Overt Disseminated Intravascular Coagulation Research Articles

Overt disseminated intravascular coagulation and antithrombin III predict bleeding and in-hospital mortality in patients undergoing extracorporeal membrane oxygenation.

Limited data are available on the relationship of disseminated intravascular coagulation (DIC) with mortality in patients receiving extracorporeal membrane oxygenation (ECMO). Thus, we investigated the association of DIC score and antithrombin (AT) III with clinical outcomes in patients undergoing ECMO. We analyzed 703 patients who underwent ECMO between January 2014 and May 2022 at Samsung Medical Center. The DIC score was calculated using laboratory findings within 24 h of the ECMO initiation, and ≥ 5 was defined as overt DIC. In addition, the AT III level was measured to identify the correlation with the DIC score. Among the study patients, 169 (24.0%) were diagnosed with overt DIC (DIC group) during early maintenance therapy. In-hospital mortality was significantly higher in the DIC group than in the non-DIC group (55.0% vs. 36.5%, p < 0.001). Bleeding events were significantly higher in the group of patients with a DIC score of 7 or 8 than in the other group (20.8% vs. 8.4%, p = 0.038). DIC score negatively correlated with AT III level (r = -0.417, p < 0.001). The predictive performance of AT III for overt DIC had statistical significance with a c-static of 0.81 (95% confidence interval (CI), 0.77-0.84, p < 0.001). Overt DIC was associated with higher in-hospital mortality and a tendency to bleed in ECMO patients. Furthermore, AT III plasma levels can easily predict overt DIC in patients undergoing ECMO. These findings suggest that monitoring AT III plasma levels may be important in the management of ECMO.

The ISTH DIC-score predicts early mortality in patients with non-promyelocitic acute myeloid leukemia

Coagulation disorders frequently complicate the clinical course of acute myeloid leukemia (AML) patients. This study examined the frequency and prognostic significance, with regards of early mortality, of the presence of overt disseminated intravascular coagulation (DIC) at AML diagnosis and its correlation with clinical and biological characteristics.A retrospective analysis of 351 newly diagnosed non-promyelocytic AML patients was conducted, utilizing the 2018 ISTH DIC-Score criteria to evaluate the presence of overt DIC at AML onset. The study cohort had a median age of 65 years with a predominance of male gender (59 %). Overt DIC was present in 21 % of cases and was associated with advanced age, comorbidities, poor performance status, hyperleukocytosis, LDH levels, NPM1 mutations, expression of CD33 and CD4, and lack of expression of CD34. With a median follow-up of 72 months (3–147 months), the 6-year overall survival (OS) was 17.4 %, with patients having overt DIC showing significantly poorer outcomes (7.2 % compared to 20.3 % of those without DIC, p < 0.001). Patients with overt DIC showed markedly high early mortality rates at 30 (42.5 % vs 8 %), 60 (49.3 % vs 16.9 %), and 120 days (64.4 % vs 25.6 %) from disease onset. In multivariate analysis overt DIC retained its independent prognostic value for early mortality.In conclusion, the prevalence and clinical relevance of DIC in non-promyelocytic AML is not negligible, underlining its potential as an unfavorable prognostic marker. In newly diagnosed patients with AML, early recognition and measure to counteract coagulation disturbances might help mitigate the elevated mortality risk associated with DIC.

Rotational Thromboelastometry and Clot Waveform Analysis as Point-of-Care Tests for Diagnosis of Disseminated Intravascular Coagulation in Critically Ill Children in Thailand.

This study aimed to determine the test performances of rotational thromboelastometry (ROTEM) and activated partial thromboplastin time-based clot waveform analysis (aPTT-CWA) compared with the International Society on Thrombosis and Hemostasis disseminated intravascular coagulation (ISTH-DIC) score for diagnosis of overt disseminated intravascular coagulation (ODIC) in critically ill children. Prognostic indicators of DIC complications were also evaluated. A prospective cross-sectional observational study was conducted. ROTEM and aPTT-CWA were assessed alongside standard parameters based on the ISTH-DIC score and natural anticoagulants. Both conventional and global hemostatic tests were repeated on days 3-5 for nonovert DIC. PICU of the Department of Pediatrics, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand. Infants and children who were admitted to PICU with underlying diseases predisposed to DIC, such as sepsis, malignancy, major surgery, trauma, or severe illness, were included in the study between July 1, 2021, and November 30, 2022. None. Sixty-four children were enrolled in this study. The prevalence of ODIC was 20.3%. Regarding ROTEM parameters, using EXTEM clot formation time (CFT) cutoff of greater than 102 seconds provided sensitivity and specificity of 90.9% and 80.9%, respectively, for diagnosing ODIC, with the area under the curve (AUC) of 0.86. In the case of aPTT-CWA performance, no biphasic waveform was observed, whereas both maximum coagulation acceleration (Min2) of less than 0.35%/s 2 and maximum coagulation deceleration of less than 0.25%/s 2 demonstrated identical sensitivities of 76.9% and specificities of 79.6%. Combining two global hemostatic tests significantly improved the diagnostic performance (INTEM CFT + EXTEM CFT + Min2 AUC 0.92 [95% CI, 0.80-1.00] vs. EXTEM CFT AUC 0.86 [95% CI, 0.75-0.96], p = 0.034). Bleeding was the most common consequence. In multivariable logistic regression analysis, Min2 of less than 0.36%/s 2 was an independent risk factor for bleeding complications, with an adjusted odds ratio of 15.08 (95% CI, 1.08-211.15, p = 0.044). ROTEM and aPTT-CWA were valuable diagnostic tools in critically ill children who might require point-of-care tests. Min2 showed significant clinical implications for predicting bleeding events in this population.

