The outcomes of the study were embolism, valve thrombosis, and major hemorrhage. The median follow-up was 23 months. The two treatments offered similar antithrombotic protection. The incidence of embolic episodes was 1.32 per 100 patient-years (95% confidence interval 0.53 to 2.7) for arm A and 1.48 per 100 patient-years (95% confidence interval 0.59 to 3.03) for arm B. Major hemorrhage occurred in 1.13 per 100 patient-years (95% confidence interval 0.41 to 2.45) for arm A and 2.33 per 100 patient-years (95% confidence interval 1.17 to 4.14) for arm B. Gastrointestinal bleeding was not increased by this combined reduced dose of aspirin and coumarin.

A total of 277 patients with untreated Hodgkin's disease, clinical stages I-II, were randomized to cyclophosphamide, vinblastine, procarbazine, and prednisone (CVPP) alone for 6 monthly cycles or to CVPP plus radiation therapy (RT), 3,000 rad, to involved areas (CVPP plus RT). One or more of the following factors were considered as unfavorable prognosis: age greater than 45 years, more than two lymph node areas involved, or bulky disease. In the favorable group, disease-free survival (77% vs. 70%) or overall survival (92% vs. 91%) at 84 months for CVPP versus RT plus CVPP was similar. Patients with unfavorable prognosis treated with RT plus CVPP had longer disease-free survival (75% vs. 34%) (P = .001) and overall survival (84% vs. 66%) than patients treated with CVPP alone.

SummaryIn a study of 170 haemophilia A patients, 43 were found to have an inhibitory effect; seven had anti-factor VIII inhibitors (a-fVIII) (A), 18 had lupus anticoagulants (LAs) with a strong (B: 12) or weak (C: 6) time-dependent effect and 18 had no time-dependent LAs (D). The a-fVIII showed a neutralizing effect only against factor VIII and negative diluted Russell viper venom time (dRVVT). The LAs were diagnosed by dRVVT; the Staclot® LA agreed with the dRVVT. During the study, three patients changed from an a-fVIII to an LA pattern; they also modified their clinical response.Our prevalence of a-fVIII was low (4%) and we found 21% of LA, with a high (50%) prevalence of time-dependent inhibition. This pattern raises the possibility of the coexistence of LA and a-fVIII, stressing the need to develop specific tests to identify a-fVIII and LA.

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.

We performed a prospective, randomized, open study in 109 outpatients under chronic anticoagulation with acenocoumarine, presenting with International Normalized Ratios (INRs) > or = 6.0 and no or minor bleeding. All the patients withheld one dose of acenocoumarine; in addition, a treated group also received 1 mg oral vitamin K1. We aimed at a post-intervention INR < 6.0, with a target zone of 2.0-4.0. The INRs were lowered from a mean of 8.1 +/- 1.7 to 4.9 +/- 2.5 in the controls (P = 0.0000) and from 8.4 +/- 2.4 to 3.3 +/- 3 in the treated patients (P = 0.0000). There were no differences in the percentage of patients with post-intervention INRs < 6.0 or within the therapeutic zone. One-third of the treated patients and only 2% of the controls reached INRs < 2.0 (P = 0.0003). Oral vitamin K1 offered no advantage to the simple discontinuation of one dose of acenocoumarine. A substantial number of treated patients were consequently exposed to under-anticoagulation.

