[Clinical guidelines for disseminated intravascular coagulation].

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.

Resuscitative endovascular balloon occlusion of the aorta: A novel approach for treating amniotic fluid embolism with disseminated intravascular coagulopathy-A report of two cases.

We present two critical cases of life-threatening postpartum hemorrhage (PPH) due to amniotic fluid embolism (AFE) complicated by disseminated intravascular coagulopathy (DIC). These cases are the first to show the effectiveness of resuscitative endovascular balloon occlusion of the aorta (REBOA) for patient survival. In Case 1, the patient, experiencing critical conditions with severe PPH and DIC despite conventional treatments, including rapid blood transfusion and fibrinogen concentrate, was air-transferred to our hospital, where REBOA was promptly employed before hysterectomy was completed. Case 2 involved an ambulance-transferred patient with massive PPH and DIC despite conventional treatments. Prehospital REBOA was performed to prevent cardiac arrest during transfer, and hysterectomy was performed in the hospital. Given the rapid deterioration associated with AFE, REBOA can serve as a bridge until complete hemostasis to maintain vital signs and control bleeding in patients unresponsive to standard therapies before hemostatic interventions or during transfer.

Multidisciplinary approach to obstetric disseminated intravascular coagulopathy management in low-income country: A survey.

OBJECTIVE: To assess the uptake of a multidisciplinary team approach in obstetric disseminated intravascular coagulopathy (DIC) management in a low- to middle-income country. METHODS: A cross-sectional observational study, in which a semi-structured and pre-tested questionnaire was used to collect data on the uptake by Nigerian obstetricians of the multidisciplinary team approach to obstetric DIC management. RESULTS: A total of 171 obstetricians responded, 82 (48.0%) were consultants and 89 (52.0%) were specialist registrars. Most (165; 96.5%) practiced in tertiary healthcare facilities and the multidisciplinary team approach was the most preferred (162; 94.7%) management approach. In all, 142 (83.0%) supported the invitation of hematologists always in the management whereas 115 (67.3%) participants recommended that involvement of specialists in the treatment should be when clinical presentation was suggestive of DIC. No significant association existed between years of obstetric practice and adoption of a multidisciplinary team-based approach (χ2 = 9.590; P = 0.252). CONCLUSION: A multidisciplinary approach is widely adopted in the management of obstetric DIC, with hematologists being a key member of the team.

Amniotic fluid embolism rescued using venoarterial extracorporeal membrane oxygenation without initial anticoagulation: A case report and literature review.

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.

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.

To bite the hand that feeds you: A case of thrombotic microangiopathy due to Tiger snake bite.

This report details the case of a 51-year-old man with a Tiger snake bite who developed systemic envenomation, coagulopathy and thrombotic microangiopathy (TMA) requiring renal replacement therapy. He received plasma exchange as additional therapy while awaiting confirmation of the cause of the TMA. We discuss clinical decision making in detection of systemic envenomation and management of the rare complication of TMA, as well as current Australian guidelines around antivenom administration. This is the fourth known documented case of TMA from a Tiger snake bite in Australia.

Disseminated Intravascular Coagulation in Acute Promyelocytic Leukemia Patients: A Retrospective Analysis of Outcomes and Healthcare Burden in US Hospitals

