A deep vein thrombosis is the formation of a thrombus (blood clot) within deep-lying veins in the leg.
Causes
The cause is usually a combination of slow blood flow through one part of the body (such as when sitting for long periods or when the tissues are compressed, as occurs in long-haul aircraft flights) and an increase in the clotting tendency of the blood, which occurs in dehydration, after surgery or injury, during pregnancy, in some inherited conditions (see thrombophilia), and in women taking oral contraceptives. Deep vein thrombosis may also be due to polycythaemia (increased numbers of red cells in the blood). Deep vein thrombosis is common in people with heart failure and those who have had a stroke; it also commonly occurs in people who have been bedridden.
Symptoms
Clots in the leg veins may cause pain, tenderness, swelling, discoloration, and ulceration of the skin, but they can be symptomless. A deep vein thrombosis is not necessarily serious in itself, but part of the clot may break off and travel in the bloodstream to the lungs. This is known as a pulmonary embolism.
Diagnosis and treatment
A diagnosis is made by doppler ultrasound scanning. Treatment depends on the site and extent of the clots. Small clots may not need treatment if they are confined to the calf and the patient is mobile. Otherwise, anticoagulant drugs or thrombolytic drugs are given. If there is a high risk of pulmonary embolism, thrombectomy (surgical removal of the clot) may be performed.
Prevention
The risk of deep vein thrombosis during long-haul flights can be reduced by wearing elastic stockings, moving the legs and feet around frequently, and drinking plenty of nonalcoholic fluids.
Deep vein thrombosis in more detail - technical
Essentials
Deep venous thrombosis (DVT) is diagnosed in 1 to 2% of hospitalized patients, but is often silent and is found much more frequently at autopsy. Patients typically complain of pain and/or swelling of the leg, but often the diagnosis will be considered only when the physician detects unilateral leg swelling.
Investigation—given the sinister nature of untreated DVT, it is important to confirm or refute the diagnosis with appropriate investigations whenever clinical suspicion is aroused, unless the general condition of the patient makes this inappropriate. Management algorithms have been developed to guide strategy for investigation. These typically use scoring systems to stratify the clinical probability that the particular patient has a DVT (or pulmonary embolism). Those with a low clinical probability proceed to D-dimer testing, with further investigation not pursued if this is negative. Patients with either a high clinical probability, or a low clinical probability but elevated D-dimer, proceed to tests for the presence of thrombus in the leg veins, typically by ultrasonography.
Management—a first episode of symptomatic isolated calf venous thrombosis, diagnosed by noninvasive testing, should be treated with anticoagulation for 3 months. Longer duration of treatment may be recommended for those whose thrombosis occurred in the absence of a reversible risk factor or in those with a thrombophilic condition. Indefinite treatment is recommended for those with two or more episodes of thromboembolism. Treatment is initiated with heparin (low molecular weight or unfractionated) for ≥ 5 days and warfarin (or other vitamin K antagonist), with the heparin stopped when the international normalized ratio (INR) is greater than 2.0 or ≥ 24 h.
DVT carries extensive morbidity irrespective of pulmonary embolism: severe postphlebitic syndrome occurs in 9% of patients by 5 years.
Deep venous thombosis (DVT) and pulmonary embolism (PE) are sometimes described together using the term ‘thromboembolism’. PE is a complication of DVT, with thrombi in 80% or more of cases originating in the legs. Management strategies have been developed that are based on the diagnosis of either PE or DVT, provided the patient has good respiratory reserve. Treatment with anticoagulants is the same for both, although some physicians believe that patients can be managed better if it is known whether acute PE is present, even if a diagnosis of DVT is already established.
The frequency of fatal PE in patients with untreated DVT has diminished as diagnostic tests have made it possible to diagnose DVT before it becomes extensive. In 1955, prior to the use of sensitive noninvasive tests for the early detection of DVT, the risk of fatal PE in untreated patients with clinically apparent DVT was 37%. Based on a diagnosis by radioactive fibrinogen scintiscans, the risk of fatal PE in patients with untreated DVT, most of which were subclinical, was about 5%.
