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Cause And Symptoms

Complications

Diagnosis And Treatment

Overview

Prevention

References

thrombosis

Thrombosis

Venous thromboembolism incidence among patients recommended for pharmacologic thromboembolism prophylaxis after cesarean delivery in selected guidelines
Adapted from Federspiel JJ, et al. J Thromb Haemost. 2021;19:830–838.

<h2>Key Takeaway</h2>
Incidence of VTE for high-risk caesarean delivery is unclear in the guidelines and risk stratification approaches are widely promulgated. This retrospective cohort study highlights widely different proportions of risk of VTE following delivery across different guidelines in US
Based on the chosen guideline:
<ul>
 <li>Incidence of pharmacologic recommendation varied from 0.2% (2018 ASH) to 73.4% (2015 RCOG)</li>
 <li>Incidence of VTE varied from 2.5 (2015 RCOG) to 35.2 (2018 ASH) per 1000 deliveries</li>
</ul>

<h2>Why This Matters</h2>
<ul>
 <li>VTE, particularly PE is a leading cause of pregnancyrelated morbidity and mortality in US and the incidence is increasing</li>
 <li>In the US, it is unknown what drives the implementation of the guidelines identifying the need of pharmacologic prophylaxis after cesarean delivery</li>
 <li>The relationship between the various patient selection criteria for pharmacologic prophylaxis and the subsequent incidence of VTE is unclear</li>
</ul>

<h2>Study Design</h2>
To estimate the percentage of cesarean delivery patients for which pharmacologic VTE would be recommended and subsequent incidence of VTE based on selected guidelines: ACOG, RCOG, ACCP, or ASH
Retrospective cohort study 
 (N = 1,235,149 from 4620 hospitals)
Women who underwent cesarean delivery and were recommended for pharmacologic prophylaxis according to guidelines were included
Outcomes:
<ul>
 <li>Incidence of VTE among patients recommended for pharmacologic prophylaxis</li>
 <li>Length of stay, inpatient charges, and discharge disposition</li>
</ul>
October 2015 – December 2017
Nationwide Readmissions Database, Healthcare Cost and Utilization project, Agency for Healthcare Research and Quality
<ul>
 <li>Diagnosis and procedure codes* were used to identify patients undergoing cesarean delivery, the incidence of VTE, and risk factors used to stratify risk in the existing guidelines</li>
 <li>Time–to–event analysis was used to analyze data, stratified by risk categorization in ACOG 2011, ACCP 2012, RCOG 2015, and ASH 2018 guidelines</li>
</ul>

<h2>Key Highlights</h2>
<ul>
 <li>Patients (N = 1,235,149) had a mean age of 29.8 years and the mean length of stay for the hospitalizations was 3.5 days</li>
 <li>Patients requiring pharmacologic prophylaxis</li>
</ul>
ACOG 2011–0.3%
ASH 2018-0.2%
ACCP 2012–16.2%
RCOG 2015–73.4%
The criteria which yielded biggest difference in VTE risk between low and high-risk patients
<ul>
 <li>ACOG 2011&nbsp;(RR:&nbsp;15.7; 95% CI, 11.7–19.9)</li>
 <li>ASH 2018 (RR:&nbsp;17.3; 95% CI, 12.3–22.2)</li>
 <li>ACCP 2012&nbsp;(RR:&nbsp;3.9; 95% CI, 3.4–4.3)</li>
 <li>RCOG 2015&nbsp;(RR:&nbsp;2.2; 95% CI, 1.9–2.5)</li>
</ul>
Large sample size and data designed to be representative of the US population is the strength of this stud

<h2>Limitations</h2>
<ul>
 <li>Retrospective study design</li>
 <li>Use of administrative (billing) data, which may lead to inaccuracies, missing information, code complications or measurement errors</li>
 <li>Any VTE identified and managed solely on an outpatient basis would be excluded</li>
</ul>
*Performance of cesarean delivery was identified using ICD–10–CM procedure codes 10D00Z0, 10D00Z1, and 10D00Z2

Abbreviations

Reference

VTE Incidence after Cesarean Delivery in Selected Guidelines

THROMBOSIS

CARDIOLOGY

Recurrence of venous thromboembolism in patients with recent gestational deep vein thrombosis or pulmonary embolism: Findings from the RIETE Registry
Adapted from Barillari G, et al. European Journal of Internal Medicine. 2016; 32:53-9.

