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PubMed1990

Inhibition by recombinant hirudins of experimental venous thrombosis and disseminated intravascular coagulation induced by tissue factor in rats.

Antithrombotic potency of recombinant hirudins rHV2, rHV2-Lys47 and rHV2-Arg47 was studied in a model of experimental thrombosis induced by tissue factor in the rat. Venous thrombosis was induced by i.v. injection of 25 mg/kg tissue factor followed by stasis of the inferior vena cava. In this model natural recombinant hirudins, rHV2 and rHV2-Lys47 injected 5 min before thrombo-plastin totally inhibited thrombosis in the same micrograms range as heparin or natural hirudin extracted from leeches. However, the mutant variant rHV2-Arg47 gave a maximal 60% inhibition of thrombosis. Variants rHV2-Lys47 (30 micrograms/kg) and rHV2-Arg47 (157 micrograms/kg) injected 5 min before thromboplastin prevented by 90 to 100% the drop in platelet count observed during the disseminated intravascular coagulation induced by thromboplastin injection. Recombinant hirudins were less anticoagulant than heparin as measured by an APTT on rat plasma. After rat tail transection, rHV2-Lys47 caused a 2-fold smaller prolongation of the bleeding time than an equivalent antithrombotic dose of heparin. Plasmatic elimination of rHV2-Lys47 from rat plasma after i.v. injection had a fast distribution phase with a half-life of 3 min during which 90% of injected rHV2-Lys47 was lost and was followed by a slower elimination phase. Thus recombinant hirudin rHV2-Lys47 appears as a promising potent antithrombotic agent for the prevention of thrombin-dependent venous thrombosis and disseminated intravascular coagulation.

Animals↗

PubMed1989

[Thrombosis due to venous catheters--evaluation using CT].

Venous catheters for therapy and parenteral nutrition can cause thrombosis. A diagnostic elucidation and the evaluation of the extent of the thrombosis is indispensible for therapy decision. Besides phlebography, CT is a means for this. The results of CT-investigations of three patients with severe thrombosis caused by permanent venous catheters are shown. In all cases we were able to achieve the correct diagnosis and a reliable evaluation of the extent of the thrombosis. Small amounts of contrast medium are required and the investigation is tolerated even by seriously ill patients. CT therefore is an alternative to phlebography for the diagnostics and evaluation of the extent of thrombosis of the large veins.

Adult↗

PubMed1989

Perioperative asymptomatic venous thrombosis: role of duplex scanning versus venography.

We compared combined B-mode/Doppler (duplex ultrasonic scanning and venography in routine preoperative and postoperative screening for major proximal deep vein thrombosis in 78 patients undergoing total hip or knee arthroplasty. Of 309 extremity examinations, duplex scanning had an overall sensitivity of 85.7% (12/14) and a specificity of 97.3% (287/295). The preoperative prevalence and postoperative incidence of major deep vein thrombosis were 2.5% and 14.1% of patients, respectively, despite intensive mechanical and pharmacologic prophylaxis. In addition, venography documented a preoperative prevalence and postoperative incidence of isolated calf deep vein thrombosis in 2.5% and 16.7% of patients, respectively. Whereas such disease extended proximally even in the absence of anticoagulation in only 18% of patients studied by serial duplex scans, calf deep vein thrombosis accounted for the only two instances of pulmonary embolism in this study. There were no deaths related to pulmonary embolism. This study suggests that duplex scanning is useful in screening for perioperative deep vein thrombosis in patients undergoing total hip or knee arthroplasty, which carries a significant risk of venous thromboembolism despite routine prophylaxis.

Adult↗

PubMed1989

[Leg-/pelvic vein thrombosis from the viewpoint of the surgeon].

The pathogenesis of venous thrombosis is far less clear than that of arterial thrombosis. In spite of physical and medical prophylaxis, there is still a risk of thrombosis of approx. 5% left after elective abdominal surgery. Ascending phlebography cannot be dispensed with in case of an active therapeutic procedure such as fibrinolysis or venous thromectomy. In order to settle the question of thrombolysis or thrombectomy, we have to consider (1) the extent of the thrombosis, (2) the time of existence of the thrombosis, and (3) possible contra-indication of either method. Thus the two techniques do not compete with each other but are complementary. Because of the heterogeinity of the patients and the different indications for treatment, the results obtained in these two methods are hardly comparable.

