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Peter Quehenberger

Publications and source records attributed to Peter Quehenberger.

At least 19 recordsLinked to original sources
PubMed2007

Tissue factor-positive microparticles: cellular origin and association with coagulation activation in patients with colorectal cancer.

The pathogenesis of hypercoagulability in cancer is not entirely understood. We hypothesized that in cancer patients circulating tissue factor-positive microparticles (TF (+) MPs) are increased and associated with hemostatic system activation. In 20 patients with advanced colorectal cancer and in 20 age- and sex-matched controls, number and cellular origin of TF (+) MPs were determined in plasma by flow cytometry. D-dimer was determined as an indicator of hemostatic system activation. Compared to controls, the median (interquartile range) number of TF (+) MPs was two-fold higher in cancer patients: 25.9 (15.4 - 42.0) x 10 (3) /ml plasma versus 13.1 (11.9 - 19.7) x 10 (3) /ml plasma, p = 0.007. This was mainly due to a higher amount of TF (+) MPs from platelets (13.4 [5.0 - 17.4] x 10 (3) /ml plasma vs. 5.8 [4.5 - 7.5] x 10 (3) /ml plasma, p = 0.017). TF (+) MPs correlated with D-dimer ( ? = 0.48, p = 0.002). High levels of TF (+) MPs in cancer patients and their correlation with D-dimer suggest that TF (+) MPs might be involved in hemostasis activation in cancer patients.

Blood Coagulation↗
PubMed2006

Clinical evaluation of a new functional test for detection of activated protein C resistance (Pefakit APC-R Factor V Leiden) at two centers in Europe and the USA.

A new clotting assay, Pefakit APC-R Factor V Leiden (Pentapharm Ltd., Switzerland), for the detection of an increased resistance of coagulation factor V against degradation by activated protein C, caused mainly by the factor V Leiden mutation, was evaluated in clinical studies at two University Centers in Europe and the US. The performance was compared with the performance of the routinely used predicate device COATEST APC Resistance V (Chromogenix IL, USA). Both tests were run in parallel on a STA-R analyzer (Diagnostica Stago, France). Samples from subjects undergoing routine laboratory thrombophilia screening were examined, 187 at the Institute of Medical and Chemical Laboratory Diagnostics (IMCLD), University of Vienna, Austria, and 236 at the Duke University Medical Center (DUMC), Durham/Raleigh NC, USA. All samples were analyzed for factor V Leiden mutation and prothrombin 20210 G/A mutation using standard PCR methods. The data show that the Pefakit APC-R Factor V Leiden assay discriminates very well between healthy controls and carriers of the factor V Leiden mutation, even in patients with lupus anticoagulant or with deficiency in Protein C or Protein S. Furthermore, this new test is able to discriminate well between heterozygous and homozygous carriers of the factor V Leiden mutation. In both studies the Pefakit assay showed 100% sensitivity and 100% specificity for detection of the factor V Leiden mutation, compared to 93.1% sensitivity and 93.0% specificity for the COATEST APC Resistance V in the IMCLD study and 93.9% sensitivity and 95.6% specificity in the DUMC study. The new test has PCR-like discrimination power which will help to decrease costs by reducing the need for PCR verification of borderline cases.

Activated Protein C Resistance↗
PubMed2006

The formation of platelet-leukocyte aggregates varies during the menstrual cycle.

Platelet-leukocyte aggregates are considered to play a significant role in blood coagulation and inflammatory processes. We hypothesized that hormonal changes during the menstrual cycle affect the formation of heterotypic aggregates and therefore may constitute cycle-dependent variations of the susceptibility for thromboembolic events and inflammatory disease. We therefore measured platelet-leukocyte interaction by the determination of platelet-leukocyte aggregates (PLA), platelet P-Selectin expression, and platelet fibrinogen receptor activation by PAC-1 binding in 20 healthy women during their menstrual cycle by flow cytometry. The number of platelet-granulocyte aggregates (PGA) and platelet-monocyte aggregates (PMA) was higher at ovulation compared to any other time-point of the menstrual cycle (p = 0.005, p = 0.022, respectively). Likewise, P-Selectin expression peaked on day 14 (p = 0.040). The course of PLA formation during the menstrual cycle followed the course of estrogen levels, strongly suggesting direct effects of estrogen on platelet-leukocyte interaction. The susceptibility to form platelet-leukocyte aggregates that are inducible in vitro by a suboptimal concentration of thrombin receptor activating peptide-6 decreased slightly during the transition from day 1 to 14 (p = 0.040). These data indicate that platelet function varies during particular phases of the normal menstrual cycle.

