PubMed Health⌕ Search

Biomedical subjects

Nic J G M Veeger

Publications and source records attributed to Nic J G M Veeger.

At least 19 recordsLinked to original sources
PubMed2007

Reduction of high fetal loss rate by anticoagulant treatment during pregnancy in antithrombin, protein C or protein S deficient women.

Hereditary thrombophilia is associated with an increased risk of fetal loss. Assuming that fetal loss is due to placental thrombosis, anticoagulant treatment might improve pregnancy outcome. In an observational family cohort study, we prospectively assessed the effects of anticoagulant drugs on fetal loss rates in women with hereditary deficiencies of antithrombin, protein C or protein S. The cohort contained 376 women (50 probands and 326 deficient or non-deficient relatives). Probands were consecutive deficient patients with venous tromboembolism. Thromboprophylaxis during pregnancy was recommended in deficient women, irrespective of prior venous thromboembolism, and in non-deficient women with prior venous thromboembolism. Outcome of first pregnancy was analysed in 55 eligible women. Of 37 deficient women, 26 (70%) received thromboprophylaxis during pregnancy, compared with three of 18 (17%) non-deficient women. Fetal loss rates were 0% in deficient women with thromboprophylaxis versus 45% in deficient women without (P = 0.001) and 7% in non-deficient women without thromboprophylaxis (P = 0.37). The adjusted relative risk of fetal loss in women who received thromboprophylaxis versus women who did not was 0.07 (95% confidence interval 0.001-0.7; P = 0.02). Our data suggest that anticoagulant treatment during pregnancy reduces the high fetal loss rate in women with hereditary deficiencies of antithrombin, protein C or protein S.

Adolescent↗
PubMed2006

The pathogenesis of venous thromboembolism: evidence for multiple interrelated causes.

BACKGROUND: Venous thromboembolism (VTE) is thought to result from interactions between multiple genetic and environmental risk factors. OBJECTIVE: To assess the contribution of multiple thrombophilic defects and exogenous risk factors to the absolute risk for VTE. DESIGN: Retrospective family cohort study. SETTING: Single university hospital. PARTICIPANTS: 468 relatives of 91 probands with a symptomatic hereditary deficiency of protein S, protein C, or antithrombin. MEASUREMENTS: All relatives were tested for 10 thrombophilic deficiencies and defects in addition to the index deficiency and were assessed for exogenous risk factors (surgery, trauma, immobilization, use of oral contraceptives, and pregnancy). The authors compared annual incidences and relative risks for VTE in deficient and nondeficient relatives. RESULTS: Annual incidences of VTE in relatives with 0, 1, and 2 or more additional thrombophilic deficiencies or defects were 1.16 (95% CI, 0.60 to 2.03), 1.75 (CI, 1.17 to 2.53), and 2.64 (CI, 1.67 to 3.96) per 100 person-years, respectively, compared with 0.06 (CI, 0.002 to 0.33) per 100 person-years in nondeficient relatives without additional deficiencies or defects. Adjusted relative risks were 16.3 (CI, 2.0 to 131.0), 50.3 (6.5 to 389.7), and 102.8 (12.5 to 843.4). Of deficient relatives, 38% with no additional defect, 57% with 1 additional defect, and 81% with 2 or more additional defects had VTE at age 65 years compared with 5% of nondeficient relatives (P < 0.001). In deficient relatives with additional deficiencies or defects, exogenous risk factors increased the risk for VTE from 1.20% to 2.51% per year (relative risk, 2.1 [CI, 1.1 to 4.2]). LIMITATIONS: This was a retrospective study without the ability to distinguish interactions between specific thrombophilic deficiencies and defects. CONCLUSION: Additional thrombophilic defects and exogenous risk factors increase the risk for VTE in persons with hereditary deficiencies of protein S, protein C, or antithrombin and provide evidence that multiple genetic and environmental risk factors contribute to VTE.

Aged↗
PubMed2006

Verapamil versus digoxin and acute versus routine serial cardioversion for the improvement of rhythm control for persistent atrial fibrillation.

