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PubMed1994

Antithrombotic effect of recombinant truncated tissue factor pathway inhibitor (TFPI1-161) in experimental venous thrombosis--a comparison with low molecular weight heparin.

The aim was to investigate whether a truncated recombinant Tissue Factor Pathway Inhibitor (TFPI1-161), which lacked the third Kunitz-type domain and the basic c-terminal region, had an antithrombotic effect comparable to LMWH in a randomised double-dummy study. The experimental thrombosis was induced in jugular veins, in a total of 40 rabbits by a combination of destruction of the endothelium and restricted blood flow. Group 1: placebo, gr 2: LMWH 60 anti-FXa IU/kg, gr 3-5: 0.1, 1.0 and 10.0 mg/kg TFPI1-161. TFPI1-161 reduced the thrombus weights in all treated groups, significantly in doses of 1.0 and 10.0 mg/kg compared to placebo. The frequency of thrombosis and occlusive thrombosis were also significantly reduced in those doses. The antithrombotic properties of TFPI1-161 (1.0-10.0 mg/kg) measured as thrombus weight, frequency of thrombosis and frequency of occlusive thrombosis was equivalent to the anti-thrombotic properties of LMWH. In the anti-FXa, APTT and PT-assays TFPI1-161 displayed a dose dependent increase of activity. Recombinant-TFPI1-161 did not influence the anti-FIIa-assay. No haemorrhagic side effects were noted.

Animals↗

PubMed1993

[Color-coded duplex ultrasound and contrast medium enhanced duplex ultrasound in deep venous thrombosis].

Even with highly developed ultrasound systems, diagnosis of deep leg vein thrombosis is difficult in lower leg veins and in the area of the adductor channel. In order to evaluate color duplex-sonography, contrast media duplex-sonography and phlebography in comparison, 79 patients (38 men and 40 women aged 54 to 89) with deep leg vein thrombosis were examined. As a result, patients suffering from thrombosis were characterized by a vein-artery quotient of > 2.0 (p < 0.01). In color Doppler duplex-sonography false negative findings occurred in 12 cases of lower leg vein thrombosis and in 3 cases of thrombosis within the adductor channel. By contrast media duplex-sonography the diagnostic reliability could be increased to a sensitivity of over 95 per cent.

Aged↗

PubMed1995

[Jugular vein thrombosis as incidental ultrasound finding in tumor patients].

At present thrombosis of the internal jugular vein is an uncommon event that is now more frequently associated with diagnostic or therapeutic catheterization. If an apparent spontaneous thrombosis occurs, malignancy should be considered in the differential diagnosis. Two cases of clinically asymptomatic thrombosis of the internal jugular vein are presented. A 69-year-old female patient with metastasizing renal cell carcinoma had bilateral thrombosis and a 73-year-old male with a small laryngeal carcinoma had a unilateral thrombosis. Increased blood coagulability as part of a paraneoplastic syndrome was considered to be the possible etiology. The role of sonography in the diagnosis is emphasized.

Aged↗

PubMed1996

Prophylaxis of deep venous thrombosis after total hip arthroplasty by using intermittent compression of the plantar venous plexus.

A randomized, prospective, blinded study comparing the efficacy of prophylaxis of deep venous thrombosis by using (A) heparin-aspirin therapy, (B) intermittent pulsatile pneumatic-pump compression of the plantar venous plexus, or (C) both methods, was conducted in patients undergoing elective total hip replacement arthroplasty. Duplex ultrasonography was obtained in all 75 patients before surgery, at 1 week, and 2 weeks after surgery, to detect the presence or absence of deep venous thrombosis, with venograms confirming all positive results. Five of 25 patients in group A (heparin-aspirin) developed deep vein thrombosis. No deep venous thrombi were detected in groups B or C. One pulmonary embolus was detected in group A. The reduction in detectable deep venous thrombosis by the use of intermittent compression of the plantar venous plexus was significant. Wound drainage was decreased by 2 to 3 days (P < 0.05) in group B. It is concluded that, in this group of 75 consecutive patients, intermittent pulsatile compression of the plantar venous plexus was superior to heparin/aspirin pharmacologic prophylaxis for the prevention of deep venous thrombosis proximal to the calf.