Adult↗
PubMed2006

Treatment of adult patients with sepsis-induced coagulopathy and purpura fulminans using a plasma-derived protein C concentrate (Ceprotin).

BACKGROUND AND OBJECTIVES: The aim of this study was to document the effects of supplementation with a plasma-derived protein C concentrate in adult patients with infectious purpura fulminans. MATERIALS AND METHODS: We report the effect of the administration of a human protein C concentrate (Ceprotin, Baxter, Vienna, Austria) in eight adult patients with purpura fulminans. Five patients received the concentrate as level-adjusted continuous infusion (10 U/kg/h, target protein C activity 100%) and three patients received the concentrate as bolus infusions (100 U/kg every 6 h) in addition to standard sepsis therapy. Heparin, fresh-frozen plasma, antithrombin- and fibrinogen concentrates, low-dose rtPA, and platelet transfusions were given when appropriate. RESULTS: Six patients had overt disseminated intravascular coagulation: platelets, 19 g/l; fibrinogen, 60 mg/dl; antithrombin, 47%; prothrombin time, 32%; activated partial thromboplastin time (APTT), 88 s; d-dimer, 66 microg/ml; protein C activity, 29% (medians). Five patients had septic shock, six renal failure and four respiratory failure. Patients received between 5000 and 77,000 U of protein C concentrate over 2.5 days (median); the protein C activity increased to 184% (median) and coagulopathy resolved within 3 days in seven of the eight patients. Six patients survived, one died early from fulminant sepsis, and one died after 14 days from candida sepsis. CONCLUSIONS: Our data suggest that treatment with a plasma-derived protein C zymogen concentrate might be a useful support in adult patients with purpura fulminans.

Adolescent↗
PubMed2006

Extended monitoring of hemostatic activation after varicose vein surgery under general anesthesia.

BACKGROUND: Postoperative heparin prophylaxis after stripping of the long saphenous vein is a matter of controversial discussion, and practices vary by surgeon and country. OBJECTIVE: The aim of this study was to assess the extent of hypercoagulability by continued monitoring of activation markers of coagulation and fibrinolysis for a period of 3 weeks after stripping of the long saphenous vein and concomitant phlebectomy. METHODS: Including 21 patients, the following markers were measured preoperatively and on postoperative day 1, 2, 3, 7, 14, and 21: Activation products of coagulation: thrombin-antithrombin complex (TAT), thrombus precursor protein (TPP), and prothrombin-fragment F1+2 (F1+2), and markers of fibrinolysis: plasmin-alpha(2)-antiplasmin complexes (PAP), D-Dimer, tissue plasminogen activator (t-PA) antigen, and plasminogen activator inhibitor 1 (PAI-1) antigen. RESULTS: TAT levels increased significantly until day 3 (p=.008) and normalized within 14 days. TPP levels increased significantly until day 7 (p=.02), decreasing to initial values within 21 days. PAP complexes increased significantly until day 2 (p=.02) reducing to baseline within the observation period. D-Dimer levels increased immediately after surgery (p<.001) until day 14 (p<.001) and returned to baseline until day 21. CONCLUSIONS: Significant hemostatic activation after varicose vein surgery was observed and persisted until 3 weeks postoperatively, indicating that heparin prophylaxis for 2 to 3 weeks is advisable for at-risk patients.

Adult↗
PubMed2006

Preeclampsia and pregnancy loss in women with a history of venous thromboembolism and prophylactic low-molecular-weight heparin (LMWH) during pregnancy.