Early diagnosis has also reduced the risk of death from PE. In the early 1960s the mortality in untreated patients with acute PE, diagnosed on the basis of clinical features, was 26 to 37%, and an additional 36% died of recurrent PE. In 1998, the estimated case fatality rate from acute PE was 7.7%. In recent years, among patients with mild PE who inadvertently escaped treatment, the mortality was 4% to 5%.
Deep venous thrombosis in detail - technical
Incidence and pathology
In 2006, DVT was diagnosed in 1.5% of hospitalized patients ≥ aged 18 years in the United States of America. This represented 208 patients / 100,000 adult population. The condition is often silent: among patients with DVT detected by screening with 125I-fibrinogen scans, clinical evidence was present in 49%. Proximal DVT was found at autopsy in 22% of patients who died of various causes in a tertiary care hospital.
Thrombosis of the leg veins usually occurs without inflammation. Inflammation of the walls of the veins, when it occurs, is usually secondary to the thrombosis. No clear evidence indicates that inflammation of the veins prevents embolization, or that embolization is more frequent in those patients with thrombi not associated with venous inflammation. The valve pockets are a frequent site of origin of thrombi.
Clinical features
Patients may complain of pain or swelling of the leg, but physical examination remains the means by which attention is usually drawn to the potential diagnosis of DVT. DVT sometimes, but not always, leads to swelling of the leg. If restricted to the popliteal and calf veins, swelling is confined to below the knee, but if thrombosis involves the femoral and pelvic veins (or inferior vena cava), then swelling of the thigh is also expected. A difference of circumference of the calves of 1.0 cm or more, measured 10 cm below the tibial tuberosity, is abnormal. It is important to repeat the measurement of circumference of the calves and thighs at frequent intervals: proximal extension of a thrombus is likely to cause increased swelling, and to allow repeated measurements to be made from a fixed point it is good practice for the position of the first measurement to be marked indelibly on the patient’s skin.
Homans’ sign is positive when active and/or passive dorsiflexion of the foot associated with any of the following: (1) pain, (2) incomplete dorsiflexion (with equal pressure applied) to prevent pain, or (3) flexion of the knee to release tension in the posterior muscles with dorsiflexion. This sign was present in 44% of patients with DVT of the lower leg, and in 60% of patients with femoral venous thrombosis.
The elicitation of pain with inflation of a blood pressure cuff around the calf to 60 to 150 mm Hg has been recommended as a test for DVT. However, this test has not been shown to be more helpful than the assessment of direct tenderness or leg circumference.
In one study, the sensitivity of oedema, erythema, calf tenderness, palpable cord, or Homans’ sign alone, or 1 cm or more calf asymmetry alone was 55 to 80%, but the specificity was only 49%. The combination of one of these signs plus 1 cm or more ipsilateral calf asymmetry increased the specificity to 87%, but decreased the sensitivity to 15 to 33%. The specificity increased to 91% with one of these signs in combination with 2 cm or more calf asymmetry. Only 3 to 10% of patients had one or more qualitative signs plus 3 cm or more ipsilateral calf asymmetry: in these the specificity for DVT was 96%.
Other clinical features of DVT, whose sensitivity and specificity have not been tested, include increased temperature on the affected side, cyanotic discoloration of the limb, and persistent engorgement of superficial veins. Superficial varicose veins almost always empty when the patient lies down: if they remain engorged, this suggests problems with drainage through the deep veins. In very rare cases, tense venous oedema can cause arterial compression and venous gangrene.
Differential diagnosis
The clinical diagnosis of DVT is not always straightforward. Many of the findings described above can also be found in those with muscular strains and bruising, ruptured Baker’s cyst or plantaris tendon, superficial thrombophlebitis, cellulitis, and other traumatic conditions. The presence of bruising near either malleolus suggests ruptured Baker’s cyst or other cause of calf haematoma.
