Treatment with Antithrombin or Thrombomodulin and Mortality from Heatstroke-Induced Disseminated Intravascular Coagulation: A Nationwide Observational Study

2019 ◽  
Vol 45 (08) ◽  
pp. 760-766
Author(s):  
Hiroyuki Ohbe ◽  
Shunsuke Isogai ◽  
Taisuke Jo ◽  
Hiroki Matsui ◽  
Kiyohide Fushimi ◽  
...  
Keyword(s):  
Treatment Group ◽  
Confidence Interval ◽  
Hospital Mortality ◽  
Disseminated Intravascular Coagulation ◽  
Risk Difference ◽  
Control Group ◽  
Robust Analysis ◽  
Intravascular Coagulation ◽  
Doubly Robust ◽  
Inpatient Database

AbstractHeatstroke-induced disseminated intravascular coagulation represents potential targets for specific intensive treatments. However, the effect of antithrombin or thrombomodulin treatment remains uncertain. Using a large nationwide inpatient database in Japan, this study aimed to evaluate whether treatment with antithrombin or thrombomodulin could reduce mortality among patients with heatstroke-induced disseminated intravascular coagulation. Using the Japanese Diagnosis Procedure Combination inpatient database from April 2014 to March 2017, we identified heatstroke patients who developed disseminated intravascular coagulation. We allocated patients who started treatment with antithrombin or thrombomodulin within 2 days after admission to the treatment group and allocated others to the control group. A primary outcome was in-hospital mortality. We used a doubly robust analysis to ensure the robustness of our findings. We also conducted two sensitivity analyses for thrombomodulin versus others and antithrombin versus others. We identified 1,606 eligible patients during the 81-month study period. Of these, 556 (35%) received antithrombin or thrombomodulin. The doubly robust analysis demonstrated that in-hospital mortality was significantly lower among patients in the treatment group than among those in the control group (risk difference −6.5%; 95% confidence interval: −12 to −1.4%). In-hospital mortality was significantly lower in patients with thrombomodulin than in others (risk difference −5.5%; 95% confidence interval: −9.5 to −1.6%). There was no significant difference in in-hospital mortality between patients with antithrombin and others (risk difference −4.2%; 95% confidence interval: −9.3 to 0.9%). Treatment with recombinant human thrombomodulin may be associated with lower in-hospital mortality among patients with heatstroke-induced disseminated intravascular coagulation.

scholarly journals Effect of antithrombin Ⅲ among patients with disseminated intravascular coagulation in obstetrics: a nationwide observational study in Japan

2021 ◽  
Author(s):  
Yudai Iwasaki ◽  
Hiroyuki Ohbe ◽  
Daisuke Shigemi ◽  
Kiyohide Fushimi ◽  
Hideo Yasunaga
Keyword(s):  
Propensity Score ◽  
Observational Study ◽  
Confidence Interval ◽  
Maternal Mortality ◽  
Propensity Score Matching ◽  
Disseminated Intravascular Coagulation ◽  
Control Group ◽  
Intravascular Coagulation ◽  
Nationwide Observational Study ◽  
Inpatient Database

Abstract Objective: Pregnant women may develop disseminated intravascular coagulation (DIC), possibly resulting in massive maternal haemorrhage and perinatal death. The Japan guideline recommends use of antithrombin Ⅲ (ATⅢ) for DIC in obstetrics; however, its effect remains uncertain. The present study therefore aimed to investigate the effect of ATⅢ for DIC patients in obstetrics, using a national inpatient database in Japan. Design: Nationwide observational study Setting: Japan Population: We used the Diagnosis Procedure Combination inpatient database to identify patients who delivered at hospital and were diagnosed with DIC from July 2010 to March 2018. Methods: Propensity score matching analyses were performed to compare in-hospital maternal mortality and hysterectomy during hospitalization between users and non-users of ATⅢ on the day of delivery. Main Outcome Measures: In-hospital mortality, hysterectomy Results: A total of 9,920 patients were enrolled, including 4,329 patients (44%) who used ATⅢ and 5,511 patients (56%) who did not use ATⅢ. One-to-one propensity score matching created 3290 pairs. In-hospital maternal mortality did not differ significantly between the propensity-matched groups (0.3% in the ATⅢ group vs. 0.5% in the control group; odds ratio, 0.73; 95% confidence interval, 0.35–1.54). Patients in the ATⅢ group, compared with those in the control group, had a significantly lower proportion of receiving hysterectomy during hospitalization (5.3% vs. 8.7%; difference, -2.9%; 95% confidence interval, -4.2 to -1.6%). Conclusions: The present study did not show mortality-reducing effect of ATIII for patients with DIC in obstetrics. ATⅢ may have clinical benefit in terms of reduction in receiving hysterectomy.

