Previous History Of Thrombosis Research Articles

Essential Thrombocythemia: Analysis of Risk Factors for Thrombotic Events in a Series of 306 Patients.

Essential thrombocythemia (ET) is a chronic myeloproliferative disorder characterized by peripheral thrombocytosis and abnormal proliferation of megakariocytes in the bone marrow. Even thought thrombosis is frequently associated to ET, the risk factors of this clinical complication are still controversial. The aim of this retrospective, single institution study was to investigate clinical and laboratory characteristics associated with the occurrence of thrombotic events, with the purpose of identifying subgroups of patients who could benefit from antiaggregant and/or cytostatic treatment. 306 consecutive ET patients (109 men and 197 females, median age 58 yr) diagnosed between January 1979 and December 2002 were included in the study. At the time of analysis, 196 patients were still alive with a median follow up of 96 months. The following variables were investigated for the association with thrombotic complications: age, platelet count, previous history of thrombotic events, time from diagnosis, treatment with antiaggregant/cytostatic drugs, and cardiovascular risk factors such as arterial hypertension, obesity, hypercolesterolemia, diabetes, cigarette smoking. At the time of last follow up, 46 patients (15%) experienced at least one thrombotic event. The occurrence of thrombotic events was observed in 26/64 (40.6%) patients with previous history of thrombosis and in 20/242 (8.3%) patients with no previous history of thrombosis (p<0.0001 Fisher's exact test, odd ratio 7.6). A significant difference between the two groups of patients was also confirmed when Kaplan Meier estimates of thrombosis-free survival were compared by log-rank test (p<0.0001). By logistic regression, platelet number at diagnosis did not associate with occurrence of thrombosis in the whole patient population. When patients without previous history of thrombosis were stratified according to the number of cardiovascular risk factors (none vs one vs more than one), a significant correlation with occurrence of thrombotic events was observed (Mantel-Haenszel Chi-square 5.47, p<0.05). This study confirms that history of thrombosis is strongly related with risk of further thrombotic events in patients with ET, whereas platelet number at diagnosis does not seem to represent a prognostic factor. In patients with no previous history of thrombosis, the presence of other cardiovascular risk factors has to be taken into account when establishing the therapeutic approach.

Increased Granulocyte CD11b and Monocyte Tissues Factor Expression in Patients with Essential Thrombocythemia and Thrombosis.

The mechanisms accounting for the increased risk of thrombosis in patients with essential thrombocythemia (ET) are not well known. Recently, a possible role for the granulocytes in the development of thrombosis in ET has been suggested. To analyze the possible relationship between granulocyte activation and a history of thrombosis in ET, granulocyte activation was studied in 53 ET patients (26 with a previous history of thrombosis and 27 without) and 26 healthy controls. Neutrophil and monocyte CD11b expression, monocyte tissue factor (mTF) expression, and platelet-neutrophil (PNC) and platelet-monocyte (PMC) complexes were studied using whole blood cytometry and the results were expressed as percentages and in MESF (molecules of equivalent soluble fluorochrome) units. Granulocyte CD11b and mTF expression were measured at baseline and after activation with lipopolysaccharide (LPS). The results are as follows: 1) ET patients had significantly higher baseline percentages of circulating PNC and PMC as well as neutrophil CD11b MESF expression than the controls (p=0.0001); 2) monocyte CD11b expression was higher in patients with ET and thrombosis (mean 151241 MESF) than in those without (127191 MESF) and in the controls (65717 MESF) (p= 0.0001); 3) mTF baseline surface expression was increased in ET patients as compared with the controls (15635 vs 9385 MESF, p= 0.0001); 4) following LPS activation, patients with ET and previous thrombosis had significantly higher mean percentage of mTF expression than those without thrombosis and the controls (48%, 36% and 25%, respectively) (p= 0.0001). No differences were noted when the results were analysed according to the treatment that the patients were receiving at the time of study. In conclusion, patients with ET and a history of thrombosis show a marked increase in granulocyte activation, especially in monocyte activation, and therefore such alteration might play a role in the pathogenesis in these patients.

