Bromadiolone may cause severe acute kidney injury through severe disorder of coagulation: a case report.

BACKGROUND: Bromadiolone is a wide-use long-acting anticoagulant rodenticide known to cause severe coagulation dysfunction. At present, there have been no detailed reports of acute kidney injury (AKI) resulting from bromadiolone poisoning. CASE PRESENTATION: A 27-year-old woman was admitted to the hospital due to severe coagulopathy and severe AKI. Coagulation test revealed a prothrombin time exceeding 120 s and an international normalized ratio (INR) greater than 10. Further examination for coagulation factors showed significantly reduced level of factors II, VII, IX and X, indicating a vitamin K deficiency. The AKI was non-oliguric and characterized by gross dysmorphic hematuria. Following the onset of the disease, the patient's serum creatinine rose from 0.86 to 6.96 mg/dL. Suspecting anticoagulant rodenticide poisoning, plasma bromadiolone was identified at a concentration of 117 ng/mL via gas chromatography/mass spectrometry. All other potential causes of AKI were excluded, except for the presence of a horseshoe kidney. The patient's kidney function fully recovered after the coagulopathy was corrected with high doses of vitamin K and plasma transfusion. At a follow-up 160 days post-discharge, the coagulation function had normalized, and the serum creatinine had returned to 0.51 mg/dL. CONCLUSION: Bromadiolone can induce AKI through a severe and prolonged coagulation disorder. Kidney function can be restored within days following treatment with high-dose vitamin K1.

Complexities in diesel oil inhalation: case study of respiratory injury and coagulation anomalies.

Diesel inhalation poisoning represents a rare yet critical medical condition necessitating prompt medical attention due to its potential to induce severe respiratory distress and coagulation dysfunction. The present case study describes the distinctive clinical presentation of a male patient in his early 40s who experienced acute respiratory distress and manifested coagulation factor VII deficiency subsequent to unintentional inhalation of diesel oil during engine repair. The patient demonstrated symptoms including chest tightness and dyspnea, indicative of chemical aspiration pneumonia, alongside an unforeseen coagulation abnormality. Treatment involved rigorous intervention, comprising endotracheal intubation, mechanical ventilation, and administration of pharmacotherapy, including ambroxol, dihydroxypropylline, and methylprednisolone. Moreover, procedural measures, such as repeated bronchoscopic alveolar lavage, pathogen culture, and targeted antibiotic therapy, were employed to mitigate respiratory complications. The patient's clotting disorder was treated with blood transfusions, and he was discharged with improvement. The present case highlights the imperative nature of immediate medical intervention in instances of diesel inhalation to avert further clinical deterioration and unfavorable outcomes. Additionally, it underscores the necessity for expanded research endeavors aimed at elucidating the indirect repercussions of diesel inhalation on the coagulation cascade, an area that remains relatively underexplored within the medical literature.

Development and internal validation of a model for predicting cefoperazone/sulbactam-associated coagulation disorders in Chinese inpatients.

BACKGROUND AND AIM: The use of cefoperazone/sulbactam (CPZ/SAM) could commonly cause vitamin K-dependent coagulation disorders and even hemorrhage sometimes. However, there is a lack of prediction tools estimating the risk for this. This study aimed at developing and internally validating a model for predicting CPZ/SAM-associated coagulation disorders in Chinese inpatients. METHODS: A case-control study was conducted in 11,092 adult inpatients admitted to a Chinese general hospital between 2020 and 2021 and treated with CPZ/SAM. Patients with CPZ/SAM-associated coagulation disorders were identified through the Adverse Drug Events Active Surveillance and Assessment System-II and subsequent manual evaluation. Controls were selected from eligible patients who didn't develop coagulation disorders after CPZ/SAM therapy, with a 1:1 propensity score matching. The final predictors were obtained by univariable and multivariable logistic regression analyses. Internal validation and calibration for the model were performed using 1000 bootstrap resamplings. RESULTS: 258 patients were identified as CPZ/SAM-associated coagulation disorders in 2184 patients eligible for inclusions and exclusions and the incidence was 11.8%. A final population of 252 cases and 252 controls was included for model development and validation. Malnutrition (OR = 2.41 (1.56-3.77)), history of recent bleeding (OR = 1.95 (1.32-2.90)), treatment duration (OR = 1.10 (1.07-1.14)), combination with carbapenems (OR = 4.43 (1.85-11.88)), and serum creatinine (OR = 1.01 (1.00-1.01)) were identified as final predictors. The model showed good discrimination, calibration, and clinical practicality, with the validated area under the receiver operating characteristic curve being 0.723 (0.683-0.770). CONCLUSIONS: The model with good performance quantifies the risk for CPZ/SAM-associated coagulation disorders, and may support individual assessment and interventions to mitigate the risk after external validation.

