Activated partial thromboplastin time waveform analysis: a new tool to detect infection?

OBJECTIVE: An abnormality of the optical transmission waveform obtained during measurement of the activated partial thromboplastin time (aPTT) has been described to identify a high-risk intensive care unit population consisting of patients with sepsis or with higher mortality rates than patients with normal aPTT waveforms. We investigated the abnormal aPTT biphasic waveform as a diagnostic and prognostic marker of infection. DESIGN: Prospective, observational study investigating the predictive value of aPTT waveform analysis for the diagnosis and prognosis of sepsis. SETTING: Surgical intensive care unit of a university hospital. PATIENTS: We studied 187 consecutive patients who fulfilled at least two or more criteria of the systemic inflammatory response syndrome at admission or during intensive care stay and classified as having systemic inflammatory response syndrome, sepsis, severe sepsis, or septic shock during an 8-month period. INTERVENTIONS: Laboratory analyses including aPTT waveform analysis and procalcitonin and C-reactive protein concentrations were measured at days 1-3. MEASUREMENTS AND MAIN RESULTS: The final diagnoses were systemic inflammatory response syndrome in 49%, sepsis in 16%, severe sepsis in 12%, and septic shock in 23% of patients. On day 1, the biphasic waveform was significantly more abnormal in patients with severe sepsis or septic shock than in patients with systemic inflammatory response syndrome or sepsis. The biphasic waveform was more accurate than procalcitonin and C-reactive protein for differentiating patients with severe sepsis and septic shock, with 90% sensitivity and 92% negative predictive value. Biphasic waveform values were significantly more abnormal during days 1-3 in septic nonsurvivors than in survivors and nonseptic nonsurvivors. The biphasic waveform exhibited the best specificity (91%) and negative predictive value (98%) for the prognosis of sepsis-related mortality on day 3. CONCLUSIONS: In intensive care units, when the analyzer is available, aPTT waveform analysis is an inexpensive, rapid, effective, and readily available tool providing information for the diagnosis of severe sepsis and the prognosis of septic patients.     

Coagulation system and platelets are fully activated in uncomplicated sepsis

OBJECTIVE: To test the hypothesis that the coagulation system and platelets are activated in sepsis, the uncomplicated and usually earliest stage of the septic process, and to compare the findings detected in sepsis with those found in severe sepsis and septic shock. DESIGN: Prospective study comparing patients with sepsis, severe sepsis, and septic shock, and healthy volunteers. SETTING: General intensive care unit in a tertiary university hospital. PATIENTS: Seventy-four consecutive septic patients (45 with sepsis, 15 with severe sepsis, and 14 with septic shock). Fourteen healthy volunteers served as control subjects. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: After blood sampling, molecular activation markers of coagulation (prothrombin fragments 1 and 2, fibrinopeptide A, thrombin-antithrombin complexes, and monomers of fibrin) and of platelets (beta-thromboglobulin and platelet factor 4), several coagulation factors, global tests of coagulation (prothrombin time and activated partial thromboplastin time), and platelet count (PTL) were measured. In sepsis, prothrombin fragments 1 and 2, fibrinopeptide A, thrombin-antithrombin complexes, and monomers of fibrin were increased to 2.52+/-0.21 nmol/L, 20.88+/-2.52 ng/mL, 33.8+/-2.9 microg/L, and 69% positive, respectively, compared with control subjects (0.86+/-063 nmol/L, 1.14+/-0.15 ng/mL, 16.07+/-1.01 microg/L, and 0%, respectively). Beta-Thromboglobulin and the beta-thromboglobulin-to-platelet factor 4 ratio were also increased to 107.87+/-11.87 IU/mL and 8.86+/-1.06, compared with controls (18.36 +/-2.99 IU/mL and 2.67+/-0.52, respectively). With the exception of a decrease in factor XII and an increase in fibrinogen, coagulation factors, global coagulation tests, and PTL were not changed in sepsis. In severe sepsis and mainly in septic shock, coagulation factors were markedly decreased, global coagulation tests were prolonged, and PTL was reduced. All changes were independent of the causative infectious pathogen. CONCLUSION: Coagulation system and platelets are strongly activated in sepsis. In this stage, only factor XII is decreased. In contrast, in severe sepsis and mainly in septic shock, most of the coagulation factors are depleted, PTL is decreased, and global coagulation tests are prolonged, indicating exhaustion of hemostasis. Finally, Gram-positive, Gram-negative, and other microorganisms produce identical impairment of coagulation.     

