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Deep vein thrombosis (DVT) guidelines


Deep vein thrombosis (DVT) guidelines

Abstract:

Deep vein thrombosis (DVT) continues to be a major source of concern for health care providers, especially surgeons and chest physicians both in the developed countries and worldwide.

The results of DVT can range from complete resolution without any long term complications to a fatal pulmonary embolism episode, yet it remains one of the most preventable medical problems of our time. This really stresses the importance of early diagnosis and treatment of DVT in order to save the lives of those affected.

 

Historical Background:

Over a century ago, Rudolf Virchow described 3 factors that are critically important in the development of venous thrombosis: (1) venous stasis, (2) activation of blood coagulation, and (3) vein damage. Ongoing research showed that multiple factors are often implemented in the setting of developing DVT .The broad titles were that DVT is closely associated with low flow sites such as soleal sinuses, behind venous valve pockets and at venous confluences. Yet, stasis alone does not sufficiently explain the etiology and  although, patients that are immobilized for long periods of time seem to be at high risk for the development of venous thrombosis, an additional stimulus is required to develop deep venous thrombosis (DVTs).
 
Mechanical injury to the venous wall was also cited as a causative factor in developing DVT, since endothelial injury can turn the endothelium to being prothrombotic instead of being antithrombiogenic due to the release of multiple factors (tissue factore, Von Willebrand and fibronectin).
In the early 1990s according to a study published by the Tropical and Infectious Disease Unit, Royal Liverpool University Hospital, Liverpool ,UK in May 2004,  a large number of patients  were intravenous drug users (IDUs), and that a significant number had DVT or arterial injury, thereby adding a new category to the already established list of the patients at risk.

DVT Injury

 

Who is at risk for developing DVT?

  • Patients with a prior history of thrombosis episodes. These remain the category most at risk for developing DVTs since previous thrombi are seen in the specimens of the new thrombi.
  • Patients with hypercoagulable states such as protein S or protein C deficiency. Abnormalities within the coagulation cascade are the direct result of discrete genetic mutations within the coagulation cascade.
  • Age is an independent risk factor, although there seems to be an increase in the incidence of DVT in the elderly population, this could easily be explained by the fact that most of the population this age group tends to be more immobile and suffering from venous stasis.
  • The obese patient.
  • Women of childbearing age that have either given birth during the last 6 months or are currently taking oral contraceptives.
  • International overseas travelers by plane.
  • Patients recovering from major surgery (prolonged bed rest).
  • Patients diagnosed with malignancy or those receiving chemotherapy.

 

Diagnosing DVT:

In order to be more capable of diagnosing DVT, aims of various researches were to be more aware of this still elusive diagnosis.
The classic signs and symptoms of deep venous thrombosis (DVT) are those associated with obstruction to venous drainage and include pain, tenderness, and unilateral leg swelling. Other associated nonspecific findings are warmth, erythema, a palpable cord, and pain upon passive dorsiflexion of the foot (Homan sign). But these all remain uncertain methods of diagnosis since many clinical scenarios may mimic DVT. For instance, the differential diagnosis of leg swelling (which is the most common clinical sign of DVT) includes: cases of venous insufficiency (DVT, post thrombotic syndrome, chronic venous insufficiency, venous obstruction and superficial thrombophlebitis) in addition to other cases such as cellulitis, backer’s cyst, arterial insufficiency, lymphedema, hematoma and ruptured muscle tendons.

In 2006, Scarvelis and Wells overviewed a set of clinical prediction rules for DVT , on the heels of a widely adopted set of clinical criteria for pulmonary embolism, and it was appropriately named the Well’s criteria.