Objective: Acute promyelocytic leukemia (APL) is associated with an elevated risk of developing disseminated intravascular coagulation (DIC). The purpose of this study was to assess the outcomes of hospitalizations related to DIC in APL and their impact on healthcare. Materials and Methods: This study entailed a cross-sectional and retrospective analysis of the US National Inpatient Sample database. We identified adults with APL and categorized them into groups of patients with and without DIC. Our focus areas included in-hospital mortality, length of stay, charges, and complications associated with DIC. Unadjusted odds ratios/coefficients were computed in univariate analysis, followed by adjusted odds ratios (aOR)/coefficients from multivariate analysis that accounted for confounding factors. Results: Our analysis revealed that APL patients with DIC had a substantially higher aOR for mortality (aOR: 6.68, 95% confidence interval [CI]: 4.76-9.37, p<0.001) and a prolonged length of stay (coefficient: 10.28 days, 95% CI: 8.48-12.09, p<0.001) accompanied by notably elevated total hospital charges (coefficient: $215,512 [95% CI: 177,368-253,656], p<0.001), thereby emphasizing the reality of extended medical care and economic burden. The presence of DIC was associated with increased odds of sepsis, vasopressor support, pneumonia, acute respiratory failure, intubation/mechanical ventilation, and acute kidney injury, reflecting heightened vulnerability to these complications. Patients with DIC demonstrated significantly higher odds ratios for major bleeding, intracranial hemorrhage, gastrointestinal bleeding, red blood cell transfusion, platelet transfusion, fresh frozen plasma transfusion, and cryoprecipitate transfusion, highlighting the pronounced hematological risks posed by DIC. Conclusion: This study has revealed the significant associations between DIC in APL and various outcomes, underscoring the clinical and economic implications of these conditions. The hematological risks further increase patients' vulnerability to bleeding events and the need for transfusions.

Cancer-associated thrombosis and bleeding.

Development of thrombosis is closely associated with poor prognosis in cancer patients. Cancer patients often fulfill Virchow's triad of hyper-coagulable state, vascular endothelial injury, and venous stasis. Cancer cells aberrantly express a variety of procoagulant factors, including tissue factor and podoplanin. Chemotherapeutic agents and radiation cause vascular endothelial injury, and reduced daily activity and bed rest for chemotherapy lead to venous stasis. Due to these factors, cancer patients are at high risk of developing thrombosis. Cancer patients are also at high risk of bleeding when they have disseminated intravascular coagulation and/or chemotherapy-induced thrombocytopenia as complications. International societies, such as the American Society of Clinical Oncology and the International Initiative on Thrombosis and Cancer (ITAC), have published clinical guidelines to help physicians better manage cancer-associated thrombosis (CAT). These guidelines recommend use of low molecular weight heparin or direct oral anticoagulants for the prevention of CAT, but unfortunately use of these drugs is not approved in Japan. This gap between Japan and other countries needs to be closed.

Treatments and outcomes of neonatal disseminated intravascular coagulation with and without neonatal asphyxia: A retrospective study using nationwide data in Japan.

BACKGROUND: Although neonatal disseminated intravascular coagulation (DIC) is associated with high mortality and severe complications, few studies have reported its clinical course. We aimed to describe the characteristics, treatments, and outcomes of neonatal DIC by using a national inpatient database. METHODS: Using the Japanese Diagnosis Procedure Combination database, we identified 5533 patients with neonatal DIC who were admitted to neonatal intensive care units between July 2010 and March 2020. We categorized the patients into those with asphyxia (n = 2911) and those without asphyxia (n = 2622). We investigated the patient characteristics, treatments, and outcomes. We further categorized neonates with asphyxia according to its severity. RESULTS: The gestational age of neonates with asphyxia was significantly lower than that of neonates without asphyxia (P < 0.001). Antithrombin was most commonly used for DIC (40%). Neonates with asphyxia were more likely to receive antithrombin (43% vs. 38%; P < 0.001), recombinant human soluble thrombomodulin (28% vs. 20%; P < 0.001), and fresh frozen plasma transfusion (68% vs. 51%; P < 0.001) than those without asphyxia. Neonates with asphyxia had higher in-hospital mortality (17% vs. 10%; P < 0.001), severe bleeding (11% vs. 6.8%; P < 0.001), and hospitalization costs than those without asphyxia. Additionally, neonates with severe asphyxia were more likely to receive several DIC therapies (such as recombinant human soluble thrombomodulin [30% vs. 24%]) and had higher in-hospital mortality (19% vs. 11%) and hospitalization costs than those with mild asphyxia. CONCLUSIONS: In this large retrospective study of neonatal DIC, patients with asphyxia received several treatments and demonstrated unfavorable outcomes when compared to those without asphyxia.