Adolescent↗

PubMedDate not supplied

Diagnosis of deep venous thrombosis of the leg using immunoscintigraphy with 111In-labelled monoclonal antifibrin antibody fragments.

Fourteen unselected consecutive patients with clinically suggested deep venous thrombosis were studied using 111In-labelled monoclonal antibody Fab-fragments (59D8) in order to evaluate the accuracy of antifibrin imaging. Scintigrams of the legs were obtained at 1 to 4 h and 20 to 28 h in all patients and in seven dynamic studies were also performed. Contrast medium phlebography used as diagnostic standard revealed thrombosis in six patients who also had increased uptake of the tracer at immunoscintigraphy. Three patients had a positive finding at immunoscintigraphy without thrombosis. Because of the high sensitivity of this method, normal antifibrin images may be used to exclude thrombosis. Phlebography may then be restricted to positive cases to confirm the presence of thrombosis.

Aged↗

PubMed1988

Utility of impedance plethysmography in the diagnosis of recurrent deep-vein thrombosis.

Serial impedance plethysmography has been shown to be a safe and effective alternative to venography in the management of patients with clinically suspected acute venous thrombosis. The rate of normalization of an initial abnormal impedance plethysmogram and, consequently, the usefulness of impedance plethysmography in the management of patients with recurrent symptoms is, however, unknown. In a prospective cohort follow-up study, 161 consecutive patients with proved venous thrombosis and abnormal impedance plethysmograms were studied for one year. After 3, 6, 9, and 12 months, the impedance plethysmograms had normalized in 67%, 85%, 92%, and 95% of the patients, respectively. Thirty-five patients (22%) returned with clinically suspected recurrent thrombosis, of whom 31 had normal impedance plethysmograms prior to their return. In 18 of these patients, repeated tests were normal; these patients did not undergo anticoagulant therapy, and follow-up disclosed no subsequent adverse consequences. In the other 13 patients, the test again became abnormal; 11 patients were shown by venograms to have recurrent deep-vein thrombosis. Consequently, 29 (83%) of the 35 patients in whom the suspicion of recurrent thrombosis arose could have been managed with impedance plethysmography alone without the necessity for venography or anticoagulant therapy. It is concluded that normalization of impedance plethysmography tests occurs in almost all patients within nine months, and that serial impedance plethysmography is useful for patient management in nearly 90% of patients presenting with recurrent symptoms.

Acute Disease↗

PubMed1986

Septic deep vein thrombosis.

Anticoagulation is the cornerstone in the treatment of deep vein thrombosis. However, the treatment of septic deep vein thrombosis is controversial. Unlike septic superficial vein thrombosis, venous excision is often associated with limb-threatening or even life-threatening complications. Some authors have suggested thrombectomy as the only means of resolving the sepsis. We reviewed our experience with seven patients who had septic deep vein thrombosis. Phlebography or noninvasive studies documented deep vein thrombosis and blood cultures were positive in all patients. The mean age was 31.5 years with a male/female ratio of 5:2. All patients were treated with anticoagulants and intravenous antibiotics. One patient required surgical exploration for associated abscess of the groin. The patients became afebrile with normal white blood cell counts from 3 to 18 days after therapy was begun. No cases of recurrent sepsis occurred. We conclude that antibiotic therapy and anticoagulation are adequate treatment and therefore consider venous thrombectomy unnecessary.

Adult↗

PubMed1979

[Thrombosis of the portal and superior mesenteric veins in a patient with a congenital and familial deficiency in antithrombin III (author's transl)].

Thrombosis of the visceral veins is an extremely rare condition in cases of congenital and hereditary deficiency of antithrombin III, associated with recurring venous thorbosis of the limbs. The authors report such a case in a man of 40 years of age, who had this deficiency, associated with thrombosis of the portal and superior mesenteric veins and a portal cavernoma. They stress the frequent association of recurring peripheral vein thrombosis, portal vein thrombosis in adults, and thrombosis of the mesenteric vein, and the importance of systematic measurements of antithrombin III levels in these pathological conditions.