Limited data are available regarding complications of pregnancy and pregnancy outcome under prophylaxis with low-molecular-weight heparin (LMWH) in women with a history of thromboembolism (TE). We retrospectively evaluated pregnancy complications in a cohort of 80 women. All had a history of TE (76 venous, two arterial and two venous and arterial) and received prophylactic LMWH during 86 pregnancies. The rate of preeclampsia and stillbirth in these women was compared to that of a control group of 313 women without a history of TE and LMWH. Prophylaxis was started at a median of 10 weeks of gestation and usually continued until six weeks post partum. In 94% of the cases the outcome of pregnancy was favourable with a live birth. Four pregnancies (4.7%) ended in miscarriage. Two (2.3%) pregnancies were complicated by a thromboembolic event (one deep leg vein thrombosis and PRIND, respectively). One patient developed HELLP-syndrome. Severe preeclampsia occurred in three (3.8%) and stillbirth in one (1.3%) of the patients (n = 80), whereas this was the case in four (1.3%, odds ratio 3.01; 95% confidence interval (CI) 0.66-13.73, p = 0.15) and 10 (3.2%, OR = 0.38; 95% CI 0.05-3.04, p = 0.72) control women. Mean birth weight and standard deviation of infants was 3,160 +/- 930 g in patients and 3,300 +/- 540 g in controls (p = 0.11). We conclude that a favourable pregnancy outcome in women with a history of thromboembolism who use prophylactic LMWH during pregnancy can be expected. There was a trend towards a higher risk of preeclampsia, and these women should be carefully monitored for this complication.

Abortion, Spontaneous↗
PubMed2006

Anti-beta2-glycoprotein I antibodies are associated with pregnancy loss in women with the lupus anticoagulant.

The presence of lupus anticoagulant (LA) predisposes to fetal loss and to venous and arterial thrombosis; however, a subgroup of women is unaffected by pregnancy loss. Currently, no predictive markers are available for the identification of women positive for LA at increased risk for pregnancy loss. It was the aim of our study to investigate whether increased anti-beta2-GPI-antibodies predict pregnancy loss in women positive for LA. We performed a cross-sectional study in a cohort of 39 women with persistent LA, who had in total 111 pregnancies. Fifteen women had exclusively normal pregnancies (30 pregnancies) and 24 women had pregnancy losses (81 pregnancies). Anti-beta2-GPI-antibodies were determined using a semiquantitative enzyme linked immunoassay (QUANTA Lite beta2 GPI IgG and IgM; Inova Diagnostics). Increased levels of anti-beta2-GPI antibodies were significantly associated with pregnancy loss [odds ratio (OR) 9.6, 95% confidence interval (CI) 1.6-56.4]. This risk was even higher in the subgroup of women (n = 16) with more than two miscarriages or fetal loss after the first trimester [OR 13.1, 95% CI 1.4-126.3]. There was no significant association between anticardiolipin antibodies and pregnancy loss [OR 3.5, 95% CI 0.7-17.6]. The co-existence of anti-beta2-GPI and anticardiolipin antibodies was also predictive for pregnancy loss [OR 6.1, 95% CI 1.3-29.7]. Interestingly, the prevalence of thrombosis was similar between women with normal pregnancy (87%) and those with pregnancy loss (75%). We conclude that increased levels of anti-beta2-GPI antibodies are predictive for pregnancy loss among women positive for LA, and that prophylactic treatment should be considered in these women even without a history of previous pregnancy loss.

Adult↗
PubMed2005

Prognostic impact of fibrinogen in carotid atherosclerosis: nonspecific indicator of inflammation or independent predictor of disease progression?

