Cristina Falcón

High prevalence of hyperhomocyst(e)inemia in patients with juvenile venous thrombosis.

We determined the prevalence of hyperhomocyst(e)inemia before and 4 hours after a methionine load (3.8 g/m2) in 80 patients (25 mean and 55 women) who had had at least one verified episode of venous thromboembolism before the age of 40 years and in 51 healthy control subjects. No patient had any of the hemostatic abnormalities known to be associated with increased risk of venous thrombosis, and all had normal renal and liver function and no evidence of neoplastic disease. Hyperhomocyst(e)inemia was defined as fasting plasma homocyst(e)ine levels or absolute postload increments of homocyst(e)ine above the normal range. According to these diagnostic criteria, 15 patients (18.8%) and 1 control subject (1.9%) had hyperhomocyst(e)inemia. In 1 of these patients only, hyperhomocyst(e)inemia could be explained by low serum concentrations of vitamin B12 and folates. The family history for venous thromboembolism was positive for 7 of the 15 patients. Family studies, performed for eight kindreds, showed that for more than half of the studied probands the abnormality was inherited. This study indicates that moderate hyperhomocyst(e)inemia is associated with an increased risk of developing venous thromboembolism at a young age and that measurements of fasting and postmethionine plasma homocyst(e)ine levels may be useful in the evaluation of patients with juvenile venous thromboembolism, particularly if their family history suggests the presence of an inherited abnormality.

Pregnancy loss and autoantibodies against phospholipid-binding proteins.

Objective To evluate the relationship between anibodies against β2-glycoprotein I or prothrombin and pregnancy losses in women with antiphospholipid antibodies. Methods Women with antiphospholipid antibodies, (lupus anticoagulant and/or anticardiolipin antibodies), with (n = 41) and without (n = 61) a history of pregnancy loss were evaluated. Thirty-one out of the frty-one patients with pregnancy loss had early miscarriages (at less than 13 weeks) and ten patients had late iscarriages. Immunoglobulin (Ig)-G and IgM anti-β2-glycoprotein I and anti-linked immunosorbent assay method. Results A significant association between pregnancy loss and positive IgM anti-β2-glycoprotein I antibodies was found (odds ratio 2.6; 95% confidence interval 1.03, 6.6; P = .043). Women with late pregnancy loss had higher levels of both IgG and IgM anti-β2-glycoprotein I antibodies compared with controls (P < .05). There was a good correlation between anticardiolipin and anti-β2-glycoprotein I antibodies levels (IgG: r = 0.75; IgM: r = 0.73). In contrast, there was no correlation between the levels of anticardiolipin or anti-β2-glycoprotein I antibodies and the levels of anti-prothrombin antibodies. furthermore, the presence of antiprothrombin antibodies was not associated with a history of pregnancy loss. Conclusion The result of our study shows that there is a relationship between the presence of IgM anti-β2-glycoprotein I and previous miscarriages in women with antiphospholipid antibodies.

Inhibition of human platelet aggregation and thromboxane B2 production by melatonin. Correlation with plasma melatonin levels

Abstract: Plasma melatonin concentrations and the effect of melatonin on arachidonic acid (AA)‐induced aggregation and thromboxane B2 (TxB2) production by platelet‐rich plasma (PRP) were examined in five normal male volunteers, sampled at 2 hr intervals from 21:30 to 09:30 hr. Peak plasma melatonin concentration was found at 03:30 hr. Inhibition by 10−6 M melatonin of AA‐induced PRP aggregation was observed only in samples taken at 01:30 hr. Assessment of the inhibitory effect of 10−9–10−6 M melatonin on AA‐induced TxB2 production indicated that melatonin activity was greater at 01:30 h as compared to late night. Assessed as a global effect, the inhibitory activity of melatonin on PRP TxB2 showed a maximum at 01:30 hr and minimal effects at 03:30 hr, at the time when plasma concentrations of melatonin were highest. These results indicate the existence of a nocturnal variation in sensitivity of human platelets to melatonin, with a peak that precedes the maximum in circulating melatonin levels.

Comparison of Various Screening and Confirmatory Tests for the Detection of the Lupus Anticoagulant

Several assay systems have been proposed for detection of the lupus anticoagulant (LA). We compared several screening and confirmatory tests used for the detection of LA in 108 patients. LA was detected in 52 plasmas. The activated partial thromboplastin time (APTT) and the dilute Russell viper venom time (DRVVT) were the most sensitive screening tests as compared to the kaolin clotting time (p less than 0.001). The platelet neutralization procedure in both the APTT and DRVVT systems was superior to APTT performed with high phospholipid concentration (p less than 0.01) and tissue thromboplastin inhibition (p less than 0.001) as confirmatory tests. There was an association between the presence of LA and antiphospholipid antibodies detected by the enzyme-linked immunosorbent assay (p less than 0.001). In summary, our results show that APTT may be a sensitive test for the detection of LA when an appropriate reagent is employed, and that freeze-thawed platelets are more effective than phospholipids to neutralize LA activity.