Adult↗

PubMed1996

[Surgical treatment of deep venous thrombosis--indications, possibilities and limitations in venous thrombectomy].

Venous thrombectomy as a treatment of deep venous thrombosis is discussed extremely controversial. Occasionally, however, surgical technique, goal of the therapy, indications and limitations are not really known. Indication for surgical treatment is an extensive acute deep vein thrombosis with clinical symptoms of less than 7 days. Goal of the therapy is the preservation of valve function and prevention of a postphlebitic syndrome. Further indications are an embolizing venous thrombosis, a floating thrombus and an ischemic thrombosis. In these cases the single goal of the treatment is to reduce the individual risk of the patient. The best long term results can be achieved in young patients (below 40 years of age) with no preexisting venous lesion and an acute iliofemoral thrombosis. Advantages, drawbacks and results of venous thrombectomy are discussed.

Adult↗

PubMed1996

Doppler color flow imaging surveillance of deep vein thrombosis in high-risk trauma patients.

To determine the prevalence of upper and lower extremity deep vein thrombosis in high-risk trauma patients, 136 consecutive high-risk trauma patients were prospectively evaluated with weekly Doppler color flow imaging. Incomplete compressibility and visualized intraluminal thrombus were considered diagnostic of deep vein thrombosis. Pulmonary embolus was documented by pulmonary arteriography. Deep vein thrombosis occurred at 27 non-contiguous sites in 19 patients (14%). Eight of 27 cases of deep vein thrombosis (30%) involved the upper extremity and 19 (70%) occurred in the lower extremity. Twenty-one of 27 deep vein thromboses (78%) were partially occlusive, whereas six (22%) were occlusive. Pulmonary embolus was documented in three patients (2.2%). Doppler color flow imaging detected occult deep vein thrombosis in 14% of high-risk trauma patients (30% occurring in the upper extremity).

Adolescent↗

PubMed1996

[Comprehensive prevention of postoperative thrombosis].

Thromboembolic disease with its high mortality and morbidity is currently one of the most serious postoperative complications. Its occurrence in high-risk patients in surgical wards is 25-50%. Since 1979, the authors have examined 160 risk patients in whom no prevention had been performed. In this group of patients they detected the occurrence of profound venous thrombosis by means of the accumulation fibrinogen test, targeted phlebography under skiascopic control. At the same time the clinical symptomatology was followed in detail. Since the thrombosis is a multifactorial process, the effective preventive measure must affect and normalize as many disturbed homeostatic processes as possible. Into the group of 176 high-risk patients, the authors introduced a complex prevention into surgical routine residing in classical low-dose heparinization by 5000 u.s.c. with the first dose administered 1 hours prior to surgery, preoperational haemodilution with the administration of minimally 500 ml of Dextran and in preoperation administration of antiaggregants (Acylpyrin). by means of this tactic, the greatest antithrombotic effect is brought about preoperatively and in the first postoperative hours while the patient is protected minimally 5 to 7 postoperative days. Both preoperative and postoperative procedures are monitored by means of a complex haemocoagulation examination of the basic 10 haemocoagulation factors. The occurrence of thrombosis in patients without prevention with minimally 5 thrombogenetic risk factors during the control by means of the accumulation fibrinogen test was 32.4% and during the control by means of targeted phlebography is 24%. The differences are not statistically significant. In the group of patients with prevention the occurrence is 5.6%. In this group the screening is represented by the accumulation fibrinogen test and its positivity is verified by its localization by means of selective phlebography. The occurrence of deep vein thrombosis in the group with prevention and in the control groups statistically highly significant p > 0.0005. Haemocoagulation examination is aimed at the determination of the normalization impact of prevention on the state of hypercoagulation ability associated with the depression of spontaneous fibrinolysis in patients without prevention. The thrombi detected in patients with prevention are localized in short segments of crural veins. Clinically more significant bleeding in the group of patients with prevention occurred only in 2 patients, i.e. in 1%. Complex multifactorial prevention is not only simple and safe for patients, but also highly effective in the group of patients with high risk of postoperative thrombosis. The clinical diagnosis is unreliable and misleading with low sensitivity and specificity. (Tab. 2, Fig. 2, Ref. 28.).