Given the sinister nature of untreated DVT it is important to confirm or refute (so far as is possible) the diagnosis with appropriate investigations whenever clinical suspicion is aroused, unless the general condition of the patient makes this inappropriate.
Investigation
Detection of evidence of thrombus within the circulation: D-dimer
D-dimer is a specific degradation product released into the circulation by endogenous fibrinolysis of a cross-linked fibrin clot. A D-dimer measured by enzyme-linked immunosorbent assay (ELISA) below a cut-off of 300 to 540 ng/ml (the values differ slightly from one study to another) make the diagnosis of DVT (or PE) unlikely. However, a concentration of D-dimer above the cut-off level is not useful for making a positive diagnosis because of the large number of false positive tests.
Conventional ELISA assays are cumbersome and not suited for emergency use, which limited the practical utility of D-dimer measurements until the development of rapid ELISA assays. These provide the best balance of sensitivity and specificity among the various assays for the safe diagnostic handling of patients with suspected DVT and PE.
Detection of the physical presence of thrombus in leg veins
The ‘gold standard’ is contrast venography, but this can be unpleasant for patients, time consuming for radiology departments, and expensive. This has driven the search for acceptable noninvasive methods of diagnosis and contrast venography is now rarely performed, except as part of research protocols.
In most centres contrast venography has been replaced by B-mode ultrasonography as the preferred first line diagnostic technique. Among patients with DVT proven by contrast venography, B-mode ultrasonography using compression showed a 95% sensitivity in symptomatic patients. In asymptomatic patients who were evaluated because of a high risk of DVT, venous compression ultrasound showed a sensitivity of only 67%. Regarding veins of the calves, venous compression ultrasound was 93% sensitive in symptomatic patients, but only 26% sensitive in asymptomatic high-risk patients subsequently found to have DVT. In all instances, specificity was 97 to 99%.
Venous-phase contrast-enhanced spiral CT is useful for imaging the veins of the pelvis and thighs, particularly in combination with spiral CT pulmonary angiograms. This offers a comprehensive study for thromboembolism, but increases exposure to ionizing radiation. Whether CT pulmonary angiography should routinely be accompanied by CT venography is a matter of controversy. Among patients with suspected PE who were evaluated by 64-detector CT, 10.8% were shown to have PE by CT angiography and an additional 1.3% had venous thromboembolism based on a positive CT venogram with a negative CT angiogram. A 1.3% yield would seem poorly cost effective, however—among the patients shown to have venous thromboembolism, 11% were diagnosed only by CT venography—a proportion that some would consider sufficiently high to merit consideration of its use.
Gadolinium-enhanced magnetic resonance venography following an intravenous injection, was sensitive for DVT in the veins of the thighs and pelvis but often technically inadequate. Specificity in all regions was 95 to 100%. Usage is restricted by cost, availability and risk of nephrogenic systemic fibrosis/nephrogenic fibrosing dermopathy in patients with poor renal function.
Fibrinogen uptake radionuclide scanning was used extensively in the 1960s. It is more sensitive for DVT in the calves than in the thighs, meaning that its value is limited because of the greater risk of PE with DVT in the thighs than in the calves.
