**[SEQUELLAE OF VENOUS THROMBOEMBOLISM PROPHYLAXIS]{.underline}**

**Samuel Z. Goldhaber, MD**

**Professor of Medicine**

**Harvard Medical School**

**Director, Venous Thromboembolism Research Group**

**Director, Anticoagulation Service**

**Brigham and Women's Hospital**

**July 3, 2006**

**Cardiovascular Division**

**Brigham and Women's Hospital**

**75 Francis Street**

**Boston, MA 02115**

**Phone: 617-732-7566**

**FAX: 617-264-5144**

**[E-mail: ]{.underline}**

[When patients are diagnosed with deep vein thrombosis (DVT) or
pulmonary embolism (PE), we tend to focus on immediate issues such as
ensuring adequate and timely anticoagulation, stratifying the patient
into high risk or low risk for complications, and determining whether
hospitalization is necessary and, if so, for how long and for what
objectives. The diagnosis of venous thromboembolism (VTE) is rarely
anticipated, so that when DVT or PE is detected, a sense of urgency and
a need for immediate disposition becomes of paramount importance. This
approach is understandable and necessary, but it obscures the
intermediate and long-term issues with which patients, families, and
health care professionals must grapple. ]{.underline}

[Though we tend to think of PE as a "life or death" issue, most
sequellae of DVT and PE affect quality of life rather than survival. The
three most common follow-up problems are: 1) chronic venous
insufficiency, 2) recurrent DVT or PE, and 3) chronic thromboembolic
pulmonary hypertension. ]{.underline}

[Patients stricken with VTE often have difficulty dealing with the
psychological aftermath of their illness. This consequence of VTE may
not be apparent and often requires specific questioning to elicit.
]{.underline}

**[CHRONIC VENOUS INSUFFICIENCY]{.underline}**

The five stages of chronic venous insufficiency (also called
"postthrombotic syndrome") are outlined in Table 1. Varicose veins may
be mild or extensive. At times they cause concern because they are
cosmetically unappealing. However, when extensive, they can cause
chronic pain and burning. Ankle and lower leg edema occurs because of
permanent damage to the valves of the leg veins from the initial DVT,
even if subsequent anticoagulation control is excellent.

[ Brownish skin pigmentation changes are especially common in the area
of the medial malleolus. These pigmentation abnormalities are caused by
deposition of hemosiderin. The changes tend to be permanent and
irreversible. Under the most severe circumstances, chronic venous
insufficiency can progress to skin ulceration. ]{.underline}

[ In one cohort of VTE patients followed for 10 years, more than half
developed clinical evidence of at least mild venous insufficiency (1).
The likelihood of developing severe disease was 6%. Risk factors for
developing chronic venous insufficiency include proximal (as opposed to
isolated calf) leg DVT, male gender, and high D-dimer levels. Patients
with chronic venous insufficiency have an increased risk of suffering
recurrent VTE (2). ]{.underline}

**[RECURRENT VENOUS THROMBOEMBOLISM]{.underline}**

[ DVT and PE often recur following cessation of anticoagulation.
Overall, the recurrence rate is about 30% with 8-year follow-up of
patients who receive 3-6 months of initial anticoagulation that is then
discontinued (3). Recurrence is more likely if the initial episode was
not provoked by trauma, surgery, or hormonal changes due to pregnancy,
oral contraceptives, or hormone replacement. Therefore, the trend has
been to prescribe prolonged and at times indefinite duration
anticoagulation when the initial VTE is spontaneous. ]{.underline}

[ Patients with symptomatic PE have a higher risk of recurrent VTE than
those presenting with DVT symptoms alone. Those who initially presented
with PE are more likely to have a PE recurrence than a DVT recurrence
(4). For reasons that remain unclear, the risk of recurrent VTE is
higher among men than women (5). ]{.underline}

**[CHRONIC THROMBOEMBOLIC PULMONARY HYPERTENSION]{.underline}**

[ Chronic thromboembolic pulmonary hypertension used to be considered a
rare complication of acute PE that occurred as a sequella in
approximately 1 of 500 cases of PE. However, a long-term prospective
follow-up study of 223 patients has shown that this serious complication
of PE is relatively common. After 2 years of follow-up, the incidence
was 3.8%. No new cases occurred after 2 years of follow-up. Risks for
developing chronic thromboembolic pulmonary hypertension included a
history of prior PE, an anatomically large PE, and an initial
presentation with an unprovoked spontaneous PE (6). ]{.underline}