Anticoagulants↗

PubMed1995

[Association of dysfibrinogenemia and thrombosis. Apropos of a family (Fibrinogen Melun) and review of the literature].

We report a family with history of deep and superficial venous thrombosis. A large number of siblings had numerous episodes of deep venous thrombosis and less frequently arterial thrombosis. The most frequent site was lower limb. Dysfibrinogenaemia seems to play an essential role in predisposition to thromboembolism in this family, other known aetiologies having been excluded. Genetic studies of fibrinogen gene show a point mutation in the gamma chain (364 Asp-Val), the site close to gamma 363 one of the sites involved in fibrin monomers polymerisation, although fibrinogen polymerisation is normal. Review of the 250 families with dysfibrinogenaemia published up to now shows that the prevalence of dysfibrinogenaemia in patients with a history of thromboembolism is about 0.7%, and that thrombosis is observed in about 10% of cases of dysfibrinogenaemia. Abortion risk seems to be increased in women with dysfibrinogenaemia. In contrast thromboembolism risk does not seem to be higher during pregnancy, but may be increased after delivery. The main mechanisms which have been proposed to explain thromboembolism observed in dysfibrinogenaemia are: resistance of the clot to thrombolysis; defective thrombin binding; enhanced platelet aggregation; increased blood viscosity, alteration of clot architecture. This family study together with the previously reported cases supports the hypothesis that there is a link between thrombosis and dysfibrinogenaemia in a small number of patients.

Female↗

PubMed1996

[Value of Doppler ultrasonic studies in the diagnosis of deep venous thrombosis of the lower limbs].

To compare the operating characteristics of the venous echo-doppler and that of venous phlebography in our setting, 90 consecutive patients admitted on suspicion of deep vein thrombosis of one leg underwent both examinations. Phlebography confirmed the diagnosis in 46 patients (51%). The sensitivity, specificity, and positive and negative predictive values of the echo-doppler were 91, 92, 94 and 90% respectively. For the subgroup of patients with proximal deep vein thrombosis, these values were 97, 97, 97 and 97%, respectively; for the subgroup with distal deep vein thrombosis, these values were 60, 95, 75 and 90%, respectively. This study confirms the excellent performance of the venous echo-doppler for the diagnosis of deep vein thrombosis of the leg in our hospital. However, in the subgroup of patients with distal deep vein thrombosis, only the sensitivity of the venous echo-doppler is relatively low and the diagnosis may still require color echo-doppler or phlebography.

Diagnosis, Differential↗

PubMed1996

A fixed-dose combination of low molecular weight heparin with dihydroergotamine versus adjusted-dose unfractionated heparin in the prevention of deep-vein thrombosis after total hip replacement.

