I. VENOUS THROMBOEMBOLISM (VTE)
A. General principles.
1. Includes deep venous thrombosis (DVT), pulmonary embolism (PE), and superficial venous thrombosis (SVT); DVT 65% (90% lower extremity, 10% upper extremity), PE-35%.
2. Epidemiology.
a. Annual incidence varies by age from 1/100,000 in children to 700/100,000 in 80 year olds.
b. Annual incidence varies by racial group from 141/100,000 in African Americans to 104/100,000 in Caucasians, 55/100,000 in Latinos, and 21/100,000 in Asians.
c. Incidence in the intensive care unit (ICU)—2.7% on admission, 9.6% over ICU stay.
3. Etiology: hypercoagulability, stasis, vascular damage (Virchow triad).
b. ICU-specific risk factors: personal/family history of VTE (hazard ratio [HR] 4.0), end-stage renal disease (HR 3.7), platelet transfusion (HR 3.2), vasopressor use (HR 2.8).
c. Upper extremity DVT risk factors—central venous catheter (CVC) or pacemaker wires, intrathoracic tumors.
B. Prevention.
1. Assess all patients at admission for risk factors for VTE and contraindications to prophylaxis (see
Tables 91-1 and
91-4).
2. VTE prophylaxis: pharmacologic and mechanical (see
Tables 91-2 and
91-3); pharmacologic prophylaxis preferred due to greater compliance in routine practice.
3. Dalteparin 5,000 units q24 h superior to unfractionated heparin (UFH) 5,000 units q12 h for prevention of PE in the PROTECT study.
4. Reassess patients’ VTE risk factors and contraindications to prophylaxis often.
5. Graduated compression stockings (GCS): size appropriately before application; check daily for skin complications.
6. CVC-VTE prophylaxis: Low-dose warfarin and prophylactic dose anticoagulants (e.g., enoxaparin 40 mg daily) are ineffective. Dose-adjusted warfarin international normalized ratio (INR 1.5 to 2) reduced the incidence of
CVC-VTE compared to low-dose warfarin in an open randomized clinical trial, but was associated with a trend toward more bleeding complications.
C. Clinical manifestations of VTE.
1. Deep venous thrombosis.
a. Upper extremity DVT: pain and swelling in arms, neck, face, or chest, dysfunction of CVC.
b. Lower extremity DVT: cramping pain, swelling, erythema of leg. Groin swelling indicates pelvic vessel involvement; lower abdominal wall swelling, flank collaterals, and bilateral leg swelling indicate inferior vena cava (IVC) involvement.
2. PE—tachycardia, tachypnea, dyspnea, pleuritic chest pain, hypoxemia, hypotension, syncope/presyncope.
D. Diagnosis of VTE—Wells criteria can be used to assess the likelihood of DVT and PE prior to obtaining diagnostic imaging (see
Tables 91-5 and
91-6).
1. Upper extremity DVT.
a. Duplex ultrasound—imaging study of first choice (97% sensitive, 96% specific); proximal subclavian and brachiocephalic veins difficult to image; duplex ultrasound in stress positions important for diagnosis of thoracic outlet syndrome.
b. Computed tomographic (CT) venography: if duplex negative and suspicion high, CT venography a worthwhile follow-up study; CT venography valuable in documenting intrathoracic tumors resulting in vascular compression. Corrective surgery is essential for the best long-term outcome with thoracic outlet syndrome.
2. Lower extremity DVT.
a. Duplex ultrasound—sensitivity 95%, specificity 98%, calf DVT sensitivity 60% to 80%. Sensitivity also lower for iliac vein and IVC.
b. CT venography recommended if duplex study is negative and iliac, pelvic, or IVC thrombosis is suspected. If an anatomic reason for thrombosis suspected (e.g., May-Thurner syndrome), CT venography essential for establishing the diagnosis.
3. Pulmonary embolism.
a. CT angiography is study of first choice—sensitivity 94%, specificity 94%.
b. Ventilation/perfusion ([V with dot above]/[Q with dot above]) scan in patients with intravenous (IV) contrast allergies and renal insufficiency and in pregnant patients.
4. D-dimer: not recommend for diagnosis of VTE among inpatients (often elevated in hospitalized patients and suppressed in patients receiving anticoagulants).
E. Treatment.
1. Timing of treatment initiation: If diagnostic suspicion is high for VTE and risk benefit is favorable for anticoagulation then anticoagulation should be initiated immediately. If diagnostic suspicion is intermediate, one could delay initiation of anticoagulation as long as 4 hours to allow diagnostic imaging. If diagnostic suspicion is low, then anticoagulation could be held until diagnostic confirmation is possible up to 24 hours. Wells DVT and PE models are available to assess the likelihood of VTE (
Tables 91-5 and
91-6).
2. Acute anticoagulation options (see
Table 91-7).
3. Choice of anticoagulant.
a. Half-life—In patients who may need to have invasive procedures, agents with a shorter half-life may be preferable. Fondaparinux has the longest half-life followed by rivaroxaban, tinzaparin, dalteparin, and enoxaparin, in descending order of half-lives.
b. Reversibility—In patients likely to have invasive procedures or considered at higher risk of bleeding, use of agents with potential for reversal is advised. UFH is 100% reversible with IV protamine, while tinzaparin (86%), dalteparin (74%), and enoxaparin (54%) are protamine reversible to a lesser degree. No antidotes are available for fondaparinux or rivaroxaban (see also
Chapter 90: Antithrombotic Therapy in Critically Ill Patients).
c. Renal insufficiency—reduced doses of enoxaparin recommended for patients with creatinine clearance (CrCl) < 30 mL/minute; other low molecular weight heparins (LMWHs) may accumulate at reduced CrCl. Do not use fondaparinux and rivaroxaban in patients with CrCl < 30 mL/minute.
d. Subcutaneous absorption—impaired in patients on vasopressors; subcutaneous absorption can be impaired; IV UFH may be preferable.
e. Vitamin K antagonists (warfarin) are generally not initiated during acute management until therapeutic anticoagulation with a parenteral agent is achieved.
f. CVC-associated DVT—CVC removal not necessarily required upon initiation of anticoagulation; if no resolution of symptoms after 1 to 2 weeks of therapy, remove CVC.
4. PE risk stratification—the risk of death from PE varies from <1% to almost 60%. Indicators of submassive PE include demonstration of right ventricular overload on echocardiogram or CT or elevations of troponin or pro-brain natriuretic peptide (BNP). A bedside risk assessment tool, the Pulmonary Embolism Severity Index (PESI) score, can be used to determine a patient’s mortality risk (see
Table 91-8).
5. Thrombolytic therapy.
a. Indications: massive PE (hypotension systolic blood pressure [SBP] <90 mm Hg); consider for submassive PE if patient judged to be at high risk for adverse outcomes and low risk for bleeding.
b. PE thrombolytic regimen—tissue plasminogen activator (tPA) 100 mg over 2 hours (10 mg bolus followed by 90 mg over 2 hours).
c. Anticoagulation should be discontinued during the thrombolytic therapy infusion and then restarted once the infusion is complete, and the activated partial thromboplastin time (aPTT) is <80 seconds.
d. Catheter-directed pharmacomechanical thrombolytic therapy (CD-PMT) for DVT: consider for patients at low risk for bleeding who have acute extensive proximal (i.e., iliofemoral) DVT; results are best within the first few weeks after thrombosis.
