Diagnosis of deep vein thrombosis, and prevention of deep vein thrombosis recurrence and the post-thrombotic syndrome in the primary care medicine setting anno 2014

Abstract

The requirement for a safe diagnostic strategy of deep vein thrombosis (DVT) should be based on an overall objective post incidence of venous thromboembolism (VTE) of less than 1% during 3 mo follow-up. Compression ultrasonography (CUS) of the leg veins has a negative predictive value (NPV) of 97%-98% indicating the need of repeated CUS testing within one week. A negative ELISA VIDAS safely excludes DVT and VTE with a NPV between 99% and 100% at a low clinical score of zero. The combination of low clinical score and a less sensitive D-dimer test (Simplify) is not sensitive enough to exclude DVT and VTE in routine daily practice. From prospective clinical research studies it may be concluded that complete recanalization within 3 mo and no reflux is associated with a low or no risk of PTS obviating the need of MECS 6 mo after DVT. Partial and complete recanalization after 3 to more than 6 mo is usually complicated by reflux due to valve destruction and symptomatic PTS. Reflux seems to be a main determinant for PTS and DVT recurrence, the latter as a main contributing factor in worsening PTS. This hypothesis is supported by the relation between the persistent residual vein thrombosis (RVT = partial recanalization) and the risk of VTE recurrence in prospective studies. Absence of RVT at 3 mo post-DVT and no reflux is predicted to be associated with no recurrence of DVT (1.2%) during follow-up obviating the need of wearing medical elastic stockings and anticoagulation at 6 mo post-DVT. The presence or absence of RVT but with reflux at 3 to 6 mo post-DVT is associated with both symptomatic PTS and an increased risk of VTE recurrence in about one third in the post-DVT period after regular discontinuation of anticoagulant treatment. To test this hypothesis we designed a prospective DVT and postthrombotic syndrome (PTS) Bridging the Gap Study by addressing at least four unanswered questions in the treatment of DVT and PTS. Which DVT patient has a clear indication for long-term compression stocking therapy to prevent PTS after the initial anticoagulant treatment in the acute phase of DVT? Is 3 mo the appropriate point in time to determine candidates at risk to develop DVT recurrence and PTS? Which high risk symptomatic PTS patients need extended anticoagulant treatment?

Keywords: Anticoagulation; Deep Venous thrombosis; ELISA VIDAS D-dimer; Medical elastic stockings; Post-thrombotic syndrome; Ultrasonography.

Figure 1

Rotterdam approach to safely exclude and diagnose deep vein thrombosis[8,9]. CUS: Compression ultrasonography; DVT: Deep vein thrombosis.

Figure 2

Recanalization of proximal deep vein thrombosis is usually delayed and may be completed after 3, 6 to 9 mo post-deep vein thrombosis with a high incidence of reflux, deep vein thrombosis recurrence and PTS. A: The relationship between the time of complete recanalization after deep vein thrombosis (DVT) (lysis time of leg vein thrombosis) appears to be 3 mo for those DVT patients who did not develop reflux, but appeared to be about 9 to 12 mo for those DVT patients who developed reflux as a main determinant for the development of PTS [Common femoral vein (CFV), superficial femoral vein (SFV), middle superficial femoral vein (SFM), distal superficial vein (SFD), popliteal vein (PPT), posterior tibial vein (PTV), greater saphena vein (GSV)][15]; B: Localization of reflux in patients with delayed recanalization (Figure 2A) of deep vein thrombosis[15].

Figure 3

Event free recurrence rate of venous thromboembolism in 78 “low risk” DVT patients with no residual vein thrombosis at 3 mo post-DVT (RVT Neg) as compared to 92 "high risk" DVT patients with RVT at 3 mo post-DVT (RVT Pos group) after discontinuation of anticoagulation during 2 years follow-up in the prospective study of Siragusa et al[18]. RVT: Residual vein thrombosis.

Figure 4

Incidence of the post-thrombotic syndrome according to the CEAP classification in patients with deep vein thrombosis during long-term follow-up[32].

Figure 5

Rotterdam approach to the post-thrombotic syndrome according to Wentel et al[33]. PTS: Postthrombotic syndrome; MECS: Medical elastic compression stockings.

Figure 6

2007 Rotterdam Erasmus study design, time schedule, clinical score assessment and procedures for prospective evaluation of post-DVT venous thromboembolism-recurrence and postthrombotic syndrome. PTS: Postthrombotic syndrome; MECS: Medical elastic compression stockings.

Figure 7

European DVT - postthrombotic syndrome Bridging the Gap study design 2014. MECS: Medical elastic compression stockings.

Figure 8

Algorith modification of the D-dimer strategy according to the modified PROLONG study 23 for the duration and extension of anticoagulant treatment in post-DVT patients on top of objective risk stratification in Figure 7.