Prophylaxis of Venous Thromboembolic Disease in Trauma Patients & Orthopaedic Surgery

Prophylaxis of Venous Thromboembolic Disease in Trauma Patients:

  1. Chemical Prophylaxis
  2. Mechanical Prophylaxis
  3. Vena Cava Filters

Chemical Prophylaxis:

  • 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 thrombocytopaenia (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 were more frequent than Enoxaparin); should not be used with Epidural anesthesia/analgesia.

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.

 

Mechanical Prophylaxis:
-work by reducing the luminar diameter of a vein→ an increase in venous flow velocity.
-commonly utilized in trauma setting- easy to use & low risk of associated bleeding.
– Graduated compression stockings (GCS), Sequential pneumatic compression devices (PCDs)/Intermittent pneumatic compression(IPC) devices, & Pneumatic plantar (A-V) foot pumps.

  • Graduated compression stockings (GCS):
    –     mainly used for prevention and treatment of DVT in nontrauma patients; effective in diminishing the risk of DVT in hospitalized patients.
  • Pneumatic compression devices (PCD):
    –    increasingly used in trauma patients
    –     Sequental Compression Device (SCD)/ Graduated compression stockings/Intermittent pneumatic compression
    – can be used alone or in combination with chemical prophylaxis.
  • Arterio-venous (A-V) foot pump:
    –    increases venous blood flow in popliteal vein by 250%
    -early mechanical prophylaxis with foot pumps & the addition of enoxaparin on a delayed basis- a very successful strategy for prophylaxis against venous thromboembolic disease following serious musculoskeletal injury.

Vena Cava Filters (VCFs):

  • Traditionally, used in pts with acute proximal DVT or a recent PE in pt for which heparin is contraindicated, or had bleeding during heparin treatment, or who developed a PE despite anticoagulation.
  • So, can be used in trauma pts with contraindications to chemoprophylaxis & mechanical prophylaxis.
  • Permanent VCFs has  disadvantages of increasing the long-term risk of DVT.
  • Retrievable VCFs offers a dual advantage: first protection against PE during the risk period, & second the option of filter removal thus avoiding late complications.

 

Reference:
Deep Vein Thrombosis Prophylaxis in Trauma Patients
Serdar Toker, David J. Hak, & Steven J. Morgan [PMC free Article]

 

 

 

ACCP (American College of Chest Physicians) guidelines,2008:

  • ACCP recommends the use of LMWH for major trauma patients as soon as it is considered safe to do so.
  • An acceptable alternative is the combination of LMWH and the optimal use of a mechanical method.
  • If there is a contraindication for LMWHs, mechanical thromboprophylaxis with PCD (Pneumatic Compression Devices) or possibly with GCS (Graduated Compression Stockings) alone was recommended.
  • For major trauma patients with impaired mobility, ACCP recommends thromboprophylaxis until hospital discharge.
  • ACCP recommends against the use of a VCF (Vena Cava Filters) as thromboprophylaxis for trauma and SCI patients. For patients with acute SCI, ACCP recommends thromboprophylaxis with LMWH, alternatively, combined PCD and either LDH or LMWH. If anticoagulant therapy is contraindicated, the optimal use of PCD and/or GCS is recommended.

 

ACCP recommendations for major orthopedic surgery and knee arthroscopy (2012):

based on the 9th edition of its evidence-based clinical practice guidelines for antithrombotic therapy and prevention of thrombosis.

Recommendations for pts undergoing major orthopedic surgery (total hip arthroplasty [THA], total knee arthroplasty [TKA], or hip fracture surgery [HFS]) included the following :

  • In patients underoing TKA or THA- LMWH, fondaparinux, apixaban, dabigatran, rivaroaxaban, LDUH, adjusted-dose vitamin K antagonist (VKA), aspirin, or an IPC(intermittent pneumatic compression) device for at least 10-14 days is preferable to no prophylaxis.
  • In patients underoing HFS- LMWH, fondaparinux, LDUH, adjusted-dose VKA, aspirin, or an IPC device for at least 10-14 days is preferable to no prophylaxis
  • In patients who receive LMWH, prophylaxis should be started at least 12 hours preoperatively or postoperatively.
  • Regardless of concomitant IPC device use or duration of treatment, LMWH is favored over alternative recommended agents.
  • Thromboprophylaxis should be extended in the outpatient period for up to 35 days from the day of surgery.
  • During the hospital stay, dual prophylaxis with and IPC device and an antithrombotic agent is advised.
  • In patients who are at ↑ed risk for bleeding, an IPC device or no prophylaxis is favored over pharmacologic prophylaxis
  • In patients who refuse or will not cooperate with injections or an IPC device, apixaban or dabigatran (or, if these are unavailable, rivaroxaban or adjusted-dose VKA) is recommended
  • In patients who are at increased risk for bleeding or in whom both mechanical and pharmacologic prophylaxis are contraindicated, placement of an inferior vena cava filter is not recommended
  • In patients who are asymptomatic after surgery, Doppler ultrasound screening before discharge is not recommended

In patients undergoing knee arthroscopy who do not have a prior history of VTE, no thromboprophylaxis was recommended.

 

 

Recommendations of EAST group for the VTE prophylaxis in trauma patients: