Deep vein thrombosis

Lower extremity venous thromboembolism (VTE) including DVT of the leg is common.

The incidence rate for DVT ranges from 88-112 per hundred thousand person-years.

Rates of recurrent DTE range from 20-36% during the 10 years after an initial event.

Isolated distal DVT is defined as thrombosis involving one or more of the deep calf veins without reaching the popliteal vein and is associated with a one-year all-cause mortality rate of 4.6 per hundred person-years.

Complications result in approximately 200,000 deaths a year.

Risk of developing deep vein thrombosis and its complications, including pulmonary embolism and post thrombotic syndrome or increased in older adults, and the risk is estimated to double for each 10 years after the age of 50 years.

All-cause in hospital mortality in patients with a primary diagnosis of DVT has been decreasing.

Mortality due to pulmonary embolusism in patients with DVT has been decreasing.

Mortality from DVT increases with age.

Clinical signs include unilateral leg pain, redness, swelling, edema, warmth, tenderness, a palpable cord, and prominent venous collaterals.

Patient with lower extremity DVT commonly describes swelling (71%) or a cramping or pulling discomfort in the thigh or calf (53%) that may worsen with ambulation (10%).

Clinically can be indistinguishable from cellulitis, hematoma, superficial thrombophlebitis, and congestive heart failure.

Can not be diagnosed based on signs and symptoms alone and should be confirmed by ultrasound, as the diagnosis is confirmed in less than 20% suspected cases.

Clinical decision alone does not exclude the presence of DVT, and D-dimer testing and imaging are appropriate tools for diagnosis,

The negative predictive value of a high sensitive D-dimer testing is high but its specificity is low, and its  negative predictive value decreases when the DVT prevalence increases.

In patients  with a high probability of DVT, a negative predictive value of a D-dimer level less than 500 ng/mL is 92%.

D-dimer cannot be use to exclude DVT without an assessment of pretest probability.

A normal D-Dimer level of less than 500 ng/mL essentially excludes acute deep vein thrombophlebitis when combined with the low pretest probability, that is a Wells DVT score of one or less.

D-dimer Levels increase with age, leading to lowest specificity for DVT diagnosis in  older patients.

Among unselected white persons with an initial presentation of symptomatic deep venous thrombosis 12-20% will be heterozygous for factor V Leiden mutation and 6% will be heterozygous for Prothrombin G20210A mutation, compared with 6% and 2%, respectively of asymptomatic control populations.

Risk increased in malignancy, hip fracture, traumatic head/spinal trauma, stroke and following a major orthopedic procedure.

History of 5451 patients with ultrasound confirm DVT, thrombophilia was observed in only 5% of patients, compared with cancer 32%, immobility 34%, and obesity in 27% of patients.

Thrombophilia should be suspected in patients with VTE in young age, and first-degree relatives, Venous thrombosis in unusual locations, such as the cerebral venous sinuses or splanchnic veins, idiopathic or recurrent VTE or a history of recurrent miscarriage.

Venous  ultrasonography is the first line imaging test for DVT.

Ultrasound findings in the presence of DVT include venous non-compressibility, direct thrombus visualization with venous dilation, abnormal spectral  and colored Doppler blood flow.

Sonography abnormalities are typically classified as acute DVT, acute on chronic thrombus, chronic post thrombotic changes, or indeterminate

Acute thrombus is characterized by ultrasound by a deformable shape, central location, and venous dilation.

A  more chronic appearing thrombus has intraluminal material that is rigid and non-deformable with applied pressure.

Chronic thromboembolic findings on ultrasound include wall thickening with evidence of renanalization and scarring.

Venography is considered the gold standard for the diagnosis.

Alternative imaging modalities to assess for acute lower extremity DVT include: CT imaging, MRI imaging, and contrast venography.

Venous ultrasound is the primary diagnostic test when pregnancy is associated with DVT.

