Disseminated intravascular coagulation and its immune mechanisms.

Disseminated intravascular coagulation (DIC) is a syndrome triggered by infectious and noninfectious pathologies characterized by excessive generation of thrombin within the vasculature and widespread proteolytic conversion of fibrinogen. Despite diverse clinical manifestations ranging from thrombo-occlusive damage to bleeding diathesis, DIC etiology commonly involves excessive activation of blood coagulation and overlapping dysregulation of anticoagulants and fibrinolysis. Initiation of blood coagulation follows intravascular expression of tissue factor or activation of the contact pathway in response to pathogen-associated or host-derived, damage-associated molecular patterns. The process is further amplified through inflammatory and immunothrombotic mechanisms. Consumption of anticoagulants and disruption of endothelial homeostasis lower the regulatory control and disseminate microvascular thrombosis. Clinical DIC development in patients is associated with worsening morbidities and increased mortality, regardless of the underlying pathology; therefore, timely recognition of DIC is critical for reducing the pathologic burden. Due to the diversity of triggers and pathogenic mechanisms leading to DIC, diagnosis is based on algorithms that quantify hemostatic imbalance, thrombocytopenia, and fibrinogen conversion. Because current diagnosis primarily assesses overt consumptive coagulopathies, there is a critical need for better recognition of nonovert DIC and/or pre-DIC states. Therapeutic strategies for patients with DIC involve resolution of the eliciting triggers and supportive care for the hemostatic imbalance. Despite medical care, mortality in patients with DIC remains high, and new strategies, tailored to the underlying pathologic mechanisms, are needed.

How we manage a high D-dimer.

D-dimer, a soluble fibrin degradation product that originates from plasmin-induced degradation of cross-linked fibrin, is an important biomarker of coagulation activation and secondary fibrinolysis that is routinely used to rule out venous thromboembolism (VTE), and to evaluate the risk of VTE recurrence, as well as the optimal duration of anticoagulant therapy. Besides VTE, D-dimer may be high due to physiologic conditions, including aging, pregnancy, and strenuous physical activity. In addition, several disorders have been associated with increased D-dimer levels, ranging from disseminated intravascular coagulation to infectious diseases and cancers. Thus, it is far from unusual for hematologists to have to deal with ambulatory individuals with increased D-dimer without signs or symptoms of thrombus formation. This narrative review is dedicated to the management of these cases by the hematologist.

The two therapeutic strategies of surgical intervention and medical management in a patient with enhanced-fibrinolytic type of disseminated intravascular coagulation after aortic replacement for Stanford type A aortic dissection with chronic heart and renal failure.

BACKGROUND: Management of the enhanced-fibrinolytic type of disseminated intravascular coagulation (DIC) caused by aortic disorders is the two strategies of surgical intervention and medical treatment based on the patient's age and comorbidities. CASE PRESENTATION: An 81-year-old woman with a history of two previous aortic surgeries and chronic heart and renal failure was admitted for uncontrollable subcutaneous hemorrhage. The hemorrhage was caused by the enhanced-fibrinolytic type of disseminated intravascular coagulation (DIC) caused by periprosthetic graft hematoma after aortic replacement for Stanford type A aortic dissection. Open thoracic hemostasis temporarily controlled the subcutaneous hemorrhage, but she was readmitted for the recurrence seven months after discharge. On the second admission, the combination of anticoagulant and antifibrinolytic agents was successful. CONCLUSION: Management of the enhanced-fibrinolytic type of DIC caused by aortic disorders is important of a successful combination of surgical and medical therapy tailored the patient's condition.

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

OBJECTIVES: 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. DESIGN: 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. SETTING: PICU of the Department of Pediatrics, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand. SUBJECTS: 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. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: 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). CONCLUSIONS: 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.

A novel predictive marker for placental abruption with composite adverse outcomes: creatinine-fibrinogen ratio.