OBJECTIVES: The VERDICT (Verapamil Versus Digoxin and Acute Versus Routine Serial Cardioversion Trial) is a prospective, randomized study to investigate whether: 1) acutely repeated serial electrical cardioversions (ECVs) after a relapse of atrial fibrillation (AF); and 2) prevention of intracellular calcium overload by verapamil, decrease intractability of AF. BACKGROUND: Rhythm control is desirable in patients suffering from symptomatic AF. METHODS: A total of 144 patients with persistent AF were included. Seventy-four (51%) patients were randomized to the acute (within 24 h) and 70 (49%) patients to the routine serial ECVs, and 74 (51%) patients to verapamil and 70 (49%) patients to digoxin for rate control before ECV and continued during follow-up (2 x 2 factorial design). Class III antiarrhythmic drugs were used after a relapse of AF. Follow-up was 18 months. RESULTS: At baseline, there were no significant differences between the groups, except for beta-blocker use in the verapamil versus digoxin group (38% vs. 60%, respectively, p = 0.01). At follow-up, no difference in the occurrence of permanent AF between the acute and the routine cardioversion groups was observed (32% [95% confidence intervals (CI)] 22 to 44) vs. 31% [95% CI 21 to 44], respectively, p = NS), and also no difference between the verapamil- and the digoxin-randomized patients (28% [95% CI 19 to 40] vs. 36% [95% CI 25 to 48] respectively, p = NS). Multivariate Cox regression analysis revealed that lone digoxin use was the only significant predictor of failure of rhythm control treatment (hazard ratio 2.2 [95% CI 1.1 to 4.4], p = 0.02). CONCLUSIONS: An acute serial cardioversion strategy does not improve long-term rhythm control in comparison with a routine serial cardioversion strategy. Furthermore, verapamil has no beneficial effect in a serial cardioversion strategy.

Aged↗
PubMed2006

Effects of early treatment with statins on short-term clinical outcomes in acute coronary syndromes: a meta-analysis of randomized controlled trials.

CONTEXT: The short-term effects of early treatment with statins in patients after the onset of acute coronary syndromes (ACS) for the outcomes of death, myocardial infarction (MI), and stroke are unclear. OBJECTIVE: To evaluate relevant outcomes of patients from randomized controlled trials comparing early statin therapy with placebo or usual care at 1 and 4 months following ACS. DATA SOURCES AND STUDY SELECTION: Systematic search of electronic databases (MEDLINE, EMBASE, PASCAL, Cochrane Central Register) from their inception to August 2005, which was supplemented by contact with experts in the field. Two reviewers independently determined the eligibility of randomized controlled trials that compared treatment with statins with a control, were initiated within 14 days after onset of ACS, and had a minimal follow-up of 30 days. Trials with cerivastatin were only included in a sensitivity analysis. DATA EXTRACTION: Information on baseline characteristics of included trials and patients, reported methodological quality, lipid levels, and clinical outcome was independently extracted by 2 investigators. Investigators from each included trial contributed additional data if necessary. DATA SYNTHESIS: Twelve trials involving 13 024 patients with ACS were included in the meta-analysis. The risk ratios for the combined end point of death, MI, and stroke for patients treated with early statin therapy compared with control therapy were 0.93 (95% confidence interval [CI], 0.80-1.09; P = .39) at 1 month and 0.93 (95% CI, 0.81-1.07; P = .30) at 4 months following ACS. There were no statistically significant risk reductions from statins for total death, total MI, total stroke, cardiovascular death, fatal or nonfatal MI, or revascularization procedures (percutaneous coronary intervention or coronary artery bypass graft surgery). Sensitivity analyses with restriction to trials of high quality or with additional data from a large trial using cerivastatin indicated summary risk ratios even closer to 1. CONCLUSION: Based on available evidence, initiation of statin therapy within 14 days following onset of ACS does not reduce death, MI, or stroke up to 4 months.

Angina, Unstable↗
PubMed2006

Randomized controlled trial of adjuvant oral dexamethasone pulse therapy in pemphigus vulgaris: PEMPULS trial.