Strategy for diagnosis
Management algorithms have been developed to identify patients at low risk of DVT or PE who can be spared extensive testing. These algorithms typically use scoring systems to stratify the clinical probability that the particular patient has a DVT (or PE) and then proceed to D-dimer testing of those with low probability. Patients with a low clinical probability and a negative D-dimer test should not be investigated further for thromboembolic disease. Patients with either a high clinical probability, or a low clinical probability but elevated D-dimer, proceed to tests for the presence of thrombus in the leg veins, typically by ultrasonography. An example of a pretest scoring system and management algorithm is shown in Table 1
| Table 1 Pre-test clinical probability scoring system and care pathway for the patient with suspected deep venous thrombosis |
|---|
| (a) Pre-test probability score | |||
| Criteria | Score | ||
| Active cancer | +1 | ||
| Paralysis, plaster cast | +1 | ||
| Bed rest >3 days, surgery within 4 weeks | +1 | ||
| Tenderness along veins | +1 | ||
| Entire leg swollen | +1 | ||
| Calf swollen >3 cm | +1 | ||
| Pitting oedema | +1 | ||
| Collateral veins | +1 | ||
| Alternative diagnosis likely | –2 | ||
| (b) Pre-test probability | |||
| Low | 0 | ||
| Moderate | 1 or 2 | ||
| High | 3 or more | ||
| (c) Management algorithm | |||
| Pre-test probability score | Action | Result | Further action |
| 0 or 1 | Perform D-dimer | Negative | No further investigation |
| Positive | Perform ultrasonography | ||
| 2 or more | Do not perform D-dimer | ||
| Perform ultrasonography | Negative | Withhold treatment and repeat ultrasonography in 10–14 days. If serial ultrasonography is negative, pulmonary embolism rarely occurs. | |
| Positive | Diagnosis of venous thrombosis established | ||
|
Notes 1. Pre-test probability score from Wells et al. (1997). 2. This management algorithm is typical of many used, but further prospective evaluation is warranted. 3. If the physician’s judgement is that deep venous thrombosis is very likely in a particular case, then they should proceed to investigations directed at detecting thrombus in leg veins whatever the scoring algorithm would suggest. If the result of ultrasonography is negative, and repeat ultrasonography in 10–14 days is also negative, pulmonary embolism rarely occurs. 4. All patients who are discharged with ‘deep venous thrombosis excluded’ should be given written information describing how they can be reassessed if symptoms worsen or fail to settle over the next few days. |
Prevention of DVT and PE
The prevention of DVT is critical in the prevention of PE. Risk factors for DVT are almost certainly the same as those for PE. Recommendations for the prevention of DVT are shown in Tables 2, 3, 4, 5, 6 and 7. Despite recommendations for the prevention of DVT in hospitalized patients, an increase in secondary DVT in patients hospitalized in the United States of America from 1991 through 2006 suggests that efforts to prevent DVT in high-risk patients are inadequate. In the UK, recognition of such inadequacy has led commissioners of health care to mandate use of a risk scoring tool for venous thromboembolism in all patients admitted to hospital, with the possibility of financial penalties for those that do not achieve a very high rate of compliance.
| Table 2 Recommendations for prevention of deep venous thrombosis in patients undergoing general, vascular, gynecological, urological and laparoscopic surgery |
|---|
| Indication | Recommendation |
| General surgery | |
| Low risk patients (minor procedure, age <40 years, no additional risk factors) | Early and frequent mobilization |
| Moderate-risk (age 40–60 years with no additional risk factors, or major surgery and age <40 years with no additional risk factors). | Unfractionated heparin 5000 U two or three times daily or LMWH once daily or fondaparinux 2.5mg daily |
| Higher-risk general surgery (nonmajor surgery and age >60 years or have additional risk factors, or major surgery and age >40 years or have additional risk factors) | Unfractionated heparin 5000 U three times daily or LMWH or fondaparinux 2.5mg daily |
| High-risk general surgery (multiple risk factors). | Unfractionated heparin 5000 U three times daily or LMWH or fondaparinux 2.5mg daily combined with graduated compression stockings and/or intermittent pneumatic compression |