PURPOSE: To develop a new cost-effective marker named creatinine-fibrinogen ratio (CFR) for the prediction of composite adverse outcomes (CAO) in placental abruption cases. METHODS: A total of 109 placental abruption patients (30 with adverse outcomes, 79 without adverse outcomes) were enrolled in this retrospective cohort study. Patients with at least one of the features listed below were included in the abruption with CAO group: requirement of blood product transfusion (erythrocyte suspension, fresh frozen plasma, pooled thrombocyte, thrombocyte apheresis), development of acute kidney injury or disseminated intravascular coagulation, and need for intensive care unit. Laboratory parameters and CFR values at admission to the hospital were compared between the two groups. RESULTS: Higher creatinine and lower fibrinogen levels were found in the CAO group (p = 0.007 and p < 0.001 respectively). The CFR value of the CAO group was significantly higher (p < 0.001). In the ROC curve analysis performed to investigate the value of CFR in CAO prediction, the area under the curve (AUC) was calculated as 0,802 (95% CI 0.709-0.895, 77% sensitivity, 65% specificity). CONCLUSION: CFR seems to be a practical marker for the prediction of CAOs in pregnant women with ablatio placenta.

A Curious Case of Autoimmunity, Pancytopenia, and Disseminated Intravascular Coagulation.

HISTORY AND EXAMINATION: A 21-year-old female patient presented to us with severe low back pain for 4 months. On examination, patient was afebrile, with severe pallor, and tenderness in both sacroiliac (SI) joints. Patient was being admitted and evaluated, and during the course of evaluation, developed severe headache, which was severe in intensity and associated with nausea and projectile vomiting. Initial investigations: An X-ray of the bilateral SI joints revealed inflammation, and the antinuclear antibody (ANA) turned out to be 4+ with pancytopenia and raised lactate dehydrogenase (LDH), but the liver function tests were normal. Rest of the rheumatological profile was unremarkable. During the course of the evaluation, she developed a severe headache, which, on imaging, showed presence of cerebral edema with chronic subdural hematoma, and a concomitant coagulopathy workup revealed evidence of disseminated intravascular coagulation (DIC). DISCUSSION: Taking the whole picture into consideration, a malignant process in the body was suspected, and serum tumor markers carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), and cancer antigen 125 (CA-125) were sent, all of which were raised. Validating the clinical clue was the bone marrow biopsy done for pancytopenia, which revealed malignant epithelial infiltration. A contrast-enhanced computed tomography (CECT) thorax and whole abdomen were done to find out the primary, which showed a neoplastic mass at the gastroesophageal junction along with bony metastases in the vertebrae and left adrenal. Tissue from the primary lesion was taken for histopathological examination (HPE) through upper gastrointestinal endoscopy. Although HPE revealed grade III poorly differentiated stomach adenocarcinoma, the patient had succumbed to the disease process by the time the diagnosis came to light. CONCLUSION: In short, this case perfectly illustrates how solid organ malignancies might be a mimicker of multisystem disorders, thereby delaying diagnosis and worsening the prognosis even further.

A newly proposed heatstroke-induced coagulopathy score in patients with heat illness: A multicenter retrospective study in China.

PURPOSE: In patients with heatstroke, disseminated intravascular coagulation (DIC) is associated with greater risk of in-hospital mortality. However, time-consuming assays or a complex diagnostic system may delay immediate treatment. Therefore, the present study proposes a new heatstroke-induced coagulopathy (HIC) score in patients with heat illness as an early warning indicator for DIC. METHODS: This retrospective study enrolled patients with heat illness in 24 Chinese hospitals from March 2021 to May 2022. Patients under 18 years old, with a congenital clotting disorder or liver disease, or using anticoagulants were excluded. Data were collected on demographic characteristics, routine blood tests, conventional coagulation assays and biochemical indexes. The risk factors related to coagulation function in heatstroke were identified by regression analysis, and used to construct a scoring system for HIC. The data of patients who met the diagnostic criteria for HIC and International Society on Thrombosis and Haemostasis defined-DIC were analyzed. All statistical analyses were performed using SPSS 26.0. RESULTS: The final analysis included 302 patients with heat illness, of whom 131 (43.4%) suffered from heatstroke, including 7 death (5.3%). Core temperature (OR = 1.681, 95% CI 1.291 - 2.189, p < 0.001), prothrombin time (OR = 1.427, 95% CI 1.175 - 1.733, p < 0.001) and D-dimer (OR = 1.242, 95% CI 1.049 - 1.471, p = 0.012) were independent risk factors for heatstroke, and therefore used to construct an HIC scoring system because of their close relation with abnormal coagulation. A total score ≥ 3 indicated HIC, and HIC scores correlated with the score for International Society of Thrombosis and Hemostasis -DIC (r = 0.8848, p < 0.001). The incidence of HIC (27.5%) was higher than that of DIC (11.2%) in all of 131 heatstroke patients. Meanwhile, the mortality rate of HIC (19.4%) was lower than that of DIC (46.7%). When HIC developed into DIC, parameters of coagulation dysfunction changed significantly: platelet count decreased, D-dimer level rose, and prothrombin time and activated partial thromboplastin time prolonged (p < 0.05). CONCLUSIONS: The newly proposed HIC score may provide a valuable tool for early detection of HIC and prompt initiation of treatment.