OBJECTIVE: To determine the therapeutic effect of adjuvant dexamethasone pulse therapy when given in addition to conventional treatment of pemphigus vulgaris. DESIGN: A randomized, placebo-controlled trial. SETTING: International European, multicenter outpatient and inpatient study. PATIENTS: Of the 20 enrolled patients, 11 were randomized to the dexamethasone pulse (DP) group and 9 to the placebo pulse (PP) group. INTERVENTIONS: Oral dexamethasone in 300-mg pulses or PPs 3 days per month. During the intervention, the DP and PP groups received conventional treatment with prednisolone, 80 mg/d, which was tapered across 19 weeks, and azathioprine sodium, 3 mg/kg per day, until the end of the study. Monthly pulses were continued until prednisolone treatment was tapered to 0 mg. MAIN OUTCOME MEASURES: Number of patients in remission, time to and duration of remission, cumulative prednisolone dose, and occurrence of adverse events during 1 year of follow-up. RESULTS: Eight of the 11 DP-treated patients and all 9 PP-treated patients achieved remission. Mean time to remission was 173 days with DP and 176 days with PP. The mean duration of remission within the first year was 151 days for DP and 141 days for PP. Mean cumulative prednisolone dose was 5300 mg for DP and 4882 mg for PP. Weight gain (>5% of baseline) occurred in 8 DP-treated patients compared with 1 PP-treated patient (P<.01). We found no statistically significant difference (P>.05) of an adjuvant effect of DP on remission of pemphigus vulgaris. CONCLUSION: In patients with new pemphigus vulgaris disease activity, there was no benefit of oral DP therapy given in addition to conventional treatment. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00127764.

Administration, Oral↗
PubMed2006

RAte Control Efficacy in permanent atrial fibrillation: a comparison between lenient versus strict rate control in patients with and without heart failure. Background, aims, and design of RACE II.

BACKGROUND: Recent studies demonstrated that rate control is an acceptable alternative for rhythm control in patients with persistent atrial fibrillation (AF). However, optimal heart rate during AF is still unknown. OBJECTIVE: To show that in patients with permanent AF, lenient rate control is not inferior to strict rate control in terms of cardiovascular mortality, morbidity, neurohormonal activation, New York Heart Association class for heart failure, left ventricular function, left atrial size, quality of life, and costs. METHODS: The RACE II study is a prospective multicenter trial in The Netherlands that will randomize 500 patients with permanent AF (< or = 12 months) to strict or lenient rate control. Strict rate control is defined as a mean resting heart rate < 80 beats per minute (bpm) and heart rate during minor exercise < 110 bpm. After reaching the target, a 24-hour Holter monitoring will be performed. If necessary, drug dose reduction and/or pacemaker implantation will be performed. Lenient rate control is defined as a resting heart rate < 110 bpm. Patients will be seen after 1, 2, and 3 months (for titration of rate control drugs) and yearly thereafter. We anticipate a 25% 2.5-year cardiovascular morbidity and mortality in both groups. RESULTS: Enrollment started in January 2005 in 29 centers in The Netherlands and is expected to be concluded in June 2006. Follow-up will be at least 2 years with a maximum of 3 years. CONCLUSION: This study should provide data how to treat patients with permanent AF.

Anti-Arrhythmia Agents↗
PubMed2006

Diurnal variation of ventricular repolarization in a large family with LQT3-Brugada syndrome characterized by nocturnal sudden death.

BACKGROUND: In patients with long-QT syndrome type 3 (LQT3), symptoms occur particularly at rest or during sleep. As to the underlying mechanism, excessive prolongation of the QT interval at slow heart rates probably plays a role. OBJECTIVES: The purpose of the present study was to investigate QT interval prolongation unrelated to heart rate comparing nighttime and daytime in a family with features of both LQT3 and Brugada syndrome. METHODS: The study group consisted of 38 carriers of the mutant gene (SCN5A, 1795insD) and 30 noncarrier family members, who served as controls. Holter monitoring was performed with beat-to-beat QT interval measurement. In addition, in a subset of subjects, an exercise test and a pacing test (carriers only) with measurement of the RT interval were performed. RESULTS: In carriers, the slope between heart rate and QT interval was significantly steeper during nighttime (0:00 a.m. to 6:00 a.m.) than during daytime (8:00 a.m. to 22:00 p.m.) (regression coefficient -6.18 and -2.80, respectively), (p=0.03),no such effect being observed in the noncarriers. Further, the RT interval was markedly shorter during recovery than during exercise in carriers but not in noncarriers. In contrast, during AAI pacing in the carriers, RT interval shortening along with increasing heart rate was followed by a comparable prolongation of the RT interval along with subsequent decreasing heart rate. CONCLUSIONS: In this large LQT3-Brugada syndrome family, carriers of the mutant gene (SCN5A, 1795insD) are characterized by diurnal variation of ventricular repolarization by exhibiting QT interval prolongation, which is more pronounced during nighttime compared with daytime, even when taking into account differences in heart rate. The autonomic nervous system appears to play a role in mediating this effect. This observation may be of relevance for explaining the high incidence of nocturnal sudden death in this family, but this remains to be proven. In addition, whether our findings also apply to other families with LQT3 is uncertain.

