Today, we will discuss the well-known and concerning topic of deep venous thrombosis, which is under the umbrella term of venous thromboembolism. VTE (venous thromboembolism) encompasses deep vein thromboses (DVT) and pulmonary embolisms (PE).
In the general United States population, the incidence of a first DVT is around 100 per 100,000 persons per year. This increases with aging population.
About 66% of patient’s with VTE will present with DVT symptoms, whereas the remainder will present with PE symptoms. The mortality rate of DVT is 6 percent within the first month after diagnosis. The mortality rate is higher in cases of PE (12%) than DVT’s, but unfortunately, around 40% of patients with a proximal DVT have an associated PE simultaneously.
The pathophysiology and risk factors of a DVT are often described by Virchow’s triad. This triad states that a deep venous thrombosis is caused by at least one of three etiologies, including alterations in natural blood flow (stasis), hypercoagulability, and/or endothelial injury.
In 75 to 96 percent of DVT cases, it is found that at least one of Virchow’s triad is present at the time of diagnosis. If a DVT is suspected, their risk factors should be assessed, and a pretest probability should be calculated.
Below is a chart of risk factors for thromboembolism:
A clinical risk calculator for an individual patient’s risk of a DVT is the Well’s Score for DVT. This clinical calculator has been widely legitimized and is regularly used for pretest probability of DVT.
When using the calculator for each person’s risk of a DVT, patients can be divided into groups with a “likely DVT” or “unlikely DVT.”
A score of zero or less is associated with an unlikely DVT (low pretest probability) with a prevalence of a DVT of 5%.
A score of 1-2 is considered moderate/intermediate risk with a pretest probability of DVT being 17%.
A score of 3 or higher suggests that a DVT is likely (high pretest probability) with a probability of 17-53%.
Based on the pretest probability provided by the Well’s Score, this will direct us toward the appropriate diagnostic tool, which will be discussed later.
Deep Venous Thrombosis Presentation
Now for the presentation of DVTs. Classically, they will present with pain, redness, warmth, and swelling of the lower extremity. However, DVTs can present asymptomatically as well.
These “classic symptoms” however are not specific, nor sensitive for a DVT.
Other etiologies such as cellulitis, PAD/PVD, trauma, different types of infection, or venous diseases can present with findings similar to that of a DVT.
Additionally, it does not always have to be just PAD, cellulitis, or a DVT; it could be a combination of any multiple diagnoses!!
Below is an algorithmic approach to the diagnosis of DVT.
When calculating the pretest probability, if the risk is intermediate or higher, a lower extremity ultrasound should be completed. In patients that are symptomatic the sensitivity of a lower extremity ultrasound is 89 to 96 percent with a specificity of 94 to 99 percent.
In patients with intermediate to high-risk pretest probability of a DVT that have a negative ultrasound, this is not good enough to definitively rule out a DVT. Further analysis with a d-dimer is needed.
If the d-dimer testing is negative, then a DVT then can be excluded. If the d-dimer is elevated, a repeat ultrasound is needed in one week.
If the initial pretest probability is considered low risk, then the testing is reversed compared to intermediate or high risk. One should start with a d-dimer. If the d-dimer is negative, then a DVT can be ruled out. If the d-dimer is positive, then an ultrasound should be ordered. If the ultrasound is negative, a DVT can be ruled out.
Alternative Imaging for Deep Venous Thrombosis
Regarding other imaging techniques for diagnosis of a DVT, impedance plethysmography can be used. This measures the change in blood volume in the calf while a thigh cuff is inflated. The sensitivity and specificity of this modality is 91 and 96 percent for a DVT. In patients with preexisting venous disease, CHF, or PAD there is an increased risk of false-positive results.
However, impedance plethysmography is not regularly available in the United States.
Contrast venography has been considered the gold standard for diagnosis of DVT. However, it is no longer recommended in the initial evaluation due to the invasiveness, technical difficulties, and risks associated, such as pain involved, vessel damage, and allergic reaction to contrast media.
Venography is typically reserved for particular situations when the clinical suspicion for a DVT is high and non-invasive testing is indeterminate.
CT venogram has been studied as an imaging modality for diagnosis of DVT. It has been found to be comparable to ultrasound at diagnosis of DVT. However, with the radiation and contrast exposure needed for the CT venogram compared with the ultrasound (no radiation exposure or contrast required), it is rarely performed.
