Deep Venous Thrombosis (DVT)

• Incidence of DVT - 1 person per 1,000 population per year.
• It is a relatively common complication of trauma.
• About 20% of multiply injured patients die as a result of a DVT.

✫ It is also an important complications after THA (total hip arthroplasty) & TKA (total knee artheoplasty), possibly resulting in life-threatening PE (Pulmonary Embolism). 

0. Risk Factors for Venous Thromboembolic Disease

• Proximal thrombi, in the popliteal vein and above (less common), has higher risk of PE than thrombi in calf veins (more common)
• Femoral or tibial diaphyseal fractures -> higher risk of DVT
• Regional anesthesia is associated with reduced the incidence of DVT from 73% to 23% compared with general anesthesia. 

Etiology

• Venous thrombi are mainly composed of fibrin & erythrocytes and also platelets and leucocytes.
• They usually form in venous sinuses in the deep calf veins and in veins damaged by trauma. 
• Damage to the endothelium of the veins leads to platelet adhesion, leucocyte accumulation, and the activation of the intrinsic and extrinsic pathways.
• Cytokines and tumor necrosis factor may be released, causing distant venous damage leading to coagulation.
• Venous stasis during surgery or as a result of trauma may contribute by slowing the clearance of coagulation factors.
• This is particularly important in lower limb surgery because the normal pumping action of the calf muscles may be slowed or abolished.

• Most significant PEs arise from the proximal veins. 

Diagnosis

• The clinical signs of DVT include

1. Leg pain and swelling,
2. Edema,
3. Altered temperature,
4. Dilated superficial veins, and 
5. Erythema.

• Clinical Tests include assesment of leg circumference and Homan's sign, which is calf pain caused by forced dorsiflexion of the ankle with the knee flexed.
• Clinical examination is unreliable
• Diagnosis of DVT requires the use of venography, ultrasound, or impedance plethysmography.

I. Venography is the standard investigation.

• Contrast material is injected into the superficial veins of the foot and x-rays are used to differentiate areas of inadequate venous filling.
• It has risk of anaphylactic reaction to the contrast media and a small risk of inducing DVT.

II. Duplex ultrasound - useful screening test, because of its minimal morbidity, low cost, and repeatability with minimal patient discomfort.

    ✫ It is particularly useful for visualization of proximal vein DVT and is less effective for calf vein DVT.

III. Impedance plethysmography has high accuracy in the diagnosis of thigh DVT in particular.

• These are the standard diagnostic tests for proving the presence of a DVT.
• The diagnosis of PE is best done by angiography or by a perfusion lung scan.
• Investigations should also include an ECG to exclude cardiac problems, a chest x-ray, and arterial blood gases. 

Prophylaxis
The most commonly used prophylactic methods  are

1. 1)  Early mobilization
   
• Prolonged immobilization is related to the development of deep vein thrombosis.
  
• Patients should be mobilized as early as their general condition permits.
  
• Active exercises of both lower extremities help reduce venous stasis & thrombus formation.
  
2. 
   
3. 2)  Mechanical methods
   
• These include graduated elastic compression stockings (GECS), intermittent pneumatic compression, and mechanical foot pumps.
  
• They are limited by patient compliance and short duration of hospitalization.
  
4. 
   
5. 3)  Antiplatelet medication
   
• The combination of GECS with pharmacological prophylaxis is more effective than pharmacological prophylaxis alone.
  
• Prophylaxis with aspirin alone has not been proved to be effective.
  
• Aspirin also increases the risk of perioperative bleeding.
  
6. 
   
7. 4)  Heparin.
   
8. 
   

Warfarin

• Warfarin prophylaxis usually is begun on the evening before or after surgery and is adjusted according to the daily prothrombin time.
  
• The use of the international normalized ratio (INR) allows standardization of anticoagulant effect as measured by the prothrombin time.
  

 The current goal of warfarin therapy is to keep the INR between 2.0 and 3.0.

• Advantages of warfarin include oral administration and low cost.
  
• 
  
• The main disadvantages of warfarin therapy are
  
  1. Drug interactions
     
  2. Continued monitoring
     
  3. Delayed onset of action, and
     
  4. Bleeding complications.
     
  
  

Low Molecular Weight Heparin

• Includes Enoxaparin, ardeparin, logiparin, dalteparin, and nadroparin.
  
• The pharmacological properties of these agents are different from those of unfractionated heparin.
  

     Their relative lack of antithrombin activity causes minimal elevation of activated partial thromboplastin time (APTT), and they can be administered subcutaneously once or twice daily without the need for monitoring levels of activity.

   ✫ The advantages are a standard dose regimen and the absence of routine laboratory monitoring.

• The disadvantages include greater medication cost, subcutaneous administration, and increased incidence of bleeding (the risk of epidural hematoma formation with enoxaparin)

Fondaparinux, 

• an inhibitor of factor Xa given in a single daily injection, is the most recent anticoagulant for thromboembolism prophylaxis for total hip, total knee, and hip fracture patients.
• Similar to LMWH, fondaparinux is associated with risk of bleeding complications and thrombocytopenia.
• Contraindications include Renal insufficiency.
  

• LMWH, fondaparinux, or adjusted-dose vitamin K antagonist (INR target 2.5; range 2.0 to 3.0) may be used for patients undergoing elective total hip or knee arthroplasty. 
  
• Thromboprophylaxis of at least 10 days is recommended for patients undergoing hip or knee arthroplasty or hip fracture surgery.

✫LMWH or warfarin is given for 10 to 14 days postoperatively, along with mechanical compression devices during the initial hospital stay.

Enteric-coated aspirin is used in low-risk patients for another 4 weeks (6 weeks for high risk patients with history of previous thromboembolism) after the LMWH or warfarin is discontinued.

Contraindications To Pharmacologic DVT Prophylaxis

1. Uncorrected bleeding disorders
   
2. Major hemorrhage
   
   1. a)  Intracranial bleed
      
   2. b)  Pelvic hemorrhage
      
   3. c)  Esophageal varices 
   4. d) Peptic ulcer
   5. e) Spinal cord injury
3. Anemia
4. Allergy
5. Heparin-associated thrombocytopenia
6. Aspirin-induced asthma
7. Severe liver impairment
8. Severe renal impairment

Treatment

• Despite using the prophylactic measures, and careful clinical monitoring, some patients develop DVT and PE and require full therapeutic anticoagulation.
  
• These patients may require Respiratory support, serial arterial blood gas determinations, and repeat lung scans.
  

•  Heparin is administered to provide initial anticoagulation.
  
•  Warfarin is then introduced, and the dose adjusted acc to the INR, which should be within the range of 2.0 to 3.0.
  

• Warfarin treatment is continued for at least 3 months.
  
• If additional pulmonary emboli develop despite adequate anticoagulation, or if bleeding complications occur because of anticoagulation, it may be necessary to place a filter in the inferior vena cava.

• Thrombolytic enzymes, such as urokinase and streptokinase, have been used to dissolve emboli, but these can produce massive hemorrhage from the surgical wound. 
  

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