Infusional fluorouracil and weekly docetaxel as first-line therapy for gastric cancer with bone marrow metastasis and disseminated intravascular coagulation: A multi-center, phase II trial (Zhen Long).

337 Background: Gastric cancer (GC) with bone marrow metastasis (BMM) and disseminated intravascular coagulation (DIC) constitute a highly aggressive GC (HAGC) sub-type with distinctive features. The prognosis is poor and most HAGC patients die in weeks without effective treatment. Undue concerns about the myelosuppression mitigate against the application of cytotoxics in HAGC which is characterized by thrombocytopenia. Retrospective analysis showed low dose chemotherapy might relieve the DIC and bring with survival benefit but the standard of care (SOC) has not yet been established without a prospective study available. We completed a multi-center phase II trial evaluating the safety and efficacy of infusional fluorouracil and weekly docetaxel as first-line (1L) treatment for HAGC. Methods: This was a single-arm trial. A Simon's two-stage optimal design was applied. Eligible cases were: 18-75 years old, histologically confirmed GC, established BMM, overt DIC, platelet ≤ 50*109/L and Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 3. Fluorouracil 200mg/m2/d continuous infusion on days 1-21 and docetaxel 25mg/m2/d on days 1, 8, 15 were given every four weeks. Hematological response (HeR) was defined as the platelet restored to normal range. The primary end point was HeR rate. Secondary end points were time to HeR (TTHeR), one month mortality (OMM), overall survival (OS), adverse events (AEs) and quality of life (QoL). Results: From Jan 2021 to Sep 2022, 24 HAGC cases from three Chinese centers were enrolled (details shown in table below). 20 HeRs were achieved and the HeR rate was 83.3%. Median TTHeR was 13 days and OMM was 12.5%. Till the data cut-off date (Jul 31, 2023), 3 patients were still alive with a median follow-up of 403 days. The median OS was 242 days. Totally, twelve Grade 3 AEs were recorded in 7 (29.2%) patients, among which stomatitis (4, 16.7%) and aminotransferase elevation (3, 12.5%) were the most frequent. No drug-related grade 4 or 5 AEs were observed. QoL outcomes were significantly improved both during and after the treatment. Conclusions: Anti-cancer treatment is the key point to control DIC of HAGC. The Zhen Long regimen was well tolerated and showed promising efficacy in the 1L setting. It should be considered as the SOC in current practice, but further randomized trials are still needed. Clinical trial information: NCT04547153 . [Table: see text]

Low ADAMTS13 Activity in Patients with Liver Disease- Thrombotic Thrombocytopenic Purpura or Not?