The low dose heparin regimen (LDH) is not appropriate for prevention of intra- and postoperative thromboembolic complications in high risk patients, especially those undergoing elective hip replacement. Despite LDH prophylaxis, the incidence of deep-vein thrombosis (DVT) remains in a range of 20 to 35%. Adjusted-dose unfractionated heparin prophylaxis is thought to be one of the most effective regimens for thrombosis prophylaxis in this indication, but it requires two or three daily injections as well as precise monitoring of the activated partial thromboplastin time (aPTT). As an attractive alternative, we investigated the efficacy and safety of the low molecular weight heparin (LMWH) certoparin combined with dihydroergotamine (DHE) given once daily. In a randomised, open clinical trial, a total number of 305 patients undergoing total elective hip replacement were enrolled and divided into two groups, either receiving a fixed-dose combination of LMWH (3,000 IU) and DHE (0.5 mg) subcutaneously once daily, or adjusted-dose unfractionated heparin (UFH) subcutaneously every 8 h. The UFH dosage was adjusted daily to keep an aPTT of about 50 s. The aPTT was determined 3 h after the morning injection. During the study, the starting dose (15,000 IU/day) was increased to a plateau value of 28,800 +/- 7,150 IU/day (mean +/- SD) to maintain the aPTT in the prescribed range. The plateau value was achieved after 8 postoperative days. For analysis of efficacy 289 patients were evaluable. The occurrence of deep vein thrombosis was determined by bilateral ascending venography, which was performed on the same day in patients with clinical signs suggesting DVT; and in all remaining patients at the end of the prophylaxis period. Deep vein thrombosis was diagnosed in 17 of 142 patients (12.0%) treated with LMWH/DHE and in 13 of 147 patients (8.8%) treated with adjusted-dose UFH. Combined distalproximal thrombosis was more frequently in patients receiving UFH (n = 5; 3.4%) compared to the LMWH/DHE group (n = 2; 1.4%). These differences are statistically not significant. In the UFH group one case of non-fatal pulmonary embolism occurred. Both prophylaxis regimens were well tolerated; wound bleeding was observed in 8 (5.3%) patients in the LMWH group and in 6 (4.0%) patients in the UFH group. Intraoperative blood-loss volume (mean +/- SD) was 751 +/- 339 mL (LMWH/DHE) and 736 +/- 380 mL (UFH), whereas postoperative drain-loss volume (mean +/- SD) was found to be 523 +/- 333 mL (LMWH/DHE) and 581 +/- 404 mL (UFH). Whole blood transfusion volumes (mean +/- SD) were 570 +/- 202 mL (LMWH/DHE) and 748 +/- 455 mL (UFH). Additionally, red cell replacement volumes (mean +/- SD) were 804 +/- 435 mL (LMWH/DHE) and 720 +/- 328 mL (UHF). Revision of wound or additional drainage were necessary in 3 LMWH/DHE and 7 UFH patients. One patient needed reoperation due to bleeding, 3 (2.0%) had petechia and 1 exhibited an allergic exanthema, all of them in the UFH group. A slight erythema at the injection site was observed in 6 (3.9%) patients receiving LMWH/DHE. During the course of prophylaxis, injection hematomas were documented in 57.9% (LMWH/DHE) and in 61.4% (UFH) of the patients. All differences were statistically not significant. Single daily subcutaneous injections of LMWH/DHE appeared to be safe and efficacious compared to adjusted-dose UFH for prophylaxis of DVT in high-risk patients.

Aged↗

PubMed1996

[Short-term change in sural venous thrombosis in patients in surgical intensive care when anticoagulants are contraindicated].

Venous thrombo-embolic disease in neurosurgical and surgical intensive care units is a frequent disorder (between 4.3 and 43 per cent of patients according to studies). The treatment is often difficult. We carried out a retrospective study from January 1994 to September 1995 of 57 patients in neurosurgical and surgical intensive care who developed thrombosis of a sural vein and in whom anticoagulant at therapeutic doses was contraindicated. After a median follow up 14 days echography showed proximal extension of the thrombosis in 4 patients and distal extension in 3 others. Five cases of pulmonary embolism occurred during the follow up period, one of which led to death. No complications (pulmonary embolism or proximal extension of venous thrombosis) occurred in those patients receiving heparin at prophylactic doses (0/11 versus 8/46 in the non-heparin group; p = 0.13). No case of pulmonary embolus occurred in those patients with partial or complete regression of the thrombosis (0/21 versus 5/36 in the group with stable or extending thrombi, p = 0,05). Echographic monitoring enabled therapeutic modification in 5 cases. These results indicate that sural venous thrombosis in the context of neurosurgical and surgical intensive care is a potentially grave situation and that the prescription of anticoagulant therapy even at preventive dose should always be considered. Further, we propose regular echographic monitoring until the patient is mobile.

Adult↗

PubMed1997

Resistance to activated protein C caused by the factor VR506Q mutation is a common risk factor for venous thrombosis.

