DVT/Pulmonary Embolism Case File
Eugene C. Toy, MD, Manuel Suarez, MD, FACCP, Terrence H. Liu, MD, MPH
Case 13:
A 43-year-old woman was struck by an automobile while crossing the street. She sustained bi-frontal cerebral contusions, a right tibial plateau fracture, left-sided rib fractures, and a grade 2 splenic laceration. Her brain, chest, and abdominal injuries are being managed nonoperatively. On hospital day 4, the patient develops respiratory distress and is transferred to the ICU. On examination, her blood pressure is 130/80 mm Hg, pulse rate is 110 beats/minute, respirations are 32 breaths/minute, and Glasgow coma scale (GCS) is 15. Her chest radiograph is normal. You are called to evaluate and manage the patient.
⯈What is the most likely diagnosis and risk factors for the patient's respiratory condition?
⯈What are the priorities in this patient's management?
⯈What is the differential diagnosis of the patient's respiratory condition?
ANSWER TO CASE 13:
DVT/Pulmonary Embolism
Summary: A 43-year-old woman with multiple injuries following blunt trauma develops acute respiratory distress requiring transfer to the ICU on hospital day 4.
- Likely diagnosis and risk factors: Pulmonary embolism (PE). Risk factors for venous thromboembolic diseases include stasis (bed rest, immobilization), hypercoaguability (trauma, estrogen), and endothelial injury (trauma). Factors that are associated with increased risk of PE after trauma include age >40, pelvic fracture, lower extremity fracture, shock, spinal cord injury, and brain injury. Variables associated with very high risk for PE are major operative procedure, venous injury, >3 ventilator days, and having 2 or more high-risk factors.
- Priorities in management: The initial priority is to determine adequacy of oxygenation and ventilation. In this case, we must determine her ability to maintain airway patency; she should be placed on high-flow oxygen. The patient's mental status, level of pain, oxygenation, and acid/base status must also be taken into account as we determine whether intubation and/or mechanical ventilation is needed. Given her recent history of major multisystem trauma, she is at high risk for venous thromboembolic complications. A contrast-enhanced helical CT scan and PE protocol should be obtained to confirm or exclude the diagnosis. Documenting the presence of a deep venous thrombosis (DVT)/PE would be important prior to starting anticoagulation, given the bleeding risks associated with her brain and splenic injuries. In a patient with a low risk of bleeding and/or if a long delay is expected before CT scan evaluation can be obtained, immediate anticoagulation therapy is appropriate when a PE is suspected.
- Differential diagnosis: Other possible causes of the respiratory distress include pneumonia, mucus plugging, pneumothorax, acute lung injury, fluid overload, PE, and cardiac ischemia.
ANALYSIS
Objectives
- To learn the risk factors and preventive strategies for DVT/PE in the critical care setting.
- To learn the diagnostic strategies for patients with suspected DVT/PE.
- To learn the treatment strategies for patient with PE.
Considerations
This woman who is a victim with multiple trauma including closed head injury, chest injury, splenic injury, and orthopedic injuries develops acute respiratory distress on hospital day 4. Immediately following the stabilization of the respiratory status, we need to determine the cause responsible for her sudden clinical deterioration.
A chest x-ray, EKG, and serum troponin levels are helpful to identify causes such as primary cardiac process, acute lung injury, and pulmonary infections. A CT angiography of the chest would help determine if pulmonary embolic disease is the cause of her problem. Systemic anticoagulation would be indicated if PE is identified.
Approach To:
Venous Thromboembolism
DEEP VENOUS THROMBOSIS
Deep venous thrombosis refers to clot formation in the deep veins of the body located predominantly in the lower extremities and pelvis. A deep vein is defined as any vein paired with a named artery. The majority of deep venous thrombosis occurs when clots form in the valve cusps of the calf. Once developed, 20% of distal lower extremity (tibial level) DVTs will propagate proximally, resulting in the potential for PE. Rudolph Virchow, a 19th century German physician, first described the triad of circulatory stasis, hypercoaguability, and endothelial injury as factors that contribute to venous thromboembolic diseases. Circulatory stasis refers to stagnation of normal blood flow in the veins. Stagnation of blood allows time for the cross-linking of fibrin polymers and clot formation. Conditions associated with stasis are bed rest, travel (eg, long airline flight), immobility (eg, casting a lower extremity in extension), limb paralysis, spinal cord injury, and obesity.
