Treatment of Deep Vein Thrombosis. A Trial of Heparin,Streptokinase, and Arvin

Thirty patients with deep vein thrombosis of the legs of less than four days'' duration were allocated at random to treatment with heparin, streptokinase, or Arvin under laboratory control. When the fate of the thrombi was assessed by objective techniques—phlebography and the ¹²⁵I-labelled fibrinogen test—the incidence of complete thrombolysis was greatest in the streptokinase group. Complications arose during treatment in each group but were least with Arvin. The natural history of the disease favours clinical but not always anatomical recovery.     

Prevention of deep vein thrombosis after hip replacement: randomised comparison between unfractionated heparin and low molecular weight heparin.

OBJECTIVE--To evaluate the efficacy and safety of two subcutaneous prophylactic regimens for postoperative deep vein thrombosis after total hip replacement. DESIGN--Prospective open randomised multicentre trial. SETTING--28 European departments of orthopaedic surgery. INTERVENTION--All patients had bilateral phlebography 10 days after surgery. 31 patients receiving low molecular weight heparin and 29 receiving unfractionated heparin were excluded from the efficacy analysis for various reasons. PATIENTS--349 patients undergoing total hip replacement between September 1988 and May 1989. 174 patients received subcutaneously a low molecular weight heparin (Fraxiparine) with anti-factor Xa activity of 41 IU/kg/day for three days, then 62 IU/kg/day from day 4 to day 10. 175 patients received subcutaneous unfractionated heparin at intervals of eight hours; doses were adjusted to maintain the activated thromboplastin time at two to five seconds above control values. MAIN OUTCOME MEASURE--Total incidence of deep vein thrombosis and incidence of proximal deep vein thrombosis on bilateral phlebography. RESULTS--The total incidence of deep vein thrombosis was 16% in patients receiving unfractionated heparin and 12.6% in patients receiving low molecular weight heparin (p = 0.45), and the incidence of thrombosis of the proximal veins was 13.1% and 2.9% respectively (p less than 0.001). Four patients receiving unfractionated heparin and one receiving low molecular weight heparin developed pulmonary embolism. The incidence of bleeding complications was low and comparable in the two groups. CONCLUSION--Low molecular weight heparin is at least as effective as unfractionated heparin in preventing deep vein thrombosis and is more effective at preventing thrombosis of the proximal veins in patients undergoing hip replacement. Low molecular weight heparin is not more likely to cause bleeding complications and is simpler to give than unfractionated heparin.     

Short-term lysis of venous thrombosis with ultra-high streptokinase doses

11 patients with deep pelvic and leg vein thrombosis were treated with ultra-high streptokinase infusion, 1.5. 10(6) IE streptokinase per hour over a six hour period. Opening of the vein occlusion was achieved in four cases completely and in five cases partially. The frequency of complications was lower at short-time thrombolysis with ultra-high streptokinase infusion in contrast to long-time thrombolysis. Bleedings did not occur. Because of the slight side effects ultra-high streptokinase infusion is an alternative in the fibrinolytic treatment of risk patients with pelvic and leg vein thrombosis.     

Low-molecular-weight heparin and prevention of postoperative deep vein thrombosis.

The efficacy of low-molecular-weight heparin as a prophylactic agent was assessed in 150 consecutive patients over the age of 40 undergoing major abdominal surgery. Fifty of these patients received 1250 activated partial thromboplastin time (APTT) units of low-molecular-weight heparin every 12 hours: three developed isotopic deep vein thrombosis, which was confirmed by phlebography in two cases. The other 100 patients received a single injection of 1850 APTT units of low-molecular-weight heparin. Three of them developed isotopic deep vein thrombosis; phlebography failed to confirm the presence of thrombi in each case. None of the 150 patients studied died from fatal or contributory pulmonary emboli. Low-molecular-weight heparin was not associated with any increase in preoperative or postoperative bleeding. The effect of equal amounts of postoperative bleeding. The effect of equal amounts of low-molecular-weight heparin and unfractionated heparin on the coagulation mechanism during surgery was investigated in another 30 patients. The clotting assays and results of in-vivo platelet function tests indicated that both preparations produced similar effect. Intragroup comparisons, however, showed significant differences in the anti-factor Xa activity, lipoprotein lipase release, and plasma prekallikrein concentrations. A single injection of low-molecular-weight heparin daily is a convenient way of preventing deep vein thrombosis in high-risk patients undergoing major abdominal surgery.     

