Characteristics of anticoagulants/thrombolytics used for acute VTE in pediatrics
| Agent . | Class and mechanism of action . | Route . | Half-life . | Metabolism and excretion . | Drug interactions . | Use in liver or renal impairment . | Preparations . |
|---|---|---|---|---|---|---|---|
| UFH | Binds to AT to increase AT inhibitory effect on FIIa and FXa | IV (preferred), SQ (lower bioavailability in children) | Nonlinear 60-90 min | Metabolized by the liver; renally cleared and excreted in urine | None | Careful monitoring | N/A |
| LMWH | Smaller than UFH; binds to AT increasing AT’s inhibitory effect on FXa (less FIIa effect) | SQ (rarely IV) | Enoxaparin 3-7 h; dalteparin 3-5 h | Metabolized by the liver; renally cleared and excreted in urine | None | Dose adjustment required in patients with decreased CrCl | Enoxaparin: prefilled syringes: 30 mg/0.3 mL, 40 mg/0.4 mL, 60 mg/0.6 mL, 80 mg/0.8 mL, and 100 mg/1mL; graduated prefilled syringes: 60 mg/0.6 mL, 80 mg/0.8 mL, and 100 mg/1 mL; multipledose vial: 300 mg/3 mL Dalteparin: prefilled syringes: 2 500 IU/0.2 mL, 5 000 IU/0.2 mL, 7 500 IU/0.3 mL, 10 000 IU/1 mL, 12 500 IU/0.5 mL, 15 000 IU/0.6 mL, and 18 000 IU/0.72 mL; multidose vials: 10 mL containing 10 000 IU/mL, 3.8 mL containing 25 000 IU/mL |
| Fondaparinux | Synthetic pentasaccharide; binds to AT and increases AT inhibitory effect on FXa | SQ | 17-21 h | Renally cleared and excreted unaltered in urine | None | Contraindicated in severe renal impairment (CrCl of <30 mL/min) | Prefilled syringes: 1.5 mg, 2.5 mg, 5 mg, and 10 mg doses |
| Warfarin, acenocoumarol, and phenprocoumon (VKAs) | VKAs; inhibit vitamin K epoxide reductase and interruption in the synthesis of activated vitamin K, preventing carboxylation of FII, FVII, FIX, and FX (proteins S and C) | po | 20-60 h | Metabolized in the liver by CYP2C9 with minor contributions from CYP2C18 and VYP2C19; excreted in urine and feces | Multiple drug and food interactions, including OTC drugs; caution with concurrent use of antimicrobials, anti-arrhythmic drugs, and other anticoagulant agents Food interactions: foods rich in vitamin K | No dose adjustment for renal impairment Hepatic impairment requires close INR monitoring, response may be increased in obstructive jaundice, hepatitis, or cirrhosis | No liquid preparation Warfarin sodium (Coumadin: 1 mg, 2 mg, 2.5 mg, 5 mg, and 10 mg; Marevan: 1 mg, 3 mg, and 5 mg) Acenocoumarol (Sintrome: 1 mg) Phenprocoumon (1.5 mg and 3 mg) |
| Rivaroxaban | FXa inhibitor; directly binds to free and prothrombinase-complex-bound FXa inhibiting its function (reversible inhibition) | po, NG, or GT | Mean half-life: adolescents, 4.2 h; age 2 to <12 y, 3 h; age 0.5 to <2 y, 1.9 h; age <0.5 y, 1.6 h | Metabolized by the liver; renally cleared and excreted in urine | Concurrent use of P-gp and strong CYP3A4 inducers and inhibitors | Avoid in moderate and severe hepatic impairment or with any hepatic disease associated with coagulopathy Avoid in children with eGFR of <50 mL/min per 1.73 m2 (serum Cr of >97.5th percentile in infants) | Oral suspension: 1 mg/mL Tablets: 2.5 mg, 10 mg, 15 mg, and 20 mg; no pediatric data with 2.5 mg tablets Tablets can be crushed and mixed with water or applesauce Availability varies based on jurisdiction |
| Dabigatran | Direct thrombin inhibitor; directly binds to free and fibrin bound thrombin, blocking conversion of fibrinogen to fibrin (reversible inhibition) | po (all dosage forms) NG or GT (oral suspension only) | Elimination half-life: 9-11 h | Rapid and complete conversion into active form after intestinal absorption; renally cleared and excreted in urine | Concurrent use of P-gp inducers and inhibitors | Avoid in active liver disease, including active hepatitis, or elevated ALT, AST, or AP of >3× ULN Contraindicated in renal dysfunction with eGFR of <50 mL/min per 1.73 m2 (serum Cr of >97.5th percentile in infants) | Oral capsules: 75 mg, 110 mg, and 150 mg; cannot be crushed Oral pellets: 20 mg, 30 mg, 40 mg, 50 mg, 110 mg, and 150 mg per packet. Powder and solvent for oral solution (6.25 mg/mL). Availability varies based on jurisdiction. Cannot combine different preparations The oral solution is compatible with nasal tubes made of PVC, polyurethane, and silicone |
| t-PA | Thrombolytic/fibrinolytic; Cleaves plasminogen to plasmin, which can then degrade fibrin (and fibrinogen). Binds to fibrin in blood clot activating clot-bound plasminogen (clot-specific fibrinolysis) | IV | Alteplase: initial half-life of 5 min; terminal half-life of 72 min | Hepatic clearance | None | No contraindications in renal or liver disease, although risk of bleeding may be higher | N/A |
| Agent . | Class and mechanism of action . | Route . | Half-life . | Metabolism and excretion . | Drug interactions . | Use in liver or renal impairment . | Preparations . |