Adolescent↗
PubMed2005

Mending the rhythm does not improve prognosis in patients with persistent atrial fibrillation: a subanalysis of the RACE study.

AIMS: To compare outcome of AF patients with effective rhythm control with patients treated with rate control. METHODS AND RESULTS: Out of the 266 AF patients randomized to rhythm control in the RACE study, 49 patients turned to long-term sinus rhythm and were continuously treated with oral anticoagulation. The incidence of the primary endpoint in these patients was compared to that in 178 patients out of the initial 256 rate-control patients of RACE who were in AF and using oral anticoagulation continuously. Baseline characteristics of both groups were not different. After a mean follow-up of 2.3+/-0.6 years, the primary endpoint (a composite of cardiovascular mortality, heart failure, thrombo-embolic complications (TECs), bleeding, serious adverse effects of antiarrhythmic drugs and pacemaker implants) was 22.4% in the rhythm-control group vs. 15.2% in the rate-control group. Multivariable regression analysis indicated coronary artery disease, heart failure, and digitalis as independent risk indicators of cardiovascular morbidity and mortality. Chronic sinus rhythm did not matter. CONCLUSION: Among patients who remained on warfarin, those who mostly were maintained in sinus rhythm under a rhythm-control strategy did not have a superior prognosis compared to those who remained in AF under a rate-control strategy.

Aged↗
PubMed2005

Compliance in heart failure patients: the importance of knowledge and beliefs.

AIMS: Non-compliance in patients with heart failure (HF) contributes to worsening HF symptoms and may lead to hospitalization. Several smaller studies have examined compliance in HF, but all were limited as they only studied either the individual components of compliance and its related factors or several aspects of compliance without studying the related factors. The aims of this study were to examine all dimensions of compliance and its related factors in one HF population. METHODS AND RESULTS: Data were collected in a cohort of 501 HF patients. Clinical and demographic data were assessed and patients completed questionnaires on compliance, beliefs, knowledge, and self-care behaviour. Overall compliance was 72% in this older HF population. Compliance with medication and appointment keeping was high (>90%). In contrast, compliance with diet (83%), fluid restriction (73%), exercise (39%), and weighing (35%) was markedly lower. Compliance was related to knowledge (OR=5.67; CI 2.87-11.19), beliefs (OR=1.78; CI 1.18-2.69), and depressive symptoms (OR=0.53; CI 0.35-0.78). CONCLUSION: Although some aspects of compliance had an acceptable level, compliance with weighing and exercise were low. In order to improve compliance, an increase of knowledge and a change of patient's beliefs by education and counselling are recommended. Extra attention should be paid to patients with depressive symptoms.

Aged↗
PubMed2005

Gender-related differences in rhythm control treatment in persistent atrial fibrillation: data of the Rate Control Versus Electrical Cardioversion (RACE) study.

