Haemostasis Change in Intensive Care Patients with Severe Sepsis and Patients with Organ Failure without Sepsis

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1233-1233
Author(s):  
Patrick Van Dreden ◽  
Barry John Woodhams ◽  
Bernard Lenormand ◽  
Marc Vasse
Keyword(s):  
Severe Sepsis ◽  
Intensive Care ◽  
Organ Failure ◽  
Healthy Subjects ◽  
Protein C ◽  
Thrombin Generation ◽  
Protein S ◽  
Healthy Controls ◽  
Coagulation Abnormalities ◽  
The Mean

Abstract Abstract 1233 Introduction: Despite recent advances in understanding the pathophysiology of sepsis, multiple organ failure remains one of the leading causes of death in intensive care units (ICUs). A wide range of coagulation abnormalities have been observed in patients diagnosed with severe sepsis (SS). Its magnitude in relationship to organ failure without sepsis is less well documented. In this study, we examined and compared the results of plasma levels of coagulation tests and thrombin generation (calibrated automated thrombography (CAT) in patients with sepsis, patients with organ failure (OF) without sepsis and controls. We investigated whether the CAT and procoagulant phospholipids would be good prognostic markers and whether these markers would show a significant correlation with coagulation disorders. Patients and Methods: 21 patients with severe sepsis, 24 non-sepsis patients with organ failure were compared with 30 healthy subjects as controls. The delay between the onset of SS or OF and blood sampling was less than 12 hours. Analytical determinations of prothrombin time, activated partial thromboplastin time, and the levels of factors V,VII,VIII,X antithrombin, fibrinogen, protein C, protein S, D-Dimers were analysed using the STA-R analyser (Diagnostica Stago, France), Tissue factor activity (TFa) and thrombomodulin activity (TMa) were measured with two home-test. Free tissue factor pathway inhibitor (fTFPI), Soluble endothelial protein C receptor (sEPCR), and soluble thrombomodulin antigen were measured by ELISA assays (Diagnostica Stago, France). CAT was performed on PPP using PPP-reagent 5pM (Thrombinoscope, The Netherlands). Procoagulant phospholipids (PPL) were evaluated using the STA Procoag PPL assay (Diagnostica Stago, France). Results: The mean levels of factors V, VII, X, antithrombin, protein S, protein C, sEPCR were decreased in both SS and OF (p<0.001) compared with controls. Protein S, factor VII and X were significantly lower in the SS group than in the OF group (p<0.05). Factor VIII, D-Di, and fibrinogen level were increased in SS and OF groups (p<0.001). Activity and antigen thrombomodulin were significantly higher in SS and OF groups (p<0.01) than in healthy subjects, with no difference between patients groups. TFa was strongly increased in SS and OF (p<0.001) and not compensated by any increase in TFPI. We also observed that TF/fTFPI ratio were significantly increased in the SS and OF groups (p<0.001). Elevated thrombin generation was observed in patients with SS and OF. In particular lag-time and time to peak were prolonged (p<0.05), peak thrombin was significantly decreased only in SS group. However the mean total amount of thrombin generated in the groups of patients by endogenous Thrombin Potential (ETP) was equivalent to healthy controls. Procoagulant phospholipids were significantly higher in SS and OF groups than controls (p<0.001 and p<0.05 respectively). Non-surviving patients showed higher ETP, D-Di, TFa, PPL than survivors in both groups (p<0.05). No difference in fTFPI levels were observed between patients with negative outcome and survivors in the two groups of patients. IL-6 levels as inflammatory status were higher in SS and OF than in healthy controls, with a more pronounced increase in SS group. The levels of IL-6 were more important in non-survivors compared with survivors (p<0.05). Conclusion: This study suggests that severe septic and non septic patients with organ failure have similar coagulation abnormalities independently of the triggering event. Marked TFa generation was not adequately balanced by TFPI and inflammation may synergistically play a role in the pathogenesis of OF and death. Thrombin generation results showed that while the total amount of thrombin generated (ETP) was unchanged the initiation of thrombin generation was delayed and peak thrombin was reduced. This could be explained by the decreased levels of FVII, X, II causing a delay in the generation of thrombin. PPL and TGT may be useful in determining clinical outcome in patients and perhaps as a predictive parameter for an increased risk of bleeding or thrombotic complications in these patients. Their role to develop useful new markers in the management of patients remains to be defined. Disclosures: Van Dreden: Diagnostica Stago: Employment. Woodhams:Diagnostica Stago: Employment. Lenormand:Hospital: Employment. Vasse:hospital: Employment.

