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Biomedical subjects

P Simioni

Publications and source records attributed to P Simioni.

At least 91 records · Page 5Linked to original sources
PubMed1995

Coagulation and plasma fibronectin parameters in HELLP syndrome.

OBJECTIVES: HELLP syndrome (hemolysis, elevated liver enzymes and low platelets) has a high fetal mortality and maternal morbidity, partly due to its late diagnosis. In order to facilitate earlier diagnosis, we studied the changes occurring in natural coagulation inhibitors, fibronectin and haptoglobin as potential early markers of endothelial damage, coagulation cascade activation and intravascular hemolysis. METHODS: The study compared antithrombin (AT-III), protein C and S activity, plasma fibronectin, 'prothrombin time' and 'partial prothrombin time' (AST, ALT), lactate dehydrogenase (LDH), bilirubin and serum haptoglobin in 17 asymptomatic controls, 19 preeclampsia patients and 11 HELLP syndrome patients. RESULTS: HELLP syndrome patients had higher fibronectin and D-dimer values, lower AT-III and protein C activity, a lower platelet count and higher LDH than healthy controls; only 25% had raised bilirubin. Serum haptoglobin was lower in HELLP syndrome. CONCLUSIONS: Early on in HELLP syndrome, there is probably a pro-coagulatory imbalance in the placental microcirculation. Endothelial damage causes tissue thromboplastin release and coagulation cascade activation due to collagen exposure; the vascular lesion increases thromboplastin in the bloodstream and triggers distant coagulation processes, suggesting compensated disseminated intravascular coagulopathy. Measuring plasma fibronectin and coagulation inhibitors should be supported by testing haptoglobin as a marker of intravessel hemolysis to differentiate conventional preeclampsia from HELLP.

Adult↗
PubMed1995

Ischemic stroke in young patients with activated protein C resistance. A report of three cases belonging to three different kindreds.

BACKGROUND: A new pathological condition termed "activated protein C (APC) resistance" has recently been reported to be the most common hereditary blood coagulation disorder associated with familial thrombosis. APC resistance is characterized by a poor anticoagulant response to APC in the plasma of patients and is due to a defect of factor V. CASE DESCRIPTIONS: This report deals with three Italian families with inherited APC resistance in which stroke had occurred at a young age in one of the family members. One of the patients exhibited ischemic stroke at 8 months of age. Although deep vein thrombosis is considered the main clinical manifestation of the defect, its possible association with stroke is discussed. DNA analysis confirmed the presence of the 1691GA mutation in the factor V gene (factor V Leiden) in all patients with a normalized APC sensitivity ratio of less than 0.70. In three cases the APC sensitivity ratios were very low (approximately 1.2), with a normalized APC sensitivity ratio of approximately 0.4. DNA analysis confirmed that these patients were homozygous for the mutation. The clinical history of these patients suggests that homozygosity for the defect is compatible with life and does not seem to be associated with early or more severe thrombophilia compared with homozygous defects of other clotting inhibitors. CONCLUSIONS: The cases reported here suggest a possible association of inherited APC resistance with ischemic stroke in young patients. Case-control studies should be performed to assess the true association.

Adult↗
PubMed1995

The utility of non-invasive tests for detection of previous proximal-vein thrombosis.

BACKGROUND: Despite the availability of several diagnostic methods for the detection of deep-vein thrombosis (DVT), the identification of previous episodes of DVT remains a diagnostic challenge. STUDY OBJECTIVE: To assess the reliability of a combination of a standardized clinical score with three non-invasive tests: compression ultrasonography (CUS), Doppler ultrasound (DUS), and photoplethysmography (PPG), in determining the presence or the absence of previous proximal DVT. METHODS: One hundred consecutive unselected outpatients were identified, who had undergone contrast venography six to nine years previously because of the clinical suspicion of DVT (confirmed in 43). They were blindly reinvestigated by a panel of trained operators unaware of venography results. They underwent a clinical evaluation of the lower limb, by applying a standardized score to five symptoms and six signs (grading each item from 0 to 3); a PPG test to determine the venous refilling time; a DUS test to determine the venous reflux separately in the common femoral and the popliteal vein; and a CUS test to determine vein compressibility in the same regions. RESULTS: An abnormal CUS test and/or the demonstration of venous reflux in the popliteal region and/or a high clinical score (> or = 8) identified twenty-four of the 43 (56%) DVT + patients with a specificity of 89%. The combination of normal CUS with the absence of venous reflux in both the common femoral and popliteal vein and a low clinical score excluded previous thrombosis in 45 (79%) of the 57 DVT-patients (negative predictive value, 78%). Abnormal venous reflux in the isolated common femoral vein did not reliably predict the presence or absence of previous DVT. However, this occurred in only 13 (13%) patients. The PPG determination of venous refilling time did not improve the results obtained with the other tests. CONCLUSIONS: The combination of a standardized clinical evaluation with the results of CUS and DUS can reliably diagnose or exclude previous proximal-vein thrombosis in almost 90% of patients with previous episodes of suspected DVT.