Combination of thrombin-antithrombin complex,plasminogen activator inhibitor-1, and protein C activity for early identification of severe coagulopathy in initial phase of sepsis: a prospective observational study

Introduction

Current criteria for early diagnosis of coagulopathy in sepsis are limited. We postulated that coagulopathy is already complicated with sepsis in the initial phase, and severe coagulopathy or disseminated intravascular coagulation (DIC) becomes overt after progressive consumption of platelet and coagulation factors. To determine early diagnostic markers for severe coagulopathy, we evaluated plasma biomarkers for association with subsequent development of overt DIC in patients with sepsis.

Methods

A single-center, prospective observational study was conducted in an adult ICU at a university hospital. Plasma samples were obtained from patients with sepsis at ICU admission. Fourteen biomarkers including global markers (platelet count, prothrombin time, activated partial thromboplastin time, fibrinogen and fibrin degradation product (FDP)); markers of thrombin generation (thrombin-antithrombin complex (TAT) and soluble fibrin); markers of anticoagulants (protein C (PC) and antithrombin); markers of fibrinolysis (plasminogen, α₂-plasmin inhibitor (PI), plasmin-α₂-PI complex, and plasminogen activator inhibitor (PAI)-1); and a marker of endothelial activation (soluble E-selectin) were assayed. Patients who had overt DIC at baseline were excluded, and the remaining patients were followed for development of overt DIC in 5 days, and for mortality in 28 days.

Results

A total of 77 patients were enrolled, and 37 developed overt DIC within the following 5 days. Most patients demonstrated hemostatic abnormalities at baseline with 98.7% TAT, 97.4% FDP and 88.3% PC. Most hemostatic biomarkers at baseline were significantly associated with subsequent development of overt DIC. Notably, TAT, PAI-1 and PC discriminated well between patients with and without developing overt DIC (area under the receiver operating characteristic curve (AUROC), 0.77 (95% confidence interval, 0.64 to 0.86); 0.87 (0.78 to 0.92); 0.85 (0.76 to 0.91), respectively), and using the three together, significantly improved the AUROC up to 0.95 (vs. TAT, PAI-1, and PC). Among the significant diagnostic markers for overt DIC, TAT and PAI-1 were also good predictors of 28-day mortality (AUROC, 0.77 and 0.81, respectively).

Conclusions

Severe coagulation and fibrinolytic abnormalities on ICU admission were associated with subsequent development of overt DIC. A single measurement of TAT, PAI-1, and PC activity could identify patients with ongoing severe coagulopathy, early in the course of sepsis.     

弥散性血管内凝血评分在脓毒症中的应用

目的 研究弥散性血管内凝血(DIC)评分系统与脓毒症患者病情评估及预后间的关系.方法 回顾性分析2005年1月-2008年12月本院重症监护病房(ICU)收治315例脓毒症患者的资料,按住院28 d的预后分为生存组(194例)与死亡组(121例).比较两组患者血小板计数(PLT)、纤维蛋白原(Fib)、凝血酶原时间(PT)及纤维蛋白单体的差异;用logistic单因素回归分析急性生理学与慢性健康状况评分系统Ⅱ(APACHEⅡ)评分、DIC评分与预后的关系,评价APACHEⅡ评分、DIC评分在脓毒症诊断中的价值.结果 死亡组PLT、Fib显著低于生存组,PT、活化部分凝血活酶时间(APTT)、凝血时间(ACT)和纤维蛋白单体值显著高于生存组,且APACHEⅡ评分、DIC评分显著高于生存组(P<0.05或P<0.01).APACHEⅡ评分、DIC评分与脓毒症预后间均呈显著正相关[DIC评分:χ2=17.741,P<0.001,优势比(OR)=1.413,95%可信区间(CI)为1.203～1.659;APACHEⅡ评分:χ2=36.456,P<0.001,OR=1.109,95%CI为1.072～1.147].APACHEⅡ评分曲线下面积(0.706)高于DIC评分曲线下面积(0.611).结论 APACHEⅡ评分、DIC评分均可作为脓毒症预后的预测指标,但DIC评分对脓毒症的诊断和预后判断价值低于APACHEⅡ评分.     

