38 Venous Thromboembolism Flashcards
1
Q
Epidemiology
- Venous thromboembolism (VTE) consists of two interrelated conditions
- Both of these…
- Incidence
A
- Venous thromboembolism (VTE) consists of two interrelated conditions
- Deep vein thrombosis (DVT)
- Pulmonary embolism (PE)
- Both of these…
- Frequently occur in the absence of any symptoms or signs
- Incidence
- Unknown
- ~5 million episodes of DVT occur annually in the US
- > 10 % (500,000) lead to PE
- > 10 % of (50,000) die each year
2
Q
Risk factors
- Most conditions that predispose to VTE can be linked to at least one of three basic factors
- The risk of VTE increases with…
A
- Most conditions that predispose to VTE can be linked to at least one of three basic factors: “Virchow’s triad”
- Hypercoagulability
- Stasis of blood flow
- Vessel injury
- The risk of VTE increases with…
- The number of predisposing factors
3
Q
Risk factors:
Hypercoagulable states
- Disorders that predispose to blood coagulation may be due either to…
- Primary disorders
- Frequency of primary disorders
A
- Disorders that predispose to blood coagulation may be due either to…
- Inborn abnormalities of the coagulation or fibrinolytic systems (primary)
- Acquired (secondary) conditions
- Primary disorders
- Protein C deficiency
- Protein S deficiency
- Antithrombin III deficiency
- Hyperhomocystinemia
- Plasminogen deficiency
- Frequency of primary disorders
- Occur in a very small percentage of patients with VTE
4
Q
Risk factors:
Hypercoagulable states:
Most common primary disorders
- Most common
- General
- Defect
- Factor V Leiden
- General
- Prevalence
- Risk of VTE
- Second most common
- General
- Defect
A
- Most common
- Inability of activated protein C (APC) to cleave and inactivate the activated form of factor V
- The molecular defect responsible for APC resistance
- A single point mutation in the factor V gene
- Causes glutamine to be substituted for argenine, rendering the factor V
molecule resistant to cleavage by APC
- Factor V Leiden
- The most common primary hypercoagulable disorder
- Prevalence of the factor V Leiden mutation
- Varies among ethnic group
- ~3-5% of caucasians are carriers of the mutation
- Much less common in noncaucasians
- Found in ~20% of patients with DVT
- Varies among ethnic group
- The risk of VTE is increased by 5-10 fold in heterozygous carriers of the factor V Leiden mutation and by up to 80 times in homozygotes
- Second most common
- A genetic variant that increases the plasma prothrombin concentration
- This defect: prothrombin 20210A mutation
- Present in 5-6% of patients with DVT
- Heterozygotes have a 2-5 fold increased risk of developing VTE
5
Q
Risk factors:
Hypercoagulable states:
Conditions that produce an acquired or secondary hypercoagulable state that predisposes to VTE
- Malignancy
- Estrogens
- Pregnancy
- Anti-phospholipid antibodies
A
- Malignancy
- Hypercoagulability is believed to result from procoagulant material released by malignant cells
- The risk of VTE is greatest in patients with adenocarcinomas and appears to increase with tumor burden
- Estrogens
- The risk of VTE increases with estrogen dose
- Patients receiving high-dose estrogens (e.g. for prostate cancer) have the greatest risk
- Pregnancy
- The risk of VTE is increased throughout pregnancy, but is actually greater in the post-partum period
- Anti-phospholipid antibodies
- Includes the “lupus anticoagulant” and anticardiolipin antibodies associated with a variety of disorders
6
Q
Risk factors:
Venous stasis:
Most important conditions leading to stasis of blood in the venous system that predispose to VTE
- Surgery
- Lower extremity paralysis
- Immobilization
A
- Surgery
- Orthopedic procedures on the legs, especially those involving the knee and hip, are accompanied by a very high risk of VTE
- In the absence of prophylactic therapy, the incidence of DVT and PE is approximately 50% and 5%, respectively
- Other major surgical procedures including abdominal, pelvic, thoracic, and neurosurgery also carry a significant risk of VTE
- Lower extremity paralysis
- Any disorder leading to paralysis of the legs significantly increases the risk of VTE
- Patients with acute spinal cord injury are at particularly high risk, especially in the first 2-4 weeks following injury
- Immobilization
- This category includes any condition that decreases the use of the legs, such as bed rest, fracture of the pelvis or femur, and immobilization in a cast
- The risk of VTE increases with the degree and duration of immobility
7
Q
Risk factors:
Vessel injury
A