Diagnosis of Deep Vein Thrombosis with 99mTc-streptokinase: A Clinical Comparison with Phlebography

Nineteen patients with signs of deep vein thrombosis in the legs were investigated with a new technique using ^{9 9m}Tc-streptokinase. This compound is probably superior to iodine-labelled fibrinogen in detecting established thrombi. The ratio between the activity in the leg with suspected thrombosis and the other leg was calculated. The results were compared with those obtained with phlebography. A pathologically high activity ratio was found in 11 out of 13 patients in whom phlebography showed a thrombus, while the ratio was normal in the remaining six patients who showed no thrombus on phlebography. No negative correlation was found between the activity ratio and the titrated initial dose of streptokinase. The activity ratio as well as diagnosing the presence of a thrombus may also provide a guide for therapy.     

Continuous intravenous infusion versus intermittent administration of streptokinase in patients with deep venous thrombosis of the lower extremity]

In a multicenter randomized trial, the efficacy and safety of two streptokinase (SK) dosage regimens have been evaluated in patients with proximal deep vein thrombosis of inferior limbs. Twenty-nine patients received SK by a continuous intravenous infusion (250,000 IU as initial dose, 100,000 IU/h as maintenance dose), and 26 patients were treated with intermittent SK administration (500,000 IU as initial dose, followed by 250,000 IU every 12 h). Thrombolytic therapy was continued for 4 days, then the patients received heparin for 5 days and oral anticoagulant for 3 months. The results of treatment as judged by phlebographic examinations were similar in the two groups. Complete, substantial or partial thrombolysis was achieved in 52% of patients in the continuous infusion group and in 58% of patients in the intermittent treatment group. During SK administration, major bleeding complications occurred in 6 patients treated by continuous infusion and in 2 of the second group. The results showed that the intermittent SK administration is as effective and safe as the method of continuous SK infusion in the treatment of deep vein thrombosis.     

Subclavian-axillary vein thrombosis: successful treatment with streptokinase.

Proximal vein thrombosis has been associated with residual disability from the postphlebetic syndrome in patients receiving symptomatic therapy or heparin and sodium warfarin. This paper describes a man with painless swelling of the right arm secondary to subclavian-axillary vein thrombosis that was successfully treated with streptokinase and conventional anticoagulant therapy.     

Subcutaneous calcium heparin versus intravenous sodium heparin in treatment of established acute deep vein thrombosis of the legs: a multicentre prospective randomised trial.

One hundred patients with phlebographically proved acute deep vein thrombosis of the legs were prospectively randomised into two treatment groups to compare the safety and efficacy of subcutaneous calcium heparin versus intravenous sodium heparin administered by constant infusion pump. The dose of heparin was determined by daily measurement of the kaolin cephalin clotting time. Treatment was maintained for up to 14 days, after which phlebography was repeated. Of 49 patients who received subcutaneous calcium heparin, two showed an increase in thrombus size, while eight showed complete lysis. In the 47 patients who received intravenous sodium heparin thrombus increased in size in 13 while only one showed evidence of complete lysis. These differences were significant. There were no significant differences between the two groups in the incidence of serious complications, although almost half of those receiving intravenous heparin had some minor problem with the constant infusion pump and just over half of those receiving subcutaneous heparin had some bruising at the injection site. This study showed that subcutaneous calcium heparin was more effective in helping lyse existing thrombus and preventing its propagation than intravenous sodium heparin.     

Subcutaneous injections and intravenous infusion of sodium salt of heparin in the treatment of thrombosis of deep veins of the lower extremities

Ninety-four patients with deep vein thrombosis of inferior limbs were randomly allocated to receive sodium heparin either by subcutaneous injections or by continuous intravenous infusion for six days. No significant difference was observed in the therapeutic efficiency as judged by phlebographic examinations and in rate of symptomatic pulmonary embolism between the two groups. There was one instance of major bleeding in the subcutaneous group. Minor bleedings occurred in 10 of the 48 patients treated with subcutaneous heparin and in 13 of the 46 patients receiving intravenous heparin. The results showed that subcutaneous injections of sodium heparin are as effective and safe as continuous intravenous infusion of this drug in the treatment of deep vein thrombosis.     

Diagnosis and treatment of venous thromboembolism by consultants in Scotland.

