Venous Thromboembolism - Management Signs and Symptoms

Definition

Venous Thromboembolism (VTE)

• Most commonly manifested as pulmonary embolism (PE) and deep venous thrombosis (DVT), and is associated with significant morbidity and mortality
  • One-third of patients present with symptoms of PE and two-thirds with DVT 
• Also manifests as superficial vein thrombosis (SVT) of the arms and legs; rarely develops into a DVT  
• All patients admitted for major trauma, surgery or acute medical illness should be assessed for risk of VTE and bleeding before starting prophylaxis of VTE 
  • Studies show that appropriate VTE prophylaxis should be given to surgical patients in Asia who are at risk for VTE

Deep Vein Thrombosis (DVT)

• A frequent manifestation of VTE in which there is a blood clot blocking a deep vein in the lower extremities which may progress proximally
• Patients are generally asymptomatic with a calf DVT but becomes symptomatic with proximal extension of the DVT and venous outflow obstruction
• Upper extremity DVT may also develop and may be primary (eg effort thrombosis, idiopathic or thoracic outlet syndrome) or secondary (eg mediastinal tumors, cancer-associated, catheter or surgery related) 

Pulmonary Embolism (PE)

• Blockage of the blood vessels in the lungs usually due to blood clots from the veins, especially the veins in the legs and pelvis
• Subsegmental PE is PE which does not involve the proximal pulmonary arteries

Epidemiology

• Incidence of VTE increases with age; 60% of VTE events occur in >65-year-old patients
  • PE is more frequent in older age groups than DVT
    • Prevalence of clinically silent PE increases with age in patients with DVT and is higher in patients with proximal DVT
  • Higher incidence in African Americans and lower in Asians
  • Higher incidence in winter with a peak in February
• Slightly more common in men; at ages 20-45 years, incidence is higher in women and at ages 45-60 years, incidence is higher in men
• Third most common cause of acute cardiovascular disease (CVD) worldwide
• One of the most common life-threatening CVDs in the United States and with increasing incidence and mortality rates in Asia
• Annual incidence of first symptomatic DVT episode in adults ranges from 50-100 per 100,000 population

Pathogenesis

• Virchow’s triad theorizes three factors contributing to the development of VTE: Hypercoagulability, endothelial damage, and venous stasis
• Hypercoagulability has been associated with factor V Leiden mutation and prothrombin gene mutation
  • Cancer also produces a hypercoagulable state due to the procoagulant activity produced by malignant cells and also secondary to effects of chemotherapeutic agents
• Major contributing risk factors include history of trauma, surgical procedures, spinal cord injury, long bone fractures, and previous VTE 
• VTE occurrence can also be spontaneous or unprovoked in 20-40% of VTE episodes

Risk Factors

Transient or Reversible Provoking 

• Surgery within the past 4 weeks (eg hip or knee replacement [lower limb orthopedic procedure]) 
• General anesthesia >30 minutes
• Major trauma
• Immobilization for at least 3 days
• Bedridden for ≥3 days 
• Oral contraceptives or hormone replacement therapy (eg Estrogen therapy)
• Pregnancy/postpartum
• Cesarean section
• Acute inflammation 
• Indwelling venous catheters 
• Travel-associated immobility (5-6 hours) 
• Heparin-induced thrombocytopenia 
• Medications (eg Tamoxifen, Lenalidomide, erythropoietin, L-asparaginase)

Chronic, Non-reversible or Persistent Provoking 

• Active cancer
• Active autoimmune disease (eg antiphospholipid antibody syndrome, rheumatoid arthritis, systemic lupus erythematosus, immune/thrombotic thrombocytopenic purpura)  
• Chronic infections or immobility (eg spinal cord injury)
• Chronic inflammatory states (eg inflammatory bowel disease)
• Morbid obesity (body mass index [BMI] >40)

