Consultations regarding deep venous thrombosis (DVT) may be daunting. The decision to commit a young patient to indefinite anticoagulation (AC), or to cease AC in an older patient at increased risk for recurrence often gives the physician pause.
Here we discuss some of the highlights of our approach to venous thromboembolism. The individual components are discussed at length in other chapters, including principles of AC (Chap. 25), DVT (Chap. 133), hereditary thrombophilia (Chap. 130), and the antiphospholipid antibody syndrome (APS; Chap. 131).
Patients often have significant anxiety after a thrombotic event. Although considerable progress has been made in the safety and convenience of AC, the process still poses serious risk and may impair the patient’s quality of life. It is important to communicate that AC management is inherently complex, therapeutic approaches must be individualized, and, ultimately, no approach is without risk, including life-threatening bleeding and/or thrombosis.
One should begin the evaluation of a new DVT by defining the context of the event. Critical questions include:
Were there any risk factors, such as surgery, immobility, trauma, indwelling catheters, cirrhosis, nephrotic syndrome, inflammatory disorders, or systemic estrogen therapy (Chap. 133)?
If present, are those risk factors modifiable and might they have reasonably provoked the event?
If dealing with a reoccurrence while on AC, had the patient been compliant with therapy?
Are there historical or physical clues that might suggest malignancy, APS, or a hereditary thrombophilia?
When probing hard enough, one is often able to identify a “risk factor” for thrombosis. This alone is insufficient to label an event “provoked”; rather, that risk factor must be thought to have reasonably caused the event. Attribution of causality is arduous and ultimately subjective.
When dealing with recurrent events in patients on AC, compliance must be probed at length. Labeling a patient as having “failed” therapy has significant consequences. First, this might suggest an underlying thrombophilia, such as malignancy or APS. Second, the lack of clear superiority data of one agent over another makes management decisions murky.
The physical exam must of necessity focus on the affected extremity. However, a comprehensive exam may provide valuable clues. Adenopathy or temporal wasting might suggest malignancy. Arthritis and malar rash might suggest an autoimmune diathesis such as lupus. Organomegaly and erythromelalgia should trigger concern for an MPN such as PV or ET. Spontaneous upper-extremity events might suggest thoracic outlet syndrome whereas unprovoked left iliofemoral DVT, particularly in young women, may represent May-Thurner syndrome.
Screening for underlying hereditary thrombophilias is often pursued although the general utility of this approach is not clear. This is discussed at length in Chap. 130. In general, such screening rarely changes management and has the potential for error if performed at the incorrect time. For example, levels of antithrombin III, protein C, and protein S may be falsely low in the acute setting. Functional protein S levels might be reduced when the factor V Leiden mutation is present, leading to erroneous diagnosis. Anticardiolipin antibodies require sustained elevation over 12 weeks to satisfy criteria for APS. Pregnancy and hepatic disease can also affect the serum levels of various pro- and anticoagulants and confound diagnosis.
The decision regarding the duration of therapy is complex (Chap. 133). These decisions must incorporate the risk of recurrence, risk of bleeding, and patient preferences. Generally, patients with either a provoked or distal DVT may be treated for a finite course, generally three months. Patients with unprovoked DVT/pulmonary embolism (PE), APS, recurrent thromboses, or active malignancy are often considered for indefinite therapy should the bleeding risk be acceptable.
In patients with unprovoked events who discontinue AC after a finite course, efforts aimed at risk stratification via D-dimer assays appear to be useful. Thromboprophylaxis with aspirin, has shown promise. However these approaches are not standardized. The American College of Chest Physicians publishes evidence-based antithrombotic guidelines that provide specific recommendations for a variety of scenarios and are a useful resource.
The availability of new, oral anticoagulants has dramatically changed AC management from both the patient and physician perspectives. Dabigatran, a direct thrombin inhibitor, and rivaroxaban, a factor Xa inhibitor, are FDA approved for the treatment of venous thromboembolism, with the former requiring an initial 5 to 10 days of parenteral AC. Both agents are oral, require adequate renal function, and produce a reliable anticoagulant effect that need not be monitored or titrated. They lack reliable antidotes in the event of bleeding, although such products are in development. It should be noted that patients with poor warfarin compliance are equally poor candidates for these agents. Because of their short half-life, skipped doses will result in a prompt loss of AC and increased risk of recurrent thrombosis.
In general, there is insufficient information regarding the superiority of one anticoagulant over another. There is abundant experience with warfarin (Coumadin) and LMWH. The latter is often preferred in patients with malignancy, although high-quality evidence in its support is lacking. Dabigatran and rivaroxaban lack specific data in hereditary thrombophilias, malignancy, and APS, and therefore caution should be exercised in these settings. Dabigatran showed an excess risk of bleeding and thrombosis when compared to Coumadin in patients with mechanical heart valves, exemplifying the potential peril in assuming anticoagulants are of equal efficacy in different settings.
Decisions regarding AC touch upon every aspect of a patient’s life and are not taken lightly. They are not as black and white as standardized chemotherapy regimens and require an understanding of the patient’s lifestyle, values, and risk of recurrence. Such assessment is difficult in the modern time-constrained environment. Furthermore, such decisions should not be made in a single-instance and then followed indefinitely. Rather, the decision to continue (or withdraw) AC is dynamic and should be revisited serially depending on the tolerance of therapy and other medical comorbidities.
Consultation is often requested in patients with arterial thrombosis, such as myocardial infarction, cerebrovascular accident, or acute limb ischemia. In the vast majority of cases, however, this is related to underlying atherosclerosis with local inflammation rather than a primary hypercoagulable state. Risk factors, mechanisms, and treatment of atherothrombosis are discussed in Chap. 134.
In rare cases where underlying risk factors for atherothrombosis are absent or there is a strong family history of thrombosis, particularly at young ages, we perform a limited hypercoagulable evaluation, including studies for the APS. Paroxysmal nocturnal hemoglobinuria (PNH) and MPNs may rarely result in arterial thromboses. We rarely find it helpful to obtain studies for protein C, protein S, or antithrombin III deficiency, and do not obtain studies for factor V Leiden or prothrombin 20210A mutations as these do not have a meaningful effect on management. Furthermore, routine screening for the thermolabile variant of the methylenetetrahydrofolate reductase (MTHFR) should be discouraged as there is no evidence of benefit in reducing plasma homocysteine levels.
Hence, broad hypercoagulable evaluations are not useful in isolated arterial thrombosis, as most findings are likely incidental rather than causal, and do not have a direct impact on patient management.