Wells score or criteria: (Possible score -2 to 8)

  1. Active cancer (treatment within last 6 months or palliative) -- 1 point
  2. Calf swelling >3 cm compared to other calf (measured 10 cm below tibial tuberosity) -- 1 point
  3. Collateral superficial veins (non-varicose) -- 1 point
  4. Pitting edema (confined to symptomatic leg) -- 1 point
  5. Swelling of entire leg - 1 point
  6. Localized pain along distribution of deep venous system—1 point
  7. Paralysis, paresis, or recent cast immobilization of lower extremities—1 point
  8. Recently bedridden > 3 days, or major surgery requiring regional or general anesthetic in past 4 weeks—1 point
  9. Previous documented DVT-1 point.
  10. Alternative diagnosis at least as likely—Subtract 2 points


Interpretation:
Score of 2 or higher - deep vein thrombosis is likely. Consider imaging the leg veins.
Score of less than 2 - deep vein thrombosis is unlikely. Consider blood test such as D-dimer test to further rule out deep vein thrombosis.
According to what has already been mentioned, deep venous thrombosis (DVT) simply cannot be diagnosed or excluded based on clinical findings; thus, diagnostic tests must be performed whenever the diagnosis of deep venous thrombosis (DVT) is being considered.


Is it DVT or not?

Workups for this dangerous condition "range from the accurate but expensive (contrast venography) to the cheap but unreliable (clinical assessment)," noted the researchers who conducted an extensive analysis, seeking a cost-effective strategy to put into practice throughout the United Kingdom's National Health Service. The work up for this diagnosis falls into two broad categories: screening tests and definitive diagnosis methods.

DVT Clot
 

Screening tests:

D-dimer tests:

  • Laboratory tests: Enzyme linked immunosorbent assay (ELISA) latex agglutination.
  • Near patient tests: SimpliRED (agglutination test) and Simplify (immunochromatograpy test)

Plesthysmography:

  • Digital photoplesthysmography.
  • Strain gauge plesthysmography.
  • Impedence plesthysmography.


Plasma D-dimers: Plasma D-dimers are specific cross linked derivatives of fibrin, produced when fibrin is degraded by plasmin, so concentrations are raised in patients with venous thromboembolism. Although sensitive for venous thromboembolism, the differential diagnoses for elevated levels of plasma D-dimers include states of malignancy, pregnancy, infection and recent operations. Nevertheless, D-dimer tests generally have a high negative predictive value and are useful rule-out tests that reduce the need for imaging when used in conjunction with clinical probability, plethysmography, or ultrasonography.

Several forms of plasma D-dimer tests are available for clinical use nowadays, but the two most commonly used in clinical practice are the laboratory based VIDAS enzyme linked immunosorbent essay (ELISA) test and the SimpliRED whole blood agglutination test.

The SimpliRED test provides a qualitative result (positive or negative) within 10 minutes, which makes it very suitable for near patient testing. But, unfortunately, up to this date no published data managed to confirm its usefulness.

On the other hand, recent evidence exists to support the idea of measuring D-dimer at the end of the anticoagulation period in order to determine the risk of re-thrombosis.

Plethysmography:  A term given to the recording of changes in the size of the limb due to tissue fluid or pooled blood in the veins. This measurement can be undertaken in various ways: photoplethysmography, strain gauge, and electrical impedance.

Digital photoplethysmography - Photoplethysmography depends on the absorption of light by hemoglobin in the red cells. Digital photoplethysmography is assisted by a microprocessor, and the test is easy to perform. A digital measurement probe is placed on the skin, 10 cm above the medial malleolus of the affected leg. The patient then dorsiflexes the foot 10 times according to a standard protocol and then rests for 45 seconds. Based on the characteristics of the reflected light the venous, refilling time is calculated and presented as a printed graph. In one study of 100 hospital inpatients, a venous refilling time of longer than 20 seconds excluded a deep vein thrombosis and had a sensitivity of 100% and a specificity of 47%.  Digital photoplethysmography is a simple screening test to perform, but bigger studies are needed to evaluate its usefulness fully.

Computerized strain gauge plethysmography - The principle behind computerized strain gauge plethysmography is to measure changes in calf dimensions while venous outflow is occluded by inflation of a thigh cuff. The rate of decrease in calf size when this occlusion is removed gives a measure of venous outflow. Rapid emptying is the rule in a healthy venous system. Obstruction to outflow is seen with thrombotic occlusion of proximal vessels. Computer software is used to calibrate the strain gauge and calculate blood flow measurements in the leg. The test can be performed in 15 minutes, and the procedure can be performed with minimal training. One study of 307 consecutive patients showed a sensitivity of 90% for proximal (popliteal, femoral, or iliac vein) deep vein thrombosis and 66% for distal (calf vein) deep vein thrombosis.