<h2>Key Takeaway</h2>
<ul>
 <li>This study provides new insights on VTE recurrence rate in DVT or PE patients during pregnancy and postpartum period</li>
 <li>PE is the most frequent type of VTE occurring in pregnant women with history or recent or previous surgery</li>
 <li>Assessment of thrombotic risk is important for better decision making regarding antithrombotic management</li>
</ul>

<h2>Why This Matters</h2>
<ul>
 <li>1 in 1000 pregnant women are estimated to have complications due to VTE, which is the leading cause of maternal mortality and morbidity worldwide1-3</li>
 <li>VTE during pregnancy or post-partum is an instigated event such as VTE secondary to&nbsp;surgery, prolonged immobilization, oral contraception, trauma, or hormonal replacement therapy4-8</li>
 <li>There is discrepancy in VTE management in pregnancy among different centers and countries as no clear clinical trials has studied this population</li>
</ul>

<h2>Objective</h2>
<ul>
 <li>To investigate rate of DVT or PE recurrence, major bleeding, or death in women during pregnancy or puerperium</li>
 <li>To identify predictors for VTE recurrence</li>
</ul>

<h2>Study Design</h2>
Inclusion criteria:&nbsp;Women confirmed with symptomatic, acute DVT or PE developed during pregnancy or puerperium (up to 42 days after delivery) enrolled in the international, multicenter, prospective RIETE registry
Study period:&nbsp;January 2001 and June 2013
Exclusion criteria:&nbsp;Patient involvement in therapeutic trials with a blind medication or a follow-up of less than three months after the diagnosis
Primary outcome:&nbsp;Recurrent PE (with or without DVT signs), recurrent DVT or major bleeding
Secondary outcome:&nbsp;Fatal VTE and fatal bleeding

<h2>Key Results</h2>
Of the total 46,770 RIETE registry patients, 607 women were objectively confirmed with VTE during pregnancy or puerperium

<ul>
 <li>Women with recent surgery showed the incidence of PE more than DVT</li>
 <li>During pregnancy DVT was more common than PE, PE was more common during puerperium</li>
 <li>The most common drug used as initial therapy was LMWH, and then UFH</li>
</ul>

<ul>
 <li>The cumulative incidence of VTE recurrence was low at 2 years 3.3% (95% CI, 1.5–5.0)</li>
 <li>Recurrent incidence rate was 2.28 events/100 patients-year</li>
 <li>No significant differences were observed between DVT and PE for initial VTE presentation</li>
 <li>Use of thrombolytics and inferior vena cava filter in initial treatment was associated with increased risk of VTE recurrence</li>
</ul>

<h2>Limitations</h2>
RIETE is an observational registry, therefore, results must be interpreted with caution while suggesting changes or adapting any treatment strategies

Recurrence of VTE in Patients with Recent Gestational DVT or PE

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

<h2>Key Takeaway</h2>
In this session, Prof. Susan R. Kahn discusses PTS in women and suggests that:
<ul>
 <li>It is a common, occasionally severe DVT complication, even in young women</li>
 <li>Main risk factors include extensive and recurrent ipsilateral DVT, persisting leg symptoms 1 month post DVT, obesity, older age, smoking, post-natal DVT</li>
 <li>ECS is the current standard of care for treatment of PTS</li>
 <li>Ongoing research seeks to identify medication and interventional approaches</li>
</ul>

<h2>Why This Matters</h2>
<ul>
 <li>PTS develops in 33–50% of patients with DVT after anticoagulation therapy and adversely affects QoL, decreases productivity, and is severe in 5–10%.</li>
</ul>

