scholarly journals Prognostic Factors in Patients with Septic Disseminated Intravascular Coagulation Treated with Thrombomodulin: The Effect of Reduced Thrombomodulin Dose; a Single-center, Retrospective, Observational Study

2021 ◽  
Author(s):  
Yoshihiro Nishita ◽  
Masatoshi Taga ◽  
Masaru Sakurai ◽  
Yoshitsugu Iinuma ◽  
Togen Masauji
Keyword(s):  
Prognostic Factors ◽  
Side Effects ◽  
Renal Dysfunction ◽  
Dose Reduction ◽  
Disseminated Intravascular Coagulation ◽  
Sofa Score ◽  
Single Center ◽  
Intravascular Coagulation ◽  
Reduced Dose ◽  
All Cause Mortality

Abstract Background: Human soluble recombinant thrombomodulin (TM alfa), a treatment for septic Disseminated intravascular coagulation (DIC), is recommended for patients with severe renal dysfunction in reduced doses. However, no studies have examined yet how dose reduction affects clinical efficacy. In this study, we investigated the significance of the TM alfa dose as a prognostic factor in clarifying the clinical background factors related to the clinical effect of TM alfa in patients with septic DIC.Methods: This study involved 102 patients with septic DIC admitted to a single-center intensive care unit between April 2013 and March 2020, receiving TM alfa. The following factors were retrospectively collected from the medical records of the target patients: (1) patient background, (2) sequential organ failure assessment (SOFA) score, (3) Japanese Association for Acute Medicine DIC diagnostic criteria score, (4) DIC treatment information, (5) TM alfa dose per bodyweight (normal dose: 0.06 mg/kg or reduced dose: 0.02 mg/kg), (6) DIC resolution within 7 days after the start of TM alfa administration (DIC resolution), (7) all deaths within 30 days after the start of TM alfa administration (30-days-all-cause mortality), (8) presence or absence of new hemorrhagic side effects after the start of TM alfa administration. Multiple logistic regression analysis was used to assess factors associated with DIC resolution and 30-days-all-cause mortality.Results: The SOFA score (odds ratio: 95% confidence interval, 0.76: 0.66–0.89), pneumonia (0.24: 0.08–0.75), and reduced dose administration of TM alfa (0.23: 0.08–0.66) were independent of and negatively related to the DIC resolution. For the 30-days-all-cause mortality, the SOFA score (1.66: 1.31–2.09), pneumonia (9.50: 2.49–36.25), and TM alfa dose reduction (3.52: 1.06–11.69) were independent, poor prognostic factors. We found no association between the hemorrhagic side effects and the TM alfa dose per bodyweight.Conclusions: The reduced dose of TM alfa for patients with severe renal dysfunction was observed to be an influential factor for DIC resolution and 30-day all-cause mortality in addition to SOFA score and pneumonia. Further studies are required in the future to verify this finding.

Hepatic and Metabolic Complications In Adult Patients With Acute Lymphoblastic Leukemia (ALL) Treated With Asparaginase-Containing Combination Chemotherapy: A Single Center Experience

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1405-1405
Author(s):  
Jason N. Barreto ◽  
Kristen B. McCullough ◽  
Candy S Peskey ◽  
Louis Letendre ◽  
William Hogan ◽  
...  
Keyword(s):  
Side Effects ◽  
Dose Reduction ◽  
Combination Chemotherapy ◽  
Adult Patients ◽  
Comparable Efficacy ◽  
Hepatic Toxicity ◽  
Single Center ◽  
Confounding Variables ◽  
Grade 3 ◽  
The Impact

