Deep vein thrombosis
Deep vein thrombosis | |
---|---|
Other names | Deep venous thrombosis |
unfractionated heparin, warfarin | |
Frequency | From 0.8–2.7 per 1000 people per year, but populations in China and Korea are below this range[8] |
Deep vein thrombosis (DVT) is a type of
The most common life-threatening concern with DVT is the potential for a clot to
The mechanism behind DVT formation typically involves some combination of
People suspected of having DVT can be assessed using a
Using
Signs and symptoms
Symptoms classically affect a leg and typically develop over hours or days,[20] though they can develop suddenly or over a matter of weeks.[21] The legs are primarily affected, with 4–10% of DVT occurring in the arms.[11] Despite the signs and symptoms being highly variable,[5] the typical symptoms are pain, swelling, and redness. However, these symptoms might not manifest in the lower limbs of those unable to walk.[22] In those who are able to walk, DVT can reduce one's ability to do so.[23] The pain can be described as throbbing and can worsen with weight-bearing, prompting one to bear more weight with the unaffected leg.[21][24] Additional signs and symptoms include tenderness, pitting edema (see image), dilation of surface veins, warmth, discoloration, a "pulling sensation", and even cyanosis (a blue or purplish discoloration) with fever.[5][20][21] DVT can also exist without causing any symptoms.[22] Signs and symptoms help in determining the likelihood of DVT, but they are not used alone for diagnosis.[19]
At times, DVT can cause symptoms in both arms or both legs, as with bilateral DVT.
Potential complications
A
A rare and massive DVT that causes significant obstruction and discoloration (including cyanosis) is phlegmasia cerulea dolens.[31][32] It is life-threatening, limb-threatening, and carries a risk of venous gangrene.[33] Phlegmasia cerulea dolens can occur in the arm but more commonly affects the leg.[34][35] If found in the setting of acute compartment syndrome, an urgent fasciotomy is warranted to protect the limb.[36] Superior vena cava syndrome is a rare complication of arm DVT.[11]
DVT is thought to be able to cause a
-
A CT image with red arrows indicating PE (grey) in thepulmonary arteries(white)
-
A case of phlegmasia cerulea dolens in the left leg
-
A depiction of a patent foramen ovale
Differential diagnosis
In most suspected cases, DVT is ruled out after evaluation.
Classification
DVT and PE are the two manifestations of the
DVT is classified as
DVT in a leg above the knee is termed proximal DVT (
DVT can be classified into provoked and unprovoked categories.[52] For example, DVT that occurs in association with cancer or surgery can be classified as provoked.[52] However, the European Society of Cardiology in 2019 urged for this dichotomy to be abandoned to encourage more personalized risk assessments for recurrent VTE.[53] The distinction between these categories is not always clear.[54]
Causes
Traditionally, the three factors of
Acquired risk factors include the strong risk factor of older age,
Infections, including
Cancer can grow in and around veins, causing venous stasis, and can also stimulate increased levels of tissue factor.
Dozens of genetic risk factors have been identified,
Blood alterations including dysfibrinogenemia,[65] low free protein S,[58] activated protein C resistance,[58] homocystinuria,[92] hyperhomocysteinemia,[62] high fibrinogen levels,[62] high factor IX levels,[62] and high factor XI levels[62] are associated with increased risk. Other associated conditions include heparin-induced thrombocytopenia, catastrophic antiphospholipid syndrome,[93] paroxysmal nocturnal hemoglobinuria,[94] nephrotic syndrome,[58] chronic kidney disease,[95] polycythemia vera, essential thrombocythemia,[96] intravenous drug use,[97] and smoking.[d]
Some risk factors influence the location of DVT within the body. In isolated distal DVT, the profile of risk factors appears distinct from proximal DVT. Transient factors, such as surgery and immobilization, appear to dominate, whereas thrombophilias[e] and age do not seem to increase risk.[101] Common risk factors for having an upper extremity DVT include having an existing foreign body (such as a central venous catheter, a pacemaker, or a triple-lumen PICC line), cancer, and recent surgery.[11]
Pathophysiology
Blood has a natural tendency to clot when blood vessels are damaged (
DVT often develops in the calf veins and "grows" in the direction of venous flow, towards the heart.[42][103] DVT most frequently affects veins in the leg or pelvis[9] including the popliteal vein (behind the knee), femoral vein (of the thigh), and iliac veins of the pelvis. Extensive lower-extremity DVT can even reach into the inferior vena cava (in the abdomen).[104] Upper extremity DVT most commonly affects the subclavian, axillary, and jugular veins.[11]
The process of fibrinolysis, where DVT clots can be dissolved back into the blood, acts to temper the process of thrombus growth.