Under usual circumstances, the coagulation/fibrinolytic systems maintain a delicate balance between thrombogenesis and thrombolysis. A hypercoaguable state implies an imbalance in coagulation homeostasis usually associated with a derangement of a protein or protein receptor involved in the clotting cascade. Clinical examples of hypercoagulable states include malignancy, trauma, pregnancy, inflammatory conditions, and thrombocythemia.
Deficiency of protein S, protein C, and antithrombin III are host conditions producing hypercoagulable states. Protein S and C deficiency leads to an overabundance of Factors Va and VIlla, causing thrombosis. Antithrombin III deficiency results in the activation of factors Xlla, Xla, and IXa leading to thrombosis. Factor V Leiden mutation renders factor V resistant to protein C, and this mutation is the most common genetic cause of hypercoagulability and occurs in 5 % to 8% of the population; heterozygotes with factor V Leiden mutation carry a 7-fold increased risk of thrombosis, and homozygotes have an 80-fold increased risk in comparison to the general population.
Endothelial injury may occur as the result of surgery or injury, which then activates the extrinsic pathway of the coagulation cascade. Activation of the extrinsic pathway leads to the activation of factor VIla, and tissue factor/factor VIIa/calcium complex then activates factor Xa and joins the common pathway of the coagulation cascade.
DVT/PE Prevention (Thromboprophylaxis) Strategies
Prevention strategies should be implemented for all hospitalized patients, especially those with moderate and high risk. Low-risk patients are minor surgery patients and medical patients who are fully mobile, and these individuals are generally not encountered in the ICU setting. Moderate-risk patients include most general surgery, open gynecological surgery, and urological surgery patients, as well as medical patients who are sick or bedridden. High-risk patients include those following hip or knee arthroplasty, hip fracture surgery, major trauma, and spinal cord injury. With this risk-stratification scheme, the estimated DVT risk without prophylaxis is <10% for low-risk patients, 10% to 40% for moderate-risk patients, and 40% to 80% for high-risk patients. The recommended prophylaxis strategy for low-risk group is simply early and aggressive ambulation. The recommendation for the moderate-risk group include low molecular weight heparin (LMWH) , lowdose unfractionated heparin (LDUH) , or fondaparinux; however, if the patient has a high bleeding risk, then mechanical thromboprophylaxis should be implemented instead. For high-risk patient, prophylaxis with LMWH, fondoparinux, or oral vitamin K antagonist (INR 2-3) is recommended, and for high-risk patients with a high bleeding risk, mechanical thromboprophylaxis is recommended.
Diagnosis of DVT
The diagnosis of DVT can be made by a combination of clinical, laboratory, and
imaging data. Imaging studies provide the most sensitive and specific diagnostic
information. The Wells score consists of a list of clinical criteria with a single point
awarded per criteria (Table 13-1) and calculates the clinical probability of the diagnosis
of DVT in hospitalized patients.
- Wells scores >3 is associated with a high probability of DVT.
- Scores from 1 to 2 are associated with a moderate probability.
- Scores of 0 represent a low probability of DVT.
The Wells score has correlated with imaging confirmation of DVT in 76%, 21%, and 10% of patients in the high-, medium-, and low-probability groups, respectively. The Homans sign, or pain in the calf with ankle flexion, is not reliable for DVT diagnosis, as it is only present in one-third of DVT cases.
The fibrin degradation product D-dimer can be elevated with DVT. The most common method of D-dimer quantification is the ELISA test. D-dimer screening
is useful for the evaluation of asymptomatic medical patients and outpatients. In the ICU patient population, D-dimer elevations can occur as a result of medical interventions, thus making it an unreliable test in this population.