<h2>Key results</h2>
Common clinical features of PTS&nbsp;(<a href="https://www.sciencedirect.com/science/article/pii/S000649712032228X?via%3Dihub" target="_blank">Rabinovich A and Kahn SR, 2018</a>)
<ul>
 <li>Leg symptoms: Most common ones are heaviness, pain, and swelling, while others include itching, cramping, paresthesia, and bursting pain</li>
 <li>Signs: Edema, hyperpigmentation, peri-malleolar telangiectasia, venous ectasia, redness, dependent cyanosis, lipodermatosclerosis, leg ulceration</li>
 <li>Features may be intermittent or persistent, and may vary across patients 
 <ul>
 <li>Worsens while standing and walking; improves with leg elevation, and rest</li>
 <li>Ranges from mild to severe symptoms, limiting work and functioning</li>
 </ul></li>
 <li>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.</li>
</ul>
How often does PTS occur in women?&nbsp;(<a href="https://onlinelibrary.wiley.com/doi/full/10.1046/j.1365-2141.2000.01877.x?sid=nlm%3Apubmed">McColl MD, et al. 2000</a>)
<ul>
 <li>Retrospective cohort study of 43 young women (≤50 years) with prior VTE episodes (63% pregnancy-related); examined ~4 years after VTE</li>
</ul>
<table border="1" cellpadding="10" cellspacing="1" style="width:100%;">
 <tbody>
 <tr>
 <td style="background-color: rgb(229, 231, 235);">Prior VTE</td>
 <td style="background-color: rgb(229, 231, 235);">N</td>
 <td style="background-color: rgb(229, 231, 235);">All PTS</td>
 <td style="background-color: rgb(229, 231, 235);">Mild PTS</td>
 <td style="background-color: rgb(229, 231, 235);">Moderate PTS</td>
 </tr>
 <tr>
 <td>Single DVT</td>
 <td>43</td>
 <td>74%</td>
 <td>67%</td>
 <td>7%</td>
 </tr>
 <tr>
 <td>Recurrent DVT</td>
 <td>9%</td>
 <td>100%</td>
 <td>55%</td>
 <td>44</td>
 </tr>
 </tbody>
</table>
Risk of PTS is quite high following pregnancy-related DVT due to:
<ul>
 <li>More involvement of femoral and iliac veins than in non-pregnant DVT</li>
 <li>More anatomically extensive proximal DVT being a risk factor itself</li>
</ul>
<table border="1" cellpadding="10" cellspacing="1" style="width:100%;">
 <tbody>
 <tr>
 <td style="background-color: rgb(229, 231, 235);">Study</td>
 <td style="background-color: rgb(229, 231, 235);">N</td>
 <td style="background-color: rgb(229, 231, 235);">Proximal DVT (%)</td>
 <td style="background-color: rgb(229, 231, 235);">Left DVT (%)</td>
 <td style="background-color: rgb(229, 231, 235);">Antenatal DVT (%)</td>
 <td style="background-color: rgb(229, 231, 235);">Duration of assessment</td>
 <td style="background-color: rgb(229, 231, 235);">PTS (%)</td>
 <td style="background-color: rgb(229, 231, 235);">Severity (%)</td>
 </tr>
 <tr>
 <td><a href="https://www.sciencedirect.com/science/article/abs/pii/S0049384815302292?via%3Dihub" target="_blank">Wik HS, et al 2016</a></td>
 <td>
 182</td>
 <td>82</td>
 <td>75</td>
 <td>60</td>
 <td>9.6 post pregnancy</td>
 <td>41</td>
 <td>19 (moderate or severe)</td>
 </tr>
 <tr>
 <td><a href="https://onlinelibrary.wiley.com/doi/10.1111/j.1538-7836.2012.04690.x" target="_blank">Wik HS, et al 2012</a></td>
 <td>
 313</td>
 <td>83</td>
 <td>75</td>
 <td>49</td>
 <td>9.1 after first VTE</td>
 <td>42</td>
 <td>7 (severe)</td>
 </tr>
 </tbody>
</table>
Independent predictors of PTS after pregnancy related DVT*&nbsp;(<a href="https://www.sciencedirect.com/science/article/abs/pii/S0049384815302292?via%3Dihub" target="_blank">Wik HS, et al. 2016</a>)
<ul>
 <li>Age &gt;33 vs ≤33 (Ref) years: aOR = 3.9 (95% CI: 1.8–8.3),&nbsp;P&nbsp;&lt;0.001</li>
 <li>Daily vs non-daily (Ref) smokers: aOR = 2.9 (95% CI: 1.3–6.4),&nbsp;P&nbsp;= 0.011</li>
 <li>Post- vs ante-natal (Ref) pregnancy: aOR = 3.5 (95% CI: 1.8–7.0),&nbsp;P&nbsp;&lt;0.001</li>
 <li>Proximal vs distal (Ref) DVT location: aOR = 2.6 (95% CI: 1.1–6.4),&nbsp;P&nbsp;= 0.037</li>
 <li>HsCRP (&gt;0.84 g/L): aOR = 2.4 (95% CI: 1.2–4.8),&nbsp;P&nbsp;= 0.01</li>
</ul>