Introduction: Patients with liver injury have hemostatic defects including reduced ADAMTS13 (A disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13). Severe deficiency of ADAMTS13 (ADMS13) activity (&amp;lt; 10%) is pathognomonic for thrombotic thrombocytopenic purpura (TTP), a rare thrombotic microangiopathy (TMA). Differentiating TTP from severe liver injury is complex for multiple reasons including 1) low baseline ADMS13 2) concomitant coagulopathies complicating differentiation from disseminated intravascular coagulation (DIC) 3) ADMS13 activity (ADMS13:AC) assay interference (hyperbilirubinemia (&amp;gt;30mg/dL) can cause artifactual reduction of ADMS13:AC). Here we sought to characterize the clinical presentation, management, and outcomes of patients with liver injury presenting with thrombocytopenia (TCP), microangiopathic hemolytic anemia (MAHA) and low ADMS13:AC at our institution. Methods: In this retrospective study, after IRB approval, electronic medical records (EMR) of institutional patients who had ADMS13:AC and inhibitor profile performed in our special coagulation laboratory between 2018 and July 17, 2023, were reviewed. Eligible patients had ADMS13:AC ≤20% were ≥ 18 years and had evidence of liver injury at time of ADMS13. Liver injury was defined as ALT or AST elevations greater than two times the upper level of normal within one month prior to ADMS13:AC testing, history of end stage liver disease or cirrhosis, or liver transplant with evidence of graft dysfunction. Details regarding clinical presentation, management and outcomes were extracted from the EMR. PLASMIC and ISTH DIC scores were retrospectively calculated. Results: 70 patients had at least one ADMS13:AC &amp;lt; 20% during the study period. 28/70 patients met liver injury inclusion criteria and 20/28 had TCP and MAHA. Of those 20 patients, median age at initial ADMS13:AC was 56.5 years (29-85). Most patients (n=14) had ADMS13:AC of 10-20%. ADMS13:AC was &amp;lt; 5% and 5-10% in 3 patients each. Eleven patients had a positive inhibitor with a median Bethesda titer of 1.85 BU (0.5-3.9). Etiology of liver included: ischemic hepatopathy (n=8), liver graft failure (n=4), liver metastasis (n=3), cirrhosis (n=2), alcoholic hepatitis (n=1), unknown (n=2). Median hemoglobin and platelet (plt) count at time of ADMS13 was 7 g/dL (6.4-13.2) and 30 x10 9/L (3-98), respectively. 7/20 patients had a PLASMIC score of ≥5; PLASMIC score was ≥5, in 2/6 patients with ADMS13:AC &amp;lt;10%. 16/18 patients had an ISTH DIC score ≥5. 18/20 patients had a creatinine &amp;gt; 2 mg/dL or were receiving renal replacement therapy the time of ADMS13: AC. 7/20 patients had total or direct bilirubin of &amp;gt;30mg/dL. Eight/20 patients were treated with plasma exchange (PEX) for a median duration of 7 days (2-13). 66.7% of pts with ADMS13:AC &amp;lt;10% received PEX. Glucocorticoids and Rituximab were used with the intent to treat TTP in 7 and 3 patients, respectively. Caplacizumab was used in 2 patients. 3/8 (37.5%) patients receiving PEX demonstrated normalization of MAHA. One of these patients demonstrated improvement but not normalization of plts (Table 1B, case 5). All patients had recurrence of hematologic abnormalities after PEX was stopped. One patient was treated with plasma infusion with stabilization in plt count. There were 13 and 15 deaths within 1 and 6 months of first ADMTS13:AC, respectively. One death was potentially attributable to management of TTP (Table 1B, case 1). There was no difference in time to death or mortality with the use of PEX. Repeat ADMS13:AC remote from PEX, TCP and MAHA was available for 1/5 surviving patients. This patient (Table1, case 2) had normalization of ADMS:AC after undergoing liver transplant. Conclusion: The differential diagnosis of TCP and MAHA in patients with liver injury includes hepatic dysfunction, DIC and TMA. In the current cohort, 89% of evaluable patients met criteria for overt DIC per ISTH criteria. Due to a low ADMTS13:AC, 40% of patients underwent a trial of PEX with 37.5% demonstrating improvement in MAHA that was not sustained upon discontinuation of PEX due to persistent liver dysfunction. Six-month mortality was 75% and use of PEX did not affect mortality. Given the high mortality, further studies evaluating which patients with TMA and liver injury are more likely to benefit from therapies typically used to treat TTP are necessary.

Persistent and Late-Onset Disseminated Intravascular Coagulation Are Closely Related to Poor Prognosis in Patients with Sepsis.

Septic-associated disseminated intravascular coagulation (DIC) is heterogeneous regarding prognosis and responsiveness to anticoagulant therapy. To investigate the relationship between the timing of development and recovery of DIC, its prognosis, and the difference in response to anticoagulant therapy in sepsis-associated DIC patients. This study was performed with a dataset from a multicenter nationwide retrospective cohort study (J-Septic DIC registry) in Japan between 2011 and 2013 to reveal the subgroup "high risk of death in DIC" and investigate the relationship between anticoagulant use and mortality. Patients were assigned to four groups based on the International Society on Thrombosis and Haemostasis-overt DIC status at days 1 and 3: non-DIC (-/-), early-recovered DIC (+/-), late-onset DIC (-/+), and persistent DIC (+/+). A total of 1,922 patients were included. In-hospital mortality in persistent and late-onset DIC patients was significantly higher than in patients with non-DIC and early-recovered DIC. This finding indicates that persistent DIC and late-onset DIC were a poor-prognosis subgroup, "high-risk" DIC. Meanwhile, patients with high-risk DIC treated with anticoagulants had significantly better outcomes than those without anticoagulants after adjusting for confounding factors. This study showed that individuals with a high risk of death, persistent DIC, and late-onset DIC were a poor-prognostic subgroup in septic DIC; however, high-risk DIC is also a subgroup that can obtain more benefits from anticoagulant therapy.

The International Society of Thrombosis and Hemostasis (ISTH) criteria in intensive care units

BackgroundDisseminated Intravascular Coagulation (DIC) has been assessed by the International Society of Thrombosis and Hemostasis (ISTH) 2001 and the ISTH 2018-modified version. More investigations are needed to assess usability and visibility of those DIC scoring systems in the intensive care units (ICU). AimsThis study investigated the predictive performance of the ISTH–Overt DIC versions of 28–day mortality in ICUs compared to SOFA as a gold standard assessment tool of sepsis. MethodsA retrospective design (2015–2017) included 220 adult patients enrolled from medical and surgical ICUs in two major hospitals in Jordan. We calculated ISTH–Overt DIC scores and SOFA score on time of DIC diagnosis. Overt DIC was categorized based on a score of ≥ five for ISTH DIC 2001; and ≥ 4 for ISTH DIC 2018. Provided, a score > 12 was categorized as Multiple–Organ– Dysfunction–Syndrome (MODS) for Sequential Organ Failure Assessment (SOFA) score. Then, 28–day mortality follow-up was performed. ResultsMore than half of sample died before 28–days of follow–up. The analysis of Receiver Operating Characteristic (ROC) showed that higher scores of ISTH DIC 2001(≥ 5), ISTH DIC 2018 (≥ 4), and SOFA score (>12) were highly associated with 28–day mortality. The ISTH DIC 2001 and SOFA score were superior on the modified ISTH 2018 in predicting 28–day mortality, with an Area Under the Curve (AUC) of (0.724 vs. 0.822 vs. 0.507, respectively). Yet, the accuracy of the SOFA score was better than the ISTH DIC 2001. Conclusion: This study suggests that ISTH DIC 2001 score is helpful when applied on medical and surgical ICU Jordanian populations. It showed better results compared to the Modified ISTH DIC 2018 in mortality prediction, regardless of the underlying diseases.