Tackling a deadly global phenomenon: sepsis induced coagulopathy: A narrative review.

Sepsis is a potentially fatal illness marked by organ failure and the two main causes of which are shock and disseminated intravascular coagulation. Multi-organ dysfunction in sepsis is mediated by the inflammatory cytokine storm, while sepsis induced coagulopathy is mediated and accelerated by activation of pro-coagulative mechanisms. Regardless of the severity of sepsis, disseminated intravascular coagulation is a potent predictor of mortality in septic patients. Additionally, oxidative stress in sepsis causes renal ischaemia and eventually acute kidney injury. The first and foremost goal is to initiate resuscitation immediately, with treatment mainly focussing on maintaining a balance of coagulants and anticoagulants. A simpler and more universal diagnostic criteria is likely to improve studies on the spectrum associated with sepsis.

Hemophagocytic lymphohistiocytosis and disseminated intravascular coagulation are underestimated, but fatal adverse events in chimeric antigen receptor T-cell therapy.

Hematotoxicity is the most common long-term adverse event (AE) after chimeric antigen receptor T-cell (CAR T) therapy. However, patients who receive CAR T therapy in pivotal clinical trials are subjected to restrictive selection criteria, and this means that rare but fatal toxicities are underestimated. Here, we systematically analyzed CAR T-associated hematologic AE using the US Food and Drug Administration Adverse Event Reporting System (FAERS) between January 2017 and December 2021. Disproportionality analyses were performed using reporting odds ratios (ROR) and information component (IC); the lower limit of the ROR and IC 95% confidence interval (CI) (ROR025 and IC025) exceeding one and zero was considered significant, respectively. Among the 105,087,611 reports in FAERS, 5,112 CAR T-related hematotoxicity reports were identified. We found 23 significant over-reporting hematologic AE (ROR025 >1) compared to the full database, of which hemophagocytic lymphohistiocytosis (HLH; n=136 [2.7%], ROR025 = 21.06), coagulopathy (n=128 [2.5%], ROR025 = 10.43), bone marrow failure (n=112 [2.2%], ROR025 = 4.88), disseminated intravascular coagulation (DIC; n=99 [1.9%], ROR025 = 9.64), and B-cell aplasia (n=98 [1.9%], ROR025 = 118.16, all IC025 > 0) were highly under-reported AE in clinical trials. Importantly, HLH and DIC led to mortality rates of 69.9% and 59.6%, respectively. Lastly, hematotoxicity-related mortality was 41.43%, and 22 death-related hematologic AE were identified using LASSO regression analysis. These findings could help clinicians in the early detection of those rarely reported but lethal hematologic AE, thus reducing the risk of severe toxicities for CAR T recipients.

Value of the FDP/FIB ratio in predicting early severe bleeding events in patients with newly diagnosed acute promyelocytic leukemia.

