Comparative thrombotic event incidence after infusion of recombinant factor VIIa versus factor VIII inhibitor bypass activity

تعليق: المقال صلته بالموضوع هو مشاكل الإبلاغ عن الأعراض الجانبية للأدوية ظاهرة ويبر الخاصة بإنخفاض الإبلاغ عن العراض الجانبية وعدم توقعها في أحد الأدوية وهم ما ينطبق أيضاً على الأوميبراز وأخواته. ونحن نحتاج لدراسات مماثلة لهذه الدراسة لتقدير حجم المشكلة والتعامل معها. من المؤكد وجود مشكلة لكنها غير ظاهرة على السطح أو متناثرة القطع. مثلا تأثير مشاكل الإبصار على أنشطة الحياة.--احمد شوقي محمدين 07:37، 21 أكتوبر 2016 (ت ع م)

Comparative thrombotic event incidence after infusion of recombinant factor VIIa versus factor VIII inhibitor bypass activity

Aledort LM. Comparative thrombotic event incidence after infusion of recombinant factor VIIa versus factor VIII inhibitor bypass activity. J Thromb Haemost 2004; 2: 1700–08.

Discussion

This pharmacovigilance investigation provides evidence that thrombotic AEs are rare following infusion of either rFVIIa or FEIBA. It also challenges the view that rFVIIa poses less thrombotic risk than FEIBA. Thrombotic AEs were three times as frequent after rFVIIa as FEIBA infusion. This finding needs to be interpreted with caution, however, since it is possible differences in reporting rates might at least partly account for an apparent disparity in thrombotic AE incidence.

It is nevertheless unsurprising that rFVIIa would not prove to be free of thrombotic complications, since it is an activated coagulation factor circulating at supraphysiologic concentration following therapeutic infusion and can be inhibited neither by antithrombin nor, until formation of a complex with tissue factor and FXa, by tissue factor pathway inhibitor [10]. There is also evidence that (دراسات مضخة البروتون في الشبكية) rFVIIa can directly activate FX and generate thrombin in the absence of tissue factor [43,44].

Under-reporting is a well-known limitation of spontaneous AE reporting systems such as MedWatch [45]. Consequently, the estimates of thrombotic AE incidence reported here are most probably lower than the true rates. Empirical studies involving recombinant FVIII treatment in hemophilia patients [46] and other clinical settings such as cardiopulmonary bypass surgery [47] and pharmacotherapy in family practice [48] suggest that the true incidence of serious AEs may be approximately twice the apparent incidence from passive surveillance. In the present investigation a single thrombotic AE was documented after each 4065 rFVIIa infusions and each 12 136 FEIBA infusions. Because of under-reporting, perhaps two thrombotic AEs will have actually occurred after these numbers of infusions. Even so, thrombotic AEs appear to be rare both after rFVIIa and FEIBA exposure. لا نعرف الحقيقة

For some medications, AE reporting may decline with the lapse of time, usually after the first two years of clinical availability [49]. This phenomenon is termed the �Weber effect [50]. rFVIIa was introduced outside the USA in 1996 and is hence a much newer agent than FEIBA, which has been available for nearly 30 years. It could be speculated in light of the Weber effect that reporting of thrombotic AEs could be lower in FEIBA than rFVIIa recipients. However, there was no evidence of declining rFVIIa-related thrombotic AEs during the study period, so it is unclear whether rFVIIa is among the agents subject to the Weber effect.

AE reporting has been shown to be similar for most pairs of drugs belonging to the same therapeutic class and used in the same clinical setting [51]. This observation suggests that reporting rates for rFVIIa and FEIBA may not differ markedly. On the other hand, there might be greater reporting of thrombotic AEs related to FEIBA than rFVIIa. Clinician preconceptions can bias AE reporting for a specific agent [52].

It has been widely claimed that rFVIIa is largely free of thrombotic AE risk, and according to the package insert for this medication that risk is �considered to be low. Conversely, thrombotic AEs of FEIBA are well-recognized, and the package insert carries a warning concerning this risk. Plausibly, clinicians may be disinclined to report thrombotic AEs in patients receiving rFVIIa because of a belief that this agent is unlikely to have contributed to such AEs. كلام خطير ومشابه لنظريتنا

http://onlinelibrary.wiley.com/doi/10.1111/j.1538-7836.2004.00944.x/pdf