scholarly journals Antithrombin use and mortality in patients with stage IV solid tumor-associated disseminated intravascular coagulation: a nationwide observational study in Japan

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Kohei Taniguchi ◽  
Hiroyuki Ohbe ◽  
Kazuma Yamakawa ◽  
Hiroki Matsui ◽  
Kiyohide Fushimi ◽  
...  
Keyword(s):  
Disseminated Intravascular Coagulation ◽  
Solid Tumor ◽  
Stage Iv ◽  
Therapeutic Strategies ◽  
Control Group ◽  
Intravascular Coagulation ◽  
High Care ◽  
Nationwide Observational Study ◽  
General Wards ◽  
Inpatient Database

Abstract Background Terminal-stage solid tumors are one of the main causes of disseminated intravascular coagulation (DIC); effective therapeutic strategies are therefore warranted. This study aimed to investigate the association between mortality and antithrombin therapy in patients with stage IV solid tumor-associated DIC using a large nationwide inpatient database. Methods From July 2010 to March 2018, patients with stage IV solid tumor-associated DIC in the general wards, intensive care unit, or high care unit were identified using the Japanese Diagnosis Procedure Combination Inpatient Database. Patients who received antithrombin within 3 days of admission were allocated to the antithrombin group, while the remaining patients were allocated to the control group. One-to-four propensity score matching analyses were applied to compare outcomes. The primary outcome was the 28-day in-hospital mortality. Results Of the 25,299 eligible patients, 919 patients had received antithrombin within 3 days of admission and were matched with 3676 patients in the control group. There were no significant differences in the 28-day mortality between the two groups (control vs. antithrombin: 28.9% vs. 30.3%; hazard ratio, 1.08; 95% confidence interval, 0.95–1.23). There were no significant differences in the organ failure score and the proportion of critical bleeding between the two groups. Subgroup analyses showed that the effects of antithrombin were not significantly different among different tumor types. Conclusion Using a nationwide Japanese inpatient database, this study showed that there is no association between antithrombin administration and 28-day mortality in patients with stage IV solid tumor-associated DIC. Therefore, establishing other therapeutic strategies for solid tumor-associated DIC is required.

Recombinant Thrombomodulin in Disseminated Intravascular Coagulation Associated with Stage IV Solid Tumors: A Nationwide Observational Study in Japan

2020 ◽  
Author(s):  
Kohei Taniguchi ◽  
Hiroyuki Ohbe ◽  
Kazuma Yamakawa ◽  
Hiroki Matsui ◽  
Kiyohide Fushimi ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Disseminated Intravascular Coagulation ◽  
Gynecological Cancer ◽  
Stage Iv ◽  
Control Group ◽  
Soluble Thrombomodulin ◽  
Entire Cohort ◽  
Intravascular Coagulation ◽  
Significant Difference ◽  
Inpatient Database

Abstract Objective The terminal stage of solid tumors sometimes induces disseminated intravascular coagulation (DIC); however, no useful therapeutic strategies have been established. This study investigated the relationship between mortality and recombinant human soluble thrombomodulin (rTM) therapy for patients with DIC associated with stage IV solid tumors using a large nationwide inpatient database. Methods Using the Japanese Diagnosis Procedure Combination Inpatient Database, patients with stage IV solid tumors who developed DIC were identified. Those who received rTM within 3 days of admission were included in the treatment group; the remaining were included in the control group. The primary outcome was the 28-day in-hospital mortality. Results Of 25,299 eligible patients, 1 to 4 propensity score matching was used to select 1,979 rTM users and 7,916 nonusers. There was no significant difference in the 28-day mortality (control vs. rTM: 37.4% vs. 34.3%; hazard ratio, 0.95; 95% confidence interval [CI], 0.88–1.04) and critical bleeding rate (control vs. rTM: 3.7% vs. 3.8%; odds ratio, 1.04; 95% CI, 0.75–1.42) between groups. Subgroup analyses showed that the 28-day mortality rate among patients with colorectal and gynecological cancer was significantly lower in the rTM than in the control group (p for interaction 0.033 and 0.010, respectively). Conclusion Although we identified a possibly beneficial association between rTM administration and mortality in specific populations of patients with colorectal and gynecological cancer, no such association was found when considering the entire cohort of patients with DIC associated with stage IV solid tumors.