In arterial thrombosis, blood vessel wall damage is required, as it initiates
Tissue factor, via the tissue factor–
Often, DVT begins in the valves of veins.
Diagnosis
A
While the Wells score is the predominant and most studied clinical prediction rule for DVT,
Criteria | Wells score for DVT[g] | Dutch Primary Care Rule |
---|---|---|
Active cancer (treatment within last 6 months or palliative) | +1 point | +1 point |
Calf swelling ≥ 3 cm compared to asymptomatic calf (measured 10 cm below tibial tuberosity )
|
+1 point | +2 points |
Swollen unilateral superficial veins (non-varicose, in symptomatic leg) | +1 point | +1 point |
Unilateral pitting edema (in symptomatic leg) | +1 point | — |
Previous documented DVT | +1 point | — |
Swelling of entire leg | +1 point | — |
Localized tenderness along the deep venous system | +1 point | — |
Paralysis, paresis, or recent cast immobilization of lower extremities | +1 point | — |
Recently bedridden ≥ 3 days, or major surgery requiring regional or general anesthetic in the past 12 weeks | +1 point | +1 point |
Alternative diagnosis at least as likely | −2 points | — |
Positive D-dimer (≥ 0.5 mcg/mL or 1.7 nmol/L) | — | +6 points |
Absence of leg trauma | — | +1 point |
Male sex | — | +1 point |
Use of oral contraceptives | — | +1 point[5][116] |
Compression
-
An ultrasound with a blood clot visible in the left common femoral vein. (The common femoral vein is distal to the external iliac vein.)
-
Doppler ultrasonography showing absence of flow and hyperechogenic content in a clotted femoral vein (labeled subsartorial[h]) distal to the branching point of the deep femoral vein. When compared to this clot, clots that instead obstruct the common femoral vein (proximal to this branching point) cause more severe effects due to impacting a significantly larger portion of the leg.[122]
-
An abdominal CT scan demonstrating an iliofemoral DVT, with the clot in the right common iliac vein of the pelvis
Management
Treatment for DVT is warranted when the clots are either proximal, distal and symptomatic, or upper extremity and symptomatic.[2] Providing anticoagulation, or blood-thinning medicine, is the typical treatment after patients are checked to make sure they are not subject to bleeding.[2][i] However, treatment varies depending upon the location of DVT. For example, in cases of isolated distal DVT, ultrasound surveillance (a second ultrasound after 2 weeks to check for proximal clots), might be used instead of anticoagulation.[5][124] Although, those with isolated distal DVT at a high-risk of VTE recurrence are typically anticoagulated as if they had proximal DVT. Those at a low-risk for recurrence might receive a four to six week course of anticoagulation, lower doses, or no anticoagulation at all.[5] In contrast, those with proximal DVT should receive at least 3 months of anticoagulation.[5]
Some anticoagulants can be taken by mouth, and these oral medicines include
The duration of anticoagulation therapy (whether it will last 4 to 6 weeks,
Treatment for acute leg DVT is suggested to continue at home for uncomplicated DVT instead of hospitalization. Factors that favor hospitalization include severe symptoms or additional medical issues.[12] Early walking is suggested over bedrest.[134] Graduated compression stockings—which apply higher pressure at the ankles and a lower pressure around the knees[126] can be trialed for symptomatic management of acute DVT symptoms, but they are not recommended for reducing the risk of post-thrombotic syndrome,[125] as the potential benefit of using them for this goal "may be uncertain".[5] Nor are compression stockings likely to reduce VTE recurrence.[135] They are, however, recommended in those with isolated distal DVT.[5]
If someone decides to stop anticoagulation after an unprovoked VTE instead of being on lifelong anticoagulation, aspirin can be used to reduce the risk of recurrence,[136] but it is only about 33% as effective as anticoagulation in preventing recurrent VTE.[52] Statins have also been investigated for their potential to reduce recurrent VTE rates, with some studies suggesting effectiveness.[137]
Investigations for cancer
An unprovoked VTE might signal the presence of an unknown cancer, as it is an underlying condition in up to 10% of unprovoked cases.
Interventions
A mechanical thrombectomy device can remove DVT clots, particularly in acute iliofemoral DVT (DVT of the major veins in the pelvis), but there is limited data on its efficacy. It is usually combined with thrombolysis, and sometimes temporary IVC filters are placed to protect against PE during the procedure.