A Rare Cause of Coagulopathy in the Emergency Department: Cefoperazone Use.

Cefoperazone (CPZ) is an antibiotic widely used for moderate to severe infections, especially in countries where resources are difficult to access. This case report aimed to draw attention to coagulopathy, a potential side effect of CPZ. This side effect can cause high mortality and morbidity in patients. In the mechanism of CPZ causing coagulopathy, it is reported that effects such as binding to vitamin K, disrupting vitamin K metabolism, and preventing platelet aggregation are responsible. In this presentation, a case who came to the emergency department with the complaint of hematuria caused by coagulopathy after the use of CPZ-containing antibiotics (CPZ + sulbactam) is presented.

Unveiling the Rare Presentation of Acetylsalicylate Overdose: Grand Round.

BACKGROUND: This case report highlights a rare occurrence of aspirin overdose presenting only as severe coagulopathy. CASE PRESENTATION: An 85-year-old woman was admitted to the hospital with multiple lumbar vertebral compression fractures causing severe back pain. The patient had self-medicated with excessive consumption of Bufferin A containing 330 mg of aspirin. On arrival, she showed no typical symptoms of salicylate toxicity, such as nausea, vomiting, hyperventilation, tinnitus, or hearing loss. However, blood work revealed a significant decrease in vitamin K-dependent coagulation factors leading to coagulopathy. The administration of 20-mg menatetrenone (vitamin K) resulted in rapid improvement in coagulation abnormalities. The patient's blood salicylate level was later determined to be 42.7 mg/dL. DISCUSSION: Acute salicylate poisoning is known to cause coagulopathy because of the inhibition of vitamin K-dependent coagulation factors. However, this case is unique because it demonstrates coagulopathy as the sole manifestation of aspirin toxicity without any other symptoms. CONCLUSIONS: This case highlights the importance of considering the possibility of aspirin toxicity in patients with coagulopathy, especially those who are regularly consuming aspirin.

Serum trough concentration threshold and risk factors of cefoperazone-induced coagulopathy in critically ill patients: A retrospective case-control study.

PURPOSE: To analyze the risk factors influencing the development of cefoperazone-induced coagulopathy in critically ill patients and determine the threshold of serum trough concentration. METHODS: A retrospective case-control study was conducted in the intensive care unit patients treated with cefoperazone, and it was approved by the Ethical Committee of Drum Tower Hospital affiliated with the Medical School of Nanjing University (NO.2023-158-01). Patients were divided into the normal group and coagulopathy group based on prothrombin time. The clinical characteristics of the two groups were compared using univariate analysis. The serum concentration threshold and influencing factors of cefoperazone-induced coagulopathy in critically ill patients were analyzed using the receiver operating characteristic curve and multivariate logistic regression analysis. RESULTS: A total of 113 patients were included, and cefoperazone-induced coagulopathy occurred in 39 patients, with an incidence of 34.5%. These patients experienced significant prothrombin time prolongation around day 6 (median) after cefoperazone application. The serum trough concentration threshold of cefoperazone-induced coagulopathy in critically ill patients was 87.765 mg/l. Multivariate logistic regression analysis revealed that the APACHE II score (p = 0.034), prophylactic use of vitamin K1 (p < 0.001), hepatic impairment (p = 0.014), and Cmin ≥ 87.765 mg/l (p = 0.005) were associated with cefoperazone-induced coagulopathy. CONCLUSION: Cefoperazone-induced coagulopathy usually occurs on the 6th day of cefoperazone use in critically ill patients. The risk will increase in patients with an APACHE II score > 25, hepatic impairment, and cefoperazone Cmin ≥ 87.765 mg/l. Vitamin K1 is effective in preventing this adverse reaction.