Double-Blind Method↗
PubMed1995

Recombinant thromboplastin inhibition assay for the detection of lupus anticoagulant.

Tissue thromboplastin inhibition assay (TTI) is a sensitive test for lupus anticoagulant (LA). We have performed TTI in 12 LA positive patients using a new recombinant human tissue factor (Innovin, IN) and compared it with Thromborel S (TH), a commonly used human placenta thromboplastin. The effect of using two different dilutions of each thromboplastin (1:10 & 1:26) was investigated. A 1:26 dilution discriminated better than the 1:10 and this was more evident for Innovin. The mean value obtained with a 1:26 IN dilution was statistically different from that observed with TH at the same dilution. Furthermore, when PT and TTI ratios were considered, differences were statistically significant and seemed to increase depending on thromboplastin dilutions. When we used IN at 1:26 all LA positive patients had a value > 1.2. Then we compared TTI at a 1:26 dilution with dilute Russell's Viper Venom Time (dRVVT) in 50 consecutive patients with suspected lupus anticoagulant not treated with warfarin or heparin. In these patients the diagnosis of lupus anticoagulant was carried out using dilute APTT mixing studies and a platelet neutralization procedure: four out of 50 patients thus tested were LA positive. When dRVVT or TTI-I 1:26 were used, five patients were positive for lupus anticoagulant. Innovin showed similar sensitivity of dRVVT for detection of lupus anticoagulant. It is likely that higher dilutions of thromboplastins could further improve the specificity of this method.

Adult↗
PubMed1994

Acquired risk factors for deep-vein thrombosis in symptomatic outpatients.

BACKGROUND: Epidemiologic studies on deep-vein thrombosis (DVT) have been mainly confined to the inpatient population. The aim of this study was to investigate the association between DVT and acquired risk factors in a large cohort of outpatients with clinically suspected DVT. METHODS: Consecutive outpatients with clinically suspected DVT were enrolled in the study. Before objective testing, all patients were interviewed by a trained physician for the presence of risk factors for DVT development. Subsequently, the presence or absence of DVT was assessed with venography. RESULTS: Approximately 50% of cases of DVT were considered to be secondary to a major risk factor (immobilization, trauma, and/or recent surgery). Among additional risk factors, only increased age (over 60 years), male gender, malignant neoplasm, heart failure, systemic lupus erythematosus, and arteriopathy were independently associated with the risk of acute DVT. CONCLUSION: Major risk factors for venous thromboembolism are a common cause of DVT among symptomatic outpatients; therefore, the usefulness of extending DVT prophylaxis in the outpatient setting should be tested. The role of additional risk factors in the development of DVT needs to be established by properly designed studies.

Ambulatory Care↗
PubMed1994

Clotting inhibitors and fibronectin as potential markers in preeclampsia.

OBJECTIVES: As conventional laboratory tests fail to identify early preeclampsia, the aim of this study was to seek a marker of endothelial injury and select more sensitive tests for monitoring the activation of the coagulation cascade. METHODS: Using routine blood sampling methods, PT, PTT, AT-III, proteins C and S, platelets, fibrinogen and fibronectin were measured in 18 preeclamptic patients and 17 controls with a normal pregnancy. RESULTS: Preeclampsia was associated with higher fibronectin and lower AT-III, protein C and protein S. The platelet count, fibrinogen and PT were similar. PTT was longer in preeclampsia. CONCLUSION: As AT-III revealed compensated coagulopathy and fibronectin demonstrated preeclamptic vascular lesions before these were apparent from routine tests, measuring these elements could contribute to the earlier diagnosis and better treatment of chronically-altered coagulation in preeclampsia.

