ASH/ISTH 2024 Updated Guidelines for Treatment of Venous Thromboembolism in Paediatric Patients

Blood Advances · 27 May 2025 · Vol 9, No 10, pp 2587–2606 · DOI: 10.1182/bloodadvances.2024015328

Paul Monagle et al (30 co-authors) · GRADE Methodology

20Recommendations

2Good Practice Stmts

1Strong Rec (Rec 10a)

⊕○○○Mostly Very Low Certainty

Key Takeaways

All recommendations are conditional except Rec 10a (strong recommendation AGAINST thrombolysis in non-life-threatening neonatal RVT)
Nearly all are based on very low certainty evidence (⊕○○○); Rec 16 is LOW certainty (⊕⊕○○)
DOACs (rivaroxaban/dabigatran) now preferred over SOC (LMWH/UFH/VKA) in most paediatric patients — Recs 17–20
Kids-DOTT trial supports 6 weeks over 3 months for select provoked VTE (strict criteria apply) — Rec 3
CSVT recommendation downgraded from Strong (2018) to Conditional (2024) — Rec 5
Anticoagulation in symptomatic CVAD-related VTE: specific exceptions for neonates and trauma — Rec 1
Apixaban and edoxaban: NOT included — phase 3 paediatric trial data not yet published
A paediatric haematologist or haematology-trained paediatrician should implement these guidelines (GPS 1)

📋 Overview & Methods

Publication Details

Full title: American Society of Hematology/International Society on Thrombosis and Haemostasis 2024 updated guidelines for treatment of venous thromboembolism in pediatric patients
Journal: Blood Advances, Vol 9, No 10, pp 2587–2606+
Published: 27 May 2025
DOI: 10.1182/bloodadvances.2024015328
Lead author: Paul Monagle et al (30 co-authors)
Total recommendations: 20 plus 2 Good Practice Statements

Methodology

Framework: GRADE methodology
All recommendations: Conditional unless stated
Certainty: Predominantly very low (⊕○○○); Rec 16 = low (⊕⊕○○)
Strong recommendation: Rec 10a only
Scope: Update to 2018 ASH guidelines; addresses 20 new/updated PICO questions
Update trigger: Publication of EINSTEIN-Junior, DIVERSITY, and Kids-DOTT RCTs

ℹ

GRADE Certainty Summary: ⊕⊕⊕⊕ High ⊕⊕⊕○ Moderate ⊕⊕○○ Low ⊕○○○ Very Low — Most recommendations in this guideline are ⊕○○○ (Very Low)

Category Colour Key

DVT/PE

CSVT

RAT

RVT

PVT

SVT

PE Thrombolysis

CVAD

DOACs/Drugs

👶 Age Definitions (Panel Terminology)

Term	Age Range	Notes
Neonates	Birth to day 28	Highest bleeding risk; specific considerations apply
Infants	Day 29 to 1 year	Distinct pharmacokinetics; weight-based dosing critical
Children	Age 1–11 years	Most paediatric dosing studies include this group
Adolescents	Age 12–18 years	Closer to adult pharmacokinetics; menstrual bleeding relevant (rivaroxaban)
Paediatric patients	All age groups combined	Used when all ages are included in the recommendation
Neonates AND paediatric patients	Neonates separated from all others	Used when neonatal data are specifically distinguished

⚠

Dosing and pharmacokinetics vary substantially across age groups. Recommendations cannot be assumed to apply uniformly across the entire age spectrum — neonates in particular require individual assessment.

✅ Good Practice Statements

Good Practice Statements (GPS) are not derived from formal evidence review but reflect actions that, in the panel's view, are self-evidently beneficial given the complexity of care.

Good Practice Statement 1 — Specialist Involvement

A paediatric haematologist or a paediatrician in consultation with a haematologist will be best suited to implement these recommendations given the complexity of the care involved in children with VTE.

Good Practice Statement 2 — High Bleeding Risk: Prefer Short Half-Life Agents

For paediatric patients who are at high risk of bleeding (e.g., CSVT and associated haemorrhage secondary to venous congestion, immediately after or anticipated invasive procedures), consider the use of a short half-life agent such as UFH rather than LMWH or DOACs if anticoagulation is needed, to decrease the risk of worsening haemorrhage or bleeds.

