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Biomedical subjects

G Hafner

Publications and source records attributed to G Hafner.

At least 19 recordsLinked to original sources

[Monitoring of the heparin therapy during acute haemodialysis].

Anticoagulation during renal replacement therapy is recommended to avoid thrombosis of the filter devices and to maintain the blood flow. However, in the case of multiorgan failure and sepsis, an imminent bleeding complication in patients with acute renal failure may cause the need for an extracorporeal circulation without anticoagulation. The most common drug used in renal replacement therapy is the unfractionated heparin (UFH). With low molecular weight heparin (LMWH) good experiences are reported, too. Based on the level of evidence from clinical studies plasma measurement of heparin is indispensable for patients with renal insufficiency. The activated whole blood clotting time (ACT), the activated partial thromboplastin time (aPTT), and the determination of the anti-factor Xa activity (anti Xa) with chromogenic substrates are available as routine as well as as point-of-care tests. To monitor plasma levels of LMWH the anti Xa assay serves exclusively as a suitable monitoring. The anti Xa assay using chromogenic substrates is the most specific and valid one for monitoring heparin therapy. In lack of large controlled studies for the anticoagulation therapy and its monitoring with the anti Xa test in acute renal failure, the current experiences are based on the results of chronic renal replacement therapy.

Anticoagulants↗

[Prevention of thromboembolism in trauma surgery by dose adjustment of low molecular weight heparin depending on levels of TAT and D-dimer].

Deep vein thrombosis (DVT) is reported in up to 40% of trauma patients. The individual risk is nearly unpredictable. A daily single dose of a low molecular weight heparin (LMWH) was administered as prophylaxis to 518 trauma patients who were examined preoperatively and up to 10 days postoperatively in a prospective study. They were divided into two groups: group I comprised surgery of the hip and femur as well as total knee replacement and group II knee and lower leg surgery. Thrombin-antithrombin complex and D-dimer were analyzed. A second daily dose of LMWH was added if D-dimer exceeded the cutoff. If ultrasound was suspicious for DVT venography was added. Deep vein thrombosis was seen in five cases (group I=4, group II=1), without pulmonary embolism. TAT and D-dimer were significantly higher in group I than in group II ( p<0.005). One hundred patients, 79 of them belonging to group I, were treated with a second dose of LMWH. The daily cutoff had the highest sensitivity and specificity for day 4. Due to individual monitoring of coagulation markers, the risk for thromboembolism compared to actual data in the literature seems to be reduced.

Anticoagulants↗

[Coronary revascularization: off-pump versus on-pump--a comparison of behavior of biochemical cardiac ischemia markers].

BACKGROUND: Recently, coronary artery bypass grafting (CABG) on the beating heart with avoidance of extracorporeal circulation (off-pump CABG technique) has been gaining increasing importance in modern cardiac surgery. The object of this prospective study was to compare postoperative kinetic and patterns of cardiac troponin I (cTnI), T (cTnT), and creatine kinase MB (CKMB) activities after off-pump CABG versus conventional on-pump CABG. METHODS: We studied 106 patients who underwent first-time elective on-pump (group I, n = 69, 56 male, 13 female, mean age: 64.3 +/- 9.9 years, mean ejection fraction: 56 +/- 15%) or off-pump (group II, n = 37, 24 male, 13 female, mean age: 68.4 +/- 9.1 years, mean ejection fraction: 57 +/- 13%) CABG surgery via median sternotomy. CTn I and cTnT levels, total creatine kinase (CK) and CK-MB activities in the serum were measured before operation, up on arrival at the ICU and 6, 12, 24, 48 and 120 hours later. Serial 12-lead ECGs were recorded preoperatively and on days 1, 2 and 5. RESULTS: Serum concentrations of cardiac troponins in all patients were preoperatively either not detectable or in the normal range and significantly increased after surgery. In group I, one patient developed a Q wave myocardial infarction, one patient a non-Q wave infarction and two patients a new left bundle branch block on the ECG. One patient of group II developed a new Q-wave myocardial infarction and another patient permanent atrial fibrillation associated with a continuous arrhythmia. All patients with a myocardial infarction in the ECG showed significant elevation of concentrations or activities of these biochemical markers. The median postoperative peak values for cTnI were measured at 24 h in both groups (2.7 micrograms/l, 95%-CI: [2.2, 3.2] in group I and 1.1 micrograms/l, 95%-CI: [0.5, 1.3] in group II). CTnT postoperatively presented an earlier median peak of 0.128 microgram/l at 12 h in group II (95%-CI: [0.041, 0.146]) than in group I at 48 h (0.298 microgram/l, 95%-CI: [0.254, 0.335]). CONCLUSIONS: All patients undergoing CABG surgery with or without extracorporeal circulation postoperatively showed an increase of cardiac troponin levels. After uncomplicated coronary revascularization, patients with the off-pump CABG technique continuously presented lower serum cardiac troponin concentrations than those with the on-pump CABG technique. CTnI showed the same patterns of release in both groups with different median postoperative peak values at 24 h. The patterns off cTnT release following CABC surgery with or without extracorporal circulation were different: CTnT reaches its postoperative peak value in patients with the off-pump CABG technique earlier than those with the on-pump CABG technique (12 h postoperatively versus 48 h).

