Anti-factor

The Trial of Org 10172 in Acute Stroke Treatment (TOAST) was a randomized, double-blind, placebo-controlled trial of danaparoid in 1281 patients within 24 hours of onset of acute ischemic stroke. A three-stage dosage regime was used to achieve plasma anti-factor Xa activity of 0.8 unit/mL. Favorable outcome was defined as the combination of a Glasgow Outcome Scale (GOS) score of 1 or 2 and a modified Barthel Index (BI) score of 12 or greater (on a scale of 0-20) at 3 months or 7 days. Very favorable outcome required the combination of a GOS score of 1 and a Barthel Index (BI) score of 19 or 20 at 3 months or 7 days. 

VTE in pediatric patients. Children less than 1 year old require higher doses (e.g., enoxaparin 1.5 mg/kg SC every 12 hours). Monitor anti-factor Xa activity to guide dosing in children.32... 

If the patient is to be treated with UFH, measure aPTT (or anti-factor Xa activity) 6 hours after initiating the IV infusion. Adjust dose if necessary (Table 7-5) and measure aPTT (or anti-factor Xa activity) every 6 hours after each dose change until therapeutic. Measure aPTT (or antifactor Xa activity) daily thereafter. 

Figure 12.7 Purification of factor VIII complex using immunoaffinity chromatography. The immobilized anti-factor VIII antibody is of mouse origin. Antibodies raised against specific epitopes on both the VIII C and vWF components have both been successfully used. Industrial-scale columns would often exhibit a bed volume of several litres. Note that the different elements in this diagram are not drawn to the correct scale relative to each other...

The production of anti-factor VIII C antibodies renders necessary administration of higher therapeutic doses of the product. In severe cases, the product may even become ineffective. Several approaches may be adopted in order to circumvent this problem. These include ... 

Exchange transfusion of whole blood. This will transiently decrease circulating anti-factor VIII C antibodies. 

Some 5-25 per cent of individuals suffering from haemophilia A develop anti-factor VIII antibodies, and 3-6 per cent of haemophilia B sufferers develop anti-factor IX antibodies. This complicates treatment of these conditions and, as mentioned previously, one approach to their treatment is direct administration of factor Vila. The therapeutic rationale is that factor Vila could directly activate the final common steps of the coagulation cascade, independently of either factor VIII or IX (Figure 12.1). Factor Vila forms a complex with tissue factor that, in the presence of phospholipids and Ca2+, activates factor X. 

Approximate anti-Factor Xa activity of 100 units/1 mg enoxaparin sodium (with reference to the WHO First International Low Molecular Weight Heparin Reference Standard). 

Calculated volume based on the 9.5 ml multiple-dose vial (10,000 anti-Factor Xa units/mL). ... 

Information listed without regard to dosage or indication. Maximum anti-Factor Xa and antithrombin activities. 

Mechanical prosthetic heart valves The use of enoxaparin injection has not been adequately studied for thromboprophylaxis or long-term use in patients with mechanical prosthetic heart valves. Isolated cases of prosthetic heart valve thrombosis have been reported in patients with mechanical prosthetic heart valves who have received enoxaparin for thromboprophylaxis. Some of these cases were pregnant women in whom thrombosis led to maternal and fetal deaths. Frequent monitoring of peak and trough anti-Factor Xa levels and dose adjustment may be needed. 

The anti-Factor Xa activity of fondaparinux can be measured by anti-Xa assay using the appropriate calibrator. 

Fig. 7.15 Number of capillaries per mm in anterolateral, posterior, and septal walls of studied heart. (A) Anti-factor Vlll-associated antigen counterstained with hematoxylin. (B) Anti-smooth muscle-actin antigen counterstained with hematoxylin. (C) Capillaries reacted with anti-factor VIII-associated antigen inside fibrotic areas only in anterolateral and posterior walls, n = 108 microscope fields for A 96...

Lectin affinity chromatography may be used to purify glycoproteins Immobilized antibodies may be used as affinity absorbants for the antigen that stimulated their production (e.g. purification of factor VIII using immobilized anti-factor VIII antibodies)... 

Purification entails use of an immunoaffinity column containing immobilized murine antifactor VII antibody. It is initially produced as an unactivated, single chain 406 amino acid polypeptide, which is subsequently proteolytically converted into the two-chain active factor Vila complex. After sterilization by filtration, the final product is aseptically filled into its final product containers and freeze-dried. The excipients present in the product include sodium chloride, calcium chloride, polysorbate 80, mannitol and glycylglycine. When freeze-dried in the presence of these stabilizing substances and stored under refrigerated conditions, the product displays a shelf-life of at least 2 years. It has proved effective in the treatment of serious bleeding events in patients displaying anti-factor VIII or IX antibodies. 

Table 17.1 Anti-factor Xa/anti-factor Ha ratio for marketed low molecular weight heparins (LMWHs)...

Parenteral 2500, 5000, 10000, 15000, 18000 anti-factor Xa units/0.2 mL for SC injection only Danaparoid (Orgaran)... 

Dalteparin, tinzaparin and danaparoid (an LMW heparanoid containing heparan sulfate, dermatan sulfate, and chondroitin sulfate that is no longer available in the United States), on the other hand, are specified in anti-factor Xa units. 

Prophylactic enoxaparin is given subcutaneously in a dosage of 30 mg twice daily or 40 mg once daily. Full-dose enoxaparin therapy is 1 mg/kg subcutaneously every 12 hours. This corresponds to a therapeutic anti-factor Xa level of 0.5—1 unit/mL. Selected patients may be treated with enoxaparin 1.5 mg/kg once a day, with a target anti-Xa level of 1.5 units/mL. The prophylactic dose of dalteparin is 5000 units subcutaneously once a day therapeutic dosing is 200 units/kg once a day for venous disease or 120 units/kg every 12 hours for acute coronary syndrome. The use of LMW heparins is discouraged or contraindicated in patients with renal insufficiency or body weight greater than 150 kg. 

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