In DVT in the arm, the first (topmost) rib can be surgically removed as part of the typical treatment when the DVT is due to
-
The first rib, which is removed in a first rib resection surgery, is labeled 1 in this image
-
A venogram before catheter-directed thrombolysis forPaget–Schroetter syndrome, a rare and severe arm DVT shown here in a judo practitioner, with highly restricted blood flow shown in the vein
-
After treatment with catheter-directed thrombolysis, blood flow in thesequelae from thoracic outlet compression.[147]
The placement of an
Field of medicine
Patients with a history of DVT might be managed by
Prevention
For the
Hospital (non-surgical) patients
Acutely ill hospitalized patients are suggested to receive a parenteral anticoagulant, although the potential net benefit is uncertain.[63] Critically ill hospitalized patients are recommended to either receive unfractionated heparin or low-molecular weight heparin instead of foregoing these medicines.[63]
After surgery
Major orthopedic surgery—
Options for VTE prevention in people following non-orthopedic surgery include early walking, mechanical prophylaxis, and blood thinners (low-molecular-weight heparin and low-dose-unfractionated heparin) depending upon the risk of VTE, risk of major bleeding, and person's preferences.[159] After low-risk surgeries, early and frequent walking is the best preventive measure.[7]
Pregnancy
The risk of VTE is increased in pregnancy by about four to five times because of a more hypercoagulable state that protects against fatal
Travelers
Travelling "is an often cited yet relatively uncommon" cause of VTE.[28] Suggestions for at-risk[n] long-haul travelers include calf exercises, frequent walking, and aisle seating in airplanes to ease walking.[162][163] Graduated compression stockings have sharply reduced the levels of asymptomatic DVT in airline passengers, but the effect on symptomatic DVT, PE, or mortality is unknown, as none of the individuals studied developed these outcomes.[164] However, graduated compression stockings are not suggested for long-haul travelers (>4 hours) without risk factors for VTE. Likewise, neither aspirin nor anticoagulants are suggested in the general population undertaking long-haul travel.[63] Those with significant VTE risk factors[o] undertaking long-haul travel are suggested to use either graduated compression stockings or LMWH for VTE prevention. If neither of these two methods are feasible, then aspirin is suggested.[63]
Prognosis
DVT is most frequently a disease of older age that occurs in the context of nursing homes, hospitals, and active cancer.[3] It is associated with a 30-day mortality rate of about 6%, with PE being the cause of most of these deaths.[1] Proximal DVT is frequently associated with PE, unlike distal DVT, which is rarely if ever associated with PE.[39] Around 56% of those with proximal DVT also have PE, although a chest CT is not needed simply because of the presence of DVT.[1] If proximal DVT is left untreated, in the following 3 months approximately half of people will experience symptomatic PE.[9]
Another frequent complication of proximal DVT, and the most frequent chronic complication, is post-thrombotic syndrome, where individuals have chronic venous symptoms.
In the 10 years following an initial VTE, about 30% of people will have a recurrence.[3] VTE recurrence in those with prior DVT is more likely to recur as DVT than PE.[167] Cancer[5] and unprovoked DVT are strong risk factors for recurrence.[60] After initial proximal unprovoked DVT with and without PE, 16–17% of people will have recurrent VTE in the 2 years after they complete their course of anticoagulants. VTE recurrence is less common in distal DVT than proximal DVT.[44][45] In upper extremity DVT, annual VTE recurrence is about 2–4%.[130] After surgery, a provoked proximal DVT or PE has an annual recurrence rate of only 0.7%.[60]
Epidemiology
About 1.5 out of 1000 adults a year have a first VTE in high-income countries.[168][169] The condition becomes much more common with age.[3] VTE rarely occurs in children, but when it does, it predominantly affects hospitalized children.[170] Children in North America and the Netherlands have VTE rates that range from 0.07 to 0.49 out of 10,000 children annually.[170] Meanwhile, almost 1% of those aged 85 and above experience VTE each year.[3] About 60% of all VTEs occur in those 70 years of age or older.[9] Incidence is about 18% higher in males than in females,[4] though there are ages when VTE is more prevalent in women.[15] VTE occurs in association with hospitalization or nursing home residence about 60% of the time, active cancer about 20% of the time, and a central venous catheter or transvenous pacemaker about 9% of the time.[3]
During pregnancy and after childbirth, acute VTE occurs in about 1.2 of 1000 deliveries. Despite it being relatively rare, it is a leading cause of maternal morbidity and
DVT occurs in the upper extremities in about 4–10% of cases,[11] with an incidence of 0.4–1.0 people out of 10,000 a year.[5] A minority of upper extremity DVTs are due to Paget–Schroetter syndrome, also called effort thrombosis, which occurs in 1–2 people out of 100,000 a year, usually in athletic males around 30 years of age or in those who do significant amounts of overhead manual labor.[69][147]
Social
Being on blood thinners because of DVT can be life-changing because it can prevent lifestyle activities such as contact or winter sports to prevent bleeding after potential injuries.[175] Head injuries prompting brain bleeds are of particular concern. This has caused NASCAR driver Brian Vickers to forego participation in races. Professional basketball players including NBA players Chris Bosh and hall of famer Hakeem Olajuwon have dealt with recurrent blood clots,[176] and Bosh's career was significantly hampered by DVT and PE.[177]
Tennis star
Other notable people have been affected by DVT. Former United States (US) President
History
The book
In 1856, German physician and pathologist Rudolf Virchow published his analysis after the insertion of foreign bodies into the jugular veins of dogs, which migrated to the pulmonary arteries. These foreign bodies caused pulmonary emboli, and Virchow was focused on explaining their consequences.[189] He cited three factors, which are now understood as hypercoaguability, stasis, and endothelial injury.[190] It was not until 1950 that this framework was cited as Virchow's triad,[189] but the teaching of Virchow's triad has continued in light of its utility as a theoretical framework and as a recognition of the significant progress Virchow made in expanding the understanding of VTE.[189][190]
Methods to observe DVT by ultrasound were established in the 1960s.