BACKGROUND: Fibrinogen is a key factor in the coagulation cascade, it exhibits proinflammatory properties, and it is suggested to play a pivotal role in atherogenesis. We investigated whether fibrinogen predicts future progression of carotid atherosclerosis, analyzing whether fibrinogen levels add to the prognostic information of other inflammatory parameters. METHODS: We prospectively studied 1268 consecutive patients without recent (12 months) symptoms from cerebrovascular disease. Patients underwent serial ultrasound investigations in 6- to 9-month intervals, categorizing carotid arteries as 0% to 29%, 30% to 49%, 50% to 69%, 70% to 89%, or 90% to 99% stenosed, or occluded. Fibrinogen levels were determined at baseline and follow-up. The risk for progressive carotid atherosclerosis according to fibrinogen levels was calculated, adjusting for traditional risk factors and other inflammatory parameters (C-reactive protein and serum amyloid A). RESULTS: Progression of carotid atherosclerosis was found in 117 of 1268 patients (9.2%) after a median of 8 months (range 6 to 18). Adjusted hazard ratios for atherosclerosis progression with increasing quartiles of baseline fibrinogen were 1.83 (P=0.037), 2.09 (P=0.008), and 2.45 (P=0.002), respectively, compared with the lowest quartile. Fibrinogen at follow-up also was associated with progressive disease (P=0.004). However, additionally adjusting for other inflammatory parameters diminished these associations to a nonsignificant level. CONCLUSIONS: Elevated fibrinogen, reflecting the level of inflammatory activity, is associated with progression of carotid atherosclerosis, as it was demonstrated previously for other inflammatory parameters. However, this association seems to be nonspecifically related to the extent of the inflammatory process in atherosclerotic disease rather than to specific properties of fibrinogen.

Aged↗
PubMed2005

The course of anticardiolipin antibody levels under immunoadsorption therapy.

BACKGROUND: The emergence of anticardiolipin antibodies in patients with systemic lupus erythematosus is a serious occurrence in regard to a high risk for thrombosis and thromboembolic complications, fetal loss, and renal insufficiency. In an observational analysis, we studied anticardiolipin antibodies during immunoadsorption therapy. METHODS: We analyzed the magnitude and time course of serum concentrations of the immunoglobulin G (IgG) and IgM subtypes of anticardiolipin antibodies (CIgG and CIgM) along with IgG and IgM, antinuclear antibodies, and antibodies to double-stranded DNA before and after single immunoadsorption sessions and their long-term course in 11 patients with systemic lupus erythematosus. RESULTS: Single immunoadsorption sessions (n = 842) led to a rapid decline in CIgG and CIgM levels by 62.94% +/- 21.60% and 42.02% +/- 22.14%, respectively (P < 0.0001), along with a corresponding decline in serum levels of antinuclear antibodies (65.04% +/- 18.83%), antibodies to double-stranded DNA (64.67% +/- 21.20%), IgG (58.11% +/- 16.84%), and IgM (32.15% +/- 15.58%). Reduction rates of CIgG and CIgM levels were greater when high initial concentrations (P < 0.0001) and low IgG levels (P < 0.0001) were present. Mean reductions in pretreatment values of CIgG and CIgM during 6 months of immunoadsorption therapy were 42.85% +/- 39.94% and 29.39% +/- 70.41% (mean number of sessions/patient = 21.55) and for the 1-year period were 63.20% +/- 22.49% and 58.05% +/- 40.16% (mean number of sessions/patient = 30.46). CONCLUSION: We observed that immunoadsorption therapy is an effective method to reduce anticardiolipin antibody levels rapidly and keep them at a low level in the long term.

Abortion, Habitual↗
PubMed2005

High dose dexamethasone increases circulating P-selectin and von Willebrand factor levels in healthy men.

Although glucocorticoids are widely used in a number of inflammatory disorders associated with endothelial and platelet activation, their effect on the endothelium and platelets in humans remain poorly defined. Hence,we measured changes of a specific endothelial cell marker (von Willebrand factor [vWF]) and of a platelet marker (soluble P-selectin) by infusing therapeutic doses of dexamethasone (0.04 mg/kg and 1.0 mg/kg b.i.d on two days) or placebo into nine healthy men. Venous citrated plasma was obtained before infusion, and at 24 and 48 h. Compared to baseline levels, we found increased levels of vWF at both time points at the higher dose (p=0.011). Plasma levels of sP-selectin rose at 48 h after the high dose (p=0.017). Human umbilical endothelial cells were cultured in the presence or absence of dexamethasone (0, 0.01, 1 microM), to determine the possible mechanism for the increase in vWF. The vWF-mRNA levels as quantified by RT-PCR increased 2-fold (p<0.05), and the vWF-concentrations in cell lysates increased by 38% (p<0.05), whereas the vWF-concentrations in the supernatants were unaffected. In summary, high dose DEXA increases sP-selectin and vWF. The probable underlying mechanism for the latter was a DEXA induced up-regulation of vWF-mRNA transcription. Together, this indicates that high dose glucocorticoids may enhance haemostasis, which could be beneficial under certain conditions, but which may also contribute to adverse vascular events by increasing platelet activation and vWF dependent thrombosis.

