Coagulation Changes Under An Effective Urokinase Dosage Regimen

1981 ◽  
Author(s):  
G Schöffel ◽  
R Zimmermann ◽  
J Harenberg

In preliminary studies we demonstrated an increased thrombolytic activity with higher dosages of urokinase in the therapy of deep vein thrombosis. From that time this higher urokinase dosage schedule (loading dose 250,000 IU, initial maintenance dosage 2000 IU/kg/h in combination with 1520 U heparin/kg/h) was used and suggested as ideal.In 10 patients with deep vein thrombosis treated according to this dosage schedule following coagulation parameters were determined before the beginning of the therapy, after 1,4,12 h and then at least once per day up to 7-14 days:aPTT, thrombin clotting time, fibrinogen (according to Clauss, Ratnoff and Menzie and radial immunodiffusion), TEG, euglobulin clot lysis time, inhibitors of fibrinolysis, plasminogen, antithrombin III, fpA, clotting factors V and VIII. The coagulation analysis showed a progressive decrease of fibrinogen to 50100 mg% and of plasminogen to about 40 % within 12-36 h. At this time a reduction of the urokinase dose by 30-40 % and further only slight corrections became necessary. Additional investigations demonstrated a more pronounced fibrinogenolytic effect when dissolving and applying urokinase in plastic material and avoiding contact with glass surfaces. These findings suggested a 30% saving of urokinase.The highly effective urokinase dosage schedule here described has been proved practicable and rendered too frequent coagulation controls superfluous. The saving of urokinase by using plastic material introduced a modification of our urokinase regimen:Loading dose 250,000 IU, followed by 2000 IU/kg/h for only 8 h, then 1000 IU/kg/h with further slight individual dose corrections.

1983 ◽  
Vol 50 (03) ◽  
pp. 664-668 ◽  
Author(s):  
W Theiss ◽  
F Asbeck ◽  
A Kriessmann ◽  
G Trübestein ◽  
K Knoch ◽  
...  

SummaryIn a prospective, randomized trial 33 patients with deep vein thrombosis were treated either with 2,200 or 1,100 IU/kg/h urokinase or with 100,000 IU/h streptokinase for at least 6 days. While streptokinase was given continuously, urokinase was administered intermittently (12 hr urokinase alternating with 12 hr heparin).Urokinase treatment resulted in a dose-dependent fibrinolytic state with shortening of the euglobulin clot lysis time, easily demonstrable amidolytic activity and moderate decrease of plasminogen. At the end of each urokinase-free interval the fibrinolytic activity had mostly faded, but was reproducibly elicited again by each new urokinase administration. Streptokinase immediately evoked the customary, intense fibrinolytic state, which progressively tapered off as plasminogen fell to 1% of its pretreatment concentration. In all treatment groups α-2-antiplasmin dropped to approximately 40% of its initial value during the first 12 hr with a further decrease to about 20% after 6 days, α-2-macroglo- bulin fell only moderately with either urokinase regimen, whereas it decreased progressively to 45% under streptokinase.While the fibrinolytic activity decreased under streptokinase over the 6-day infusion period, it appeared to increase with each successive urokinase infusion particularly with 1100 IU/kg/h. Thus the final euglobulin clot lysis times and the final fibrinogen concentrations were similar in all three treatment groups on the sixth day.


Blood ◽  
1981 ◽  
Vol 57 (1) ◽  
pp. 44-48 ◽  
Author(s):  
RC Carroll ◽  
JM Gerrard ◽  
JM Gilliam