- Risk factors in this category include orthopedic and vascular surgery as well as non-surgical vessel trauma
- These factors also obviously predispose to venous stasis
8
Q
Risk factors:
Miscellaneous factors
- Prior thromboembolism
- Age
A
- Prior thromboembolism
- Patients with previous VTE are much more likely to develop recurrent disease, especially when other risk factors are present
- Age
- The risk of VTE increases exponentially with increasing age above 40 years
- That is, the risk of VTE approximately doubles with each decade after age 40
9
Q
Pulmonary embolism
- Occurs when…
- The consequences of PE depend primarily on…
- The morbidity and mortality associated with PE result from…
A
- Occurs when…
- Thrombi in the deep venous system dislodge, flow through the central veins, and impact in the pulmonary arterial circulation
- The consequences of PE depend primarily on…
- The size of the embolus (i.e. on the degree to which the pulmonary vascular bed is obstructed)
- The extent of underlying pulmonary disease
- The morbidity and mortality associated with PE result from…
- Disturbances in both gas exchange and hemodynamics
10
Q
Pulmonary embolism:
Altered gas exchange
- Pulmonary emboli…
- High V/Q regions…
- Low V/Q regions…
- Intra-pulmonary shunting…
A
- Pulmonary emboli…
- Occlude a portion of the pulmonary vascular bed
- This prevents blood from reaching some ventilated alveoli and at the same time increases blood flow to normally ventilated areas
- Pulmonary embolism, therefore, produces both abnormally high and low ventilation-perfusion ratios
- High V/Q regions…
- Increase alveolar dead space and the amount of ventilation required to maintain a normal PaCO2
- Low V/Q regions…
- Lead to arterial hypoxemia and to an increase in PA-aO2
- Intra-pulmonary shunting…
- Does not occur, although acute right ventricular failure may cause a right to left intracardiac shunt through a patent foramen ovale
11
Q
Pulmonary embolism:
Altered hemodynamics
- By reducing the cross-sectional area of the pulmonary vascular bed, PE causes…
- If excessive, this leads to…
- RV dysfunction may reduce left ventricular output by two mechanisms
- Significant decreases in cardiac output can lead to…
A
- By reducing the cross-sectional area of the pulmonary vascular bed, PE causes…
- An increase in pulmonary vascular resistance, which, in turn, increases right ventricular (RV) afterload
- If excessive, this abrupt increase in afterload leads to…
- RV dysfunction, both directly and by inducing RV ischemia
- RV dysfunction may reduce left ventricular output by two mechanisms
- (1) Impaired RV systolic function decreases the amount of blood pumped to the left ventricle
- (2) As the RV fails, it dilates, and the intraventricular septum shifts toward the LV
- This decreases the size and compliance of the LV and further reduces LV preload and cardiac output
- Significant decreases in cardiac output can lead to…
- Systemic hypotension and shock, which may further impair coronary perfusion and right and left ventricular function
12
Q
Pulmonary embolism:
Source of pulmonary emboli
- The majority of clinically significant PEs arise from…
- Other potential sources of emboli
A
- The majority of clinically significant PEs arise from…
- The proximal deep veins of the legs (i.e. the popliteal and femoral veins)
- Other potential sources of emboli
- The pelvic veins
- Calf veins
- The internal jugular and subclavian veins (especially in the presence of a central venous catheter)
13
Q
Pulmonary embolism:
Clinical presentation
- Symptomatic patients with PE most commonly present with…
- The relationship between clinical suspicion and the likelihood of PE
- Although most patients present with acute symptoms and signs, an unknown (but presumably small) percentage of patients with PE develop…
A
- Symptomatic patients with PE most commonly present with…
- The acute onset of dyspnea and tachypnea
- Common features of most pulmonary diseases
- For this reason, clinical assessment alone is unreliable in distinguishing patients with and without PE
- The acute onset of dyspnea and tachypnea
- The relationship between clinical suspicion and the likelihood of PE
- High – 68%
- Intermediate – 30%
- Low – 9%
- Although most patients present with acute symptoms and signs, an unknown (but presumably small) percentage of patients with PE develop…
- Chronic, progressive dyspnea due to pulmonary hypertension
- This is believed to result from progressive occlusion of the pulmonary vascular bed from recurrent, often asymptomatic pulmonary emboli that for unknown reasons are not cleared by endogenous fibrinolysis
