Richard A. Manzo

Relationship between changes in the deep venous system and the development of the postthrombotic syndrome after an acute episode of lower limb deep vein thrombosis: A one- to six-year follow-up

PURPOSE This study investigated changes in the deep venous system and the development of the postthrombotic syndrome (PTS) after an episode of acute deep vein thrombosis (DVT). METHODS Seventy-eight patients (41 male patients, 37 female patients) with acute DVT in 83 legs (31 right, 42 left, five bilateral) underwent annual follow-up examinations for 1 to 6 years (median, 3 years) for symptoms and signs of the PTS. A venous duplex scan was performed at each visit to detect obstruction and reflux in the veins, both of which may contribute to the development of the PTS. DVT was primary in 69 limbs and recurrent in 14 limbs. RESULTS When last examined 49 limbs were free of symptoms, and 34 had the PTS (23 edema only, 11 hyperpigmentation). Only two patients had ulcers during the follow-up period; both patients had the ulcers in areas of hyperpigmentation in limbs with recurrent DVT. The extent of disease was similar in limbs with the PTS (79% multisegment, 18% single segment) and those without the PTS (69% multisegment, 12% single segment). In limbs with the PTS the deep veins were normal in only one (3%), six (18%) showed reflux only, five (15%) obstruction only, and 22 had features of both obstruction and reflux (65%). In limbs without the PTS the deep veins showed no abnormality in nine (18%), reflux only in 17 (35%), obstruction only in six (12%), and reflux with obstruction in 17 (35%). In the 11 limbs with hyperpigmentation nine had obstruction and reflux noted, one had obstruction only, and one had reflux alone. CONCLUSIONS After an episode of acute DVT 12% of the limbs returned to normal by duplex criteria. Although only 13% developed skin complications, 41% had features of the PTS. Limbs with the PTS had more than three times the odds of having combined reflux and obstruction than did limbs without the PTS (odds ratio = 3.5, 0.95 confidence intervals = 1.4, 8.6). Continued study of these patients will determine the course of those limbs with venous abnormalities that have not yet developed symptoms and signs of the PTS.

Deep venous insufficiency: The relationship between lysis and subsequent reflux

PURPOSE Although venous valvular insufficiency is well recognized as the most important etiologic mechanism in the development of the postthrombotic syndrome, the factors contributing to valve incompetence after deep venous thrombosis remain obscure. METHODS To establish the relationship between recanalization and valve competence, 113 patients with acute deep venous thrombosis were studied with serial duplex ultrasonography. RESULTS Median lysis times for segments developing reflux (214 to 474 days) were 2.3 to 7.3 times longer than for corresponding segments not developing reflux (65 to 130 days) for all except the posterior tibial vein. In the posterior tibial vein, median lysis times for those with and without reflux were nearly identical (72 vs 80 days). The median time to onset of reflux was significantly less than the median lysis time in the mid and distal superficial femoral veins and was simultaneous with recanalization in all other segments. CONCLUSIONS Early recanalization is important in preserving valve integrity for all but the posterior tibial segment. However, the small number of patients with reflux despite early lysis (< 1 month) or without reflux despite relatively late lysis (> 9 to 12 months) suggests that other factors may also contribute to the development of valvular incompetence. These factors may be particularly important in the posterior tibial vein, in which lysis time has little relationship to the ultimate development of reflux.

Valvular reflux after deep vein thrombosis: Incidence and time of occurrence

From December 1986 to December 1990, 268 patients with acute deep vein thrombosis were studied in our laboratory. From this group 107 patients (123 legs with deep vein thrombosis) were placed in our long-term follow-up program. The documentation of valvular reflux and its site was demonstrated by duplex scanning. The duplex studies were done at intervals of 1 and 7 days, 1 month, every 3 months for the first year, and then yearly thereafter. The mean follow-up time for these patients was 341 days. In addition, reflux was evaluated in 502 patients with negative duplex study results and no previous history of deep vein thrombosis or chronic venous insufficiency. In the patients with acute deep vein thrombosis, valvular incompetence was noted in 17 limbs (14%) at the time of the initial study. Reflux was absent in 106 limbs (86%). In this last group reflux developed in 17% of the limbs by day 7. By the end of the first month, 37% demonstrated reflux. By the end of the first year, more than two thirds of the involved limbs had developed valvular incompetence. The distribution of reflux at the end of the first year of follow-up was the following: (1) popliteal vein, 58%; (2) superficial femoral vein, 37%; (3) greater saphenous vein, 25%; and (4) posterior tibial vein, 18%. Reflux seems to be more frequent in the segments previously affected with deep vein thrombosis. Among cases where segments were initially affected with thrombi, after 1 year the incidence of reflux was 53%, 44%, 59%, and 33% for the common femoral vein, superficial femoral, popliteal vein, and posterior tibial vein, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Determinants of chronic venous disease after acute deep venous thrombosis

