Thrombotic Disorders - DVT/PE

Question 1

How does the body prevent thrombus at the venous valves?

Answer 1

• In the erect position, blood is propelled proximally from the calf veins by muscular action
• Back flow is prevented by an extensive system of valves, located all along the veins from the lower leg to the pelvis
  
  • While the valves prevent blood pooling distally, there is increased turbidity within the valve sinus potentially stimulating thrombus formation
• To prevent thrombus formation, the levels of the anticoagulant factors, endothelial cell protein C receptor and thrombomodulin are higher in the valvular sinus endothelium (D and E) than in the luminal endothelium (A and B)
  
  • The levels of the procoagulant, von Willebrand factor, are lower in the valvular sinus endothelium than in the luminal endothelium (F versus C)

Question 2

What are the possible causes of venous thrombosis?

Answer 2

• The precise cause of venous thrombosis is unknown, but tears in the vein wall or pressure necrosis of the delicate endothelium are likely
  
  • Platelets and neutrophils adhere at the site of injury and activate procoagulants
  • Thrombin is generated, fibrin formed, and red cells are trapped within the growing thrombus
• Proximal thrombi are located in the iliac, femoral, and popliteal veins
  
  • Distal thrombi are in the tibial and peroneal veins
  • Embolization occurs when the adherent thrombus becomes dislodged, either spontaneously or by increased muscular activity
• Venous thrombosis also occurs with direct injury or prolonged compression of the veins
  
  • For example, when you fall asleep during a long trip with your legs crossed, or you assist during surgery and inadvertently lean on the leg of the anesthetized patient!
  • Other examples are compression of the left iliac vein by the right iliac artery in pregnancy
  • Compression of the retinal vein by the retinal artery in hypertensive patients

Question 3

What is the incidence of DVT and PE?

Answer 3

• Deep vein thrombosis (DVT) is a major cause of death and morbidity. It is estimated that DVT occurs in approximately 2 million Americans each year
• Pulmonary embolism (PE), the most serious sequela to DVT, occurs in up to 600,000 patients each year and an estimated 60,000 die of this complication
  
  • ​The incidence of DVT/PE rises with age

Question 4

What are some of the major risk factors of DVT?

Answer 4

• DVT are unprovoked or provoked by specific risk factors:
  
  • Immobility in medical patients after a stroke, and in surgical patients during the post-operative period, is a common triggering event
  • DVT/PE is a major complication of total hip arthroplasty, and the risk persists for up to 4 weeks post-operatively
  • Patients with lower extremity fractures and plaster casts are also vulnerable
  • The risk of DVT/PE with air travel is 27/million/travelers, and increases with the duration of flight
• Other risk factors are:
  
  • Genetic thrombophilia
  • Obesity, usually in combination with other risk factors
  • Pregnancy, oral contraceptives, estrogens, anti-estrogens
  • Cancer - Most frequent with adenocarcinomas and metastatic disease
    
    • Migratory thrombophlebitis is sequential inflammation of several superficial veins, very characteristic of high-grade tumors
    • DVT in cancer patients is often resistant to antithrombotic agents and recurrences are common
    • Thrombi also occur in unusual locations, such as axillary, mesenteric, and portal veins

Question 5

What are the common sites of involvement of DVTs?

Answer 5

• Superficial and deep veins of the arms are the brachiocephalic and subclavian
  
  • Thrombi in these veins are usually associated with intravenous catheters
• Superficial veins of the legs are the greater & lesser saphenous
  
  • Involvement of these veins is called superficial thrombophlebitis, and the veins are usually tender, red, and palpable
• Deep veins of the legs: iliac, superficial femoral, popliteal, gastrocnemius, tibial - these are the traditional “DVT”
  
  • Note: although called “superficial” femoral, this is the major deep vein of the thigh
  • The deep femoral vein is short and rarely the site of thrombi
• Pulmonary artery emboli (“PE”) usually arise from DVT
• Thrombi in mesenteric, portal, ovarian, axillary, cerebral, and retinal, veins are uncommon

Question 6

Describe the clinical diagnosis of DVT.