14
Q
Pulmonary embolism:
Diagnostic studies:
D-dimer
- During clot formation,…
- During endogenous fibrinolysis,…
- D-dimers
- D-dimer assays
A
- During clot formation,…
- Thrombin cleaves fibrinogen to form fibrin molecules, which cross-link in a region referred to as the “D-domain”
- During endogenous fibrinolysis,…
- Plasmin degrades cross-linked fibrin to yield covalently bonded D-Page domains from two adjacent fibrin molecules
- These fragments are referred to as D-dimers
- D-dimers
- Unlike other fibrin or fibrinogen degradation products, D-dimers are specific for the lysis of cross-linked fibrin and are increased by any condition in which coagulation and fibrinolysis occur
- D-dimer assays
- A means of diagnosing and excluding VTE
- Have a very high negative predictive value (i.e. very few patients with a negative test have PE)
- A negative result can effectively rule out VTE
- A positive result, on the other hand, is not helpful in making the diagnosis because of a very low positive predictive value
15
Q
Pulmonary embolism:
Diagnostic studies:
CT angiography
- Modern CT scanning is performed by…
- This technique allows…
- Pulmonary emboli appear as…
A
- Modern CT scanning is performed by…
- Scanning continuously as the patient is rapidly advanced through the machine (spiral or helical CT)
- This technique allows…
- The pulmonary arteries to be well-visualized when intravenous contrast is rapidly injected during the scan
- Pulmonary emboli appear as…
- Filling defects in the opacified pulmonary arteries
16
Q
Pulmonary embolism:
Diagnostic studies:
Venous ultrasonography
- What venous ultrasound detects
- The major criterion for diagnosing DVT with ultrasound
- Normally, when imaged by ultrasound, the lumen of a deep vein…
- When a thrombus is present in the vein,…
A
- What venous ultrasound detects
- Since most clinically significant PE originate from thrombi in the proximal deep veins of the legs, finding or excluding a DVT would aid in the diagnosis of PE
- The major criterion for diagnosing DVT with ultrasound
- The loss of compressibility of the vein
- Normally, when imaged by ultrasound, the lumen of a deep vein…
- Will completely disappear when pressure is applied by the ultrasound probe
- When a thrombus is present in the vein,…
- This does not occur
17
Q
Pulmonary embolism:
Diagnostic studies:
Venous ultrasonography
- Accuracy
- Why the usefulness of ultrasound in the evaluation of patients with suspected PE is limited
- The absence of DVT…
- A positive venous ultrasound…
A
- Accuracy
- Ultrasound is very accurate at detecting DVT in symptomatic patients
- Sensitivity and specificity exceed 90%
- Why the usefulness of ultrasound in the evaluation of patients with suspected PE is limited
- ~50% of patients with PE have no evidence of leg DVT by venous ultrasound
- The majority of patients with DVT do not have PE
- The absence of DVT…
- Does not exclude a PE
- A positive venous ultrasound…
- Is helpful though, not because it confirms the presence of PE, but because the therapy of DVT and PE are identical in most cases
18
Q
Pulmonary embolism:
Therapy:
Anticoagulation
- Anticoagulation
- Heparin
- Acts by…
- Discontinued only after…
- Warfarin
- Acts…
- Given…
A
- Anticoagulation
- The standard therapy for VTE
- Heparin and warfarin sodium (Coumadin)
- Heparin
- Acts by enhancing the effect of antithrombin III so that it more efficiently combines with and inactivates a number of clotting factors, most notably factor II (thrombin), factor X, and factor IX
- Discontinued only after therapeutic anticoagulation has been achieved with warfarin
- Warfarin
- Acts in the liver by inhibiting the synthesis of the vitamin K-dependent clotting factors II, VII, IX, and X
- Given orally once a day, and is started simultaneously with heparin
- Unless a contraindication to anticoagulation exists, therapy is initiated with…
- An intravenous bolus of heparin followed by a continuous intravenous infusion
20
Q
Pulmonary embolism:
Therapy:
Inferior vena cava filters
- Several types of wire mesh screens can be…
- The three major indications for filter placement
A
- Several types of wire mesh screens can be…
- Placed percutaneously into the inferior vena cava to prevent venous thrombi in the legs and pelvis from embolizing to the lungs
- The three major indications for filter placement
- Recurrent PE despite adequate anticoagulant therapy
- Unability to use anticoagulant therapy (e.g. bleeding)
- High risk from recurrent PE
