[Haemostatic testing prior to elective surgery? Yes!]. / Laboranalytischer Ausschluss einer hämorrhagischen Diathese vor elektiven Eingriffen? Ja!

Haemorrhagic disorders must be excluded prior to any operation or other invasive procedure that has the potential to involve serious bleeding. When assessing the individual risk of bleeding, screening tests of hemostasis must be combined with the patient's clinical history and symptoms, and any history of bleeding must be explored under direct medical supervision using a standardized questionnaire. However, this bleeding history is neither very specific, nor is it particularly sensitive. Screening tests that have been found to be useful include platelet count, activated partial thrombo plastin time (aPTT), prothrombin time (PT) and clottable fibrinogen. No reliable, sensitive and specific screening test is however available today to screen for platelet dysfunction or von Willebrand disease. A specialized coagulation laboratory should be involved when the bleeding history or laboratory screening indicate a potential haemorrhagic disorder.

Prognostic value of plasma tissue factor and tissue factor pathway inhibitor for cardiovascular death in patients with coronary artery disease: the AtheroGene study.

BACKGROUND: Tissue factor (TF) and its specific inhibitor, tissue factor pathway inhibitor (TFPI), are important contributors to the initiation of the coagulation process. OBJECTIVES: To compare plasma levels of soluble TF (sTF) and free-TFPI (f-TFPI) between patients with stable angina pectoris (SAP) and acute coronary syndrome (ACS) and to assess the impact of the two variables on long-term prognosis. PATIENTS/METHODS: Patients with SAPs (n = 1146) and acute coronary syndrome (n = 523) from the AtheroGene study were included and followed for 2.3 years. Because of the strong impact of unfractionated heparin (UFH) on f-TFPI levels, but not on sTF levels, patients having received UFH before blood drawing were excluded from the analyses on f-TFPI (n = 226). RESULTS: On admission, no significant differences in sTF levels were observed between SAP and ACS patients. By comparison to patients with stable angina, f-TFPI levels significantly increased in patients with acute unstable angina and further increased in patients presenting with non-ST-elevation myocardial infarction and ST-elevation myocardial infarction (P < 10(-4)). Among the 1669 individuals with a coronary artery disease, 56 died from a cardiovascular cause. In prospective analyses, high sTF levels were independently associated with an increased risk of cardiovascular death in individuals with ACS (fully adjusted hazard ratio associated with one quartile increase = 2.06; 95% confidence interval 1.24-3.45; P = 0.006) but not in those with SAP (hazard ratio = 1.07; 95% confidence interval 0.78-1.46; P = 0.67). In SAP and ACS patients, high f-TFPI levels were not independently associated with an increased risk of cardiovascular death. CONCLUSIONS: Plasma sTF levels were predictive of cardiovascular mortality in individuals with ACS, whereas f-TFPI levels were associated with the severity of myocardial damage on admission but were not independently related to outcome.

Haemostatic factors and the risk of cardiovascular death in patients with coronary artery disease: the AtheroGene study.

OBJECTIVE: To get a better insight into the role of hemostasis in coronary artery disease (CAD), we assessed the impact of von Willebrand factor (vWF), fibrinogen, thrombin-antithrombin (TAT) complexes, D-dimers, and plasmin-antiplasmin (PAP) complexes on the risk of cardiovascular event in a prospective cohort of CAD patients. METHODS AND RESULTS: The prospective Atherogene cohort includes 1057 individuals with an angiographically proven coronary artery disease at baseline. After a median follow-up of 6.6 years, 135 individuals died from a cardiovascular cause and 97 had a nonfatal cardiovascular event. Higher levels of all 5 hemostatic markers at baseline were associated with an increased risk of cardiovascular death, but not of nonfatal event. Except for vWF, these associations remained significant after adjustment for conventional cardiovascular risk factors and C-reactive protein (CRP) levels (P for trend according to increasing tertiles=0.20, 0.011, 0.026, 0.019, and 0.01 for vWF, fibrinogen, TAT, D-Dimer, and PAP, respectively). When including the 5 hemostatic markers in a stepwise Cox regression analysis where conventional risk factors and CRP were forced into the model, fibrinogen and D-dimers remained independently associated with the risk of cardiovascular death. Adjusted hazard ratios (95% CI) associated with one SD increase of fibrinogen and D-dimers were 1.27 (1.04 to 1.55) and 1.29 (1.09 to 1.53), respectively. CONCLUSIONS: In patients with coronary artery disease, fibrinogen and D-dimer levels are independent predictors of subsequent cardiovascular death. Our data support a role of impaired coagulation/fibrinolysis process in the complications of coronary artery disease.

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.

