Prophylaxis of Venous Thromboembolic Disease in Trauma Patients:
- Chemical Prophylaxis
- Mechanical Prophylaxis
- Vena Cava Filters
Chemical Prophylaxis:
Antithrombotics– prevent the growth or formation of thrombi: – Anticoagulants and Antiplatelet drugs (aspirin or cyclooxygenase (COX)-1 inhibitors)
Anticoagulants– retard or inhibit the process of thrombosis (Coumarins, Heparin, LMWH, Fondaparinux; Factor Xa inhibitors- Rivaroxaban, Apixaban ; Direct thrombin inhibitors- Dabigatran )
Thrombolytic drugs– lyse existing thrombi
Low Dose Heparin: Unfractioned Heparin Dose- 5,000 units S/C, 2-3 times daily
-binds & increases the ability of Antithrombin III to inhibit factors IIa, III, Xa.
-Low cost
– metabolized in Liver
– the incidence of DVT can be diminished by as much as 20% to 40%
-reversal by Protamine sulphate
-not as effective as LMWH
-Risks: Bleeding; Heparin induced thrombocytopenia (HIT).
-Variable pharmacokinetics
-Requirement for aPTT monitoring for adjusted-dose regimens
-Short half-life and low bioavailability.
Low Molecular Weight Heparin (LMWH): Dose- enoxaparin 30 mg 12 hourly; Others: dalteparin, nadroparin, tinzaparin, & ardeparin.
-produced by chemical depolymerization of unfractioned heparin.
-mainly inhibits Factor Xa.
-No lab-monitoring needed
-can be reversed by Protamine sulphate
-metabolized by Kidney
-Risk of bleeding
Fondaparinux: Dose- 2.5 mg SC daily
-a nonheparin drug, the first synthetic pentasaccharide selectively inhibiting Factor Xa (through Antithrombin III).
-acts rapidly but has a long half-life (18 hours)
-protection against VTE in high-risk trauma patients
-once-daily dosing regimen- good compliance & low cost
-eliminate risk of heparin-induced thrombocytopenia(HIT).
-↓ed incidence of DVT in comparison to Enoxaparin in Pelvic/hip fractures & TKA pts.
-high risk of bleeding (episodes of major bleeding- more frequent than Enoxaparin); should not be used with Epidurals.
Reference:
Deep Vein Thrombosis Prophylaxis in Trauma Patients
Serdar Toker, David J. Hak, & Steven J. Morgan [PMC free Article]
Other drugs:
- Rivaroxaban:
-a direct factor Xa inhibitor (others: Apixaban, Edoxaban)
– once daily dose- oral
-superior in preventing DVT, nonfatal PE, or death in comparison to S/C enoxaparin following Arthroplastic surgery.
-the first orally active direct factor Xa inhibitor approved by the US-FDA
-indicated for prophylaxis of DVT/PE in pts undergoing TKR/THR surgery. - Dabigatran:
–a reversible direct thrombin inhibitor
– for prophylaxis of DVT/PE after THR surgery
– similar effectiveness & safety in preventing VTE following hip arthroplasty as compared with Enoxaparin,
– Antidote: Idarucizumab - Warfarin:
– oral anticoagulant
– inhibits Vitamin K 2,3-epoxide reductase preventing reduction of Vitamin K epoxide back to active Vitamin K
-Vitamin K is essential for gamma-carboxylation of glutamic acid for: factors II (prothrombin), VII (first affected), IX, X; protein C & protein S.
– warfarin needs 36-72 hrs to reach a stable loading dose
– The effectiveness of warfarin anticoagulation is measured & regulated by INR
– For DVT prophylaxis, the optimal INR is between 2-3, with a target of 2.5.
-When used for DVT prophylaxis after THR, warfarin reduces total DVT by 60% & proximal DVT by 70%.
– Disadvantages:
~long onset of action,
~need to monitor INR values frequently to obtain a stable dosage,
~-Reversal: vitamin K (takes up to 3 days), FFP (acts immediately)
~multiple drug & dietary interaction (adverse reaction with -rifampin, phenobarbital, diuretics, cholestyramine etc),
~variable patient response.
~Hemorrhagic complications in up to 3-5% of pts on warfarin prophylaxis.
Aspirin: an irreversible COX-1 inhibitor
-used to prevent thrombosis by Thromboxane inhibition & preventing platelet aggregation
-effective as a platelet inhibitor at very low dosages (50-100 mg/day)- significantly less than that needed to produce an anti-inflammatory effect.
-not so effective in preventing PE.