OBJECTIVES: This study sought to compare whether gender affects the outcome of rate versus rhythm control treatment in patients with persistent atrial fibrillation (AF). BACKGROUND: Large trials have shown that rate control is an acceptable alternative to rhythm control. However, the effects of treatment may differ between male and female patients. METHODS: In the Rate Control versus Electrical Cardioversion (RACE) study, 522 patients (192 female) were included and randomized to rate or rhythm control. The occurrence of cardiovascular end points and quality of life (QoL) were compared between female and male patients. RESULTS: At baseline, female patients differed from male patients with regard to age, underlying heart disease, diabetes mellitus, and left ventricular function. Female patients had more AF-related complaints, and QoL was significantly lower. After a mean follow-up of 2.3 +/- 0.6 years, cardiovascular morbidity and mortality was equally distributed between female (21%) and male patients (19%). However, in contrast to male patients, female patients randomized to rhythm control developed more end points (adjusted hazard ratio was 3.1 [95% confidence interval 1.5 to 6.3], p = 0.002), mainly heart failure, thromboembolic complications, and adverse effects of antiarrhythmic drugs, compared with rate control randomized female patients. During follow-up, QoL in female patients remained worse compared with that for male patients. Randomized strategy did not influence QoL in female patients. CONCLUSIONS: In female patients with persistent AF, a rhythm control approach leads to more cardiovascular morbidity and mortality. Because treatment strategy did not influence QoL in female patients, a rate control approach may be considered in these patients.

Aged↗
PubMed2005

HLA antigens and post renal transplant lymphoproliferative disease: HLA-B matching is critical.

Although several risk factors for posttransplant lymphoproliferative disease (PTLD) after solid organ transplantation have been identified, the immunosuppressive regimen probably as most important one, their exact pathogenic role and relevance is still unclear. In hematopoietic stem cell transplantation, HLA mismatching also is a risk factor. We analyzed factors possibly associated with development of PTLD in patients receiving a kidney transplant at our hospital between 1985 and 2002. PTLD was observed in 20 out of 1,013 patients (2.0%). Mismatches at the HLA-B locus, but not at the HLA-A or HLA-DR loci, and anti T-cell antibody therapy were both independently associated with development of PTLD. Hazard ratios increased from 1.4 (0.5-4.1) with one mismatch to 5.1 (1.4-19.0) in case of two HLA-B mismatches. Decreased surveillance by T-cells with dual specificity for Epstein-Barr virus (EBV) as well as for allo HLA antigens on the allograft might facilitate clonal expansion of B-cells latently infected with EBV.

Adolescent↗
PubMed2005

Rate control versus rhythm control for patients with persistent atrial fibrillation with mild to moderate heart failure: results from the RAte Control versus Electrical cardioversion (RACE) study.

BACKGROUND: This study was conducted to compare rate- and rhythm-control therapy in patients with persistent atrial fibrillation (AF) and mild to moderate chronic heart failure (CHF). Rate control is not inferior to rhythm control in preventing mortality and morbidity in patients with AF. In CHF, this issue is still unsettled. METHODS: In this predefined analysis of the RACE study, a total of 261 patients were in New York Heart Association (NYHA) classes II and III at baseline. These patients were analyzed. The primary end point was a composite of cardiovascular mortality, hospitalization for CHF, thromboembolic complications, bleeding, pacemaker implantation, and life-threatening drug side effects. Furthermore, quality of life was compared. RESULTS: After 2.3 +/- 0.6 years, the primary end point occurred in 29 (22.3%) of the 130 rate-control patients and in 32 (24.4%) of the 131 rhythm-control patients. More cardiovascular deaths, hospitalization for CHF, and bleeding occurred under rate control. Thromboembolic complications, drug side effects, and pacemaker implantation were more frequent under rhythm control. Quality of life did not differ between strategies. In patients successfully treated with rhythm control, the prevalence of end points was not different from those who were in AF at study end. However, the type of end point was different: mortality, bleeding, hospitalization for heart failure, and pacemaker implantation occurred less frequently. CONCLUSIONS: In patients with mild to moderate CHF, rate control is not inferior to rhythm control. However, if sinus rhythm can be maintained, outcome may be improved. A prospective randomized trial is necessary to confirm these results.

Aged↗
PubMed2005

For better and for worse: Quality of life impaired in HF patients as well as in their partners.