Antithrombin III↗
PubMed1994

Homozygous factor V-deficient patients show resistance to activated protein C whereas heterozygotes do not.

Resistance to activated protein C (APC resistance) was assessed in plasma from patients with heterozygous and homozygous factor V (FV) deficiency. Because of the identity of the new APC cofactor with non-activated FV, it was expected that the lower the FV level the higher the APC resistance in plasma. Heterozygotes for the FV defect (both antigen and activity levels around 40%) did not show APC resistance in plasma. In contrast, homozygous patients for the same defect (less than 1% antigen and activity levels), had obvious APC resistance. Whether this finding was consistent with a spurious APC resistance or whether it truly reflected the lack of the APC cofactor activity in congenital FV deficiency remains to be clarified. Mixing (1:1) plasma from patients with a homozygous FV defect with pooled normal plasma (PNP) corrected both procoagulant and anticoagulant FV activities. Whenever severely APC-resistant plasma was used in place of PNP, only procoagulant activity was corrected and APC resistance was not affected. This suggests that homozygous FV-deficient plasma completely lacks the cofactor, i.e. the second APC cofactor, which can correct APC resistance in plasma. This indirectly confirms that the second APC cofactor is related to FV.

Drug Resistance↗
PubMed1994

Changing features of proximal vein thrombosis over time.

Recently, the sensitivity of impedance plethysmography (IPG) for the diagnosis of acute deep-vein thrombosis (DVT) in symptomatic outpatients has been questioned. In order to verify whether a change in the venographic pattern of DVT has occurred over years, accounting for the decreased sensitivity of IPG, the authors compared two series of consecutive venograms demonstrating proximal DVT, performed between 1984-1988 (166 patients) and 1990-1992 (140 patients). They evaluated both the extension and the occlusiveness of deep-vein thrombi in the two series. Moreover, changes in the referral characteristics of patients were investigated. In the second series of venograms a significant decrease in thrombi extension, expressed by a lower prevalence of iliac vein thrombosis (29% versus 43%; P = 0.0074) was observed; moreover, a significant increase in the prevalence of nonocclusive thrombi (22% versus 8%; P = 0.0004) was also recorded in the second series when compared with the first. During the study period, among the referral characteristics of patients, the authors observed both a significant decrease in the prevalence of proximal DVT (from 31% to 24%; P < 0.01) and a slight and not statistically significant decrease in the median time elapsed between onset of symptoms and referral for objective testing (from eight and a half to seven days). In conclusion, proximal deep-vein thrombi are currently less extensive and occlusive than observed in the past. These results might depend on earlier referral of less symptomatic patients and might explain the recently reported decrease in IPG sensitivity for proximal DVT.

Analysis of Variance↗
PubMed1993

A novel dysfunctional protein C (protein C Padua 2) associated with a thrombotic tendency: substitution of Cys for Arg-1 results in a strongly reduced affinity for binding of Ca++.

A dysfunctional protein C (PC) molecule (Protein C Padua 2) was found in a 40-year-old man presenting with recurrent deep vein thrombosis/pulmonary embolism and a family history of thrombotic disease. The patient exhibited a normal PC antigen level, normal chromogenic activity (using Protac as PC activator) but markedly reduced coagulometric activity. After adsorption of patient plasma onto Al(OH)3, between 30% and 45% PC antigen/chromogenic activity but no coagulometric activity was detectable in the supernatant. The dysfunctional molecule exhibited reduced affinity for a Ca++ dependent anti-protein C monoclonal antibody as detected by specific ELISA assay. Immunoblotting experiments showed that PC Padua 2 had an increased MW (95 kD v 65 kD for normal PC). The lesion responsible was determined by PCR/direct sequencing to be a heterozygous CGT/TGT transition in exon 3 of the protein C gene resulting in the substitution of Arg by Cys at residue--1 in the pro-peptide leader sequence. The presence of a high MW PC was consistent with the fact that (part of) the propeptide (at least Cys-1) still was attached to the protein C molecule. This finding could also explain the strongly reduced affinity of PC Padua 2 for the Ca++ dependent anti-protein C monoclonals.

Adult↗
PubMed1993

A simple ultrasound approach for detection of recurrent proximal-vein thrombosis.

