PTS is a frequent DVT complication in women that severely impacts QoL and is under-recognized despite high disease burden.

Key Takeaway

In this session, Prof. Susan R. Kahn discusses PTS in women and suggests that:

  • It is a common, occasionally severe DVT complication, even in young women
  • Main risk factors include extensive and recurrent ipsilateral DVT, persisting leg symptoms 1 month post DVT, obesity, older age, smoking, post-natal DVT
  • ECS is the current standard of care for treatment of PTS
  • Ongoing research seeks to identify medication and interventional approaches

Why This Matters

  • PTS develops in 33–50% of patients with DVT after anticoagulation therapy and adversely affects QoL, decreases productivity, and is severe in 5–10%.

Key Results

Common clinical features of PTS (Rabinovich A and Kahn SR, 2018)

  • Leg symptoms: Most common ones are heaviness, pain, and swelling, while others include itching, cramping, paresthesia, and bursting pain
  • Signs: Edema, hyperpigmentation, peri-malleolar telangiectasia, venous ectasia, redness, dependent cyanosis, lipodermatosclerosis, leg ulceration
  • Features may be intermittent or persistent, and may vary across patients
    • Worsens while standing and walking; improves with leg elevation, and rest
    • Ranges from mild to severe symptoms, limiting work and functioning
  • Severe PTS and venous ulcer can develop in 5–10% of women and are chronic, painful, slow to heal, often recurring, and requires medical scrutiny.

How often does PTS occur in women? (McColl MD, et al. 2000)

  • Retrospective cohort study of 43 young women (≤50 years) with prior VTE episodes (63% pregnancy-related); examined ~4 years after VTE
    Prior VTE N All PTS Mild PTS Moderate PTS
    Single DVT 43 74% 67% 7%
    Recurrent DVT 9% 100% 55% 44
  • Risk of PTS is quite high following pregnancy-related DVT due to:
    • More involvement of femoral and iliac veins than in non-pregnant DVT
    • More anatomically extensive proximal DVT being a risk factor itself
      Study N Proximal DVT (%) Left DVT (%) Antenatal DVT (%) Duration of assessment PTS (%) Severity (%)
      Wik HS, et al 2016 182 82 75 60 9.6 post pregnancy 41 19 (moderate or severe)
      Wik HS, et al 2012 313 83 75 49 9.1 after first VTE 42 7 (severe)

Independent predictors of PTS after pregnancy related DVT* (Wik HS, et al. 2016)

  • Age >33 vs ≤33 (Ref) years: aOR = 3.9 (95% CI: 1.8–8.3), P <0.001
  • Daily vs non-daily (Ref) smokers: aOR = 2.9 (95% CI: 1.3–6.4), P = 0.011
  • Post- vs ante-natal (Ref) pregnancy: aOR = 3.5 (95% CI: 1.8–7.0), P <0.001
  • Proximal vs distal (Ref) DVT location: aOR = 2.6 (95% CI: 1.1–6.4), P = 0.037
  • HsCRP (>0.84 g/L): aOR = 2.4 (95% CI: 1.2–4.8), P = 0.01

PTS effect on QoL post DVT in 1,040 women (18–64 years) (Ljungqvist M, et al. 2018)

  • At 6 years median follow-up: Women with PTS had severely impaired QoL across all measures (P <0.001)
  • Other predictors: older age, obesity, physical inactivity, and recurrent VTE

ECS—Standard of care for PTS, but compliance is crucial

  • Reduces edema, leg pain, and heaviness
  • Instructed to apply in the morning and remove at bedtime or early evening
  • Knee-length ECS: More comfortable and easier to apply than thigh-length ECS, with comparable physiologic effects
  • Begin with knee length 30–40 mm Hg ECS: If difficult to apply or restrictive, try 20–30 mm Hg ECS; some patients may need higher compression strengths (e.g., 40–50 mm Hg) to control edema

Other types of compression therapy for moderate-to-severe PTS

  • Intermittent pneumatic compression devices for severe PTS: Effective, but impractical (patients need to remain stationary ≥2 h/day), costly (Ginsberg JS, et al. 1999)
  • Portable, battery-powered lower-limb venous return aid device for moderate or severe PTS: Better QoL and lower PTS severity while using the device alone or in conjugation with ECS (O’Donnell MJ, et al. 2008)

Medications for PTS treatment (Kahn SR, et al. 2016; Kahn SR, et al. 2014; Cohen JM, et al. 2012)

  • Low quality evidence for efficacy of rutosides, horse chestnut extract, hidrosmin, and defibrotide (short-term use i.e., 3–12 weeks)
  • Rigorous multi-center studies needed to assess efficacy, sustainability, safety
  • Ongoing Canadian RCT: MUFFIN PTS Trial (Galanaud JP, et al. 2021)
  • MPFF b.i.d. vs placebo b.i.d. (6 months) (Li KX, et al. 2021)

Exercise training for PTS treatment (Kahn SK, et al. 2011)

  • A 6-month RCT (26-week) comprising strengthening, stretching, and aerobic components to improve leg strength and flexibility and overall CV fitness
  • Exercise group demonstrated improved QoL, leg strength and flexibility, as well as a trend towards an improved Villalta PTS score.

Surgery or interventional approaches to treat moderate or severe PTS

  • Case reports and case series suggest that venous bypass grafting, valve reconstruction, vein dilation and stent implantation, PCDT, endophlebectomy, and interruption of perforating veins are useful for moderate or severe PTS.
  • No methodologically rigorous, comparative trials have been conducted to test the efficacy and safety of treatments for moderate or severe PTS.
  • Ongoing C-TRACT Trial seeks to address this gap.

*OR adjusted for: 1) Postnatal, proximal DVT, age >33 years at the time of index pregnancy and smoking before the index pregnancy

    Kahn SR. Post-thrombotic syndrome in women. Presented at the 10th International Symposium on Women's Health Issues in Thrombosis and Hemostasis (WHITH) Congress on October 2, 2022.