Wells scoring system for detection of DVT consists of nine distinct factors that help estimate probability for deep vein thrombophlebitis (Wells PS et al):

One point is given for the presence of each of the following: 1-active cancer, 2-immobilization of the lower extremities, 3-bedridden or having undergone recent surgery, 4-swelling of the entire lower extremity, 5-calf swelling of greater than 3 cm in the symptomatic versus the asymptomatic extremity, 6-pitting edema confined to the symptomatic leg, 7-previously documented DVT, 8 localized tenderness along the distribution of the deep venous system, 9-superficial, nonvaricose veins in the symptomatic extremity.

Impatience with the lowest wells score of -2, the prevalence is DVT is approximately 5%, underscoring the DVT cannot be excluded using the wells score alone.

Screening high-risk patients who receive prophylaxis is not warranted.

In randomized trials, the incidence of deep vein thrombosis was estimated to be 50% lower with pharmacologic thromboprophylaxis with anticoagulants than with no trouble prophylaxis in critical illness.

DVT develops in 5- 20% of critically patients despite pharmacologic thromboprophylaxis.

High-risk patients who are not treated with prophylaxis should be screened with ultrasound.

When anticoagulant prophylaxis is not instituted DVT occurs after major surgery in about 20% of cases.

When managed appropriately 4.5% of patients with deep vein thrombophlebitis have a risk of sustaining a pulmonary embolism as a complication, with a mortality rate in this setting less than 1%.

Among individuals being evaluated for deep vein thrombosis and found to have a normal venogram or ultrasound, about 1.3% and 0.6% of patients, respectively will have asymptomatic deep vein thrombosis or pulmonary embolism with long-term follow-up (Hull aR et al, Johnson SA).

Among individuals suspected of having a pulmonary embolism with normal pulmonary angiogram or CT pulmonary angiogram 1.7% and 1.2%, respectively will eventually have symptomatic DVT or pulmonary embolus (van Beek EJ et al, Mos IC et al).

Doppler ultrasound less accurate than duplex ultrasound in making the diagnosis of DVT.

The neutrophil-to-lymphocyte ratio and the platelet-to-lymphocyte ratio are better predictors of the presence or absence of deep vein thrombosis than the D-dimer test.

The neutrophil-to-lymphocyte ratio can be useful to rule out DVT when it is negative, whereas the platelet-to-lymphocyte ratio can be useful ruling in DVT when positive.

DVT is thought to be an inflammatory process.

A positive neutrophil-to-lymphocyte ratio is considered 3.4 or higher.

A positive platelet-to-lymphocyte ratio is a ratio of 230 or more

The neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio outperformed the D-dimer test in terms of sensitivity, specificity, positive predictive value, and negative predictive value.

89% of the DVT group were classified as double-positive, meaning they were both NLR and PLR positive, so that the combination provided the best diagnostic value of all.

Low molecular weight heparins as safe and effective as unfractionated heparin in the initial treatment of DVT even when given as an outpatient.

Proximal vein thrombosis is associated with a threefold higher risk of recurrent venous thromboembolism than distal vein thrombosis.

The third most common cause of cardiovascular morbidity and mortality after coronary artery disease and stroke.

Proximal DVT is defined as DVT involving the popliteal vein or above and accounts for approximately 80% of the DVT cases.

DVT associated with early mortality with death rates of approximately 6% within one month of diagnosis.

Acute in Treatment: anticoagulation is initiated promptly when DVT is diagnosed or a high clinical suspicion exists.

Anticoagulation therapy is intended to reduce mortality from pulmonary embolism and from the morbidity of thrombus extension, recurrence, and postthrombotic syndrome.

Options for management of VTE include immediate treatment with a direct oral anticoagulant, initial parenteral and coagulation followed by a direct oral anticoagulant, or initial parenteral anticoagulation overlapped by warfarin for at least five days and until the INR is more than 2.0 on two occasions 24 hours apart.