Clinical practice guideline of the spanish society of oral surgery for oral surgery in patients with coagulation disorders.

BACKGROUND: The number of patients treated with coagulation disorders, and more specifically with anticoagulant therapy, has increased worldwide in recent years due to increased life expectancy in developed countries. The protocols for managing this type of patient in oral surgery has varied over recent years, especially after the appearance of new direct-acting oral anticoagulants (DOACs). The assessment of risk of bleeding in this type of patient when undergoing a surgical procedure continues to be a controversial issue for patients, dentists and general practitioners. The objective of this document is to offer recommendations, based on evidence, for decision making for patients with coagulopathies who require dental surgical intervention. MATERIAL AND METHODS: Based on the indications of the "Preparation of Clinical Practice guidelines in the National Health System. Methodological manual", we gathered a group of experts who agreed on 15 PICO questions based on managing patients with coagulation disorders in dental surgical procedures, such as fitting of implants or dental extractions. RESULTS: The 15 PICO questions were answered based on the available evidence, being limited in most cases due to the lack of a control group. Two of the PICO questions were answered by the experts with a grade C recommendation, while the rest were answered with grade D. CONCLUSIONS: The results of this review highlight the need to undertake well designed clinical trials with control groups and with a representative sample size.

Radiological findings in poisoning by synthetic cannabinoids adulterated with brodifacoum.

OBJECTIVES: Severe coagulopathy due to consumption of synthetic cannabinoids adulterated with brodifacoum, a long-acting anticoagulant, is an emerging worldwide hazard. Here, we review the spectrum of imaging findings in adulterated cannabinoid poisoning. MATERIALS AND METHODS: In this retrospective study, we used the Israeli Poison Information Center database to identify patients with cannabinoid-associated coagulopathy who presented to the Rambam Health Care Campus, where most patients were treated during an outbreak in northern Israel between September 2021 and June 2022. All relevant imaging studies for these patients were reviewed. We estimated the sensitivity of findings for cannabinoid-associated coagulopathy. Associations between a continuous variable and a dichotomous outcome were assessed with the Mann-Whitney U test. RESULTS: We identified 48 patients (mean age 40 years ± 9 [SD], 43 males) with 54 hospitalizations due to cannabinoid-associated coagulopathy. Symptomatic hemorrhage was documented in 50 (93%) cases at presentation, most of whom (78%) had hemorrhage from multiple systems. The most common bleeding site was the genitourinary collecting system, with a characteristic sign of suburothelial bleeding in 16/18 of performed abdominal CTs (sensitivity 89% [CI 65-99%] for cannabinoid-associated coagulopathy). Intramural bowel hematomas were noted in 70% (7/10) of CTs of patients with gastrointestinal bleeding. Incidental bleeding sites were identified on imaging in 24% of patients. An increased number of bleeding sites was associated with need for vasopressors (difference in bleeding sites 3.00 [95% CI 0.99-4.00], p = 0.026). CONCLUSION: CT plays a key role in the diagnosis and work-up of adulterated cannabinoid-associated coagulopathy. Characteristic signs include suburothelial hemorrhage and intramural bowel hematomas. CLINICAL RELEVANCE STATEMENT: Recognition of radiological signs of adulterated synthetic cannabinoid-associated coagulopathy is critical for optimizing outbreak control on the public health level and ensuring timely treatment on the individual patient level. KEY POINTS: • Severe coagulopathy due to consumption of synthetic cannabinoids adulterated with brodifacoum, a long-acting anticoagulant, is an emerging worldwide threat. • Characteristic imaging signs include suburothelial bleeding, intramural bowel hematomas, and rare incidental bleeding sites. • Imaging has a pivotal role in optimizing outbreak control and ensuring timely and appropriate treatment.

[One case of bromadiolone poisoning leading to intestinal necrosis and severe coagulopathy].