| High risk of bleeding | Properly fitted compression stockings or intermittent pneumatic compression |
| Selected high-risk general surgery patients, including major cancer surgery | Post-hospital discharge prophylaxis with LMWH up to 28 days |
| If no additional risk factors | Early and frequent mobilization |
| Vascular surgery | |
| If additional risk factors | Low dose unfractionated heparin or LMWH or fondaparinux |
| Gynecological surgery | |
| Low-risk patients, minor procedures, laparoscopic procedures | Early and frequent mobilization |
| Laparoscopic procedures, additional risk factors present | Unfractionated heparin or LMWH, or intermittent pneumatic compression, or graduated compression stockings or combinations |
| Major gynecological surgery for benign disease, without additional risk factors | Unfractionated heparin or LMWH or intermittent pneumatic compression started just before surgery and used continuously whilst the patient is not ambulating or combination, or fondaparinux |
| Extensive surgery for malignancy, or patients with additional risk factors | Unfractionated heparin 5000 U three times daily or LMWH or intermittent pneumatic compression. All continued until discharge from hospital. Alternatively a combination of LMWH or low dose unfractionated heparin or fondaparinux plus mechanical thromboprophylaxis with graduated compression stockings or intermittent pneumatic compression continued until hospital discharge |
| Particularly high risk, including cancer surgery or previous PE or DVT | Continue prophylaxis up to 28 days after hospital discharge |
| Urological surgery | |
| Transurethral or other low risk | Early and frequent mobilization |
| Major open procedures | Unfractionated heparin 5000 U twice or three times daily or LMWH, or fondaparinux.. Alternatives include intermittent pneumatic compression and/or graduated compression stockings, LMWH, fondaparinux or combination |
| Actively bleeding or very high risk for bleeding |
|
| Laparoscopic surgery | |
| No additional risk factors | Early and frequent mobilization |
| Additional risk factors | Low dose unfractionated heparin or fondaparinux or LMWH, or intermittent pneumatic compression, or graduated compression stockings or combination |
|
LMWH, low molecular weight heparin. Adapted from Geerts WH, et al. (2008). Prevention of venous thromboembolism: the Eighth ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 133(Suppl): 381S–453S. |
| Table 3 Recommendations for prevention of DVT during long-distance air travel |
|---|
| Long distance travel (flights of >8 h duration) | Avoid constrictive clothing around the lower extremities or waist; maintain hydration; frequent calf muscle contraction |
| Additional risk factors | Below-knee graduated compression stockings providing 15–30 mmHg of pressure at ankle, or single dose of LMWH prior to departure |
|
LMWH, low molecular weight heparin. Adapted from Geerts WH, et al. (2008). Prevention of venous thromboembolism: the Eighth ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 133(Suppl): 381S–453S. |
|
Table 4 Recommendations for prevention of DVT in patients undergoing orthopaedic surgery |
|---|
| Surgical procedure | Recommendation |
| Elective total hip replacement | LMWH (at a usual high-risk dose, started 12 h before surgery or 12–24 h after surgery, or 4–6 h after surgery at half the usual high-risk dose and then increasing to the usual high-risk dose the following day) for 10–35 days |
|
|
|
|
| Elective total knee arthroplasty | As with total hip replacement, although intermittent pneumatic compression is an alternative |
| Hip fracture surgery | Fondaparinux or LMWH at usual high-risk dose or vitamin K antagonist (INR 2.0–3.0) or low dose unfractionated heparin for 10–35 days |
| If surgery is delayed—low dose unfractionated heparin or LMWH while waiting | |
| Mechanical prophylaxis if high risk of bleeding |
|
INR, international normalized ratio; LMWH, low molecular weight heparin. Adapted from Geerts WH, et al. (2008). Prevention of venous thromboembolism: the Eighth ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 133(Suppl): 381S–453S. |
| Table 5 Recommendations for prevention of DVT in patients undergoing neurosurgery |