Pre-operative coagulopathy management of a neonate with complex congenital heart disease: a case study

Severe coagulation defects often develop in neonates undergoing cardiac surgery, both as a result of the surgical intervention, and as pre-existing defects in the hemostatic mechanisms. The following case report describes a newborn patient with complex congenital heart disease and respiratory failure whose pre-operative coagulopathy was aggressively managed prior to surgical correction. A 5-day-old, 2.5 kg child presented with interrupted aortic arch, ventricular septal defect, atrial septal defect, and patent ductus arteriosus. On admission, he was in respiratory arrest suffering from profound acidemia. In addition, the child was hypothermic (30.1 degrees C), septic (Streptococcus viridans), and coagulopathic (disseminated intravascular coagulation-DIC). The patient was immediately intubated and initial coagulation assessment revealed the following: prothrombin time (PT) 48.9 s (international normalized ratio (INR) 15.7), activated partial thromboplastin time (aPTT) >106 s, platelet count 30,000 mm(3), fibrinogen 15 mg dL(-1) and antithrombin III (AT-III) 10%. Before cardiac surgery could be performed, the patient's DIC was corrected with the administration of cryoprecipitate (15 ml), fresh frozen plasma (300 ml), and platelets (195 ml). In spite of the large transfusion of fresh frozen plasma, the AT-III activity, measured as a percentage, remained depressed at 33. Initial thromboelastographic (TEG) determination revealed an index of +2.02, and following 100 IU administration of an AT-III concentrate, declined to -2.32. Sequential TEG profiles were performed over several days, with the results used to guide both transfusion and medical therapy. The congenital heart defect correction was subsequently performed with satisfactory initial results, but the patient developed a fungal infection and expired on the 16th post-operative day. The present case describes techniques of coagulation management for a newborn with both a severe hemostatic defect and congenital heart disease.     

大黄对脓毒症患者凝血功能的影响

目的:探讨大黄对脓毒症患者凝血功能的影响。方法:将30例无凝血功能障碍的脓毒症患者随机分为两组,对照组15例给予常规综合治疗,治疗组15例加用大黄10 g鼻饲。分别检测两组患者治疗前及治疗后1、3和7 d的凝血酶原时间(PT)、凝血酶时间(TT)、活化部分凝血活酶时间(APTT)、纤维蛋白原(FBG)和血小板(PLT)计数。结果:两组治疗后PT、TT、APTT均延长,FBG和PLT下降。治疗组治疗后第7日PT、TT、APTT均显著升高,FBG和PLT均显著降低,与对照组比较差异均有显著性(P均<0.05)。结论:大黄对脓毒症患者的凝血功能有保护作用。     

Prognostic value of protein C concentrations in neutropenic patients at high risk of severe septic complications

OBJECTIVE: To assess the prognostic value of protein C, endogenous activated protein C, and D-dimer concentrations in patients at high risk of developing severe septic complications secondary to cytostatic chemotherapy. DESIGN: Prospective, comparative, single-center study. SETTING: Specialized ward for treating patients with acute leukemia and associated intensive care unit at a university hospital. SUBJECTS: Twenty-six consecutive patients who developed either severe sepsis (n = 13) or septic shock (n = 13) during chemotherapy-induced neutropenia (leukocytes <1,000/microL). INTERVENTION: None, other than standard care. MEASUREMENTS AND MAIN RESULTS: Baseline blood samples were obtained from 97 adult patients treated with intensive cytostatic chemotherapy. Serial blood sampling was performed in 62 of 97 patients who developed fever (>38.3 degrees C). Thirteen patients progressed to severe sepsis and 13 patients to septic shock. Protein C, endogenous activated protein C, and D-dimer were measured in these 26 patients. At fever onset, protein C concentrations decreased from normal baseline concentrations and were significantly lower in the group of patients who progressed to septic shock compared with those who developed severe sepsis (medians for protein C activity: 23.1% vs. 69.5%; p = .0003). The median elapsed time between detection of fever and the diagnosis of severe sepsis or septic shock was 16 hrs and 12 hrs, respectively. All septic shock patients died, whereas patients who progressed only to severe sepsis survived. CONCLUSIONS: Septic shock in neutropenic patients is associated with increased protein C consumption. The data demonstrate that the coagulation cascade is activated and produces a hypercoagulable state before the onset of clinical symptoms of severe sepsis and septic shock. Low protein C concentrations at the onset of fever and before the onset of clinical symptoms of severe sepsis or septic shock may have prognostic value in predicting an unfavorable outcome. Protein C measurements may help identify patients at risk in an early phase of neutropenic sepsis. It is also attractive to speculate that because low protein C concentrations were seen in these patients, protein C replacement may be beneficial in sepsis.     