Age-Dependent D-dimer Cut-off to Avoid Unnecessary CT-Exams for Ruling-out Pulmonary Embolism.

PURPOSE: To evaluate the effect of an age-dependent D-Dimer cut-off in patients who underwent a computed tomography pulmonary angiogram (CTPA) for suspected pulmonary embolism (PE) Material and Methods: Retrospective application of an age-dependent D-dimer cut-off (age/100 in patients aged over 50) in 530 consecutive patients, both in- and outpatients, aged over 18, who underwent CTPA for suspected PE according to the guidelines. RESULTS: The application of an age-dependent D-dimer cut-off showed a now negative test-result in 17 of 530 patients (3.2%). The proportion was 4.1% (17 of 418) in patients aged over 50. None of these 17 cases was diagnosed with PE in CTPA, the false-negative rate was 0%. The effect could be seen in outpatients (14 of 377 [3.7%]) as well as in inpatients(3 of 153 [2.0%]) with no statistically significant difference (p > 0.05). CONCLUSION: The application of an age-dependent D-dimer cut-off as part of the guidline-based algorithm for suspected PE reduced the number of necessary CTPA in outpatients as well as in inpatients. KEY POINTS: The application of an age-dependent D-dimer cut-off reduces the number of CTPA as part of the diagnostic algorithm in patients suspected for PENo reduction in diagnostic safety was found. The age adjustement performed equally in outpatients and inpatients

Correction of truncus arteriosus in the neonate using a nonvalved conduit.

Successful correction of truncus arteriosus in two neonates, both 4 days of age, is described. Nonvalved polytetrafluoroethylene (PTFE) conduits were used because of the small size of the infants. Both recovered from operation with no signs right ventricular failure and remain well. Catheterization data on one patient show satisfactory hemodynamics 1 year after operation with only residual branch pulmonary artery stenosis. These data suggest that a conduit valve is not essential in the correction of truncus arteriosus even in the neonate.

Cystic adventitial degeneration of the femoral artery: is evacuation and cyst excision worthwhile as a definitive therapy?

A case of cystic adventitial degeneration of the left common femoral artery in a patient with localized left groin pain, normal distal pulses, and normal arteriographic findings is reported. This patient was first treated with evacuation and cyst excision. Recurrence was noted after 20 months, and an excision of the cyst and a segment of the common femoral artery with graft interposition was required. At gross examination, the cyst was unilocular and contained gelatinous material. The cyst appeared to be situated in the tunica adventitia and did not communicate with the vascular lumen. No synovial lining was present. Histologically, it was similar to a ganglion cyst with contents rich in hyaluronic acid. A review of the literature was undertaken to determine the results of treating this lesion. The disease is rare. All senior authors of case reports were contacted to construct follow-up information. A high incidence of recurrence was noted in patients treated by evacuation and cyst excision. We believe that total cyst excision with the involved artery and graft interposition at the femoral site can be done easily, safely, and with virtually no chance for recurrence.

Intestinal intubation in acute, mechanical small-bowel obstruction.

A review of 100 consecutive patients admitted with simple, mechanical small-bowel obstruction secondary to adhesions and treated for at least 24 hours with nonoperative intestinal intubation showed that of 76 patients admitted with partial small-bowel obstruction, 49 (65%) were successfully treated without operation. Of those with complete small-bowel obstruction (CSBO), 18 of 24 (75%) subsequently required surgical intervention; however, six of 24 (25%) were safely treated by nonoperative intubation. The 24-hour delay in surgery for CSBO did not increase morbidity or mortality in the 18 requiring operations. Major indications for surgical intervention were suspected strangulated obstruction or persistent obstruction, which frequently was associated with unsuccessful tube passage. Administration of antibiotics preoperatively was associated with a significant reduction in wound infections in patients requiring resection or enterotomy.

Thoracic aorta-femoral artery bypass: indications, technique, and late results.

Retroperitoneal descending thoracic aorta-femoral artery bypass was performed in 18 patients over an 11-year period. The reconstruction was carried to both femoral arteries in 12 patients; in the other 6, only a single femoral artery was revascularized. The operative indication in Group 1 (3 patients) was infection of a previous aortoiliac reconstruction; in Group 2 (12 patients), occlusion of a previous aortoiliac reconstruction; and in Group 3 (3 patients), aortoiliac occlusive disease in which a direct transabdominal procedure was considered hazardous. Follow-up ranged from 6 months to 9 years (mean, 40 months). Cumulative patency rate was 96 +/- 3.9% at 1 year and 85 +/- 8.1% at 5 years. No alterations of serum creatinine and blood urea nitrogen values were recorded seven days and 6 months after operation. Retroperitoneal thoracic aorta-femoral artery bypass is a useful technique for accomplishing lower limb revascularization in patients in whom exposure or availability of the abdominal aorta poses a specific hazard.