Aged↗

Application of C1-esterase inhibitor during reperfusion of ischemic myocardium: dose-related beneficial versus detrimental effects.

BACKGROUND: Complement activation during reperfusion of ischemic myocardium augments myocardial injury, and complement inhibition with C1-esterase inhibitor (C1-INH) at the time of reperfusion exerts marked cardioprotective effects in experimental studies. Application of C1-INH in newborns, however, was recently reported to have dangerous and even lethal side effects. This study addresses the essential role of dosage in studies using C1-INH. METHODS AND RESULTS: Cardioprotection by C1-INH was examined in a pig model with 60 minutes of coronary occlusion followed by 120 minutes of reperfusion. C1-INH was administered intravenously 5 to 10 minutes before coronary reperfusion without heparin at a dose of 40, 100, and 200 IU/kg body wt. Compared with the NaCl controls, C1-INH 40 IU/kg reduced myocardial injury (44.1+/-13.8% versus 76.7+/-4.6% necrosis of area at risk, P</=0.05) and significantly suppressed local C3a and C5a generation. Myocardial protection was accompanied by reduced plasma concentrations of creatine kinase and troponin T. In contrast, no beneficial effects were observed when 100 IU/kg C1-INH was used. Furthermore, application of 200 IU/kg C1-INH provoked severe side effects and coagulation disorders. CONCLUSIONS: When applied at the correct dose, C1-INH significantly protects ischemic tissue from reperfusion damage. However, overly high doses (>/=100 IU/kg) of C1-INH will provoke detrimental side effects, probably via its procoagulatory action.

Anaphylatoxins↗

Postoperative patterns and kinetics of cTnI, cTnT, CK-MB-activity and CK-activity after elective aortic valve replacement.

OBJECTIVES: The aim of this prospective study was to evaluate postoperative kinetics of four different biochemical ischaemic markers after elective aortic valve replacement (AVR). Additionally, pre-, peri- and postoperative data were analysed in order to identify factors with possible impact on the postoperative release of the selected enzymes. DESIGN: Forty patients (14 males, 26 females, aged 70 +/- 11 years; EF = 54 +/- 18% [mean +/- SD]) undergoing elective AVR were prospectively included in this study. For all patients, serum concentrations of cTnI, cTnT, and serum activities of CK-MB and CK were measured preoperatively as well as 0, 6, 12, 24, 48 and 120 hours after removal of the aortic cross-clamp. Clinical data were assessed in all patients and correlated with postoperative enzyme patterns. RESULTS: There were no major complications. Preoperatively, all patients showed enzyme values in the normal range whereas the four ischaemic markers reached higher values postoperatively. cTnI reached its maximum values 24 hours (XMed = 2.35 micrograms/L, 95%-CI [2.0, 3.3]) and cTnT 48 hours after the operation (XMed = 0.239 microgram/L, 95%-CI [0.174, 0.283]). Typical biphasic release kinetics could be demonstrated for cTnT. There was a high linear correlation between cTnI and cTnT at all sampling times. In contrast, a high linear correlation between cTnI, cTnT, and CK-MB-activity was only found 48 hours after aortic unclamping. cTnI nearly was in normal range 120 h postoperatively (XMed = 0.5 microgram/L, 95%-CI [0.2, 0.6]), whereas cTnT still remained pathologically elevated (XMed = 0.223 microgram/L, 95%-CI [0.137, 0.299]). No linear correlation was found between maximum values of the ischaemic markers postoperatively and age, gender, body surface area, ejection fraction, LV-hypertrophy, operating time, ECC time, time of cardiac arrest, lowest body temperature, perfusion pressure, cardioplegia volume, reperfusion time, postoperative septiformic circulatory instability, or ventilation time. CONCLUSIONS: All four ischaemic markers showed individual peak characteristics and kinetics after uncomplicated AVR. In contrast to previous findings, aortic cross-clamping time had no detectable impact on postoperative peak patterns of any ischaemic marker.