血浆置换在小儿弥散性血管内凝血的治疗作用

目的观察血浆置换在小儿弥散性血管内凝血治疗中的作用。方法选择临床确诊为小儿弥散性血管内凝血的患儿34例,在积极治疗原发病的基础上给予血浆置换治疗,观察血浆置换前后患儿的出血情况,凝血酶原时间(PT)、活化部分凝血酶时间(APTT)、纤维蛋白原(Fib)、抗凝血酶Ⅲ(ATⅢ)及D-二聚体等指标变化。结果通过血浆置换治疗后,34例患儿出血情况减轻,除血小板变化不大外,PT、APTT及Fib明显改善,ATⅢ明显升高,D-二聚体明显降低。结论血浆置换在小儿弥散性血管内凝血的治疗中临床疗效显著。     

Treatment effects of high-dose antithrombin without concomitant heparin in patients with severe sepsis with or without disseminated intravascular coagulation

BACKGROUND: Disseminated intravascular coagulation (DIC) is a serious complication of sepsis that is associated with a high mortality. OBJECTIVES: Using the adapted International Society on Thrombosis and Haemostasis (ISTH) diagnostic scoring algorithm for DIC, we evaluated the treatment effects of high-dose antithrombin (AT) in patients with severe sepsis with or without DIC. PATIENTS AND METHODS: From the phase III clinical trial in severe sepsis (KyberSept), 563 patients were identified (placebo, 277; AT, 286) who did not receive concomitant heparin and had sufficient data for DIC determination. RESULTS: At baseline, 40.7% of patients (229 of 563) had DIC. DIC in the placebo-treated patients was associated with an excess risk of mortality (28-day mortality: 40.0% vs. 22.2%, P < 0.01). AT-treated patients with DIC had an absolute reduction in 28-day mortality of 14.6% compared with placebo (P = 0.02) whereas in patients without DIC no effect on 28-day mortality was seen (0.1% reduction in mortality; P = 1.0). Bleeding complications in AT-treated patients with and without DIC were higher compared with placebo (major bleeding rates: 7.0% vs. 5.2% for patients with DIC, P = 0.6; 9.8% vs. 3.1% for patients without DIC, P = 0.02). CONCLUSIONS: High-dose AT without concomitant heparin in septic patients with DIC may result in a significant mortality reduction. The adapted ISTH DIC score may identify patients with severe sepsis who potentially benefit from high-dose AT treatment.     

Coagulopathy parameters in patients with Crimean‐Congo hemorrhagic fever and its relation with mortality

Background: Crimean‐Congo hemorrhagic fever (CCHF) is an acute illness affecting multiple organ systems and characterized by ecchymosis, visceral bleeding, and hepatic dysfunction. In this study, we aimed to investigate the profile of coagulopathy markers (platelet count, activated partial tromboplastin time (aPTT), prothrombin time (PT), international normalized ratio (INR), fibrinogen, protein C, protein S, antithrombin III, activated protein C resistance (APCR), and D‐dimer) and their clinical significance in 83 CCHF‐infected patients. Subjects and methods: We studied 83 CCHF patients who were admitted to Ankara Numune Education and Research Hospital during the spring and summer of2007. We compared the coagulopathy markers of fatal CCHF patients (n=9) with nonfatal cases (n=74). Results: Platelet count, PT, aPTT, INR, and fibrinogen were prognostic factors associated with mortality for CCHF. Especially, platelet count<20×10⁹ cells/l and aPTT>60 sec were important. Protein C, protein S, APCR, and antithrombin III levels were not associated with mortality. Conclusion: Laboratory tests including classical parameters (platelet count, PT, aPTT, INR, and fibrinogen) of coagulopathy seem to be enough for the followup of CCHF. Protein S, protein C, APCR, and D‐dimer levels were not associated with mortality. J. Clin. Lab. Anal. 24:163–166, 2010. © 2010 Wiley‐Liss, Inc.     