Impedance plethysmography - Impedance plethysmography relies on the principle that the volume of blood in the leg affects the blood's ability to conduct an electrical current, which is inversely proportional to the impedance between two electrodes placed along the calf. A cuff is inflated around the thigh to obstruct venous outflow but not arterial inflow. As blood accumulates in the leg below the cuff, impedance between the calf electrodes falls. The sudden release of the cuff results in the blood volume of the leg decreasing, resulting in a rapid increase in impedance. Obstruction to venous flow such as with a deep vein thrombosis causes a reduction in the rate of venous emptying (and slower increase in impedance) than normal. The technique is operator dependent, and the sensitivity in some studies has been low. Some centers therefore now combine impedance plethysmography with D-dimer tests.

Definitive tests:

  • Contrast venography.
  • Ultrasonography.
  • Computed tomography.
  • Magnetic resonance imaging.


The criterion standard to diagnostic imaging for deep venous thrombosis (DVT) remains venography with pedal vein cannulation, intravenous contrast injection, and serial limb radiographs. Identification of venous filling defects is diagnostic for venous thrombosis. However, the invasive nature and significant consumption of resources are only 2 of its many limitations, in addition to several cases of allergic reactions reported.

Venous duplex ultrasound has now replaced venography as the diagnostic study of choice. Its noninvasive nature, wide availability, and minimal complications are only part of its popularity. A sensitivity and specificity of 97% and 94% on meta-analysis compared with venography have made duplex ultrasound the imaging of choice for venous thrombosis. Assessment of venous flow, vein compressibility, and identification of luminal echoes are all used in the making the diagnosis. However, it cannot be readily relied on to diagnose calf vein thrombosis, since its sensitivity in reporting calf vein thrombosis has been reported to be as low as 75%. As the thrombosis can extend into the proximal veins several strategies have been used to identify patients with this condition. One diagnostic strategy has been to repeat ultrasonography after five days in patients whose result is negative. The disadvantage of this strategy is that all patients with a negative ultrasound scan must return for further evaluation.

Three ultrasonography techniques are in use.

Compression ultrasound - The simplest ultrasonic criterion for diagnosing venous thrombosis is non-compressibility of the vascular lumen under gentle probe pressure (compression ultrasound). If no residual lumen is observed the vein is considered to be fully compressible, which indicates the absence of venous thrombosis.

Duplex ultrasonography - Patients are examined in an identical way to that with conventional compression ultrasound. In addition, blood flow characteristics are evaluated by using the pulsed Doppler signal. Blood flow in normal veins is spontaneous and phasic with respiration and can be augmented by manual compression distal to the ultrasound transducer. When the phasic pattern is absent, flow is defined as continuous, indicating the presence of venous outflow obstruction.

Color flow duplex imaging - the technique of color coded Doppler ultrasonography (color Doppler) is identical to duplex ultrasonography. In color flow sonography, pulsed Doppler signals are used to produce the images. When a Doppler shift is recognized, it is assigned a color (red or blue) according to its direction towards or away from the probe. Therefore color Doppler results in a display of flowing blood as a color overlay to the grey scale ultrasound image, which makes it easier to identify the veins.

Spiral computed tomography venography and magnetic resonance imaging: Spiral computed tomography venography of the leg has shown promise for the diagnosis of deep vein thrombosis and other soft tissue diseases in patients with leg swelling.  A small study of 53 patients, in which magnetic resonance imaging was used to detect deep vein thrombosis, showed that this technique may be better than current non-invasive methods for diagnosing deep vein thrombosis in the calf. This technique is not likely to be used widely until costs decrease.