Bromadiolone is still often used in life as a poisonous rodent agent. Bromadiolone poisoning is often manifested as coagulation dysfunction, resulting in organ bleeding, including cerebral hemorrhage, intestinal bleeding, abdominal hemorrhage, etc. At present, no case of intestinal necrosis caused by bromadiolone poisoning have been reported. This article reviewed one case of intestinal necrosis and severe coagulation dysfunction, and finally confirmed bromadiolone poisoning by poison detection. The patient recovered and was discharged after surgery, vitamin K injection, plasma transfusion and other treatment methods.

Right femoral vein and right dorsal artery thrombosis in childhood acute myeloid leukemia: A case report.

BACKGROUND: It is rare for newly diagnosed (de novo) or newly treated acute myeloid leukemia (AML) complicated with thrombotic complications, especially combined arterial and venous thrombosis. METHODS: We reported a 13-year-old boy diagnosed with AML and leukocytosis, who developed right femoral vein and right dorsal artery thrombosis during chemotherapy. After treatment with low molecular weight heparin, diosmin, and alprostadil, symptoms were relieved. Unfortunately, the child suffered from coagulopathy afterward, which was unexpectedly caused by vitamin K deficiency. RESULTS: After supplementation with vitamin K and prothrombin complex concentrate, coagulation function recovered. CONCLUSION: For childhood AML patients with high thrombotic risks, close monitoring during anticoagulant treatment was necessary. Concomitantly, we should be alert to past medication history and combined medication use, especially those that may lead to vitamin K deficiency, secondary bleeding, and coagulation disorders. Rational use of antibiotics, anticoagulants, and antitumor drugs must be guaranteed.

Novel Toxicodynamic Model of Subcutaneous Envenomation to Characterize Snake Venom Coagulopathies and Assess the Efficacy of Site-Directed Inorganic Antivenoms.

Venomous snake bite adversely affects millions of people yearly, but few animal models allow for the determination of toxicodynamic timelines with hemotoxic venoms to characterize the onset and severity of coagulopathy or assess novel, site-directed antivenom strategies. Thus, the goals of this investigation were to create a rabbit model of subcutaneous envenomation to assess venom toxicodynamics and efficacy of ruthenium-based antivenom administration. New Zealand White rabbits were sedated with midazolam via the ear vein and had viscoelastic measurements of whole blood and/or plasmatic coagulation kinetics obtained from ear artery samples. Venoms derived from Crotalus scutulatus scutulatus, Bothrops moojeni, or Calloselasma rhodostoma were injected subcutaneously, and changes in coagulation were determined over three hours and compared to samples obtained prior to envenomation. Other rabbits had ruthenium-based antivenoms injected five minutes after venom injection. Viscoelastic analyses demonstrated diverse toxicodynamic patterns of coagulopathy consistent with the molecular composition of the proteomes of the venoms tested. The antivenoms tested attenuated venom-mediated coagulopathy. A novel rabbit model can be used to characterize the onset and severity of envenomation by diverse proteomes and to assess site-directed antivenoms. Future investigation is planned involving other medically important venoms and antivenom development.

Outcomes of 4-factor Prothrombin Complex Concentrate in Patients With Liver Disease and Nonvitamin K Antagonist-Related Coagulopathy: A Retrospective Study.

The administration of 4-factor prothrombin complex concentrate (4F-PCC) has expanded beyond its Food and Drug Administration (FDA)-approved indication for the emergent reversal of vitamin K antagonists (VKAs). Therefore, this study aimed to evaluate the risks and benefits associated with the expanded use of 4F-PCC. We conducted a single-center retrospective review of 4F-PCC administrations at our university hospital. Of the 159 patients who received 4F-PCC, 76% (n = 121) and 24% (n = 38) received it for the FDA-approved indication in the vitamin K-related coagulopathy (VKA) group and for expanded use in the nonvitamin K-related coagulopathy (nVKA) group, respectively. The expanded use of 4F-PCC was associated with a less robust reduction in the international normalized ratio (INR) (INR of -0.7 ± 1.3 vs INR of -1.6 ± 1.8, P = .002), and fewer patients in the nVKA group achieved a postadministration INR of less than1.5 (11% vs 79%, P = .001) than those in the VKA group. Furthermore, the 30-day mortality rate was significantly higher in the nVKA cohort than in the VKA cohort (42% vs 20%, P = .04). Notably, based on our data, underlying differences in the patient's comorbidities, particularly advanced liver disease, may have contributed to the observed outcome variations, including mortality rate. Therefore, factors, including comorbidities and the underlying etiology of coagulopathy, should be considered when deciding on the expanded use of 4F-PCC. Further research is needed to better understand the potential risks and benefits of 4F-PCC in expanded use scenarios, and the clinical decision to use 4F-PCC outside its FDA-approved indication should be made carefully, considering this information.