Traitement substitutif symptomatique des CIVD (à lˈexclusion des antithrombine et protéine C)

Disseminated intravascular coagulation (DIC) is characterized by a widespread activation of blood coagulation and deregulation of the fibrinolytic system. Acute DIC leads to intravascular fibrin formation and consumption of coagulation factors and platelets, which may result in impaired organ perfusion and bleeding. DIC is not a primary disease but an intermediary mechanism that is always secondary to an underlying disorder like sepsis, trauma, hepatic failure or obstetrical accidents. The cornerstone of DIC treatment is the management of the underlying disorder. The great variety of etiologies and clinical presentations complicate the identification of the most appropriate therapeutic strategy and represent a major obstacle against prospective trials for any treatment in DIC. Despite the lack of evidence, if the patient is bleeding seriously, as observed in severe trauma, factor coagulation and platelet replacement therapy is indicated as early as possible. In other cases, replacement therapy should not be started on the basis of laboratory findings alone. Before surgery or invasive procedures, replacement therapy is usually administered to achieve a prothrombin time (PT) < 1,5 normal PT, a platelet count >50G/L and a fibrinogen level > 0.5g/L.     

Epidemiology of severe sepsis in Japanese intensive care units: A prospective multicenter study

Severe sepsis is a leading cause of morbidity and mortality in the intensive care unit (ICU). We conducted a prospective multicenter study to evaluate epidemiology and outcome of severe sepsis in Japanese ICUs. The patients were registered at 15 general critical care centers in Japanese tertiary care hospitals when diagnosed as having severe sepsis. Of 14,417 patients, 624 (4.3%) were diagnosed with severe sepsis. Demographic and clinical characteristics at enrollment (Day 1), physiologic and blood variables on Days 1 and 4, and mortality were evaluated. Mean age was 69.0 years, and initial mean Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores were 23.4 and 8.6, respectively. The 28-day mortality was 23.1%, and overall hospital mortality was 29.5%. SOFA score and disseminated intravascular coagulation (DIC) score were consistently higher in nonsurvivors than survivors on Days 1 and 4. SOFA score, DIC score on Days 1 and 4, and hospital mortality were higher in patients with than without septic shock. SOFA score on Days 1 and 4 and hospital mortality were higher in patients with than without DIC. Logistic regression analyses showed age, presence of septic shock, DIC, and cardiovascular dysfunction at enrollment to be predictors of 28-day mortality and presence of comorbidity to be an additional predictor of hospital mortality. Presence of septic shock or DIC resulted in approximately twice the mortality of patients without each factor, whereas the presence of comorbidity may be a significant predictor of delayed mortality in severe sepsis.     

Sepsis incidence and outcome: contrasting the intensive care unit with the hospital ward

OBJECTIVE: To describe the outcome of patients with sepsis according to location on a ward or in an intensive care unit. DESIGN: Prospective multicentered observational study. SETTING: Three academic hospitals in Madrid, Spain. PATIENTS: Consecutive patients with sepsis admitted to participating hospitals from March 1 to June 30, 2003. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: During the study period, 15,852 patients >18 yrs of age were admitted. Sepsis was identified in 702 patients, giving an estimated cumulative incidence rate of 367 cases per 100,000 adult area residents per year and a cumulative incidence rate among patients admitted to the hospital of 4.4%. Most septic patients had a community-acquired infection (71%). Severe sepsis developed in 199 patients (incidence rate, 104 cases per 100,000 adult area residents per year), and 59 patients developed septic shock (incidence rate, 31 cases per 100,000 adult area residents per year). Most of the patients met the criteria for severe sepsis or septic shock on the same day that they would have qualified for the septic status one step down the scale. In the other patients, the median time between sepsis and severe sepsis was 2 days (interquartile range, 2-5) and between severe sepsis and septic shock was 3 days (interquartile range, 1-4). Only 32% of severe sepsis patients received intensive care. The hospital mortality for all septic patients was 12.8%; for severe sepsis, 20.7%; and for septic shock, 45.7%. CONCLUSIONS: This study shows the high incidence of sepsis in a general population of patients admitted to hospital. A significant proportion of patients with severe sepsis are not transferred to the intensive care unit.     

