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1.
Rinsho Ketsueki ; 65(9): 1094-1100, 2024.
Article in Japanese | MEDLINE | ID: mdl-39358265

ABSTRACT

Disseminated intravascular coagulation (DIC) is defined as systemic intravascular coagulation activity that has been acquired in the presence of various underlying diseases and is outside local or compensatory control, and is a fatal condition. Although the pathogenesis, diagnosis, and treatment of DIC are well known in Japan, each clinician has a different understanding of DIC, which makes it difficult to standardize diagnosis and treatment. Even at the international level, perception of DIC varies widely. This makes it difficult for residents and novice clinicians to standardize routine care for DIC. To meet the demands of the times, my colleagues and I are currently working on a globally unprecedented project to develop guidelines for the treatment of DIC for each underlying disease (tentative title). This article will also review the status of past guidelines from inside and outside Japan.


Subject(s)
Disseminated Intravascular Coagulation , Practice Guidelines as Topic , Disseminated Intravascular Coagulation/diagnosis , Disseminated Intravascular Coagulation/therapy , Disseminated Intravascular Coagulation/etiology , Humans , Japan , Anticoagulants/therapeutic use , Anticoagulants/administration & dosage
2.
Rinsho Ketsueki ; 65(9): 1125-1130, 2024.
Article in Japanese | MEDLINE | ID: mdl-39358269

ABSTRACT

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection, and remains a global issue due to its high incidence and mortality. Many randomized controlled trials have investigated sepsis, but no specific treatments have been established. This is due to "heterogeneity," which indicates that a diagnosis of sepsis includes various pathophysiological states. To resolve this issue, efforts are being made to identify subclasses of sepsis. Past studies have selected different variables, such as expressed genes, cytokines, and vital signs, and identified subclasses based on clinical or biomarker-expression features. We also identified subclasses of sepsis with different coagulation features, and found that a specific anticoagulant agent (recombinant human thrombomodulin) was associated with improved survival rates in only one subclass. We also developed a model that could predict the subclass. However, none of the reported subclasses had shared characteristics, and they are not in clinical use. Further research is required to identify subclasses that are strongly associated with the pathophysiological mechanism and reproducible in any cohort.


Subject(s)
Anticoagulants , Disseminated Intravascular Coagulation , Sepsis , Humans , Sepsis/drug therapy , Sepsis/complications , Anticoagulants/therapeutic use , Disseminated Intravascular Coagulation/drug therapy , Disseminated Intravascular Coagulation/etiology , Disseminated Intravascular Coagulation/diagnosis , Thrombomodulin/therapeutic use
3.
Allergol Immunopathol (Madr) ; 52(5): 65-72, 2024.
Article in English | MEDLINE | ID: mdl-39278853

ABSTRACT

Sepsis is a life-threatening condition that has the potential to multiple organ dysfunction and mortality. One of its frequent complications is disseminated intravascular coagulation (DIC), characterized by hyperactive clotting mechanisms that cause widespread clot formation and tissue damage. This study aimed to investigate early diagnostic markers of sepsis-associated DIC by comparing inflammatory factor levels, 28-day survival rates, coagulation function, and markers between patients with sepsis (non-DIC group) and those with sepsis-induced DIC (DIC group). The study analyzed the diagnostic efficacy of coagulation function and markers in predicting the occurrence and prognosis of sepsis-associated DIC, presenting survival curves. Results indicated significantly increased levels of APTT, TAT, tPAIC, PIC, and sTM in the DIC group compared to the non-DIC group. Sequential Organ Failure Assessment (SOFA) scores on days 1, 3, and 7 were notably lower in the non-DIC group. Correlation analysis revealed positive associations between PT, APTT, TAT, tPAIC, PIC, sTM levels, and SOFA scores, as well as negative associations with Fib and SOFA scores. Survival curves showed substantially lower mortality rates in the non-DIC group, highlighting significant survival disparities between groups. Combining all four coagulation indicators (TAT+ tPAIC + PIC + sTM) showed promising diagnostic value in evaluating disease severity, early DIC diagnosis, and sepsis prognosis.


