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2272 Part XII: Hemostasis and Thrombosis Chapter 133: Venous Thrombosis 2273

be done among patients with features suggesting a possible alternate hypertension was 3.8 percent at 2 years after diagnosis, despite state-of-
source of embolism to proximal DVT of the leg (e.g., upper-extremity the-art treatment for PE. The strongest independent risk factors were a
thrombosis, renal vein thrombosis, pelvic vein thrombosis, or right- history of PE (odds ratio: 19) and idiopathic PE at presentation (odds
heart thrombus). ratio: 5.7). 56

THERAPY, COURSE, AND PROGNOSIS OBJECTIVES AND PRINCIPLES OF
CLINICAL COURSE OF VENOUS ANTITHROMBOTIC TREATMENT
THROMBOEMBOLISM The objectives of treatment in patients with established VTE are to (1)
prevent death from PE, and (2) prevent morbidity from recurrent DVT
Proximal Vein Thrombosis or PE, especially the postthrombotic syndrome and chronic pulmonary
Proximal vein thrombosis is a serious and potentially lethal condition. hypertension.
Untreated proximal vein thrombosis is associated with a 10 percent rate For most patients, these objectives are achieved by providing ade-
of fatal PE. Inadequately treated proximal vein thrombosis results in a quate anticoagulant treatment. Thrombolytic therapy is indicated in
51
20 to 50 percent risk of recurrent VTE events. Prospective studies of selected patients (see “Thrombolytic Therapy” below). Use of an infe-
patients with clinically suspected DVT or PE indicate that new VTE rior vena cava filter is indicated to prevent death from PE in patients
events on followup are uncommon (≤2 percent) among patients in in whom anticoagulant treatment is absolutely contraindicated and in
whom proximal vein thrombosis is absent by objective testing. 17,32,33,47,50 other selected patients (see “Anticoagulant Therapy” below). These rec-
The aggregate data from diagnostic and treatment studies indicate that ommendations and those below are linked to the strength of the evi-
the presence of proximal vein thrombosis is the key prognostic marker dence from clinical trials and evidence-based guidelines. 9,30,57,58
for recurrent VTE.

Calf Vein Thrombosis ANTICOAGULANT THERAPY
Thrombosis that remains confined to the calf veins is associated with Anticoagulant therapy is the treatment of choice for most patients
low risk (≤1 percent) of clinically important PE. Extension of throm- with proximal vein thrombosis or PE. 9,57,58 Patients with proximal DVT
bosis into the popliteal vein or more proximally occurs in 15 to 25 require both adequate initial anticoagulant treatment with heparin or
1
percent of patients with untreated calf vein thrombosis. Patients with low-molecular-weight (LMW) heparin and adequate long-term anti-
documented calf vein thrombosis should either receive anticoagulant coagulant therapy to prevent recurrent VTE. 51,59,60 Anticoagulant ther-
treatment to prevent extension or undergo monitoring for proximal apy for at least 3 months is required to prevent a high frequency (15 to
extension using serial ultrasonography. 25 percent) of symptomatic extension of thrombosis and/or recurrent
venous thromboembolic events. 51,60,61 Adequate anticoagulant treatment
Postthrombotic Syndrome reduces the incidence of recurrence during the first 3 months after diag-
52
The postthrombotic syndrome is a frequent complication of DVT. nosis to 5 percent or less. 51,59–61
Patients with the postthrombotic syndrome complain of pain, heavi- The absolute contraindications to anticoagulant treatment include
ness, swelling, cramps, and itching or tingling of the affected leg. Ulcer- intracranial bleeding, severe active bleeding, recent brain, eye, or spinal
ation may occur. The symptoms usually are aggravated by standing or cord surgery, and malignant hypertension. Relative contraindications
walking and improve with rest and elevation of the leg. A prospective include recent major surgery, recent cerebrovascular accident, active
study documented a 25 percent incidence of moderate-to-severe post- gastrointestinal tract bleeding, severe hypertension, severe renal or
9
thrombotic symptoms 2 years after the initial diagnosis of proximal vein hepatic failure, and severe thrombocytopenia (platelets <50 × 10 /L).
thrombosis in patients who were treated with initial heparin and oral
53
anticoagulants for 3 months. The study also demonstrated that ipsilat- Parenteral Anticoagulants
eral recurrent venous thrombosis is strongly associated with subsequent Heparin and Low-Molecular-Weight Heparin Initial therapy with
development of moderate or severe postthrombotic symptoms. Thus, continuous intravenous heparin was the standard approach to treat-
prevention of ipsilateral recurrent DVT likely reduces the incidence of ment of VTE during the 1970s and 1980s. During the 1990s, LMW hep-
the postthrombotic syndrome. Application of a properly fitted graded arin given by subcutaneous injection once or twice daily was evaluated
compression stocking, as soon after diagnosis as the patient’s symptoms by clinical trials and shown to be as effective and safe as continuous
will allow, can improve edema and pain in the acute stage of DVT and intravenous heparin for the initial treatment of patients with proximal
may also help control or relieve symptoms in patients who develop the DVT and submassive PE. 57,58,62 The advantage of LMW heparin is that it
postthrombotic syndrome. Conflicting findings have been found in does not require anticoagulant monitoring. LMW heparin given subcu-
randomized trials of graded compression stockings for preventing the taneously once or twice daily is preferred over intravenous unfraction-
development of the postthrombotic syndrome. 54,55 ated heparin for the initial treatment of most patients with either DVT
or PE. 57,58 LMW heparin enables outpatient therapy for many patients
Chronic Thromboembolic Pulmonary Hypertension with uncomplicated DVT and selected patients with PE. Intravenous
Chronic thromboembolic pulmonary hypertension is a serious com- unfractionated heparin remains a useful approach for initial anticoagu-
plication of PE. Historically, thromboembolic pulmonary hypertension lant therapy in patients with severe renal failure. Initial treatment with
was believed to be relatively rare and to occur only several years after LMW heparin or unfractionated heparin should be continued for at
the diagnosis of PE. A prospective cohort study provides important least 5 days. Table 133–2 lists the specific LMW heparin regimens for
information on the incidence and timing of thromboembolic pulmo- the treatment of VTE.
nary hypertension. The results indicate that thromboembolic pulmo- If unfractionated heparin is used for initial therapy, it is important
56
nary hypertension is more common and occurs earlier than previously to achieve an adequate anticoagulant effect, defined as an activated partial
thought. On prospective followup of 223 patients with documented thromboplastin time (aPTT) above the lower limit of therapeutic range
PE, the cumulative incidence of chronic thromboembolic pulmonary within the first 24 hours. 63,64 Failure to achieve an adequate aPTT effect

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