Age-dependent differences in the anticoagulant effect of phenprocoumon in patients after heart valve surgery

Russmann, Stefan; Gohlke-Bärwolf, Ch.; Jähnchen, E.; Trenk, Dietmar; Roskamm, H.

doi:10.1007/s002280050245

Cited by 29 publications

(11 citation statements)

References 23 publications

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“…These results agree with the findings of recent studies in which the risk of life-threatening or fatal bleeding was significantly higher in older than younger patients receiving OAT. 6,16 In this study, all fatal bleeding events recorded in both groups were intracranial hemorrhages. Others have also reported that the risk of intracranial bleeding during OAT is higher in older persons.…”

Section: Commentmentioning

confidence: 57%

Oral Anticoagulation Treatment in the Elderly

Palareti¹,

Hirsh²,

Legnani³

et al. 2000

Arch Intern Med

136

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A nonsignificant trend was noted toward a higher rate of both bleeding and thrombotic complications in elderly vs matched younger patients. Intracranial bleeding and fatal thrombotic events were significantly more frequent in the elderly. Our results also indicate that lower than 2.0 INRs do not preclude bleeding in the elderly nor offer adequate protection from thrombotic events. Moderate anticoagulation (2.0-3.0 INRs) in elderly patients seems the safest and most effective.

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Section: Commentmentioning

confidence: 57%

Oral Anticoagulation Treatment in the Elderly

Palareti¹,

Hirsh²,

Legnani³

et al. 2000

Arch Intern Med

136

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“…33–35,38 We believe that these age-related imbalances in hemostatic protein regulation and production by VECs are not likely to cause spontaneous development of thrombus. However, when injury or insult occur at the valve endothelium, the aging-induced imbalance in the expression of anti-thrombotic and thrombotic proteins by VECs will lower the VEC's capability to maintain hemostasis; thus causes AV tissues to be more susceptible to thrombotic complications.…”

Section: Discussionmentioning

confidence: 92%

“…This phenomenon is consistent with clinical reports that elderly patients require lower doses of anti-coagulants after heart valve surgeries than do adult patients, due to lower clearance kinetics of the drugs and decreased clotting ability in elderly patients. 38 …”

Section: Discussionmentioning

confidence: 99%

Age-Related Changes in Aortic Valve Hemostatic Protein Regulation

Balaoing

Post

Liu

et al. 2014

ATVB

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Objective While valvular endothelial cells (VECs) have unique responses compared to vascular ECs, valvular regulation of hemostasis is not well understood. Heart valves remodel throughout a person's lifetime, resulting in changes in extracellular matrix (ECM) composition and tissue mechanical properties that may affect VEC hemostatic function. This work assessed VEC regulation of hemostasis in situ and in vitro as a function of specimen age. Approach and Results Porcine aortic valves (PAV) were assigned into one of three age groups: YNG (6 weeks), ADT (6 months), or OLD (2 years). Histology of valves showed that secreted thrombotic/anti-thrombotic proteins localize at the valve endothelium, and tissue interior. Gene expression and immunostains for von Willebrand factor (VWF), tissue factor pathway inhibitor, and tissue plasminogen activator in YNG PAVECs was higher than in OLD, while plasminogen activator inhibitor-1 levels in OLD were higher than in YNG and ADT. Histamine stimulated YNG PAVECs released higher concentrations of VWF proteins than OLD, while the fraction of cleaved VWF-140 fragments were not different between age groups. A CAVD in vitro model using valvular interstitial cells (VICs) confirmed that VWF in culture significantly increased VIC nodule formation and calcification. Conclusions Hemostatic protein regulation in AV tissues and VECs changes with age. The presence of VWF and other potential hemostatic proteins increase VIC calcification in vitro. Therefore, the increased capacity of elderly valves to sequester the hemostatic proteins, together with age-associated loss of ECM organization warrants investigation into potential roles for these proteins in the formation of calcific nodules.