The diagnosis of DVT is generally confirmed with imaging studies. Duplex ultra, sound is a noninvasive, reproducible examination that can demonstrate the flow characteristics and compressibility of the popliteal and femoral veins. It should be the first imaging study ordered. Ultrasound of the popliteal and femoral veins has a sensitivity and specificity for proximal DVT of 100% and 99%, respectively. Duplex ultrasound is less sensitive and specific (70% and 60%, respectively) for DVT of the calf. Two negative ultrasounds performed 1 week apart essentially excludes the diagnosis of DVT.
Treatment of DVT
Systemic anticoagulation is the standard treatment of DVT. Anticoagulation options include subcutaneous low molecular weight heparin (SC LMWH ), intravenous unfractionated heparin (IV UFH) , monitored subcutaneous unfractionated heparin (SC UFH ), fixed-dose SC UFH, or subcutaneous fondaparinux. When possible, an oral vitamin K antagonist (warfarin) should be initiated concurrently with heparin or LMWH. When administering IV UFH, a bolus of 80 U/kg should be given, followed by a continuous infusion of 18 U/kg/h titrated to a target PTI > 1.5 times normal. In adults, 150 to 200 U/kg of SC LMWH once a day is as effective as 100 U/kg of SC LMWH twice a day and continuous IV UFH titrated to a PTI > 1.5 times normal. Daily LMWH has the advantage of a stable dose-response curve thus obviating the need for frequent laboratory monitoring. In comparison to a heparin drip, LMWH has the advantages of being associated with a lower risk of heparininduced thrombocytopenia (HIT) and lower cost.
To prevent recurrence, patients with DVT and DVT/PE require an extended period of anticoagulation with either LMWH or warfarin. The duration of anticoagulation therapy depends on the circumstances of clot formation. DVT that occurs after a reversible inciting event ( eg, surgery, trauma, pregnancy) requires a minimum of 3 months treatment. Unprovoked DVT formation in patients with no risk factors for bleeding requires a minimum of 3 months treatment and the possibility of indefinite treatment should be entertained. Isolated distal DVT formation may be treated with 3 months of anticoagulation therapy.
Systemic fibrinolysis is not recommended for DVT treatment. Compared to heparin therapy, systemic fibrinolytic therapy results in increased thrombolysis, lower risk of postphlebitic syndrome; however, this treatment is associated with significantly increased risk of bleeding complications. There is no significant difference in the risk of death or DVT recurrence between systemic fibrinolysis and continuous heparin infusion. Catheter-directed fibrinolysis has had moderate success when used to treat DVT, with total clot dissolution in 31% and partial dissolution in 52% of the treated patients. Catheter-based treatment with fibrinolytics has evolved and may be combined with percutaneous mechanical thrombectomy. Several case series have reported this combination therapy as being 82% to 100% successful and catheter-directed thrombolysis is associated with 1% incidence of PE and no increase in deaths or strokes. Catheter site bleeding is a potential complication
requiring blood transfusions in 4% to 14% of the treated patients. Percutaneous mechanical thrombectomy appears safe, but there is insufficient evidence to support routine use at the present time.
Vena Cava Filters
The indications for inferior vena cava (IVC) filter are summarized in Table 13-2. Although rarely applied, the relative indications for IVC filters are: (1) prophylactic IVC filter placement for trauma patients, and (2) very high-risk patients, for example, immobilized hypercoagulable patients.
The PREPIC study is the only randomized controlled trial to evaluate the efficacy of IVC filter placement for the prevention of PE in patients with proximal DVT. The study found that PE occurred in 1.1 % of patients with an IVC filter and 4.8% of patients without an IVC filter in place. At 2 years, recurrent DVT was found in 20.8% of the IVC filter patients compared with 11.6% of the patients without a filter. At 8-year follow-up, symptomatic PE was found in 6.2% of the IVC filter patients and 15.1 % of patients without a filter. The incidence of post-thrombotic syndrome and death were the same in both groups. The study concluded that IVC filters are only beneficial in high-risk patients and that widespread use of filters is not recommended.
Thromboembolism After Trauma
Factors associated with a high risk of PE after trauma include age >40 years, pelvic fracture, lower extremity fracture, shock, spinal cord injury, and head trauma. High risk variables associated with major operations include venous injury, >3 days on the ventilator, and having 2 or more high-risk factors. The highest risk trauma patients are those with a spinal cord injury, with reported DVT rates of 80% and PE rates of 5%. PE is the most common cause of death in spinal cord injury patients.