Low-molecular-weight heparin therapy reduces 28-day mortality in patients with sepsis-3 by improving inflammation and coagulopathy.

Sepsis is a syndromic response to infection and is associated with high mortality, thus imposing a significant global burden of disease. Although low-molecular-weight heparin (LMWH) has been recommended to prevent venous thromboembolism, its anticoagulant and anti-inflammatory effects in sepsis remain controversial. Owing to the modification of the Sepsis-3 definition and diagnostic criteria, further evaluation of the efficacy and benefit population of LMWH is required. We performed a retrospective cohort study to assess whether LMWH improved the inflammation, coagulopathy, and clinical outcomes against Sepsis-3 and to identify the target patients. All patients diagnosed with sepsis at the First Affiliated Hospital of Xi'an Jiaotong University (the largest general hospital in northwest China) from January 2016 to December 2020 were recruited and re-evaluated using Sepsis-3 criteria. After 1:1 propensity score matching, 88 pairs of patients were categorized into the treatment and control groups based on subcutaneous LMWH administration. Compared with the control group, a significantly lower 28-day mortality was observed in the LMWH group (26.1 vs. 42.0%, p = 0.026) with a comparable incidence of major bleeding events (6.8 vs. 8.0%, p = 0.773). Cox regression analysis showed that LMWH administration was the independent protective factor for septic patients (aHR, 0.48; 95% CI, 0.29-0.81; p = 0.006). Correspondingly, the LMWH treatment group showed a significant improvement in inflammation and coagulopathy. Further subgroup analysis showed that LMWH therapy was associated with favorable outcomes in patients younger than 60 years and diagnosed with sepsis-induced coagulopathy (SIC), ISTH overt DIC, non-septic shock, or non-diabetics and in patients included in the moderate-risk group (APACHE II score 20-35 or SOFA score 8-12). Our study results showed that LMWH improves 28-day mortality by improving inflammatory response and coagulopathy in patients meeting Sepsis-3 criteria. The SIC and ISTH overt DIC scoring systems can better identify septic patients who are likely to benefit more from LMWH administration.

Coagulation Abnormalities in Severe Scrub Typhus and Their Association with Complications.

To describe coagulation abnormalities and their association with complications in patients with severe scrub typhus. A cohort study was conducted among all patients of severe scrub typhus [immunoglobulin M (IgM) positive] who reported to this facility from 1st August 2019 to 31st July 2020 and met our inclusion criteria. We estimated the incidence of severe thrombocytopenia (&lt;50,000/µL) and overt disseminated intravascular coagulation (DIC) (DIC score of ≥5). We determined the association [risk (RR) ratios] of these abnormalities with complications of scrub typhus, namely-septic shock, multiple organ dysfunction syndrome (MODS), and septic shock with MODS. In total, 71 patients were studied with a mean age of 50 ± 15.5 years, of which 45 (63.4%) were females. On presentation, fever 70 (98.5%), myalgias 22 (31.0%), loose stools 13(18.3%), cough, vomiting, headache 11 (15.5%), altered sensorium 10(14.1%), and pain abdomen 9 (12.7%) were main symptoms. On examination, hypotension 31 (43.7%), eschar 25 (35.2%), icterus 17 (23.9%), and rash 16 (22.5%) were noted. The d-dimer (&gt;0.5 µg/mL) levels were increased in all (100%) patients. Thrombocytopenia (91.5%) was the commonest hematological abnormality and 31 (43.6%) of them had severe thrombocytopenia, 25 (35.2%) patients had low fibrinogen levels (&lt;200 mg/dL) and prothrombin time (PT &gt;16.7 seconds) was prolonged in 20 (28.1%). A total of 42 (59.1%) patients developed MODS, 33 (46.4%) developed septic shock, 24 (33.8 %) had MODS with septic shock, 17 (23.9%) developed overt DIC, and eight (11.2%) died. Severe thrombocytopenia (p = -0.028) and overt DIC (p = 0.045) were significantly associated with septic shock development. In the patients admitted with severe scrub typhus; thrombocytopenia was the commonest hematological abnormality. The development of septic shock was significantly associated with severe thrombocytopenia and overt DIC.

IMMUNOSUPPRESSION CORRELATES WITH THE DETERIORATION OF SEPSIS-INDUCED DISSEMINATED INTRAVASCULAR COAGULATION.