PURPOSE The purpose of this investigation was to evaluate the relationship between the presenting features of an acute deep venous thrombosis (DVT), the subsequent natural history of the thrombus, and the ultimate outcome as defined according to the Society for Vascular Surgery and the North American Chapter of the International Society for Cardiovascular Surgery reporting standards in venous disease. METHODS Patients with an acute DVT were followed with serial clinical and ultrasound examinations. Thrombus extent within 7 venous segments was scored retrospectively according to the reporting standards (scores ranged from 0 to 3), and segmental reflux was scored as present (1) or not present (0). The initial and final thrombus scores, the rates of recanalization and rethrombosis, and the total reflux scores were then calculated from these grading scales and related to ultimate chronic venous disease (CVD) classification. RESULTS Sixty-eight patients with an acute DVT in 73 limbs were followed for 18 to 110 months (mean, 55 +/- 26 months). At the completion of the follow-up period, 20 extremities (27%) were asymptomatic (class 0), 13 (18%) had pain or prominent superficial veins (class 1), 25 (34%) had manifested edema (class 3), 13 (18%) had developed hyperpigmentation (class 4), and 2 (3%) had developed ulceration (class 5). In a univariate analysis, CVD classification was correlated with the reflux score (P =.003) but not with the initial or final thrombus score or with the rate of recanalization or rethrombosis. In a multivariate model of features documented at presentation, only the tibial thrombosis score was a significant predictor of CVD classification (R2 =.06). Outcome was better predicted (R2 =.29) with a model that included variables defined during follow-up the final reflux score, the final popliteal score, and the rate of recanalization. CONCLUSION The ability to predict the severity of CVD after an acute DVT is currently limited, although the natural history appears more important than the presenting features of the event. The extent of reflux, the presence of persistent popliteal obstruction, and the rate of recanalization are related to ultimate CVD classification, but other determinants remain to be identified.

Propagation, rethrombosis and new thrombus formation after acute deep venous thrombosis

PURPOSE The purpose of this study was to determine the incidence, timing, and outcome of further thrombotic events after an initial episode of acute deep venous thrombosis. METHODS Venous thrombi in 204 lower extremities (177 patients) were monitored with duplex ultrasonography at intervals of 1 day, 7 days, 1 month, every 3 months for 1 year, and yearly thereafter. RESULTS Among initially involved extremities, propagation to new segments occurred in 61 (30%) and rethrombosis occurred in 63 (31%). Both propagation and rethrombosis, in different segments, occurred in 27 (13%) extremities. New thrombi were also noted in nine (6%) initially uninvolved extremities. These events were not associated with identifiable clinical risk factors, although extremities with rethrombosis were more extensively involved at presentation. Propagation in initially involved extremities was an early event, occurring within a median of 40 days in all segments. New thrombotic events in initially uninvolved extremities and rethrombosis occurred as later events. The development of reflux was significantly more common among all initially uninvolved segments to which thrombus extended and among mid and distal superficial femoral and popliteal artery segments with rethrombosis. CONCLUSIONS Recurrent thrombotic events are common after acute deep venous thrombosis and adversely affect the ultimate development of valvular incompetence. Their occurrence is unrelated to recognized clinical risk factors and can occur despite standard anticoagulation measures.

Early outcome after isolated calf vein thrombosis.

PURPOSE The clinical significance of isolated calf vein thrombosis (CVT), particularly with respect to development of the postthrombotic syndrome, remains controversial. The purpose of this study was to define the early natural history of CVT in relation to persistent lower extremity symptoms, propagation, recanalization, and the development of valvular incompetence. METHODS Over a 116-month period, 499 patients with acute deep venous thrombosis (DVT) were referred to our research laboratory, of whom 58 (12%) had thrombosis confined to the calf veins of at least one extremity. The lower extremities of 268 patients (29 with isolated CVT) were followed-up clinically and with duplex ultrasonography at intervals of 1 day, 7 days, 1 month, every 3 months for the first year, and yearly thereafter. RESULTS Seventy percent of extremities with CVT were symptomatic at presentation. Although the prevalence of clinical signs and symptoms decreased to 29% by 1 month, 23% of patients had persistent pain, edema, or both at 12 months. In contrast, 9% of uninvolved extremities contralateral to a CVT and 54% of extremities with proximal DVT remained symptomatic at 1 year (p = 0.004). Recanalization proceeded rapidly such that the mean thrombus load was reduced by 50% at 1 month and to zero at 1 year. The prevalence of valvular incompetence progressively increased such that reflux was present in 24% of extremities at 1 year. Although its investigation was not a primary goal of this study, pulmonary embolism was diagnosed at presentation and during follow-up in 11% and 3% of patients, respectively. CONCLUSIONS The natural history of CVT is complicated by persistent symptoms and the development of valvular incompetence in approximately one-quarter of patients. This potential for persistent lower extremity symptoms should be considered in evaluating the clinical relevance of isolated calf vein DVT.

Venous valvular reflux in veins not involved at the time of acute deep vein thrombosis

PURPOSE The aim of this study was to determine whether, in lower extremities with documented episodes of acute deep venous thrombosis (DVT), incompetence develops in veins that were not the site of thrombosis. METHODS Patients were monitored with serial duplex ultrasonography at 1 day, 1 week, 1, 3, 6, 9, and 12 months, and then annually after detection of acute DVT. The following venous segments were analyzed: common femoral, greater saphenous, proximal superficial femoral, deep femoral, popliteal, and posterior tibial. The incidence of reflux development in both thrombosed and uninvolved segments was determined. Reflux was categorized as either transient or permanent. RESULTS A total of 227 limbs in 188 patients were serially studied. Mean follow-up was 19.9 months (range 1 to 88 months). Overall, 403 of the 1423 segments (28.3% +/- 2.3%) developed reflux during the study, of which 118 (29.3% +/- 4.4%) had no prior or concurrent history of thrombosis. Considering only the segments that developed incompetence, the percent without prior thrombosis at each level was as follows: common femoral vein (40.0%), greater saphenous vein (53.1%), deep femoral vein (20.6%), proximal superficial femoral vein (23.9%), popliteal vein (8.9%), and posterior tibial vein (31.9%). Valvular insufficiency developing in segments uninvolved with thrombus was more likely to be transient (40.2%) than was the reflux in thrombosed segments (22.6%). This difference was statistically significant (p < 0.05). CONCLUSIONS Permanent venous valvular damage can occur in the absence of thrombosis after DVT. Reflux in uninvolved venous segments has a different anatomic distribution and is more likely to be transient than the incompetence associated with thrombosis.