|---|
| Surgical procedure | Recommendation |
| Elective spine surgery | |
|
|
| Neurosurgery | |
| No additional risk factors |
|
| High risk | Graduated compression stockings and/or intermittent pneumatic compression) and low dose unfractionated heparin or LMWH |
|
LMWH, low molecular weight heparin. Adapted from Geerts WH.,et al. (2008). Prevention of venous thromboembolism: the Eighth ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 133(Suppl): 381S–453S. |
| Table 6 Recommendations for prevention of DVT in patients following trauma, acute spinal cord injury and burns |
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| Indication | Recommendation |
| Trauma |
|
| Acute spinal cord injury |
|
|
|
|
INR, international normalized ratio; LMWH, low molecular weight heparin. Adapted from Geerts WH, et al. (2008). Prevention of venous thromboembolism: the Eighth ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 133(Suppl): 381S–453S. |
| Table 7 Recommendations for prevention of DVT in patients hospitalized with medical conditions and in critical units |
|---|
| Medical conditions in hospital | Recommendation |
|
|
| Critical care | |
| Moderate risk (medically ill or postoperative) | Low dose unfractionated heparin or LMWH |
| Higher risk (major trauma or orthopaedic surgery) | LMWH |
| High risk of bleeding | Compression stockings and/or intermittent pneumatic compression |
|
LMWH, low molecular weight heparin. Adapted from Geerts WH, et al. (2008). Prevention of venous thromboembolism: the Eighth ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 133(Suppl): 381S–453S. |
Cough was common (37% and 34% in PIOPED and PIOPED II) among patients with PE and no pre-existing cardiopulmonary disease. This was nonproductive or productive of bloody (typically blood-streaked, but it can be pure blood or blood-tinged) or purulent (5% of cases) sputum.
Treatment
For the details of treatment of DVT see Table 8.
| Table 8 Recommendations for treatment of DVT and/or pulmonary thromboembolism |
|---|
| Condition | Treatment |
| High clinical suspicion of DVT or PE | Give anticoagulants while awaiting outcome of diagnostic tests |
| Confirmed DVT or PE |
|
| Nonmassive PE | LMWH preferred over unfractionated heparin |
| Massive PE, hemodynamically unstable | Systemic thrombolytic therapy, short infusion time preferred |
| Massive PE, highly compromised patients unable to receive thrombolytic therapy or whose critical status does not allow sufficient time to infuse thrombolytic therapy | Catheter extraction or fragmentation or pulmonary embolectomy |
| Extensive DVT | Catheter-directed thrombolysis: followed by balloon angioplasty and stents or systemic thrombolytic therapy. Thrombus fragmentation and/or aspiration if expertise and resources are available. |
| PE or DVT and contraindication to anticoagulants or recurrent thromboembolism despite adequate anticoagulation | Inferior vena cava filter |
| Condition | Duration of treatment |
| First episode DVT or PE, reversible risk factor | Vitamin K antagonist for 3 months |
| First episode, idiopathic DVT or PE | Vitamin K antagonist for 3 months; then consider indefinite treatment (INR 2.0–3.0) |
| DVT or PE and cancer | LMWH for 3-6 months followed by indefinite duration of anticoagulation or until cancer is resolved. |
| Two or more episodes DVT or PE | Indefinite treatment |
|
aPTT =activated partial thromboplastin, LMWH, low molecular weight heparin. Adapted from Kearon C, et al. (2008). Antithrombotic Therapy for Venous Thromboembolic Disease: the Eighth ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 133(Suppl): 454S-545S |
Complications
DVT itself carries extensive morbidity irrespective of PE. Severe postphlebitic syndrome (venous ulcer or combinations of pain, cramps, heaviness, pruritus, paresthesia, pretibial oedema, induration, hyperpigmentation, venous ectasia, redness or pain with calf compression) occurs in 9% of patients by 5 years after a 3-month course of treatment with anticoagulants. Randomized controlled trials have shown that elastic compression stockings applied directly after an episode of DVT can reduce the chances of the patient developing postphlebitic syndrome by about 70%, but there is no clear evidence on which to recommend how long such stockings should be worn after an acute episode.