|---|---|---|---|---|---|---|---|
| UFH | Binds to AT to increase AT inhibitory effect on FIIa and FXa | IV (preferred), SQ (lower bioavailability in children) | Nonlinear 60-90 min | Metabolized by the liver; renally cleared and excreted in urine | None | Careful monitoring | N/A |
| LMWH | Smaller than UFH; binds to AT increasing AT’s inhibitory effect on FXa (less FIIa effect) | SQ (rarely IV) | Enoxaparin 3-7 h; dalteparin 3-5 h | Metabolized by the liver; renally cleared and excreted in urine | None | Dose adjustment required in patients with decreased CrCl | Enoxaparin: prefilled syringes: 30 mg/0.3 mL, 40 mg/0.4 mL, 60 mg/0.6 mL, 80 mg/0.8 mL, and 100 mg/1mL; graduated prefilled syringes: 60 mg/0.6 mL, 80 mg/0.8 mL, and 100 mg/1 mL; multipledose vial: 300 mg/3 mL Dalteparin: prefilled syringes: 2 500 IU/0.2 mL, 5 000 IU/0.2 mL, 7 500 IU/0.3 mL, 10 000 IU/1 mL, 12 500 IU/0.5 mL, 15 000 IU/0.6 mL, and 18 000 IU/0.72 mL; multidose vials: 10 mL containing 10 000 IU/mL, 3.8 mL containing 25 000 IU/mL |
| Fondaparinux | Synthetic pentasaccharide; binds to AT and increases AT inhibitory effect on FXa | SQ | 17-21 h | Renally cleared and excreted unaltered in urine | None | Contraindicated in severe renal impairment (CrCl of <30 mL/min) | Prefilled syringes: 1.5 mg, 2.5 mg, 5 mg, and 10 mg doses |
| Warfarin, acenocoumarol, and phenprocoumon (VKAs) | VKAs; inhibit vitamin K epoxide reductase and interruption in the synthesis of activated vitamin K, preventing carboxylation of FII, FVII, FIX, and FX (proteins S and C) | po | 20-60 h | Metabolized in the liver by CYP2C9 with minor contributions from CYP2C18 and VYP2C19; excreted in urine and feces | Multiple drug and food interactions, including OTC drugs; caution with concurrent use of antimicrobials, anti-arrhythmic drugs, and other anticoagulant agents Food interactions: foods rich in vitamin K | No dose adjustment for renal impairment Hepatic impairment requires close INR monitoring, response may be increased in obstructive jaundice, hepatitis, or cirrhosis | No liquid preparation Warfarin sodium (Coumadin: 1 mg, 2 mg, 2.5 mg, 5 mg, and 10 mg; Marevan: 1 mg, 3 mg, and 5 mg) Acenocoumarol (Sintrome: 1 mg) Phenprocoumon (1.5 mg and 3 mg) |
| Rivaroxaban | FXa inhibitor; directly binds to free and prothrombinase-complex-bound FXa inhibiting its function (reversible inhibition) | po, NG, or GT | Mean half-life: adolescents, 4.2 h; age 2 to <12 y, 3 h; age 0.5 to <2 y, 1.9 h; age <0.5 y, 1.6 h | Metabolized by the liver; renally cleared and excreted in urine | Concurrent use of P-gp and strong CYP3A4 inducers and inhibitors | Avoid in moderate and severe hepatic impairment or with any hepatic disease associated with coagulopathy Avoid in children with eGFR of <50 mL/min per 1.73 m2 (serum Cr of >97.5th percentile in infants) | Oral suspension: 1 mg/mL Tablets: 2.5 mg, 10 mg, 15 mg, and 20 mg; no pediatric data with 2.5 mg tablets Tablets can be crushed and mixed with water or applesauce Availability varies based on jurisdiction |
| Dabigatran | Direct thrombin inhibitor; directly binds to free and fibrin bound thrombin, blocking conversion of fibrinogen to fibrin (reversible inhibition) | po (all dosage forms) NG or GT (oral suspension only) | Elimination half-life: 9-11 h | Rapid and complete conversion into active form after intestinal absorption; renally cleared and excreted in urine | Concurrent use of P-gp inducers and inhibitors | Avoid in active liver disease, including active hepatitis, or elevated ALT, AST, or AP of >3× ULN Contraindicated in renal dysfunction with eGFR of <50 mL/min per 1.73 m2 (serum Cr of >97.5th percentile in infants) | Oral capsules: 75 mg, 110 mg, and 150 mg; cannot be crushed Oral pellets: 20 mg, 30 mg, 40 mg, 50 mg, 110 mg, and 150 mg per packet. Powder and solvent for oral solution (6.25 mg/mL). Availability varies based on jurisdiction. Cannot combine different preparations The oral solution is compatible with nasal tubes made of PVC, polyurethane, and silicone |
| t-PA | Thrombolytic/fibrinolytic; Cleaves plasminogen to plasmin, which can then degrade fibrin (and fibrinogen). Binds to fibrin in blood clot activating clot-bound plasminogen (clot-specific fibrinolysis) | IV | Alteplase: initial half-life of 5 min; terminal half-life of 72 min | Hepatic clearance | None | No contraindications in renal or liver disease, although risk of bleeding may be higher | N/A |
ALT, alanine aminotransferase; AP, alkaline phosphatase; AST, aspartate aminotransferase; AT, antithrombin; Cr, creatinine; CrCl, creatinine clearance; GT, gastric tube; N/A, not applicable; NG, nasogastric; OTC, over the counter; P-gp, P-glycoprotein; po, Per oral or by mouth; PVC, polyvinyl chloride; ULN, upper limit of normal.