Prospective Cohort Study of the Incidence, Risk Factors and Long-Term Sequelae of Symptomatic Catheter-Related Thrombosis in Adults with Cancer.

Long-term indwelling central venous catheters (CVCs) are used for delivering chemotherapy, parenteral nutrition, antibiotics, and blood products, as well as for facilitating blood drawing, in many patients with malignancy. Although the important supportive role of CVCs is unquestioned, there is uncertainty regarding the prevention and treatment of catheter-related thrombosis (CRT) because there is a lack of prospective and contemporary data on the natural history of this complication. As a first step towards improving CRT management, we conducted a prospective cohort study to examine the incidence, clinical risk factors, and the long-term sequelae of symptomatic CRT in adults with cancer. Consecutive patients undergoing insertion of a CVC at a tertiary care center were enrolled and followed for the duration of their catheter-dwell time plus 4 weeks or a maximum of 52 weeks, whichever comes first. Scheduled assessments were done at weeks 1, 2, 4, 8, 12, 24, 36 and 52 weeks after insertion. Patients with symptomatic CRT were treated with anticoagulants and were followed for an additional 52 weeks from the date of CRT diagnosis. Baseline information and follow-up data regarding catheter patency, thromboprophylaxis, clinical symptoms, and thrombotic events was collected. Standardized regional guidelines for catheter care were followed and symptomatic CRT was diagnosed based on objective testing and satisfaction of prespecified criteria. Between March 2002 and July 2003, 444 patients underwent 500 catheter insertions. The mean patient age was 56 y (range 18–91 y) and 55% of patients were female. Catheters inserted included PICCs (65%), ports (18%), pheresis (11%), and Hickman catheters (6%). As of July 22, 2004, 442 patients had completed follow-up. The total catheter-dwell time was 59,959 d (median 88 d), while the total follow-up was 73,654 pt-d (median 151 d). Colorectal was the most common tumor type in 18% of patients and 41% of all patients at enrolment had metastatic solid tumor. Overall, there were 19 episodes of symptomatic CRT, representing an incidence of 4.3% (95% CI 2.6–6.6%) of patients or 0.3 CRTs per 1000 catheter-dwell days (95% CI 0.2–0.5 per 1000 d). The mean time to CRT was 53 d (range 6–162 d). Development of CRT was not associated with age, ECOG performance status, cancer treatment, catheter type, side of insertion, thromboprophylaxis, infection, or previous history of thrombosis. The only significant risk factor was ovarian cancer (P=0.02). In patients with symptomatic CRT, 89% (17/19) of CRTs were treated with anticoagulant therapy alone, 5.3% (1/19) had the catheter removed, and 5.3% (1/19) were treated with both; none had symptomatic pulmonary embolism or post-thrombotic syndrome during follow-up. In summary, the incidence of symptomatic CRT in adults with cancer is low and treatment with anticoagulant therapy alone was not associated with any serious long-term sequelae. Due to the small number of CRTs observed, larger studies are required to further evaluate risk factors and identify the optimal therapeutic approach for CRTs.

Longitudinal study of antinuclear and anticardiolipin antibodies in pregnant women with systemic lupus erythematosus and antiphospholipid syndrome

