ELISA D-dimer measurement for the clinical suspicion of pulmonary embolism in the emergency department: one-year observational study of the safety profile and physician's prescription.

OBJECTIVES: To validate the safety profile of a rapid ELISA D-dimer as the first diagnostic step in the clinical suspicion of pulmonary embolism (PE) in outpatients admitted to an emergency department (ED), and to retrospectively evaluate the appropriateness of the physician's prescription. DESIGN AND SETTING: An observational study of all patients admitted to the ED of an urban university teaching hospital with signs and symptoms justifying the prescription of a rapid ELISA D-dimer measurement (Vidas; Biomerieux; France) as the first line diagnostic test for PE. Acute PE was established or excluded according to an appropriate combination of the D-dimer concentration, the lung scintigraphy, the spiral computerized tomography (spiral CT), the venous ultrasonography, and the arteriography in case of uncertain results. All patients with D-dimer values under the cut-off point of 500 ng/ml were followed up after 6 months. RESULTS: 395 patients were studied. A normal D-dimer concentration < 500 ng/ml was found in 179 patients (45% of the cohort). The retrospective analysis showed that none of these patients were found to have a high pre-test clinical probability. None of these 179 patients received anticoagulation nor displayed a PE event during a 6-month period (negative predictive value 100%; 95% CI, 98.0 to 100%; sensitivity 100%; 95% CI, 90.3 to 100%). Among the 216 patients (55%) with D-dimer values above 500 ng/ml, PE was confirmed in 32 cases, for a prevalence of the disease of 8.1%. Eighty-six patients (22%) had no additional testing in spite of positive D dimer values > 500 ng/ml, pointing out a 22% rate of inappropriate use of the D-dimer measurement. CONCLUSION: This observational study confirms that a normal rapid ELISA D-dimer value (< 500 ng/ml) used as a first diagnostic step in ruling out the diagnosis of PE is a safe clinical practice when the pre-test clinical probability is low or intermediate. Nevertheless, the low prevalence rate of the disease (8.1%) suggests a potential overused and inappropriate prescription.

Heparin-induced thrombocytopaenia complicated by arterial and venous thrombosis: report of 2 cases successfully treated by a danaparoid sodium.

Heparin-induced thrombocytopaenia is a dreaded, although infrequent, complication of heparin therapy. We report two cases of heparin-induced thrombocytopaenia (HIT) type II occurring in a patient treated with standard (unfractionated) heparin and in another patient given a low-weight molecular heparin. The clinical course of the first patient illustrates the potentially severe thrombotic complications of HIT. Both cases were treated successfully by danaparoid sodium. Clues to the diagnosis and treatment are briefly discussed.

The prothrombin gene G20210A variant in an unselected thromboembolic population. A Belgian prospective clinical study.

The presence of the 20210A allele of the prothrombin gene has recently been shown to be a risk factor of venous thromboembolism, probably mediated through increased prothrombin levels. The aim of the study was to determine the frequency of the prothrombin 20210A allele in 193 consecutive unselected patients with venous thromboembolism and 100 healthy controls and to analyze the clinical profile associated with this new inherited thrombophilic factor. In agreement with previous reports, we found a frequency of 7.3% of heterozygous carriers of the 20210A allele among patients and 1% among controls. We confirm that plasma prothrombin levels are more elevated in the individuals bearing the prothrombin 20210A allele compared with those who do not. We did not find any relationship between the presence of the prothrombin 20210A allele and either a family history of thromboembolism, the rate of recurrences or the age at disease onset. However, the co-inheritance in the same individual of both prothrombin 20210A allele and factor V Leiden was associated with a significantly lower age at disease onset suggesting a synergistic contribution of both abnormalities.

Prevalence of activated protein C resistance and analysis of clinical profile in thromboembolic patients. A Belgian prospective study.