Low molecular wait heparin is typically used for parental anticoagulation, but unfractionated heparin may be preferred when the ability to discontinue anticoagulation rapidly is required.

Metaanalysis schir The Treatment with direct oral anticoagulants are non-inferior for first recurrent VTE or VTE related death compared with warfarin: DOAC‘s or associate with lower rate of major bleeding, intracranial bleeding and fatal bleeding.

DOAC‘s have a rapid onset of reaction, more predictable pharmacokinetics, and avoid any for routine laboratory monitoring and dose adjustments.

In patients with antiphospholipid antibodies, warfarin may be associated with a lower rate of thromboembolic events then DOAC‘s.

Short-term treatment with anticoagulants is effective to reduce recurrence from an estimated 25% to about 3% during the first 6-12 months of therapy.After anticoagulants are discontinued the risk of recurrence remains at 5-10% during the first year.

Substantial risk after brain tumor surgery.

Some studies have demonstrated 20-40% incidence in an ICU setting.

About 80% of symptomatic DVT of lower extremities affects the popliteal and more proximal veins (Bergvist D et al).

Following appropriate anticoagulation, nearly half of patients develop some degree of post phlebitic syndrome (Prandoni P et al).

The daily use of elastic compression stockings reduces risk of heat PTS by about 50%.

Patients with iliofemoral vein thrombosis have a greater than twofold higher risk of developing recurrent venous thromboembolism than patients without iliac vein involvement.

DVT of iliofemoral veins, compared to other lower extremity veins, more likely to be associated with post-thrombotic syndrome.

Ultrasound poor ability to image common iliac veins.

Anticoagulation prevents thrombus extension, pulmonary embolism, death, and recurrence, but many patients develop venous dysfunction resulting in post-thrombotic syndrome.

Acute lower limb DVT treated in a randomized fashion showed a benefit of catheter directed thrombolysis compared to conventional anticoagulation treatment resulted in a reduced post-thrombotic syndrome incidence at 24 months (Enden T et al).

At least 1/3 of the time on treatment with warfarin the target international normalized ratio is outside the target 2-3, with a majority as under anticoagulated.

In the above study there was a 14.4% absolute risk reduction in the development of the post-thrombotic syndrome when the catheter directed thrombolysis plus anticoagulation was compared with those given anticoagulation alone.

Rivaroxaban therapy for a DVT associated with lower rates of post thrombotic syndrome compared with warfarin.

In catheter directed thrombolysis should ideally not exceed 2 days of treatment.

Approximately 20-50% of patients with proximal DVT develop a postthrombotic syndrome despite current therapy.

Post-thrombotic syndrome (PTS) is characterized by pain, swelling, heaviness, edema, pigmentation, and skin deterioration including venous ulcers.

PTS is associated with impaired quality of life and economic burden.

Post-thrombotic syndrome results from inadequate treatment of acute DVT.

Post-thrombotic syndrome occurs when acute DVT is not resolved, and the clot hardens, leading to chronic venous obstruction. C

Most iliofemoral DVTs are left sided as many are caused by the right common iliac artery compressing the left common iliac vein leading to left lower extremity DVT and chronic stenosis of the left iliac vein (May-Thurner syndrome).

Prophylaxis decreases the incidence of deep vein thrombosis in patients at risk by 60%.

In a trial of dalteparin vs unfractionated heparin randomly assigned in 3764 patients, and given subcutaneoulsy 5000 u daily or 5000 u bi, respectively in ICU patients: among critically ill patients dalteparin was not superior to unfractionated heparin in decreasing the incidence of proximal deep vein thrombosis (PROTECT Investigators).

Annual incidence in women beyond childbearing age is between 1 in 1000 to 1 in 5,000.

Annual incidence in women of childbearing age is 1 in 10,000.

Of the lower extremities during pregnancy occurs at a rate of 0.13 to 0.61 per thousand pregnancies.