Subject(s)
Biomarkers , Blood Coagulation , Disseminated Intravascular Coagulation , Sepsis , Humans , Sepsis/diagnosis , Sepsis/mortality , Sepsis/blood , Disseminated Intravascular Coagulation/diagnosis , Disseminated Intravascular Coagulation/blood , Disseminated Intravascular Coagulation/mortality , Disseminated Intravascular Coagulation/etiology , Biomarkers/blood , Prognosis , Female , Male , Middle Aged , Aged , Organ Dysfunction Scores , Adult , Blood Coagulation Tests
4.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 36(7): 768-773, 2024 Jul.
Article in Chinese | MEDLINE | ID: mdl-39223895

ABSTRACT

Sepsis is a common and severe infectious disease, and its associated coagulation dysfunction can cause disseminated intravascular coagulation (DIC) and organ failure, leading to a significant increase in mortality. Pyroptosis is a form of programmed cell death mediated by caspase-1 in the classical pathway and caspase-4/caspase-5/caspase-11 in the non-classical pathway, along with the effector molecule gasdermin (GSDM) family. Recent studies have shown that pyroptosis plays an important role in the development of coagulation disorders in sepsis. Pyroptosis leads to the formation of cytoplasmic membrane pores, cell swelling and membrane rupture, as well as the release and enhanced activity of procoagulant contents, strongly promoting the development of systemic coagulation activation and DIC in sepsis. Therefore, exploring the role and molecular mechanisms of pyroptosis in sepsis-related coagulation disorders is of great significance for the prevention and treatment of sepsis. This article provides a review of the mechanisms involved in pyroptosis and coagulation disorders in sepsis, as well as the role and mechanisms of pyroptosis in sepsis-associated coagulation disorders to provide new ideas for sepsis related research.


Subject(s)
Blood Coagulation Disorders , Disseminated Intravascular Coagulation , Pyroptosis , Sepsis , Sepsis/metabolism , Sepsis/complications , Sepsis/physiopathology , Humans , Blood Coagulation Disorders/etiology , Disseminated Intravascular Coagulation/etiology , Caspases/metabolism , Caspase 1/metabolism , Animals
5.
J Cardiothorac Surg ; 19(1): 523, 2024 Sep 11.
Article in English | MEDLINE | ID: mdl-39261885

ABSTRACT

OBJECTIVES: Recombinant human soluble thrombomodulin (rTM) has recently been used as a promising therapeutic natural anti-coagulant drug for disseminated intravascular coagulation (DIC). Here we investigated the safety and efficacy of rTM after aortic surgery in patients with acute aortic dissection (AAD). METHODS: A total of 316 patients diagnosed with AAD underwent emergent ascending aortic replacement or total arch replacement between 2010 and 2019. We retrospectively analyzed the clinical information of 62 patients with the Japanese Association for Acute Medicine's acute-stage DIC diagnostic criteria (JAAM criteria) with a score of ≥ 4. We assigned 62 patients to two groups, either non-rTM group (n = 29) or rTM group (n = 33). Patient characteristics, surgical procedures, and postoperative outcome data including coagulation function and the JAAM DIC score in both groups were collected. RESULTS: The decrease in the number of platelets was clearly suppressed on days 1-3 in the rTM group. On days 1-4, fibrin degradation product levels were upregulated in the non-rTM group but significantly downregulated in the rTM group. Five operative deaths occurred within 30 days postoperative (two [6.9%] in the non-rTM group vs. three [9.1%] in the rTM group). The JAAM DIC score showed a gradually improving trend from postoperative day 1 in the rTM group. CONCLUSIONS: Postoperative rTM administration for AAD may be a safe and promising novel treatment strategy for improving the JAAM DIC score.


Subject(s)
Aortic Dissection , Disseminated Intravascular Coagulation , Recombinant Proteins , Thrombomodulin , Humans , Thrombomodulin/therapeutic use , Aortic Dissection/surgery , Aortic Dissection/complications , Disseminated Intravascular Coagulation/drug therapy , Disseminated Intravascular Coagulation/etiology , Male , Retrospective Studies , Female , Middle Aged , Recombinant Proteins/therapeutic use , Aged , Treatment Outcome , Acute Disease
6.
Clin Lab ; 70(9)2024 Sep 01.
Article in English | MEDLINE | ID: mdl-39257111

ABSTRACT

BACKGROUND: Group A Streptococcus causes a variety of human infections, including the life-threatening necrotizing fasciitis, which may be ignored by the patient. From hours to days, the infection may progress from an apparently benign skin lesion, usually mistaken for a spider or insect bite, to a highly lethal disease. We present a case of 57-year-old male with skin lesions on swelling left upper limb. METHODS AND RESULTS: The culture of secretion from epidermis and blood were positive for Group A Streptococcus (GAS), type ß hemolytic streptococcus. Intensive anti-infection therapy was applied. However, the necrosis of the limb deteriorated rapidly. He died from multiple organ failure, streptococcal toxic shock syndrome (STSS) and disseminated intravascular coagulation 13 days later. CONCLUSIONS: Necrotizing fasciitis is a rapidly progressive, destructive bacterial infection. Early recognition is the most important factor for survival.