Massive pulmonary embolism leading to cardiac arrest is associated with consumptive coagulopathy presenting as disseminated intravascular coagulation

See also Levi M. Disseminated intravascular coagulation or extended intravascular coagulation in massive pulmonary embolism. This issue, pp 1475–6; Thachil J. DIC score predicts mortality in massive clot coagulopathy as a result of extensive pulmonary embolism: a rebuttal. This issue, pp 1657–8; Leitner JM, Janata‐Schwatzek K, Spiel AO, Sterz F, Laggner AN, Jilma B. DIC score predicts mortality in massive clot coagulopathy as a result of extensive pulmonary embolism: reply to a rebuttal. This issue, pp 1658–9. Summary. Background: A consumptive coagulopathy resembling disseminated intravascular coagulation (DIC) has been seen in patients with massive pulmonary embolism (PE). We hypothesized that a DIC‐like condition is relevant in patients whose pulmonary embolism leads to cardiopulmonary arrest and cardiopulmonary resuscitation (CPR). Methods: This hypothesis was tested by the use of a database consisting of all cases of PE diagnosed at the Department of Emergency Medicine from June 1993 to October 2007. Out of 1018 cases with PE, 113 patients underwent CPR. In this cohort study, the resuscitated patients were compared with those with PE but without CPR. Results: Patients with PE and CPR had 3‐fold higher D‐dimer, prolonged prothrombin time (PT), reduced platelet counts and lower fibrinogen and antithrombin (AT) levels compared with PE patients without cardiac arrest (P < 0.001 for all). Among patients with PE and CPR, D‐dimer was abnormal in 100%, PT in 44%, AT in 53%, fibrinogen in 19% and platelets in 25%. In comparison, PE without CPR was associated with abnormal D‐dimer in 99%, abnormal PT in 15%, low AT in 6%, low fibrinogen in 1% and low platelets in 2%. Nine per cent of the resuscitated patients had a DIC score ≥ 5, indicating overt DIC. The DIC score highly correlated with 1‐year and in‐hospital mortality. Conclusions: Massive PE leading to CPR is associated with consumptive coagulopathy and overt DIC. In resuscitated patients, DIC markers may indicate pulmonary embolism as the underlying cause of arrest.     

Platelet activation and interaction with leucocytes in patients with sepsis or multiple organ failure

Abstract. This study focuses on the role of platelet membrane glycoproteins and platelet-leucocyte adhesion in patients with sepsis and multiple organ failure (MOF). Specifically, the study raises the following issues: (1) the influence of sepsis and MOF on platelet activation as assessed by surface expression of platelet membrane glycoproteins GPIIb-IIIa and thrombospondin; and (2) the effect of sepsis and MOF on platelet adhesion to circulating leucocytes. In addition, platelet activation and platelet-leucocyte adhesion are evaluated according to clinical outcome. Forty-five patients with suspected sepsis or MOF were evaluated by intensive care scoring systems (APACHE II and Elebute) to assess severity of disease. Flow cytometric techniques were used to examine platelet membrane expression of various adhesion molecules on circulating platelets and the appearance of platelet specific antigen (CD41) on leucocytes as an index of platelet-leucocyte adhesion. The results were compared with severity of disease and according to outcome in patients. Twenty-eight patients of the total study population were septic and 17 were non-septic. Twenty-two of the 28 septic patients suffered from severe MOF (APACHE II ≥20) whereas in six septic patients MOF was absent. Eleven of the non-septic group suffered from moderate MOF whereas in six, severe MOF was present. In septic patients fibrinogen receptor activity on platelets was significantly above normal values (P< 0.001). When MOF was present, thrombospondin surface expression on circulating platelets also increased significantly (P<0.05). Concomitantly, platelet-leucocyte adhesion was increased in sepsis (P<0.05) and decreased in patients with MOF (P<0.05). Significant lower levels of circulating platelet-leucocyte aggregates occurred in non-survivors (P<0.05). We conclude that sepsis is associated with increased surface expression of platelet adhesion molecules and an increased occurrence of circulating platelet-leucocyte aggregates. The decrease in circulating platelet-leucocyte aggregates in MOF might result from enhanced peripheral sequestration. An increased platelet leucocyte adhesion and sequestration might account for development of MOF in the course of sepsis.     