Recombinant human soluble thrombomodulin and mortality in sepsis-induced disseminated intravascular coagulation

2016 ◽  
Vol 115 (06) ◽  
pp. 1157-1166 ◽  
Author(s):  
Kazuma Yamakawa ◽  
Shinjiro Saito ◽  
Shigehiko Uchino ◽  
Daisuke Kudo ◽  
Yusuke Iizuka ◽  
...  
Keyword(s):  
Propensity Score ◽  
Confidence Interval ◽  
Disseminated Intravascular Coagulation ◽  
Bleeding Complications ◽  
Control Group ◽  
Clinical Settings ◽  
Soluble Thrombomodulin ◽  
Intravascular Coagulation ◽  
All Cause Mortality ◽  
Recombinant Human Soluble Thrombomodulin

SummaryRecombinant human soluble thrombomodulin (rhTM) is a novel class of anticoagulants for treating disseminated intravascular coagulation (DIC). Although rhTM is widely used in clinical settings throughout Japan, there is limited clinical evidence supporting the use of rhTM in patients with sepsis-induced DIC. Furthermore, rhTM is not approved for DIC treatment in other countries. This study aimed to clarify the survival benefits of rhTM administration in critically ill patients. Data from 3,195 consecutive adult patients who were admitted to 42 intensive care units for the treatment of severe sepsis or septic shock between January 2011 and December 2013 were retrospectively analysed, and 1,784 patients were diagnosed with DIC based on the scoring algorithm from the Japanese Association for Acute Medicine DIC (n = 645, rhTM group; n = 1,139, control group). Propensity score matching created 452 matched pairs, and logistic regression analysis revealed a significant association between rhTM administration and lower in-hospital all-cause mortality in the propensity score-matched groups (odds ratio, 0.757; 95 % confidence interval, 0.574–0.999, p = 0.049). Inverse probability of treatment weighted and quintile-stratified analyses also revealed significant associations between rhTM administration and lower in-hospital all-cause mortality. Survival time in the propensity score-matched rhTM group was significantly longer than that in the propensity score-matched control group (hazard ratio, 0.781; 95 % confidence interval, 0.624–0.977, p = 0.03). Bleeding complications were not more frequent in the rhTM groups. In conclusion, this study demonstrated that rhTM administration is associated with reduced in-hospital all-cause mortality among patients with sepsis-induced DIC.

scholarly journals Effect of high-dose vitamin C therapy on severe burn patients: a nationwide cohort study

Critical Care ◽  
2019 ◽  
Vol 23 (1) ◽  
Author(s):  
Mikio Nakajima ◽  
Morita Kojiro ◽  
Shotaro Aso ◽  
Hiroki Matsui ◽  
Kiyohide Fushimi ◽  
...  
Keyword(s):  
Propensity Score ◽  
Vitamin C ◽  
Confidence Interval ◽  
Hospital Mortality ◽  
Control Group ◽  
High Dose ◽  
Burn Patients ◽  
Severe Burn ◽  
Severe Burns ◽  
High Dose Vitamin