A prospective observational phase IV study on effectiveness of animal derived polyclonal antibody antivenoms against West African carpet viper (Echis romani) induced coagulopathy and mortality.

Conventional polyclonal antibody antivenoms are the mainstay of snakebite therapy. They have not been proven to be efficacious in randomized placebo controlled clinical trials among severely envenomed patients. There is also paucity of evidence on effectiveness especially in routine use. The current study evaluated their effectiveness in post marketing use among those managed with and without antivenom as regards to reversal of venom induced coagulopathy defined using the 20 min Whole Blood Clotting Test [20WBCT] and in averting death. The effectiveness of antivenom was evaluated among 5467 patients predominantly envenomed by the West African carpet viper (Echis romani) at 3 hospitals in Nigeria from 2021 to 2022. Two antivenoms Echitab G (EG) and Echitab ICP Plus (EP) were able to restore normal clotting within 6 h of administration in 58.0% [95% Confidence Interval (95%CI)] (51.2-64.5%) and 91.7% (90.4-93.0%) of patients respectively. They were able to restore normal clotting within 24 h of administration in 96.9% (94.0-98.7%) and 99.0% (98.4-99.4%) of patients respectively. The Odds Ratio [OR (95%CI)] of dying among patients with positive 20WBCT who were treated with ≥1 vial of either EG or EP compared to those not treated was 0.06 (0.02-0.23) and 0.07 (0.03-0.15) respectively. This equated to antivenom protection against in-hospital mortality of 93-94% among patients with confirmed coagulopathy though the benefit appeared abrogated among those without coagulopathy. The untreated natural mortality was 15.94% (95%CI:8.24-26.74%) without antivenom therapy while the overall mortality was 84/5105 (1.65%; 95%CI:1.32-2.03%. The Number Needed to Treat (NNT) to avert a death was 7 patients among those with coagulopathy. Antivenoms were safe with mild early adverse reactions observed among 2.6% (95%CI:2.13-3.08%) of antivenom recipients. Polyclonal antibody antivenoms are effective and safe for treating coagulopathic envenomed patients in Nigeria.

An outbreak of severe coagulopathy in northern Israel among users of illicit synthetic cannabinoids adulterated with brodifacoum.

INTRODUCTION: Adulteration of illicit drugs is a well-known phenomenon that may expose consumers to unexpected adverse effects. We report a large outbreak of severe coagulopathy in northern Israel during nine months in 2021-2022 among users of synthetic cannabinoids adulterated with a long-acting anticoagulant, brodifacoum. METHODS: We performed a retrospective cohort study based on data extracted from the Israeli National Poison Information Center database and from electronic medical patient records at three participating hospitals. Confiscated drug samples and blood samples obtained at admission in a subgroup of patients were tested for the presence of long-acting anticoagulants. RESULTS: We identified 98 patients affected by the outbreak. All patients had a prolonged international normalized ratio on admission, and in 69%, the blood was non-coagulating. For patients treated in the three participating centers (n = 72), the presenting complaint was overt bleeding in 79% of patients, most commonly in the urinary (53%) and gastrointestinal tracts (50%). The most severe complications were intracranial bleeding (4%), hemothorax (3%), pericardial bleeding (1%), and four patients died. Brodifacoum was detected in all available blood samples (median concentration 207 µg/L, interquartile range 112-349 µg/L, range 45-1,118 µg/L), and the drug samples contained both brodifacoum and the synthetic cannabinoid ADB-BUTINACA. All patients were treated with high-dose phytomenadione (vitamin K1) and additionally by packed red blood cell transfusions, fresh frozen plasma, and/or 4-factor prothrombin complex concentrate when indicated. The most frequent phytomenadione (vitamin K1) dose regimen was initially 20 mg intravenously every eight hours, and at discharge, 20 mg orally three times daily. CONCLUSIONS: Outbreaks of severe coagulopathies in users of synthetic cannabinoids adulterated with a long-acting anticoagulant continue to erupt in different regions of the world. Rapid recognition of an outbreak requires a high index of suspicion when confronting young, otherwise healthy subjects with otherwise unexplained severe coagulopathy.