Multiple pharmacological therapies for DVT were introduced in the 20th century: oral anticoagulants in the 1940s,
Economics
VTE costs the US healthcare system about $7 to 10 billion dollars annually.[169] Initial and average DVT costs for a hospitalized US patient is about $10,000 (2015 estimate).[196] In Europe, the costs for an initial VTE hospitalization are significantly less, costing about €2000 to 4000 (2011 estimate).[197] Post-thrombotic syndrome is a significant contributor to DVT follow-up costs.[198] Outpatient treatment significantly reduces costs, and treatment costs for PE exceed those of DVT.[199]
Research directions
A 2019 study published in Nature Genetics reported more than doubling the known genetic loci associated with VTE.[14] In their updated 2018 clinical practice guidelines, the American Society of Hematology identified 29 separate research priorities, most of which related to patients who are acutely or critically ill.[63] Inhibition of factor XI, P-selectin, E-selectin, and a reduction in formation of neutrophil extracellular traps are potential therapies that might treat VTE without increasing bleeding risk.[200]
Notes
- retinal vein thrombosis), spleen and intestines (splanchnic vein thrombosis), liver (Budd–Chiari syndrome), kidneys (renal vein thrombosis), and ovaries (ovarian vein thrombosis) are more unusual forms of venous thrombosis and they are considered as separate diseases.[10]
- combined oral contraceptives (COCs) have an approximate two to three times higher risk than second-generation COCs.[64] Progestogen-only pill use is not associated with increased VTE risk.[87]
- ^ Type I[58]
- ^ "It is important to note that smoking is not an independent risk factor, although it increases the risk for cancers and other comorbidities and works synergistically with other independent risk factors."[98]
- ^ The term 'thrombophilia' as used here applies to the five inherited abnormalities of antithrombin, protein C, protein S, factor V, and prothrombin, as is done elsewhere.[89][99] These 5 genetic factors have been referred to as the classical thrombophilias.[100]
- ^ An elevated level is greater than 250 ng/mL D-dimer units (DDU) or greater than 0.5 μg/mL fibrinogen equivalent units (FEU). A normal level is below these values.[113]
- ^ The Wells score as displayed here is the more recent modified score, which added a criterion for a previous documented DVT and increased the time range after surgery to 12 weeks from 4 weeks.[117]
- ^ Subsartorial is a proposed name for a section of the femoral vein.[121]
- NSAIDs.[123]
- ^ The international normalized ratio should be ≥ 2.0 for 24 hours minimum,[18] but if the ratio is > 3.0, then the parenteral anticoagulant is not needed for five days.[126]
- ^ An INR is determined from the ratio of a patient's prothrombin time (PT) to a standardized control PT. A normal INR for those not on anticoagulation is 1.0. A value of 5.0 or higher is considered a critical finding because of an increased risk of bleeding.[127]
- ^ "Up to 83% of patients treated by any catheter-based therapy, need adjunctive angioplasty, and stenting".[5]
- ^ Estimated in United States dollars, estimate published in 2019
- ^ Including those with "previous VTE, recent surgery or trauma, active malignancy, pregnancy, estrogen use, advanced age, limited mobility, severe obesity, or known thrombophilic disorder"[162]
- ^ For example "recent surgery, history of VTE, postpartum women, active malignancy, or ≥2 risk factors, including combinations of the above with hormone replacement therapy, obesity, or pregnancy"[63]
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