The origins of clots are described by the Virchow triad which includes stasis, endothelial injury, and hypercoagulability. Deep venous thromboses (DVT) have specific risk factors that have been widely studied to improve diagnostic approaches and, more importantly, prevention. While the most common origins are in the extremities, where the lower extremity is greater than the upper extremity, they also can occur in the mesentery or pelvic veins, which are not detectable by Doppler ultrasound (US) studies. The prophylaxis based on these risk factors is practiced in all hospitals, with the use of pneumatic pressure devices and Lovenox or other anticoagulants.
Risk factors include age, bed rest, congestive heart failure, estrogen, family history, hematologic cancers, immobility, indwelling catheters, long-distance travel, major trauma, noninfectious inflammatory conditions, obesity, pregnancy (and postpartum status), prior venous thromboembolism (VTE), recent surgery, smoking*, solid cancers, stroke, and thrombophilias.
There is no gender predominance of DVTs; however, men are more likely to experience recurrent DVTs.
DVTs, on their own, can cause morbidity due to postthrombotic syndrome involving the local tissues. This is most concerning for the mortality associated with pulmonary embolism (PE) secondary to VTE.
DVTs either can be provoked or unprovoked. Provoked thromboembolisms can be associated with known risk factors, most of which are time-limited, while unprovoked may indicate an increased tendency to clot. Most DVTs diagnosed in the emergency department are unprovoked and carry an increased risk of recurrence versus provoked: 15% versus 5% over next 12 months. Often patients with inherited thrombophilias are unaware of their condition until diagnosed with their first VTE. While their condition increases the risk of occurrence against the general population, their risk of recurrence is the same as those with unprovoked DVTs. The high number of unprovoked cases may be due to undiagnosed thrombophilias.
Provoked DVTs can be due to patient age, with a higher risk for each year over 50 years old; surgery, where extended procedures or lack of thrombophrophylaxis both increase risk; immobility, the hip a greater cause than the knee which is greater than ankle which is greater than the shoulder which is greater than the elbow; estrogen use, pregnancy, and initial postpartum; chronic disease; infection; and impaired blood flow. Postoperative risks are greatest for abdominal cancer, joint replacement, or neurosurgery with deficits. The 4-year recurrence of surgically provoked DVT is 5% to 11%, depending on the procedure. In the cancer patient, there are a host of factors that determine the thrombogenic potential. In general, the larger the tumor and the less differentiated the cell line, the higher the risk. Metastatic cancers, acute leukemias, and myeloma carry the greatest risk. The following cancers are also known for higher thromboembolic potential: pancreatic, ovarian, stomach, renal, adenocarcinoma, glioblastoma, metastatic melanoma, and lymphoma.
While other cancers carry a lower risk of provoked DVT (cervical, prostate, localized breast, nonmelanomatous skin cancers) advanced cancer and chemotherapy increase the risks of VTE/DVT. Advanced breast or breast cancer treated with chemotherapy has a 10% rate of clinically significant VTE. Clotting risk in cancers treated with chemotherapy is highest during the induction phase, especially when treated with fluorouracil, tamoxifen, or L-asparaginase. Regardless of tumor stage, chemotherapy adjunctive red blood cell growth factors (EPO) increase risk. Use of thalidomide or lenalidomide for multiple myeloma treatment has also been identified as a risk factor.
In clinical practice, the Wells Criteria is often utilized to stratify the risk of a patient having a DVT. It is pertinent to note that the criteria are intended for use with those patients in whom DVT is clinically suspected and is not a diagnostic criterion but a risk stratification. The scoring serves to provide guidance on the “next best step” for the patient workup, be it D-dimer or US Doppler imaging. This system, however, serves as evidenced-based medicine and guided care based on the study of risk factors for DVT. While it is not all-inclusive, it provides a broad grouping of the most common risk factors.
The criteria are as follows: active cancer, bedridden for more than 3 days, major surgery within last 4 weeks, calf swelling greater than 3 cm more than contralateral leg 10 cm below tibial tuberosity, collateral superficial veins present, diffuse leg swelling, localized tenderness along the deep venous system, pitting edema which is greater in symptomatic leg, paralysis, paresis, immobilization of lower extremity, previous DVT, and lack of other more likely etiology.
Scoring is completed with 1 point given for each positive response and 2 points given for a positive response to the last statement, giving credence to the clinical gestalt that has been empirically tested. The sum scores are then classified as low risk (0), medium risk (1 to 2), and high risk (3 or more). Per the originating studies, a low risk is equivalent to 5% risk, and a negative D-dimer is sufficient to rule out DVT. Medium risk carries a 17% likelihood and either a high-sensitivity D-dimer can be used or forgone in lieu of a Doppler study, with a single negative test being sufficient. High risk has a prevalence of 17% to 53%, and US doppler is recommended, although it may not be sufficient. A follow up 1-week Doppler may be indicated to prevent missed events. If both D-dimer and Doppler are negative, then it is considered sufficient to rule out DVT, even in high-risk patients. Again, remember that this is a guide and cannot replace gestalt. Also, there are specific criteria such as the Wells criteria for pulmonary embolism (PE) or the Pulmonary Embolism Rule-Out Criteria (PERC) when concern for PE exists.
D-dimer assays can vary in sensitivity depending on the lab-specific type drawn, and not all labs report the same units providing various acceptable ranges for the results. Remember that there are many things that can cause elevated D-dimer beyond venous thromboembolism (VTE), such as age or pregnancy, that will influence the need for Doppler studies or empiric treatment. The D-dimer half-life of 8 hours results in elevated levels for approximately 3 days after the inciting event. Quantitative D-dimer holds a sensitivity of 94% to 98%, yet only a specificity of 50% to 60%. This allows us to utilize it as a screening tool but requires clinical evidence from the history and physical examination with possible further testing to confirm the diagnosis.
Notes Concerning Independent Risk Factors
Congestive Heart Failure: Primarily seen with systolic dysfunction
Estrogen: All forms of exogenous estrogen increase risk, with the worst risk in first months of therapy
Immobility and Bed Rest: Risk develops after 72 hours, with the worst presentation in two contiguous joints
Indwelling Catheters: Responsible for half of arm DVTs
*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. Such as the contraindication for estrogen oral contraceptive pill use in women greater than 35 years of age who smoke.