📌 Recommendations (1–20)

Click any card to expand. Use the toggle bar above to show/hide Evidence Detail, Implementation notes, or Quick View (action steps only).

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Rec 1

Symptomatic DVT or PE — Anticoagulation vs No Anticoagulation

Conditional ⊕○○○ Very Low

PICO QuestionFor paediatric patients with symptomatic DVT or PE, should anticoagulation vs no anticoagulation be used?

For paediatric patients with symptomatic DVT or PE, the ASH/ISTH guideline panel suggests using anticoagulation rather than no anticoagulation (conditional recommendation based on very low certainty in the evidence about effects ⊕○○○).

Quick Action Steps

Confirm diagnosis of symptomatic DVT or PE
Exclude specific scenarios where anticoagulation benefit is uncertain (neonatal CVAD-associated VTE; trauma-associated VTE)
Initiate anticoagulation — select agent per Recs 17–20 (DOACs preferred if eligible)
Determine duration based on VTE type (Recs 3 or 4)
Involve paediatric haematologist (GPS 1)

Population & Exceptions

Applies to: Paediatric patients (all ages) with symptomatic DVT or PE

Exclusions / Uncertain benefit — panel NOT confident recommendation applies to:

Neonates with central venous catheter (CVAD)-associated VTE — may not benefit or may be harmed
Trauma-associated VTE — anticoagulation may result in no significant benefit or increased harm

Note: EINSTEIN-Junior and DIVERSITY eligibility criteria were restrictive — results not generalisable to all paediatric patients (e.g., excluded age <6 months, low birth weight, severe liver/renal impairment).

Action Steps

Confirm diagnosis of symptomatic DVT or PE
Check for neonatal CVAD-associated VTE or trauma-associated VTE (individualise if present)
Initiate anticoagulation — refer to Recs 17–20 for agent selection (DOACs preferred)
Determine duration (Rec 3 for provoked; Rec 4 for unprovoked)
Arrange monitoring per chosen agent
Involve paediatric haematologist (GPS 1)

Harms & Cautions

Major bleeding: EINSTEIN-Junior + DIVERSITY: 8/767 (1.0%) major bleeds; 14/767 (1.8%) CRNMB
NEOCLOT: 2/33 (6.1%) major bleeding and 1/33 (3.0%) CRNMB in anticoagulated neonates/infants
Trauma study: mortality 1/31 (3.2%) anticoagulation vs 0/10 (0%) no anticoagulation
Neonates generally at higher bleeding risk
High bleeding risk situations: consider short half-life agent UFH (GPS 2)

Evidence Summary

2 RCTs: EINSTEIN-Junior (n=500; age >37wk GA to 17y) and DIVERSITY (n=267; age >37wk GA to <18y) — DOACs vs SOC; neither included a no-anticoagulation arm
Retrospective multicenter observational study n=346 (neonates, infants, children <2y with VTE)
NEOCLOT prospective multicenter study n=115 (neonates/infants ≤6mo with CVAD-associated VTE)
Single-centre retrospective n=753 (paediatric patients with trauma-associated VTE)
Benefits: 7/223 (3.1%) receiving anticoagulation had recurrent VTE vs 4/47 (8.5%) without (RR 0.38; 95% CI 0.12–1.3)
NEOCLOT: 21/24 (87.5%) receiving anticoagulation had thrombus resolution vs 11/13 (84.6%) not; 8/25 (32.1%) not anticoagulated had thrombus extension
Certainty: very low (serious risk of bias, serious imprecision)

⚠

Research Needs: Study of paediatric patients with malignancy and thrombosis; separate reporting of symptomatic vs clinically unsuspected VTE; risk stratification of subgroups; real-world DOAC data

Implementation Notes

Strong indirect evidence from adults underpins this recommendation despite limited direct paediatric data
For most paediatric patients with symptomatic DVT/PE, anticoagulation is warranted
For neonatal CVAD-associated VTE: individuaise — observational studies suggest possible lack of benefit or harm
For trauma-associated VTE: consider carefully — retrospective study suggests no benefit and possible increased harm
Enrol patients in registries or clinical trials where possible

Rec 2

Clinically Unsuspected (Asymptomatic) DVT or PE — Anticoagulation vs No Anticoagulation

Conditional ⊕○○○ Very Low

PICO QuestionFor paediatric patients with clinically unsuspected (previously termed asymptomatic) DVT or PE, should anticoagulation vs no anticoagulation be used?

