Table 1.
—Structured Clinical Questions
| Issue (Informal Question) | Structured PICO Question |
Methodology | |||
| Population | Intervention | Comparators | Outcome | ||
| Patient with acute DVT of the leg
(2.0-3.0) | |||||
| Initial anticoagulant (2.1) |
Patients with acute DVT of the leg |
Anticoagulation |
No anticoagulation |
Recurrent DVT and PE, major bleeding, mortality, QOL, and
PTS |
RCTs |
| Whether to treat while awaiting the results of the diagnostic
work-up (2.2.1-2.2.3) |
Patients with suspected acute DVT of the leg awaiting the results of
diagnostic tests |
Anticoagulation |
No anticoagulation |
PE, major bleeding, and mortality |
RCTs and cohort studies |
| Whether to treat isolated distal thrombosis (2.3.1-2.3.4) |
Patient with acute isolated distal DVT of the leg |
Anticoagulation |
No anticoagulation |
DVT extension, PE, major bleeding, mortality, QOL, and PTS |
RCTs and cohort studies |
| Timing of initiation of VKA relative to the initiation of parenteral
anticoagulation (2.4) |
Patients with acute DVT of the leg |
Early initiation of VKA |
Delayed initiation of VKA |
DVT extension, PE, major bleeding, mortality, QOL, and PTS |
RCTs and cohort studies |
| Duration of initial anticoagulation (2.4) |
Patients with acute DVT of the leg |
Longer duration |
Shorter duration |
DVT extension, PE, major bleeding, mortality, QOL, and PTS |
RCTs and cohort studies |
| Choice and route of initial anticoagulant (2.5.1, 2.5.2,
2.6) |
Patients with acute DVT of the leg |
UFH IV or SQ |
LMWH, fondaparinux, rivaroxaban |
DVT extension, PE, major bleeding, mortality, QOL, and PTS |
RCTs |
| Setting of initial anticoagulation (2.7) |
Patients with acute DVT of the leg |
In-hospital treatment |
At-home treatment |
DVT extension, PE, major bleeding, mortality, QOL, and PTS |
RCTs |
| Role of thrombolytic and mechanical interventions
(2.9-2.12) |
Patients with acute proximal DVT of the leg |
Catheter directed thrombolysis |
No active thrombus removal or another method of thrombus
removal |
Recurrent DVT and PE, major bleeding, mortality, QOL,
PTS, shorter ICU and hospital stays, and acute
complications |
RCTs and cohort studies |
| Systemic thrombolytic therapy | |||||
| Operative venous thrombectomy | |||||
| Role of IVC filters in addition to anticoagulation
(2.13.1) |
Patients with acute DVT of the leg started on
anticoagulation |
IVC filter |
No IVC filter |
Recurrent DVT and PE, major bleeding, mortality, QOL, PTS, and
complications of procedure |
RCTs |
| Role of IVC filters when anticoagulation is contraindicated
(2.13.2) |
Patients with acute DVT of the leg and a contraindication to
anticoagulation |
IVC filter |
No IVC filter |
Recurrent DVT and PE, major bleeding, mortality, QOL, PTS, and
complications of procedure |
RCTs and cohort studies |
| Role of anticoagulation in patients who initially received an IVC
filter when contraindication to anticoagulation resolves
(2.13.3) |
Patients with acute DVT of the leg who initially received an IVC
filter, now contraindication to anticoagulation resolved |
Anticoagulation in addition to IVC filter |
No anticoagulation in addition to IVC filter |
Recurrent DVT and PE, major bleeding, mortality, QOL, PTS, and
complications of procedure |
RCTs and cohort studies |
| Role of early ambulation (2.14) |
Patients with acute DVT of the leg started on anticoagulant
treatment |
Early ambulation |
Initial bed rest |
Recurrent DVT and PE, major bleeding, mortality, QOL, PTS, and
complications of procedure |
RCTs and cohort studies |
| Long-term anticoagulation therapy (3.0) |
Patients with acute VTE of the leg |
Long-term anticoagulation therapy |
No long-term anticoagulation therapy |
Recurrent DVT and PE, major bleeding, mortality, QOL, and
PTS |
RCTs |
| Duration of long-term anticoagulation (3.1.1- 3.1.5) |
Patients with an acute DVT of the leg |
Longer duration |
Shorter duration |
Recurrent DVT and PE, major bleeding, mortality, QOL, and
PTS |
RCTs |
| Intensity of VKA (3.2) |
Patients with acute DVT of the leg |
INR 2-3 |
Higher or lower INR ranges |
Recurrent DVT and PE, major bleeding, mortality, QOL, and
PTS |
RCTs |
| Choice of long-term anticoagulant (3.3.1, 3.3.2, 3.4) |
Patients with acute DVT of the leg. |
LMWH, dabigatran, rivaroxaban |
VKA |
Recurrent DVT and PE, major bleeding, mortality, QOL, and
PTS |
RCTs |
| Whether to treat an incidentally diagnosed asymptomatic acute DVT of
