Lower limb veins should be systematically explored in patients with isolated heparin-induced thrombocytopenia.
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Anticoagulants↗
Biomedical subjects
B Tardy
Publications and source records attributed to B Tardy.
[Diagnosis and development of heparin-induced thrombocytopenia. Biological and clinical aspects].
Two types of thrombocytopenia occur during treatment with heparin: type I and type II heparin-induced thrombocytopenia (HIT). Type I HIT is due to a direct interaction between heparin and platelets. They are asymptomatic, occur early, mild and transitory. Type II HIT which is immunoallergic in nature is the most important complication of this treatment. The thrombocytopenia has a different presentation, acute with a fall in platelets over 30 per cent and is often associated with the occurrence or worsening of a venous or arterial thrombotic episode. The major problems of this secondary type are threefold: its recognition, its confirmation and its management should be as early as possible to avoid the development of often dramatic complications which compromise the prognosis. Laboratory investigations are required by highly reliable specialist laboratories following a careful clinical history. The natural history of the platelet count should enable the difficult diagnosis of HIT to be made more accurately. The treatment of confirmed HIT and/or symptomatic HIT often requires a multidisciplinary approach from a specialized team involving clinicians and hematologists. Two therapies with the benefit of large experience have just been obtained in France with marketing approval (AMM) for the management of HIT: danaparoid (Orgaran) and recombinant hidurin, lepirudin (Refludan). A declaration to the regional drugs monitoring center should not be omitted. In addition, each patient should be given a certificate confirming the immunallergy thus avoiding any further exposure with potentially dramatic consequences.
Anticoagulants↗
[Fatal voluntary poisoning with cibenzoline. Failure of conventional therapies].
BACKGROUND: Massive voluntary ingestion of cibenzoline causes major cardiotoxicity. We report on two cases where conventional treatments were ineffective. CASE REPORTS: Two patients were admitted to the intensive care unit of a University Hospital after massive voluntary intoxication with cibenzoline. Delay to admission after ingestion of cibenzoline was 1.5 and 4 hours. Circulatory impairment developed rapidly in both patients due to major atrioventricular and ventricular conduction disorders. Conventional intensive care procedures (sodium lactate and adrenaline) were performed but only provided temporary and incomplete efficacy. Outcome was fatal in both cases. DISCUSSION: The lethal potential of cibenzoline is very high. Extra-corporeal cardiocirculatory assistance might be an advisable measure if conventional therapy is unsuccessful. No clearly defined prognosis factors in cibenzoline intoxications have been reported.
Anti-Arrhythmia Agents↗
A clinical trial of vena caval filters in the prevention of pulmonary embolism in patients with proximal deep-vein thrombosis. Prévention du Risque d'Embolie Pulmonaire par Interruption Cave Study Group.
BACKGROUND: The efficacy and safety of vena caval filters in the prevention of pulmonary embolism in patients with proximal deep-vein thrombosis is still a matter of debate. METHODS: Using a two-by-two factorial design, we randomly assigned 400 patients with proximal deep-vein thrombosis who were at risk for pulmonary embolism to receive a vena caval filter (200 patients) or no filter (200 patients), and to receive low-molecular-weight heparin (enoxaparin, 195 patients) or unfractionated heparin (205 patients). The rates of recurrent venous thromboembolism, death, and major bleeding were analyzed at day 12 and at two years. RESULTS: At day 12, two patients assigned to receive filters (1.1 percent), as compared with nine patients assigned to receive no filters (4.8 percent), had had symptomatic or asymptomatic pulmonary embolism (odds ratio, 0.22; 95 percent confidence interval, 0.05 to 0.90). At two years, 37 patients assigned to the filter group (20.8 percent), as compared with 21 patients assigned to the no-filter group (11.6 percent), had had recurrent deep-vein thrombosis (odds ratio, 1.87; 95 percent confidence interval, 1.10 to 3.20). There were no significant differences in mortality or the other outcomes. At day 12, three patients assigned to low-molecular-weight heparin (1.6 percent), as compared with eight patients assigned to unfractionated heparin (4.2 percent), had had symptomatic or asymptomatic pulmonary embolism (odds ratio, 0.38; 95 percent confidence interval, 0.10 to 1.38). CONCLUSIONS: In high-risk patients with proximal deep-vein thrombosis, the initial beneficial effect of vena caval filters for the prevention of pulmonary embolism was counterbalanced by an excess of recurrent deep-vein thrombosis, without any difference in mortality. Our data also confirmed that low-molecular-weight heparin was as effective and safe as unfractionated heparin for the prevention of pulmonary embolism.