Severe bleeding is the leading cause of early death in patients with newly diagnosed acute promyelocytic leukemia (APL). However, there are no means for hemorrhagic risk stratification in APL. This study aimed to identify optimized predictors of severe bleeding events related to APL. A total of 109 consecutive patients with newly diagnosed APL from January 2015 to April 2022 were retrospectively investigated. A systematic review of computer-based patient medical records was conducted to obtain clinical date, including baseline characteristics, routine blood examination findings, coagulation and fibrinolysis indexes, and bleeding events. Among the 109 patients, 89 were classified into the no-severe bleeding group, while 20 had severe bleeding. Compared with the patients with no severe bleeding, the patients with severe bleeding had significantly higher circulating leukemic cell percentages, disseminated intravascular coagulation (DIC) scores, D-dimer (D-D) levels, and fibrin degradation product (FDP) levels. They also had lower fibrinogen (FIB) levels and a longer prothrombin time. Multivariate analysis revealed that the circulating leukemic cell percentage (OR = 1.040, CI = 1.008-1.072, P = 0.012), FIB level (OR = 0.101, CI = 0.011-0.896, P = 0.040), and FDP level (OR = 1.012, CI = 1.000-1.024, P = 0.047) were independent risk factors for severe bleeding. FDP/FIB, D-D/FIB, and seven meaningful indicators in the single-factor analysis were included in the receiver operating characteristic (ROC) curve analysis. The results showed that FDP/FIB was the best indicator for predicting severe bleeding related to newly diagnosed APL. The area under the ROC curve of FDP/FIB was 0.915, and the best cutoff value was 61.77, with 100% sensitivity and 74.2% specificity. Statistical analysis showed a higher incidence of severe bleeding and higher DIC scores when FDP/FIB was >61.77 in APL patients. FDP/FIB has obvious advantages in predicting the degree of bleeding associated with primary promyelocytic leukemia; the greater the FDP/FIB value, the more severe the bleeding. The risk of severe bleeding was the highest when FDP/FIB > 61.77.

International Survey of the Management of Disseminated Intravascular Coagulation Among Pediatric and Neonatal Health Care Practitioners.

The International Society of Thrombosis and Hemostasis (ISTH) provides objective disseminated intravascular coagulation (DIC) measurement through diagnostic criteria validated in adults. The applicability of these criteria in pediatric and neonatal DIC is controversial and unvalidated. Primary objective: to evaluate current practice in pediatric and neonatal DIC management among different specialties. Secondary objective: to understand the potential impact of developmental hemostasis on DIC laboratory evaluation. We performed a multicenter survey between January and September 2016. The questionnaire was distributed internationally through professional societies. In all, 211 responses were received, of which 160 were full responses and 51 were partial. Overall, 85% of respondents practiced in tertiary academic centers; 70% practiced in pediatric-only hospitals. The majority of respondents (42%) used their personal clinical experience in the management of DIC. Sixty percent of respondents treated DIC until the resolution of both clinical and laboratory parameters. Laboratory investigations were monitored in the majority of DIC cases without thrombosis or bleeding (80%); age-specific reference ranges for tests were lacking in 20% of pediatric-only hospitals and 35% of combined pediatric/adult hospitals. Adherence to standardized DIC guidelines was poor but varied by geographical location. This survey reveals variable practices among pediatricians in the management of DIC. Further studies are needed to validate the DIC diagnostic criteria in children.

Effectiveness of transarterial embolisation for intractable postpartum haemorrhage in a disseminated intravascular coagulation state, despite emergency hysterectomy.

PURPOSE: We evaluated the effectiveness of transarterial embolization (TAE) for intractable postpartum hemorrhage in patients with disseminated intravascular coagulation (DIC) despite emergency hysterectomy. MATERIALS AND METHODS: We retrospectively assessed TAE performed after emergency hysterectomy in 15 patients between July 2008 and January 2022. Underlying condition, technical success, clinical success, angiographic findings, laboratory findings, pregnancy-modified DIC score (The International Society on Thrombosis and Haemostasis), blood transfusion, ICU (Intensive care unit) admission day, hospital day, in-hospital mortality, and long-term sequelae were evaluated. RESULTS: All patients were diagnosed with DIC before embolization, with a 43.9 mean DIC score. All patients showed positive angiographic findings for active bleeding. Thirty-eight bleeding arteries were confirmed. The remnant uterine artery (n=25) was the most common focus of persistent bleeding, followed by the cervicovaginal artery (n=6), pudendal artery (n=3), obturator artery (n=2), vesical artery (n=1), and unspecified artery from the internal iliac artery (n=1). Technical and clinical success rates were 100% (15/15) and 93.3% (14/15), respectively. Mean nadir hemoglobin (Hb) level before embolization was 4.9 g/dL. All patients underwent massive transfusion before embolization (mean 33.2 packs of RBC). Postoperatively, a smaller amount of blood was transfused than before the procedure (mean 10.6 packs of RBC). Mean nadir Hb level after embolization was 8.2 g/dL. There was one instance each of in-hospital death, hypoxic brain damage, and ischemic acute kidney injury. CONCLUSION: Despite hysterectomy for postpartum bleeding, there could be multiple residual or uncontrolled bleeding foci, especially in case of DIC, for which TAE could be an effective treatment.