Adult↗
PubMed2005

Inflammation in patients with lupus anticoagulant and implications for thrombosis.

OBJECTIVE: The underlying mechanism of the prothrombotic state associated with the lupus anticoagulant (LAC) has not been fully elucidated. Evidence suggests involvement of inflammation in arterial and venous thrombosis, and it may be hypothesized that subclinical inflammation aggravates the tendency to thrombosis in patients with LAC. METHODS: Levels of high sensitivity C-reactive protein (hs-CRP), fibrinogen, and factor VIII (VIII) were measured in 38 patients with LAC and a history of thrombosis, 27 with LAC and no history of thrombosis, and 33 healthy controls. RESULTS: Hs-CRP, fibrinogen, and factor VIII levels were significantly higher in patients with LAC with thrombosis (hs-CRP median = 0.3 mg/dl, interquartile range, IQR, 0.11-0.62, p < 0.001 vs controls; fibrinogen mean = 395 +/- 90 SD mg/dl, p < 0.001; factor VIII mean = 181 +/- 50%, p = 0.005) as well as in those without thrombosis (median = 0.21, IQR 0.10-0.12, p < 0.001; mean = 378 +/- 91, p = 0.003; mean = 179 +/- 39, p = 0.015) compared to controls (median = 0.07, IQR 0.03-0.12; mean = 308 +/- 48; mean = 137 +/- 39). After adjustment for age, body mass index, smoking status, and blood group (only for factor VIII) the differences between LAC groups and controls remained significant, except for the comparison of fibrinogen between patients without thrombosis and controls. The association between LAC and markers of inflammation was confirmed using linear regression analysis. Markers of systemic inflammation did not differentiate between LAC patients with and without thrombosis (p = 0.829 for hs-CRP, p = 0.649 for fibrinogen, p = 0.996 for factor VIII). CONCLUSION: Our results show that LAC is associated with an inflammatory state. However, there was no evidence for an association between inflammatory markers and thromboembolism in patients with LAC.

Adult↗
PubMed2004

Thrombin-activatable fibrinolysis inhibitor and the risk for recurrent venous thromboembolism.

The impact of fibrinolysis for predicting the risk for recurrent venous thromboembolism (VTE) is low. We prospectively followed up 600 patients with a first VTE and evaluated the thrombin-activatable fibrinolysis inhibitor (TAFI) as a risk factor for recurrence. A high TAFI level (75th or higher percentile in thrombosis patients) was associated with a 2-fold higher risk for recurrence compared with lower levels. The probability of recurrence 2 years after anticoagulation was 14.5% (95% confidence interval [CI], 8.6-20.4) among patients with high TAFI levels and 6.8% (95% CI, 4.3-9.3) among patients with lower levels (P =.006). Our data also support the concept of a linkage between fibrinolysis and the coagulation system. Patients with high TAFI levels had significantly higher levels of factors XI, VIII, and IX, and a high risk of recurrence was seen among patients with high TAFI levels and high levels of one of these factors. The relative risk (RR) for recurrence was highest among patients with high TAFI and high factor XI (RR, 2.9; 95% CI, 1.3-6.9), high factor VIII (RR, 6.5; 95% CI, 2.9-14.8), or high factor IX (RR, 2.0; 95% CI, 1.0-3.9) levels compared with patients with low levels of TAFI and one of these factors.

Anticoagulants↗
PubMed2004

Prospective evaluation of coagulation activation in pregnant women receiving low-molecular weight heparin.