The objective of this study was to perform a longitudinal follow-up of antinuclear antibodies (ANAs) and anticardiolipin antibodies titers (aCL) throughout pregnancy in a group of patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) patients during their therapy for the prevention of fetal loss and to examine their relationship with pregnancy outcome. Thirty patients and 15 controls were followed in the study. Fifteen patients had SLE (group I) and 15 had APS (group II, of which seven patients had primary APS and eight had APS secondary to SLE). All patients were receiving therapy for the prevention of fetal loss with prednisone and aspirin as part of an ongoing clinical trial in lupus pregnancy. If there was a history of previous thrombosis, heparin was added. Blood samples were taken at the 1st, 2nd, and 3rd trimesters (T) of pregnancy in order to assess the presence of IgG and IgM aCL antibodies (ELISA), anti-dsDNA ( C. luciliae) ANAs (HEp-2 cells), and immunospecific antibodies (antiextractable nuclear antigens). We collected 90 samples from patients and 45 samples from healthy controls. Group I (SLE) ANAs were positive in 100% during the 1st T, 67% in the 2nd T, and 67% in the 3rd T, with various immunofluorescence patterns. In five patients, aCL antibodies were detected without a history of APS (one in 1st T, three in 2nd T, and one in 3rd T). Fetal loss was observed in two patients, in one of whom it was associated with nephritis, high titers of ANAs, and anti-dsDNA. Another patient had pulmonary hemorrhage with anti-dsDNA and aCL. In group II, all but one patient with primary APS were negative to ANAs. In secondary APS, by contrast, 6/8 patients (75%) had positive ANAs at least during the 1st T. All seven patients with primary APS and 6/8 with secondary APS had aCL during pregnancy. In 9/15 (60%) patients from the APS group with a history of previous fetal loss, aCL became negative during pregnancy and they had live births. The disappearance of aCL was associated with improved fetal survival (relative risk, or RR, 0.67). ANAs in the control group were positive in 7% at low titers, and all of them were negative for aCL. Despite treatment, ANAs are prevalent during pregnancy in SLE patients and APS secondary to SLE. During pregnancy in SLE, aCL titers may appear. Decreasing titers and/or disappearance of aCL correlated with improved fetal prognosis in a subset of patients with APS.

Prevalence of Anti‐cardiolipin, Anti‐β2 Glycoprotein I, and Anti‐prothrombin Antibodies in Young Patients with Epilepsy

To measure anti-cardiolipin (aCL), anti-beta2 glycoprotein I (anti-beta2GPI), and anti-prothrombin (aPT) antibodies in young patients with epilepsy, and to correlate their presence with demographic data, clinical diagnoses, laboratory and neuroradiologic findings, and antiepileptic drugs (AEDs). Sera from one hundred forty-two consecutive patients with epilepsy with a median age of 10 years were tested for aCL and anti-beta2GPI autoantibodies by solid-phase assays. aPT antibodies also were assayed in sera from 90 patients. Positive results were confirmed after a minimum of 6 weeks. Antinuclear antibodies (ANAs) and antibodies against extractable nuclear antigens (ENAs) also were tested. An overall positivity of 41 (28.8%) of 142 sera was found. Fifteen patients were positive for aCL, 25 for anti-beta2GPI, and 18 for aPT antibodies. Several patients (12%) displayed more than one specificity in their serum. Only one of these patients had a concurrent positivity for ANAs and ENAs. A predominance of younger patients was found in the antibody-positive group. All types of epilepsy were represented in the positive group. No relation between antibody positivity and AEDs was found. Diffuse ischemic lesions at computed tomography (CT)/magnetic resonance imaging (MRI) scans were present in higher percentages in patients who were antibody positive. No positive patient had a history of previous thrombosis or other features related to systemic lupus erythematosus (SLE), and no patient was born of a mother with SLE. Our study suggests a relation between epilepsy and aPL in young patients. A pathogenetic role for these autoantibodies cannot be excluded, and their determination might prove useful even from a therapeutic point of view.

Laboratory evaluation of hypercoagulable states in patients with central retinal vein occlusion who are less than 56 years of age

Purpose To investigate whether hypercoagulability plays a role in thrombus formation in patients with central retinal vein occlusion (CRVO) who are less than 56 years of age. Design Prospective, observational case series with retrospective comparative controls. Participants and controls Participants included 55 consecutive patients with CRVO less than 56 years of age. The laboratory’s age-matched control groups were used to compare results for the same tests. Methods Fifty-five patients with CRVO less than 56 years old (mean age, 44 years) underwent laboratory evaluation for homocysteine, activated protein C resistance, protein C activity, protein S activity, antithrombin III activity, antiphospholipid antibodies, and anticardiolipin antibodies. The results were compared with previously drawn age-matched control groups obtained by the same laboratory for statistical significance. Main outcome measures Patients were considered to have a positive test if their results were outside the laboratory’s established range. Results Fifteen of 55 patients (27%) had one positive test result suggesting hypercoagulability. Compared with the control groups, these patients less than 56 years old with CRVO had a higher incidence of coagulation abnormalities by laboratory testing. Among the parameters tested, hyperhomocysteinemia and circulating antiphospholipid antibodies were significantly more common in the CRVO patients ( P < 0.05) compared with age-matched controls. Conclusions Hypercoagulability may play a role in the pathogenesis of CRVO in patients less than 56 years old. The cause of CRVO remains multifactorial, and laboratory tests suggesting hypercoagulable states alone cannot account for the cause in most of these patients less than 56 years of age. The authors recommend examining blood pressure, intraocular pressure, complete blood count, glucose levels, and a lipid panel on all patients with CRVO. When tests for these common risk factors for CRVO are negative, consider ordering selected tests in young patients with CRVO to rule out thrombophilias, especially in patients with bilateral CRVO, a history of previous thrombosis, or family history of thrombosis.

