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Armando D'Angelo

Publications and source records attributed to Armando D'Angelo.

26 records · Page 2Linked to original sources
PubMed2002

Plasma levels of endothelial protein C receptor respond to anticoagulant treatment.

The endothelial protein C receptor (EPCR) facilitates protein C activation and plays a protective role in the response to Escherichia coli-mediated sepsis in primates. Previously, a soluble form of EPCR (sEPCR) in human plasma was characterized, and several studies indicated that generation of sEPCR is regulated by inflammatory mediators, including thrombin-mediated up-regulation of surface metalloproteolytic activity in vitro. This study addressed the question of whether plasma sEPCR levels reflect changes in thrombin generation in patients undergoing anticoagulant treatment. The sEPCR levels in patients treated with coumarin-type oral anticoagulants were significantly lower than those in healthy asymptomatic adult volunteers (105.3 +/- 70.8 ng/mL [n = 55] versus 165.8 +/- 115.8 ng/mL [n = 200]; P <.0001). A similar decline in plasma sEPCR levels was found in patients treated with unfractionated heparin. In healthy volunteers, sEPCR levels declined to about 100 ng/mL within 3 days after initiation of an 8-day period of warfarin administration and increased within 2 days after its cessation. Plasma sEPCR levels returned to pretreatment values within 1 week, and the changes in plasma sEPCR levels mirrored changes in values for international normalized ratios. A similar decline in sEPCR levels with time was observed in 7 patients beginning treatment with warfarin for a thrombotic disorder. Prothrombin fragment 1 + 2 levels also decreased in volunteers and patients given warfarin. These results show that plasma sEPCR levels decline in response to treatment with anticoagulants whose mechanism of action is known to decrease in vivo thrombin production.

Adult↗
PubMed2002

Normalization rates of compression ultrasonography in patients with a first episode of deep vein thrombosis of the lower limbs: association with recurrence and new thrombosis.

BACKGROUND AND OBJECTIVES: Delayed thrombus regression after a first episode of deep vein thrombosis (DVT) of the inferior limbs has been implicated in the development of the post-thrombotic syndrome. Whether normalization of vein segments involved in the index DVT has prognostic significance with respect to the probability of DVT recurrence or new thrombosis is currently unknown. In this study, we prospectively monitored thrombus regression in consecutive patients with symptomatic and asymptomatic DVT. Factors affecting normalization rates and the relationship between previous normalization and DVT recurrence or new thrombosis were explored. DESIGN AND METHODS: One hundred and seventy-nine patients with a first episode of symptomatic DVT of the lower limbs (38 with cancer) and 104 patients with DVT occurring after hip replacement surgery were serially monitored by real time B-mode compression ultrasonography (C-US) over a period of 12 months (months 1, 3, 6 and 12). C-US normalization of popliteal and femoral venous segments was arbitrarily assigned to be residual thrombus occupying, at maximum compressibility, less than 40% of the vein area in the absence of compression. RESULTS: In patients with no DVT recurrence or new thrombosis, C-US normalization was observed at 12 months in 100% of 99 patients with post-operative DVT, in 59% of 134 cancer-free symptomatic DVT outpatients and in 23.3% of 30 symptomatic DVT outpatients with cancer (p = 0.0001). Independent negative effects on the probability of C-US normalization were observed for younger age (p <0.05), for the outpatient presentation of the index DVT (p 0.017), for DVT involving the entire femoro-popliteal axis (p 0.05), and for the presence of cancer (p 0.05). DVT recurrence or new thrombosis was observed in 5 patients with post-operative DVT (4.8%), in 7 cancer-free patients with symptomatic DVT (5.0%) and in 8 patients with cancer (21.1%). Only 4 of these patients had shown normalization of their index DVT prior to the event. The presence of cancer was the only significant predictor of DVT recurrence and/or new thrombosis occurring within 3 months from the index DVT (OR = 4.90, p = 0.002). The absence of previous C-US normalization was the only predictor of recurrence or new thrombosis occurring after 3 and 6 months from the index DVT (OR 5.26, p 0.027). INTERPRETATION AND CONCLUSIONS: Absence of C-US normalization after a first episode of DVT appears to be a factor favoring recurrence or new thrombosis and may be relevant to the optimal duration of oral anticoagulant treatment.

Adolescent↗
PubMed2002

Relationship between international normalized ratio values, vitamin K-dependent clotting factor levels and in vivo prothrombin activation during the early and steady phases of oral anticoagulant treatment.