BACKGROUND: Quality of Life (QOL) is known to be impaired in patients with Heart Failure (HF). The involvement of a key person, most often the spouse, enables the HF patient to manage the medical regimen and therefore to sustain Quality of Life (QOL). Yet little is known on the impact of caring for an HF patient on the QOL of the caregiving partner. This study aims to explore the QOL of partners of HF patients compared to the QOL of the patients. METHODS: The study population consisted of 38 couples of hospitalized HF patients and their partners. The Cantril Ladder of Life was used to rate QOL during hospitalization, with regard to the month prior to hospitalization and as projected 3 years in the future. Demographic and clinical variables were collected by patient interview and chart review. RESULTS: On a scale from 0-10, QOL scores of partners varied from 5.9 to 6.4. At some point the QOL score of partners was even lower than the QOL scores of HF patients. In the month prior to hospital admission the QOL of partners was significantly higher in comparison to the QOL of HF patients (6.1 vs. 4.9, respectively). However, this reversed during hospital admission, with QOL scores of partners being significantly lower compared to QOL scores of HF patients (5.9 vs. 6.8, respectively), even after correcting for age and gender. CONCLUSION: In our study the QOL of partners of HF patients was low. Whether this is explicitly due to having to live with a HF patient is not clear. Further research on what partners actually do and the relationship between being a caregiver and QOL is necessary in order to support these partners in giving optimal care and support.

Adaptation, Psychological↗
PubMed2005

Effect of rate and rhythm control on left ventricular function and cardiac dimensions in patients with persistent atrial fibrillation: results from the RAte Control versus Electrical Cardioversion for Persistent Atrial Fibrillation (RACE) study.

OBJECTIVES: The purpose of this study was to evaluate left ventricular function and atrial and ventricular diameters in patients with persistent atrial fibrillation (AF) treated with rate or rhythm control. BACKGROUND: Restoration of sinus rhythm in patients with persistent AF may improve left ventricular function and reduce atrial dimensions. Adequate rate control in AF may preserve ventricular function. METHODS: In 335 patients included in the RAte Control versus Electrical Cardioversion for Persistent Atrial Fibrillation (RACE) study, echocardiography was performed at baseline and 1- and 2-year follow-up. Echocardiography was compared between patients randomized to rate control (n = 160) and rhythm control (n = 175). In the rhythm control group, echocardiography was compared between patients with AF versus sinus rhythm at study end. Multivariate analysis was performed to determine parameters related to improvement of left ventricular function and increase of atrial diameters. RESULTS: Fractional shortening improved significantly under rate and rhythm control (31 +/- 10% at baseline to 33 +/- 9% at 2 years, and from 30 +/- 10% to 34 +/- 9%; both P < .05, respectively). Under rate control, left and right atrial size increased significantly compared to baseline. Under rhythm control, only left atrial size increased. Multivariate analysis revealed that only sinus rhythm at study end was associated with an increase of fractional shortening. AF at study end, hypertension, and no use of angiotensin-converting enzyme inhibitors were independently associated with increase in atrial size. CONCLUSIONS: Routine rate control prevents deterioration of left ventricular function. Maintenance of sinus rhythm is associated with improvement of left ventricular function and reduction of atrial sizes.

Aged↗
PubMed2005

Does flecainide regain its antiarrhythmic activity after electrical cardioversion of persistent atrial fibrillation?

OBJECTIVES: The purpose of this study was to evaluate the hypothesis that presumed reversion of electrical remodeling after cardioversion of atrial fibrillation (AF) restores the efficacy of flecainide. BACKGROUND: Flecainide loses its efficacy to cardiovert when AF has been present for more than 24 hours. Most probably, the loss is caused by atrial electrical remodeling. Studies suggest electrical remodeling is completely reversible within 4 days after restoration of sinus rhythm (SR). METHODS: One hundred eighty-one patients with persistent AF (median duration 3 months) were included in this prospective study. After failure of pharmacologic cardioversion by flecainide 2 mg/kg IV (maximum 150 mg in 10 minutes) and subsequent successful electrical cardioversion, we performed intense transtelephonic rhythm monitoring three times daily for 1 month. In case of AF recurrence, a second cardioversion by flecainide was attempted as soon as possible. RESULTS: AF recurred in 123 patients (68%). Successful cardioversion by flecainide occurred only when SR had been maintained for more than 4 days (7/51 patients [14%]). Failure to cardiovert was associated with a prolonged duration of the recurrent AF episode and concurrent digoxin use. Multivariate logistic regression confirmed that successful cardioversion was determined by digoxin use (odds ratio [OR] 0.093, P = .047) and by the interaction between the duration of SR and the (inverse) duration of recurrent AF (OR 6.499, P < .001). When flecainide was administered within 10 hours after AF onset and the duration of SR was greater than 4 days, the success rate was 58%. CONCLUSIONS: Flecainide recovers its antiarrhythmic action after cardioversion of AF. However, successful pharmacologic cardioversion occurs only after SR has lasted at least 4 days and is expected only for recurrences having duration of a few hours. Immediate pharmacologic cardioversion of AF recurrence may be a worthwhile strategy for management of persistent AF.