Subject(s)
Fasciitis, Necrotizing , Shock, Septic , Streptococcal Infections , Streptococcus pyogenes , Fasciitis, Necrotizing/diagnosis , Fasciitis, Necrotizing/microbiology , Humans , Male , Middle Aged , Streptococcus pyogenes/isolation & purification , Streptococcal Infections/diagnosis , Streptococcal Infections/microbiology , Streptococcal Infections/drug therapy , Fatal Outcome , Shock, Septic/microbiology , Shock, Septic/diagnosis , Multiple Organ Failure/diagnosis , Multiple Organ Failure/etiology , Multiple Organ Failure/microbiology , Anti-Bacterial Agents/therapeutic use , Disseminated Intravascular Coagulation/diagnosis , Disseminated Intravascular Coagulation/microbiology , Disseminated Intravascular Coagulation/etiology
7.
Clin Lab ; 70(9)2024 Sep 01.
Article in English | MEDLINE | ID: mdl-39257118

ABSTRACT

BACKGROUND: The relationship between the pregnancy modified DIC score, which is applied in obstetric conditions where the risk of disseminated intravascular coagulation is high, and underlying disease, as well as its effect on the prognosis, was investigated. METHODS: Those with a DIC score ≥ 26 from obstetric conditions, such as obstetric bleeding, placental abruption, or preeclampsia/HELLP syndrome, which are at high risk of developing DIC, were included in the study. These patients were compared in terms of laboratory results, maternal morbidity/mortality, and neonatal outcomes, according to the underlying disease. RESULTS: The DIC score was ≥ 26 in 224 of 154,233 deliveries in our center, and the incidence was 0.14%. In the preeclampsia/HELLP syndrome group, the platelet count and prothrombin time were lower, and the fibrinogen level was higher than those of the obstetric hemorrhage and placental abruption groups. In addition, the rates of blood transfusion and hysterectomy were lower in women who developed DIC due to pre-eclampsia/HELLP syndrome than in those with obstetric hemorrhage. CONCLUSIONS: Considering the underlying disease is an important factor in predicting prognosis, when using the new pregnancy modified diagnostic scores for DIC diagnosis.


Subject(s)
Disseminated Intravascular Coagulation , Pregnancy Outcome , Humans , Pregnancy , Female , Disseminated Intravascular Coagulation/diagnosis , Disseminated Intravascular Coagulation/etiology , Disseminated Intravascular Coagulation/epidemiology , Disseminated Intravascular Coagulation/blood , Adult , Pregnancy Outcome/epidemiology , Pre-Eclampsia/diagnosis , Pre-Eclampsia/epidemiology , Abruptio Placentae/epidemiology , Abruptio Placentae/diagnosis , Prognosis , HELLP Syndrome/diagnosis , Retrospective Studies , Pregnancy Complications/epidemiology , Pregnancy Complications/diagnosis , Pregnancy Complications/blood
8.
Postgrad Med ; 136(7): 712-719, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39192490

ABSTRACT

OBJECTIVE: This study aimed to investigate the dynamic changes in the platelets of patients with severe heatstroke and the impact of these changes on the occurrence of disseminated intravascular coagulation (DIC) and prognosis in them. METHODS: This retrospective cohort study conducted at two tertiary hospitals recruited 264 patients with severe heatstroke. Logistic regression was used to analyze the association between platelet counts and DIC. The receiver operating characteristic (ROC) curve was used to evaluate the predictive performance of platelets count for DIC occurrence. We used mediation effect to analysis the role of DIC as a mediating variable to mediate the relationship between platelet count decrease after 24 hours and death. RESULTS: There were 214 patients with lower platelet counts compared to admission (107 × 109/L[69,168] vs.171 × 109/L[126,215], p < 0.001). The DIC patients had lower platelet counts than the non-DIC patients when measured in the emergency department and after 24 hours. The platelet count decrease after 24 hours was a risk factor for DIC (odds ratio [OR] = 2.710, 95% confidence interval [CI] = 1.069-6.869). The results of the ROC curve revealed that the predictive performance of the platelet count after 24 hours (area under the curve [AUC] = 0.8685, 95% CI = 0.8173-0.9197) was significantly better than that of the platelet count measured in the emergency department (AUC = 0.7080, 95% CI = 0.6345-0.7815). Mediation analyses showed that PLT decrease after 24 hours did not directly lead to death, but can indirectly cause death by inducing the development of DIC. CONCLUSIONS: Decreased platelet count is an independent risk factor for DIC in patients with severe heatstroke. Although the platelet counts measured in the emergency department and after 24 hours show a good predictive performance for DIC occurrence, the prediction performance of the latter is better.