Adult↗

PubMed1974

On the mechanisms responsible for selection of hepatic veins as target for thrombosis following injection of endotoxin in hyperlipemic rats.

The feeding of a butter-rich diet, to sensitize rats for studying the phenomenon of hepatic vein thrombosis, is shown to produce severe liver steatosis leading to a sinusoidal barrage and portal hypertension. The portal pressure in these animals was 210 +/- 4 mm of saline, as compared to 113 +/- 3 mm in the normal rat. Blood circulation studies using carbon suspensions revealed production of a vascular stasis in the hepatic veins after 60 to 90 minutes, when endotoxin (Salmonella typhosa, 0.3 mg/kg) is introduced into the blood circulation to initiate hepatic vein thrombosis. Similar results were observed after 15 minutes with ellagic acid (1 mg/kg/min). The stasis was found in connection with an additional intrahepatic resistance to blood flow as evidenced by a rise in portal pressure and by a reduction in liver perfusion in relation with development of systemic hypotension. In contrast with this, endotoxin initiated only slight and transient changes in the normal rat. Thrombosis immediately followed production of stasis in the hepatic vein, whether the phenomenon was initiated by endotoxin or ellagic acid. Furthermore, inhibition of the vascular stasis of alpha-adrenergic blockade (phenoxybenzamine, 3 mg/kg) was accompanied by prevention of hepatic vein thrombosis. It is concluded that stasis in the hepatic veins resulting from a mechanical obstruction of the circulation by steatosis and by an additional reduction in blood flow initiated by endotoxin, is responsible for selection of hepatic veins as targets for thrombosis following injection of endotoxin in hyperlipemic rats.

Animals↗

PubMed1982

The diagnostic value of the fibrinogen/fibrin fragment E antigen assay in clinically suspected deep vein thrombosis.

We have evaluated the fibrinogen/fibrin fragment E antigen assay as a diagnostic test in patients with clinically suspected venous thrombosis by comparing the results of this assay with venography in 272 patients. The result of the fragment E antigen assay was elevated in 79 of 80 patients with positive venograms for recent venous thrombosis (sensitivity 99%) and within the normal range in 161 of 192 patients with normal venograms (specificity 84%). The fragment E assay was also evaluated in 130 medical and surgical controls without evidence of venous thrombosis by leg scanning and the test was found to be relatively nonspecific. However, in the patient group under study, a correct clinical diagnosis of no thrombosis, based on a normal fragment E result, was made in 161 of 162 cases (negative predictive value of 99%). Therefore, a normal test result effectively excludes a diagnosis of venous thrombosis in clinically symptomatic patients. The assay, as currently performed, is technically demanding and takes 24 hr to complete. Therefore, it will have to be simplified before it can be applied to clinical practice.

Adolescent↗

PubMed1978

The relationship of intravascular coagulation and fibrinolysis to venous thrombosis following total hip replacement.

Soluble fibrin complexes, fibrin degradation products, and anti-thrombin III levels were determined in the plasma of 20 patients undergoing elective total hip replacement. The presence of deep venous thrombophlebitis was determined by venography at the end of the first postoperative week. Patients who developed thrombosis exhibited impairment of fibrinolysis as de-Patients who developed thrombosis exhibited impairment of fibrinolysis as detected levels of anti-thrombin III and soluble fibrin complexes were not useful in indicating the presence of deep venous thrombosis. However, the preoperative level of soluble fibrin complexes closely correlated with the subsequent development of thrombosis. Elevated soluble fibrin complexes appear to identify a group of patients with activated coagulation systems who are prone to develop thrombosis during total hip replacement.

Antithrombin III↗

PubMed1981

Pulmonary artery thrombosis in three dogs with hyperadrenocorticism.