BACKGROUND: The objective of this study was to develop a simple ultrasound method for measuring thrombus regression in patients with proximal deep-vein thrombosis (DVT) and to test its utility for the detection of DVT recurrence. METHODS AND RESULTS: The study comprised a cross-sectional survey and a prospective investigation (149 and 145 patients, respectively). In both phases, the normalization rate of a previously abnormal ultrasound test, applying the criterion of full compressibility of the common femoral and popliteal veins (C-US method), was assessed. In the prospective study, the vein diameter under maximum compression (thrombus thickness) was measured in the abnormal venous segments at scheduled times (1, 3, 6, and 12 months). In patients presenting with suspected DVT recurrence, the procedure was repeated and results were compared with those available from the previous examination. Noncompressibility of a previously normal(ized) venous segment and enlargement of thrombus thickness (> or = 2 mm) were considered diagnostic of proximal DVT recurrence. The diagnostic accuracy of the C-US method alone, as well as of the combined ultrasound methods (C-US + thrombus thickness), was assessed against contrast phlebography. C-US test normalization occurred in only 30% of patients within 1 year. A significant reduction of the thrombus mass (P < .0001) was recorded throughout the entire study period. However, a major decrease in thrombus mass (> 50%) was recorded within the first 3 months. Of 29 patients who developed a suspected recurrent DVT, phlebography confirmed diagnosis in 11. The C-US method alone showed an excellent accuracy (100%) but was applicable in only 6 patients (21%). Both the sensitivity and the specificity for proximal DVT recurrence of the combined ultrasound methods were 100% (95% confidence interval, 69% to 100% and 81% to 100%, respectively) and were applicable in all patients. CONCLUSIONS: The serial ultrasound measurement of thrombus mass after an acute episode of DVT may allow the correct identification of patients who develop a recurrent proximal-vein thrombosis.

Cross-Sectional Studies↗
PubMed1993

Protein C, factor VII and prothrombin time as early markers of liver function recovery or failure after liver transplantation.

Irreversible initial non-function of the graft liver is a life-threatening early complication of orthotopic liver transplantation (OLT), which needs immediate retransplantation if the patient is to survive. Since protein C (PC) is a vitamin K dependent protein synthesized in the liver and with the same half-life as factor VII (FVII), the behaviour of PC in patients undergoing OLT was studied in comparison with prothrombin time (PT) and FVII. Twelve OLT patients were divided into two groups on the basis of clinical outcome: group A (six cases) in which OLT was successful, and group B (six cases) who developed initial non-function of the graft liver. PT, FVII activity (FVII:act) and antigen (FVII:Ag) and PC activity (PC:act) and antigen (PC:Ag) were carried out on six blood samples collected during the operation. At baseline, coagulation disorders were in agreement with the underlying liver disease, but no differences were seen between the two groups when all tests were considered. Ten minutes, 1, 2 and 3 h after liver reperfusion, mean PT and FVII:act were always significantly increased in good responder patients compared to non-responders. FVII:Ag and PC:Ag were significantly higher in group A than in group B starting 2 h after the liver graft reperfusion; no difference was seen in PC:act levels between the two groups. In addition, PC:Ag mean levels were increased with respect to corresponding PC:act values in non-responder patients, suggesting a qualitative rather than quantitative defect of protein synthesis due to liver damage. In conclusion, PT and FVII:act were more sensitive than PC activity as early prognostic indices of clinical outcome in OLT.

Adult↗
PubMed1993

A family with an abnormal protein C and a thrombotic tendency.

An Italian family with a dysfunctional protein C (type II deficiency) tentatively designated Protein C Padua has been investigated. Five family members had this defect. Thrombotic manifestations occurred in the propositus, his sister, and his 87-year-old mother, who suffered from a transitory ischemic attack (TIA). All other deficient patients were asymptomatic. The abnormality was consistent with normal protein C (PC) antigen level but reduced both anticoagulant and amidolytic activities after PC activation by Protac. When thrombin was used as activator, PC activity level was also reduced. The abnormal PC molecule seemed to have a defect involving the activation region or the active site mechanism (reduced activity level regardless of the PC activators and the methods used in the functional assays). The electrophoretic mobility of the dysfunctional protein, assayed by crossed-immunoelectrophoresis (CIE), was normal in presence of both Na citrate and calcium lactate. The kinetics of antigen-antibody complex formation between the abnormal PC and anti-PC polyclonal antibody was investigated by means of a laser nephelometer and a peculiar pattern was found in the affected patients suggesting a possible anomalous interaction between the antibody and the abnormal protein.

Aged↗