Subject(s)
Disseminated Intravascular Coagulation , Heat Stroke , ROC Curve , Humans , Disseminated Intravascular Coagulation/blood , Disseminated Intravascular Coagulation/etiology , Disseminated Intravascular Coagulation/diagnosis , Male , Female , Heat Stroke/blood , Heat Stroke/complications , Platelet Count , Retrospective Studies , Prognosis , Middle Aged , Blood Platelets , Adult , Risk Factors , Aged , Severity of Illness Index
9.
Clin Appl Thromb Hemost ; 30: 10760296241271358, 2024.
Article in English | MEDLINE | ID: mdl-39109998

ABSTRACT

Disseminated intravascular coagulation (DIC) poses a high mortality risk, yet its exact impact remains contentious. This study investigates DIC's association with mortality in individuals with sepsis, emphasizing multiple organ function. Using data from the Peking University People's Hospital Investigation on Sepsis-Induced Coagulopathy database, we categorized patients into DIC and non-DIC groups based on DIC scores within 24 h of ICU admission (< 5 cutoff). ICU mortality was the main outcome. Initial data comparison preceded logistic regression analysis of mortality factors post-propensity score matching (PSM). Employing mediation analysis estimated direct and indirect associations. Of 549 participants, 131 were in the DIC group, with the remaining 418 in the non-DIC group. Following baseline characteristic presentation, PSM was conducted, revealing significantly higher nonplatelet sequential organ failure assessment (nonplt-SOFA) scores (6.3 ± 2.7 vs 5.0 ± 2.5, P < 0.001) and in-hospital mortality rates (47.3% vs 29.5%, P = 0.003) in the DIC group. A significant correlation between DIC and in-hospital mortality persisted (OR 2.15, 95% CI 1.29-3.59, P = 0.003), with nonplt-SOFA scores (OR 1.16, 95% CI 1.05-1.28, P = 0.004) and hemorrhage (OR 2.33, 95% CI 1.08-5.03, P = 0.032) as predictors. The overall effect size was 0.1786 (95% CI 0.0542-0.2886), comprising a direct effect size of 0.1423 (95% CI 0.0153-0.2551) and an indirect effect size of 0.0363 (95% CI 0.0034-0.0739), with approximately 20.3% of effects mediated. These findings underscore DIC's association with increased mortality risk in patients with sepsis, urging anticoagulation focus over bleeding management, with organ dysfunction assessment recommended for anticoagulant treatment efficacy.


Subject(s)
Disseminated Intravascular Coagulation , Multiple Organ Failure , Sepsis , Humans , Disseminated Intravascular Coagulation/etiology , Disseminated Intravascular Coagulation/mortality , Sepsis/complications , Sepsis/mortality , Multiple Organ Failure/etiology , Multiple Organ Failure/mortality , Male , Female , Middle Aged , Prognosis , Aged , Hospital Mortality
10.
Toxins (Basel) ; 16(8)2024 Aug 20.
Article in English | MEDLINE | ID: mdl-39195778

ABSTRACT

The association between sepsis and thrombotic complications is still not well known. Different mechanisms have been shown to be involved in the sepsis-induced prothrombotic state, but clinical scenarios may differ. In this review, we have summarized the role that bacterial products such as porins and toxins can have in the induction of the prothrombotic state during sepsis and the interaction that they can have with each other. Furthermore, the above-mentioned mechanisms might be involved in the pattern of the clinical presentation of thrombotic events during bacterial sepsis, which would secondarily explain the association between sepsis and venous thromboembolism, the association between sepsis and disseminated intravascular coagulation, and the association between sepsis and microangiopathic venous thromboembolism.