Aged↗
Pharmacokinetic and pharmacodynamic variations of acenocoumarol orally administrated either once or twice daily in patients with deep venous thrombosis.
The literature suggests that variations in anticoagulant effect occur when acenocoumarol is administrated in a daily dose. We assessed the anticoagulant effects of acenocoumarol with INR, factors VII and X and protein C in 12 randomly selected hospitalised patients with deep-vein thrombosis, six of them receiving a daily dose of acenocoumarol, the other six receiving twice daily doses. When the drug effect had been at a steady-state for at least 72 h, five blood samples were drawn per patient over a period of 24 h. No nycthemeral significant variations were noted for INR, factor X and protein C in the two groups (P > 0.10). Nycthemeral significant variation in factor VII when acenocoumarol was administered once daily was noted (P = 0.02), but the clinical relevance of factor VII variation at steady-state is uncertain. In spite of the short pharmacokinetic half-life of acenocoumarol, a stable nycthemeral pharmacodynamic activity was observed after once daily administration; twice-daily administration of acenocoumarol does not appear to be justified.
Acenocoumarol↗
Prevalence of factor V Leiden (APCR) and other inherited thrombophilias in young patients with myocardial infarction and normal coronary arteries.
OBJECTIVE: To investigate the role of activated protein C resistance (APCR, factor V Leiden) in coronary artery thrombosis. METHODS: The prevalence of APCR and of congenital deficiencies of antithrombin III, protein C, protein S, plasminogen, and factor XII was investigated in adult patients under 45 years of age with acute myocardial infarction. The results were compared with those of a group of 53 age and sex matched control subjects. RESULTS: Among 75 patients under the age of 45 years who were admitted from November 1994 to April 1996 for acute myocardial infarction, 22 (29.3%) had normal coronary arteriography (group I) and 53 (70.7%) had significant coronary artery disease (group II). Inherited thrombophilia was more often found in group I (4/22, 18.2%) than in group II (4/53, 7.5%) but the difference was not significant (F test: p = 0.22). The prevalence of APCR was 9.1% (2/22) in group I, 3.8% (2/53) in group 2 (p = 0.57), and 3.8% (2/53) in the normal control group (p = 0.57). CONCLUSIONS: The prevalence of congenital thrombophilias, including APCR, does not seem to be increased in young patients with myocardial infarction and normal coronary angiograms, compared with young patients with coronary atherosclerosis and with normal control subjects. However, the statistical power of the study is too low to detect a significant difference and these results are published to allow a meta-analysis of this problem in the future.
Activated Protein C Resistance↗
Evaluation of D-dimer ELISA test in elderly patients with suspected pulmonary embolism.