In 1993, inherited resistance to activated protein C (APC) was described as a novel risk factor for venous thrombosis. APC-resistance is present in 20-60% of venous thrombosis cases. It is caused by a single point mutation in the factor V gene which substitutes arginine (R) at position 506 with a glutamine (Q). The mutation is common in Caucasians with up to 15% prevalence in the population, whereas it is not found among other human races. Mutated factor V (FVR506Q, FV:Q506 or FV Leiden) is partially resistant to APC which results in a hypercoagulable state conferring a life-long increased risk of thrombosis. Individuals having FV:Q506 combined with other anticoagulant defects have a high risk of thrombosis, and it is now generally accepted that severe thrombophilia is a multigenetic disease. Easy functional and genetic tests for inherited APC-resistance will profoundly influence the development of prophylactic regimens and hopefully result in a decreased incidence of thrombosis.

Anticoagulants↗

PubMed1997

The 20210 A allele of the prothrombin gene is a common risk factor among Swedish outpatients with verified deep venous thrombosis.

A dimorphism in the 3'-untranslated region of the prothrombin gene (G to A transition at position 20210) has recently been reported to be associated with increases in plasma prothrombin levels and in the risk of venous thrombosis. We have examined the prothrombin dimorphism among 99 unselected outpatients with phlebography verified deep venous thrombosis, and in 282 healthy controls. The prevalence of the 20210 A allele was 7.1% (7/99) in the patient group, and 1.8% (5/282) in the healthy control group (p = 0.0095). The relative risk of venous thrombosis was calculated to be 4.2 (95% CI, 1.3 to 13.6), and was still significant when adjustment was made for age, sex and the factor V:R506Q mutation causing APC resistance [odds ratio 3.8 (95% CI, 1.1 to 13.2)]. As previously reported, 28% of the patients were carriers of the factor V:R506Q mutation. Thus, 34% (one patient carried both traits) of unselected patients with deep venous thrombosis were carriers of an inherited prothrombotic disorder. To sum up, our results confirm the 20210 A allele of the prothrombin gene to be an important risk factor for venous thrombosis.

Adult↗

PubMed1997

[The so-called "economy class" syndrome or travel thrombosis].

Thrombosis and pulmonary embolism associated with air travelling is known as "economy class syndrome". However, as it is observed even using other means of transportation, it can generally be described as "traveller's thrombosis". Our own observations include 5 patients with thrombo-embolic disease, which occurred after long-distance travel. In respect to the large number of travellers, the reported incidence of associated thrombosis seems to be remarkably low, and there is no epidemiological evidence about travel and thromboembolic disease. On the other hand, retrospective analysis of patients with manifest thrombosis of any origin reveals in about 5% the circumstances of transportation as possible agent. Anyhow, according to literature the risk of thrombosis could be regarded as quite low. Preventive action during long-distance travelling should be taken into consideration in patients with high risk of thromboembolism.

Aircraft↗

PubMed1997

[Effect of meteorological variations on the emergence of deep venous thrombosis of the leg].

INTRODUCTION: Recent articles have established a significant relationship between metereology variables and the development of vascular disease. We performed a retrospective study to determine relationships between the development of deep vein thrombosis in the lower limb and certain meteorology variables. MATERIALS AND METHODS: We identified 345 cases of phlebitis in 1995. We studied the distribution of the number of venous thrombosis per day, per month and per season. We compared certain meteorological data (atmospheric pressure, temperature, mean hygrometery) for days with and days without venous thrombosis and the atmospheric variations during the 48 hours prior to venous thrombosis. RESULTS: There was a significant relationship (p < 0.004) between the mean number of cases of phlebitis recorded per day and season with winter predominating. On days when phlebitis occurred, the atmospheric pressure was significantly lower (p < 0.05). The number of thrombotic events was significantly different on days when the variation was greater than 10 hectopascals than on days when the variation was less than 10 hectopascals (p < 0.05). CONCLUSIONS: In our study, deep vein thrombosis of the lower limb was significantly associated with certain meteorology variables. Prospective multicentric studies are needed to confirm these relationships.

Adult↗

PubMed1998

A randomized comparison of sequential-gradient calf compression with intermittent plantar compression for prevention of venous thrombosis in orthopedic trauma patients: preliminary results.