Pregnancy is a major risk factor for venous thromboembolism (VTE), and low-molecular weight heparin (LMWH) seems to be safe and effective in pregnant women. Normal pregnancy is accompanied by a state of hypercoagulability, indicated by an increase in markers of coagulation activation. In a prospective cohort study, we followed 61 women who received LMWH thromboprophylaxis throughout pregnancy because of a history of VTE, hereditary thrombophilia and/or previous pregnancy-related complications. The control group consisted of 113 healthy pregnant women without antithrombotics. D-Dimer, prothrombin fragment F1+2 (F1+2) and the resistance to activated protein C (APC-ratio) were measured in all women during the first, second and third trimester. Patients and controls did not significantly differ with regard to baseline characteristics and pregnancy outcome. A (recurrent) VTE was seen in one patient despite LMWH. D-Dimer levels significantly increased among patients and controls during pregnancy (p < 0.0001), and were significantly higher among patients compared with the controls (p <0.0001) [395 ng/ml (95% CI 340-458) and 249 ng/ml (95%CI 234-266); 710 ng/ml (95% CI 602-838) and 475 ng/ml (95% CI 431-523); 1089 ng/ml (95% CI 931-1273) and 822 ng/ml (95% CI 741-911); respectively]. Levels of F1+2 significantly increased while the APC-ratio significantly decreased during pregnancy among patients and controls. Despite LMWH, pregnancy is accompanied by a substantial activation of the coagulation system.

Adult↗
PubMed2004

High plasma heparin cofactor II activity protects from restenosis after femoropopliteal stenting.

High heparin cofactor II (HCII) activity has recently been described to protect from coronary instent restenosis, presumably by inactivating thrombin in injured arteries. In this study, we investigated the association of HCII activity and restenosis after femoropopliteal stenting. We studied 63 consecutive patients with peripheral artery disease who underwent femoropopliteal stent implantation after initial failure of plain balloon angioplasty due to a significant residual stenosis (>30% lumen diameter reduction) or a flow limiting dissection. HCII activity was measured before stenting and patients were followed for median 10 months (interquartile range 6 to 17) for the occurrence of a first instent restenosis, defined as a >50% lumen diameter reduction by color coded duplex sonography and confirmed by angiography. Cumulative freedom from restenosis at 6 and 12 months in patients with lower HCII activity (100%, lower tertile, n=20) was 84% and 35% as compared to 93% and 72% in patients with high HCII activity (>100%, middle and upper tertile, n=43; p=0.024 by Log Rank test). Adjusting for the material of the implanted stents (nitinol vs. Wallstents), patients with a high HCII activity had a 0.39-fold reduced risk for instent restenosis (95% CI 0.17 to 0.90, p=0.028), additional adjustment for diabetes mellitus, poor run-off, critical limb ischemia and cumulative length of the stented segment did not alter the observed effect. Higher activity of heparin cofactor II may exert a protective effect against instent restenosis also in the femoropopliteal vessel area, confirming a prior observation after coronary stenting.

Aged↗
PubMed2003

D-dimer levels and risk of recurrent venous thromboembolism.