A questionnaire was sent to 508 consultants in Scotland likely to encounter deep vein thrombosis and pulmonary embolism to assess their current standard practice in diagnosis and treatment of these disorders. Replies were received from 358 (70.5%). In deep vein thrombosis 47% and in pulmonary embolism 33% of consultants usually depended on clinical observation alone for diagnosis. In deep vein thrombosis 37% used venography to supplement clinical diagnosis and in pulmonary embolism 13% used angiography and 53% used isotopic scanning. Almost all consultants treated deep vein thrombosis (95%) and pulmonary embolism (99%) with anticoagulants. Most consultants (81%) gave heparin by intravenous infusion. Although many consultants gave intravenous heparin for more than three days (49.5% in deep vein thrombosis and 61% in pulmonary embolism), 25% of these consultants did not use any laboratory monitoring of heparin''s effect. Large numbers of consultants gave warfarin for more than three months (20% in deep vein thrombosis and 47% in pulmonary embolism). There was a significant tendency to give heparin (p less than 0.01) and warfarin (p less than 0.001) for longer periods in pulmonary embolism than in deep vein thrombosis. This survey shows a widely varying practice and underlines the need for further controlled studies to provide clear guidance in the management of deep vein thrombosis and pulmonary embolism.     

Streptokinase and Deep Vein Thrombosis

Five patients with deep vein thrombosis were given streptokinase. Five others with similar phlebograms were given anticoagulants, and the results assessed by examining changes in the iliac, femoral, and calf segments of the phlebograms when repeated 7-10 days later. Those of the anticoagulant group were unchanged. Four of the five given streptokinase had a reduction in the size and extent of their thrombosis. Fresh thrombus surrounded by flowing blood was lysed. Thrombus completely blocking a vein was not lysed.The indications for the use of streptokinase in deep vein thrombosis are reviewed.     

Failure of low-dose heparin to prevent significant thromboembolic complications in high-risk surgical patients: interim report of prospective trial. Groote Schuur Hospital Thromboembolus Study Group.

The efficacy of low-dose subcutaneous heparin (5000 IU eight-hourly) is being studied in a single-centre, prospective randomised trial of patients aged over 40 submitted to major elective intra-abdominal surgery. The trial end-points are the objectively defined incidence and extent of deep vein thrombosis (as seen on uptake of 125I-labelled fibrinogen, Doppler ultrasonography, and bilateral ascending phlebography) and non-fatal pulmonary embolus (as measured by preoperative spirometry and preoperative and postoperative chest radiography and perfusion lung scanning performed on a routine, unselected basis). An interim analysis of the first 200 patients indicates that low-dose heparin significantly reduces the incidence of calf-vein thrombosis but does not reduce the incidence of proximal segment thrombosis or non-fatal pulmonary embolism. Thus the routine use of low-dose heparin prophylaxis in all major surgical procedures in patients aged over 40 may not be advisable.     

Streptokinase in the management of limb arterial thrombosis following free-flap surgery

Intraarterial streptokinase was used in the treatment of leg vessel thrombosis following free-flap closure of a large, open wound. Attention is focused on the coagulation anomalies present in such cases and the successful use of local thrombolytic therapy to salvage the limb.     

Prophylaxis of postoperative leg vine thrombosis by low dose subcutaneous heparin or peroperative calf muscle stimulation: a controlled clinical trial.

In a randomized, controlled clinical trial of two methods of preventing postoperative leg vein thrombosis patients undergoing major surgery were divided into three groups. One received intermittent electrical calf muscle stimulation during surgery, the second subcutaneous heparin calcium 5000 IU every eight hours for six days, and the third no specific prophylaxis. Leg vein thrombosis was detected by the 125-I-fibrinogen uptake test. Neither method was effective in patients undergoing open bladder or prostatic surgery. Stimulation did not reduce the incidence of leg vein thrombosis in patients with malignant disease undergoing laparotomy, but heparin calcium was highly successful in this group (P smaller than 0-001). When the laparotomy was for a benign condition, however, both heparin calcium (P smaller than 0-001) and stimulation (P smaller than 0-01) were effective.     

Prophylaxis of postoperative deep vein thrombosis: selective use of low-dose heparin in high-risk patients.

Administration of prophylactic low-dose subcutaneous heparin to prevent postoperative deep vein thrombosis is expensive, entails treating many patients unnecessarily, and causes some side effects. By using a predictive index a population of patients who are at particularly high risk of developing postoperative deep vein thrombosis may be identified preoperatively. Prophylaxis was given only to these patients, resulting in an incidence of deep vein thrombosis of 3.8% compared with 16.1% in previous studies in which no specific prophylaxis was given. By limiting prophylaxis to the group of patients identified by the predictive index as being at high risk of developing postoperative deep vein thrombosis results may be obtained that are as good as those expected from treating the whole population. Thus many patients are saved from exposure to low-dose subcutaneous heparin.     

Diagnosis of deep vein thrombosis using autologous indium-III-labelled platelets.