Varying degrees of respiratory distress developed in 3 dogs in which hyperadrenocorticism was diagnosed. The respiratory distress was attributed to pulmonary artery thrombosis. Radiography revealed pleural effusion, increased diameter and blunting of the pulmonary arteries, lack of perfusion of the obstructed pulmonary vasculature, and overperfusion of the unobstructed pulmonary vasculature. Thrombosis was confirmed by nonselective angiocardiography in each case. In 1 case, selective angiocardiography showed marked reduction of the transit time of contrast medium from the right atrium to the aorta. Hypertension proximal to the site of thrombosis was confirmed in 2 cases by showing increases in the right ventricular systolic pressures (80 mm of Hg in one case and 54 mm of Hg in the other case). In 3 cases, there was moderate hypoxemia with hypocapnia, suggesting a ventilation-perfusion mismatch. Clinical findings other than respiratory distress included hepatomegaly, ventral edema, orthopnea, and a jugular pulse. Pulmonary artery thrombosis, as it occurred in these 3 cases, was compared with the disease in man. It was concluded that pulmonary artery thrombosis should be suspected in cases of intractable dyspnea, right-sided heart failure of unexplained origin, and acute unexplainable death.

Adrenocortical Hyperfunction↗

PubMed1978

The frequency and significance of postoperative plantar vein thrombosis judged by the 125I-fibrinogen test.

In 318 patients screening for the development of postoperative deep vein thrombosis was made with the 125I-fibrinogen test. In addition to the conventional measurements over the leg the planta pedis was also included. Of 221 legs with thrombosis 75 had an increased uptake in the planta pedis, but only in sixteen patients an isolated plantar thrombosis was found. In only eight of 70 thrombi there was evidence of a proximal extension of the plantar vein thrombosis. The time for the thrombosis debut did not differ between isolated plantar vein thrombi and more extensive thrombi; the majority beginning during the first four postoperative days.

Aged↗

PubMed1994

[Deep venous thrombosis and cancer. A one year evaluation of etiologic screening of patients hospitalized in Internal Medicine].

The aim of this study was to evaluate over one year the minimal etiologic screening carried out on each patient hospitalized in Internal Medicine for a deep venous thrombosis (DVT) and to search for clinical features possibly relating thrombosis to neoplasia. 53 patients (27 male and 26 female; mean age 63.6 years, range: 18-19) with DVT of the lower limbs were included in the study. The initial etiologic screening consisted of a complete clinical examination, a biological assessment (blood cell and platelet count, Activated Partial Thromboplastin Time, inflammation and liver investigations), a radiography of the thorax and abdomino-pelvic ultrasonography. This etiologic screening was evaluated one year after the thrombotic event. The initial assessment was positive in 44 cases (83% of the patients), 9 thrombosis remained unexplained. Neoplasia was identified in 8 cases (15% of the patients), the diagnosis being often evoked at the time of interrogation or during the clinical examination; the systematic biological assessment only revealed an etiology in one case: this was a primary thrombocythemia discovered by platelet count. On evaluation one year later, amount the 9 DVT unexplained by the initial screening, 8 remained totally unexplained. On the other hand, a cancer of the colon revealed by proctorrhagia during oral anticoagulant treatment, had been undiscovered. No significant difference was found between the two groups (cancers and noncancerous etiologies) as concerns age, sex, thrombus topography, the side affected or the embolic events. However, the occurrence of subsequent thrombosis under well controlled anticoagulant treatment clearly characterises thrombosis associated with neoplasia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1994

Plasma D-dimer as a marker for postoperative deep venous thrombosis. A study after total hip or knee arthroplasty.

Plasma levels of D-dimer have been found useful as a marker of deep venous thrombosis in those patients in whom thrombosis is suspected, but their usefulness in postoperative screening is less clear. We have investigated the relationship of D-dimer to deep venous thrombosis in 90 patients after total hip and knee arthroplasty. From the first postoperative day the D-dimer levels were found to be highly significantly raised in patients with deep venous thrombosis. A combined result over the first six postoperative days in excess of 1200 ng/ml correlated with thrombosis with a specificity of 100%, sensitivity of 45%, positive predictive value of 60%, and negative predictive value of 100%. However, individual estimations were not discriminatory.

Aged↗

PubMed1994

Transesophageal echocardiographic assessment of superior vena cava thrombosis in patients with long-term central venous hemodialysis catheters.