Abstract Background L-asparaginase (LASP) therapy in adults is associated with frequent hepatic and metabolic side effects, often resulting in dose adjustments and omissions. Pegylated asparaginase (PEGASP) substituted for LASP improves convenience of administration with comparable efficacy; however, adverse event (AE) management remains challenging. The incidence and management of LASP- and PEGASP-induced metabolic and hepatic complications in adult ALL patients is not well defined. Methods This single center, retrospective, observational study was approved by the Mayo Clinic Institutional Review Board. Consecutive adult patients with a confirmed diagnosis of ALL receiving LASP or PEGASP containing chemotherapy regimens between January 2000 and October 2012 were evaluated. Patients were followed up to 60 days after the last LASP or PEGASP dose for development of biochemical and clinical pancreatitis, hypertriglyceridemia and hepatotoxicity. Hyperglycemia was not analyzed due to confounding variables, such as concomitant corticosteroid administration. AEs were graded as per the National Cancer Institute Common Terminology Criteria (CTCAE) version 4.03. Analysis was performed using Cox proportional hazard models with odds ratios (with 95% confidence intervals) reported to demonstrate the strength of association between group and AE rate. Results Of 74 adult patients, 54 (73%) met inclusion criteria. History of dyslipidemia, diabetes mellitus, cholelithiasis and coronary artery disease was documented at baseline in 13 (24%), 4 (7%), 4 (7%) and 10 (19%) patients, respectively. Twenty eight (52%) patients received LASP, 22 (41%) received PEGASP and 4 (7%) received both. A total of 399 doses including 335 (84%) LASP and 64 (16%) PEGASP were administered. Distribution based on treatment schedules was as follows; CALGB 9111 (n=20 (37%), Larson et al, 1998), E2993 (n=13 (24%), Goldstone et al, 2008), C10403 (n=9 (17%), NLM: NCT00558519), CCG 1941 (n=7 (13%), Gaynon et al, 2006) and Augmented Hyper-CVAD (n=5 (9%), Faderl et al,2011). Six (11%), 20 (37%), and 53 (98%) patients experienced pancreatic, lipid (hypertriglyceridemia) and hepatic adverse events, respectively. In this group, CTCAE grade 3/4 AEs occurred in 0 (0%), 8 (15%), and 28 (52%) patients, respectively. No deaths were directly related to these complications. Patients receiving PEGASP were more likely to experience AE of any CTCAE grade (OR 11.5, 95% CI 4.4-30.3, p < 0.0001), including grade3/4 AEs (OR 27.9, 95% CI 11.4-68.2, p < 0.0001) in comparison to those receiving LASP. All cases of pancreatitis manifested as biochemical elevation in pancreatic enzymes, and were either grade 1 (n=4, 67%) or grade 2 (n=2, 33%). All patients were managed conservatively. Management of hypertriglyceridemia was heterogeneous across all grades and included observation (n=11, 55%), non-pharmacologic interventions (n=1, 5%), medication management (n=4, 20%) and combined strategies (n=4, 20%). The most common practice was a combination of fibrate derivatives (fenofibrate) and fish oil (n= 5). One patient with a peak triglyceride level of 2285 mg/dL was placed on an insulin/dextrose infusion for 4 days. Hepatic toxicity manifested as CTCAE grade 3/4 transaminitis in 13 (24%) patients, hyperbilirubinemia in 4 (7%) patients and both in 11 (20%) patients. Temporal correlation was used to best distinguish confounding variables including possible hepatoxicity from azole antifungals and other drugs. Management of hepatic toxicity included delay in dosing, subsequent LASP or PEGASP dose reduction and laboratory monitoring until resolution. Overall, deviations in LASP or PEGASP administration were documented in 18 (33%) patients due to metabolic or hepatic AEs. Eight (15%) patients required omission of at least 1 dose, 7 (13%) experienced delays of administration and 7 (13%) needed a dose reduction. Conclusion PEGASP administration resulted in significantly higher AE rates in comparison to LASP and this significance was retained when comparing AEs of CTCAE grade 3 and 4. Given the growing trend of using PEGASP combination chemotherapy in adults with ALL, a detailed analysis looking at the increase in side effects, their consequences (delayed tereatment and dose reductions) and the impact of these factors on disease remission and survival is needed. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Disseminated Intravascular Coagulation: A Single Center Experience