Congenital and acquired thrombotic risk factors in women using oral contraceptives: clinical aspects.

We describe the thrombophilic and clinical characteristics of a group of patients who suffered venous thrombosis (VT) (n = 36) and ischemic stroke (n = 8) while taking oral contraceptives (OC). Our purpose is to ascertain whether there are differences between users of second and third generation progestogen and to investigate the influence of concurrent congenital and acquired risk factors (other than OC) on the onset of the thrombosis. The group of patients included 36 women with VT and eight with ischemic stroke. The patients' recognized predisposing factors were recorded. We also considered age, length of time on OC, types of OC, rethrombosis, family history of VT, and the presence of thrombophilic genetic defects. In the group of patients with VT, 54% were treated with second generation OC (n = 23), and 30% (n = 11) were treated with third generation OC. We found no significant statistical differences with respect to age and length of time on OC between the two types of OC. The prevalence of genetic defects in these patients--factor V (FV) Leiden, prothrombin G20210A mutation and protein S deficiency--was 19% (n = 7), 17% (n = 6), and 8% (n = 3) respectively. We observed the shortest time lapse between initiating OC and the first thrombotic event in carriers of FV Leiden and in patients with combined defects, but the differences were not significant. In patients with ischemic stroke, 50% were treated with second generation OC and 50% were treated with third generation OC. Prothrombin G20210A mutation was detected in two patients. In both patients,the stroke occurred earlier than in the rest of the patients, but these differences were not statistically significant. With respect to preventing thrombotic events in these patients, our data suggest that OC therapy should be avoided in patients with a previous history of thrombosis and in patients with an evident thrombotic tendency in the family. In patients in whom the family history of thrombosis is not very evident, it would be recommended to screen for FV Leiden, prothrombin G20210A mutation, and protein S, and to rule out OC if the patient does in fact have one of these risk factors. Moreover, if a patient develops a thrombotic complication while taking OC, an evaluation to search for a thrombophilic defect is warranted, and at the same time, alternative methods of contraception should be considered.

Alpha 2-Macroglobulin Levels Are High in Adult Patients with Congenital Antithrombin Deficiency

Antithrombin is responsible for about 80% of the progressive inhibitory activity of thrombin in human plasma. The role of other protease inhibitors known to inhibit thrombin is not completely clarified. However, their contribution may become relevant when antithrombin is low. We elected to investigate adult patients with congenital antithrombin deficiency to assess the concentration of other naturally occurring thrombin inhibitors such as alpha 2-macroglobulin, alpha 1-antitrypsin, heparin cofactor II, and C 1-inhibitor. The study included 59 patients with congenital antithrombin deficiency with and without a previous history of thrombosis, together with an equal number of control subjects matched for age and sex. Statistically significant differences (patients vs. controls) were observed only for alpha 2-macroglobulin (i.e., 120 vs. 102%, p<0.01). Further analysis of antithrombin-deficient carriers with and without a past history of thrombosis showed that alpha 2-macroglobulin levels were higher than the 90th percentile of control distribution more often in asymptomatic than symptomatic men (odds ratio=0.04; confidence interval=0.003–0.60), but not in women (odds ratio=2.14; confidence interval=0.35–13.1). In conclusion, results from this cross sectional study showed that alpha 2-macroglobulin levels were high in patients with congenital antithrombin deficiency. Furthermore, the high levels were found more often in asymptomatic than symptomatic men. Whether this increase provides protection against thrombosis should be evaluated in a prospective study.