Lastly, magnetic resonance venogram has been studied for DVT diagnosis. It has been found to have sensitivity and specificity that is equal to ultrasound. However, the cost of an MRV is much more than ultrasound, so it has not been widely studied currently.
Treating Deep Venous Thrombosis
For quite some time, treatment of uncomplicated DVTs was narrowed to two options: Coumadin (Warfarin) and unfractionated or low molecular weight heparin.
Now, direct-acting oral anticoagulants (DOACs) have been found to be a safe option that is equally effective in treating DVTs.
Not only can we use the newer DOACs, but often these uncomplicated DVTs can be treated as an outpatient, as long as the patient is hemodynamically stable without any symptoms or signs of limb ischemia, significant comorbidities, functional limitations, high bleeding risk, or worries of nonadherence.
In those who are hemodynamically unstable, with a high likelihood of DVT, they should more often be admitted for intravenous anticoagulation and stabilization.
Once a DVT is diagnosed ALL patients must undergo anticoagulation therapy unless there is a contraindication.
The initial decision of which anticoagulation medication to use must be made. There are multiple options for providers and patients nowadays.
If warfarin, Pradaxa, or Savaysa is chosen as the anticoagulation agent, low molecular weight heparin (LMWH) is required to be given along with the aforementioned chosen anticoagulant for at least five days.
Eliquis and Xarelto are also other options for anticoagulation, and these do not require any additional anticoagulation with heparin.
A full list of anticoagulant choices for treatment, and the dosing are as listed as below:
Once patients are started on an outpatient regimen for anticoagulation, they should be seen in office periodically over the initial three-month period of therapy. During these visits, the patient should be evaluated for compliance and adherence to medication, as well as complications of increased bleeding.
If warfarin is used as the anticoagulant, patients often will require a high level of patient education on food and drug interactions, as well as the importance of regularly monitored INRs until steady state is reached.
If a DOAC is chosen, no routine laboratory (INR) monitoring is required. In addition, there are less food and drug interactions with these medications.
There are some stipulations with the DOACs, such as Xarelto should be taken with food, and it interacts with cytochrome P450 3A4 and P-glycoprotein inhibitors.
There are negatives, to the DOACs, however. First off, just like any novel medication or drug, they are costly, often ranging in the 300-450 dollar range per month. The other negative is that there is some ambiguity with the management of significant bleeding or in emergency surgeries. The only DOAC with a reversal agent currently is Pradaxa, which is called Praxbind.
DOACs also have shorter half-lives compared to warfarin, which means missed doses of the medication increases the risk of thromboembolic events in a shorter period of time.
DOACs also require renal dosing due to their elimination via the renal system. Also for Eliquis if a patient is over 80 years of age, or has a weight of 60 kg or less, dosing adjustment must be made.
Even with the risks or negatives of DOACs, the American College of Clinical Pharmacy recommends use of DOACs in treatment of DVTs over warfarin.
Inferior Vena Cava Filter
A final treatment option that I will briefly discuss is an inferior vena cava filter.
These are rarely indicated for use and evidence of safety is lacking. Only if there is an absolute contraindication to anticoagulation, an IVC filter may be considered. Use of IVC filters in patients taking anticoagulation has been shown not to reduce overall mortality, and current guidelines recommend against their use.
Now for our final topic, how long do we anticoagulate?
That is a complicated question.
The risk of a repeat DVT is highest within the first year after diagnosis, and overall a patient’s lifetime risk of recurrence compared to the general public is elevated. Lifetime reoccurrence ranges from 20 to 30 percent.
Long-term (lifelong) anticoagulation reduces the risk of repeat DVT, but this comes with increased risk of bleeding. Each individual’s risks must be accounted for when making this decision.
If there are no contraindications, patients should be anticoagulated for at least three months’ duration (sometimes is extended to 6 months based on risk factors for recurrence). If a reversible factor or etiology for the DVT is found, then anticoagulation is not needed for a longer duration.
Lifelong anticoagulation is recommended for patients without a provoking event/etiology and low risk of bleeding, and also for patients with a second DVT and low or moderate risk of bleeding.
Am Fam Physician. Deep Vein Thrombosis and Pulmonary Embolism: Current Therapy. 2017 Mar 1;95(5):295-302.
Ferri’s Clinical Advisor. Deep Venous Thrombosis. 2017.
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