the leg (3.5) |
Patients with incidentally diagnosed asymptomatic DVT of the
leg |
Anticoagulation |
No anticoagulation |
Recurrent DVT and PE, major bleeding, mortality, QOL, and
PTS |
RCTs |
| Patients with PTS of the leg | |||||
| Role of compression stocking in preventing PTS (4.1) |
Patients with acute DVT of the leg started on anticoagulant
treatment |
Compression stockings |
No compression stockings |
QOL, PTS, and recurrent DVT |
RCTs |
| Role of compression stocking in PTS (4.2.1) |
Patients with PTS of the leg |
Compression stockings |
No compression stockings |
QOL, symptomatic relief, ulceration |
RCTs and cohort studies |
| Role of intermittent pneumatic compression in PTS (4.2.2) |
Patients with PTS of the leg |
Intermittent pneumatic compression |
No intermittent pneumatic compression |
QOL, symptomatic relief, ulceration |
RCTs and cohort studies |
| Role of venoactive medications in PTS (4.3) |
Patients with PTS of the leg |
Venoactive medications |
No venoactive medications |
QOL, PTS, and recurrent DVT |
RCTs and cohort studies |
| Patient with acute PE | |||||
| Initial anticoagulant (5.1) |
Patients with acute PE |
Anticoagulation |
No initial anticoagulation |
Recurrent DVT and PE, major bleeding, mortality, QOL, and
PTS |
RCTs |
| Whether to treat while awaiting the results of the diagnostic
work-up (5.2.1-5.2.3) |
Patients with suspected acute PE awaiting the results of the
diagnostic tests |
Anticoagulation |
No anticoagulation |
Recurrent DVT and PE, major bleeding, mortality, QOL, and
PTS |
RCTs and cohort studies |
| Timing of initiation of VKA relative to the initiation of parenteral
anticoagulation (5.3) |
Patients with acute PE |
Early initiation of VKA |
Delayed initiation of VKA |
Recurrent DVT and PE, major bleeding, mortality, QOL, and
PTS |
RCTs and cohort studies |
| Duration of initial anticoagulation (5.3) |
Patients with acute PE |
Longer duration |
Shorter duration |
Recurrent DVT and PE, major bleeding, mortality, QOL, and
PTS |
RCTs and cohort studies |
| Choice and route of initial anticoagulant (5.4.1, 5.4.2) |
Patients with acute DVT of the leg |
UFH IV or SQ |
LMWH, fondaparinux, and rivaroxaban |
Recurrent DVT and PE, major bleeding, mortality, QOL, and
PTS |
RCTs |
| Setting of initial anticoagulation (5.5) |
Patients with acute PE |
In-hospital treatment |
At-home treatment |
Recurrent DVT and PE, major bleeding, mortality, QOL, and
PTS |
RCTs |
| Thrombolytic therapy in patients with acute PE (5.6.1.1, 5.6.1.2,
5.6.1.3) |
Patients with acute PE |
Thrombolytic therapy |
No thrombolytic therapy |
Recurrent DVT and PE, major bleeding, mortality, QOL, and
PTS |
RCTs |
| Infusion time for thrombolytic therapy (5.6.2.1) |
Patients with acute PE requiring thrombolytic therapy |
Longer infusion time |
Shorter infusion time |
Recurrent DVT and PE, major bleeding, mortality, QOL, and
PTS |
RCTs and cohort studies |
| Venous access for thrombolytic therapy (5.6.2.2) |
Patients with acute PE requiring thrombolytic therapy |
Peripheral vein |
Pulmonary catheter |
Recurrent DVT and PE, major bleeding, mortality, QOL, and
PTS |
RCTs and cohort studies |
| Role of catheter-assisted thrombus removal (5.7) |
Patients with acute PE |
Use of catheter-assisted thrombus removal |
No use of catheter-assisted thrombus removal |
Recurrent DVT and PE, major bleeding, mortality, QOL, and
PTS |
RCTs and cohort studies |
| Role of surgical pulmonary embolectomy (5.8) |
Patients with acute PE |
Surgical pulmonary embolectomy |
No surgical pulmonary embolectomy |
Recurrent DVT and PE, major bleeding, mortality, QOL, and
PTS |
RCTs and cohort studies |
| Role of IVC filter in addition to anticoagulation in patients with
acute PE (5.9.1) |
Patients with acute PE started on anticoagulation |
IVC filter |
No IVC filter |
Recurrent DVT and PE, major bleeding, mortality, QOL, and
PTS |
RCTs and cohort studies |
| Role of IVC filters when anticoagulation is contraindicated
(5.9.2) |
Patients with acute PE and a contraindication to
anticoagulation |
IVC filter |
No IVC filter |
Recurrent DVT and PE, major bleeding, mortality, QOL, and
PTS |
RCTs and cohort studies |
| Role of anticoagulation in patients who initially received an IVC
filter when contraindication to anticoagulation resolves
(5.9.3) |
Patients with acute PE who initially received an IVC filter, now
contraindication to anticoagulation resolved |