The authors of a National Trauma Data Bank study have proposed a thromboprophylaxis strategy for trauma patients at risk for DVT/PE. Patients at high-risk for DVT/PE and without contraindications for heparin should receive prophylactic doses of LMWH. Those patients with a contraindication for heparin should have mechanical compression stockings in place at all times. Those patients at very high risk for DVT/PE without contraindications for heparin should be treated with a prophylactic dose of LMWH combined with mechanical compression. If the very high-risk patient has a contraindication for heparin, mechanical compression stockings should be worn and either serial color-flow Doppler studies to monitor for DVT or a temporary IVC filter should be considered.
PULMONARY EMBOLISM
Most PEs occur when a thrombus breaks free from the endothelial wall, traveling through the right heart, and lodging in the pulmonary artery. PE causes ventilation/perfusion mismatching, increased pulmonary vascular resistance, and cytokinemediated pulmonary vasoconstriction. Symptoms depend on the degree of pulmonary arterial obstruction, severity of the inflammatory response, and the patient's physiological reserve. Most patients have dyspnea (79% of patients in PIOPED II study) , while some patients have hypoxemia and an increased A-a gradient. At times, extravasation of blood into the alveoli can produce pleuritic chest pain, cough, or hemoptysis.
Large PEs can present as acute right heart failure and cardiac arrest. Patients with larger PEs can demonstrate right heart strain. T-wave inversions in lead V1 and V2 may be present on EKG and are 99% specific for PE. Echocardiography is a useful adjunct in the diagnosis of PE, with sensitivity and specificity reported at 51 % and 87%, respectively. Echocardiography has a 97% sensitivity and 98% specificity in patient with passive PEs. CT angiography (CTA) is the diagnostic image of choice, with 82% to 1 00% sensitivity and 89% to 98% specificity. The sensitivity and specificity of CTA are affected by the pretest probability of disease; thus, in the high risk patients, the negative predictive value of CTA is only 60%. For the high-risk patients, the combination of a CTA and CTV (CT venography of the upper thigh and pelvis) helps improve the negative predictive value to 82%.
Empiric anticoagulation should be considered in high-risk patients without significant bleeding risks. Treatment with either unfractionated heparin or LMWH is acceptable, and treatment principles for PE are similar to those for the treatment of DVT. Hemodynamically unstable patients with large central PEs can be considered for catheter-directed therapy such as catheter-directed thrombolytic therapy or catheter-directed mechanical clot disruption therapy.
CLINICAL CASE CORRELATION
- See also Case 8 (Airway Management/Respiratory Failure) , Case 9 (Ventilator Management), Case 10 (Respiratory Weaning) , Case 11 (Asthmatic Exacerbation) , and Case 12 (Noninvasive Methods of Ventilator Support).
COMPREHENSION QUESTIONS
13.1 A 24-year-old woman is brought in by ambulance to the emergency department as a Level l trauma after crashing into a tree at 75 mph. The paramedics found the patient ejected from the automobile, semiconscious with an open left femur fracture. The patient's initial systolic blood pressure in the ER was 80 mm Hg. After a blood transfusion, the patient's mental status improved and her blood pressure increased to 96/40 mm Hg. Upon reviewing the pelvic film, you notice a diastasis of the right sacroiliac joint and pubic symphysis. The patient gives no history of medical conditions. She is currently taking oral contraceptive pills. All of the following are risk factors for venous thromboembolism in this patient except:
A. Age
B. Lower extremity fracture
C. Hypotension
D. Pelvic fractures
E. Oral contraceptive pills
13.2 After placement of a pelvic binder and rapid splinting of the left femur fracture, the patient in Question 13.1 went to the CT scanner and was found to have a 4-cm cerebral contusion in the right frontal lobe, 3 right-sided rib fractures, a grade II splenic laceration, and an extra-peritoneal pelvic hematoma with no active extravasation. All of the following thrombosis prophylaxis measures are indicated except:
A. Using bilateral sequential compression devices
B. Immediately starting prophylactic SC UFH upon arrival in the ICU
C. Using graduated compression stockings
D. Starting SC UFH after 48 hours in the ICU if there is no enlargement of the cerebral contusion
E. Administering low-dose Coumadin
13.3 The patient in question 13.1 is taken to the ICU for continuous monitoring and hourly neurological examinations. The patient develops some pain and swelling of the right thigh. What is the best test to screen for DVT?