Abstract Platelet facilitation of clot lysis was studied using the dilute clot lysis assay, a standardized assay for fibrinolysis shown to correlate with the development of postoperative deep vein thrombosis. Clots prepared from dilute platelet poor plasma showed prolonged clot lysis when compared with clots prepared in a similar fashion from dilute platelet rich plasma. Since in the presence of platelets clot retraction or contraction occurred, we evaluated a possible direct contribution of retraction to clot lysis. Dilute platelet poor plasma clots were compacted by centrifugation, to a similar extent as that achieved during clot retraction in dilute platelet rich plasma. These clots now lysed at a rate that approached that seen with dilute platelet rich plasma clots. Using an alternate alternate approach, dilute platelet rich plasma clots were treated with cytochalasin B to prevent clot retraction. Such clots now showed prolonged lysis similar to that seen with dilute platelet poor plasma. The prolonged lysis of cytochalasin B treated dilute platelet rich plasma clots was corrected by artificial compaction of the clots. The results suggest that clot retraction markedly facilitates clot lysis, and shows that a major role of platelets to facilitate clot lysis is the effect of these cells to cause clot retraction.


Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1576
Author(s):  
Leszek Gromadziński ◽  
Łukasz Paukszto ◽  
Agnieszka Skowrońska ◽  
Piotr Holak ◽  
Michał Smoliński ◽  
...  

Deep vein thrombosis (DVT) is a severe disease affecting the human venous system, accompanied by high morbidity and mortality rates caused by early and late complications. The study aimed at analyzing the changes in the transcriptome of the femoral vein caused by DVT in the porcine model based on the formation of the thrombus in vivo. The study was performed on 11 castrated male pigs: a thrombus was formed in each left femoral vein in six animals; the remaining five served as a control group. Total RNA was isolated from the left femoral veins of the experimental and control animals. High-throughput RNA sequencing was used to analyze the global changes in the transcriptome of veins with induced DVT. Applied multistep bioinformatics revealed 1474 differentially expressed genes (DEGs): 1019 upregulated and 455 downregulated. Functional Gene Ontology annotated 1220 of DEGs into 225 biological processes, 30 molecular functions and 40 cellular components categories. KEGG analysis disclosed TNF, NF-κB and apoptosis pathways’ overexpression in DVT samples. A thorough analysis of the detected DEGs indicated that a dysregulated inflammatory response and disturbed balance between clotting and anti-clotting factors play a crucial role in the process of DVT.


2020 ◽  
Vol 35 (7) ◽  
pp. 461-471 ◽  
Author(s):  
Tommy Y Cai ◽  
Saissan Rajendran ◽  
Prakash Saha ◽  
Steven Dubenec

Aim To assess the current evidence, controversies and technologies behind the various approaches and steps in the management of Paget-Schroetter syndrome. Materials and methods We performed a narrative review based on a literature search in Embase, Medline, Pubmed and Google Scholar through keyword searching related to upper extremity deep vein thrombosis, Paget-Schroetter syndrome and venous thoracic outlet syndrome. Results There is a paucity of high-quality evidence assessing the efficacy of contemporary approaches for the management of acute upper extremity deep vein thrombosis which, though promising, is largely limited to single institution case studies and small series. As a result, a formal systematic review could not be performed. Conclusions Paget-Schroetter syndrome is a rare condition, whose management approaches are largely guided by the accumulated expertise and clinical experience of vascular specialists. In the absence of randomized controlled trials, current practice has been guided by retrospective reviews and experience. Modern approaches and protocols appear to remain distinct between health care facilities, but have common features including early clot lysis, surgical decompression with first rib resection, followed by adjunctive open or endovascular procedures. Further high-quality level 1 evidence and research are required in order to standardize treatment for this condition.