Thrombin activatable fibrinolysis inhibitor is associated with severity and outcome of severe meningococcal infection in children

Summary.  Background and objectives:  In pediatric meningococcal sepsis, an imbalance between coagulation and fibrinolysis and proinflammatory action play major roles. We hypothesized that thrombin activatable fibrinolysis inhibitor (TAFI) and/or TAFI activation markers are involved in the pathogenesis of meningococcal sepsis. Patients and methods:  Children with severe meningococcal sepsis ( n  =   112) previously included in Rotterdam-based trials participated in this study. Clinical and laboratory parameters and severity scores were assessed. TAFI and TAFI activation markers were determined: TAFI activation peptide (TAFI-AP) and (in)activated TAFI [TAFIa(i)]. The –438G/A, Ala147Thr, and Thr325Ile polymorphisms were genotyped. Results:  TAFI levels were significantly decreased in patients with meningococcal disease at admission compared to the convalescence state. TAFI was decreased in patients with septic shock vs. those with no shock. TAFI-AP levels were increased in patients with disseminated intravascular coagulation (DIC) vs. patients without DIC. TAFI-AP and TAFIa(i) were significantly increased in non-survivors vs. survivors. TAFI-AP levels and the TAFI-AP/TAFI ratio were also strongly correlated to severity scores and laboratory parameters. The TAFI 325Ile/Ile genotype was overrepresented in patients with DIC. Conclusions:  Activation markers of TAFI were associated with the occurrence of DIC and mortality in meningococcal sepsis patients. A determination of TAFI, TAFI-AP, and TAFIa(i) is required to enable coherent interpretation of the role of TAFI in disease.     

Pathogenesis and treatment of disseminated intravascular coagulation in the septic patient

The incidence of sepsis and complications stemming from septicemia has remained constant in recent years despite improved levels of monitoring and care. Disseminated intravascular coagulation (DIC), a syndrome that occurs frequently in septic patients, is associated with increased mortality. Organ dysfunction is also a common sequela that is strongly correlated with DIC. Cytokines released early in the course of sepsis stimulate a procoagulant state that causes development of intravascular fibrin deposition. In a later stage of DIC, bleeding may occur in parallel because of consumption of clotting factors and inhibitors. Therapeutic strategies to attenuate or reverse these conditions have focused on multiple stages of the molecular cascade of events, including preventing cytokine induction, inhibiting coagulation processes, and promoting fibrinolysis. Recent clinical trials have supported the use of antithrombin and activated protein C supplementation in DIC associated with severe sepsis. Studies of other novel therapeutic avenues are still ongoing. Future efforts may be directed at combining 2 or more agents to achieve prompt and successful reversal of DIC. Copyright © 2002 by W.B. Saunders Company     

The evaluation of hemostatic disorders in patients with systemic lupus erythematosus]

AIM: Assessment of hemostasis in SLE patients. MATERIALS AND METHODS: We studied different coagulation parameters such as activated partial thromboplastin time (APTT), thrombin time (TT), prothrombin time (PT), activated clotting time (ACT); platelet aggregation (spontaneous and induced), fibrinolytic activity, concentration of fibrinogen, fibrinogen degradation products (FDP) and serotonin. RESULTS: Coagulation abnormalities were found with prevalence of hypercoagulation in APTT and TT tests. Fibrinolysis was inhibited. Levels of serotonin, FDP and spontaneous aggregation activity significantly increased. CONCLUSION: The above changes were typical for lingering DIC syndrome.     