A. D-dimers level
B. Platelets
C. CT venography
D. Ultrasound examination
E. Coagulation profile
13.4 By hospital day 4 the patient has been started on LMWH, her pelvis and femur fractures stabilized with external fixation devices, and she has been hemodynamically stable. She has now developed swelling and pain in her right thigh and calf. What is the best diagnostic approach for her at this time?
A. CT angiography
B. CT venography
C. Duplex ultrasonography
D. Echocardiography
E. Venography
13.5 In the absence of contraindications for anticoagulation, the most appropriate therapy for femoral DVT with associated PE is:
A. Inferior vena caval filter
B. SC UFH upon arrival in the ICU
C. SC LMWH 150 to 200 U/d followed by transition to warfarin
D. Unmonitored IV UFH drip followed by transition to warfarin
E. Aspirin 325 mg PO daily
ANSWERS TO QUESTIONS
13.1 A. The patient is at very high risk for DVT/PE because she has 2 or more high risk factors for DVT/PE. Her risk factors are pelvic fractures, a lower extremity fracture, and shock. Oral contraceptive pills contribute to and increase estrogen state, which is also a risk factor for DVT/PE. Her age in this case is not a contributing risk factor, because only age >45 is generally considered a risk factor.
13.2 B. The patient is at very high risk for a DVT/PE given her long bone fracture, pelvic fractures, and hypotension; however, she has multiple contraindications to systemic anticoagulation therapy at this time, and these are intracerebral hemorrhage and splenic injury. In the initial 48 hours, the patient should have graduated compression stockings and sequential compression devices on both lower extremities. The patient should not be started on SC UFH immediately due to the risk of bleeding. If the patient's head injury and splenic injury remain stable, she should be started on prophylactic dosing of SC UFH after 48 hours. Low-dose Coumadin is not indicated as prophylaxis in the trauma patient population.
13.3 D. The bedside ultrasound is the standard for screening for DVT. A CT venography is not an appropriate screening examination for DVT. A platelet count and coagulation profile do not diagnose the presence of DVT. The patient will have elevated D-dimer levels due to continuous clot formation and degradation occurring in the trauma patient. Although screening duplex examinations are done at a number of trauma centers, the 2008 American College of Chest Physicians Evidence-Based Clinical Practice Guidelines specifically recommend against screening studies for asymptomatic patients.
13.4 C. The concern at this time should be DVT involving the proximal veins. This can be diagnosed by CT venography, venography, or duplex sonography. Venography has the disadvantage of being invasive and requiring the administration of intravenous contrast. The CT venography is a study that requires contrast administration; therefore the duplex is the preferred diagnostic study for DVT diagnosis. CT angiography is useful only if the patient has a PE. Echocardiography would not be useful for DVT diagnosis.
13.5 C. The patient should be started on a full anticoagulation regimen starting with an LMWH, monitored IV UFH, fixed-dose SC UFH, or SC fondaparinux. The LMWH is dosed at 150 to 200 U/kg/d or 100 U/kg/twice daily. To initiate a heparin drip, give an 80 U/kg bolus and titrate the PTT to 1.5 times normal starting with 18 U/kg/h. Regardless of which anticoagulation regimen is started, warfarin should be started simultaneously and titrated to an INR of between 2.5 and 3.0. IVC filter would only have a role if the patient develops PE while on appropriate DVT treatment or if anticoagulation is contraindicated.
CLINICAL PEARLS
⯈ DVT prophylaxis is variable depending on the patients' risks for thromboembolism development.
⯈ The combination of CTA and CTV has greater negative predictive value than CTA alone for pulmonary embolism in high-risk patients.
⯈ Dyspnea is the most common presenting symptom in patients with PE.
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