Traumatic thoracobiliary fistula.

Thoracobiliary fistulas are a commonly reported complication of subphrenic or liver abscesses and biliary tract obstruction. However, they are a rare and unusual complication of traumatic thoracoabdominal wounds. Due to their rarity, the experience of any one surgeon is minimal, and there is a paucity of information available in the literature regarding their treatment. We describe a case of a traumatic thoracobiliary fistula, review the existing literature, and discuss the proper management of this potentially lethal sequela of trauma.

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.

Effects of combined therapy of clopidogrel and aspirin in preventing thrombus formation on mechanical heart valves in an ex vivo rabbit model.

BACKGROUND: The aim of our study was to investigate the efficacy of the combination of clopidogrel and aspirin in the prevention of thrombus formation on artificial heart valves in an experimental rabbit model as compared to anticoagulation with warfarin. METHODS: Studies were performed after oral administration of clopidogrel and aspirin in group I (n=9) for 5 days, after 5+/-2 days treatment with warfarin in group II (n=9) and without medication in group III (n=9). Leaflets from Sulzer Carbomedics bileaflet valves were placed in a flow chamber. The flow chamber was filled with blood in a continuous circulation between the carotid artery and the jugular vein. RESULTS: In group III, the flow chamber was clotted after a median of 15 min of circulation. Weight analysis before and after 1 h of perfusion showed that the median thrombus weight was 9.1 mg in group I, 14.4 mg in group II and 33.7 mg in group III. Further analysis by electron microscopy showed fewer platelets and erythrocytes on leaflets in group I than on leaflet surfaces in group II. CONCLUSION: Clopidogrel and aspirin were more effective than warfarin in preventing thrombus formation on artificial heart valve leaflets in our investigation. This rabbit model with a high dosage of clopidogrel and aspirin, and a short-time exposure of the heart valve leaflets to rabbit blood under laminar flow, should be further evaluated with respect to whether it can give information about antithrombotic regimens in patients after mechanical heart valve replacement.

Retinal vascular occlusion and deficiencies in the protein C pathway.

PURPOSE: To report abnormalities in the protein C pathway and other vascular occlusion risk factors in patients with retinal vascular occlusion. METHODS: In a study, we investigated 76 consecutive patients who had in-patient evaluation of venous or arterial retinal vascular occlusion. All patients underwent comprehensive tests for coagulation disorders including determinations of protein C, protein S, lupus anticoagulants, and resistance to activated protein C and were screened for vascular disease risk factors. Resistance to activated protein C was confirmed by a polymerase chain reaction method to detect the specific factor V R506Q mutation. For comparative purposes, we also screened 209 consecutive inpatients with deep vein thrombosis from the same geographic region for resistance to activated protein C as well as protein C and protein S deficiencies. RESULTS: Ten (29%) of 35 patients with central retinal vein occlusion (CRVO) had factor V R506Q mutation. The factor V R506Q mutation was detected in four (19%) of 21 patients with branch retinal vein occlusion. The higher frequency in factor V R506Q mutation compared with the expected 9% mutation prevalence in a white population was highly significant for the central retinal vein occlusion group but not for the branch retinal vein occlusion group. In all patients with resistance to activated protein C, the factor V R506Q mutation was detected; 16 were heterozygous, one homozygous. No cases of lupus anticoagulants, protein C, or protein S deficiencies were detected. Forty (19%) of 209 patients with deep vein thrombosis were carriers of the factor V R506Q mutation. CONCLUSIONS: The prevalence of the factor V R506Q mutation is similar in patients with central retinal vein occlusion and patients with deep vein thrombosis and represents a relevant risk factor. Screening for this mutation is therefore recommended in all patients with central retinal vein occlusion.

Eversion endarterectomy of the superficial femoral artery and end-to-side anastomosis to the deep femoral artery. An alternative to extended profundoplasty.

The success of aortofemoral reconstruction in patients with superficial femoral artery occlusion depends on the restoration of a satisfactory pulsatile flow to the deep femoral artery. In 18 patients with multilevel disease, widespread involvement of the deep femoral artery, and poor distal outflow, we performed an eversion endarterectomy of the proximal segment of the superficial femoral artery and constructed an end-to-side anastomosis between this segment and the distal deep femoral artery. In 10 patients, the reconstruction was performed after thrombectomy of the occluded aortofemoral graft, and in 8 the two reconstructions were simultaneous. The actuarial patency rate was 93.5 percent at 1 year and 75.2 percent at 5 years. Four late femorodistal bypasses were performed that gave an actuarial limb salvage rate of 68.8 percent at 1 year and 61.6 percent at 5 years. In selected cases, this technique is a valid alternative to an extended profundoplasty or to a femorodistal bypass.