Subject(s)
Sepsis , Thrombosis , Humans , Sepsis/microbiology , Sepsis/complications , Sepsis/physiopathology , Thrombosis/physiopathology , Thrombosis/etiology , Animals , Blood Coagulation , Disseminated Intravascular Coagulation/physiopathology , Disseminated Intravascular Coagulation/etiology , Disseminated Intravascular Coagulation/microbiology , Bacterial Toxins/toxicity , Venous Thromboembolism/etiology , Venous Thromboembolism/physiopathology
11.
Clin Appl Thromb Hemost ; 30: 10760296241271334, 2024.
Article in English | MEDLINE | ID: mdl-39196070

ABSTRACT

A new scoring system termed sepsis-induced coagulopathy (SIC) has been proposed to diagnose early sepsis-induced disseminated intravascular coagulation (DIC). This study performed DIC-related analyses in patients with confirmed SIC. Data from the intensive care unit (ICU) departments of the three hospitals between 2020 and 2022 were retrospectively analyzed. Finally, 125 patients with confirmed SIC were enrolled in the study. The diagnostic value of three widely used DIC criteria was assessed in patients with newly diagnosed SIC. In addition, the diagnostic and prognostic value of antithrombin (AT) was analyzed in patients with SIC. The Japanese Association for Acute Medicine DIC criteria (JAAM) exhibited the highest DIC diagnostic rate, while the mortality risk of SIC patients demonstrated a proportional increase with higher International Society on Thrombosis and Haemostasis (ISTH) and Chinese DIC scoring system (CDSS) scores. Low AT activity (<70%) in septic patients upon SIC diagnosis predicted a very high 28-day mortality rate, almost twice as high as in the normal AT activity (≥70%) group. A decreasing tendency in AT activity after clinical interventions was correlated with increased mortality. The area under the ROC curve (AU-ROC) of AT in DIC diagnosis was statistically significant when CDSS and ISTH were used as diagnostic criteria, but not JAAM. Each of the three DIC diagnostic criteria showed diagnostic and prognostic advantages for SIC. AT could be an independent prognostic indicator for SIC but demonstrated a relatively limited DIC diagnostic value. Adding AT to the SIC scoring system may increase its prognostic power.


Subject(s)
Antithrombins , Disseminated Intravascular Coagulation , Sepsis , Humans , Disseminated Intravascular Coagulation/blood , Disseminated Intravascular Coagulation/diagnosis , Disseminated Intravascular Coagulation/etiology , Disseminated Intravascular Coagulation/mortality , Sepsis/blood , Sepsis/complications , Sepsis/mortality , Sepsis/diagnosis , Male , Female , Prognosis , Aged , Middle Aged , Retrospective Studies
12.
Arch. argent. pediatr ; 122(4): e202310137, ago. 2024. ilus
Article in English, Spanish | LILACS, BINACIS | ID: biblio-1562880

ABSTRACT

La púrpura fulminante adquirida postinfecciosa es una entidad aguda y grave, poco frecuente, caracterizada por necrosis cutánea asociada a coagulopatía intravascular diseminada (CID), en ausencia de infección activa o alteraciones previas de la coagulación. Afecta fundamentalmente a la población pediátrica y, en el 90 % de los casos, está precedida por un proceso infeccioso. El mecanismo fisiopatológico es un déficit transitorio de proteína S mediado por autoanticuerpos que favorece un estado de hipercoagulabilidad. Se presenta el caso de un varón de 8 años previamente sano, con lesiones cutáneas purpúricas características de púrpura fulminante asociada a CID en ausencia de sepsis. Se constató deficiencia plasmática transitoria de proteína S. Requirió tratamiento sustitutivo con plasma fresco congelado y anticoagulación; la evolución fue favorable. La actividad de la proteína S permaneció disminuida durante 2 meses.


Acquired postinfectious purpura fulminans is a rare, acute, and severe disease characterized by skin necrosis associated with disseminated intravascular coagulation (DIC) in the absence of active infection or previous coagulation disorders. It mainly affects the pediatric population and, in 90% of cases, it is preceded by an infectious process. The pathophysiological mechanism is a transient autoantibodymediated protein S deficiency that favors a hypercoagulable state. Here we describe the case of a previously healthy 8-year-old boy with purpuric skin lesions typical of purpura fulminans associated with DIC in the absence of sepsis. A transient plasma protein S deficiency was confirmed. He required replacement therapy with fresh frozen plasma and anticoagulation; he had a favorable course. Protein S activity remained decreased for 2 months.