D-Dimer Levels and the Disseminated Intravascular Coagulation Score to Predict Severity and Outcomes in Sepsis or Septic Shock.

BACKGROUND: Studies investigating the diagnostic and prognostic value of D-dimer levels and the disseminated intravascular coagulation (DIC) score in sepsis or septic shock commonly include preselected subgroups of patients or were published prior to the current sepsis-3 criteria. Therefore, this study investigates the diagnostic and prognostic impact of D-dimer levels and the DIC score in patients with sepsis and septic shock. METHODS: Consecutive patients with sepsis and septic shock enrolled in the prospective and monocentric "MARSS" registry from 2019 to 2021 were included. First, the diagnostic value of D-dimer levels was compared to the DIC score to discriminate patients with septic shock from patients with sepsis without shock. Thereafter, the prognostic value of D-dimer levels and the DIC score was tested for 30-day all-cause mortality. Statistical analyses included univariable t-tests, Spearman´s correlations, C-statistics, Kaplan-Meier, as well as uni- and multivariable cox regression analyses. RESULTS: One hundred patients were included (n = 63 with sepsis and n = 37 with septic shock). The overall rate of all-cause mortality at 30 days was 51%. With an area under the curve (AUC) of 0.710 and 0.739, both D-dimer level and the DIC score revealed reliable diagnostic accuracy for the discrimination of septic shock. However, D-dimer levels and the DIC scores were shown to have poor to moderate prognostic accuracy (AUC 0.590 - 0.610) with regard to 30-day all-cause mortality. Specifically, very high D-dimer levels (i.e., > 30 mg/L) (HR = 2.648; 95% CI 1.147 - 6.112; p = 0.023) and a DIC scores ≥ 3 (HR = 2.095; 95% CI 1.095 - 4.009; p = 0.0258) were associated with highest risk of 30-day all-cause mortality. Finally, both higher D-dimer levels (HR = 1.032; 95% CI 1.005 - 1.060; p = 0.021) and DIC scores (HR = 1.313; 95% CI 1.106 - 1.559; p = 0.002) were associated with increased risk of 30-day all-cause mortality after multivariable adjustment. CONCLUSIONS: Both D-dimer levels and the DIC scores revealed reliable diagnostic accuracy for the discrimination of septic shock, but a poor to moderate prognostic value for the discrimination of 30-day all-cause mortality. Especially very high D-dimer levels (i.e., > 30 mg/L) and a DIC score ≥ 3 were associated with highest risk of 30-day all-cause mortality.

Bleeding events associated with recombinant human soluble thrombomodulin, classified according to renal function, in sepsis-induced disseminated intravascular coagulation.

OBJECTIVE: Recombinant human soluble thrombomodulin (rhsTM) is a therapeutic agent for sepsis-induced disseminated intravascular coagulation (DIC) and is associated with bleeding events. rhsTM is a renal excretion drug; however, information on the role of rhsTM in renal function is limited. MATERIALS AND METHODS: In this retrospective observational study, we assessed rhsTM-associated bleeding events according to the renal function of patients with sepsis-induced DIC. We analyzed the data of 79 patients administered a standard-dose of rhsTM for sepsis-induced DIC, at a single center. Patients were classified based on estimated glomerular filtration rate (eGFR). We measured fresh bleeding events following rhsTM administration, DIC score efficacy, and 28-day mortality. RESULTS: Fresh bleeding events were observed in 15 patients, with a significant difference in the eGFR, platelet count, and DIC scores. Furthermore, fresh bleeding events tended to increase with the deterioration of renal function (p = 0.039). The DIC scores in all renal function groups decreased after -rhsTM administration. Additionally, the 28-day mortality was less than 30% in all groups. CONCLUSION: Our results indicate that the effectiveness of the standard-dose of rhsTM is not related to renal function. However, standard-dose rhsTM therapy could potentially increase the risk of adverse bleeding events with severe renal function equivalent to G5.

Maternal Coagulation Disorders and Postpartum Hemorrhage.