Majority of deep vein thromboses during pregnancy occur in the left leg.

Occurs in the left leg in approximately 70-90% of cases in pregnancy, perhaps related to compressive effects in the left iliac vein being crossed by the right iliac artery.

Isolated deep vein thrombosis in the iliac vein occurs more often in pregnant than non pregnant women.

Isolated iliac vein thrombosis may present with abdominal and back pain and swelling of the leg, but may be asymptomatic without physical findings.

In the first few days following childbirth, the risk of a deep vein thrombosis (DVT) is relatively high as hypercoagulability increases during pregnancy and is maximal in the postpartum period.

Patients immobilized for <4 days, 4 to 7 days and greater than 7 days have a 19%, 47% and 75-90% chance of developing deep vein thrombosis, respectively.

10 year recurrence risk of 30%.

Family and twin studies suggest that genetics accounts for 60% of the risk.

Deficiencies of protein S, C, and antithrombin account for about 1% of all deep vein thromboses.

Factor V Leiden and prothrombin G20220A found in association in a fraction of cases.

7 single nucleotide polymorphisms associated with DVT with the strongest are CYP4V2, SERPINC1, and GP6 genes.

These single nucleotide polymorphisms are in or near genes that have a clear role in blood coagulation.

Suggested that 2 or more risk factors are needed for thrombosis.

Upper extremity deep vein thrombosis associated with symptoms of pain, paresthesias, and weakness in the arm.

Typical signs upper extremity DVT are swelling, edema, discoloration and prominence of venous collaterals

Upper extremity deep vein thrombosis accounts for approximately 10% of all cases of DVT.

Upper extremity DVT has an annual incidence of 0.4-1 case per 10,000 people.

Upper extremity deep vein thrombosis is increasing because of the use of central venous catheters, cardiac pacemakers and defibrillators.

Axillary subclavian veins are often involves in upper extremity DVT.

Patients with upper extremity DVT are typically younger, leaner and more likely to have a diagnosis of cancer, and less likely to have been acquired or hereditary thrombophilia.

Inherited thrombophilias, the most common of which are factor V Leiden, prothrombin gene Polymorphism, and methylenetetrahydrofolate reductase (MTHFR) gene Polymorphism, increase the rate of venous  thromboembolism, especially in people who are homozygous carriers.

With primary deep vein thrombosis of an upper extremity there is a frequent history of micro trauma to the subclavian vein by abnormalities in the costoclavicular junction that may cause inflammation or venous intimal hyperplasia and fibrosis.

Fibrosis leads to the thoracic outlet syndrome and deep vein thrombosis in the upper extremity.

Approximately two thirds of individuals, usually young men, with primary upper extremity deep vein thrombosis report strenuous force or abduction activity of the arm prior to the thrombosis, and this is known as the Paget-Schroetter syndrome.

Complications of deep vein thrombosis: Pulmonary embolism-lower extremity 15-32%, upper extremity 6%, recurrence rate at 1 year-lower extremity 10%, upper extremity 2-5%, post-thrombotic syndrome-lower extremity 56%, upper extremity 5%.

Thrombosis of the subclavian veins, as compared to other locations, and residual thrombosis at six months are associated with an increased risk of the post-thrombotic syndrome.

In a prospective study of 512 patients with upper extremity DVT, 38% of patients had cancer,the three months mortality rate less than percent with only one death from pulmonary embolism (Munoz EJ et al).

Routine screening of patients with central venous catheters reveal that up to two thirds of patients have upper extremity DVT, as do the majority of patients with catheter associated thrombosis, or with any such junctions caused by pacemaker leads and have no suggested signs or symptoms.

Patients 50 years of age or younger with DVT and no comorbid conditions can be treated safely at home with comparable results to that of hospitalized patients (Stein P et al.).

Most patients can be treated as an outpatient, with direct oral anticoagulant-based regimen.