Anticoagulation in addition to IVC filter |
No anticoagulation in addition to IVC filter |
Recurrent DVT and PE, major bleeding, mortality, QOL, and
PTS |
RCTs and cohort studies |
| Duration of long-term anticoagulation in patients with acute PE
(6.1-6.4) |
Patients with acute PE |
Longer duration |
Shorter duration |
Recurrent DVT and PE, major bleeding, mortality, QOL, and
PTS |
RCTs and cohort studies |
| Intensity of VKA (6.5) |
Patients with acute PE |
INR 2-3 |
Higher or lower INR range |
Recurrent DVT and PE, major bleeding, mortality, QOL, and
PTS |
RCTs and cohort studies |
| Choice of long-term anticoagulant (6.6, 6.7, 6.8) |
Patients with acute PE |
LMWH, dabigatran, rivaroxaban |
VKA |
Recurrent DVT and PE, major bleeding, mortality, QOL, and
PTS |
RCTs |
| Whether to treat an incidentally diagnosed asymptomatic acute PE
(6.9) |
Patients with incidentally diagnosed asymptomatic PE |
Anticoagulation |
No anticoagulation |
Recurrent DVT and PE, major bleeding, mortality, QOL, and
PTS |
RCTs and cohorts |
| Patient with CTPH | |||||
| Role of oral anticoagulation in CTPH (7.1.1) |
Patients with CTPH |
Oral anticoagulation |
No oral anticoagulation |
Recurrent DVT and PE, major bleeding, mortality, QOL, and
PTS |
RCTs and cohort studies |
| Role of pulmonary thromboendarterectomy in CTPH (7.1.2) |
Patients with CTPH |
Pulmonary thromboendarterectomy |
No pulmonary thromboendarterectomy |
Recurrent DVT and PE, major bleeding, mortality, QOL, and
PTS |
RCTs and cohort studies |
| Patient with SVT | |||||
| Role of anticoagulation in SVT (8.1.1, 8.1.2) |
Patients with SVT |
Anticoagulation |
No anticoagulation or other anticoagulant |
DVT and PE, major bleeding, mortality, QOL, symptomatic relief, and
PTS |
RCTs and cohort studies |
| Patient with acute UEDVT | |||||
| Acute anticoagulation (9.1.1, 9.1.2) |
Patients with UEDVT |
Parenteral anticoagulation |
No anticoagulation |
Recurrent DVT and PE, major bleeding, mortality, QOL, and
PTS |
RCTs and cohort studies |
| Role of thrombolytic therapy (9.2.1, 9.2.2) |
Patients with UEDVT |
Systemic thrombolytic therapy |
No systemic thrombolytic therapy |
Recurrent DVT and PE, major bleeding, mortality, QOL, PTS, shorter
ICU and hospital stays, and acute complications |
RCTs and cohort studies |
| Whether indwelling central venous catheter should be removed
(9.3.1) |
Patients with UEDVT and indwelling central venous catheter |
Removal of indwelling central venous catheter |
No removal of indwelling central venous catheter |
Recurrent DVT and PE, major bleeding, mortality, QOL, PTS, shorter
ICU and hospital stays, and acute complications |
RCTs and cohort studies |
| Duration of long-term anticoagulation (9.3.2-9.3.5) |
Patients with UEDVT and indwelling central venous catheter |
Longer duration |
Shorter duration |
Recurrent DVT and PE, major bleeding, mortality, QOL, PTS, shorter
ICU and hospital stays, and acute complications |
RCTs and cohort studies |
| Prevention of PTS of the arm (9.4) |
Patients with UEDVT |
Compression sleeves or venoactive medications |
No compression sleeves or venoactive medications |
QOL, PTS, and recurrent DVT |
RCTs and cohort studies |
| Treatment of PTS of the arm (9.5.1, 9.5.2) |
Patients with PTS of the arm |
Compression sleeves or venoactive medications |
No compression sleeves or venoactive medications |
QOL, symptomatic relief, and ulceration |
RCTs and cohort studies |
| Patient with thrombosis in unusual
sites | |||||
| Role of anticoagulation in splanchnic vein thrombosis (10.1,
10.2) |
Patients with splanchnic vein thrombosis |
Anticoagulation |
No anticoagulation |
Mortality, bowel ischemia, major bleeding, QOL, and symptomatic
relief |
RCTs and cohort studies |
| Role of anticoagulation in hepatic vein thrombosis (11.1, 11.2) | Patients with hepatic vein thrombosis | Anticoagulation | No anticoagulation | Mortality, liver failure, PE, major bleeding, QOL, and symptomatic relief | RCTs and cohort studies |
CTPH = chronic thromboembolic pulmonary hypertension; INR = international normalized ratio; IVC = inferior vena cava; LMWH = low-molecular-weight heparin, PE = pulmonary embolism; PICO = population, intervention, comparator, outcome; PTS = postthrombotic syndrome, QOL = quality of life; RCT = randomized controlled trial; SVT = superficial vein thrombosis; UEDVT = upper-extremity DVT; UFH = unfractionated heparin, VKA = vitamin K antagonist.