No treatment for low-risk thrombocythaemia: results from a prospective study.

Essential thrombocythaemia (ET) is a chronic myeloproliferative disorder characterized by the occurrence of thromboembolic episodes, particularly in patients aged > 60 years or with a previous history of thrombosis, and/or by haemorrhages in patients with an exceedingly high platelet count. In these subgroups of patients the use of cytoreductive therapy is beneficial in terms of risk/benefit ratio. Only limited anecdotal data are available on the thrombotic or haemorrhagic risk and survival in young asymptomatic ET patients with a platelet count < 1500 x 10(9)/l. Therefore the optimal management of these patients is unknown. To assess the incidence of thrombosis and haemorrhages in this group of patients we carried out a prospective observational study in a cohort of 65 patients with ET, aged < 60 years, with no history of thrombosis or haemorrhage and platelet count < 1500 x 10(9)/l, and in 65 age- and sex-matched controls. Patients were not treated with cytoreductive therapy until the occurrence of thrombosis or haemorrhage. Arterial or venous thrombotic events were objectively documented both in cases and in controls. The median follow-up was 4.1 years, with an incidence of thrombosis in patients and controls of 1.91 and 1.50 cases/100 patient-years, respectively. The age- and sex-adjusted risk rate ratio was 1.43 (95% CI 0.37-5.4). Only three minor haemorrhagic episodes occurred in patients, with an incidence of 1.12 cases/100 patient-years. Pregnancy and surgery were not associated with thrombosis in these patients. We conclude that the thrombotic risk in young ET patients, with no thrombotic history and a platelet count < 1500 x 10(9)/l, is not increased compared to the normal population and that a conservative therapeutic approach should therefore be considered in these patients.

Laboratory screening of thrombophilia. Evaluation of the diagnostic efficacy of a global test to detect congenital deficiencies of the protein C anticoagulant pathway.

Clinical laboratories are at present confronted with increasing demands for thrombophilia work-up, which may seriously overwhelm their capacity. Recently, methods able to investigate the protein C anticoagulant pathway globally have been proposed. In this study we investigated the reliability of one such method for its ability to detect patients with known defects of the pathway by testing plasmas from patients with the FVQ506 mutation, with congenital protein C, protein S or antithrombin deficiencies, and patients with previous history of thrombosis, but no identifiable defects. The results show that the new global test fulfils the requirements for congenital protein C deficiency and activated protein C resistance associated with the FVQ506 mutation, which account for more than half of the congenital defects found in thrombophilia. However, congenital protein S deficiency very often remains undetected by this test. Improvement of sensitivity toward this component of the protein C anticoagulant pathway would enroll the global test as a suitable candidate to explore the pathway. Since antithrombin, which also remains undetected by this test, is an additional important risk factor for venous thrombosis, devoting time and effort to developing global tests able to detect defects in both the antithrombin and protein C pathways is warranted.

Enhanced Lipid Peroxidation in Patients Positive for Antiphospholipid Antibodies

AbstractThe mechanism leading to the formation of antiphospholipid antibodies (aPL) is still unknown. Because an in vitro study suggested that aPL may derive from pro-oxidant conditions, we sought a relationship between aPL and isoprostanes, indices of lipid peroxidation in vivo. Thirty patients with systemic lupus erythematosus have been studied. Seventeen (56.6%) were positive for aPL because they had lupus anticoagulant and/or high titer of anticardiolipin antibodies (aCL). Plasma levels of tumor necrosis factor (TNF ) and urinary excretion of two isoprostanes, 8-epi-PGF2α and IPF2α -I, free radical catalyzed oxidation products of arachidonic acid, were measured. Patients with systemic lupus erythematosus had higher urinary excretion of 8-epi-PGF2α and IPF2α -I than controls; urinary excretion of the two isoprostanes was highly correlated (Rho = 0.74, P < .0001). Urinary 8-epi-PGF2α was highly correlated with both aCL titer (Rho = 0.70, P < .0001) and TNF (Rho = 0.84, P < .0001), a measure of disease severity. Excretion of this isoprostane was also higher in those patients who exhibited aPL (P < .0001). Comparable correlations were observed with the isoprostane IPF2α -I. No difference of 8-epi-PGF2α was observed between patients with and without previous history of thrombosis. This study, showing the existence of a close association between aPL and increased in vivo lipid peroxidation, supports the hypothesis that these antibodies may result from pro-oxidative conditions and suggests that inflammation may play an important role.