Other Risk Factors   

• Increasing age, male sex
• Past medical history or family history of VTE
• Lower limb fracture
• Myocardial infarction (MI) or hospitalization for atrial flutter/fibrillation or heart failure (HF) within the past 3 months 
• Congestive HF or respiratory failure 
• Varicose veins
• Blood transfusion and erythropoiesis-stimulating agents
• Prolonged computer-related "seated immobility syndrome"
• Hereditary risk factors including non-O blood type and heterozygous factor V Leiden gene polymorphism, deficiency of antithrombin, protein C or protein S

Signs and Symptoms

Deep Vein Thrombosis

• Localized tenderness along the distribution of the deep venous system
• Unilateral or entire leg is swollen
• Calf swelling >3 cm compared to asymptomatic leg (measured 10 cm below tibial tuberosity)
• Pitting edema is greater in the symptomatic leg
• Dilated collateral superficial veins (non-varicose)
• Erythema
• Warmth
• Superficial thrombophlebitis with a palpable cord over a superficial vein
• Phlegmasia alba dolens (pale, white/milk leg) - pallor in the edematous legs because the interstitial tissue pressure has exceeded capillary perfusion pressure
  • Due to early compromise of arterial blood flow from extensive iliofemoral DVT
  • Commonly seen in patients with thrombus in the major deep veins
• Phlegmasia cerulea dolens (blue leg) - deoxygenated hemoglobin in the stagnant veins causes a cyanotic hue in the leg
  • Advanced stage seen in severe forms of iliocaval or iliofemoral DVT causing total outflow obstruction with rapid extension of thrombosis into all deep and superficial veins, including collaterals, over a few hours leading to sudden severe ischemic pain, massive limb congestion, cyanosis, loss of function, tachycardia and shock
  • May lead to venous gangrene 

Pulmonary Embolism

• Suspicion of PE is usually raised by the clinical symptoms
  • Clinical findings are non-specific and should not be the only criteria to diagnose PE
• Dyspnea, pleuritic chest pain, syncope and tachypnea (respiratory rate [RR] ≥20/minute) occur in most cases of PE
  • Dyspnea is the most frequent symptom, while tachypnea is its most frequent sign
  • Other signs and symptoms that may be present: Tachycardia (heart rate [HR] >100 beats/minute [bpm]), cough and hemoptysis, fever, diaphoresis, non-pleuritic chest pain, apprehension, rales, increasing pulmonic component of the second heart sound, wheezing, hypotension, hypoxia, cyanosis, pleural rub, raised jugular venous pressure
  • PE should be suspected in cases of postoperative hypoxemia

Pleuritic Chest Pain

• Pleuritic chest pain with or without dyspnea is one of the most frequent presentations of PE
  • May suggest a small embolism located distally near the pleura that also causes pleural irritation

Isolated Dyspnea

• Isolated dyspnea may occur suddenly or progressively (over several weeks)
  • Usually due to a more central PE (not affecting the pleura)
  • May be associated with substernal angina-like chest pain that probably is representing right ventricular (RV) ischemia
  • Worsening dyspnea may be the only symptom that indicates PE in patients with preexisting HF or pulmonary disease

Syncope or Shock

• Syncope or shock is the hallmark sign of central PE and usually results in severe hemodynamic repercussions
  • Signs of hemodynamic compromise and reduced heart flow are also usually present (eg systemic arterial hypotension, oliguria, cold extremities and/or clinical signs of acute right HF)

Massive Pulmonary Embolism

• Dyspnea is usually the prime symptom and systemic arterial hypotension that requires pressor support is the predominant sign
  • Persistent hypotension is defined as a systolic blood pressure (SBP) of <90 mmHg or a pressure drop of at least 40 mmHg from baseline for at least 15 minutes (or needing inotropic support) not caused by new-onset arrhythmia, hypovolemia or sepsis; or absence of pulse, or sustained heart rate <40 bpm with signs or symptoms of shock
• Syncope and altered mentation
• Renal insufficiency, hepatic dysfunction
• Severe respiratory distress or hypoxemia (eg cyanosis)