scholarly journals Thrombin generation in patients with COVID-19 with and without thromboprophylaxis

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Elena Campello ◽  
Cristiana Bulato ◽  
Luca Spiezia ◽  
Annalisa Boscolo ◽  
Francesco Poletto ◽  
...  
Keyword(s):  
Intensive Care ◽  
Healthy Subjects ◽  
Thrombin Generation ◽  
Standard Dose ◽  
Lag Time ◽  
Peak Height ◽  
Healthy Controls ◽  
Icu Patients ◽  
Time To Peak ◽  
Intermediate Dose

Abstract Objectives Thrombin generation (TG) with and without thrombomodulin (TM) was evaluated in COVID-19 patients with different disease severity and thromboprophylaxis regimen, in order to understand the prothrombotic profile. Methods We enrolled consecutive patients with confirmed diagnosis of COVID-19 admitted to Medical Departments (MD) or Intensive Care Units (ICU), and 54 healthy controls. Results Eighty-nine patients were included (mean age 60.4±16.1 years, 68.5% male); 33.7% admitted to ICU. Twenty-four patients (26.9%) were enrolled before thromboprophylaxis administration; 45 patients (50.6%) received standard and 20 (22.5%) intermediate sub-therapeutic dose thromboprophylaxis. Overall, patients with COVID-19 showed a TG profile comparable to that of healthy subjects (i.e. comparable peak height, endogenous thrombin potential [ETP] with and without TM). The only exception was lag time and time to peak, prolonged in COVID-19 patients vs. controls. MD patients showed a similar TG profile to healthy controls, and ICU patients showed significantly decrease ETP (p=0.030) compared to MD. As for thromboprophylaxis, TG profile was significantly increased in COVID-19 patients without thromboprophylaxis vs. controls and vs. those with thromboprophylaxis. In this latter group, ETP inhibition was significantly decreased (p=0.0003) and positively correlated with anti-Xa activity (r=0.49, p=0.0017). However, patients with thromboprophylaxis had similar TG profile vs. controls. Intermediate dose thromboprophylaxis more effectively inhibited TG in severe COVID-19 patients by increasing ETP inhibition via ETP with TM reduction vs. standard dose. Conclusions COVID-19 patients showed increased TG at diagnosis. Standard thromboprophylaxis reduced TG to levels of healthy controls. Intermediate sub-therapeutic thromboprophylaxis more effectively inhibited TG by decreasing ETP with TM.

scholarly journals FXa Inhibition and Coagulation Changes During DVT Prophylaxis by Enoxaparin Over the Course of a 15-Day Follow-Up in Septic Patients

2009 ◽  
Vol 16 (5) ◽  
pp. 584-590 ◽  
Author(s):  
Zuzana Zenáhlíková ◽  
Jan Kvasnička ◽  
Zuzana Kudrnová ◽  
Magda Sudrová ◽  
Radka Brzežková ◽  
...  
Keyword(s):  
Severe Sepsis ◽  
Protein C ◽  
Factor Xa ◽  
Inclusion Criteria ◽  
C Reactive Protein ◽  
Once Daily ◽  
Reactive Protein ◽  
Factor Xa Inhibition ◽  
The Mean

The objective of our study was to examine the changes in coagulation parameters and inflammatory reaction over the course of 15 days in patients with severe sepsis. We tried to identify mechanisms by which sepsis-induced pathophysiological changes may influence the effectiveness of subcutaneously (SC) administered enoxaparin 40 mg once daily. A total of 16 patients (8 men, 8 women; age 35-83 years) meeting the inclusion criteria of severe sepsis were enrolled in this study. The follow-up was performed on days 1, 2, 3, 6, 9, 12, and 15 of hospitalization at the intensive care unit (ICU). Blood coagulation (activated partial thromboplastin time [aPTT], prothrombin time [PT], fibrinogen, antithrombin (AT), protein C [PC], D-dimer, fragment 1.2 [F1.2], factor Xa [FXa] inhibition) and inflammatory reactants (interleukin 6 [IL-6], C-reactive protein [CRP], orosomucoid, α-1-antitrypsin) were tested. The mean FXa inhibition was 0.17 (±0.17) IU/mL. The arbitrarily established range of FXa inhibition for prophylaxis, 0.2 to 0.4 IU/mL, was reached in 22 cases (20%), while in 74 cases (68%), it was below and in 13 cases (12%) above the aforementioned range. Factor Xa inhibition positively correlated with AT (r = .42; P < .001) and PC (r = .45; P < .001) activities. A negative correlation was found between the FXa inhibition and α-1-antitrypsin concentrations (r = —.33; P = .01) but only in the subgroup with α-1-antitrypsin concentrations ≥2.2 g/L. We confirmed that in most patients with sepsis, the prophylaxis with enoxaparin did not lead to the required FXa inhibition. The inhibition of FXa by enoxaparin depends mainly on the AT and PC activities.