Aged↗

Circulating cell adhesion molecules and death in patients with coronary artery disease.

BACKGROUND: Vascular cell adhesion molecule (VCAM)-1, intercellular adhesion molecule (ICAM)-1, and E-selectin mediate adhesion and transmigration of leukocytes to the vascular endothelial wall and may promote plaque growth and instability. In a prospective study, we evaluated the effect of soluble adhesion molecules on the risk of future cardiovascular events among patients with angiographically documented coronary artery disease (CAD). Methods and Results- -We obtained baseline samples from a prospective cohort of 1246 patients with CAD. Besides various markers of inflammation, soluble VCAM-1 (sVCAM-1), sICAM-1, and sE-selectin were determined. Follow-up information on cardiovascular events was obtained (mean, 2.7; maximum, 4.1 years). Independently higher levels of sVCAM-1 (1932 versus 1128 ng/mL; P<0.0001), sICAM-1 (353 versus 287 ng/mL; P=0.015), and sE-selectin (81 versus 63 ng/mL; P=0.003) were observed in patients with future death from cardiovascular causes. In a multivariate model, fatal risk was 2.1-fold (1.1 to 4.0) higher in patients within the top quartile of baseline sVCAM-1 concentrations compared with lower quartiles. This association was present independent of general inflammatory response as reflected by low or high C-reactive protein (hs-CRP) levels. In a model that simultaneously controlled for all inflammatory and soluble adhesion markers determined, only sVCAM-1 remained independently significant for future fatal cardiovascular events, with a 2.8-fold increase in risk (P=0.003). CONCLUSIONS: Soluble adhesion molecules sVCAM-1, sICAM-1, and sE-selectin were significantly related to future death from cardiovascular causes among patients with documented CAD. Especially sVCAM-1 added to the predictive value of classic risk factors and hs-CRP in determining the risk of future cardiovascular death.

Aged↗

Impact of viral and bacterial infectious burden on long-term prognosis in patients with coronary artery disease.

BACKGROUND: The number of infectious pathogens to which an individual has been exposed (infectious burden) may correlate with coronary artery disease (CAD). In a prospective study, we evaluated the effect of 8 pathogens and the aggregate pathogen burden on the risk for future fatal cardiac events among patients with angiographically documented CAD. Methods and Results-In 1018 patients, IgG or IgA antibodies to herpes simplex virus types 1 and 2, cytomegalovirus, Epstein-Barr virus, Haemophilus influenzae, Chlamydia pneumoniae, Mycoplasma pneumoniae, and Helicobacter pylori were determined. Moreover, highly sensitive C-reactive protein was measured. Follow-up information on cardiovascular events was obtained (mean 3.1 years, maximum 4.3 years). Seropositivities to Epstein-Barr virus (P=0.001), H pylori (P=0.002), and herpes simplex virus type 2 (P=0.045) were independently associated with the future risk of cardiovascular death. An increasing number for pathogen burden was significantly predictive of the long-term prognosis (P<0.0001). Infectious burden divided into 0 to 3, 4 or 5, and 6 to 8 seropositivities was associated with an increasing mortality of 3.7%, 7.2%, and 12.6%, respectively. Patients seropositive to >5 pathogens compared with those seropositive to <4 pathogens had a 5.1 (1.4 to 18.3) higher risk of future cardiac death. This result was mainly driven by the pathogen burden of seropositivities to Herpesviridae (P<0.0001). The prognostic impact of total or viral pathogen burden was independent of the C-reactive protein level. CONCLUSIONS: These results support the hypothesis that the number of infectious pathogens to which an individual has been exposed independently contributes to the long-term prognosis in patients with documented CAD.