Single-visit venous ulcer assessment clinic: The first year

Venous ulceration is a significant clinical problem to both clinicians and patients. To optimize the management of patients with ulcers a single-visit, dedicated venous ulcer assessment clinic was set up. All patients referred to the clinic during the first year were recorded prospectively. Each patient was assessed clinically and with colour-coded venous and, where indicated, arterial duplex scanning. Ulcers were classified as venous, arterial, mixed or non-vascular on a basis of ankle:brachial pressure indices and venous duplex scanning. Eighty-eight patients (104 limbs with ulcers) were assessed. Seventy-nine per cent of ulcers were venous, 2 per cent arterial, 12 per cent mixed and 7 per cent non-vascular. Of the 95 limbs with demonstrable venous reflux, reflux was confined to the superficial system in 57 per cent, the deep system in 6 per cent and was combined in 37 per cent of limbs. Of the 22 patients who reported previous deep vein thrombosis, nine had normal deep vein function. Some 38 per cent of limbs with no history of previous thrombosis had abnormal deep vein function. In this clinic 14 per cent of leg ulcers had a significant arterial component and over half of venous ulcers may benefit from superficial venous surgery. In many ulcerated limbs, clinical assessment alone is inadequate to detect superficial reflux or previous deep vein thrombosis.

The use of an anti‐β2‐glycoprotein‐I assay for discrimination between anticardiolipin antibodies associated with infection and increased risk of thrombosis

Antiphospholipid antibodies (aPAs), occurring in association with infection, are not generally associated with an increased risk of thrombosis. Anticardiolipin antibodies (aCL) from patients with infection, unlike those from patients with SLE, do not have the beta 2GPI cofactor requirements. Antibodies to beta 2GPI (alpha beta 2GPI) are more closely associated with a previous history of thrombosis than aCL in patients with SLE. In the present study we have investigated the reactivity of the alpha beta 2GPI assay for aPAs associated with infection. Serum from 114 patients with infections including syphilis (n = 11), tuberculosis (n = 63) and Klebsiella (n = 42) were assayed for alpha beta 2GPI and aCL antibodies. The incidence of aCL in serum of patients with tuberculosis. Klebsiella infection and syphilis was 6.0%, 5.0% and 64.0%, respectively, but all patients were negative for alpha beta 2GPI. These results indicate that the alpha beta 2GPI assay is negative in patients with transiently positive aCL assays associated with infection.

Issues in the Diagnosis and Management of Essential Thrombocythemia

To summarize the current trends in the diagnosis and management of essential thrombocythemia (ET) and to discuss the treatment of young and pregnant patients with ET. We review our experiences in the diagnosis and management of ET. A definitive diagnosis of ET at initial examination is seldom possible because of the low incidences of associated clonal cytogenetic abnormalities and palpable splenomegaly. The criteria of the Polycythemia Vera Study Group for the diagnosis of ET are provided, as are the clinical and laboratory features that help to distinguish ET from reactive thrombocytosis. Patients with ET have an almost normal life expectancy if thrombohemorrhagic complications are controlled. Although a previous history of thrombosis is an established risk factor for further episodes, the adverse effects of extreme thrombocytosis and age are less well defined. Determining which patients require therapy is controversial. The management of young or pregnant patients necessitates special considerations. Until additional data become available, no strong recommendations can be given in support of or against specific therapy for asymptomatic young patients. We favor treatment in asymptomatic patients with cardiovascular risk factors but not in asymptomatic women who are pregnant or are of childbearing age.

