А каими схемами профилактики тромботических осложений вы пользуетесь?

[Sereda Andrey]

Собственно сабж.
+ использует ли кто-нибудь арикстру?
Спасибо.

[Winer]

Только начали, ничего особенного.

[Gilarov]

Мы использовали. Меня лично смущает универсальность дозы - и для лечения и для профилактики независимо от веса - 2,5 мг

[Deathmorozz]

Только начали: фраксипарин 0,3 или 0,6(зависит от массы тела) №6, после варфарин, или тромбоасс, + компрессия ниж. кончностей.

[Gilarov]

Сообщение от Deathmorozz

Только начали: фраксипарин 0,3 или 0,6(зависит от массы тела) №6, после варфарин, или тромбоасс, + компрессия ниж. кончностей.

Мне казалось, что доза фраксипарина зависит скорее не от массы тела, а от риска тромбоза. ТромбоАСС же с точки зрения профилактики венозного тромбоза бесполезен.

[Sereda Andrey]

..................В ортопедической практике профилактическую дозу надропарина подбирают с учетом массы тела больного. Для пациентов с массой 50-70 кг дозы составляют 0,3 мл до операции и в течение 3-х суток после нее, затем 0,4 мл, а при большей массе тела - 0,4 и 0,6 мл соответственно. В многочисленных рандомизированных исследованиях при использовании таких схем введения надропарина установлена его более высокая по сравнению с НФГ эффективность в отношении профилактики тромбоза глубоких вен и клинически проявляющейся тромбоэмболии легочной
артерии. Доказано клиническое превосходство фраксипарина по сравнению с механической компрессией, применяемой для профилактики тромбоза глубоких вен после перенесенной артропластики коленного сустава. При этом степень риска воз*никновения кровотечения или раневой гематомы ниже или не отличается от таковой НФГ. Отмечена и достоверно более низкая (по сравнению с НФГ и другими НМГ) частота отказов больных от дальнейшего введения препарата из-за местной болезненности и кровоточивости.......................
[Ссылки доступны только зарегистрированным пользователям ]

[Winer]

Сообщение от Sereda Andrey

..................В ортопедической практике профилактическую дозу надропарина подбирают с учетом массы тела больного. Для пациентов с массой 50-70 кг дозы составляют 0,3 мл до операции и в течение 3-х суток после нее, затем 0,4 мл, а при большей массе тела - 0,4 и 0,6 мл соответственно.[/url]

И мы так работаем

[Gilarov]

Уважаемый Андрей!
А при более высоком риске (ТЭЛА в анамнезе, например) дозу не увеличиваете?

[Dr.]

У нас вон трайл по эноксапарину/апексабану идет. Дело-то хорошее, будем ждать результатов

Вот информация к размышлению ©



ANTICOAGULANTS IN DEVELOPMENT

Tissue factor and factor VII as potential targets*—*The recombinant form of tissue factor pathway inhibitor (TFPI), the physiologic inhibitor of the TF/FVIIa complex, is being tested, and there are also specific TF/FVIIa and factor VIIa inhibitors (eg, nematode anticoagulant protein) undergoing development [77-80] . (See "Prevention of venous thromboembolic disease", section on Investigational agents).

Factor V and factor VIII as potential targets*—*All the above anticoagulants target the active enzymes in the clotting cascade. An alternative method is to target the two cofactors in the cascade, factor Va and factor VIIIa. There is a potential advantage in this approach. Inhibition of the cofactors dampens the clotting cascade but does not completely block the generation of thrombin as might occur with a thrombin inhibitor if present in excess. This problem may account for the relatively narrow therapeutic window observed for hirudin.

One way of targeting factor Va and factor VIIIa is to use recombinant activated protein C, which is now in phase III clinical trials. Activated protein C, in association with protein S on phospholipid surfaces, proteolytically inactivates factors Va and VIIIa, thereby inactivating prothrombinase. (See "Overview of hemostasis"). Other possibilities include a protein C activator such as soluble recombinant thrombomodulin which, when bound to thrombin, converts protein C to activated protein C.

Selective inhibition of the procoagulant properties of thrombin*—*Use of the above noted activated protein C approaches is based upon the premise that thrombin's procoagulant and anticoagulant properties can be dissociated and exploited. Thrombin is unique among the serine proteases in the clotting cascade in that it possesses both procoagulant and anticoagulant properties: The procoagulant properties include fibrin clot formation, activation of the protease activated receptor (PAR-1) or thrombin receptor on platelets and other vascular cells, activation of factors V, VIII, XI, and XIII, and activation of thrombin-activatable fibrinolysis inhibitor, leading to inhibition of fibrinolysis [81] . (See "Overview of hemostasis"). When thrombin is bound to thrombomodulin on the vascular endothelial cell surface, it undergoes a remarkable switch in its substrate specificity [82] . It loses all of its procoagulant properties as it will no longer cleave fibrinogen or activate platelets. Instead, thrombin becomes an anticoagulant enzyme by activating protein C. A knockout mouse model in which the thrombomodulin gene was ablated from vascular endothelium was associated with unfettered activation of the coagulation system and widespread juvenile-onset thrombosis [83] .

All of the active site inhibitors of thrombin inhibit both types of activities, and an ideal thrombin inhibitor may be one that will selectively inhibit its procoagulant properties while retaining thrombin's ability to activate protein C, thereby exploiting this powerful natural anticoagulant pathway [84] .

Two experimental approaches to selective procoagulant inhibition are the creation of thrombin mutants and of molecules which act like thrombomodulin. A thrombin mutant (E229K) has been identified in which glutamic acid in position 229 in wild-type thrombin is replaced by lysine [85] . This protein has less than 1 percent of the procoagulant properties of wild-type thrombin, while retaining approximately 50 percent of its protein C activation capability [86] . As a result, it functions as an anticoagulant. It does not consume fibrinogen, clotting factors, or platelets, and, even at the peak of its anticoagulation effect, it does not prolong the bleeding time in contrast to hirudin or the platelet glycoprotein IIb/IIIa antagonists.

A small molecule has been identified that suppresses fibrinogen clotting and enhances protein C activation by thrombin, thereby functioning in part like a soluble thrombomodulin [87] . This change in substrate specificity appears to mediated by an alteration in thrombin's substrate recognition site, a mechanism seemingly different from the allosteric changes induced by thrombomodulin.

Activated Protein C*—*Recombinant activated protein C (drotrecogin alfa), which has both anticoagulant and antiinflammatory properties [88,89] , has been shown to be efficacious for treatment of severe sepsis in a randomized, double-blind, placebo-controlled trial [90] . It ameliorated the coagulopathy associated with severe sepsis, as demonstrated by reduction of fibrin D-dimer, and reduced the mortality rate from 30.8 percent in the placebo group to 24.7 percent in the treatment group. Recombinant activated protein C was approved by the FDA for reduction of mortality from severe sepsis (associated with organ dysfunction) in adults at high risk of death (eg, APACHE II score ≥ 25). (See "Management of severe sepsis and septic shock in adults", section on Recombinant human activated protein C and see "Clinical features, diagnosis, and treatment of disseminated intravascular coagulation in adults", section on Activated protein C)

[Sereda Andrey]

Сообщение от Gilarov

Уважаемый Андрей!
А при более высоком риске (ТЭЛА в анамнезе, например) дозу не увеличиваете?

Нет, назначаем стандартно из расчета 0,5 мг на кг.