 

Treating DVT:

The standard initial management of deep vein thrombosis has traditionally meant admission to hospital for continuous treatment with intravenous unfractionated heparin. Treatment then continued with a transition to long term use of oral anticoagulants (vitamin K antagonists). Recently a change has taken place, and low molecular weight heparins are being used.
Guidelines recommend that patients receive heparin for at least four days and treatment should not be discontinued until the international normalized ratio has been in the therapeutic range for two consecutive days. According to these guidelines, a patient with a first episode of a proximal vein thrombosis should receive anticoagulants for six months, with a target international normalized ratio of 2.5. the issue of length of anticoagulation is still under debate.
Worth of note is that the absolute contraindications to anticoagulation treatment include intracranial bleeding, severe active bleeding, recent brain, eye, or spinal cord surgery, and malignant hypertension. Relative contraindications include recent major surgery, recent cerebrovascular accident, and severe thrombocytopenia.

Heparins: Unfractionated heparin is a heterogenous mixture of polysaccharide chains. Low molecular weight heparins are fragments of unfractionated heparin created by depolymerisation. Advantages of low molecular weight heparin over unfractionated heparin are that it offers a more consistent and predicable anticoagulant response, has a longer half life, and so permits once daily subcutaneous administration without the need to monitor activated partial thromboplastin time.

Low molecular weight heparin is at least as effective as unfractionated heparin in preventing recurrent venous thromboembolism, and statistically significantly reduces the occurrence of major haemorrhage during initial treatment and overall mortality at the end of follow up.

Thrombolytic drugs: There is weak evidence that thrombolytics such as streptokinase may produce more rapid resolution of symptoms and preserve venous valve integrity and hence decrease the incidence of the post-phlebitic syndrome. However, the risk of bleeding complications is three times greater, and for this reason thrombolytics are now seldom used.

Inferior vena cava filter: Inferior vena cava filters are inserted to reduce the rate of pulmonary embolism.

  • Absolute indications
  1. DVT or PE in patient with contraindication for anticoagulation
  2. Recurrent thromboembolism while on anticoagulation
  3. Anticoagulation complications requiring termination of  therapy

 

  • Relative contraindication
  1. Large, free-floating iliofemoral thrombus in high-risk patients
  2. Propagating iliofemoral thrombus while on anticoagulation
  3. Chronic PE in patient with pulmonary hypertension and cor pulmonale
  4. Patient with significant fall risk

In the United Kingdom most vena cava filters are temporary and removed three weeks after the period during which the risk of embolisation is greatest.
 
Elastic compression stockings: Patients with a deep vein thrombosis should wear compression stockings as the rate of post-thrombotic syndrome may be reduced. In one study of 194 patients (with a first episode of proximal deep vein thrombosis) the rate of post thrombotic syndrome was reduced by 50% if graded compression stockings were used.

Outpatient treatment of deep vein thrombosis: With the advent of low molecular weight heparins, outpatient treatment of deep vein thrombosis without monitoring activated partial thromboplastin time is now possible. Many trials have compared a home treatment regimen with hospital treatment for the initial phase of treatment for deep vein thrombosis. Most of the trials have been uncontrolled, and their limited evidence shows that home treatment is cost effective, preferred by patients, and no more liable to lead to complications than hospital treatment.

  

Special considerations: 