Antibodies, Bacterial↗

Cytomegalovirus infection with interleukin-6 response predicts cardiac mortality in patients with coronary artery disease.

BACKGROUND: Prospective data relating previous exposure to cytomegalovirus (CMV) to the risk of cardiac mortality are controversial. We investigated the effect of previous exposure to CMV infection on the risk of future cardiac disease-related death in relation to an underlying inflammatory response. METHODS AND RESULTS: coronary angiography was performed in 1134 subjects, and 989 patients with documented coronary artery disease were studied prospectively. CMV-IgG titers and interleukin (IL)-6 levels were measured before angiography. Increasing titers of CMV correlated with the elevation of IL-6 levels (P<0.001) after adjustment for possible confounders. All patients were followed up for a median of 3.1 years (maximum 4.3 years). During follow-up, 96 patients died, 70 of cardiac disease. Overall, CMV seropositivity was not related to cardiac mortality after adjustment for confounding variables (P=0.19). In contrast, in patients with elevated IL-6 levels (>/=11.9 pg/mL, median level), CMV seropositivity was independently associated with a 3.2-fold (95% CI 1.4 to 7.3, P=0.007) increase in risk of future cardiac death, whereas in individuals without IL-6 elevation, previous CMV infection had no effect on cardiac mortality. CONCLUSIONS: MV seropositivity in patients with an inflammatory response is independently associated with future cardiac mortality, whereas this association is lost in patients who do not demonstrate an inflammatory response. These data support the hypothesis that the atherosclerotic effects of CMV are mediated through an underlying inflammatory response.

Aged↗

[The role of inflammation and infection in acute coronary syndrome].

UNLABELLED: INFLAMMATORY PROCESS: Within the vessel wall is considered to be crucial for initiation and progression of atherosclerosis. As response to endothelial injury a focal inflammatory response arises which can lead to plaque vulnerability and rupture and a consecutive acute coronary syndrome. Systemic markers of inflammation like C-reactive protein (CRP) or interleukin (IL) 6 are elevated in stable angina and acute coronary syndrome and are associated with future cardiovascular events even in initially healthy people. Alongside classical risk factors infectious agents like cytomegalovirus or Chlamydia pneumoniae are discussed to be involved in the local and systemic inflammatory response. Seroepidemiological studies revealed disparate results of the association between antibody titers against Chlamydia pneumoniae or cytomegalovirus and prevalence of coronary artery disease or future cardiovascular events. In animal models Chlamydia pneumoniae and cytomegalovirus increase accelerated neointimal response, however, molecular mechanisms are not entirely clear. CONCLUSION: Whereas local and systemic inflammatory processes play a crucial role in atherogenesis and prognosis the causal role of infection in atherogenesis remains controversial.

Acute Disease↗

Troponin I concentrations of shed blood might influence monitoring of myocardial injury after coronary operations.