Subject(s)
Humans , Male , Child , Purpura Fulminans/diagnosis , Purpura Fulminans/etiology , Protein S Deficiency/complications , Protein S Deficiency/diagnosis , Disseminated Intravascular Coagulation/diagnosis , Disseminated Intravascular Coagulation/etiology
13.
Rinsho Ketsueki ; 65(6): 498-501, 2024.
Article in Japanese | MEDLINE | ID: mdl-38960647

ABSTRACT

A 43-year-old man with pancytopenia was diagnosed with acute promyelocytic leukemia (APL). On the first day of induction therapy with all-trans retinoic acid (ATRA) alone, he presented with high fever and was found to have coronavirus disease 2019 (COVID-19) infection by SARS-CoV2 antigen test. While it is generally recommended to delay treatment for APL patients with COVID-19 unless urgent APL treatment is required, this patient needed to continue treatment due to APL-induced disseminated intravascular coagulation (DIC). Considering the challenge of distinguishing between differentiation syndrome (DS) and COVID-19 exacerbation, the ATRA dosage was reduced to 50%. The patient was able to continue treatment without development of DS or exacerbation of DIC, leading to his recovery from COVID-19 and remission of APL.


Subject(s)
COVID-19 , Leukemia, Promyelocytic, Acute , Remission Induction , Tretinoin , Humans , Leukemia, Promyelocytic, Acute/drug therapy , Leukemia, Promyelocytic, Acute/complications , Tretinoin/administration & dosage , Tretinoin/therapeutic use , Male , Adult , COVID-19/complications , Treatment Outcome , Disseminated Intravascular Coagulation/drug therapy , Disseminated Intravascular Coagulation/etiology
14.
J Assoc Physicians India ; 72(4): 94-96, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38881089

ABSTRACT

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.


Subject(s)
Disseminated Intravascular Coagulation , Pancytopenia , Humans , Female , Pancytopenia/diagnosis , Pancytopenia/etiology , Disseminated Intravascular Coagulation/diagnosis , Disseminated Intravascular Coagulation/etiology , Young Adult , Autoimmunity
15.
J Clin Rheumatol ; 30(5): e125-e128, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38831495

ABSTRACT

INTRODUCTION: Adult-onset Still disease (AOSD) is a rare inflammatory condition with a monophasic, intermittent, or chronic clinical course, and a subset may experience life-threatening complications such as hemophagocytic lymphohistiocytosis (HLH). This study aims to characterize concurrent AOSD and HLH and identify variables independently associated with in-hospital death. METHODS: We performed a medical records review of AOSD with and without HLH from the 2016-2019 National Inpatient Sample database. We performed a multivariable logistic regression analysis for in-hospital death. Results were reported as adjusted odds ratios (OR adj ). RESULTS: There were 5495 hospitalizations with AOSD, of which 340 (6.2%) had HLH. Thirty (9.0%) of the combined AOSD and HLH group died in the hospital compared with 75 (1.5%) of those without HLH. Multivariable analysis in AOSD inpatients showed that disseminated intravascular coagulation (OR adj 6.13), hepatic failure (OR adj 7.16), infection (OR adj 3.72), respiratory failure (OR adj 6.89), and thrombotic microangiopathy (OR adj 14.05) were associated with higher odds of death. However, HLH itself was not an independent predictor of mortality in AOSD population. CONCLUSIONS: HLH occurred in a small minority of inpatients with AOSD. HLH itself was not an independent risk factor for in-hospital death. Disseminated intravascular coagulation, hepatic failure, infection, respiratory failure, and thrombotic microangiopathy were associated with higher odds of in-hospital death in AOSD. Better awareness of these life-threatening complications may improve hospital outcomes.


