Chemical Prophylaxis of Venous Thromboembolic Disease in Trauma Patients

Prophylaxis of Venous Thromboembolic Disease in Trauma Patients:

  1. Chemical Prophylaxis
  2. Mechanical Prophylaxis
  3. 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.

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%.
    ~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.