Consumptive coagulopathy in the ICU.

A consumptive coagulopathy describes a situation where there is a loss of hemostatic factors, which leads to an increased risk of bleeding. Some recent studies have used the term interchangeably with disseminated intravascular coagulation (DIC), but we have reverted to the older definition, which covers a broader range of issues where there is loss of hemostatic factors due to multiple causes, which includes systemic activation of coagulation as seen in DIC. Therefore, the term consumptive coagulopathy covers conditions from the hemostatic effects of major hemorrhage to the use of extracorporeal circuits to true DIC. We review the current understanding of the pathophysiology, diagnosis, and management of common consumptive coagulopathy in critical care patients, focusing on recent advances and controversies. Particular emphasis is given to DIC because it is a common and often life-threatening condition in critical care patients and is characterized by the simultaneous occurrence of widespread microvascular thrombosis and bleeding. Second, we focus on the effect of modern medical technology, such as extracorporeal membrane oxygenation, on hemostasis.

Varicella-associated disseminated intravascular coagulation secondary to Henoch-Schönlein purpura with renal and gastrointestinal system involvement in a child: A case report.

RATIONALE: Immunocompromised patients who developed varicella-zoster virus (VZV)-associated disseminated intravascular coagulation (DIC) previously included recipients of bone marrow, hematopoietic stem cell, or organ transplantations, patients with primary nephropathy receiving corticosteroid therapy, cancer patients receiving chemotherapy, and patients with human immune deficiency virus infection. The case reported here is novel because, to our knowledge, there has been no report of VZV-associated DIC after the onset of Henoch-Schönlein purpura (HSP). PURPOSE: To report the successful treatment of a novel pediatric case with VZV-associated DIC secondary to HSP. DIAGNOSIS AND INTERVENTION: An 8-year-old girl developed VZV-associated DIC 24 days after diagnosis of HSP with renal and gastrointestinal involvement. She was treated with methylprednisolone at a local hospital for 19 days, and suddenly developed fever starting from day 4 in our hospital. Her fever persisted with vesicular skin rashes on her back, strong abdominal and lower back pain, epistaxis, hematochezia, erosion and bleeding on her lips, in her mouth and at puncture sites on day 5. She was diagnosed with DIC with the laboratory evidence of dramatically decreased platelet count and fibrinogen, prolonged activated partial thromboplastin time and prothrombin time, and increased fibrin degradation products including d-dimers. She also developed multiple organ dysfunction syndrome. On day 7, the patient VZV nucleic acid result turned out to be positive. Methylprednisolone treatment was discontinued, and she was given a multi-modality therapy including medications of acyclovir and antibiotics, intravenous gamma-immunoglobulin, various blood product transfusions, continuous renal replacement therapy, plasma exchange, and administration of liver and gastrointestinal system protection drugs. OUTCOMES: The patient multi-organ function damage gradually recovered. After VZV control, the patient was treated with oral methylprednisolone again for HSP with nephritis. Urine analysis was normal 1 year later, and oral hormone was discontinued. No complication or relapse occurred during 2 years of follow-up. SIGNIFICANCE: This case report, for the first time, adds HSP treated with corticosteroids to the spectrum of clinical conditions that progressed to life-threatening secondary varicella-associated DIC. Early identification of varicella infection and DIC, combined with timely antiviral, immunoglobulin transfusion, plasma exchange, and other combined therapies are essential for saving patients' lives.

A 16-year-old man with leptospirosis and atypical disseminated intravascular coagulation: a case report.