Trauma patients with fractures of the pelvis, acetabulum, or femur are at risk for deep venous thrombosis complicating the treatment of their injuries. This risk can be lessened with anticoagulant medications or with mechanical methods such as sequential pneumatic compression. However, many patients in this population group have contraindications to systemic anticoagulation and cannot use sequential limb compression devices because of leg injuries or appliances. Intermittent pneumatic compression of the plantar venous plexus is able to provide prophylaxis against deep venous thrombosis in many of these patients. We performed a prospective, randomized, controlled comparison between plantar compression and leg compression for prevention of deep venous thrombosis in an orthopedic trauma population of 124 patients. Patients were evaluated with duplex ultrasonagraphy at intervals after surgery. Both methods proved protective in comparison with reported rates in patients not given prophylaxis, and although the numbers were too small to give statistically meaningful results, we observed no significant difference in the thrombosis rate (4% for plantar compression versus 0% for leg compression). We conclude that foot pumps are an effective alternative to calf compression for prevention of deep venous thrombosis after a lower extremity fracture.

Adolescent↗

PubMed1998

Possible involvement of Von Willebrand factor in pancreatic graft thrombosis after kidney-pancreas transplantation: a retrospective study.

Early postoperative graft thrombosis remains the second cause of failure in pancreas transplantation. Thus, the aim of this study was to compare retrospectively coagulation and fibrinolysis in type I diabetic recipients of simultaneous kidney pancreas transplants having or not experienced thrombosis of their pancreatic graft. From December 1990 to August 1996, 30 simultaneous kidney pancreas transplants were performed in 30 uremic type I diabetic patients. Acute thrombosis of the pancreatic graft was observed among 6 patients (group A), whereas 24 did not develop thrombosis (group B) although 4 died from other causes. The control groups were composed of kidney transplant (group C) or haemodialysed (group D) non-diabetic patients, type I diabetics with HbA1C < 8% (group E) or > or = 8% (group F) who were not in end-stage renal failure and kidney transplant type I diabetic patients (group G). Beginning at least 6 months after transplantation, we analysed hemostatic factors (fibrinogen, thrombin, and prothrombin times), coagulation inhibitors (proteins C and S), fibrinolysis (plasminogen activator inhibitor) and endothelial cell abnormalities (Von Willebrand factor: VWf). Micro and macrovascular complications were evaluated on a score ranging from 0 to 12. Hemostatic factors, coagulation inhibitors and fibrinolysis were similar in groups A and B whereas VWf differed significantly in group A (3.49 +/- 0.93 IU/ml) as compared to group B (2.04 +/- 0.92 IU/ml) (p < 0.05). VWf was also significantly increased in group A relative to the control groups C, D, E, F, and G. The score of vascular complications was increased in groups A and B and significantly higher in group A (9 +/- 0.81 vs. 6.07 +/- 1.75) (p < 0.01), while a correlation (r = 0.812, p > 0.05) was observed between VWf levels and the severity of vascular complications. These results point out the possible involvement of VWf in the pathogenesis of pancreatic vein thrombosis in kidney-pancreas transplantation.

Adult↗

PubMed1998

Deep venous thrombosis prophylaxis for knee replacement: warfarin and pneumatic compression.

A prospective study of the prevalence of proximal deep venous thrombosis in total knee replacement patients who had prophylaxis for thrombosis with a combination of low-dose warfarin and intermittent pneumatic compression was done. Two hundred and ninety-seven patients who underwent 377 consecutive total knee replacements were studied. All patients were treated with low-dose warfarin and intermittent pneumatic compression using thigh-high sleeves. Surveillance for proximal thrombosis was done by duplex ultrasonography. Proximal thrombosis was detected in 19 patients, for a prevalence of 5%. There were 3 patients who had a major bleeding complication, for a prevalence of 0.9% for the 337 procedures performed. Although there was no concurrent control group of patients treated with another means of prophylaxis to compare with these patients, the low prevalence of proximal thrombosis and the low risk of major bleeding complications that was found compares well with recent reports on the effectiveness and safety of low-molecular-weight heparin.

Adult↗