For paediatric patients with clinically unsuspected (previously termed asymptomatic) DVT or PE, the ASH/ISTH guideline panel suggests either using anticoagulation or no anticoagulation (conditional recommendation based on very low certainty in the evidence about effects ⊕○○○).

ℹ

This is an "either/or" conditional recommendation — no preference for treating or not treating. Decision must be individualised for each patient.

Quick Action Steps

Confirm incidental/clinically unsuspected VTE finding
Assess patient subpopulation (neonates, cardiac disease, critically ill, trauma)
Individualise decision to treat or not treat based on risk-benefit assessment
If treating, select agent per Recs 17–20
If not treating, arrange monitoring for thrombus extension/symptom development

Population

Applies to: Any paediatric patient in whom DVT or PE is detected incidentally (clinically unsuspected / previously termed asymptomatic)

Subpopulations where benefits/harms vary:

Neonates with CVAD-related VTE
Critically ill neonates
Patients with cardiac disease
Patients who have experienced trauma

Natural history: Clinically unsuspected DVT/PE carries lower risk of acute and long-term sequelae than symptomatic VTE, especially in certain subpopulations.

Action Steps

Confirm clinically unsuspected VTE — distinguish from symptomatic
Review subpopulation (neonates/cardiac/trauma/critically ill)
Weigh benefits (preventing extension, organ complications) vs harms (bleeding)
Make individualised decision with patient/family shared decision-making
If treating: select agent (Recs 17–20); determine duration (Recs 3–4)
If not treating: schedule follow-up imaging; monitor for symptoms
Involve paediatric haematologist (GPS 1)

Harms & Cautions

Major bleeding in 1/3 (33.3%) patients receiving anticoagulation for asymptomatic VTE (very small study)
Mortality: 1/13 (7.7%) anticoagulation vs 0/9 (0.0%) no anticoagulation (very small study)
PTS risk 21.4% at 13 months in trauma patients; 16.6% in asymptomatic CVAD-related VTE at 2 years
EINSTEIN-Junior and DIVERSITY did NOT separately report outcomes for symptomatic vs unsuspected

Evidence Summary

3 studies (1 single-arm non-comparative, 1 observational non-randomised, 1 retrospective comparative); total <100 patients
Thrombus extension: 0/1 (0.0%) anticoagulation vs 2/5 (40.0%); resolution 9/13 (69.2%) vs 1/1 (100.0%); recurrence 0/1 (0.0%) vs 0/3 (0%)
Certainty: very low (serious risk of bias and very serious imprecision)

⚠

Research Needs: Outcomes of clinically unsuspected VTE in cancer, short gut, end-stage renal disease, long-term central lines; consistent use of international standard definitions; separate presentation of symptomatic vs unsuspected outcomes in future trials

Implementation Notes

No routine screening for clinically unsuspected VTE is recommended
If unsuspected VTE is detected, individualise the decision
Single institution observational retrospective studies suggest not treating does not lead to severe outcomes in select subpopulations
Use shared decision-making with patient/family regarding treatment vs surveillance

Rec 3

Provoked VTE — Duration: 6 Weeks vs 3 Months (Kids-DOTT)

Conditional ⊕○○○ Very Low

PICO QuestionFor paediatric patients with provoked VTE, should anticoagulation for 6 weeks vs 3 months be used?

For select paediatric patients with provoked VTE, the ASH/ISTH guideline panel suggests 6 weeks rather than 3 months of anticoagulation. Exclusions to this recommendation include (1) PE, (2) recurrent VTE, (3) persistent occlusive thrombus at 6 weeks, (4) cancer-associated thrombosis, (5) patients with persistent antiphospholipid antibodies (APAs) or major thrombophilia, and (6) ongoing VTE risk factors (conditional recommendation based on very low certainty in the evidence of effects ⊕○○○).

ℹ

Based on Kids-DOTT RCT — First RCT to evaluate duration of anticoagulation in paediatric provoked VTE. Strict eligibility criteria apply; results cannot be extrapolated beyond the studied population.