Subject(s)
Hospital Mortality , Lymphohistiocytosis, Hemophagocytic , Still's Disease, Adult-Onset , Humans , Lymphohistiocytosis, Hemophagocytic/diagnosis , Lymphohistiocytosis, Hemophagocytic/epidemiology , Lymphohistiocytosis, Hemophagocytic/mortality , Still's Disease, Adult-Onset/diagnosis , Still's Disease, Adult-Onset/epidemiology , Still's Disease, Adult-Onset/complications , Male , Female , Middle Aged , Adult , United States/epidemiology , Disseminated Intravascular Coagulation/epidemiology , Disseminated Intravascular Coagulation/diagnosis , Disseminated Intravascular Coagulation/etiology , Liver Failure/etiology , Liver Failure/epidemiology , Liver Failure/diagnosis , Risk Factors , Aged , Thrombotic Microangiopathies/epidemiology , Thrombotic Microangiopathies/diagnosis , Retrospective Studies , Respiratory Insufficiency/etiology , Respiratory Insufficiency/epidemiology , Hospitalization/statistics & numerical data , Databases, Factual
16.
Biochem Biophys Res Commun ; 724: 150140, 2024 09 10.
Article in English | MEDLINE | ID: mdl-38852506

ABSTRACT

Sepsis is a severe inflammatory disease characterized by cytokine storm, often accompanied by disseminated intravascular coagulation (DIC). PANoptosis is a novel form of cell death triggered by cytokine storms, characterized by a cascade reaction of pyroptosis, apoptosis, and necroptosis. It exists in septic platelets and is closely associated with the onset and progression of DIC. However, there remains an unmet need for drugs targeting PANoptosis. The anti-PANoptosis effect of myricetin was predicted using network pharmacology and confirmed through molecular docking. In vitro platelet activation models demonstrated that myricetin significantly attenuated platelet particle release, integrin activation, adhesion, spreading, clot retraction, and aggregation. Moreover, in a sepsis model, myricetin reduced inflammatory infiltration in lung tissue and platelet activation while improving DIC. Additionally, whole blood sequencing samples from sepsis patients and healthy individuals were analyzed to elucidate the up-regulation of the PANoptosis targets. Our findings demonstrate the inhibitory effect of myricetin on septic platelet PANoptosis, indicating its potential as a novel anti-cellular PANoptosis candidate and therapeutic agent for septic DIC. Furthermore, our study establishes a foundation for utilizing network pharmacology in the discovery of new drugs to treat various diseases.


Subject(s)
Blood Platelets , Disseminated Intravascular Coagulation , Flavonoids , Sepsis , Flavonoids/pharmacology , Flavonoids/therapeutic use , Sepsis/drug therapy , Sepsis/blood , Humans , Blood Platelets/drug effects , Blood Platelets/metabolism , Disseminated Intravascular Coagulation/drug therapy , Disseminated Intravascular Coagulation/etiology , Disseminated Intravascular Coagulation/pathology , Disseminated Intravascular Coagulation/blood , Animals , Male , Molecular Docking Simulation , Platelet Activation/drug effects , Mice, Inbred C57BL , Mice , Pyroptosis/drug effects
18.
Medicine (Baltimore) ; 103(20): e38176, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38758915

ABSTRACT

RATIONALE: Amniotic fluid embolism (AFE) is a fatal obstetric condition that often rapidly leads to severe respiratory and circulatory failure. It is complicated by obstetric disseminated intravascular coagulation (DIC) with bleeding tendency; therefore, the introduction of venoarterial extracorporeal membrane oxygenation (VA-ECMO) is challenging. We report the case of a patient with AFE requiring massive blood transfusion, rescued using VA-ECMO without initial anticoagulation. PATIENTS CONCERNS: A 39-year-old pregnant patient was admitted with a complaint of abdominal pain. An emergency cesarean section was performed because a sudden decrease in fetal heart rate was detected in addition to DIC with hyperfibrinolysis. Intra- and post-operatively, the patient had a bleeding tendency and required massive blood transfusions. After surgery, the patient developed lethal respiratory and circulatory failure, and VA-ECMO was introduced. DIAGNOSIS: Based on the course of the illness and imaging findings, the patient was diagnosed with AFE. INTERVENTIONS: By controlling the bleeding tendency with a massive transfusion and tranexamic acid administration, using an antithrombotic ECMO circuit, and delaying the initiation of anticoagulation and anti-DIC medication until the bleeding tendency settled, the patient was managed safely on ECMO without complications. OUTCOMES: By day 5, both respiration and circulation were stable, and the patient was weaned off VA-ECMO. Mechanical ventilation was discontinued on day 6. Finally, she was discharged home without sequelae. LESSONS: VA-ECMO may be effective to save the lives of patients who have AFE with lethal circulatory and respiratory failure. For safe management without bleeding complications, it is important to start VA-ECMO without initial anticoagulants and to administer anticoagulants and anti-DIC drugs after the bleeding tendency has resolved.


