SummaryHaemostatic disorders caused by Lonomia obliqua caterpillars has reached epidemic proportions in southern Brazil. Here we evaluated coagulation and fibrinolysis in 105 patients after accidental contact with Lonomia obliqua caterpillars. Global coagulation tests were prolonged in most cases and patients were divided into 3 groups according to fibrinogen (Fg) level: 0.5 g/l (group A); 0.51–1.5 g/l (group B), >1.5 g/l (group C). There was a significant reduction of factors V, XIII, VIII and prekallikrein in group A, with no change in factors X, II and von Willebrand factor. Thrombin-antithrombin and prothrombin F1+2 were elevated in most patients. Antithrombin and protein S were not changed whereas protein C levels were reduced in group A. Plasminogen and alfa2-antiplasmin levels were significantly reduced in group A and D-Dimer levels were extremely high in all groups, showing that fibrinolysis had been activated, possibly secondary to fibrin production. Levels of t-PA were normal and PAI-1 was mildly elevated in group A. The platelet count remained above 150 × 109 platelets/ml in 97% of cases. In summary, our results suggest that Lonomia obliqua envenoming is characterized by a consumption coagulopathy and secondary fibrinolysis.

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To cite this article: Rodrigues CA, Rocha LKA, Morelli VM, Franco RF, Lourenç o DM. Prothrombin G20210A mutation, and not factor V Leiden mutation, is a risk factor for cerebral venous thrombosis in Brazilian patients. J Thromb Haemost 2004; 2: 1211-12. Prothrombin G20210A mutation, factor (F)V Leiden mutation and oral contraceptive (OC) use were previously shown to be associated with an increased risk of cerebral venous thrombosis (CVT) [1][2][3]. We investigated the prevalences of prothrombin G20210A mutation, FV Leiden mutation and OC use in 42 consecutive patients with objectively confirmed diagnosis of CVT (median age of 28 years and 67% being women), and compared them with 134 healthy subjects, recruited from biologically unrelated acquaintances or partners of patients without history of venous thromboembolism (VTE) or known systemic diseases (median age of 34 years and 60% being women).Prothrombin G20210A mutation was found in 16.7% of patients and 0.7% of the control group, yielding an odds ratio (OR) for CVT of 26.6 [95% confidence interval (CI): 3.2-223.5]. FV Leiden mutation was detected in 4.8% of patients and in 2.2% of the control group (OR: 2.2, 95% CI: 0.4-13.5). It is noteworthy that the majority of carriers of prothrombin G20210A mutation and FV Leiden mutation were Caucasian.Our prevalence of prothrombin G20210A mutation was similar to an Italian study (20%) [3], and to a previous Brazilian report with 14 CVT patients (14.3%) [4]. In accordance to previous reports [2,3], prothrombin G20210A mutation was a significant risk factor for CVT. The proportion of patients carrying FV Leiden was also similar to the previous Brazilian report (7.1%) [4], but lower as compared with the Italian series (15%) [3]. The high prevalence of the prothrombin G20210A mutation in Brazilian patients may derive from the ethnic background of the study populations. Brazilian general population has an extremely heterogeneous ethnic composition, unevenly distributed in the country with variable degrees of admixtures. Brazilian citizens of Caucasian descent originate mainly from Southern Europe (specially Portugal, Italy and Spain), where prevalence of the prothrombin G20210A mutation is twice as high as compared to Northern Europe [5]. Patients and controls had a heterogeneous ethnic distribution: among patients, 55% were Caucasians and 43% were of Caucasian and Black descent and among controls, 20% were Caucasians and 80% were of Caucasian and Black descent. It is important to point out that the high OR for the prothrombin G20210A mutation may be in part attributable to the relatively low frequency of Caucasians among controls, since carriers of prothrombin G20210A mutation were in general Caucasians.Eighty-nine percent of women had thrombosis between 20 and 50 years of age (Fig. 1). For this age group, 60% of the patients were OC users and 20% were in the puerperium when CVT was diagnosed. Among the five women with inherited thrombophilia, there were four who were also OC users. Among patients, 60% were OC users as c...