Forty-eight patients who had undergone surgical reduction of a fractured neck of femur or in whom deep vein thrombosis was suspected clinically were studied by ascending phlebography and imaging after injection of autologous indium-111-labelled platelets to assess the accuracy and value of the radioisotopic technique in diagnosing deep vein thrombosis. Imaging was performed with a wide-field gammacamera linked with data display facilities. Phlebography showed thrombi in 26 out of 54 limbs examined and a thrombus in the inferior vena cava of one patient; imaging the labelled platelets showed the thrombi in 24 of the 26 limbs and the thrombus in the inferior vena cava. The accumulation of indium-111 at sites corresponding to those at which venous thrombi have been shown phlebographically indicates that this radioisotopic technique is a useful addition to methods already available for the detection of deep vein thrombosis.     

Diagnosis of Established Deep Vein Thrombosis with the 125I Fibrinogen Uptake Test

One hundred and two patients with clinical signs indicating a possible diagnosis of deep vein thrombosis were studied with the fibrinogen uptake test and phlebography to assess the reliability of the test as a means of diagnosing established venous thrombosis. The test gave a correct diagnosis in 78% of the 85 legs shown to contain thrombus by phlebography and only 19 (10%) false-negative results in the 195 legs examined. The duration of the symptoms, the administration of anticoagulants, and mild leg swelling did not affect the accuracy of the test. Very old thrombus, phlebographically more than 11 days old, was associated with an increased false-negative rate.The fibrinogen uptake test is accurate enough to make it a valuable method of clinical investigation.     

Heparin in the Prevention of Deep Vein Thrombosis after Myocardial Infarction

A trial of continuous intravenous heparin in the prevention of deep vein thrombosis was undertaken in 48 patients who had suffered a myocardial infarction. Of the 24 control patients who did not receive heparin seven (29%) developed calf vein thrombosis as detected by the radioactive fibrinogen technique. None of the 24 heparinized patients had any evidence of venous thrombosis. This difference is significant at the 1% level.     

Streptokinase in Recent Myocardial Infarction: A Controlled Multicentre Trial

In this controlled multicentre trial treatment with either streptokinase or heparin was allocated at random to patients suffering from myocardial infarction of less than 24 hours'' duration. Treatment with either drug was standardized and lasted for 24 hours. A total of 764 patients entered the trial; 34 patient charts were rejected (including all 28 charts from one centre) because of data failure. On retrospective analysis of the 730 remaining patients the two groups were found to have been comparable at the start.The total hospital mortality was 18·5% of 373 patients allotted to streptokinase treatment and 26·3% of 357 given herapin. The mortality after infusion (24 hours) was 10·6% of 340 patients treated with streptokinase and 17·8% of 320 given herapin (P=0·011). Reinfarction in hospital after the 24-hour period of infusion occurred significantly less often in patients treated with streptokinase (P=0·036). Bleeding from puncture sites and pyrexia occurred more frequently during streptokinase treatment.After exclusion of those patients whose diagnosis was unconfirmed on retrospective assessment, the total hospital mortality rate was 19·0% of 357 patients treated with streptokinase and 27·4% of 339 treated with heparin (P=0·011). These results indicate that in recent myocardial infarction streptokinase was superior to heparin in reducing mortality and reinfarction rate during an average period of six weeks in hospital.     

Comparison of the Effects of Streptokinase and Heparin on the Early Rate of Resolution of Major Pulmonary Embolism

The extent of early resolution of major pulmonary embolism observed in 10 patients after 24 hours of treatment with heparin was compared with that seen in 17 patients after 24 hours of treatment with streptokinase. The patients in the streptokinase group also received a loading dose of heparin and were treated with heparin by continuous infusion when their thrombin time returned to normal levels. All had pulmonary hypertension. Pulmonary embolism was classified as acute in the 10 patients in the heparin group. Seven of these patients showed no angiographic change, two showed slight improvement and one showed angiographic deterioration. There was a moderate and statistically insignificant fall in mean pulmonary arterial pressure and total pulmonary resistance. Fourteen of the 17 patients who were studied before and after streptokinase were classified as acute and three as subacute progressive major pulmonary embolism. Eight showed marked angiographic improvement, four moderate and two slight angiographic improvement. There was a moderate and statistically significant fall in the mean pulmonary arterial pressure and pulmonary vascular resistance. In addition, all seven patients in whom no angiographic improvement occurred during heparin therapy showed moderate or marked angiographic improvement after a further 24 hours of treatment with streptokinase. The results strongly suggest that streptokinase therapy accelerates thrombolysis in patients with acute major pulmonary embolism.