Aged↗
PubMed2005

Protein S type III deficiency is no risk factor for venous and arterial thromboembolism in 168 thrombophilic families: a retrospective study.

Free protein S rather than total protein S levels are currently measured to detect inherited protein S deficiency. Because type III (free protein S) deficiency is still not established as risk factor for thrombosis, we assessed the absolute risk of venous and arterial thromboembolism in a family cohort study. Annual incidences in first-degree relatives with and without protein S deficiency type III were compared. Probands had experienced thrombosis and had either the prothrombin G20210A mutation, increased factor VIII:C levels or hyperhomocysteinemia. Relatives were tested for these thrombophilic disorders and factor V Leiden. Levels of antithrombin, protein C, total and free protein S, and factor XI:C were additionally measured. Of 500 relatives enrolled, 105 were excluded from analysis because they could not be classified, due to acquired conditions. Protein S deficiency type III was demonstrated in 60/395 remaining relatives (15%). Other thrombophilic defects were equally distributed among deficient and non-deficient relatives. Annual incidences of venous thromboembolism were 0.28 per 100 person-years [95% confidence interval (CI), 0.09-0.66] in deficient relatives versus 0.20 per 100 person-years (95% CI, 0.12-0.30) in non-deficient relatives [hazard ratio, 1.4 (95% CI, 0.4-4.0)]. For arterial thromboembolism these values were 0.16 per 100 person-years (95% CI, 0.03-0.46) versus 0.10 per 100 person-years (95% CI, 0.05-0.19) [hazard ratio, 1.5 (95% CI, 0.3-6.0)]. These results suggest that protein S deficiency type III is not associated with an increased risk of either venous or arterial thromboembolism.

Adolescent↗
PubMed2005

Individual time within target range in patients treated with vitamin K antagonists: main determinant of quality of anticoagulation and predictor of clinical outcome. A retrospective study of 2300 consecutive patients with venous thromboembolism.

The efficacy and safety of vitamin K antagonists (VKA) are related to the actual level of anticoagulation (given as the international normalized ratio, INR). It is often difficult to maintain an optimal INR over time. We assessed the clinical impact of the individual time spent within INR target range (ITTR) in 2304 consecutive patients with venous thromboembolism. Annual incidences of recurrent thromboembolism and major bleeding were 6.2% and 2.8% respectively. The relative risk (RR) of thromboembolism was 4.5 [95% confidence interval (CI) 3.1-6.6, P < 0.001] at INR < 2.0, for major bleeding it was 6.4 (2.5-16.1, P < 0.001) at INR > 5.0, compared with INR 2.0-3.0. Patients with ITTR < 45% were at higher risk than those with ITTR > 65% (RR 2.8, 1.9-4.3, P < 0.001), while no difference was demonstrated comparing ITTR 45-65% and ITTR > 65% (RR 1.2, 0.7-1.8, P = 0.54). Annual incidences of recurrent thromboembolism were 16.0%, 4.9% and 4.6% at ITTR < 45%, 45-60% and >65% respectively. For major bleeding these were 8.7%, 2.1% and 1.9% respectively. ITTR < 37% during the first 30 treatment days was highly predictive for the total treatment time ITTR < 45% (RR 24.2, 13.5-43.1, P < 0.001). In conclusion, ITTR can be used to identify patients on VKA at risk of recurrent thromboembolism or major bleeding. Since the 30-d ITTR is highly predictive for total treatment ITTR, these patients can be identified soon after start of treatment.

Anticoagulants↗