Abstract Background Vitamin C is a well-documented antioxidant that reduces oxidative stress and fluid infusion in high doses; however, the association between high-dose vitamin C and reduced mortality remains unclear. This study evaluates the effect of high-dose vitamin C in severe burn patients under two varying thresholds. Methods We enrolled adult patients with severe burns (burn index ≥ 15) who were registered in the Japanese Diagnosis Procedure Combination national inpatient database from 2010 to 2016. Propensity score matching was performed between patients who received high-dose vitamin C within 1 day of admission (vitamin C group) and those who did not (control group). High-dose vitamin C was defined as a dosage in excess of 10 g or 24 g within 2 days of admission. The primary outcome was in-hospital mortality. Results Eligible patients (n = 2713) were categorized into the vitamin C group (n = 157) or control group (n = 2556). After 1:4 propensity score matching, we compared 157 and 628 patients who were administered high-dose vitamin C (> 10-g threshold) and controls, respectively. Under this particular threshold, high-dose vitamin C therapy was associated with reduced in-hospital mortality (risk ratio, 0.79; 95% confidence interval, 0.66–0.95; p = 0.006). In contrast, in-hospital mortality did not differ between the control and high-dose vitamin C group under the > 24-g threshold (risk ratio, 0.83; 95% confidence interval, 0.68–1.02; p = 0.068). Conclusions High-dose vitamin C therapy was associated with reduced mortality in patients with severe burns when used under a minimum threshold of 10 g within the first 2 days of admission. While “high-dose” vitamin C therapy lacks a universal definition, the present study reveals that different “high-dose” regimens may yield improved outcomes.

Increasing concentrations of prothrombin complex concentrate induce disseminated intravascular coagulation in a pig model of coagulopathy with blunt liver injury

Blood ◽  
2011 ◽  
Vol 118 (7) ◽  
pp. 1943-1951 ◽  
Author(s):  
Oliver Grottke ◽  
Till Braunschweig ◽  
Henri M. H. Spronk ◽  
Stephanie Esch ◽  
Annette D. Rieg ◽  
...  
Keyword(s):  
Liver Injury ◽  
Blood Loss ◽  
Disseminated Intravascular Coagulation ◽  
Prothrombin Complex Concentrate ◽  
Safety Data ◽  
Control Group ◽  
Total Blood ◽  
Intravascular Coagulation ◽  
Blunt Liver Injury ◽  
Ringer’S Lactate

Abstract Despite increasing use of prothrombin complex concentrate (PCC) to treat hemorrhage-associated coagulopathy, few studies have investigated PCC in trauma, and there is a particular lack of safety data. This study was performed to evaluate PCC therapy in a porcine model of coagulopathy with blunt liver injury. Coagulopathy was induced in 27 anesthetized pigs by replacing approximately 70% blood volume with hydroxyethyl starch 130/0.4 and Ringer's lactate solution; erythrocytes were collected and retransfused. Ten minutes after trauma, animals randomly received PCC (35 or 50 IU/kg) or saline. Coagulation parameters including thromboelastometry, thrombin generation, and blood loss were monitored for 2 hours. Internal organs were examined macroscopically and histologically to determine the presence of emboli and assess liver injury. Total blood loss was significantly lower and survival was higher in both PCC groups versus the control group (P < .05). These outcomes appeared to be dose-independent. Thromboembolism was found in all animals treated with 50 IU/kg PCC; 44% also showed signs of disseminated intravascular coagulation. Liver injury was similar in all animals. In conclusion, 35 IU/kg PCC safely improved coagulation and attenuated blood loss. However, the higher dose of PCC (50 IU/kg) appeared to increase the risk of thromboembolism and disseminated intravascular coagulation.

scholarly journals Perioperative blood loss in total hip and knee arthroplasty: Outcomes associated with intravenous tranexamic acid use in an academic medical center

2016 ◽  
Vol 4 ◽  
pp. 205031211663702 ◽  
Author(s):  
Craig A Hogan ◽  
Larry K Golightly ◽  
Suzanne Phong ◽  
Michael R Dayton ◽  
Clark Lyda ◽  
...  
Keyword(s):  
Treatment Group ◽  
Blood Loss ◽  
Confidence Interval ◽  
Tranexamic Acid ◽  
Knee Arthroplasty ◽  
Control Group ◽  
Control Groups ◽  
Joint Replacement Surgery ◽  
Replacement Surgery ◽  
And Control