Fasting total homocysteine (tHcy) and the methylenetetrahydrofolate reductase (MTHFR) C677T mutation were evaluated in 91 patients with venous thromboembolism and without acquired thrombophilia, and in 91 age-matched and sex-matched controls. Hyperhomocysteinemia was detected in 11 patients (12.1%) and in two controls (2.2%), yielding an odds ratio (OR) for venous thrombosis of 6.1 [95% confidence interval (CI), 1.3-28.4]. After excluding 21 patients and four controls with other known genetic risk factors for venous thrombosis, the OR was not substantially changed (7.0; 95% CI, 1.5-33.1). The prevalence of the MTHFR 677TT genotype was not significantly different in patients (9.9%) and in controls (5.5%), with an OR for venous thrombosis of 1.8 (95% CI, 0.6-5.8). Subjects with the MTHFR 677TT genotype showed higher levels of tHcy compared with the 677CC genotype in patients (P = 0.010) and in controls (P = 0.030). In conclusion, we found that fasting hyperhomocysteinemia is a risk factor for venous thrombosis in patients without known acquired thrombophilia and other genetic risk factors for venous thrombosis. Although tHcy levels are significantly higher in those homozygous for the MTHFR C677T mutation, this genotype does not increase the thrombotic risk in our study population.

Summary.We assessed the effect of a recently described mutation in the MTHFR gene (1298 A → C) on the risk of deep venous thrombosis (DVT) by determining its prevalence in 190 patients with verified DVT and in age-, race-and gender-matched controls. MTHFR 1298 A → C was found in 42·1% of patients and in 41·1% of controls. The OR for venous thrombosis was 1·07 (95% CI 0·70-1·65) for heterozygotes and 0·83 (95% CI 0·33-2·08) for homozygotes. The OR for the factor V Leiden (FVL) mutation was 3·40 (95% CI 1·22-9·48), for FII 20210 G → A was 5·22 (95% CI 1·12-24·2) and for MTHFR 677 C → T, 1·24 (95%

Severe consumption coagulopathy has been detected in rats after Lopap (a prothrombin activator from Lonomia obliqua caterpillar bristles) infusion and in humans after accidental contact with L. obliqua bristles. However, platelet count and antithrombin (AT) levels were only modestly affected, suggesting that a different form of blood coagulation activation may be involved in this hemorrhagic syndrome. Here we describe that Lopap had no effect on aggregation of washed human platelets induced by several agonists, suggesting that it might not impair platelet function in vivo. AT was able to inhibit the amidolytic activity of thrombin generated by incubation of Lopap with prothrombin in a purified system, which may be different from that generated by the prothrombinase complex in vivo. The surface expression of both ICAM-1 and E-selectin but not of VCAM-1 was upregulated by Lopap in cultured HUVEC, suggesting that it may behave differently from other mediators, such as thrombin and tumor necrosis factor-α.

Tests were performed before (T0) and after 3 (T3), 6 (T6) and 12 (T12) months of treatment. AT was determined by an amidolytic method, whereas F1+2 and TAT complex were measured by ELISA. RESULTS: There was a significant reduction in the AT level of patients who received oral CEE plus MP at T3. There was no AT reduction in patients taking either oral CEE alone or transdermal 17beta-estradiol plus MP. F1+2 increased in all patients, but it reached statistical significance only in patients receiving transdermal 17beta-estradiol MP at T3. CONCLUSIONS: The CEE associated with MP treatment may reduce AT levels, whereas unopposed CEE or transdermal 17beta-estradiol plus MP does not change AT. These changes might not be clinically relevant in the general population; however, hormonal replacement therapy may increase the risk of thrombosis in women with congenital or acquired thrombophilia.