2018 ◽  
Vol 23 (1) ◽  
pp. 31-35
Author(s):  
Omer Ekinci ◽  
Omer Candar ◽  
Ali Dogan ◽  
Ramazan Esen ◽  
Cengiz Demir
Keyword(s):  
Disseminated Intravascular Coagulation ◽  
Single Center ◽  
Intravascular Coagulation ◽  
Single Center Experience

scholarly journals Kidney Transplantation from Donors with Severe Disseminated Intravascular Coagulation

2013 ◽  
Vol 2013 ◽  
pp. 1-4 ◽  
Author(s):  
Lena Sibulesky ◽  
Reginald Gohh ◽  
Kevin Charpentier ◽  
Paul Morrissey
Keyword(s):  
Renal Dysfunction ◽  
Disseminated Intravascular Coagulation ◽  
Organ Donor ◽  
Machine Perfusion ◽  
Intravascular Coagulation ◽  
Tissue Plasminogen ◽  
Successful Transplantation ◽  
Organ Recovery ◽  
The Brain ◽  
Fibrin Thrombi

Disseminated intravascular coagulation (DIC) is a syndrome characterized by massive formation of thrombin, which can lead to renal dysfunction or failure. Many transplant centers are reluctant to accept the kidneys from donors with DIC especially if renal dysfunction is present. We developed protocol of machine perfusion followed by tissue plasminogen activator (tPA) infusion in order to treat and evaluate DIC kidneys prior to transplantation. The kidneys were placed on machine preservation with tPA added to the perfusate prior to transplantation. Three kidneys were transplanted from two donors who sustained gunshot injuries to the brain. A biopsy at the time of organ recovery documented widespread fibrin thrombi in approximately 80% of the glomeruli. Serial biopsies showed interval improvement following machine perfusion and a normal appearing kidney three months after successful transplantation. The histological presence of DIC in a deceased organ donor, even if associated with renal dysfunction, is not a contraindication to renal transplantation. Machine perfusion and tPA infusions may contribute to the recovery and successful transplantation of such kidneys.

scholarly journals Usefulness of Measuring Changes in SOFA Score for the Prediction of 28-Day Mortality in Patients With Sepsis-Associated Disseminated Intravascular Coagulation

2019 ◽  
Vol 25 ◽  
pp. 107602961882404 ◽  
Author(s):  
Toshiaki Iba ◽  
Makoto Arakawa ◽  
Katsunori Mochizuki ◽  
Osamu Nishida ◽  
Hideo Wada ◽  
...  
Keyword(s):  
Disseminated Intravascular Coagulation ◽  
Sofa Score ◽  
Operating Characteristic ◽  
Japanese Society ◽  
Characteristic Curve ◽  
Curve Analysis ◽  
Acute Medicine ◽  
Intravascular Coagulation ◽  
Failure Assessment ◽  
Sepsis Trial

The primary end point for sepsis trial is 28-day mortality. However, additional methods for determining the efficacy may have benefits. The purpose of this study was to search a useful indicator of anticoagulant therapy in patients with sepsis with disseminated intravascular coagulation (DIC). Data from 323 patients with sepsis with coagulopathy treated with antithrombin supplementation were analyzed. The changes in the Sequential Organ Failure Assessment (Δ SOFA) score, the overt-DIC (Δ overt-DIC) score, and the Japanese Society for Acute Medicine DIC (Δ JAAM DIC) score from baseline to day 7 were retrospectively analyzed in relation to the 28-day mortality. Significant correlations were found between the 28-day mortality and Δ SOFA, Δ overt-DIC score, and Δ JAAM DIC score. The accuracy of the prediction was higher for Δ SOFA (80.5%) than for Δ overt-DIC (66.7%, P < .001). The areas under the curve for mortality calculated using a receiver operating characteristic curve analysis were 0.812 for Δ SOFA, 0.655 for Δ overt-DIC, and 0.693 for Δ JAAM DIC. The mortality rate was significantly lower among cases with an improved SOFA score compared to those without an improvement. The Δ SOFA had the strongest association with the 28-day mortality in patients with sepsis and DIC.

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