BACKGROUND: Leptospirosis is known for its pulmonary form characterized by intra-alveolar hemorrhage, exhibiting a high mortality rate. Management by venous-venous extracorporeal membrane oxygenation has been reported in a small number of cases. CASE PRESENTATION: We report herein the case of a 16-year-old Caucasian male who was admitted with rapidly deteriorating respiratory and digestive complaints. He developed severe acute respiratory distress syndrome secondary to disseminated intravascular coagulation and intra-alveolar hemorrhage, requiring initiation of venous-venous extracorporeal membrane oxygenation. Initial infectious and immunological assessments were inconclusive, but repeat serology on the tenth day of admission confirmed a diagnosis of leptospirosis. The patient received multiple transfusions, and upon favorable response to treatment with corticosteroids and antibiotics, he was successfully weaned off venous-venous extracorporeal membrane oxygenation, which was discontinued after 12 days. CONCLUSION: Leptospirosis is a rare cause of severe acute respiratory failure following pulmonary hemorrhage. It is typically diagnosed by serology, with detectable IgM antibodies 5-7 days after the onset of symptoms. We report that early support with respiratory extracorporeal membrane oxygenation favors timely clearance of endobronchial clotting, parenchymal recovery, and prevention of ventilator-induced lung injury. Major hypofibrinogenemia, which did not seem to worsen during extracorporeal membrane oxygenation application, was managed by repeated transfusions. Further studies investigating the pathogenesis of this coagulopathy are required to further optimize the management of this rare and severe complication.

The impact of vascular endothelial glycocalyx on the pathogenesis and treatment of disseminated intravascular coagulation.

Disseminated intravascular coagulation (DIC) is a complex disorder characterized by widespread activation of blood clotting mechanisms throughout the body. Understanding the role of vascular endothelial glycocalyx in the pathogenesis and treatment of DIC is crucial for advancing our knowledge in this field. The vascular endothelial glycocalyx is a gel-like layer that coats the inner surface of blood vessels. It plays a significant role in maintaining vascular integrity, regulating fluid balance, and preventing excessive clotting. In the pathogenesis of DIC, the disruption of the vascular endothelial glycocalyx is a key factor. Pathological conditions trigger the activation of enzymes, including heparanase, hyaluronase, and matrix metalloproteinase. This activation leads to glycocalyx degradation, subsequently exposing endothelial cells to procoagulant stimuli. Additionally, the ANGPTs/Tie-2 signaling pathway plays a role in the imbalance between the synthesis and degradation of VEG, exacerbating endothelial dysfunction and DIC. Understanding the mechanisms behind glycocalyx degradation and its impact on DIC can provide valuable insights for the development of targeted therapies. Preservation of the glycocalyx integrity may help prevent the initiation and propagation of DIC. Strategies such as administration of exogenous glycocalyx components, anticoagulant agents, or Tie-2 antibody agents have shown promising results in experimental models. In conclusion, the vascular endothelial glycocalyx plays a crucial role in the pathogenesis and treatment of DIC. Further research in this field is warranted to unravel the complex interactions between the glycocalyx and DIC, ultimately leading to the development of novel therapies.

Successful perioperative management with damage control surgery following cardiac arrest due to massive postpartum hemorrhage: A case report.

INTRODUCTION: Although declining, maternal mortality due to postpartum hemorrhage (PPH) remains significant. Here we report the case of a 31-year-old primipara patient admitted with cardiac arrest due to PPH. CASE PRESENTATION: Labor was induced at gestational week 39, and the infant was delivered rapidly. Cardiac arrest due to PPH occurred during the transfer to our hospital, and the patient underwent cardiopulmonary resuscitation upon arrival to the emergency room. On admission, her hemoglobin level was 0.7 g/dL and she was in hypovolemic shock. Resuscitation and hysterectomy were performed immediately, including damage control surgery and gauze packing, to control the diffuse oozing bleeding due to severe disseminated intravascular coagulation. Relaparotomy for hemostasis was subsequently performed because of a decrease in hemoglobin level and blood pressure, and gauze packing was reinserted with temporary abdominal closure. Two days later, the abdominal wall was closed after confirming the absence of bleeding and the patient recovered well without further intervention. CONCLUSION: A prompt and assertive intensive response through collaborative efforts, utilizing feasible damage control surgery, can elegantly salvage uncontrolled bleeding in PPH patients with disseminated intravascular coagulation.