scholarly journals Diurnal Corrected QT Interval and QT Dispersion Variation in Non-Alcoholic Cirrhotic Patients and Healthy Control: A Case-Control Study, Iran

2020 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Taghi Amiriani ◽  
Vahid Khori ◽  
Ali Davarian ◽  
Niloofar Rajabli ◽  
Mahsa Niknam ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Diurnal Variation ◽  
Healthy Subjects ◽  
Alcoholic Cirrhosis ◽  
Qt Dispersion ◽  
Qtc Interval ◽  
Healthy Controls ◽  
Cirrhotic Patients ◽  
The Mean

Background: Cirrhosis could lead to a long corrected QT (QTc) interval in a subgroup of patients, but there are spare data on its diurnal variation. Objectives: The present study aimed to determine the diurnal variation of QTc interval and its relationship to heart rate and blood pressure variation during 24-hour Holter-monitoring in non-alcoholic cirrhosis in comparison with the healthy controls. Methods: The study population comprised 15 patients with non-alcoholic cirrhosis and 15 healthy subjects, undergoing 24-hour electrocardiogram (ECG), heart rate, and blood pressure monitoring. The mean QT interval, mean QTc, maximum and minimum QT, QT dispersion (QT disp), heart rate, and mean arterial blood pressure were measured for each person for 24 hours. Liver stiffness measurement (LSM) was performed by FibroScan® 502 machine (EchoSense, Paris, France, 5 MHz). The results were demonstrated as percentages and mean ± SD. P value ≤ 0.05 was considered significant. Results: Mean QTc was significantly higher in cirrhosis (438 ms) than healthy controls (401.7 ms) (P = 0.03). The mean heart rate was significantly different in cirrhotic patients (79.6 ± 2.9/bpm) compared to healthy controls (72.47 ± 2.0/bpm) (P = 0.05). Conclusions: In this study, QTc was prolonged and increased with the severity of cirrhosis, and its diurnal variation in cirrhosis was different from healthy subjects.

Hyperaggregability Of Platelets In Cancer, Especially In Reference To Genesis Of DIC

1981 ◽  
Author(s):  
H Yamazaki ◽  
Y Yahara ◽  
T Motomiya ◽  
K Tanoue ◽  
I Isohisa ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Time Course ◽  
Mean Value ◽  
Activated Partial Thromboplastin Time ◽  
Healthy Controls ◽  
Triggering Mechanism ◽  
Coagulation Abnormalities ◽  
Activated Platelets ◽  
The Mean

To clarify the role of platelets in the genesis of DIC in cancer, platelets of cancer patients with and without DIC were examined. Patients studied were 29 cases with cancer in stomach, 17 in lung, 7 in pancreas, 6 in liver (hepatoma), 6 in throat, nose and jaw, 2 in the gall bladder and bilary duct, 2 in uterus and 1 each in the small bowel, rectum and prostate, and 1 each with osteosarcoma, mesothelioma and chorionepithelioma. All patients were in stage 3 or 4. 105 healthy controls were also studied. They were evaluated on a scale of coagulation abnormalities, one point was given for each of the following criteria full-filled, and the score (0 to 4) was used. 1. Platelet count<150xl03Anl. 2. Prothrombin time prolonged more than 1 sec over control and/or activated partial thromboplastin time prolonged more than 10 sec over control. 3. Fibrinogen<250 mg/dl (mean fibrinogen value of the cancer patients minus 1 SD). 4. FDP>20 µg/ml. The patients were distributed with 27 % for score 0, 38 % for 1, 20 % for 2, 7 % for 3 and 8 % for 4. Degrees of abnormality in groups with scores of 3 and 4 were significant when compared to scores 0 and 1, but score 2 was not clearly distinguishable. Platelet mode volume in score 4 was smaller than the other groups. Platelet aggregation by adrenaline and ADP decreased in score 3 and 4, while it increased significantly in score 0 and 1 respectively (P<0.01 -0.05). The mean value of plasma β-TG in the cancer patients as a whole (44±24 ng/ml) was significantly higher than that of control (22±13 ng/ml)(P<0.01). PF4 showed the same tendency. During the time course of the disease, hyperaggrega- bility of platelets associated with increases in β-TG and PF4 was observed before an appearance of DIC syndrome in several cases. The results suggest the existence of hyperfunction of platelets in cancer patients and the possibility of triggering mechanism of such activated platelets in the genesis of DIC in cancer.