Kids-DOTT Eligibility Checklist — All Must Be Met for 6-Week Treatment

First episode provoked VTE
NOT PE
NOT recurrent VTE
NOT persistently occlusive thrombus at 6 weeks
NOT cancer-associated thrombosis
NOT positive APA at 6 weeks (re-test if elevated at diagnosis)
NOT major thrombophilia
NOT ongoing VTE risk factors
NOT active cancer, SLE, proximal PE, or requiring thrombolysis (Kids-DOTT exclusions)

If ANY exclusion criterion is met → use 3 months anticoagulation. For persistent provoking risk factors → longer duration may be considered.

Who Qualifies for 6-Week Duration (Strict Kids-DOTT Criteria)

All criteria must be met:

First episode provoked VTE
NOT PE
NOT recurrent VTE
NOT persistently occlusive thrombus at 6-week imaging
NOT cancer-associated thrombosis
NOT positive APA at 6 weeks (re-test if elevated at diagnosis)
NOT major thrombophilia
NOT ongoing VTE risk factors
NOT active cancer, SLE, proximal PE, or requiring thrombolysis

Does NOT meet criteria: Use 3 months anticoagulation
Persistent provoking risk factors: Longer duration may be considered

Most common provoking factors in Kids-DOTT: CVAD (52%), infection (34%), surgery/trauma (20%); >85% received LMWH

Action Steps

Confirm first-episode provoked VTE (not PE, not recurrent)
Test APA at diagnosis; plan re-test at 6 weeks if initially elevated
Initiate anticoagulation (refer to Recs 17–20 for agent)
At 6 weeks: repeat imaging to assess thrombus resolution
Re-test APA at 6 weeks if initially positive
If thrombus resolved, APA negative, and all other criteria met → stop anticoagulation at 6 weeks
If persistent occlusive thrombus, APA positive, or other exclusion criterion → continue to 3 months
Assess for ongoing VTE risk factors → if present, consider longer duration

Harms & Cautions

Kids-DOTT: symptomatic recurrent VTE 1/154 (0.6%) 6-week vs 2/143 (1.4%) 3-month — non-inferior
No difference in mortality (4/206 [1.9%] vs 4/206 [1.9%])
Kids-DOTT was NOT powered to detect small differences in recurrence
Critical: Cannot extrapolate beyond Kids-DOTT inclusion criteria — many paediatric patients with provoked VTE were excluded from the trial
Certainty very low despite RCT: serious imprecision

Evidence Summary

Kids-DOTT RCT (n=417 randomised; 297 per-protocol): first RCT evaluating duration; demonstrated non-inferiority of 6 weeks vs 3 months for recurrent VTE and clinically relevant bleeding
Single-centre retrospective cohort (n=74, CVAD-related VTE): 39 patients treated shorter duration — no inferior outcomes
Retrospective cohort (n=23, rivaroxaban 6w/3m/6m) — no recurrent VTE or relevant bleeding
Kids-DOTT excluded: active cancer, major thrombophilia, SLE, proximal PE, patients requiring thrombolysis

⚠

Research Needs: Whether 6-week shortening applies to patients with occlusive thrombus at 6 weeks; further investigation of thrombus resolution at 6 weeks as a decision criterion

Implementation Notes

6-week imaging to assess thrombus occlusion is essential to determine eligibility for stopping
APA testing: required at diagnosis and again at 6 weeks if initially elevated
CVAD removal may affect thrombus resolution — consider CVAD status in duration decision
Anticoagulation agent used in Kids-DOTT was predominantly LMWH (>85%) — evidence for 6-week shortening specifically with DOACs less direct

Rec 4

Unprovoked DVT or PE — Duration: 6–12 Months vs Indefinite

Conditional ⊕○○○ Very Low

PICO QuestionFor paediatric patients with unprovoked DVT or PE, should anticoagulation for 6 to 12 months vs indefinite anticoagulation be used?

For paediatric patients with unprovoked DVT or PE, the ASH/ISTH guideline panel suggests using anticoagulation for 6 to 12 months rather than indefinite anticoagulation (conditional recommendation based on very low certainty in the evidence of effects ⊕○○○).

⚠

Adult data extrapolation: No paediatric studies evaluate treatment duration for unprovoked VTE. This recommendation draws on adult evidence. The panel considered that indefinite anticoagulation would more negatively affect QOL in younger patients than adults.