In a prospective study we evaluated the concentration of cardiac troponin I (cTnI) and creatine kinase activities (CK) in shed mediastinal blood in the early postoperative period after coronary artery bypass grafting (CABG). Forty seven patients who underwent first time elective CABG were studied. CTnI levels and CK activities in arterial blood and shed mediastinal blood were measured after admission to the intensive care unit (ICU) and 6 h after unclamping the aorta. Mediastinal shed blood samples were drawn from 23 patients (group A) before the filter of the cardiotomy reservoir and from 24 patients (group B) behind. Additionally, both markers were measured in blood samples collected from the cell-saver. There were no significant differences between both groups (A and B) with regard to perioperative parameters. Mean loss of mediastinal shed blood in all patients was 207 +/- 127 ml within the first 6 h after operation. There was a positive correlation between CK activities and cTnI concentrations in serum and mediastinal shed blood, but shed blood contained significantly higher concentrations of cTnI as well as CK activities than the circulating blood after admission to the ICU and 6 h after unclamping the aorta. At both time points the cTnI-concentrations and CK activities in shed blood in group B were lower than those in group A but much higher than in serum. The effects of the use of a blood filter diminishes with time. Mediastinal shed blood contains extremely high cTnI concentrations and CK activities. Retransfusion of higher quantities of shed blood might lead to false-positive diagnosis of perioperative myocardial infarction.

Aged↗

Patterns and diagnostic value of cardiac troponin I vs. troponin T and CKMB after OPCAB surgery.

BACKGROUND: Cardiac troponin I (cTnI) has been shown to be a specific marker for myocardial injury in cardiac surgery. The object of this prospective study was to determine the patterns and kinetic and diagnostic value of cTnI, cardiac troponin T (cTnT), and creatine kinase MB (CKMB) activity after minimally invasive coronary revascularization using an octopus device on the beating heart (OPCAB). METHODS: 48 patients (33 male/15 female, mean age 68.3 +/- 8.7 years) underwent their first elective OPCAB surgery with median sternotomy without mortality. The mean number of grafts was 2.0 +/- 0.8 per patient. Preoperative mean ejection fraction was 56.6 % +/- 14.9%. CTnI and T levels, total creatine kinase (CK) and CK-MB activity in the serum were measured before operation, at arrival at the ICU, and 6, 12, 24, 48 and 120 hours afterward. Serial 12-lead ECGs were recorded preoperatively and at days 1, 2 and 5. The relationship between perioperative data and postoperative cTnI and cTnT levels and CKMB were statistically identified for all variables. RESULTS: The best cutoff value for cTnI was 8.35 micrograms/l. The patients were grouped by the ECG findings and maximal slopes of cTnI postoperatively (group I: unchanged ECG and cTnI < 8.35 micrograms/l, n = 38; group II: unchanged ECG and cTnI > 8.35 micrograms/l n = 6; group III: Q-wave in ECG and cTnI > 8.35 micrograms/l, n = 4). Baseline serum concentrations of cTnI were in the normal range, and significantly increased after surgery with a peak 24h after the operation. Maximal slopes of cTnI ranged in group II between 9.1 and 18.0 micrograms/l, and in group III between 35.9 and 88.8 micrograms/l. There was strong concordance between maximum cTnI, cTnT (p < 0.0001) and CK-MB levels (p = 0.003). First cTnI levels immediately post-op correlated with the maximum cTnI levels during the postoperative course (p = 0.009). CONCLUSIONS: CTnI after minimal invasive surgery shows a characteristic pattern with a maximum at 24h after the operation. The measurement of postoperative biochemical marker concentrations, specially cTnI, reflects myocardial injury incurred during the procedure. It is an accurate method for confirming or excluding a perioperative myocardial injury diagnosis after OPCAB surgery.

Aged↗

Comparison of diagnostic performance of cardiac troponin I on the IMMULITE system with other automated troponin I assays in minor myocardial damage.

An analytical and clinical evaluation of cardiac troponin I (cTnI) on the IMMULITE system is presented. The assay results were compared with those of the Stratus II and the Dimension RxL-HM. A between-run imprecision CV < 20% was found at a cTnI concentration of 0.23 microg/L (functional limit of detection). On the basis of a reference study including 215 patients without ischemic heart disease (97.5th percentile: 0.294 microg/L) and 36 patients clinically classified as having stable angina pectoris (<0.22 microg/L) a preliminary cutoff level of 0.3 microg/L was defined. Assay linearity, sample stability, influence of sample material and method comparison studies were performed. In patients with Duchenne's disease, chronic hemodialysis treatment, pulmonary embolism, coronary artery bypass surgery and minimally cardiac surgery the cTnI results of the IMMULITE agreed better with the Dimension RxL-HM than with the Stratus II data. Of 142 samples from patients with unstable angina 67 samples were classified as cTnI positive with the IMMULITE, 76 with the Dimension RxL-HM, and 62 with the Stratus II. In conclusion, the new assay is sensitive for the determination of cTnI and easy to perform within 45 min.