The chronic thromboembolic material is fibrous and hardens into the wall
of the pulmonary artery. It cannot be thrombolysed and requires surgical
pulmonary thromboendartectomy for removal (7). This complex operation
requires median sternotomy, cardiopulmonary bypass, profound
hypothermia, and circulatory arrest. Balloon pulmonary angioplasty (8)
and medical treatment with drugs such as sildenafil (9) are emerging
options for inoperable patients.

# [CONCLUSIONS]{.underline}

Our concept of VTE has changed. DVT and PE no longer constitute
time-limited short-term illnesses. Patients who suffer VTE are
susceptible to long-term consequences, including chronic venous
insufficiency, recurrent VTE, and chronic thromboembolic pulmonary
hypertension. The realization that these problems may be long-term can
lead to psychological difficulty in coping with VTE as well as medical
debility.

**[REFERENCES]{.underline}**

[1. Schulman S, Lindmarker P, Holstrom M. Larfars G, Carlsson A, Nicol
P, Svensson E, Ljungberg B, Viering S, Nordlander S, Leijd B, Jahed K,
Hjorth m, Linder O, Beckman M. Post-thrombotic syndrome, recurrence, and
death 10 years after the first episode of venous thromboembolism treated
with warfarin for 6 weeks or 6 months. ]{.underline}

[2. Stain M, Schonauer V, Minar E, Bialonczyk C, Hirschl M, Weltermann
A, Kyrle PA, Eichinger S. The post-thrombotic syndrome: Risk factors and
impact on the course of thrombotic disease. J Thromb Haemost
2005;3:2671-2676.]{.underline}

[3. Prandoni P, Lensing AWA, Cogo A, Cuppini S, Villalta S, Carta M,
Cattelan AM, Polistena P, Bernardi E, Prins MH. The long-term clinical
course of acute deep venous thrombosis. Ann Intern Med 1996; 125:
1-7.]{.underline}

[4. Eichinger S, Weltermann A, Minar E, Stain M, Schonauer V, Schneider
B, Kyrle PA. Symptomatic pulmonary embolism and the risk of recurrent
venous thromboembolism. Arch Intern Med 2004;164:92-96.]{.underline}

[5. Kyrle PA, Minar E, Bialonczyk C, Hirschl M, Weltermann A, Eichinger
S. The risk of recurrent venous thromboembolism in men and women. N Engl
J Med 2004;350:2558-2563.]{.underline}

[6. Pengo V, Lensing AWA, Prins MH, Marchiori A, Davidson BL, Tizzo F,
Albanese P, Biasiolo A, Pegoraro C, Iliceto S, Prandoni P, for the
Thromboembolic Pulmonary Hypertension Study Group. Incidence of chronic
thromboembolic pulmonary hypertension after pulmonary embolism. N Engl J
Med 2004;350:2257-2264.]{.underline}

[7. Jamieson Sw, Kapelanski DP, Sakakibara N, Manecke GR, Thistlethwaite
PA, Kerr KM, Channick RN, Fedullo PF, Auger WR. Pulmonary
endarterectomy: Experience and lessons learned in 1,500 cases. Ann
Thorac Surg 2003;76:1457-1464.]{.underline}

[8. Feinstein JA, Goldhaber SZ, Lock JE, Ferndandes SM, Landzberg MJ.
Balloon pulmonary angioplasty for treatment of chronic thromboembolic
pulmonary hypertension. Circulation 2001;103:10-13.]{.underline}

[9. Hoeper MM, Mayer E, Simonneau G, Rubin LJ. Chronic thromboembolic
pulmonary hypertension. Circulation 2006;113:2011-2020.]{.underline}

**[Table 1. Stages of Chronic Venous Insufficency]{.underline}**

1.  [Varicose veins]{.underline}

2.  [Ankle/ leg edema]{.underline}

3.  [Stasis dermatitis]{.underline}

4.  [Lipodermatosclerosis]{.underline}

5.  [Venous stasis ulcer]{.underline}