Objectives: Clinical trials have reported decreased blood loss with the use of tranexamic acid during joint reconstruction. The purpose of this study was to assess the individual practice implications of tranexamic acid use in joint replacement surgery. Methods: Health records of adults undergoing total knee arthroplasty and total hip arthroplasty over a 12-month period were retrospectively reviewed. The treatment group comprised patients who received intravenous tranexamic acid perioperatively. The control group comprised patients who did not receive tranexamic acid. Results: Patients in the treatment group (n = 64) and the control group (n = 99) were well matched for demographics, orthopedic diagnosis, and comorbidities. In-hospital postsurgical mean decreases in hemoglobin concentrations were −4.05 g/dL and −4.94 g/dL in the treatment and control groups, respectively (p < 0.001). Postsurgical mean decreases in hematocrit levels were −11.2% and −14.2% in the treatment and control groups, respectively (p < 0.001). Three patients in the treatment group (5%) and 21 patients in the control group (21%) received red blood cell transfusions (p = 0.006). As compared to control, the relative risk of transfusion in the treatment group was 0.23 (95% confidence interval = 0.07–0.76) and the number needed to treat to avoid one transfusion was 7.0 (95% confidence interval = 3.8–14.4). No evidence of thromboembolism or other serious complications were observed in either group. Conclusions: In patients undergoing joint replacement surgery, perioperative administration of tranexamic acid was associated with diminished blood loss and lesser resource utilization.

Dysregulation of Inflammatory and Hemostatic Markers in Sepsis Associated Disseminated Intravascular Coagulation.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2223-2223 ◽  
Author(s):  
Jawed Fareed ◽  
Debra Hoppensteadt ◽  
Josephine Cunanan ◽  
Michael Mosier ◽  
Yutaka Osawa ◽  
...  
Keyword(s):  
Disseminated Intravascular Coagulation ◽  
Inflammatory Mediators ◽  
Protein C ◽  
Control Group ◽  
Functional Protein ◽  
Double Blind ◽  
Intravascular Coagulation ◽  
Hemostatic Markers ◽  
Circulating Levels ◽  
Pai 1

Abstract Abstract 2223 Disseminated intravascular coagulation (DIC) represents a complex pathophysiologic syndrome where marked alterations in the hemostatic system are manifested. As a result several inflammatory mediators are up regulated through multiple mechanisms. The up regulation of inflammatory mediators such as anaphylatoxin C5a (C5a), procalcitonin (PCT), interleukin 6 (IL-6), interleukin 10 (IL-10), myeloperoxidase (MPO), C reactive protein (CRP), and circulating levels of hemostatic markers including protein C inhibitor (PCI), plasminogen activator inhibitor 1 (PAI-1), and protein C (Pr C) were evaluated in 758 subjects enrolled in a randomized, double-blind, placebo-controlled, Phase-2B study evaluating the safety and efficacy of recombinant thrombomodulin (ART-123) in subjects with sepsis and suspected DIC. Thirty healthy male and female volunteers served as the control group. Commercially available ELISA methods were used to measure the various mediators. Marked deviations in the circulating levels of these markers, as compared to controls, were noted as shown in the following table. Compared with controls, subjects in DIC showed an increase in the circulating levels of most inflammatory markers. The levels of PCT, IL-6 and CRP, where considerably higher in the DIC subjects whereas PCI, Pr C and AT exhibited slight decreases. Wide individual variations were present. The PAI-1 levels were also increased in the DIC subjects. These results are tabulated below. These results clearly indicate that inflammation and impairment of fibrinolysis play a key role in the pathogenesis of DIC Parameter Nomal (NHP Mean+SEM) DIC (Baseline Mean+SEM) % Change Protein C (% Ag) 82.5 ± 13.6 47.6 ± 23.7 −42.2% Functional Protein C (%) 83.4 ± 13.2 46.2 ± 29.8 −44.6% PCI (% Inhibition) 130.0 ± 24.6 79.4 ± 105.5 −38.9% PAI-1 (ng/ml) 35.4 ± 10.8 140.6 ± 165.6 297.1% CRP (ug/ml) 2.6 ± 0.4 48.0 ± 14.2 1736.9% C5a (ng/ml) 9.2 ± 3.2 17.2 ± 13.3 85.1% IL-6 (pg/ml) 9.3 ± 3.7 620.3 ± 1883.4 6583.9% IL-10 (pg/ml) 13.9 ± 13.1 130.2 ± 118.6 836.1% MPO (ng/ml) 16.0 ± 4.2 108.1 ± 68.6 574.6% PCT (ng/ml) 0.2 ± 0.13 21.9 ± 43.3 14514.5% Disclosures: Osawa: Asahi Kasei Pharma America Corporation: Employment. Kaul:Asahi Kasei Pharma America Corporation: Employment.