Answer 6

• Suspect DVT in patient with unilateral leg swelling, pain, and calf tenderness
  
  • These findings are simulated by a ruptured Baker’s cyst, usually located in the patella fossa
  • Other differential diagnoses are muscle cramps, cellulitis, and heterotopic bone formation (in paralyzed patients)
• PE is suspected in patients with cough, shortness of breath, tachycardia or other arrhythmias, and fever
  
  • ​If the lung is infracted, there is pleuritic chest pain and hemoptysis, and with massive PE, syncope
  • Differential diagnosis includes pneumonia, heart failure, sepsis, and cancer
  • Pre-test probability indicates likelihood of disease (Wells Criteria)

Question 7

Describe the Well’s Criteria for DVTs.

Answer 7

• Major surgery within 4wks - 1pt
• Paralysis, recent casts - 1pt
• Cancer in past 6 months - 1pt
• Tenderness along veins - 1pt
• Leg swelling 3 cm > nl leg - 1pt
• Edema of symptomatic leg - 1pt
• Collateral veins - 1pt
• Alternative diagnosis more likely - subtract 2pts
• Intermediate 1-2; High ≥ 3

Question 8

What are the Well’s Criteria for pulmonary embolism?

Answer 8

• Major surgery within 4wks - 1.5pts
• Previous venous thromboembolism - 1.5pts
• Cancer in past 6 months - 1.0pts
• DVT signs/symptoms - 3.0pts
• Heart rate >100 - 1.5pts
• Alternative diagnosis less likely - 1.0pts
• Intermediate 2-6; High >6

Question 9

What are the lab tests for DVT and PE?

Answer 9

• D-dimer is a cross-linked fibrin degradation product
  
  • Elevated levels occur in thrombotic disorders but also in cancer, pregnancy, renal failure, and rise with age
  • Therefore, it is necessary to use the d-dimer test in conjunction with the pre-test probability:
    
    • If pre-test probability is intermediate or low and age-adjusted d-dimer is normal, DVT/PE is unlikely and no further testing is indicated
    • If pre-test probability and d-dimer are both high, DVT/PE is likely and venous ultrasound or CT pulmonary angiogram will show the location & extent of the thrombus
    • If there are discrepancies between the pre-test probability and d-dimer, do venous ultrasound for DVT or CT pulmonary angiogram for PE.
    • If diagnosis is still uncertain, do venography for DVT or pulmonary angiography for PE

Question 10

What is the main complication of DVTs and what is the occurrence rate?

Answer 10

• The main complication of DVT is PE, which might be fatal
• Other complications are recurrent DVTs and the post-thrombotic syndrome
• Recurrences usually occur after anticoagulants are discontinued, even after 2 or more years of treatment
• The recurrence rate in men is 30%, but only 10% in women
  
  • ​This difference might be due to transient risk factors, such as pregnancy, oral contraceptives, and estrogens, for DVT
  • Avoidance of these risk factors leads to fewer recurrences

Question 11

What is postphlebitic syndrome?

Answer 11

• The postphlebitic syndrome is characterized by:
  
  • pain
  • muscle cramps
  • pruritus
  • paresthesias
  • a feeling that the involved leg is heavy
• The skin is:
  
  • indurated
  • pigmented
  • becomes ulcerated
  • the entire leg is edematous
• Repeated attacks of pain and swelling occur, and it becomes difficult to distinguish between new onset thrombi or extension of existing thrombi
• Frequent hospitalizations for medical and surgical procedures, including plastic surgery to manage the ulcers, are common, and patients experience major disability

Question 12

What is chronic thromboembolic pulmonary hypertension?

Answer 12

• Chronic thromboembolic pulmonary hypertension occurs in about 4% of patients following repeated clinical and subclinical (inapparent) pulmonary emboli
• The pulmonary vasculature becomes attenuated due to vessel wall thickening and luminal narrowing
• The resulting pulmonary hypertension is associated with symptoms such as:
  
  • dyspnea
  • fatigue
  • anorexia
  • hemoptysis
• This complication occurs in about 4% of patients with recurrent PE