Mechanisms and management of the coagulopathy of trauma and sepsis: trauma-induced coagulopathy, sepsis-induced coagulopathy, and disseminated intravascular coagulation.

Disseminated intravascular coagulation can occur due to different causes but commonly following sepsis. Trauma-induced coagulopathy (TIC) occurs on hospital arrival in approximately 25% of seriously injured patients who initially presents with impaired hemostasis and a bleeding phenotype that can later progress to a prothrombotic phase. Following traumatic injury, ineffective hemostasis is driven by massive blood loss, tissue damage, and hyperfibrinolysis. This initial impaired hemostasis continues until surgical or other management strategies not only to stop the causes of hemorrhage but also progresses to a prothrombotic and hypofibrinolytic state, also termed fibrinolytic shutdown. Prothrombotic progression is also promoted by inflammatory mediator release, endothelial injury, and platelet dysregulation, which is commonly seen in sepsis with increased mortality. Unlike TIC, the early phase of sepsis is frequently complicated by multiorgan dysfunction described as sepsis-induced coagulopathy (SIC) that lacks a hemorrhagic phase. The phenotypes of SIC and TIC are different, especially in their initial presentations; however, patients who survive TIC may also develop subsequent infections and potentially sepsis and SIC. Although the pathophysiology of SIC and TIC are different, endothelial injury, dysregulated fibrinolysis, and coagulation abnormalities are common. Management includes treatment of the underlying cause, tissue injury vs infection is critical, and supportive therapies, such as hemostatic resuscitation and circulatory support are essential, and adjunct therapies are recommended in guidelines. Based on clinical studies and certain guidelines, additional therapies include tranexamic acid in the limited timing of initial traumatic injury and anticoagulants, such as antithrombin and recombinant thrombomodulin in disseminated intravascular coagulation.

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.

Sepsis-Induced Coagulopathy and Disseminated Intravascular Coagulation: What We Need to Know and How to Manage for Prolonged Casualty Care.

Coagulopathy can occur in trauma, and it can affect septic patients as a host tries to respond to infection. Sometimes, it can lead to disseminated intravascular coagulopathy (DIC) with a high potential for mortality. New research has delineated risk factors that include neutrophil extracellular traps and endothelial glycocalyx shedding. Managing DIC in septic patients focuses on first treating the underlying cause of sepsis. Further, the International Society on Thrombolysis and Haemostasis (ISTH) has DIC diagnostic criteria. "Sepsis-induced coagulopathy" (SIC) is a new category. Therapy of SIC focuses on treating the underlying infection and the ensuing coagulopathy. Most therapeutic approaches to SIC have focused on anticoagulant therapy. This review will discuss SIC and DIC and how they are relevant to prolonged casualty care (PCC).

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.

Disseminated Intravascular Coagulation Post Endovascular Aortic Repair.

BACKGROUND: Disseminated Intravascular Coagulation (DIC) after Endo-Vascular Aneurysm Repair (EVAR) is a highly uncommon clinical entity. With only a few case-reports available, its management strategy still remains enigmatic. OBJECTIVES: The purpose of this study was to retrieve, synthesize, and appraise all existing data for DIC after EVAR. MATERIALS AND METHODS: All published articles regarding DIC post-EVAR were identified from 3 major databases and analyzed. Clinical parameters, predisposing factors, along with mortality and morbidly were assessed. RESULTS: The total number of publications included in the review was 15 describing 17 cases. DIC presented with a broad spectrum of clinical manifestations, while the time of diagnosis varied significantly. Endoleak was the main causative factor, with an incidence reaching 71%. The mortality of DIC after EVAR reached 29%, regardless of the therapeutic approach chosen. DIC was treated effectively in 47% of the patients (8/17), with better outcomes among patients who received conservative therapy or among those who were submitted to endovascular interventions. CONCLUSIONS: DIC after EVAR, although rare, is a potentially lethal clinical condition which requires prompt diagnosis and urgent medical consideration. Treatment of endoleak may help in quick restoration of normal parameters.