Background: The dysregulated host responses play a crucial role in the pathophysiology process of sepsis-induced disseminated intravascular coagulation (DIC). The study aimed to characterize the dynamic alternation of immune-related biomarkers and their relationship with the progression of DIC during sepsis. Methods: A prospective, observational study was conducted in a tertiary care academic hospital. Six hundred forty patients with sepsis were classified into three groups according to the International Society on Thrombosis and Hemostasis (ISTH) score: 383 involved patients without DIC (ISTH = 0), 168 sepsis with nonovert DIC (ISTH = 1-4), and 89 sepsis with overt DIC (ISTH ≥5). Eighteen immune-related biomarkers and six routine coagulation variables were examined at D1, D3, and D7 upon enrollment. The association between the immune parameters and the DIC deterioration was assessed during sepsis. Results: The study showed a 40% coagulation disorder and a 14% incidence of overt DIC in patients with sepsis. The patients with overt DIC displayed pronounced immune disorders from D1 to D7 upon sepsis, which was characterized by the decreased percentage of monocyte HLA-DR (mHLA-DR), increased percentage of regulatory T cells, the levels of procalcitonin, neutrophil CD64 index, and systemic inflammatory cytokines relative to nonovert DIC or non-DIC patients. In multivariate analysis, the combination of anti-inflammatory cytokine IL-10 and mHLA-DR at D1 upon enrollment had a superior predictive value for predicting DIC deterioration in sepsis (area under the curve = 0.87, P < 0.0001). Conclusion: These data illustrate that immunosuppression can crosstalk with coagulation disorder during sepsis and present an additional evaluation tool to predict DIC deterioration.

Outcomes of Overt and Non-overt Disseminated Intravascular Coagulation Using the ISTH DIC Scoring System in Children: A Single-Center Study.

Several disseminated intravascular coagulation (DIC) scoring systems are used for prognosticating the clinical outcomes of patients with DIC. However, research on children is scarce. Therefore, this study compared the clinical outcomes of overt and non-overt DIC using the International Society on Thrombosis and Hemostasis (ISTH) DIC scoring system. This retrospective study reviewed data on children aged one month to 15 years diagnosed with DIC between 2003 and 2014. Of 244 patients, 179 (73.4%) had overt DIC, and 65 (26.6%) had non-overt DIC. The most common causes were infection (84.8%), tissue injury (7%), and malignancies (2.9%). The 28-day case fatality rate was significantly higher for overt than non-overt DIC (76% vs. 15.6%; P < 0.001). DIC scores were significantly associated with mortality (R2 = 0.89). Each clinical parameter (platelet count, prothrombin time, and fibrin degradation products) was associated with mortality (P = 0.01). On multivariable analysis, the factors associated with death were platelet counts ≤ 50 000 cells/mm3 (OR, 2.42; 95% CI, 1.08-5.42; P = 0.031); overt DIC score (OR, 7.62; 95% CI, 2.94-19.75; P < 0.001); renal dysfunction (OR, 2.92; 95% CI, 1.34-6.37; P = 0.007); shock (OR, 39.62; 95% CI, 4.99-314.84; P = 0.001); and acute respiratory distress syndrome (OR, 25.90; 95% CI, 3.12-214.80; P = 0.003). The 28-day case-fatality rate was significantly higher for patients with overt than non-overt DIC and concordant with ISTH scores. ISTH DIC scores can be used as a clinical predictor for DIC in children.

Diagnosis of Disseminated Intravascular Coagulation in Patients Suffering from Sepsis using the Modified International Society of Thrombosis and Haemostasis Criteria and Japanese Association of Acute Medicine Criteria

Introduction: The international task force defines sepsis as ‘life- threatening organ dysfunction caused by a dysregulated host response to infection’. Disseminated Intravascular Coagulation (DIC) is a coagulopathy syndrome that causes microvascular and macrovascular thrombosis and increases the risk of bleeding due to consumptive coagulopathy. Sepsis causes dysfunction in coagulation due to release of inflammatory markers which leads to inappropriate deposition of intravascular fibrin. In order to facilitate the diagnostic process for detecting DIC, the scoring system recommended by International Society of Thrombosis and Haemostasis (ISTH) and Japanese Association of Acute Medicine (JAAM) were used which are based on the global coagulation tests such as the platelet count, Prothrombin time, International Normalised Ratio (INR) and Fibrin Degradation Products (FDPs)/D-dimer. Aim: To determine the prevalence and outcome of DIC in patients suffering from sepsis using ISTH criteria and JAAM criteria. Materials and Methods: A prospective cohort was carried out from January 2021 to July 2022 in the haematology section of pathology department of Government Medical College and Hospital, Aurangabad, Maharashtra, India. Hundred patients suffering from clinically suspected sepsis were included in the study. Venous blood was collected from patients in Ethylene Diamine Tetra-acetic Acid (EDTA) and Citrate bulbs. The tests performed were Complete Blood Count (CBC), Prothrombin Time (PT), INR and D-Dimer. CBC was performed on Fully automated three part cell counter. PT, INR, D-Dimer testing was done on fully automated coagulometer. The above test results were used to diagnose DIC in patients suffering from sepsis using the modified ISTH and JAAM criterias. The results were analysed using Microsoft excel 2019 i.e., chi-square test was applied for p-value calculation. Results: Out of 100 patients with clinically suspected sepsis 35 patients (35%) suffered from Overt DIC using ISTH criteria and 58 patients (58%) suffered from DIC using JAAM criteria. The total mortality in patients with sepsis in the present study was 40%. The mortality in patients with DIC in sepsis using the ISTH criteria was 26 patients (74.28%) and 37 patients (63.79%) using the JAAM criteria. Conclusion: Coagulation abnormalities are widely prevalent in patients with sepsis and are likely to play a key role in multi- organ dysfunction. Both ISTH and JAAM criteria are good predictors of mortality.