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“…The average INR result was nearly identical in the various age groups, but the average dose decreased with age whereas the instability index increased. It has been previously shown that steady‐state warfarin doses decrease with age and that this is mainly due to a significantly reduced metabolic clearance in the elderly (Russmann et al , 1997). A reduced metabolic clearance, resulting in a narrow therapeutic range, might also explain both the increased individual variable response to treatment in the elderly, and the observed association between the minimum INR value and the likelihood of over‐anticoagulation.…”

Section: Discussionmentioning

confidence: 99%

Oral anticoagulants in the elderly

Froom¹,

Miron

Barak³

2003

Br J Haematol

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Summary. Over a 1-year period, 34 998 prothrombin time tests were performed on 2379 patients aged 40-89 years with a recommended target International Normalized Ratio (INR) value of 2AE5. At least one INR value of ‡ 5 was found in 507/2379 patients (21AE3%). The elderly demonstrated higher maximum and lower minimum INR values, lower warfarin doses, and an increased number of tests performed.After adjustment for these factors, the risk of INR values ‡ 5 increased with age by 15% every 10 years (95% CI 4-28%). We conclude that age is a risk factor for more unstable prothrombin time results.Keywords: INR, elderly, anticoagulation, control, instability.Older age is associated with an increased risk of bleeding in patients treated with oral anticoagulants (Hutten et al, 1999). The risk of bleeding increases in parallel to the International Normalized Ratio (INR) (Van Der Meer et al, 1996) and cessation of treatment is required when the INR is ‡ 5 (Hirsh et al, 1998). However, such values have not been consistently associated with older age, and the increased risk of bleeding in the elderly might not be due to an increased risk of over-anticoagulation, but rather to an increased bleeding tendency (Panneerselvam et al, 1998). On the other hand, the small number of patients in previous studies has limited their power and might explain inconsistent findings.We studied 2379 patients on chronic oral anticoagulation therapy aged 40-89 years in order to determine the effect of age on anticoagulation control. PATIENTS AND METHODSWe identified 2379 patients (1237 men/1142 women) aged 40-89 years, who had received warfarin treatment between 1 January and 31 December 2000, had received treatment for at least 2 months before the study's inception and had conditions requiring a target INR of 2AE5. Patients were treated by general practitioners without the aid of a computer algorithm. In this region, the health maintenance organization serves approximately 750 000 people.Blood was obtained from patients being treated with warfarin using commercially prepared vacutainer sodium citrate tubes of 3AE17 ml draw and 13 · 75 mm size (Becton Dickinson, Franklin Lakes, NJ, USA). The blood samples arrived within 3 h from the various outpatient clinics. Prothrombin times (PTs) were performed on automatic microprocessor-controlled coagulation analysers (SYSMEX CA-6000; TOA Medical Electronics Company, LTD, Kobe, Japan) using dried rabbit brain thromboplastin with calcium (Dade Thromboplastin IS; Dade Behring, Marburg, Germany). The coefficient of variation between tests was 1AE5%, between analysers was 1AE4% and between days was 1AE9% (Froom et al, 2001). The laboratory is a member of an external quality control programme [UK National External Quality Assessment Scheme (NEQAS)].Patients were divided up into age groups of 10 years increments and into two subgroups: those with and without at least one PT result of ‡ 5 INR units, which is the recommended value for temporary cessation of treatment (Hirsh et al, 1998). For continuous variables, the...

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Age-dependent differences in the anticoagulant effect of phenprocoumon in patients after heart valve surgery

Abstract: Older patients (> 70 years) require a dose approximately 30% lower than younger patients (< 160 years). Pharmacokinetic reasons (reduced metabolic clearance) are mainly responsible for the lower dose requirement of the older patients after heart valve surgery.

Cited by 29 publications

References 23 publications

Oral Anticoagulation Treatment in the Elderly

Oral Anticoagulation Treatment in the Elderly

Age-Related Changes in Aortic Valve Hemostatic Protein Regulation

Oral anticoagulants in the elderly

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