BACKGROUND AND OBJECTIVES: In vitro studies have shown that the rate of prothrombin activation is linearly related to the concentration of factor II (FII) in the assay system, suggesting a key role of prothrombin levels in the expression of the antithrombotic activity of oral anticoagulant treatment (OAT). We investigated the in vivo relationship between prothrombin activation and vitamin K-dependent clotting factor levels during the early and steady phases of OAT in patients and in healthy volunteers. DESIGN AND METHODS: The changes in international normalizezd ratio (INR) and in the plasma levels of FVII, FX, FII, protein C (PC) and prothrombin fragment 1.2 (F1+2) induced by OAT were monitored over 9 days in 10 patients not on heparin starting warfarin after heart valve replacement (HVR) and in 9 healthy volunteers submitted to an 8-day course of warfarin treatment. FII and F1+2 plasma levels were also measured in 100 patients on stable oral anticoagulant treatment with INRs ranging from 1.2 to 6.84. RESULTS: Because HVR patients had subnormal FVII, FX and FII levels after surgery, INR values > 2.0 were attained already 24 hours after the first warfarin dose. In healthy volunteers, INR values greater than 2.0 were first observed after 72 hours. Nadir levels of FVII, PC, FX and FII were reached between 40 and 88 hours in HVR patients and between 72 and 192 hours in healthy volunteers. The FII apparent half-disappearance time (t/2) was 99 hours in HVR patients and 115 hours in healthy volunteers (p = ns). In HVR patients there was no normalization of initially elevated F1+2 levels until day 7 with an apparent t/2 of 132 hours. In healthy volunteers, a decrease to subnormal F1+2 levels was observed by day 8 of treatment (apparent t/2 = 107 hours). In both HVR patients and healthy volunteers, FII and PC levels were independent predictors of the changes in F1+2 levels (p = 0.0001). In patients on stable OAT, only FII levels were independent predictors of the variation in F1+2 levels (p = 0.0001). INTERPRETATION AND CONCLUSIONS: During the early phase of oral anticoagulant treatment in vivo prothrombin activation is a function of the balance between FII and PC levels and is not significantly prevented until nadir levels of FII are obtained. This provides an explanation for the requirement of overlapping heparin and oral anticoagulant treatment for at least 48 hours after the achievement of therapeutic INR values in patients with thromboembolic diseases. In addition, in vivo prothrombin activation is a function of FII levels rather than INR values also in patients on stable oral anticoagulant treatment.

Acenocoumarol↗
PubMed2002

Discrepant sensitivity of thromboplastin reagents to clotting factor levels explored by the prothrombin time in patients on stable oral anticoagulant treatment: impact on the international normalized ratio system.

BACKGROUND AND OBJECTIVES: We tested the principle of local International Normalized Ratio (INR) calibration using INR calibrator plasmas (PT Calibration Plasma Kit, Behring), two thomboplastin reagents (Neoplastin plus, rabbit brain, Stago, and Recombiplastin, recombinant human tissue factor, Ortho Diagnostics) and the same coagulometer (STA, Stago) on 92 patients on stable oral anticoagulant treatment. DESIGN AND METHODS: A four-point calibration was obtained with each reagent by linear regression (sec/INR) on a log-log scale (r > or = 0.999). The bias between the two reagents (Recombiplastin - Neoplastin Plus) was reduced from 31.7% to 17.5% and 7.5% (p=0.001) when results were expressed, respectively, as PT ratio (using the mean normal prothrombin time as denominator term), INR (using instrument-specific ISI supplied by the manufacturers) and calibrated INR, but there was a consistently significant regression of the differences over the average values even after log transformation (r > or = 0.586). The bias between the reagents was reduced to 1% (p=ns) when assuming Recombiplastin as the reference thromboplastin and applying Tomenson's correction, but limits of agreements were as large as 20%. Factor VII, X, V and II activity was measured with the two thromboplastin reagents in all plasma samples using immunodepleted plasmas (Stago). RESULTS: Statistically significant biases were observed for all clotting factors with the two reagents (Recombiplastin Neoplastin Plus) and ranged from 3.5 % (FII) to 37.2% (FVII). In addition, for FVII and FV there was a significant regression of the difference over the average value (after log-transformation, r > or = 0.282). The patients were divided into 3 groups according to their degree of anticoagulation (INR <2.0; INR between 2.0 and 3.5; INR >3.5). Factor levels differed significantly with the two reagents throughout the 3 groups of patients. In addition, the relative distributions of the 3 vitamin K-dependent factors also differed in the 3 groups with the two thromboplastin reagents. INTERPRETATION AND CONCLUSIONS: The discrepant sensitivity to factor VII, X and V levels of the two thromboplastin reagents explored in this study prevents INR calibration with commercially available calibrator plasmas and is responsible for a significant variability in INR values even under optimal conditions of INR calibration.

Adult↗
PubMedDate not supplied

Gene-gene and gene-environment interactions in mild hyperhomocysteinemia.

Mild/moderate hyperhomocysteinemia (HHcy), a highly prevalent condition, is independently associated with an increased risk of arterial and venous thromboembolic diseases. Early reports of the association of mild/moderate HHcy with juvenile venous thromboembolism have shown familiarity for HHcy in relatives of index cases with thrombosis. Similar to inherited thrombophilia defects, inheritance of the HHcy phenotype was accordingly retained important for the definition of HHcy as an independent risk factor for thrombosis. A number of common polymorphisms in genes coding for methylenetetrahydrofolate reductase(MTHFR), methionine-synthase, methionine-synthase reductase and cysthationine beta-synthase (CBS) have been explored for their association with homocysteine levels, fasting and post-methionine load, and with thrombotic diseases. MTHFR thermolability accounts for a 10-fold increase in the risk of mild/moderate HHcy. With the possible exception of the CBS844ins68 insertion, there is no evidence for an increased risk of HHcy for any of these polymorphisms, isolated or in association with MTHFR thermolability. Environmental factors and MTHFR thermolability are main determinants of the HHcy phenotype.If mild/moderate HHcy is a pathogenetic risk factor for thrombosis, intervention aimed to improve the vitamin status appears of major importance, irrespective of common gene polymorphisms of the homocysteine metabolism.

Environment↗