Anticoagulant therapies against sepsis-induced disseminated intravascular coagulation.

Disseminated intravascular coagulation (DIC) is a frequent but lethal complication in sepsis. Anticoagulant therapies, such as heparin, antithrombin, activated protein C, and recombinant human-soluble thrombomodulin, were expected to regulate the progression of coagulopathy in sepsis. Although a number of randomized controlled trials (RCTs) have evaluated the survival effects of these therapies over the past few decades, there remains no consistent evidence showing a significant survival benefit of anticoagulant therapies. Currently, anticoagulant therapies are not conducted as a standard treatment against sepsis in many countries and regions. However, most of these RCTs were performed overall in patients with sepsis but not in those with sepsis-induced DIC, who were theoretically the optimal target population of anticoagulants. Actually, multiple lines of evidence from observational studies and meta-analyses of the RCTs have suggested that anticoagulant therapies might reduce mortality only when used in septic DIC. In addition, the severity of illness is another essential factor that maximally affects the efficacy of the therapy. Therefore, to provide evidence on the true effect of anticoagulant therapies, the next RCTs must be designed to enroll only patients with sepsis-induced overt DIC and a high severity of illness. To prepare these future RCTs, a novel scientific infrastructure for accurate detection of patients who can receive maximal benefit from anticoagulant therapies also needs to be established.

Prognostic Accuracy of the Different Scoring Systems for Assessing Coagulopathy in Sepsis: A Retrospective Study.

There is no gold standard for the diagnosis of coagulation dysfunction in sepsis, and the use of the current scoring systems is still controversial. The purpose of this study was to assess the performance of sepsis-induced coagulopathy (SIC), the Japanese Association for Acute Medicine Disseminated Intravascular Coagulation (JAAM DIC), and the International Society on Thrombosis and Haemostasis overt DIC (ISTH overt-DIC). The relationship between each scoring system and 28-day all-cause mortality was examined. Among 452 patients (mean age, 65 [48,76] years), 306 [66.7%] were men, the median SOFA score was 6 [4,9], and the median APACHE II score was 15 [11,22]. A total of 132 patients (29.2%) died within 28 days. Both the diagnosis of SIC (AUROC, 0.779 [95% CI, 0.728-0.830], P < 0.001) and ISTH overt-DIC (AUROC, 0.782 [95% CI, 0.732-0.833], P < 0.001) performed equally well in the discrimination of 28-day all-cause mortality (between-group difference: SIC versus ISTH overt-DIC, -0.003 [95% CI, -0.025-0.018], P = 0.766). However, the SIC demonstrated greater calibration for 28-day all-cause mortality than ISTH overt-DIC (the coincidence of the calibration curve of the former is higher than that of the latter). The diagnosis of JAAM DIC was not independently associated with 28-day all-cause mortality in sepsis (RR, 1.115, [95% CI 0.660-1.182], P = 0.684). The SIC scoring system demonstrated superior prognostic prediction ability in comparison with the others and is the most appropriate standard for diagnosing coagulopathy in sepsis.

The Relationship Between COVID-19 Related Coagulopathy with Organ Damage and Prognosis

Objective: Coagulopathy and thromboembolic complications are frequently seen in COVID-19. We aimed to evaluate the relationship of coagulopathy with organ dysfunction and mortality in COVID-19.&#x0D; Methods: COVID-19 patients requiring intensive care for treatment and follow-up were retrospectively analyzed. In the definition of coagulopathy, the International Society on Thrombosis and Hemostasis (ISTH) overt disseminated intravascular coagulation (DIC) scoring system was used. Patients were divided into three groups according to the ISTH scores as follows; patients with no coagulopathy (ISTH score 2) and mechanical ventilation requirement, acute kidney injury (AKI), acute hepatic injury (AHI) and mortality rates were compared between these groups.&#x0D; Results: One hundred fifty-five critically ill adult patients with COVID-19 were included in the study. An abnormal coagulation profile developed in 94 (60.6%) patients; of those, 56 (36.1%) patients had non-evident abnormal coagulation, and 38 (24.5%) had evident abnormal coagulation. While there was a significant difference between the groups regarding coagulopathy and development of AKI, requirement for mechanical ventilation, and mortality, no significant difference was found in AHI and length of stay in the intensive care unit. Both mortality and development of AKI increased in correlation with the severity of coagulopathy. ISTH score and development of AKI and AHI were risk factors for both mortality and mechanical ventilation requirement.&#x0D; Conclusion: COVID-19-related coagulopathy, as determined by the ISTH overt DIC scoring system, is a predictor of organ damage and mortality.