Effect of Cefoperazone/Sulbactam on Blood Coagulation Function in Infected Emergency Department Patients and the Necessity of Vitamin K1 (VK1) Preventive Intervention: A Single-Center, Retrospective Analysis.

BACKGROUND Owing to its broad-spectrum antibacterial activity, strong antibacterial effects, and ß-lactamase stability, cefoperazone/sulbactam has been recognized as a first-line empirical drug for treating severe infections. However, its administration is also characterized by numerous adverse effects, including coagulation dysfunction. Here, we summarize past clinical treatment data to provide data support for clinical use of cefoperazone sulbactam. MATERIAL AND METHODS We retrospectively analyzed the clinical medical records of 820 patients treated with cefoperazone/sulbactam from January 2015 to December 2020. A retrospective cohort study design was used. We assessed the general data of patients, age and sex distribution, type of primary disease, and incidence and days of abnormal blood coagulation with cefoperazone sulbactam. The chi-square test and t test were used to analyze the effect of cefoperazone sulbactam on coagulation function and the effect of vitamin K intervention on prognosis. RESULTS The rate of coagulation dysfunction was 24.39% (200 patients). Among these 200 patients, 50 were treated with vitamin K1. With increasing patient age, the number of patients with cefoperazone/sulbactam-induced coagulation dysfunction increased (peak at 81-90 years). APACHE II of coagulation dysfunction (15.54±4.095) was significantly higher than that in the normal group. It occurred at days 2-19 after administration of 9.0 g/day of cefoperazone/sulbactam. Measured coagulation indices were significantly higher after treatment with cefoperazone/sulbactam than before treatment, including international normalized ratio, prothrombin time, and activated partial thrombin time (P<0.0001). CONCLUSIONS All coagulation indices decreased significantly after vitamin K1 intervention, indicating improved coagulation function, especially in patients with high APACHE II scores. Hence, regulated vitamin K1 administration can benefit patients with coagulation dysfunction in clinical treatment.

A case report of Ovophis monitcola (Mountain pit-viper) envenoming in northeastern India resulting in prolonged coagulopathy.

India is home to a diverse spectrum of medically-significant snakes accounting for one of the world's largest burdens of envenoming, morbidity and mortality. Indian polyspecific antivenom is derived from the venom of four snake species (Daboia russelii, Echis carinatus, Naja naja and Bungarus caeruleus), considered to be responsible for the majority of snakebite morbidity and mortality in India. The treatment of envenoming from other less-commonly encountered venomous snake species can be challenging. In this report, we describe the case of a 32-year-old male who presented with local swelling and coagulopathy following a bite from Ovophis monitcola (mountain pit-viper) in Nagaland, Northeast India. Local and systemic envenoming, failed to respond to Indian polyspecific antivenom and venom-induced consumption coagulopathy, confirmed by bedside and laboratory-based clotting assays, persisted for more than three weeks. Remote consultation with a national-level Poison Control Centre helped establish the responsible snake species and guide appropriate medical management.

Robust coagulation activation and coagulopathy in mice with experimental acetaminophen-induced liver failure.