Thrombin Generation Is Normal in Most Patients with Cirrhosis despite a Prolonged INR.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1826-1826
Author(s):  
Alexander Gatt ◽  
Anne Riddell ◽  
Vincenza Calvaruso ◽  
Michael Makris ◽  
Edward Tuddenham ◽  
...  
Keyword(s):  
Liver Disease ◽  
Tissue Factor ◽  
Patient Group ◽  
Protein C ◽  
Thrombin Generation ◽  
Control Sample ◽  
Normal Subjects ◽  
Sensitivity Index ◽  
Clotting Factors ◽  
The Mean

Abstract Introduction: Advanced liver disease is associated with prolongation of the prothrombin time (PT). In order to decrease the inter-laboratory variability of PT measurement, the international normalised ratio (INR) calculated as the ratio of patient’s PT to a normal (control) sample, raised to the power of the international sensitivity index (ISI) of the particular thromboplastin used was developed. However, the ISI is derived from PT results of patients on warfarin and results cannot be extrapolated to liver patients. Despite this, the INR is still commonly performed to assess bleeding risk in patients with liver disease worldwide. Furthermore the INR is only affected by factors I, II, V, VII, and X and is not influenced by other factors such as factor VIII which is usually raised in hepatic cirrhosis. Recently it has been reportd that thrombomodulin addition (to take into account the protein C pathway) normalises thrombin generation (TG)1 despite these patients having a low TG if thrombomodulin is not used. Aim: We speculated that TG, which is a global assay of coagulation and sensitive to all coagulation factors, when triggered by a low tissue factor (TF) concentration might not correlate with the INR in patients with liver disease and that contact inhibition with corn trypsin inhibitor (CTI) might better reflect the coagulation potential in this patient group. Results: 73 unselected patients with liver cirrhosis due to various diseases and 25 normal subjects were studied. INR and TG using the calibrated automated thrombogram (CAT) at 1pM tissue factor (TF) with CTI, 5pM without CTI and with and without Protac (a Protein C activator) were performed using platelet poor plasma (PPP). The INR range was 0.8–4.0 (mean 1.6). At 5pM TF without Protac, the patient group had a significantly lower endogenous thrombin potential (ETP) than the controls (mean ETP difference 752nM/min; P &lt;0.0001). With Protac, no significant differences could be detected between the 2 groups. However, if the ETP without Protac was divided by the ETP with Protac x 100, the liver group showed more resistance to PC activation (mean % difference 25.4; P 0.0002). At 1pM TF, the mean ETP in the cirrhosis cohort was slightly lower than the normal group (difference between means 216nM/min; P 0.03). However, only 7 (9.6%) patients had ETP values less than the normal range (mean±2SD). No correlation was found between the ETP at 1pM and the INR. The mean FVIII:C was raised at 185.6 (78–420U/dl). Conclusion: TG measured at low TF with CTI is normal in the majority of patients with cirrhosis. These patients are also more resistant to PC activation and have supranormal FVIII:C. Thus most patients have a normal or high thrombin potential despite an abnormal INR. These findings have important implications as in the absence of bleeding, “prophylactic” plasma and clotting factors are unnecessary.