Coagulation disorders are rare causes of postpartum hemorrhage. Disturbances in coagulation should be suspected in patients with a family history of coagulopathy, those with a personal history of heavy menstrual bleeding, and those with persistent bleeding despite correction of other causes. The coagulopathic conditions discussed include disseminated intravascular coagulation, platelet disorders, and disturbances of coagulation factors. These should not be overlooked in the evaluation of obstetric hemorrhage, as diagnosis and appropriate treatment may prevent severe maternal morbidity and mortality.

Dielectric Blood Coagulometry for the Early Detection of Sepsis-Induced Disseminated Intravascular Coagulation: A Prospective Observational Study.

OBJECTIVES: To evaluate the utility of dielectric blood coagulometry for early sepsis-induced disseminated intravascular coagulation diagnosis. DESIGN: Single-center, prospective observational study. SETTING: Patients with sepsis or septic shock at the Tokyo Medical and Dental University Hospital of Medicine between September 2019 and September 2020. PATIENTS: The patients were divided into three groups according to the timing of disseminated intravascular coagulation diagnosis based on the Disseminated Intravascular Coagulation score by the Japanese Association for Acute Medicine: 1) no disseminated intravascular coagulation group, 2) late-diagnosed disseminated intravascular coagulation group: not diagnosed with disseminated intravascular coagulation on day 1 but diagnosed within 48 hours after admission, and 3) disseminated intravascular coagulation group: diagnosed with disseminated intravascular coagulation on day 1. The study evaluated 80 patients (no disseminated intravascular coagulation, 31 [38.8%]; late-diagnosed disseminated intravascular coagulation, 34 (42.5%); disseminated intravascular coagulation, 15 [18.8%]). MEASUREMENTS AND MAIN RESULTS: We compared the clinical severity scores and mortality of the groups and assessed the correlation between the dielectric blood coagulometry-derived coagulation marker, thrombin levels, and Disseminated Intravascular Coagulation score using Spearman rank correlation. The mortality rate was 0% (0/31) in the no disseminated intravascular coagulation group, 35.3% (12/34) in the late-diagnosed disseminated intravascular coagulation group, and 33.3% (5/15) in the disseminated intravascular coagulation group. Although the Disseminated Intravascular Coagulation score on day 1 did not reflect disseminated intravascular coagulation in approximately 70% of patients who developed disseminated intravascular coagulation by day 2, dielectric clot strength measured by dielectric blood coagulometry on day 1 strongly correlated with disseminated intravascular coagulation development by day 2 (Spearman ρ = 0.824; p < 0.05) and with thrombin level on day 1 (Spearman ρ = 0.844; p < 0.05). CONCLUSIONS: Dielectric blood coagulometry can be used to detect early-phase disseminated intravascular coagulation in patients with sepsis and is strongly correlated with thrombin levels. Larger studies are needed to verify our results for developing clinical applications.

Disseminated Intravascular Coagulation: The Past, Present, and Future Considerations.

Disseminated intravascular coagulation (DIC) has been understood as a consumptive coagulopathy. However, impaired hemostasis is a component of DIC that occurs in a progressive manner. The critical concept of DIC is systemic activation of coagulation with vascular endothelial damage. DIC is the dynamic coagulation/fibrinolysis disorder that can proceed from compensated to decompensated phases, and is not simply impaired hemostasis, a misunderstanding that continues to evoke confusion among clinicians. DIC is a critical step of disease progression that is important to monitor over time. Impaired microcirculation and subsequent organ failure due to pathologic microthrombi formation are the pathophysiologies in sepsis-associated DIC. Impaired hemostasis due to coagulation factor depletion from hemodilution, shock, and hyperfibrinolysis occurs in trauma-associated DIC. Overt-DIC diagnostic criteria have been used clinically for more than 20 years but may not be adequate to detect the compensated phase of DIC, and due to different underlying causes, there is no "one-size-fits-all criteria." Individualized criteria for heterogeneous conditions continue to be proposed to facilitate the diagnosis. We believe that future research will provide therapeutics using new diagnostic criteria. Finally, DIC is also classified as either acute or chronic, and acute DIC results from progressive coagulation activation over a short time and requires urgent management. In this review, we examine the advances in research for DIC.

D-dimers-"Normal" Levels versus Elevated Levels Due to a Range of Conditions, Including "D-dimeritis," Inflammation, Thromboembolism, Disseminated Intravascular Coagulation, and COVID-19.