Abdominal aortic aneurysm in elderly patients. Selective management based on clinical status and aneurysmal expansion rate.

The records of 125 patients 75 years of age or older with a diagnosis of unruptured abdominal aortic aneurysm were reviewed. Operative mortality was 4.3 percent in 69 patients considered at low risk and 39.8 percent in 13 patients at high risk who underwent aneurysmectomy shortly after diagnosis. Forty-three patients with an asymptomatic abdominal aortic aneurysm initially measuring 3.5 to 6 cm did not undergo aneurysmal resection and were followed for 6 to 72 months (mean 24 months) with serial echography. The mean enlargement rate was 0.48 cm/year. In the 43 patients, resection of the abdominal aortic aneurysm was performed for aneurysmal expansion to greater than 6 cm, development of symptoms, or a sudden change in aneurysmal diameter. Two patients were lost to follow-up, 21 underwent elective resection, aneurysms ruptured in 2, 9 died from other causes, and 9 were alive and asymptomatic at last follow-up. An aggressive surgical approach seems appropriate, even in the asymptomatic elderly patient with a small aneurysm of 4.5 to 6 cm. Serial echographic measurement appears useful in determining which patients with a very small aneurysm of less than 4.5 cm or who are considered to be high risk surgical candidates require elective aneurysmectomy.

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.

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.

Differences in zinc status and the leptin axis in anorexic and recovered adolescents and young adults: a pilot study.

BACKGROUND: Evidence from animal studies suggests that leptin metabolism is associated with zinc (Zn) status. However, research investigating this relationship in adolescents and young adults with anorexia nervosa (AN) is scarce; the present study aims to fill that gap. METHODS: Serum concentrations of leptin, the soluble leptin receptor (sOB-R) and the free leptin index (FLI) were obtained in healthy control subjects (n=19), acutely ill individuals (n=14) and recovered patients with AN (n=15). Serum Zn concentrations noted in previous research data were also incorporated for all groups. RESULTS: Leptin, FLI and Zn concentrations were higher in recovered subjects with AN when compared with acutely ill AN patients. Remitted patients showed higher sOB-R concentrations but no difference in FLI compared with the control group. Leptin and FLI were lower in the acutely ill patients compared with the control subjects, who showed no differences in Zn concentrations. Zn concentrations were not correlated with leptin, sOB-R or FLI concentrations in any of the three investigated subgroups. CONCLUSIONS: The present investigation does not entirely support an association between Zn, Leptin and FLI concentrations in subjects with AN, possibly due to limited statistical power. Further research and replication of the present findings related to the interaction between leptin and Zn is warranted. However, with respect to serum leptin levels the data of the present investigation indicate that acutely ill and remitted patients with AN differ as regards serum leptin concentrations and FLI, which is in line with previous research.

Long- and short-term in vitro D-dimer stability measured with INNOVANCE D-Dimer.

In vitro D-dimer stability in plasma is widely assumed, but has not yet been documented by systematic studies using samples covering a wide range of D-dimer. We investigated the short- and long-term stability of D-dimer in clinical citrated plasma samples with normal and pathological levels. The short-term stability was analysed by measuring D-dimer fresh, after storage of plasma for 4 hours at room temperature (RT) and after an additional 24 h storage at +2 to +8 degrees C (n=40). Long-term stability samples (n=40) were measured fresh and after storage for 19, 25 and 36 months at < or =-60 degrees C. The effect of repeated freezing was analysed by measuring samples (n=50) fresh and after four consecutive freeze-thaw cycles. D-dimer was measured on the BCS System using the INNOVANCE D-Dimer assay (Siemens Healthcare Diagnostics Products GmbH, Marburg, Germany). D-dimer values at baseline ranged from 0.23-22.2 mg/l FEU. The mean percentage change after storage for 4 hours at RT and additional 24 hours at +2 to +8 degrees C was +3.8% and +2.7%, respectively. The mean percentage change after frozen storage for 19, 25 and 36 months at < or =-60 degrees C was -11.7%, -4.8% and -9.3%, respectively. The small decrease of D-dimer values after frozen storage was not time-dependent. Repeated freezing did not significantly alter D-dimer values (mean change < or =5%). The data demonstrate stability of D-dimer in plasma prior to freezing for up to 4 hours at RT and for up to 24 hours at +2 to +8 degrees C as well as in plasma stored for up to three years at < or =-60 degrees C.

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.