Procoagulant Status In Patients With Immune Thrombocytopenia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3528-3528 ◽  
Author(s):  
Ihosvany Fernández Bello ◽  
Mayte Álvarez Román ◽  
Elena G. Arias Salgado ◽  
Monica Martin Salces ◽  
Miguel Canales ◽  
...  
Keyword(s):  
The Netherlands ◽  
Tissue Factor ◽  
Protein C ◽  
Thrombin Generation ◽  
Red Cells ◽  
Procoagulant Activity ◽  
Platelet Counts ◽  
Significant Difference ◽  
The Mean ◽  
Spearman Test

Abstract Introduction Immune thrombocytopaenia (ITP) is an acquired immune-mediated disorder characterized by mild to severe thrombocytopaenia caused by autoantibodies against platelet proteins. Bleeding risk in patients with ITP is increased with platelet counts less than 20 or 30 x 109/L. However, patients with ITP often have few bleeding symptoms despite very low platelet counts suggesting the existence of compensatory mechanisms. Moreover, an increased risk for thrombosis in patients with ITP has been described (Nørgaard M, 2012). It has been recently reported that increased production of platelet- and red cells-derived microparticles (MP) might be one of the causes of increased thrombotic risk in ITP patients (Sewify, 2013). Objective The aim of this study was to evaluate the microparticle-associated and plasma procoagulant activities in ITP patients with thrombocytopaenia. Methods Sixty-eight patients with chronic ITP and platelet count less than 50 x 109/L and twenty-two healthy controls were included. Platelet counts were determined with a Coulter Ac. T Diff cell counter (Beckman Coulter, Madrid, Spain). Citrated blood was centrifuged at 1,500 g for 15 min at 23°C. Platelet-poor plasma obtained was additionally centrifuged twice at 23°C (15 min at 1,500 g, and 2 min at 13,000 g) and aliquots were stored at -70ºC until analysis. Phosphatidylserine-MP (Ph-MP) and tissue factor-MP (TF-MP) dependent procoagulant activities were determined with the ZYMUPHEN kits (Hyphen BioMed, Neuville sur Oise, France) following the manufacturer’s instructions. Plasma thrombin generation was measured using the Calibrated Automated Thrombogram (CAT) test as described by Hemker et al (2000) at a final concentration of 1 pM tissue factor and 4 μM phospholipids (PPP-Reagent LOW, Thrombinoscope BV, Maastricht, The Netherlands). We evaluated the endogenous thrombin potential (ETP, the total amount of thrombin generated over time); the lag time (the time to the beginning of the explosive burst of thrombin generation); the peak height of the curve (the maximum thrombin concentration produced); and the time to the peak. To test resistance to protein C, CAT experiments were performed without and with the addition of thrombomodulin (TM) (PPP and PPP with thrombomodulin reagents, Thrombinoscope BV, Maastricht, The Netherlands). Results were expressed as the ratio [(ETP with TM)/(ETP without ETP)]x100. Results were expressed as mean±SD. Comparisons of quantitative variables were made with Mann-Whitney test and correlations with Spearman test. Values of p≤0.05 were considered statistically significant. Results Ph-MP associated procoagulant capacity in ITP patients was higher than in controls (p<0.05) whereas MP-TF associated procoagulant activity was practically negligible in both groups. Plasma procoagulant activity was higher in ITP patients than in controls (ETP: 1604±616 nM x min in ITP patients and 1302±416, p=0.012 in controls; Peak: 328±123 nM in ITP patients and 203±74 nM in controls, p<0.001). We tested whether the higher procoagulant activity of plasma from ITP patients was due to a resistance to protein C. We observed that the mean Ratio value in ITP patients was slightly higher than the mean Ratio of controls (60±18 and 50±13 respectively, p=0.034). Despite this significant difference in the Ratio, no correlation was found between this value and the CAT parameters. Conclusion ITP patients with thrombocytopaenia had a higher Ph-MP associated and plasma procoagulant activity than controls. The fact that the increased MP-procoagulant activity was not accompanied by a higher TF-MP associated procoagulant activity brings further support to the previous observation that MPs in ITP patients are from platelets and red cells, as both cells express very low levels of TF (Sewify, 2013). Regarding the increased plasma procoagulant capacity observed in ITP patients, our results suggest that resistance to protein C does not seem to be the main mechanism involved. References • Nørgaard M. Thromb Res. 2012;130 Suppl 1:S74-75. • Sewify EM, et al. Thromb Res. 2013;131:e59-63. Hemker HC, et al. Thromb Haemost 2000;83:589-9. Disclosures: No relevant conflicts of interest to declare.

