Maria A. Lazzari

Patients’ perceptions regarding oral anticoagulation therapy and its effect on quality of life

ABSTRACT Objective: Anticoagulation clinics have improved the time spent within therapeutic range and decreased hemorrhagic complications and costs in chronic oral anticoagulation. Whether these benefits correlate to patients’ quality of life (QOL) remains to be determined. The impact of patients’ perceptions about anticoagulation on QOL has not been evaluated. The objective of this study was to evaluate prospectively patients’ perceptions and quality of life in patients chronically anticoagulated. Research design and methods: A cross-sectional study was designed to investigate the prevalence of positive and negative perceptions about oral anticoagulation therapy (OAT) and to identify vulnerable groups. Patients anonymously completed the SF-36 survey and a questionnaire that focused on patients’ perceptions of protection from thrombotic complications or fear of haemorrhage due to the anticoagulation. We related those perceptions to the General Health SF-36 score, to the patients characteristics, the absolute bleeding risk (i.e. intended International Normalized Ratio [INR]), duration of therapy and medical attention. Results: One thousand patients were included and 905 questionnaires evaluated. Most patients felt protected and better since the beginning of therapy (71.5% and 61.5%, respectively). Patient characteristics associated with negative perceptions were; female sex (Odds Ratio [OR] 1.58, 95% Confidence Interval [CI] 1.06–2.36, p = 0.01); patients with less than 1 year of therapy (OR 2.16, 95% CI 1.34–3.48, p = 0.006); those not satisfied with medical attention (OR 2.86, 95% CI 1.53–5.18, p = 0.0001); and those that modified their lifestyle (OR 2.75, 95% CI 1.49–4.91, p = 0.0002). Patients with a lower bleeding risk (INR 2.0–3.0) had more negative perceptions than those with a higher risk. Patients with negative perceptions achieved the lowest score in the SF-36 survey. Haemorrhages did not affect patients’ perception or QOL. Conclusions: Patients’ perceptions correlated with QOL. We were able to identify patient characteristics associated with poor QOL and thus the group of patients whose negative perceptions most warranted special attention from their clinicians.

Circulating platelet/polymorphonuclear leukocyte mixed–cell aggregates in patients with mechanical heart valve replacement

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. Am. J. Hematol. 65:93–98, 2000.

Identification of p.W246L As a Novel Mutation in the GP1BA Gene Responsible for Platelet-Type von Willebrand Disease

Platelet-type von Willebrand disease (PT-VWD) and type 2B von Willebrand disease (2B-VWD) are rare bleeding disorders characterized by increased ristocetin-induced platelet aggregation (RIPA) at low concentrations of ristocetin. Diagnosis of either condition is not easy and the differential diagnosis between the two entities is especially challenging as evidenced by high levels of misdiagnosis of both conditions, but particularly PT-VWD. Five mutations in the GP1BA gene related to PT-VWD and less than 50 patients are currently reported worldwide. We herein describe a patient with severe bleeding symptoms, macrothrombocytopenia, mild spontaneous platelet aggregation, positive RIPA at 0.3 and 0.4 mg/mL, von Willebrand factor ristocetin cofactor (VWF:RCo) to antigen (VWF:Ag) < 0.2, normal VWF propeptide/VWF:Ag ratio, and RIPA mixing tests and cryoprecipitate challenge positive for PT-VWD. GP1BA gene was studied in the patient, in his mother, and in 100 healthy control subjects. We identified a heterozygous substitution G > T located at nucleotide 3805 in the g.DNA of the patients GP1BA gene, resulting in a Trp to Leu amino acid change at residue 246 (p.W246L). This mutation was absent in his unaffected mother and also in the 100 controls, and was predicted as damaging by in silico analysis. The residue W246 is located within the VWF-binding region and exists in a strongly conserved position in the phylogenetic tree, which is expected to be unable to tolerate substitutions without changing its functional characteristics. These findings argue strongly in favor of the view that this substitution does not represent a polymorphism and is therefore responsible for the PT-VWD phenotype of the patient.

Effect of Low-Dose Aspirin on the International Normalized Ratio Variability in Patients with Mechanical Heart Valve Prostheses

An increased risk of bleeding is associated with a more intense oral anticoagulation, a greater international normalized ratio (INR) variability and the use of aspirin. We studied the INR variability of patients (n = 121) with modern heart valves who had been prospectively randomized to receive acenocoumarol at a targeted INR of 2.4–3.6 plus aspirin 100 mg/day or acenocoumarol alone at the same dosage, to evaluate whether aspirin influences variability and thus the risk of bleeding. Variability was similar in patients with no events regardless of the use of aspirin. A statistically significantly higher variability was observed in patients with bleeding events independently of the use of aspirin. Nevertheless, the concomitant use of aspirin in patients with a high variability should be monitored closely and thoroughly.

Purification and partial characterization of a bioactive substance from rat's vessel wall independent of prostacyclin production

The bioactive substance from rats vessel wall was purified by Sephadex G-75 gel filtration and by a combination of DEAE Cellulose ion exchange and Sephadex G-50 gel filtration chromatographies. Purifications of 12.5 fold and 70 fold over the initial material were achieved. PAGE of the purified material resulted in a single major band with a molecular weight estimated at 55kd-65kd. Trypsin (0.3 mg/ml) and chymotrypsin (30 mg/ml) abolished platelet antiaggregating activity. Neuraminidase (1.2 units) had no effect on platelet antiaggregating activity. This is the report of purification of aortic vessel wall antiaggregating activity independent of prostacyclin production.

A new ADAMTS13 missense mutation (D1362V) in thrombotic thrombocytopenic purpura diagnosed during pregnancy.

A new ADAMTS13 missense mutation (D1362V) in thrombotic thrombocytopenic purpura diagnosed during pregnancy -