  1. First-episode venous thrombosis or thrombotic event due to a transient reversible risk factor should be treated for at least 3 months. Interruption of therapy prior to 12 weeks results in an 8% absolute increase in recurrent thrombosis within the following 12 months. Treatment for the entire 3 months results in an annual recurrent DVT incidence of 3%.
  2. For patients with first episode idiopathic venous thrombosis, treatment length should be 6-12 months.  However, the benefit of anticoagulation is lost after stopping treatment at one year, prompting many physicians to continue treatment indefinitely.  The decision to continue anticoagulation should be tailored to each patient, taking into consideration bleeding risk and patient preference with treatment reassessment at periodic intervals.
  3. For patients with a first-episode venous thrombosis and a documented antiphospholipid antibodies or 2 or more thrombophilic conditions (combined factor V Leiden and prothrombin 20210A gene mutations), at least 12 months of treatment is indicated. Six to 12 months of initial therapy is indicated in those patients with any one of the following: deficiencies of antithrombin, protein C, or protein S; factor V Leiden; prothrombin 20210A; hyperhomocysteinemia; or high factor VIII levels (>90th percentile).
  4. Indefinite therapy is recommended for patients with recurrent episodes of venous thrombosis regardless of the cause. The risk of recurrent thromboembolism during a 4-year follow-up period was reduced from 21% to 3% with continued anticoagulation. However, the incidence of major bleeding increased from 3% to 9%.
  5. Long-term therapy with LMWH has been shown to be as effective as warfarin in the treatment of venous thrombosis, except in those patients with a concurrent malignancy. In this subgroup, LMWH was shown to be more effective than oral therapy.
  6. Initial studies have also shown LMWH to be effective in pregnant patients, but long-term, large randomized trials have yet to be completed.
  7. Intravenous heparin remains the treatment of choice for those with endstage renal failure.
  8. A debate still exists regarding treating DVT in pregnant women, with some centers advocating prolonged use of LMWH instead of oral anticoagulants .In the United Kingdom it is still the current protocol to use LMWH or Warfarin for 6-12 months after birth.
  9. Patients should be tested for probable causes of DVT after treatment. Cancer and immobility are the leading causes of deep vein thrombosis in people over 45, and in people under that age thrombophilia becomes important.

 

Ongoing research:

  • A study published by the Journal of Family Practice, December 2007, suggested that a combination of the Well’s score and D-dimer levels can successfully predict DVT and thereby avoid the need for costly work-up.
  • A study conducted by the Radiologic society of North America in January 2008 revealed that direct intraclot injection of Alteplase is an effective treatment for DVT. The study was published in the February issue of Radiology.
  • The University of Michigan Health system conducted a study on lab mice on March 2008 that indicated that heparin heals vein walls damaged by DVT, stressing the current aggressive anticoagulation treatment protocols.
  • The American College of chest physicians published in October 2008 the results of a prospective randomized controlled trial precluding that statins show promise for blood clot prevention, although authors couldn’t draw conclusions about the cause and effect relationship between statins and VTE.
  • The University of Edinburgh supervised the biggest clinical trial to date suggesting that treating hospital patients with thigh length surgical stockings rather than knee length stockings can reduce life threatening blood clots, in September 2010.

 

Conclusions and recommendations:

It may look at first glance as if we are very well equipped when it comes to DVT, both in matters of diagnosis and management. But, there are still fields that need ongoing research to help better tailor the current treatment guidelines.

For instance, no clear consensus is available regarding the exact length of anticoagulation treatment (The British Thoracic Society is currently organizing a large multicentre trial to answer this question).

And on the other hand, large randomized trials are needed in order to solve the controversy regarding treating DVT in pregnant women.
To this date no clear answer is available as to whether patients with long term IVC filters need continuous anticoagulation or not.

And last but not least; large campaigns and awareness sessions should be done in order to raise the clinical level of suspicion when it comes to DVT.


اضغط هنا للقراءة باللغة العربية

Prepared by: Dr. Zaina Habrawi


Source :

Deep Vein Thrombosis. Author: Kaushal (Kevin) Patel, MD, Vascular Surgeon, Kaiser Permanente Los Angeles Medical Center. Updated Jan, 16 2009.
Diagnosis, investigation and management of DVT. Clive Tovey, consultant in emergency medicine and Suzanne Wyatt, consultant in emergency medicine. BMJ. May 31 2003.
Journal of Family Practice .Dec 2007 by Sarah-Anne Schumann, Bernard Ewigman.
Radiological society of North America. Jan 2008.
University of Michigan Health system .Mar 2008.
American college of chest physicians. Oct 2008.
University of Edinburgh. Sep 2010.
Lower limb deep vein thrombosis in a general hospital: risk factors, outcomes and the contribution of intravenous drug use, F.F. Syed and N.J. Beeching. November 1, 2004.
Society of International Radiology  






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