Decreased plasma levels of activated factor VII in patients with deep vein thrombosis

Abstract BackgroundThere is a high incidence of deep vein thrombosis (DVT) among cancer patients undergoing chemotherapy. Chemotherapy-induced vascular endothelial cell activation (VECA) is characterized by increased plasma levels of von Willebrand factor (vWF) and soluble P-selectin (sP-selectin), leading to the activation of endothelial cells and signaling cascades. The biological role of a disintegrin-like and metalloproteinase with thrombospondin type 1 motif, member 13 (ADAMTS-13) is to control the activity of vWF and consequently the risk of thrombosis. The objective of this study was to investigate the roles of sP-selectin, vWF, and ADAMTS-13 as risk factors for the first episode of DVT in cancer patients undergoing chemotherapy.MethodsThis prospective cohort study was conducted at Dr. Kariadi Hospital, Indonesia, on 40 cancer patients. Prechemotherapy (baseline) and postchemotherapy sP-selectin, vWF antigen (vWF:Ag), and ADAMTS-13 plasma levels were determined with ELISAs before and 3 months after chemotherapy. The clinical characteristics of the patients, cancer type, cancer stage, chemotherapy regimen, ABO blood type, D-dimer level and Khorana risk score were also analyzed using logistic regression. Patients were observed for the possibility of developing DVT during chemotherapy.ResultsDVT was confirmed in 5 patients (12.5%) after a period of 3 months. In patients with DVT, sP-selectin and vWF were significantly higher while ADAMTS-13 was lower than in their counterparts. The levels of baseline vWF:Ag and ADAMTS-13, with cut-off points ≥ 2.35 IU/mL and ≤ 1.03 IU/mL, respectively, were found to independently predict the incidence of DVT. In the multivariate logistic regression analysis, the relative risk (RR) for DVT in patients with high vWF:Ag was 3.80 (95% CI 1.15-12.48, p=0.028), and that for patients with low ADAMTS-13 was 2.67 (95% CI 1.22-23.82, p=0.005). The vWF:Ag/ADAMTS-13 ratio and both vWF:Ag and ADAMTS-13 dynamics during treatment were also able to differentiate those with prospective DVT. However, sP-selectin and other covariates showed no statistical significance. ConclusionPrechemotherapy plasma levels of vWF:Ag ≥ 2.35 IU/mL and ADAMTS-13 ≤ 1.03 IU/mL are independent risk factors for DVT incidence.

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A Pilot Study of Subcutaneous Recombinant Hirudin (HBW 023) in the Treatment of Deep Vein Thrombosis

Thrombosis and Haemostasis ◽

10.1055/s-0038-1642482 ◽

1994 ◽

Vol 71 (05) ◽

pp. 558-562 ◽

Cited By ~ 28

Author(s):

F Schiele ◽

A Vuillemenot ◽

Ph Kramarz ◽

Y Kieffer ◽

J Soria ◽

...

Keyword(s):

Deep Vein Thrombosis ◽

Plasma Levels ◽

Degradation Products ◽

Subcutaneous Administration ◽

Pulmonary Angiography ◽

Heparin Therapy ◽

Hemorrhagic Complication ◽

Recombinant Hirudin ◽

Vein Thrombosis ◽

Deep Vein

SummaryBackground: Recombinant hirudin, a pure, specific antithrombin could be more effective than heparin in the treatment of deep vein thrombosis, but its short half-life requires constant intravenous infusion, whereas subcutaneous administration of recombinant hirudin can ensure stable and prolonged plasma levels. The aim of our study was to assess the pharmacokinetics, the results on the coagulation variables, and the safety of a recombinant hirudin (HBW 023) administered subcutaneously in patients suffering from deep vein thrombosis.Methods: Recombinant hirudin (HBW 023) was administered subcutaneously to 10 patients with recent deep vein thrombosis, at a dose of 0.75 mg/kg of body weight twice daily for 5 days, after which standard heparin and acenocoumarol were introduced. Bilateral lower limb venography, and pulmonary angiography, and/or ventilation-perfusion lung scan were carried out on day 1 prior to recombinant hirudin injection and repeated on day 5. aPTT and recombinant hirudin plasma levels were serially assessed after the 1st and the 10th injections. Prothrombin fragments 1 + 2, thrombin-antithrombin III complexes, fibrin degradation products were collected on days 1 and 5.Results: Clinical evolution was uneventful in all but one patient who had a probable recurrence of pulmonary embolism on day 4. No hemorrhagic complication, no untoward biological event was observed. On days 5, Mardcr score was unchanged or had decreased. Plasma levels of recombinant hirudin peaked in between 3 and 4 h following the injection. aPTT values paralleled, and were significantly correlated with plasma levels of recombinant hirudin on day 1 as well on day 5 (r = 0.903, r = 0.948 respectively). Fragment 1 + 2, and thrombin antithrombin complexes non-significantly decreased from day 1 to day 5.Conclusions: Subcutaneous administration of recombinant hirudin ensures prolonged stable plasma levels of recombinant hirudin which results in efficient anticoagulation. A dose-ranging study conducted with subcutaneous recombinant hirudin in comparison to conventional heparin therapy may answer the question as to efficacy.

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Coagulation disorders in the patients with deep vein thrombosis of lower extremity

Srpski arhiv za celokupno lekarstvo ◽

10.2298/sarh0306201m ◽

2003 ◽

Vol 131 (5-6) ◽

pp. 201-207 ◽

Cited By ~ 1

Author(s):

Dragan Milic ◽

Miljko Pejic ◽

Danilo Stojiljkovic ◽

Aleksandar Karanikolic ◽

Sasa Zivic ◽

...

Keyword(s):

Deep Vein Thrombosis ◽

Factor Vii ◽

Common Finding ◽

Diagnostic Strategy ◽

Coagulation Disorders ◽

Coagulation Activity ◽

Vein Thrombosis ◽

Deep Vein ◽

D Dimer

PURPOSE Venous thromboembolism is a relevant social and health care problem for its high incidence, pulmonary embolism-related mortality and long-term sequelae which may be disabling (post-thrombotic syndrome and ulceration). PROCEDURES The aim of our work was to establish the presence of coagulation disorders (hypercoagulable states) in the patients with deep vein thrombosis (DVT) of the leg. Prospectively we have analyzed a group of 30 patients with echosono-graphicaly verified DVT of the leg who were admitted to the department of vascular surgery from August 1st 2000 to July 31st 2001.The following parameters were monitored: prothrombin time (PT) partial thromboplastin time (PTT), fibrinogen (Fib), alpha 2 antiplasmin (A-2 AP), D-dimer (DD), antithrombin III (AT III) and factor VII. FINDINGS Activation of the coagulation process was registered. The values of monitored coagulation parameters are shown in table 1. Plasma levels of monitored parameters in the patients with DVT of the leg were significantly higher than in the control subjects. CONCLUSION In patients with a DVT a hypercoagulable state is common finding. Some parameters of coagulation activity such as D-dimer might be of great interest in the diagnostic strategy of DVT.

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