Subject(s)
Embolism, Amniotic Fluid , Extracorporeal Membrane Oxygenation , Humans , Female , Embolism, Amniotic Fluid/therapy , Embolism, Amniotic Fluid/diagnosis , Extracorporeal Membrane Oxygenation/methods , Adult , Pregnancy , Cesarean Section/adverse effects , Blood Transfusion/methods , Tranexamic Acid/therapeutic use , Tranexamic Acid/administration & dosage , Disseminated Intravascular Coagulation/etiology , Disseminated Intravascular Coagulation/therapy , Anticoagulants/therapeutic use , Anticoagulants/adverse effects , Anticoagulants/administration & dosage
19.
J Innate Immun ; 16(1): 337-353, 2024.
Article in English | MEDLINE | ID: mdl-38815564

ABSTRACT

BACKGROUND: Sepsis-associated coagulopathy specifically refers to widespread systemic coagulation activation accompanied by a high risk of hemorrhage and organ damage, which in severe cases manifests as disseminated intravascular coagulation (DIC), or even develops into multiple organ dysfunction syndrome (MODS). The complement system and the coagulation system as the main columns of innate immunity and hemostasis, respectively, undergo substantial activation after sepsis. SUMMARY: Dysfunction of the complement, coagulation/fibrinolytic cascades caused by sepsis leads to "thromboinflammation," which ultimately amplifies the systemic inflammatory response and accelerates the development of MODS. Recent studies have revealed that massive activation of the complement system exacerbates sepsis-induced coagulation and even results in DIC, which suggests that inhibition of complement activation may have therapeutic potential in the treatment of septic coagulopathy. KEY MESSAGES: Sepsis-associated thrombosis involves the upregulation or activation of procoagulant factors, down-regulation or inactivation of anticoagulant factors, and impairment of the fibrinolytic mechanism. This review aims to summarize the latest literature and analyze the underlying molecular mechanisms of the activation of the complement system on the abnormal coagulation cascades in sepsis.


Subject(s)
Complement Activation , Sepsis , Humans , Sepsis/immunology , Complement Activation/immunology , Animals , Blood Coagulation , Disseminated Intravascular Coagulation/immunology , Disseminated Intravascular Coagulation/etiology , Immunity, Innate , Complement System Proteins/immunology , Complement System Proteins/metabolism , Multiple Organ Failure/immunology , Multiple Organ Failure/etiology , Fibrinolysis , Blood Coagulation Disorders/immunology , Blood Coagulation Disorders/etiology , Thrombosis/immunology , Thrombosis/etiology
20.
Intensive Care Med ; 50(6): 849-860, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38748265

ABSTRACT

Hematological malignancies may require rapid-onset treatment because of their short doubling time, notably observed in acute leukemias and specific high-grade lymphomas. Furthermore, in targeted onco-hematological scenarios, chemotherapy is deemed necessary as an emergency measure when facing short-term, life-threatening complications associated with highly chemosensitive hematological malignancies. The risks inherent in the disease itself, or in the initiation of treatment, may then require admission to the intensive care unit (ICU) to optimize monitoring and initial management protocols. Hyperleukocytosis and leukostasis in acute leukemias, tumor lysis syndrome, and disseminated intravascular coagulation are the most frequent onco-hematological complications requiring the implementation of emergency chemotherapy in the ICU. Chemotherapy must also be started urgently in secondary hemophagocytic lymphohistiocytosis. Tumor-induced microangiopathic hemolytic anemia and plasma hyperviscosity due to malignant monoclonal gammopathy represent infrequent yet substantial indications for emergency chemotherapy. In all cases, the administration of emergency chemotherapy in the ICU requires close collaboration between intensivists and hematology specialists. In this review, we provide valuable insights that aid in the identification and treatment of patients requiring emergency chemotherapy in the ICU, offering diagnostic tools and guidance for their overall initial management.


Subject(s)
Hematologic Neoplasms , Intensive Care Units , Humans , Intensive Care Units/organization & administration , Hematologic Neoplasms/drug therapy , Hematologic Neoplasms/complications , Tumor Lysis Syndrome/etiology , Tumor Lysis Syndrome/drug therapy , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/adverse effects , Disseminated Intravascular Coagulation/drug therapy , Disseminated Intravascular Coagulation/etiology , Lymphohistiocytosis, Hemophagocytic/drug therapy , Lymphohistiocytosis, Hemophagocytic/complications
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