CONTEXT: Widespread screening of patients with venous thromboembolism (VTE) for thrombophilic risk factors has become common clinical practice. Because of the increasing number of risk factors, assessing the risk of recurrence in an individual patient is intricate; therefore, a laboratory method that measures multifactorial thrombophilia is required. OBJECTIVE: To prospectively study the relationship between the risk of recurrent VTE and D-dimer, a global marker of coagulation activation and fibrinolysis. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study of 610 patients older than 18 years who were treated with oral anticoagulants for at least 3 months with a first spontaneous VTE, in whom D-dimer levels were measured shortly after discontinuation of oral anticoagulation. The study was conducted at the Department of Internal Medicine I, University Hospital, Vienna, Austria. Patients entered the study at time of discontinuation of oral anticoagulants and were observed at 3-month intervals during the first year and every 6 months thereafter from July 1992 to October 2002. MAIN OUTCOME MEASURE: Objectively documented symptomatic recurrent VTE. RESULTS: A total of 79 (13%) of 610 patients had recurrent VTE with a mean observation time of 38 months. Patients with recurrence had significantly higher D-dimer levels compared with those without recurrence (553 ng/mL vs 427 ng/mL, P =.01). Compared with patients with D-dimer levels of 750 ng/mL or higher, the relative risk (RR) of recurrence was 0.6 (95% confidence interval [CI], 0.3-1.4), 0.6 (95% CI, 0.3-1.2), and 0.3 (95% CI, 0.1-0.6) in patients with D-dimer levels of 500 to 749 ng/mL, 250 to 499 ng/mL, and less than 250 ng/mL, respectively. The cumulative probability of recurrent VTE at 2 years was 3.7% (95% CI, 0.9%-6.5%) among patients with D-dimer levels of less than 250 ng/mL compared with 11.5% (95% CI, 8.0%-15.0%) among patients with higher levels (P =.001). Patients with D-dimer levels of less than 250 ng/mL had a 60% lower RR of recurrence compared with patients with higher levels (RR, 0.4; 95% CI, 0.2-0.8). CONCLUSION: Patients with a first spontaneous VTE and a D-dimer level of less than 250 ng/mL after withdrawal of oral anticoagulation have a low risk of VTE recurrence.

Adult↗
PubMed2003

Validation of a novel tissue factor assay in experimental human endotoxemia.

BACKGROUND: Nuclear factor kappa B (NF-kappa B) activation and tissue factor (TF) expression may contribute to lethality in sepsis. Inappropriate in vivo expression of TF is likely responsible for fibrin deposition in sepsis-associated disseminated intravascular coagulation (DIC). Clinical assessment of TF expression has remained a major challenge. No point-of-care assays are currently available to measure the level of TF activity in whole blood. The current study examined the suitability of the TiFaCT assay as a point-of-care assay to detect TF expression. METHODS: 30 healthy male volunteers received 2 ng/kg of LPS. Tissue factor-dependent coagulation was quantified with a novel assay called tissue factor clotting time (TiFaCT), and by measurement of activation markers of downstream coagulation. RESULTS: Ex vivo addition of anti-TF antibodies to blood slightly increased clotting times at 0-24 h (p<0.01) indicating that some tissue factor activity was present in whole blood at any time. LPS bolus infusion decreased TiFaCT clotting time by -23% compared to baseline (p<0.01), when in vivo clotting increased, as demonstrated by a 10-fold increase in prothrombin fragment levels (F1+2). Ex vivo incubation with LPS considerably shortened TiFaCT (from 1000s to 400s as compared to control incubation; p<0.01). This effect was blunted at 2-4 h after LPS infusion (i.e. the time of monocytopenia), but twofold enhanced 24 h after LPS challenge (p<0.01). CONCLUSIONS: In summary, the TiFaCT assay was validated in our in vivo model of LPS-induced coagulation. It detected minute quantities of circulating TF even at baseline. TiFaCT is shortened at times of in vivo thrombin generation.

Adult↗
PubMed2003

Thrombus precursor protein, endogenous thrombin potential, von-Willebrand factor and activated factor VII in suspected deep vein thrombosis: is there a place for new parameters?

Because of its high negative predictive value, D-Dimer is an important parameter in the exclusion of deep vein thrombosis (DVT) but it produces a high number of false-positive results. We therefore evaluated different blood parameters in 74 consecutive patients with suspected DVT, whose final diagnosis was based on the results of Duplex ultrasound or venography. DVT was diagnosed in 52.7%. While D-Dimer, thrombin-antithrombin complexes, prothrombin fragment 1+2, von-Willebrand factor and thrombus precursor protein were significantly increased in patients with DVT, there was no influence concerning endogenous thrombin potential and activated factor VII. There was no significant correlation between the thrombus extension or the duration of symptoms with any of these parameters. D-Dimer showed the best sensitivity (94.9%) to specificity (45.7%) ratio and neither the sole nor the additional evaluation of any other investigated parameter increased its diagnostic performance. We, therefore, conclude that the determination of D-Dimer remains the 'gold standard' in the laboratory testing of patients with suspected DVT.

Adult↗