Effects of Hereditary and Acquired Risk Factors of Venous Thrombosis on a Thrombin Generation-Based APC Resistance Test

2002 ◽  
Vol 88 (07) ◽  
pp. 5-11 ◽  
Author(s):  
Joyce Curvers ◽  
M. Christella Thomassen ◽  
Janet Rimmer ◽  
Karly Hamulyak ◽  
Jan van der Meer ◽  
...  
Keyword(s):  
Risk Factors ◽  
Venous Thrombosis ◽  
Protein C ◽  
Thrombin Generation ◽  
Contraceptive Use ◽  
Hormone Replacement ◽  
Protein S ◽  
Resistance Test ◽  
Prothrombin G20210a ◽  
Apc Resistance

SummarySeveral hereditary and acquired risk factors for venous thromboembolism (VTE) are associated with impaired down-regulation of thrombin formation via the protein C pathway. To identify individuals at risk, functional tests are needed that estimate the risk to develop venous thrombosis.We determined the effects of hereditary and acquired risk factors of venous thrombosis on an APC resistance test that quantifies the influence of APC on the time integral of thrombin formation (the endogenous thrombin potential, ETP) initiated in plasma via the extrinsic coagulation pathway. APC sensitivity ratios (APCsr) were determined in plasma from carriers of factor VLeiden (n = 56) or prothrombin G20210A (n = 18), of individuals deficient in antithrombin (n = 9), protein C (n = 7) or protein S (n = 14) and of women exposed to acquired risk factors such as hormone replacement therapy (n = 49), oral contraceptive use (n = 126) or pregnancy (n = 35). We also analysed combinations of risk factors (n = 60).The thrombin generation-based APC resistance test was sensitive for the factor VLeiden and prothrombin G20210A mutation, to protein S deficiency, hormone replacement therapy, oral contraceptive use and pregnancy. The assay was not influenced by antithrombin-or protein C deficiency. The presence of more than one risk factor of venous thrombosis resulted in more pronounced APC resistance. The APCsr of individuals with a single or combined risk factors of VTE correlated well with reported risk increases.The thrombin generation-based APC resistance test identifies individuals at risk for venous thrombosis due to acquired risk factors and/or hereditary thrombophilic disorders that affect the protein C pathway.

Patients with severe sepsis vary markedly in their ability to generate activated protein C

Blood ◽  
2004 ◽  
Vol 104 (13) ◽  
pp. 3958-3964 ◽  
Author(s):  
Patricia C. Y. Liaw ◽  
Charles T. Esmon ◽  
Kamyar Kahnamoui ◽  
Shelley Schmidt ◽  
Sarah Kahnamoui ◽  
...  
Keyword(s):  
Severe Sepsis ◽  
Protein C ◽  
Thrombin Generation ◽  
Activated Protein C ◽  
Cell Protein ◽  
Health Evaluation ◽  
On Demand ◽  
Evaluation Scores ◽  
Plasma Markers

Abstract Activated protein C (APC) supplementation significantly reduces mortality in patients with severe sepsis, presumably by down-regulating coagulation, inflammation, and apoptosis. In vivo, endogenous APC is generated from protein C (PC) “on demand” in response to elevated thrombin levels. Thrombomodulin and endothelial cell protein C receptor are endothelial receptors required to generate APC endogenously. Since these receptors may be down-regulated in sepsis, we measured plasma markers of APC generation in 32 patients with severe sepsis to determine whether APC generation is impaired and whether markers of APC generation correlate with 28-day mortality. Relative to normals, all patients had elevated F1 + 2 and thrombin-antithrombin complex (TAT) levels (markers of thrombin generation and inhibition, respectively), and 28 of 32 patients had reduced PC levels. In 20 patients, APC levels paralleled elevated F1 + 2 levels, whereas 12 patients had low APC levels despite elevated F1 + 2 levels, suggesting that APC generation is impaired in the latter. No significant differences exist between survivors and nonsurvivors with respect to baseline PC levels, F1 + 2 levels, and APACHE II (acute physiology and chronic health evaluation) scores. Baseline APC levels were higher in survivors (P = .024), and baseline F1 + 2/APC ratios were lower in survivors (P = .047). Larger studies are warranted to establish whether APC generation profiles aid in managing sepsis. (Blood. 2004;104:3958-3964)