Association between hypomagnesemia and coagulopathy in sepsis: a retrospective observational study

BackgroundHypomagnesemia reportedly has significant associations with poor clinical outcomes such as increased mortality and septic shock in patients with sepsis. Although the mechanism underlying these outcomes mostly remains unclear, some experimental data suggest that magnesium deficiency could potentiate coagulation activation in sepsis. However, in sepsis, the association between serum magnesium levels and coagulopathy, including disseminated intravascular coagulation (DIC), remains unknown. Thus, we aimed to investigate the relationship between serum magnesium levels and coagulation status and the association between hypomagnesemia and DIC in patients with sepsis.MethodsThis retrospective observational study was conducted at the intensive care unit (ICU) of a university hospital from June 2011 to December 2017. Patients older than 19 years who met the Sepsis-3 definition were included. We categorized patients into three groups according to their serum magnesium levels: hypomagnesemia (< 1.6 mg/dL), normal serum magnesium level (1.6–2.4 mg/dL), and hypermagnesemia (> 2.4 mg/dL). We investigated the association between serum magnesium levels and overt DIC at the time of ICU admission according to the criteria of the International Society on Thrombosis and Haemostasis.ResultsAmong 753 patients included in this study, 181 had DIC, 105 had hypomagnesemia, 552 had normal serum magnesium levels, and 96 had hypermagnesemia. Patients with hypomagnesemia had a more activated coagulation status indicated by lower platelet counts, lower fibrinogen levels, higher prothrombin time-international normalized ratios, higher thrombin-antithrombin complex, and more frequent DIC than those with normal serum magnesium levels and hypermagnesemia (DIC: 41.9% vs. 20.6% vs. 24.0%, P < 0.001). The coagulation status in patients with hypomagnesemia was more augmented toward suppressed fibrinolysis than that in patients with normal serum magnesium levels and hypermagnesemia. Multivariate logistic regression revealed that hypomagnesemia was independently associated with DIC (odds ratio, 1.69; 95% confidence interval, 1.00–2.84; P = 0.048) after adjusting for several confounding variables.ConclusionsPatients with hypomagnesemia had a significantly activated coagulation status and suppressed fibrinolysis. Hypomagnesemia was independently associated with DIC in patients with sepsis. Therefore, the treatment of hypomagnesemia may be a potential therapeutic strategy for the treatment of coagulopathy in sepsis.

Disseminated intravascular coagulation in a cohort of adult acute leukemia patients: a single center experience.

We aimed to detect the incidence of disseminated intravascular coagulation (DIC) in patients with acute leukemia (AL) and find out its association with types of AL and patients' clinical and pathological parameters. In this prospective study, 59 newly diagnosed adults with AL were clinically examined and screened for DIC presentation time. Coagulation tests, including prothrombin time, activated partial thromboplastin time, fibrinogen level, D-dimer, antithrombin, and protein C and protein S levels were all assessed. The International Society for Thrombosis and Hemostasis scoring system was adopted to diagnose overt DIC. The age of the studied patients ranged from 15 to 81 years with a median of 41 years; male to female ratio was 1.1:1. acute myeloid leukemia (AML) constituted 64.4% of the total cases (38 patients). DIC was detected in 28 patients (47.5%); its incidence was higher in AML than in acute lymphoblastic leukemia (ALL) (52.6% vs. 38.1%). Overt DIC was significantly associated with bleeding manifestations, duration of symptoms, and leukocytosis ( P -values = 0.050, 0.044, and 0.003, respectively). Bleeding events were encountered in 50.8% of patients (25 AML and 5 ALL patients). Bleeding was associated significantly with leukocytosis, thrombocytopenia, and low fibrinogen level. Thrombosis was found in two patients (3.4%) at presentation. Overt DIC was common in patients with AL at presentation, mostly in AML. Routine testing for coagulopathy in newly diagnosed AL patients will possibly aid in improving the overall patients' survival.