OBJECTIVES: To assess the prevalence of activated protein C resistance (APC-R) among healthy subjects and thromboembolic patients and to determine the clinical characteristics associated with APC-R. DESIGN: A prospective study. SETTING: One academic medical centre. SUBJECTS: 91 health controls and 126 thromboembolic patients. MEASUREMENTS: Patients and control were genotyped for the factor V Leiden (VaQ506) mutation. The anticoagulant response of the patient's plasma to activated protein C was also determined. RESULTS: The frequency of APC-R was 3.3% among healthy control subjects and 22% among thrombotic patients of whom 18% were heterozygous and 4% were homozygous. The mean age at the first thrombotic event and the severity of thrombotic disease including the proportion of proximal deep vein thrombosis and the frequency of lung embolism were identical among APC-R positive and negative patients. A family history of thromboembolic disease was elicited more frequently in APC-R positive than in APC-R negative patients (57% vs. 22%, P < 0.001). The recurrence rate was higher for APCR-R positive patients (57% vs. 34%, P < 0.05). The percentage of cases with a factor predisposing to thrombosis was very similar in APC-R positive (57%) and negative (68%) patients. CONCLUSIONS: A familial history of thromboembolic disease and recurrences are significantly more frequent among APC-R positive than APC-R negative patients.

Comparative study of antiphospholipid antibody detection in eleven Belgian laboratories.

Twenty-six plasma samples have been sent to 11 different Belgian laboratories in order to detect the presence of antiphospholipid antibodies, either by immunological methods and/or by coagulation tests. A good concordance between laboratories was observed for coagulation tests. Laboratories using detection tests and performing mixing procedures and neutralisation procedures displayed the highest sensitivity as compared with laboratories which did not perform one of these two latter procedures. The concordance between laboratories for the immunological methods was much worse as compared with coagulation tests. This may be attributable either to an intrinsic problem of the immunological tests or to a selection bias due the fact that the plasmas used in this study were selected in coagulation laboratories only where the chance to find a lupus anticoagulant positive/ELISA antiphospholipid negative sample is high.

Large increase in plasmatic 11-dehydro-TxB2 levels due to oral contraceptives.

Coagulation factors, 11-dehydro-TxB2 (metabolite of TxA2) and 6-keto-PGF1 alpha (metabolite of PGI2) levels in 87 women who were treated for 9 months with oral contraceptives (OC) containing low doses of oestrogens and progestogens (Triquilar, Trinovum or Cilest) were investigated. In plasma, increases in F I, II, VII, VIII-c and 11-dehydro-TxB2 levels, but no modification of 6-keto-PGF1 alpha were observed. In urine, FPA concentration rose, but no change occurred in 11-dehydro-TxB2 and 6-keto-PGF1 alpha levels. No marked difference between the 3 OC preparations were noted. These data, and particularly the large increase of 11-dehydro-TxB2 (p < 0.01) suggest that a hypercoagulable state persists in low dosage OC users.

Hemostasis variables in type I diabetic patients without demonstrable vascular complications.

OBJECTIVE: To determine hemostasis variables in type I diabetic patients without clinically demonstrable micro- and macroangiopathy and to relate them to glycemic control. RESEARCH DESIGN AND METHODS: Fifty patients and 50 comparable control subjects were enrolled in this study. The patients were subdivided in two groups, according to their level of HbA1c (group 1, n = 30, HbA1c < or = 8%; group 2, n = 20, HbA1c > 8%). We determined the platelet count, the platelet aggregation in the spontaneous state and in the presence of ADP or collagen, beta-thromboglobulin, platelet factor 4, fibrinogen, von Willebrand factor (factors VIII:C, VIIIR:Ag, and VIIIR:VW), plasma and urinary fibrinopeptide A, euglobulin lysis time, anticoagulant proteins C and S, and plasma viscosity. RESULTS: All coagulation variables were significantly higher in diabetic patients compared with control subjects. Moreover, when the patients were subdivided according to their levels of HbA1c, the hemostatic disturbances appeared significantly more pronounced in the poorly controlled than in the well-controlled subjects. CONCLUSIONS: This study confirms the existence of a state of hypercoagulability in type I diabetes. This hypercoagulability may be related to poor glycemic control. Our study suggests that the hemostasis disturbances precede demonstrable vascular complications.

Triflusal versus acetylsalicylic acid: a double-blind study for the prophylaxis of deep vein thrombosis after hip surgery.

The authors report the results of a randomised double-blind study comparing the antithrombotic activity of a new anti-platelet drug (Triflusal) with that of acetylsalicylic acid (ASA). 99 patients who underwent hip surgery were included in the study (total hip replacement, osteosynthesis of a pertrochanter fracture or Moore's prosthesis for intracapsular fracture of the femoral neck). Of the 48 patients having received Triflusal, 7 (14.5%) developed deep vein thrombosis as indicated by 125I-fibrinogen isotopic scanning and confirmed by phlebography. Of the 51 patients treated with ASA, 11 (21.6%) presented the same complication as diagnosed by the same techniques. This difference is not statistically significant, considering the number of cases studied. Nevertheless, Triflusal appears to provide prevention of thromboembolic risk to patients who have undergone hip surgery, particularly total hip replacement.