STUDY OBJECTIVE: To determine the clinical usefulness of D-dimer ELISA test in elderly patients with clinically suspected pulmonary embolism (PE). DESIGN: Prospective cohort study. PATIENTS: Ninety-six consecutive outpatients older than 70 years with a duration of symptoms shorter than one week and without metastatic cancer or recent surgery, trauma, infection, stroke, myocardial infarction, deep vein thrombosis (DVT) or PE, or treatment with curative doses of heparin or oral anticoagulant. INTERVENTION: All patients underwent at least ventilation/perfusion scan and bilateral ultrasonic duplex scan and a blood sample collection within 24 hours of admission. When necessary a pulmonary angiography and/or a bilateral venography were also performed. Patients were classified as follows: (1) PE-positive: positive angiography or high probability V/Q scan and deep vein thrombosis (proven either by venography or by ultrasonic duplex scan) or non high probability V/Q scan and either DVT (proven at presentation by venography or by ultrasonic duplex scan) or symptomatic thromboembolic event within 3 months of follow-up; or (2) PE-negative; normal V/Q scan or normal angiography or non high probability V/Q scan and either negative ultrasonic duplex scan or normal venography and low clinical probability and absence of symptomatic thromboembolism within 3 months of follow-up. D-dimer measurements were performed using both a conventional and a single semi-quantitative ELISA test (Asserachrom D-di, Instant I.A.D-dimer). RESULTS: Using a cutoff value of 500 ng/ml, the conventional ELISA D-dimer test showed a sensitivity and a negative predictive value of 100% with poor specificity and positive predictive value of 14.3% and 45.5% respectively. The new rapid semi-quantitative D-dimer test displays worse results with sensitivity, negative predictive value, specificity and positive predictive value of 92.3%, 82.4%, 25% and 46% respectively. CONCLUSION: In a geriatric population, conventional ELISA D-dimer is a good marker to exclude PE but, due to the comorbid conditions, only a few patients presented with D-dimer values less than 500 ng/ml.
Aged↗
Fatal danaparoid-sodium induced thrombocytopenia and arterial thromboses.
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Aged↗
Totally implantable vascular access and emergent management of refractory recurrent grand mal status epilepticus.
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Adult↗
Evolution of blood coagulation and fibrinolysis parameters after abrupt versus gradual withdrawal of acenocoumarol in patients with venous thromboembolism: a double-blind randomized study.
A double-blind randomized trial was conducted to research a hypercoagulable state rebound after abrupt versus gradual withdrawal of acenocoumarol, 20 patients were included: 10 in the abrupt withdrawal group (AW) and 10 in the gradual withdrawal group (GW). Between days 1 and 15,F1 + 2 was higher in group AW (P < 0.002). A significant increase of D-dimer with time was found (P < 0.001) without difference between the two groups, tPA and PAI-1 levels remained stable throughout without difference between the two groups. No rebound phenomenon was observed. Four thrombotic recurrences were observed: group AW: 1, group GW: 3 (P = 0.29). There is neither clinical nor biological support for a gradual anticoagulation withdrawal.
Acenocoumarol↗
Absence of cross-reactivity of SR90107A/ORG31540 pentasaccharide with antibodies to heparin-PF4 complexes developed in heparin-induced thrombocytopenia.
New carbohydrate-based anticoagulants devoid of the side effects of unfractionated heparin are currently under development and show a major potential for patients with heparin-induced thrombocytopenia (HIT) who still require efficient antithrombotic therapy. As HIT is usually associated with antibodies to heparin-platelet factor 4 (H-PF4) complexes, cross-reactivity of the heparin pentasaccharide SR90107A/ORG31540 was tested in the presence of PF4 with the plasma from 49 patients with HIT. No cross-reactivity was observed whatever the pentasaccharide concentrations. Although more extensive studies are required for excluding its total absence of immunogenicity and pathogenicity, this pentasaccharide is a candidate for use in emergency situations in patients with HIT.
Autoantibodies↗
Effects of long travels in sitting position in elderly volunteers on biological markers of coagulation activation and fibrinolysis.
OBJECTIVE: To evaluate whether long travel in sitting position is associated with an increase of coagulation activation and/or a decrease of fibrinolytic activity. DESIGN: Comparison of blood coagulation and fibrinolysis parameters before and after two pleasure trips by bus organized in winter period (600 km in 8 hours) and in summer period (1200 km in 16 hours). SUBJECTS: 31 and 23 healthy elder volunteers for the winter and the summer trip respectively. Nine other elder volunteers were selected as a control group for the winter study. MAIN OUTCOME MEASURES: prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin III (TAT), D-dimers (D-D), factor VII activated, plasminogen activator inhibitor (PAI), tissue-type plasminogen activator (t-PA), plasma albumin. RESULTS: A significant difference before and after the travel was only observed for TAT in the summer period. However all values of TAT were in the normal range. No volunteer presented with thromboembolic disease during the month following the travel. CONCLUSION: In the condition of our study, long travel in sitting position does not lead to an enhanced procoagulant state for elderly with varicose veins. These results suggest that there is no biological support to propose heparin prophylactic therapy for the elderly with varicose veins wishing to travel by bus.