A rational approach to detection of significant reflux with duplex Doppler scanning and air plethysmography

Purpose: Several techniques are currently available for the detection of venous reflux. We have attempted to determine the relative value and accuracy of available techniques to develop a logical strategy of investigation in reflux venous insufficiency.Methods: The morphologic distribution of venous incompetence (erect duplex and descending venography); the results of ambulatory venous pressure measurement, venous refilling time, the Valsalva test, and air-plethysmography (venous refilling index, VFI); and the clinical severity were described in 118 consecutive limbs. In an attempt to validate the tests, results were correlated with the clinical severity classification (class 0, n = 34; class 1, n = 42; class 2, n = 11; class 3, n = 31) and with a standardized quantification of reflux (multisegment score) as seen on standing duplex Doppler scanning with rapid deflation cuffs.Results: Twenty-nine percent of limbs with severe venous disease (class 23) had pure deep insufficiency, only 6% had pure superficial disease, and the remainder had a combination. A history of previous thrombosis and the presence of posterior tibial vein incompetence were markedly common with ulcer disease (84% and 42%, respectively). The duplex Doppler multisegment score correlated strongly with clinical severity classification (r = 0.97). The venous refilling time and VFI had the highest sensitivity in identifying severe venous disease (class 23), and the ambulatory venous pressure had excellent specificity.Conclusions: For noninvasive determination of reflux, the combination of VFI and duplex scanning not only localized the reflux but also separated severe clinical vein disease from mild, with high sensitivity and specificity. Air plethysmography may also provide valuable information regarding calf muscle pump and outflow obstruction.

IgG Binding to Endothelial Cells in Systemic Lupus Erythematosus

Endothelial-associated IgG were determined in 20 patients with systemic lupus erythematosis (SLE)-8 of whom had a lupus anticoagulant (LA) and 6 a history of thrombosis. The binding of IgG present in patient plasma to cultured human endothelial cells was detected using radiolabeled staphylococcal protein A. Thirteen samples gave positive results and a significant association between endothelial-associated IgG and lupus anticoagulant was found (p less than 0.05). No statistically significant relationship with a previous history of thrombosis was found. These results suggest that the lupus anticoagulant may be directly involved in immune vascular injury induced by either antibodies or immune complexes in SLE.

The Fast Inhibitor of Tissue Plasminogen Activator in Plasma During Pregnancy

The novel fast inhibitor to tissue plasminogen activator in plasma has been determined in 20 healthy non-pregnant women, 48 apparently healthy pregnant women and 136 women with risk pregnancies (preeclampsia, suspected fetal growth retardation, thrombosis or previous history of thrombosis, diabetes and others). In healthy fertile non-pregnant women, the inhibitor concentration was found to be 0.4 +/- 0.7 U/ml. In pregnant women the concentration stayed at this level until week 10, but then an almost linear increase was found, reaching about 6.5 U/ml at week 40. In plasma samples from the patients with risk pregnancies many with deviating concentrations were found. Thus, in the last trimester a range of 0-24.0 U/ml was found in these patients, as compared to 4.0-6.4 U/ml in healthy pregnant women. The pathophysiological impact of this finding is at present unclear.

Relation between antithrombin III and clinical and serological parameters in systemic lupus erythematosus.

The increased frequency of thromboembolic events in patients with systemic lupus erythematosus (SLE) has been attributed to reduced or dysfunctional antithrombin III (At-III). We analysed At-III values, measured by three different assay techniques, in SLE patients, patients with rheumatoid arthritis, and normal and hospitalised controls. In addition, attempts were made to correlate At-III activities of SLE patients with specific clinical and serological parameters such as disease activity, renal involvement, previous thrombosis, degree of proteinuria, and serum complement concentrations. Our results failed to show a significantly reduced At-III in SLE with any method. At-III titres did not correlate with disease activity, concentrations of serum complement or albumin (both only minimally reduced in most patients), or a previous history of thrombosis. At-III deficiency does not appear to be an inherent feature of SLE, and reduced activities should only be anticipated when there are specific aetiological factors present, such as massive proteinuria, extensive hepatic disease, or active thrombosis.