凝血试验预测口腔颌面外科手术出血的价值

目的:评估术前常规凝血试验(coagulation tests,CTs)预测口腔颌面外科手术出血的价值。方法:对2002年12月- 2003年12月接受口腔颌面外科大手术的387例病人进行回顾性研究,通过术前常规CTs筛选出12例凝血功能异常的病人并匹配24例对照,对两组间出血相关临床事件及手术时间、术中失血和输血量进行分析。结果:凝血功能异常的发病率为3.10%,其中血小板计数(PC)异常的发生率为2.07%,凝血酶原时间(PT)和活化部分凝血活酶时间(aPTT)异常的发生率为1.34%,CTs筛选出的无任何临床症状和体征的凝血功能异常为1.29%(5/387)。病例组和对照组相比,在延缓手术或改变手术方式(66.7%vs.0%,P=0.000016)、术中术后全身使用生物止血剂(58.3%vs.8.3%,P=0.0025)等方面存在显著差异, 病例组平均手术时间明显短于对照组(5.77±1.37h vs.5.84±2.54h,P<0.01);而在术中因失血引起低血压(16.7%vs. 4.2%,P=0.28),因出血再次手术(8.3%vs.4.2%,P=0.56),因出血导致死亡(8.3%vs.0%,P=0.33)及术中失血和输血量无显著差异(P>0.05)。结论:口腔颌面外科术前常规CTs检查不能预测多数和术中出血相关的临床事件的发生,但对术前已有凝血功能异常病史和症状、体征的患者,CTs的结果能反映凝血功能异常的程度,对预测可能出现的出血性并发症有一定的     

严重脓毒症和脓毒性休克的急诊集束化治疗依从性调查分析

目的 调查严重脓毒症和脓毒性休克在急诊患者中的发生率以及针对严重脓毒症和脓毒性休克早期集束化治疗的依从性.方法 选择2009年5月至6月由救护车送至上海交通大学医学院附属瑞金医院急诊科的患者为调查对象,统计严重脓毒症和脓毒性休克的发生率,对符合诊断标准的患者分别统计早期复苏集束化治疗各项指标完成的依从性.结果 共纳入急诊就诊患者917例,其中符合严重脓毒症和脓毒性休克诊断标准者96例,发生率为10.47%.在符合诊断标准的患者中,早期复苏集束化治疗、使用抗菌药物前留取病原学标本、2 h内放置深静脉导管并监测中心静脉压(CVP)与中心静脉血氧饱和度(ScvO2)、3 h内使用广谱抗菌药物、6 h内早期目标导向治疗(EGDT)达标、12 h内乳酸下降或原乳酸≤2 mmol/L的依从性分别为1.04%、3.12%、2.08%、83.33%、1.04%、23.96%,急诊内科各指标的依从性依次为1.19%、3.57%、2.38%、83.33%、1.19%、26.19%,急诊外科各指标的依从性依次为0、0、0、83.33%、0、8.33%,急诊内、外科依从性比较差异均无统计学意义(均P＞0.05).结论 严重脓毒症和脓毒性休克在急诊就诊患者中占相当比例,但医师的认识不足;早期集束化治疗依从性较低,需加大指南的教育及执行程度.

Abstract：

Objective To evaluate the occurrence of severe sepsis and septic shock and the rate of compliance with sepsis bundle in patients with severe sepsis and septic shock in emergency department.Methods A prospective study was conducted on consecutive adult patients who were sent to Emergency Department of Ruijin Hospital, Shanghai Jiaotong University School of Medicine by ambulance from May to June in 2009. The occurrence of severe sepsis and septic shock, and the number of the patients in whom who met the criteria of compliance with sepsis bundle were analyzed. Results Nine hundred and seventeen patients who were sent to the emergency department by ambulance in that period were enrolled in the study.The number of patients with severe sepsis and septic shock was 96. The incidence of severe sepsis and septic shock was 10.47%. Among these patients, the number of patients in whom the sepsis bundle was complied,i.e. sepsis bundle, appropriate cultures were taken before antimicrobial therapy, placement of central venous catheter and monitoring of central venous pressure(CVP)as well as central venous oxygen saturation (ScvO2)within 2 hours, antibiotic therapy within 3 hours, early goal-directed therapy(EGDT)within 6 hours, and lactate clearance in 12 hours reached 1.04%, 3. 12%, 2.08%, 83. 33%, 1.04%, 23.96%.The results were 1.19%, 3. 57%, 2.38%, 83.33%, 1.19%, 26.19% and 0, 0, 0, 83.33%, 0, 8. 33% in medical and surgical emergency department respectively. There was no statistical difference between the two divisions(all P＞0. 05). Conclusion The incidence of severe sepsis and septic shock was high in emergency department, but the rate of recognition of it and the compliance with sepsis bundle were inadequate. It is urgently necessary to enhance the learning and implementation of the guideline.