Aged↗
Presence of autoantibodies to interleukin-8 or neutrophil-activating peptide-2 in patients with heparin-associated thrombocytopenia.
Eighty-seven patients with heparin-associated thrombocytopenia (HAT) showed either a positive heparin platelet aggregometry test result and/or the presence of antibodies to heparin-platelet factor 4 (H-PF4) complexes by enzyme-linked immunosorbent assay (ELISA). Fifteen of these patients lacked antibodies to H-PF4, and plasma from these patients was analyzed for the presence of antibodies to PF4-related chemokines, Neutrophil-activating peptide-2 (NAP-2) and interleukin-8 (IL-8). Of these 15 patients, 6 showed antibodies to IL-8 and 3 to the platelet basic protein (PBP)-derived protein, NAP-2. Antibodies to IL-8 and NAP-2 were not observed in control patients (n = 38), patients with HAT and H-PF4 autoantibodies (n = 72), patients with autoimmune diseases (n = 21), or patients with non-HAT thrombocytopenia (n = 30). Five of these nine patients with anti-IL-8 or anti-NAP-2 developed thrombosis during heparin treatment, which is not statistically different from the patients with H-PF4 antibodies. The existence of autoantibodies to IL-8 and NAP-2 in HAT patients highlights the significance of chemokines in the pathogenesis of HAT. The contribution of heparin in vitro was minimal in patients with anti-IL-8 and anti-NAP-2 antibodies, suggesting a biologic difference from the majority of patients with HAT and anti-PF4 antibodies. It may be that antibodies to IL-8 and NAP-2 have weaker affinity for heparin and that the ELISA system may not reflect in vivo heparin-chemokine complex formation. Alternatively, antichemokine autoantibodies may predate heparin exposure, and the role of heparin in initiating HAT may be to mobilize the chemokines and to target them to platelets, neutrophils, or endothelial cells. Subsequent chemokine-binding autoantibodies then lead to cell activation resulting in thrombocytopenia and thrombosis.
Adult↗
Symptomatic inferior vena cava filter thrombosis: clinical study of 30 consecutive cases.
Inferior vena cava (IVC) filter thrombosis has not been described as a clinical entity. Thirty patients with IVC percutaneous filter thrombosis were assessed by cavography, computed tomographic (CT) scan and/or duplex ultrasonography. All patients had proximal venous thrombosis when the filter was placed, and the indication for filter placement was a contraindication to anticoagulant therapy in eight patients (27%). Filter thrombosis occurred within 6 months following filter placement in 15 patients (early filter thrombosis group). Among these patients, 10 were not treated with oral anticoagulant, and none of the other five received adjusted anticoagulation. No patients with late filter thrombosis received anticoagulant at the time of the diagnosis. Early filter thrombosis was mainly associated with LGM filters (12 of the 15 cases). Occlusion was revealed by recurrent venous thrombosis in 18 cases. A thrombus above the filter and pulmonary embolism was found in 10 patients (33%). Thrombolytic therapy failed in 5 out of 7 cases, and all but two patients were treated with anticoagulant therapy. In conclusion, early filter thrombosis appears to be due to intracaval extension of deep vein thrombosis, and this emphasizes the need for appropriate anticoagulation. In the case of temporary contraindication to anticoagulation at the time of the filter placement, anticoagulant should be reassessed later.
Adult↗
Computed tomography in first uncomplicated generalised seizure. Should always be performed.
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Alcoholism↗
[Justification of routine puncture of ascites in cirrhotic patients admitted to emergency hospital units].