Clinical Experience with Drotrecogin Alfa in Treating Gram-Positive and -Negative Pathogens in Patients with Severe Sepsis

2004 ◽  
Vol 52 (7) ◽  
pp. 470-474 ◽  
Author(s):  
Lawrence A. Cone ◽  
Richard A. Stone ◽  
Kenneth Jesser ◽  
Richard Nelson
Keyword(s):  
Severe Sepsis ◽  
Mortality Rate ◽  
Organ Failure ◽  
Protein C ◽  
Antimicrobial Agents ◽  
Survival Rates ◽  
Activated Protein C ◽  
Gram Positive ◽  
Gram Negative ◽  
Local Disease

BackgroundNewer concepts in the management of severe sepsis and, in particular, in the understanding of the relationship between proinflammatory and procoagulant activities during severe infection have led to the introduction of activated protein C (drotrecogin) into the therapeutic program. The combination of effective antimicrobial therapy, aggressive supportive care, and efforts to antagonize procoagulants and inhibitors of fibrinolysis was used in this study.MethodsWe treated 12 patients with severe sepsis using this combination of antimicrobial agents and drotrecogin. All patients presented with hypotension and organ failure and some with multiple organ failure. Infected patients were separated into those with gram-positive and those with gram-negative infections.ResultsIn contrast to an expected mortality rate of nearly 40% in this group of patients, only 2 (9%) expired. Both deaths were due to infection by gram-negative organisms in patients with complicated abdominal infections and concurrent cancer. All patients with gram-positive organisms survived.ConclusionThose patients with infections caused by gram-positive organisms seemed to have a better prognosis than those with gram-negative infections, perhaps because their illnesses are less complicated by local disease. Although our study is small, it suggests that activated protein C will have a significant beneficial effect on the future treatment of severe sepsis and can reduce the mortality rate significantly. Further improvement in survival rates will require more effective treatment of local disease and associated noninfectious ailments.

Patients with Antineutrophil Cytoplasmic Antibodies Associated Vasculitis in Remission Are Hypercoagulable

2013 ◽  
Vol 40 (12) ◽  
pp. 2042-2046 ◽  
Author(s):  
Marc Hilhorst ◽  
Kristien Winckers ◽  
Benjamin Wilde ◽  
René van Oerle ◽  
Hugo ten Cate ◽  
...  
Keyword(s):  
Protein C ◽  
Tissue Factor Pathway Inhibitor ◽  
Severe Renal Impairment ◽  
Protein S ◽  
Endothelial Activation ◽  
Antineutrophil Cytoplasmic Antibodies ◽  
Low Grade ◽  
Healthy Controls ◽  
Free Protein ◽  
Tissue Factor Pathway

Objectives.The risk of venous thromboembolism (VTE) is increased in patients with antineutrophil cytoplasmic antibodies (ANCA) associated vasculitides (AAV) as compared to healthy subjects. The mechanisms underlying this increased occurrence of VTE are not completely understood. We hypothesize that AAV patients in remission are more procoagulant than healthy controls.Methods.Patients with AAV in remission and no VTE for the last 6 months were included. Patients with severe renal impairment (serum creatinine > 250 μmol/l) were excluded. Age and sex matched healthy controls were included. The endogenous thrombin potential (ETP) was determined together with hemostatic variables: fibrinogen, D-dimers, factor VIII (FVIII), tissue factor pathway inhibitor (TFPI), protein C, and free protein S.Results.Thirty-one patients were included. In 27 patients not taking anticoagulants, ETP was measured and found to be elevated: 137.1% as compared to a median of 90.0% for healthy controls (p < 0.01). Fibrinogen and D-dimer levels were not elevated in patients (median 3.5 g/l and 279 μg/l, respectively). FVIII and TFPI levels were also significantly increased in patients as compared to healthy controls (159% vs 137%; 122.5% vs 101%, respectively), whereas protein C and free protein S levels were not elevated (126.5% vs 118.6% and 124.6% vs 118.3%, respectively).Conclusion.Patients with AAV in remission are more procoagulant than healthy controls, as indicated by an increased ETP. The increased FVIII level measured in these patients suggests persistence of endothelial activation and/or dysfunction. This endothelial dysfunction may cause a continuous low-grade procoagulant state.

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