PTS effect on QoL post DVT in 1,040 women (18–64 years)&nbsp;(<a href="https://journals.sagepub.com/doi/10.1177/0268355517698620?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub%20%200pubmed" target="_blank">Ljungqvist M, et al. 2018</a>)
<ul>
 <li>At 6 years median follow-up: Women with PTS had severely impaired QoL across all measures (P &lt;0.001)</li>
 <li>Other predictors: older age, obesity, physical inactivity, and recurrent VTE</li>
</ul>
ECS—Standard of care for PTS, but compliance is crucial
<ul>
 <li>Reduces edema, leg pain, and heaviness</li>
 <li>Instructed to apply in the morning and remove at bedtime or early evening</li>
 <li>Knee-length ECS: More comfortable and easier to apply than thigh-length ECS, with comparable physiologic effects</li>
 <li>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</li>
</ul>
Other types of compression therapy for moderate-to-severe PTS
<ul>
 <li>Intermittent pneumatic compression devices for severe PTS: Effective, but impractical (patients need to remain stationary ≥2 h/day), costly (<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1230312/" target="_blank">Ginsberg JS, et al. 1999</a>)</li>
 <li>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 (<a href="https://www.thieme-connect.com/products/ejournals/abstract/10.1160/TH07-09-0546" target="_blank">O’Donnell MJ, et al. 2008</a>)</li>
</ul>
Medications for PTS treatment&nbsp;(<a href="https://www.ahajournals.org/doi/10.1161/CIR.0000000000000130?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub%20%200pubmed">Kahn SR, et al. 2016; Kahn SR, et al. 2014; Cohen JM, et al. 2012</a>)
<ul>
 <li>Low quality evidence for efficacy of rutosides, horse chestnut extract, hidrosmin, and defibrotide (short-term use i.e., 3–12 weeks)</li>
 <li>Rigorous multi-center studies needed to assess efficacy, sustainability, safety</li>
 <li>Ongoing Canadian RCT: MUFFIN PTS Trial (<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8438950/" target="_blank">Galanaud JP, et al. 2021</a>)</li>
 <li>MPFF b.i.d. vs placebo b.i.d. (6 months) (<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8438950/" target="_blank">Li KX, et al. 2021</a>)</li>
</ul>
Exercise training for PTS treatment&nbsp;(<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3017252/" target="_blank">Kahn SK, et al. 2011</a>)
<ul>
 <li>A 6-month RCT (26-week) comprising strengthening, stretching, and aerobic components to improve leg strength and flexibility and overall CV fitness</li>
 <li>Exercise group demonstrated improved QoL, leg strength and flexibility, as well as a trend towards an improved Villalta PTS score.</li>
</ul>
Surgery or interventional approaches to treat moderate or severe PTS
<ul>
 <li>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.</li>
 <li>No methodologically rigorous, comparative trials have been conducted to test the efficacy and safety of treatments for moderate or severe PTS.</li>
 <li>Ongoing&nbsp;<a href="https://bloodclotstudy.wustl.edu/c-tract/" target="_blank">C-Tract Trial</a>&nbsp;seeks to address this gap.</li>
</ul>
*OR adjusted for: 1) Postnatal, proximal DVT, age &gt;33 years at the time of index pregnancy and smoking before the index pregnancy

Post Thrombotic Syndrome in Women

VTE Safety Zone: VTE in general surgery from risk assessment to appropriate thromboprophylaxis

A faculty of Prof. Juan Arcelus and Prof. Ajay Kakkar discuss the importance of routine use of VTE risk assessment model for surgical patients and the current practice for VTE prevention

VTE Safety Zone: The Role of Thromboprophylaxis for the Prevention of VTE

Prof. Le Gal MD, PhD, Division of Hematology in the Department of Medicine, University of Ottawa, Canada provides insights into what is the optimal strategy for prevention of VTE in hospitalized medically-ill patients.

Venous Thromboembolism in Acutely Medically Ill Patients

Watch Dr. Muhamed Al Rohani, Consultant Nephrology, Head of Medical Department, MOH, UAE discussing how to deal with inpatients in the short and long term and what is the dangers with those patients.