In some patients with end-stage renal failure, arteriovenous fistulas cannot be created due to poor vessel conditions. Alternatively, hemodialysis (HD) can be performed using long-term central venous catheters. However, these dialysis catheters are associated with a presently unknown risk of superior vena cava (SVC) thrombosis. We examined 20 patients (11 female, 9 male, age 29-83 years) 1-48 (mean 15) months after transjugular insertion of a permanent single lumen silicone rubber HD catheter. All patients underwent both transthoracic (TTE) and biplane transesophageal (TEE) echocardiography. TTE visualized the catheter only when its tip was localized in the right atrium (2 patients), but did not succeed in adequate imaging of the SVC. In contrast, TEE allowed high quality imaging of the SVC in all patients and detected a SVC thrombosis in 6 patients; in 3 of them, caval thrombosis was subtotal. One additional patient showed a thrombus attached to the catheter tip alone. Dwelling time of catheters since insertion in the SVC was not significantly different in patients with and without thrombosis. Reduced blood flow during HD was observed in 5 of 7 patients with catheter-associated thrombi but also in 4 of 13 patients without evidence for caval thrombosis by TEE. It is concluded that thrombotic occlusion of the SVC is frequent in patients with long-term central venous access; it does not necessarily correlate with clinical signs but can easily be detected by TEE. Patients with long-term central venous hemodialysis catheters should undergo transesophageal echocardiography at regular intervals.

Adult↗

PubMed1994

[Which antithrombotic agents should be prescribed in deep venous thrombosis of the limbs?].

Anticoagulants are generally prescribed for the treatment of thrombosis occurring in deep veins. Recent progress in both heparin therapy and in antivitamin K agents require a new look at the therapeutic choice. Due to its immediate anticoagulant action heparin is essential as first intention therapy. Indeed, initial oral anticoagulants are less effective, both in terms of clinical extension and in radiological outcome, than an initial heparin/antivitamin K combination. Non-fractionated heparin administered with an automatic syringe after a priming bolus is the reference treatment for venous thrombosis since it has now been established that 2 subcutaneous injections of heparin are less effective than the intravenous route. Both the effect and safety of low molecular weight heparin have been shown to be comparable with that of non-fractionated heparin. When the dose is adapted to patient weight, 70% are within therapeutic limits after the first injection. Two daily injections of 100 IU per kg body weight can be recommended as initial treatment for deep vein thrombosis. Anticoagulation must be continued for several days but the risk of induced thrombocytopenia persists with low molecular weight heparin. Long-term use should be retained essentially for pregnant women with deep vein thrombosis due to the foetal risk of oral antivitamin K. Antivitamin K oral agents may be initiated early without hindering the anticoagulant effect of heparin. With oral agents, anticoagulant equilibrium is reached, on the average, after 6 days and is a function of vitamin K-dependent half-lives. Since antivitamin K agents affect the stability of prothrombin times during the day/night cycle, it has been recommended to favour long half-life molecules. Standardized prescription protocols can improve safety and anticoagulant equilibrium. To date, the recommended management of deep vein thrombosis includes combining low molecular weight heparin and long half-life antivitamin K. Further progress may be forthcoming with the development of new antithrombotic agents such as hirudine or sulfated heparanes.

4-Hydroxycoumarins↗

PubMed1994

Different incidence of venous thrombosis in patients with inherited deficiencies of antithrombin III, protein C and protein S.

A cohort study was undertaken to compare the incidence of thrombosis in patients with inherited deficiency of Antithrombin III (n = 9), Protein C (n = 36) and Protein S (n = 36). The patients were stratified for schedule of antithrombotic prophylaxis and followed for a total period of 160 patient-years. Seven venous thrombosis were observed for a total incidence of 4.3% pts.-ys. The incidence of thrombosis was not significantly different in patients of different age, sex and schedule of prophylaxis, although there was a trend to a lower incidence in young individuals and in those receiving long-term oral anticoagulation. Patients with AT III deficiency had an higher incidence of thrombosis than patients with Protein C or Protein S deficiency (12 vs. 2.8 vs. 3.3% pts.-ys, p < 0.05), despite the fact that they were, on average, younger and more prophylaxed. This study suggests that congenital Antithrombin III deficiency constitutes a greater risk of thrombosis than congenital deficiencies of Protein C and Protein S.

Administration, Oral↗