BACKGROUND: Patients with acetaminophen (APAP)-induced acute liver failure (ALF) display both hyper- and hypocoagulable changes not necessarily recapitulated by standard hepatotoxic doses of APAP used in mice (eg, 300 mg/kg). OBJECTIVES: We sought to examine coagulation activation in vivo and plasma coagulation potential ex vivo in experimental settings of APAP-induced hepatotoxicity and repair (300-450 mg/kg) and APAP-induced ALF (600 mg/kg) in mice. RESULTS: APAP-induced ALF was associated with increased plasma thrombin-antithrombin complexes, decreased plasma prothrombin, and a dramatic reduction in plasma fibrinogen compared with lower APAP doses. Hepatic fibrin(ogen) deposits increased independent of APAP dose, whereas plasma fibrin(ogen) degradation products markedly increased in mice with experimental ALF. Early pharmacologic anticoagulation (+2 hours after 600 mg/kg APAP) limited coagulation activation and reduced hepatic necrosis. The marked coagulation activation evident in mice with APAP-induced ALF was associated with a coagulopathy detectable ex vivo in plasma. Specifically, prolongation of the prothrombin time and inhibition of tissue factor-initiated clot formation were evident even after restoration of physiological fibrinogen concentrations. Plasma endogenous thrombin potential was similarly reduced at all APAP doses. Interestingly, in the presence of ample fibrinogen, ∼10 times more thrombin was required to clot plasma from mice with APAP-induced ALF compared with plasma from mice with simple hepatotoxicity. CONCLUSION: The results indicate that robust pathologic coagulation cascade activation in vivo and suppressed coagulation ex vivo are evident in mice with APAP-induced ALF. This unique experimental setting may fill an unmet need as a model to uncover mechanistic aspects of the complex coagulopathy of ALF.

Expression and Release of Tumor Cell Tissue Factor Triggers Recurrent Thromboembolism in a Patient with Endometrial Cancer.

Although cancer-associated thrombosis (CAT) is a frequent complication in patients with malignancies, its treatment remains a challenge in daily practice. Here, we report the clinical course of a 51-year-old woman presenting with a highly thrombogenic paraneoplastic coagulopathy. Despite therapeutic anticoagulation with various agents, including rivaroxaban, fondaparinux, and low-molecular-weight heparin, the patient suffered from recurrent venous and arterial thromboembolism. Locally advanced endometrial cancer was identified. Tumor cells showed strong expression of tissue factor (TF), and significant concentrations of TF-bearing microvesicles were detected in patient plasma. Coagulopathy was controlled only by continuous intravenous anticoagulation with the direct thrombin inhibitor, argatroban. Multimodal antineoplastic treatment, including neoadjuvant chemotherapy followed by surgery and postoperative radiotherapy, resulted in clinical cancer remission, which was paralleled by normalization of tumor markers, CA125 and CA19-9, D-dimer levels, and TF-bearing microvesicles. In summary, continuous anticoagulation with argatroban and multimodal anticancer treatment may be necessary to control TF-driven coagulation activation with recurrent CAT in endometrial cancer.

Vitamin E-induced coagulopathy in a young patient: a case report.

BACKGROUND: High-dose vitamin E intake is known to inhibit vitamin K-derived coagulation factor synthesis, which can cause serious bleeding events such as gastrointestinal bleeding and intracranial hemorrhage. We report a case of coagulopathy induced by marginally increased levels of vitamin E. CASE PRESENTATION: A 31-year-old Indian man presented with oral bleeding, black tarry stools, and bruising over his back. He had been taking non-steroidal anti-inflammatory drugs for low backache and vitamin E for hair loss. He had mild anemia with normal platelet count, thrombin time, and prolonged bleeding time, activated partial thromboplastin time, and prothrombin time. Serum fibrinogen was slightly raised. Mixing studies with pooled normal plasma, aged plasma, and adsorbed plasma were suggestive of deficiency of multiple coagulation factors due to acquired vitamin K deficiency. Serum phylloquinone was normal, while prothrombin induced by vitamin K absence-II level was increased. Serum alpha-tocopherol was slightly raised. Upper gastrointestinal endoscopy showed multiple gastroduodenal erosions. A final diagnosis of vitamin E toxicity-related coagulopathy was made. The patient responded well to pantoprazole, vitamin K supplementation, multiple fresh frozen plasma transfusions, and other supportive treatments besides the discontinuation of vitamin E supplementation. The coagulation parameters normalized, and the patient was discharged with complete resolution of symptoms and remained asymptomatic during the follow-up for 6 months. CONCLUSIONS: Vitamin E-related inhibition of vitamin K-dependent factors with coagulopathy may occur even at marginally increased levels of serum vitamin E. This risk becomes significant in patients receiving other drugs that may increase the risk of bleeding.