclear until more information is published regarding response rates and survival patterns. Also, therapy must be highly individualized according to the nature of DIC, patient's age, origin of DIC, site and severity of hemorrhage or thrombosis, and hemodynamic and other clinical parameters. Finally, many syndromes that are often categorized as organ-specific disorders and are sometimes identified as independent disease entities, such as AFE syndrome, HELLP syndrome, adult shock lung syndrome, eclampsia, and many others, either share common pathophysiology with DIC or are simply a form of DIC. These entities represent the varied modes of clinical expression of DIC and illustrate the diverse clinical and anatomic manifestations of this syndrome.

Cellular regulation of tissue factor

Tissue factor is the initiator of the extrinsic coagulation pathway and is an important regulator of haemostasis. Tissue factor is constitutively expressed in numerous cells and tissues, and can be induced in monocytes and endothelial cells by different inflammatory agents. Lymphocytes and serum factors can modulate the expression of tissue factor in monocytes. The regulation of tissue factor expression in monocytes appears to be different from that in endothelial cells. Phorbol myristate acetate can inhibit as well as induce tissue factor activity in monocytes, whereas phorbol myristate acetate only induces the expression of tissue factor in endothelial cells. Tissue factor expression in monocytes from patients with infections is not always associated with DIC. The extrinsic pathway inhibitor may play a role in the development of DIC in patients with sepsis. Deposition of extravascular fibrin may be an important determinant of tissue injury.

An Analysis of DIC in Patients with Multiple Organ Failure

An Analysis of DIC in Patients with Multiple Organ Failure

Treatment of disseminated intravascular coagulation.

The treatment of DIC is extremely complex, stemming from the fact that it complicates many different disorders and may have a variety of clinical manifestations. In addition, there continues to be a lack of well-controlled studies regarding various methods of management in relatively homogeneous groups of patients. Therefore treatment continues to be controversial and probably will remain so in the near future. However, it is clear that any careful clinical and laboratory observations in groups of patients with the same underlying disorder are extremely helpful in elucidating the natural history of the process, in determining its effect on the patient, and clarifying whether certain therapeutic interventions may be helpful. Therefore the continued accumulation of careful clinical studies will help in determining the proper management of DIC in patients with the same underlying disorder and in given individual situations.