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Idraparinuxe

DX 9065a Rivaroxaban (oral)

Note: Agents are parenteral unless indicated otherwise. Agents mentioned in italics are currently being evaluated in randomized control trials.

Several anti-Xa inhibitors in earlier phases of development are included in Table 3. aXimelagatran has been withdrawn because of hepatotoxicity. bLow molecular weight heparins have an anti-Xa:anti-IIa ratio of between 2:1 and 4:1. cBemiparin is an ultra low molecular weight inhibitor with an anti-Xa:anti-IIa ratio of about 8:1. dDanaparoid is a mixture of chondroitin sulfate, dermatan sulfate, and heparin sulfate (see Chapter 13). It has an anti-Xa:anti-IIa ratio of >20:1.

eBiotinylated idraparinux is currently being evaluated in clinical trials. Abbreviations: AT, antithrombin; HCII, heparin cofactor II.

Note: Agents are parenteral unless indicated otherwise. Agents mentioned in italics are currently being evaluated in randomized control trials.

Several anti-Xa inhibitors in earlier phases of development are included in Table 3. aXimelagatran has been withdrawn because of hepatotoxicity. bLow molecular weight heparins have an anti-Xa:anti-IIa ratio of between 2:1 and 4:1. cBemiparin is an ultra low molecular weight inhibitor with an anti-Xa:anti-IIa ratio of about 8:1. dDanaparoid is a mixture of chondroitin sulfate, dermatan sulfate, and heparin sulfate (see Chapter 13). It has an anti-Xa:anti-IIa ratio of >20:1.

eBiotinylated idraparinux is currently being evaluated in clinical trials. Abbreviations: AT, antithrombin; HCII, heparin cofactor II.

thrombin. Thrombin too is a serine protease with even more substrates within the coagulation cascade, notably soluble fibrinogen (converted to insoluble fibrin), and also factors XI, VIII, and V (Fig. 1).

There is debate surrounding the preferential targeting of factor Xa versus IIa, and the role of direct versus indirect (AT-mediated) inhibition. Direct inhibition of thrombin will likely impair both procoagulant (fibrin, XIa, VIIIa, Va generation) and anticoagulant (protein C generation) functions (Fig. 1). However, the pharmacologic utility of commercially available direct thrombin inhibitors (DTIs) suggests that the dominant effect of targeting IIa is anticoagulation. Additionally, thrombin has physiologic roles beyond coagulation that can be abrogated by DTI therapy, such as effects on platelets, wound-healing, and endothelium. In contrast, inhibition of factor Xa is expected to be associated with a purely anticoagulant pharmacodynamic effect, as factor Xa is not known to influence directly natural anticoagulant pathways.

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