Patricia Casais

Bleeding risk factors in chronic oral anticoagulation with acenocoumarol

We studied major bleeding complications, death related to hemorrhage, and tried to identify predisposing factors for bleeding in outpatients treated with acenocoumarol. We evaluated 811 outpatients attending a specialized anticoagulant therapy unit. The intended INR range was 3.5–4.5 for mechanical heart valve replacement (N= 384) and 2.0–3.0 for other indications (N= 427). The variability of INR for the total follow‐up and the 2 months before the hemorrhage was calculated. The total follow‐up was 1,963.26 years with 27,321 control tests. We observed 47 major bleeding episodes, including 2 fatal (central nervous system hemorrhages), in 37 patients. 49.5% of the patients had underlying diseases. The rate of major and fatal hemorrhage was 2.39 and 0.10 episodes per 100 patients year, respectively. Hemorrhagic complications were more frequently observed in patients with a more intense intended range (8.2% in the INR 3.5–4.5 group vs. 1.5% in the 2.0–3.0 INR group). The risk of major bleeding increased in patients with an achieved INR higher than 6 and in those with higher INR variability during follow‐up. The estimated probability of bleeding also increased with time: it was 0.102% at 78 months, and at the beginning of therapy it was 0.006% and 0.007% at 1 and 4 months, respectively. The intensity of anticoagulation and the deviation of the INR from the target are the most important risk factors for bleeding in patients taking acenocoumarol. Monitoring the variability of INR can help identifying patients predisposed to bleeding. However, the screening for underlying disease should always be performed. Am. J. Hematol. 63:192–196, 2000.

Pilot study of homocysteine and cysteine in patients with thrombosis in different vascular sites. Epidemiology and response to folate.

Hyperhomocysteinemia is a risk factor for arterial and venous thrombosis. However, lowering homocysteine (Hcy) with vitamins not only failed to improve outcomes but also may lead to recurrent events. Our objectives were to evaluate Hcy and cysteine (Cys) levels in patients with thrombosis in different vascular sites, and their response to folate. One hundred and sixty four consecutive patients with thrombosis (42.1% arterial (AT), 36% venous (VT), 4.9% both venous and arterial thrombosis (AVT) and 17% unusual site (UST)) were included. Hcy and Cys were highest in patients with AVT and UST (p=0.0006). Ninety-three patients were treated, 70% were followed-up. Hcy levels normalized after therapy in all patients. Cys levels tended to vary after therapy according to the site of thrombosis. We observed a significant correlation between folate and Hcy (r: 0.48; p=0.005) among homozygous for MTHFR. A significant inverse relation was observed between Hcy and folate among homozygous and heterozygous (r: 0.462, p=0.007 and r: 0.267; p=0.04, respectively). No correlation was observed between folate and Cys. In conclusion, our observations suggest that Hcy and Cys might be implicated in thrombosis in different vascular sites, and respond differently to folate.

R924Q substitution encoded within exon 21 of the von Willebrand Factor gene related to mild bleeding phenotype

R924Q substitution encoded within exon 21 of the von Willebrand Factor gene related to mild bleeding phenotype -

Antiphospholipid antibodies and hyperhomocysteinaemia in patients with vascular occlusive disease

Hyperhomocysteinemia (HHcy), lupus anticoagulant (LA) and anticardiolipin antibodies (ACA) are independent risk factors for thrombosis. Even though risks are cumulative, the clinical impact of the association is unknown. Preliminary data suggested that HHcy might be associated with transient LA and ACA, disappearing after lowering HHcy. We prospectively evaluated the association of HHcy and LA/ACA, the effect of lowering HHcy with folic acid in LA behavior, and the correlation of the initial dRVVT with LA behavior after folic acid in 210 patients with thrombosis and adverse pregnancy outcomes. Prevalence of HHcy among patients with LA/ACA was 40%. Thirty-one patients exhibited only HHcy (15%; Group 1), 106 (50%; Group 2) had only LA/ACA, while 73 (35%; Group 3) had both. After therapy, 63% and 64% of LA/ACA remained positive in Group 3 and 2, respectively. We observed a trend towards a more positive dRVVT in persistent LA after lowering HHcy. No differences in clinical presentation or in outcomes after two years of followup were observed among the groups. Even though the association of HHcy and LA/ACA is common in patients with thrombosis, it might have no prognostic implications if Hcy levels are lowered. Currently, no laboratory findings correlate with LA behavior, which is independent of homocysteine levels and vitamin treatment.

Prosthetic Valve Thrombosis in Pregnancy A Promising Treatment for a Rare and Mostly Preventable Complication

Prosthetic heart valve thrombosis (PVT) is a rare complication, with an estimated incidence of 0.1% to 5.7% per patient-year.1 However, during pregnancy, changes in the hemostatic system lead to a procoagulant state that increases the risk of PVT up to 10%.2 This maternal and fetal life-threatening complication is mostly preventable with long-term adequate anticoagulation therapy. When anticoagulation fails, treatment focuses on choosing between cardiac surgery and thrombolysis, 2 therapeutic strategies with risks and benefits for the mother and fetus that are difficult to assess. Article see p 532 The study by Ozkan et al3 in this issue of Circulation is the largest series of pregnant patients with prosthetic mitral valve thrombosis reported to date and offers interesting results in a scenario in which randomized, clinical trials are not feasible. A protocol of low-dose, slow infusion of tissue-type plasminogen activator with repeated doses as needed that was guided by transesophageal echocardiography was associated with a successful thrombolysis in all episodes, with no maternal deaths and a fetal mortality rate of 20%, results that seem to be better than those obtained with other thrombolytic strategies reported. The authors’ conclusions on the superiority of thrombolysis over surgery and the redefinition of the lytic option as a first-line therapy in pregnant patients with PVT require careful evaluation. Previous studies of cardiac surgery showing maternal and fetal mortality rates of 6% and 30%, respectively, were published a decade ago and were based mostly on coronary revascularization procedures. Since then, some recommendations have been included, such as appointing the procedure during the second …

Mechanical heart valve prostheses and persistent lupus anticoagulant: is the thrombotic risk increased?

The risk of thrombosis in patients with mechanical heart valve prostheses in spite of life-long adequate anticoagulation is 1–2% per year. Current recommendations for anticoagulation take into account the prosthesis itself and the co-morbid conditions that enhance the thrombotic risk. Lupus anticoagulant is diagnosed in many thrombotic recurrences.We designed an ambispective case–control study to evaluate thrombotic events in patients with mechanical heart valve prostheses and persistent lupus anticoagulant. Our objectives were to determine whether persistent lupus anticoagulant increased the risk of embolism in that population and thus, if a more intense anticoagulation would be recommended, even at the risk of increasing bleeding episodes.We included 16 patients and 16 controls with more than 80 patient-years of follow-up and with other risk factors for embolism. We observed no increased rate of thromboembolic events in patients than in controls, even during high-risk situations (i.e. bacterial endocarditis). Our population spent most of the time within the intended anticoagulation range.We conclude that adequate anticoagulation is the most important issue to prevent events, protecting against thrombosis without increasing the bleeding risk.