Objective-To evaluate the outcome of pregnancy in women with mechanical heart valve prostheses in relation to the anticoagulant treatment used in the first trimester and the incidence of thrombotic and bleeding complications. Methods-92 pregnancies in 59 women were followed between 1986 and 1997. In 31 pregnancies, oral anticoagulants were discontinued when pregnancy was diagnosed and subcutaneous heparin was started (12 500 U every 12 hours) adjusted to prolong the adjusted partial thromboplastin time to twice the control level. In the second trimester oral anticoagulants were resumed but changed to heparin again 15 days before the expected delivery date. In 61 pregnancies oral anticoagulants were continued during the first trimester. The same regimen of heparin was used for delivery. Results-Abortion or fetal losses were similar (p = 0.5717) in women exposed to oral anticoagulants in the first trimester (13/61; 25%) compared with those who received adjusted subcutaneous heparin (6/31; 19%). Embolic episodes were more common (p = 0.0029) in women who received heparin (4.92%) compared with those on oral anticoagulants (0.33%). Embolic episodes were cerebral and transient. No valve thromboses were observed. No malformations appeared in the 71 newborns, except for one case of hydrocephalus. There were no maternal deaths secondary to thrombotic complications. The only death was the result of major bleeding after the delivery of a premature stillborn. Conclusions-Oral anticoagulants seem to be safer for the mother than adjusted subcutaneous heparin. Heparin does not oVer a clear advantage over oral anticoagulation in the pregnancy outcome. (Heart 1999;82:23-26) Keywords: pregnancy; oral anticoagulants; heparin; prosthetic valvesThe use of oral anticoagulants during pregnancy is controversial and there is no agreement on the most suitable treatment for patients with mechanical prosthetic heart valves, who have a high risk of thromboembolism.Coumarin derivatives carry the risk of embryopathy when given between the sixth and the 12th week of pregnancy, 1 but this complication can be prevented when heparin is substituted for oral anticoagulants. The reports of coumarin embryopathy vary widely, from 0% 2-6 up to 29.6% in a study by Iturbe Alessio et al, 7 in which malformations were mostly aesthetic and overdiagnosis by geneticists has been proposed. The estimated risk of malformation is now believed to be less than 5%. 8 Both oral anticoagulants and heparin carry the risk of fetal loss, probably from diVerent mechanisms. Heparin can induce retroplacental haemorrhage and although its administration during the first trimester can prevent the occurrence of malformations, it certainly does not improve the outcome of the pregnancy.Pregnancy induces several changes in the haemostatic system resulting in a hypercoagulability state with higher risk of thromboembolism. Recently the eYcacy of heparin in preventing thrombotic complications in patients with prosthetic heart valves has been questioned in a retrospective s...

There is convincing evidence that cell adhesion plays an important role in cardiovascular pathology and is frequently associated to "in vivo" cellular activation. This study involves patients with mechanical heart valve replacement (MHVR patients) who have increased platelet polymorphonuclear leukocyte (PMN) reactivity. Dual-color cytometry was used to determine the expression of adhesive molecules on cellular surfaces, platelet, and PMN-bound fibrinogen as well as the presence of circulating platelet/PMN mixed-cell aggregates (MCA) in 55 MHVR patients, 49 control patients under oral anticoagulant therapy, and 22 healthy volunteers. The results demonstrated that (a) PMN from MHVR patients showed an increased PMN-bound fibrinogen (mean +/- SEM: 1,420 +/- 169 anti-fibrinogen fluorescence intensity, P= 0.0012), when compared to controls (mean +/- SEM: 747 +/- 32 anti-fibrinogen fluorescence intensity) and healthy volunteers (mean +/- SEM: 692 +/- 25 anti-fibrinogen fluorescence intensity; (b) platelet activation in MHVR patients was evidenced by the higher expression of CD62P (mean +/- SEM: 128 +/- 19 anti-CD62P fluorescence intensity, P = 0.003) compared to controls (mean +/- SEM: 65 +/- 15 and 50 +/- 10 anti CD62P fluorescence intensity) and by increased levels of platelet-bound fibrinogen (mean +/- SEM: 625 +/- 20 anti-fibrinogen fluorescence intensity, P = 0.0043 versus 496 +/- 45 and 480 +/- 30 for control patients and for healthy volunteers, respectively); and (c) the proportion of MCA in MHVR patients (15 +/- 2%) was significantly higher (P = 0.009) compared to controls (7 + 1%) and healthy volunteers (6 +/- 2%). The results indicate that the presence of stable circulating MCA represents another marker of "in vivo" PMN activation in MHVR patients.

This method offers better results in less time than traditional phlebotomy. EA with rHuEPO is an effective therapeutic alternative for patients with HH.