PB1844: THROMBOTIC EVENTS DURING REMISSION INDUCTION OF ACUTE MYELOID LEUKEMIA – FREQUENCY AND RELATED FACTORS

Background: Thrombotic events in newly diagnosed patients with acute myeloid leukemia (AML) have been considered rare and have not received a great deal of attention. These events may occur at the diagnosis, during the remission induction, or later. The incidence of thromboembolism in AML varied markedly among studies, ranging from 2 to 13%, and are usually divided between arterial and venous events. Limited evidence points that using markers of disseminated intravascular coagulation (DIC) might predict thrombosis in AML, and the Khorana score is not useful for this purpose. Aims: In this work, we evaluated a cohort of intensively treated adults with non-promyelocytic AML in order to assess the thrombosis rate and baseline factors that might be associated with this event. Methods: This is a retrospective cohort encompassing newly diagnosed AML adult patients (pts) treated at Instituto do Cancer do Estado de Sao Paulo, Brazil, between June 2011 and June 2020. All patients received the “7 + 3” regimen as the frontline regimen, and all thrombotic events until day 60 from diagnosis were captured. Logistic regression was used to find risk factors for thrombosis. Cutoffs for numeric variables were defined by Akaike’s information criteria. Results: Overall, 204 pts were included, with a median age of 54 years (range,17-74). The main baseline features of this cohort are summarized in Table 1. Overall, 24 thrombotic events were registered – the thrombotic rate of 11.9% (95% CI 7.9-17.4%). Most events were catheter-related (9/24), followed by upper (10) and lower (3) limb events. Two patients presented spontaneous jugular vein thrombosis. DIC score (Taylor et al., 2001) was calculated for 107 patients with laboratory data fully available and resulted in overt DIC (≥ 5) in 45.2%. By univariate analysis, morphologic subtype, AML genetic classification, fibrinogen, d-dimer, and DIC score were not associated with thrombosis during induction in AML. Excluding those catheter-related cases, we noticed a higher monocyte count in patients who developed thrombosis (15.8 vs. 4.7x109/L, p=0.009). Incidence of thrombosis in patients with monocyte count >8.5x109/L was 16% vs. 6.2%. The overall 60-day mortality was 25.8%, with no death related to thrombosis. DIC score was not associated with early mortality during AML induction (p=0.19). Remaining coagulation parameters when individually assessed were also not linked with thrombosis or mortality during induction. Image:Summary/Conclusion: In this study with intensively treated newly diagnosed AML, we noticed a similar incidence of thrombosis to that previously reported. While most events reported in this cohort were related to catheter devices, spontaneous thrombosis was associated with a higher baseline monocyte count. While monocytic AML may present with DIC at the diagnosis, monocytic cells are a major source of blood tissue factor, pointing it as an independent marker for thrombosis in AML. Our data, although limited, highlights that the understanding of the thrombosis landscape in AML is complex, and the sole use of already recognized markers of coagulation activation might not be sufficient for prediction.

Clinicopathological features, treatment outcome and survival of 115 cases of gastric adenocarcinoma with bone marrow metastasis and disseminated intravascular coagulation.

e16035 Background: Bone marrow (BM) infiltration is a special subtype of bone metastasis in gastric cancer (GC) and frequently complicated with disseminated intravascular coagulation (DIC) and other hematological disorders, which constitute a critical but poorly defined clinical syndrome (GBD syndrome). At present, only case reports are available about this peculiar disease. This pooled analysis was to describe its detailed clinicopathological features and treatment outcome. Methods: Cases reported in medical literatures or treated in our hospital from 2000 to 2021 were systemically scrutinized. The inclusion criteria were: adenocarcinoma in gastroesophageal junction or stomach, carcinomatosis in BM, and overt DIC. Detailed clinical and pathological data were reviewed. Based on the chronological order of the diagnosis of GC, BM infiltration and DIC, GBD syndromes could be classified as synchronous and metachronous type. Descriptive statistics, chi-square test, Fisher's exact tests, and survival analysis were performed as appropriate. Results: 115 cases of GBD syndrome were identified. 91 (79.1%) were synchronous and 24 (20.9%) were metachronous. Female patients were more than half in the study (61, 53.1%). The median age of 51 (9-87) was relatively younger than that of normal GC. ECOG PS 3-4 were present in 67 (58.3%) cases. 109 (94.8%) had poorly differentiated adenocarcinoma. Her-2 overexpression were only seen in 8 (6.9%) cases and none were d-MMR. 88.3% (53 out of 60) cases treated in our hospital showed remarkable CKMB elevation which was not mentioned in previous reports. Abnormal level of LDH and ALP were seen in 91.2% and 64.3% cases. Totally, 82 patients received anticancer therapy. 70 (85.3%) went through the first DIC strike. 5-FU and docetaxel were the most applied agents. Patients treated with BSC only survived 14 days (2-61). After the remission of DIC, patients with synchronous and metachronous BD syndrome achieved 168 and 182 days of overall survival, respectively (p = 0.932). Conclusions: CKMB might be a distinctive marker for GBD syndrome. Active chemotherapy achieved numerous remissions of DIC and a considerable survival. Further translational research and prospective trial are urgently needed.

Overt Disseminated Intravascular Coagulation with Severe Hypofibrinogenemia During Veno-Venous Extracorporeal Membrane Oxygenation

Disseminated intravascular coagulation (DIC) is a life-threatening hematologic derangement characterized by dysregulated thrombin generation and excessive fibrinolysis. However, DIC is poorly characterized in the extracorporeal membrane oxygenation (ECMO) population, and the underlying mechanisms are not well understood. Several mechanisms contribute to DIC in ECMO, including consumption of coagulation factors, acquired von Willebrand’s syndrome leading to thrombocytopenia, and hyperfibrinolysis. There are few case reports of DIC in adult ECMO patients. Most are in the context of venoarterial ECMO, which is typically used in the setting of cardiogenic shock and cardiac arrest. These disease states themselves are known to be associated with DIC, liver failure, impaired anticoagulant mechanisms, and increased fibrinolysis. We present an unusual case of a 74-year-old man who developed overt DIC during veno-venous (VV) ECMO. DIC resulted in clinical bleeding and severe hypofibrinogenemia requiring massive cryoprecipitate transfusion of 87 pooled units. When the patient was decannulated from ECMO, his platelet count and fibrinogen concentration improved within 24 hours, suggesting that ECMO was a proximate cause of his DIC.