Low plasma FVII:C and activated FVII as predictive markers for overt disseminated intravascular coagulation

2017 ◽  
Vol 117 (08) ◽  
pp. 1471-1477 ◽  
Author(s):  
Surapong Lertthammakiat ◽  
Nattachai Anantasit ◽  
Usanarat Anurathapan ◽  
Nongnuch Sirachainan ◽  
Praguywan Kadegasem ◽  
...  
Keyword(s):  
Cohort Study ◽  
Confidence Interval ◽  
Tissue Factor ◽  
Disseminated Intravascular Coagulation ◽  
Prospective Cohort ◽  
Hepatic Dysfunction ◽  
Factor Vii ◽  
Blood Samples ◽  
Intravascular Coagulation ◽  
Activated Factor Vii

SummaryIn sepsis, binding of factor VII (FVII:C) and activated factor VII (FVIIa) with tissue factor is the key step of coagulation resulting in disseminated intravascular coagulation (DIC). We conducted a prospective cohort study among 47 septic patients, aged 8 months to 18.8 years. They were initially divided into three groups of no DIC (n=27), non-overt DIC (n=14) and overt DIC (n=6). Blood samples were collected at 0, 24 and 48 hours (h) after the onset of sepsis. At the onset of sepsis, FVII:C tended to be lower in the non-overt DIC [median 57% (interquartile range [IQR] 41–80)] and overt DIC groups [33% (23–52)] than that in the no DIC group [65% (44–87)]. Whereas FVIIa tended to be lower in the overt DIC group [1.29% (0.50–4.19)] than those in the non-overt DIC [3.01% (1.01–5.24)] and no DIC groups [2.49% (1.14–3.13)]. At 24 h, FVII:C was significantly lower in the non-overt DIC [57% (41–101)] and overt DIC groups [31% (28–49)] than that in the no DIC group [83% (70–102)]. While FVIIa was significantly lower in the overt DIC group [2.15% (0.86–3.96)] than that in the no DIC group [3.83% (2.90–5.46)]. Using FVII:C <65% or FVIIa <3% at 24 h among patients without hepatic dysfunction to determine overt DIC at 24 h, the sensitivity was 83.9% and 77.4%, respectively, and the specificity was both 83.3%. Patients with low FVII:C and low FVIIa at 24 h after the onset of sepsis had a 20.8-fold (95% confidence interval [CI], 2.0–213.0, p=0.010) and 14.4-fold (95%CI, 1.5–142.4, p=0.023) chance of overt DIC.

scholarly journals Mortalidad por aborto séptico en el Hospital Nacional Cayetano Heredia. 1985 - 1992

2015 ◽  
Vol 40 (1) ◽  
pp. 55-59
Author(s):  
Raúl Castro ◽  
Eduardo Maradiegue
Keyword(s):  
Septic Shock ◽  
Renal Failure ◽  
Acute Renal Failure ◽  
Mortality Rate ◽  
Disseminated Intravascular Coagulation ◽  
Control Group ◽  
Uterine Perforation ◽  
Intravascular Coagulation ◽  
Foul Odor ◽  
Septic Abortion

This is a retrospective epidemiological control case type study of twenty-four deaths caused by septic abortion attended at our Hospital from 1985 through 1992. Control group consisted of 72 pregnant women who survived.. Septic abortion mortality rate was 67,3 per 100000 live newborns. Highest rate, 176,6, occurred in 1991. Mortality rate factor were 5 or more pregnancies (OR=1,7), gestational age over 16 week (OR=5,0), time from abortion maneuvers over 5 days (OR=1,7), septic shock (OR=8,5), anemia (OR=3,4), acute renal failure (OR=17,0), uterine perforation (OR=3,4), disseminated intravascular coagulation (OR=60,0), pelvic thrombophlebitis (OR = 10,2), multisystemic failure (OR=6,5) and lung shock (OR = 6,5). Significant symptoms were yellowish foul odor discharge, jaundice, petechiae, disnea and muscular pain. Main medical and surgical treatment consisted in blood and plasma transfusions, cardiotonics and anticoagulation, and hysterectomy and bilateral salpingoophorectomy. Main causes of death, were septic shock, acute renal failure, multisystemic failure, disseminated intravascular coagulation and lung thromboembolism.

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