Adult↗

Evaluation of the new ImmuliteTurbo cTnI assay and the original immulite cTnI assay.

OBJECTIVES: An analytical and clinical evaluation of cTnI on the ImmuliteTurbo system with 15 min assay time compared to 45 min with the original Immulite assay is presented. METHODS AND DESIGN: Detection limit, functional sensitivity, AMI decision limit, assay linearity, influence of sample material (serum, heparin, citrate and EDTA plasma), interference, analytical and clinical method comparison studies were performed. RESULTS: Functional sensitivity (at CV 20%) was 0.35 compared to 0.23 microg/L for the original assay. AMI decision limit (99th percentile of a reference control group) was 0.48 microg/L for both assays. In patients with acute coronary syndromes, chronic renal failure or pulmonary embolism the assays showed concordant results in 87.2-96.5%. Differing results were only found around the cut-off level and were attributed to assay imprecision. CONCLUSION: The new assay is sensitive for the determination of cTnI, shows comparable results to the original assay version and is easy to perform within 15 min.

Adolescent↗

Association between P-selectin gene polymorphisms and soluble P-selectin levels and their relation to coronary artery disease.

P-selectin is a cellular adhesion molecule that mediates the interaction of activated endothelial cells or platelets with leukocytes. Increased levels of soluble P-selectin have been reported in various cardiovascular disorders. We measured serum soluble P-selectin levels as well as 3 polymorphisms of the P-selectin gene (C-2123G, A-1969G, and Thr715Pro) in a large cohort of patients with documented coronary artery disease (n=869) and a healthy control group (n=334). The 3 P-selectin polymorphisms were strongly associated with P-selectin levels and altogether explained 7.3% and 18.6% of the P-selectin variability in patients and controls, respectively. Genotype distributions did not significantly differ between patients and controls. P-selectin levels were increased in patients younger than 55 years of age compared with controls (135.2 vs 114.3 ng/mL, P<0.01). On the contrary, patients older than 65 years of age had significantly lower P-selectin levels than did controls (121.5 vs 134.7 ng/mL, P<0.02). In intermediate age groups, P-selectin levels did not significantly differ between the 2 groups. In conclusion, this study revealed a strong association between P-selectin gene polymorphisms and serum P-selectin levels and a complex age-dependent relation between soluble P-selectin levels and coronary artery disease, which suggests that this molecule might have different roles in the atherothrombotic process.

Cohort Studies↗

Postoperative reduction of fibrinolysis as a prognostic factor of fatal outcome.

For the resection of an esophagus carcinoma a mortality rate of 2 to 30% was described. It is still unclear whether an abdominothoracic or transhiatal intervention is superior regarding the outcome. To investigate the prognostic value of fibrinolytic markers, plasmin-alpha2-antiplasmin (PAP) and D-dimer (DD) values were determined daily in the early postoperative period for 11 days. In addition, the course of PAP and DD concentrations was compared with the method of esophagectomy. Of the 28 patients enclosed in the study, 5 died between day 10 and day 34 owing to adult respiratory distress syndrome and septicemia. The PAP and DD concentrations increased in survivors after surgery until day 5 and day 7, respectively. The concentrations were twofold and 10-fold higher than the upper reference level. In contrast, four of five nonsurvivors showed an inadequate increase in PAP concentrations within the reference range, whereas the course of DD was inconspicuous. The sensitivity and specificity of PAP and DD in respect to a fatal outcome was calculated by receiver operating characteristic analysis based on all results: sensitivity 76% (PAP-cut off value 760 microg/L) and 49% (DD 6 mg/L), specificity 77% and 72%, respectively. The biochemical markers showed no significant differences between the abdominothoracic and transhiatal esophagectomy. In the abdominothoracic intervention, lower PAP and higher DD concentrations were observed. The results showed that the PAP concentrations could detect a fatal outcome within the first 5 days after surgery.