OBJECTIVES: Spontaneous bacterial peritonitis (SBP) is a frequent, serious, recurrent complication, occurring in 10 to 30% of cirrhotic patients hospitalized with ascites. The key to diagnosis of SBP is ascites paracentesis and polymorphonuclear count in ascitic fluid. The purpose of our study was to evaluate sensitivity and specificity of clinical and biological criteria in diagnosis of 5 BP. METHODS: We prospectively reviewed 30 adult cirrhotic patients admitted in our emergency department with ascites. Ascites paracentesis was performed in each patient, and SBP diagnosis was based on either positive bacteriological culture or polymorphonuclear count above 250/mm3 in ascitic fluid. Classical criteria for SBP were recorded: blood pressure under 90 mm of Hg, abdominal pain, temperature above 38.5 or under 36.5, jaundice, encephalopathy, increased serum bilirubin or creatinine, leukocyte blood count about 12 G/l. We evaluated sensitivity and specificity of those criteria in SBP, and compared their frequency in patients with SBP or sterile ascitic fluid. RESULTS: Thirty patients were included in our series, and in 14 of them a SBP was diagnosed. A significant difference was observed between spontaneous bacterial peritonitis and sterile ascitic fluid for abdominal pain and temperature abnormalities, but specificity and sensitivity of these criteria were very low. Moreover, SBP was asymptomatic in 7%. CONCLUSION: Due to the high rate of mortality in patients with SBP we recommend diagnostic procedures for this frequent complication as soon as patient is admitted in emergency department. This diagnosis must be based on ascitic fluid paracentesis, which has to be performed, in the emergency department, in every cirrhotic patient admitted with ascites. Indeed, SBP is often asymptomatic, and no clinical or bacteriological criteria can be considered as completely reliable for the diagnosis of spontaneous bacterial peritonitis.
Ascites↗
[Thrombotic thrombocytopenic purpura disclosing cancer: apropos of 2 cases].
Thrombotic thrombocytopenic purpura (TTP) causes severe haemolytic anaemia, thrombopenia, fever and neurological and renal involvement. Currently five large aetiologic groups have been identified: viral or bacterial infection, drugs, conjunctive tissue diseases, pregnancy and solid tumours. We observed two cases resulting from an adenocarcinoma. In the first case, a 71-year-old man with chronic silicosis, the presenting signs were asthenia, fever, epistaxis with diffus purpura and spontaneous haematomas of the lower limbs. Diagnosis of TTP was based on routine laboratory tests and the patient responded well to fresh frozen plasma. On the 5th day of treatment, haemoglobin level dropped sharply and melana occurred. Upper digestive tract endoscopy revealed a tumoural formation of the antrum-fundic junction and histology examination of the biopsy confirmed the diagnosis of adenocarcinoma. Ten months after gastrectomy the patient was in excellent health with no relapse of the TTP. In the second case, the presenting signs included spontaneous haematomas, rectorrhagia and low grade fever. Microscopic haematuria and renal failure were observed in addition to the biological syndrome of TTP. The patient responded poorly to fresh frozen plasma and packed cell transfusions. Plasma exchange was equally unsuccessful. The disease continued a fulminant course and the diagnosis of adenocarcinoma located in a pulmonary lymph nodes was made at autopsy. These rare cases of TTP caused by cancer emphasize the importance of a thorough aetiological research. Plasma exchange has been shown to be effective but mortality at 1 year approximately 85% in cancer related cases. Early diagnosis and specific anti-cancer therapy might improve prognosis. We report our personal experience with 16 other similar cases.
Adenocarcinoma↗
Adult first generalized seizure: etiology, biological tests, EEG, CT scan, in an ED.
The purpose of this study was to evaluate adult first seizures in an emergency department by analyzing etiologic and epidemiological data and studying the usefulness of biological screening, electroencephalogram (EEG), and cerebral computed tomography (CT) scan. This was a retrospective study of a 3-year period during which 247 patients were admitted to an emergency department for a first generalized seizure. A CT scan had been performed in 247 patients and an EEG in 209. Etiologies were found to be (1) unknown, (2) alcohol abuse, (3) stroke, and (4) tumor. Early recurrence rate was 18.5%. EEG was of low interest in emergency. The rate of cerebral focal lesions on CT scan was significantly lower when both examination results and EEG were normal. The rate of metabolic abnormalities was 4.9%. It was concluded that (1) a short hospitalization is advisable because of recurrences, (2) recurrence rate does not increase significantly in patients with focal cerebral lesion, (3) metabolic screening is necessary, and (4) CT scan will be an outpatient procedure for most patients.
Adolescent↗