1981 ◽  
Author(s):  
A C de Boer ◽  
A G G Turpie ◽  
R Butt ◽  
E Genton

Intermittent pneumatic compression (IPC) consistently prevents venous stasis by increasing venous return of the legs but fails to prevent deep vein thrombosis (DVT) in some patients, especially patients with malignancy and subarachnoid haemorrhage (SAH). This suggests a mechanism in addition to preventing stasis is required for the prophylactic effect of IPC. IPC increases fibrinolysis and this may contribute to DVT prevention. In 74 patients with SAH treated with anti fibrinolytic drugs, 21% of 42 randomized to IPC prophylaxis developed DVT and 19% of 32 controls. In 143 neurosurgical patients aged >55 years and not treated with antifibrinolytic drugs, 30% of controls (n=76) developed DVT compared to 16% treated with IPC (n=67; p>0.05), in contrast to 187 patients <55 years in whom 20% of controls (n=88) developed DVT, compared with none in the IPC group (n=99; p< 0.001). The effect of IPC on fibrinolytic activity in 80 of these patients was evaluated using a modification of the dilute blood clot lysis time (mean ± SEM, hrs). In 64 medical control patients there was a correlation between age and lysis time (r=0.33; p<0.05). In operative patients aged <55 years, lysis time was significantly shortened in patients given IPC compared with age-matched controls (6.3 + 0.6 v 8.8 + 0.8; p<0.05). In patients aged >55, there was no difference in lysis time in IPC patients compared with age-matched controls (10.2 ± 1.4 v 9.7 ± 0.8; p> 0.1). In all patients treated with antifibrinolytic drugs, lysis times were markedly prolonged. The data show that ineffectiveness of IPC in certain patient groups was related to failure of enhancement of fibrinolytic activity and this is consistent with the hypothesis that activation of fibrinolysis contributes to the prevention of DVT with IPC.


2001 ◽  
Vol 86 (09) ◽  
pp. 817-821 ◽  
Author(s):  
N. Hunt ◽  
R. K. Strachan ◽  
A. N. Nicolaides ◽  
K. T. Delis

Summary Aims: to determine the incidence, anatomical distribution and extent of deep vein thrombosis (DVT) in limbs undergoing elective unilateral knee arthroscopy without active prophylaxis, to evaluate its effect on venous function following early diagnosis, and to quantify the impact of risk factors on its incidence. Methods: 102 consecutive patients undergoing unilateral knee arthroscopy without prophylaxis were studied. A history was obtained with emphasis on the risk factors for thromboembolism, and physical examination and colour duplex were performed prior to and within a week after surgery. Patients who developed calf DVT were given aspirin (150 mg) and compression stockings; those with proximal DVT were admitted for anticoagulation (heparin followed by warfarin). Follow-up (mean 118 [range 84-168] days) entailed weekly physical and duplex examinations during the first month and monthly thereafter. Results: 8 patients developed calf DVT in the operated leg (incidence 7.84% [95% Cl: 2.7%-13.2%]); thrombosis was asymptomatic in 4 of those (50%), caused calf tenderness in 4 (50%) and a positive Homan’s sign in one (12.5%). DVT occurred in the following veins: peroneal 4 subjects (50%), soleal 4 (50%), gastrocnemial 2 (25%) and tibial 2 (25%). Propagation of a calf DVT to the popliteal vein was identified in 1 patient (12.5%). After a median period of 118 days, total clot lysis was found in 50% of DVTs, with partial thrombus resorption in the rest; reflux in the thrombosed veins was present in 75% of limbs with DVT. 43% of patients had 1 risk factor for DVT and 20% had ≥2. The incidence of DVT was higher amongst those with two or more risk factors for thromboembolism (p <.05) or those with previous thrombosis alone (p <.005). Symptoms or signs of pulmonary embolism were not documented. Conclusions: Elective unilateral knee arthroscopy performed without prophylaxis is complicated by ipsilateral calf DVT in 7.8% (95% CI: 2.7%-13.2%) of cases. The risk is higher in the presence of previous thrombosis (relative risk: 8.2) and two or more risk factors for DVT (relative risk: 2.94). Thrombosis may propagate to the proximal veins, despite early diagnosis. 50% of calf clots totally lyse in 4 months, yet reflux develops in at least 75% of limbs with DVT. Further studies to determine optimal prophylaxis are warranted.