Adult↗

[Acute mesenterial artery occlusion--an unusual symptom of primary antiphospholipid antibody syndrome].

BACKGROUND: The antiphospholipid-antibody syndrome (APS) is a thrombophilic disorder, in which venous and arterial thrombosis can occur. We report the rare case of a patient with mesenteric infarction due to primary APS. CASE REPORT: A 46-year-old male patient was admitted to the hospital because of severe abdominal pain. A laparotomy was performed and revealed infarction of a jejunal loop which was resected. At pathohistological examination mesenteric artery infarction was found. Preoperatively prolonged partial thromboplastin time led to coagulation analysis. Lupus anticoagulant and anticardiolipin antibodies were found. TREATMENT: The diagnosis of primary APS was made and the patient was treated with aspirin (100 mg/day) and low molecular weight heparin (2,500 IE/day) permanently. Eighteen months after mesenteric infarction the patient is free of further thromboembolic events.

Antibodies, Anticardiolipin↗

Dose-adjusted thrombosis prophylaxis in trauma surgery according to levels of D-Dimer.

In 234 trauma surgery patients, thrombosis prophylaxis with Nadroparin-Calcium low-molecular-weight heparin (LMWH) was adjusted according to levels of D-Dimer. Basic prophylaxis was 2,850 IU per day. If D-Dimer concentrations rose above 2 mg/L after the fourth postoperative (p.o.) day, LMWH was administered twice a day. Color Doppler ultrasound was performed between the fifth and seventh p.o. days. Patients were divided into a high-risk (group 1: hip, femur, or knee replacement surgery, n=102) and a moderate-risk group (group 2: other surgery of the knee, tibia, fibula, or foot, n=132). Group 1 showed significantly higher D-Dimer levels than group 2 (p<0.001). Measurement of D-Dimer on days 2 and 4 p.o. showed a sensitivity of 100% and a specificity of 72.8% in identifying patients at risk (i.e., D-Dimer>2 mg/L after day 4 p.o.). The overall deep vein thrombosis (DVT) rate in group 1 was 3.9%, and the rate of proximal DVT was 1.96%. In group 2, one distal DVT (0.8%) occurred. The results show that D-Dimer is a useful marker to monitor p.o. coagulation activation and to manage LMWH prophylaxis in trauma surgery patients.

Adult↗

Screening for abnormalities of the protein C anticoagulant pathway using the ProC Global assay. Results of a European multicenter evaluation.

ProC Global is a new global clotting assay designed to evaluate the functionality of the protein C anticoagulant pathway. It is based on the ability of endogenous activated protein C, generated by activation of protein C by Protac, to prolong an activated partial thromboplastin time, and the results are expressed in protein C activation time normalized ratio (PCAT-NR), after normalization. This multicenter trial involving five European laboratories was designed in order to determine the ability of the ProC Global assay to distinguish patients with and without abnormalities of the protein C pathway. The PCAT-NR was significantly lower in the patients with a thrombotic history not on oral anticoagulant treatment (n = 627) than in the healthy controls (n = 148), even after exclusion from both groups of the patients with abnormality of the protein C pathway. Using receiver operator characteristics analysis, the cut-off level of PCAT-NR = 0.80 was found to provide the best sensitivity-specificity ratio. All the carriers of the factor V Leiden mutation (n = 73), as well as all the patients with activated protein C resistance (n = 42), had a PCAT-NR below 0.80. The ProC Global assay performed well in patients with combined defects (97.0%, n = 33) or protein C deficiency (91.3%, n = 46), but it failed to detect all of them, and one patient with combined defects as well as four patients with a low protein C level had a PCAT-NR above the cut-off level. The sensitivity of the assay for protein S deficiency (n = 58) was weak (only 69.0%) and, surprisingly, more than 40% of the 375 patients without any of these abnormalities of the protein C pathway had a PCAT-NR below the cut-off level.

Activated Protein C Resistance↗