D-dimers reflect a breakdown product of fibrin. The current narrative review outlines how D-dimers can arise in normal individuals, as well as in patients suffering from a wide range of disease states. D-dimers in normal individuals without evident thrombosis can arise from background fibrinolytic activity in various tissues, including kidney, mammary and salivary glands, which ensures smooth flow of arising fluids where any blood contamination could be immediately lysed. In addition, healthy individuals can also regularly sustain minor injuries, often unbeknown to them, and wound healing follows clot formation in these situations. D-dimers can also arise in anxiety and following exercise, and are also markers of inflammation. Lung inflammation (triggered by microbes or foreign particles) is perhaps also particularly relevant, since the hemostasis system and fibrinolysis help to trap and remove such debris. Lung inflammation in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may contribute to D-dimer levels additive to thrombosis in patients with COVID-19 (coronavirus disease 2019). Indeed, severe COVID-19 can lead to multiple activation events, including inflammation, primary and secondary hemostasis, and fibrinolysis, all of which may contribute to cumulative D-dimer development. Finally, D-dimer testing has also found a role in the diagnosis and triaging of the so-called (COVID-19) vaccine-induced thrombotic thrombocytopenia.

Relationship of acute type A aortic dissection and disseminated intravascular coagulation.

OBJECTIVE: Acute type A aortic dissection (ATAAD) is a critical disease presenting with disseminated intravascular coagulation (DIC). However, the relationship between the degree of DIC and false lumen conditions remains unclear. In the present study, we evaluated the degree of preoperative DIC and the outcomes of ATAAD treatment. METHODS: A total of 124 patients with ATAAD (70 men and 54 women) treated from January 2012 to January 2020 were included in the present study. The correlation between the preoperative Japanese Association for Acute Medicine (JAAM) DIC score and the false lumen diameter and length, measured using preoperative computed tomography, was examined retrospectively. The correlations were calculated using liner regression analysis. The level of statistical significance was set at P < .05. RESULTS: The patients were divided into two groups: a low JAAM DIC score group and a high JAAM DIC score group. The preoperative JAAM DIC scores in the high- and low-score groups were 4.8 ± 1.2 and 1.7 ± 2.3, respectively (P < .001). The 5-year survival rates and aortic event-free rates in the low-score group were favorable compared with the high-score group; however, the differences were not statistically significant (80.8% vs 54.5%, P = .065; 63.9% vs 59.8%, P = .15, respectively). The false lumen diameter in the ascending aorta was greater in the high-score group than that in the low-score group (P < .05). The JAAM DIC score correlated significantly with the ascending false lumen diameter and the dissection length (r = 0.32 and P < .001; r = 0.29 and P = .001, respectively). A high JAAM DIC score was associated with communicating-type ATAAD (P < .05). CONCLUSIONS: Our results suggest that high preoperative JAAM DIC scores are associated with a large false lumen and communicating-type ATAAD.

Case report of Salmonella derby septicemia complicated with co-occurrence of disseminated intravascular coagulation and thrombotic microangiopathy.

BACKGROUND: Both disseminated intravascular coagulation and thrombotic microangiopathy are complications of sepsis as Salmonella septicemia, respectively. They are related and have similar clinical characteristics as thrombopenia and organ dysfunctions. They rarely co-occur in some specific cases, which requires a clear distinction. CASE PRESENTATION: A 22-year-old woman had just undergone intracranial surgery and suffered from Salmonella derby septicemia with multiorgan involvement in the hospital. Laboratory workup demonstrated coagulation disorder, hemolytic anemia, thrombocytopenia, and acute kidney injury, leading to the co-occurrence of disseminated intravascular coagulation and secondary thrombotic microangiopathy. She received antibiotics, plasma exchange therapy, dialysis, mechanical ventilation, fluids, and vasopressors and gained full recovery without complications. CONCLUSION: Disseminated intravascular coagulation and secondary thrombotic microangiopathy can co-occur in Salmonella derby septicemia. They should be treated cautiously in diagnosis and differential diagnosis. Thrombotic microangiopathy should not be missed just because of the diagnosis of disseminated intravascular coagulation. Proper and timely identification of thrombotic microangiopathy with a diagnostic algorithm is essential for appropriate treatment and better outcomes.