Author(s):  
Burçin Abud ◽  
Kemal Karaarslan ◽  
Mahir Utku Yıldırım ◽  
Gökhan Albayrak ◽  
Koray Aykut

INTRODUCTION: Deep Vein Thrombosis leads to post thrombotic syndrome in the long term. The risk of developing a post thrombotic syndrome increases when anticoagulation is the only treatment. Catheter-directed thrombolysis methods were developed because of the high bleeding risk of systemic thrombolytic therapy. Along with hybrid approaches Catheter-directed thrombolysis aim to reduce the frequency of post thrombotic syndrome. We retrospectively report the early and follow-up results of our patients in whom we performed Catheter-directed thrombolysis. METHODS: 31 patients(aged 23-87) had been diagnosed with acute proximal Deep Vein Thrombosis(≤15 days’ duration). Catheter-directed thrombolysis and if needed stent implantations were performed successfully. The patients who had a thrombosis of the inferior vena cava also underwent the placement of a vena cava filter. Patients were evaluated at 1, 6 and 12 months. Villalta scores were also determined for the diagnosis of post thrombotic syndrome. RESULTS: 19 had a thrombus in the iliofemoral. The thrombus was extending to the inferior vena cava in six patients. In 12 patients the thrombus was femoropopliteal. The six patients whose thrombus extended to the inferior vena cava, underwent venous filter placement. In five of the iliofemoral-thrombus patients, intraoperative control venography revealed iliac stenosis. This stenosis was treated with iliac stent implantation. Clot-lysis was completely(>90% lysis) in twelve, partially(50-90% lysis) in seven of the 19 iliofemoral-thrombus patients. Ten of the femoropopliteal-thrombus patients achieved a complete and two a partial clot-lysis. There was minor bleeding in two patients. Major bleeding was not reported. DISCUSSION AND CONCLUSION: Catheter-directed thrombolysis reduce the frequency of post thrombotic syndrome. Residual venous obstruction after Catheter-directed thrombolysis should be treated by balloon dilatation/stent implantation to prevent re-thrombosis. We believe that treatment with a hybrid approach may be more effective in protecting patients from post thrombotic syndrome.


2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Anetta Undas

Prothrombotic fibrin clot phenotype, involving faster formation of dense meshwork composed of thinner and highly branched fibers that are relatively resistant to plasmin-induced lysis, has been reported in patients with not only myocardial infarction or stroke, but also venous thromboembolism (VTE), encompassing deep vein thrombosis (DVT), and/or pulmonary embolism (PE). Prothrombotic fibrin clot phenotype, in particular prolonged clot lysis time, is considered a novel risk factor for VTE as well as venous thrombosis at unusual location, for example, cerebral sinus venous thrombosis, retinal vein obstruction, and Budd-Chiari syndrome. Growing evidence from observational studies indicates that abnormal fibrin clot properties can predict recurrent DVT and PE and they are involved in serious complications of VTE, for example, thromboembolic pulmonary hypertension and postthrombotic syndrome. The purpose of this article is to review our current understanding of the role of fibrin clot structure and function in venous thrombosis with emphasis on clinical issues ranging from prognosis to therapy.


1975 ◽  
Vol 33 (03) ◽  
pp. 435-443 ◽  
Author(s):  
Peter N Walsh

SummaryRecent studies of the role of platelets in blood coagulation have shown that platelets can trigger intrinsic coagulation by two alternative pathways, protect platelet-associated active clotting factors from inactivation by plasma inhibitors and catalyze intrinsic coagulation reactions on the platelet surface to form fibrin. These platelet coagulant activities (i.e., contact product forming activity, collagen-induced coagulant activity, intrinsic factor-Xa forming activity and platelet factor 3 activity) were found to be increased in patients with deep vein thrombosis developing after hip surgery, in patients with established retinal vein thrombosis and in patients with established deep vein thrombosis. It is suggested that increases in platelet coagulant activities concerned with triggering and catalyzing intrinsic coagulation reactions may play a role in the pathogenesis of venous thrombosis.


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