Immunoassay by particle counting for coagulation testing: application to the determination of protein C.

Latex particles coated with F(ab)'2 fragments of anti-protein C IgG antibodies are agglutinated by protein C, and the quantity of particles agglutinated is proportional to the concentration of protein C. The reaction can be quantitated by optical particle counting. Based on this system, we designed an immunoassay for protein C. Precision measured at low, medium and high levels of protein C varied from 3.3% to 13.7%. Specificity was evaluated by dilution recovery. A correlation coefficient of r = 0.959 was found when the new method was compared with a chromogenic technique on 131 plasmas.

Immunoassay by particle counting for coagulation testing: application to the determination of antithrombin III, von Willebrand factor antigen (vWF:Ag) and plasminogen.

Based on immunoassay by particle counting, three methods for antithrombin III, von Willebrand factor and plasminogen were developed on an automated IMPACT machine and on a semi-automated MULTIPACT system. Precision of the techniques, measured at low, medium and high level of the calibration curve showed coefficients of variation varying from 4.3 to 13.8%. Accuracy was evaluated by dilution recovery test and by correlation with rocket immunoelectrophoresis and chromogenic substrate techniques. The results show that the proposed methods correlate well with existing techniques and that immunoassay by particle counting is applicable to several coagulation tests.

Changes in myocardial metabolism during therapy in patients with chronic stable angina: a comparison of long-term dosing with propranolol and nicardipine.

The long-term effects of antianginal therapy on coronary blood flow and myocardial metabolism were studied in 35 patients with chronic stable angina. Arterial and coronary sinus blood samples and coronary blood flow measurements were obtained before and after 1 month of oral administration of propranolol or of the calcium antagonist nicardipine. When the data obtained at a fixed heart rate (10% to 15% above the pretreatment sinus rhythm) were compared, no significant differences were evidenced between the propranolol and the nicardipine groups. Coronary blood flow and myocardial oxygen uptake were unchanged with both drugs. Myocardial lactate uptake increased in 11 patients of the propranolol group (from -2 +/- 42 to 66 +/- 47 mumol/min, p less than .001) and in 11 patients of the nicardipine group (from 0 +/- 36 to 31 +/- 29 mumol/min, p less than .001). In these 22 patients, the increase in lactate uptake was accompanied by reductions in uptake of free fatty acids and by a decrease in the coronary sinus concentration of thromboxane B2 from 131 +/- 87 to 61 +/- 32 pg/ml (p less than .01), whereas the transcardiac release of prostacyclin increased. None of these changes in free fatty acids or in prostanoid handling were observed in the nine patients (five in the propranolol and four in the nicardipine group) in whom lactate uptake was not augmented. During pacing-induced tachycardia, the metabolic effects of the two drugs appeared different. Myocardial lactate uptake decreased more in the patients receiving propranolol than in those receiving nicardipine and the combined productions of alanine and glutamine rose by 3.2 +/- 5.8 mumol/min in the propranolol group while it decreased by 3.1 +/- 8.2 mumol/min in the nicardipine group (p less than .025 propranolol vs nicardipine). In conclusion, long-term antianginal therapy with propranolol or nicardipine improved several markers of myocardial ischemia in approximately two-thirds of the patients. Although the changes observed at low heart rates were similar with the two drugs, the data also suggest that better metabolic protection is provided by the calcium antagonist during pacing-induced tachycardia.

Circulating lupus type anticoagulant and pulmonary hypertension associated with mixed connective tissue disease.

We report the case of a young woman, with mixed connective tissue disease (MCTD), associated with disabling pulmonary hypertension and presence of the "lupus anticoagulant". The "lupus anticoagulant", an antibody directed against phospholipid components, was linked in our patient to extensive thrombophlebitis and premature labor. Raynaud's phenomenon progressed towards finger necrosis in spite of optimal vasodilating treatment. The part played by the "lupus anticoagulant" in pulmonary hypertension remains to be established. Both these complications responded to prednisolone therapy, but the improvement was limited and short-lived.