Quick Action Steps

Confirm unprovoked VTE (no identifiable provoking factor)
Complete thrombophilia screen
Initiate anticoagulation — select agent per Recs 17–20
Plan for 6–12 months total duration
Consider patient values, preferences, and QOL in duration decision
Discuss risks of recurrence (21–36% at 3.5 years) with patient/family

Population

Applies to: Paediatric patients with unprovoked DVT or PE (no identifiable provoking factor)

Higher recurrence risk:

Age >12 years at index VTE
Inherited thrombophilia
Recurrence rates 21%–36% at 3.5 years in paediatric patients aged >1 year with unprovoked VTE

Note: Unprovoked VTE is rare in paediatrics. Patient values and preferences should be central to the decision.

Action Steps

Confirm unprovoked VTE
Thrombophilia screen (including APA, factor V Leiden, prothrombin gene mutation, protein C/S/AT)
Initiate anticoagulation — agent per Recs 17–20
Target 6–12 months total duration
Assess thrombophilia results and anatomical risk factors during treatment
Discuss recurrence risk (21–36% at 3.5 years in children aged >1 year)
Shared decision-making re: extended vs stopping at 6–12 months
If persistent risk factors: consider longer duration (individualise)

Harms & Cautions

Adult evidence: indefinite anticoagulation significantly reduces PE (RR 0.29) and DVT (RR 0.20) — high-certainty evidence in adults
But: indefinite anticoagulation increases major bleeding (RR 2.17; 95% CI 1.20–3.35 — high-certainty in adults)
In paediatric patients: additional impact on QOL (no injections, no monitoring, ability to participate in activities)
No direct paediatric RCT evidence exists for this PICO question

Evidence Summary

No new paediatric studies since 2018 evaluating treatment duration in unprovoked VTE
Adult ASH 2020 meta-analysis: indefinite anticoagulation reduces VTE recurrence significantly — high certainty; increases major bleeding — high certainty
Paediatric observational data: recurrence 21%–36% at 3.5 years in patients aged >1 year
Certainty for paediatric population: very low; extrapolation from adults is problematic

Implementation Notes

No robust paediatric evidence exists — treatment decision is largely value-based and clinical judgement
Strongly recommend paediatric haematology involvement for all patients with unprovoked VTE
Anatomical abnormalities (e.g., May-Thurner, nutcracker) may be relevant to recurrence risk and should be sought
Thrombophilia results should be considered but currently evidence for changing duration based on specific thrombophilia is limited in paediatric patients

Rec 5

CSVT — Anticoagulation vs No Anticoagulation (incl. with Haemorrhage)

Conditional ⊕○○○ Very Low (Paediatric Data)

PICO QuestionFor paediatric patients with CSVT, should anticoagulation vs no anticoagulation be used?

For paediatric patients with cerebral sinus venous thrombosis (CSVT) with and without haemorrhage secondary to venous congestion, the ASH/ISTH guideline panel suggests using anticoagulation rather than no anticoagulation (conditional recommendation based on very low certainty in the evidence based on paediatric data ⊕○○○).

🚨

Do NOT withhold anticoagulation for haemorrhage due to venous congestion (thrombus obstruction) in CSVT. Evidence of venous congestion with or without haemorrhage should be managed with anticoagulation.

⚠

Downgraded from 2018: The 2018 guideline made this a STRONG recommendation. The 2024 update downgrades it to conditional based on paediatric-specific data review.

Quick Action Steps

Confirm CSVT diagnosis
Determine aetiology of any haemorrhage — is it secondary to venous congestion? → YES: anticoagulate; NO: individualise
Assess underlying aetiology (infection, trauma, cancer) and treat appropriately (including surgical if infection-associated)
Initiate anticoagulation — consider UFH if high bleeding risk (GPS 2)
Monitor for neurologic deterioration

Population

Applies to: All paediatric patients with CSVT — with or without haemorrhage secondary to venous congestion

Key nuances by subgroup:

Haemorrhage DUE TO venous congestion: ANTICOAGULATE — do not withhold
Haemorrhage from other aetiology: Individualise carefully
Intracranial haemorrhage unrelated to CSVT: Do not automatically anticoagulate
Premature neonates with IVH: Higher bleeding risk — careful individual assessment
Infection-associated CSVT: Also treat underlying infection (surgical intervention if needed)
Cavernous sinus thrombosis: Panel notes anticoagulation if no contraindications (pathophysiology may differ)

Key Clinical Nuances

Evidence of venous congestion secondary to thrombus obstruction — with OR without haemorrhage — should be managed with anticoagulation
Different populations may have different risks: neonates, infection-associated, trauma, surgery, cancer
High bleeding risk: prefer short half-life agent (UFH) over LMWH or DOACs (GPS 2)
Ensure appropriate treatment for associated conditions (e.g., surgical drainage for infection-associated CSVT)
If neurologic deterioration despite anticoagulation → consider thrombolysis/reperfusion (Rec 6)
Cavernous sinus thrombosis: anticoagulate if no contraindications

Harms & Cautions

Bleeding: 3/64 (4.7%) anticoagulation vs 1/31 (3.2%) no anticoagulation (not significantly different)
Pooled RR of bleeding 1.90 (95% CI 0.27–13.31) — very wide confidence intervals
EINSTEIN-Junior CSVT substudy: 6/114 (5.4%) total bleeding (1 major, 5 CRNMBs)
Premature neonates with IVH: significantly higher bleeding risk
Caution in patients with absolute contraindications to anticoagulation

Evidence Summary

9 paediatric studies encompassing >700 paediatric patients; neonates to adolescents aged 18 years
Mortality: anticoagulation 5/366 (1.4%) vs no anticoagulation 9/82 (11.0%); RR 0.12 (95% CI 0.04–0.36)
Neurologic deficit: RR 0.95 (95% CI 0.69–1.30) — no significant difference
Thrombus resolution: 64/79 (78%) with anticoagulation had partial or complete resolution vs 38/71 (53.5%) without (RR 1.5; 95% CI 1.2–1.9)
Recurrence: relative effects not estimable (no events reported)
Certainty very low: risk of bias and confounding
Panel downgraded from strong (2018) to conditional (2024)

⚠

Research Needs: Impact of degree of CSVT resolution/recanalisation on neurological outcomes; further studies on harms/benefits in subgroups; efficacy and safety of thrombolysis in paediatric CSVT management

Implementation Notes

Use UFH rather than LMWH or DOACs in high bleeding risk scenarios for easier reversal (GPS 2)
Neuroimaging to distinguish haemorrhage secondary to venous congestion vs other causes is essential
Duration of anticoagulation in CSVT: generally 3–6 months (per earlier guidelines, individual assessment)
Follow-up neuroimaging to assess thrombus resolution

Rec 6

CSVT — Anticoagulation Alone vs Thrombolysis + Anticoagulation

Conditional ⊕○○○ Very Low

PICO QuestionFor paediatric patients with CSVT, should thrombolysis followed by anticoagulation vs anticoagulation alone be used?

For paediatric patients with CSVT, the ASH/ISTH guideline panel suggests using anticoagulation alone rather than thrombolysis followed by anticoagulation (conditional recommendation based on very low certainty in the evidence about effects ⊕○○○).

Quick Action Steps

Initiate anticoagulation (per Rec 5)
Use anticoagulation alone as first-line — do NOT routinely add thrombolysis
Monitor closely for neurologic deterioration or evidence of ischaemia
If deterioration despite anticoagulation: consider thrombolysis/reperfusion if resources available and patient/family accept risks

Exceptions — When Thrombolysis May Be Considered

Neurologic deterioration despite anticoagulation
Evidence of ischaemia
Availability of paediatric interventional radiology resources
Patient/family acceptability of anticipated risks and benefits

Note: Adult RCT of endovascular treatment did NOT show benefit vs anticoagulation alone; higher mortality in endovascular arm. Endovascular options depend on patient size and institutional resources.

Harms & Cautions

No randomised trial for thrombolysis in paediatric CSVT
Adult RCT: endovascular treatment did NOT show benefit; higher mortality in endovascular arm
Evidence is sparse — balance of benefits and harms of thrombolysis uncertain in paediatrics
Reperfusion therapies may be considered in neurologic deterioration depending on local resources

Evidence Summary

No new paediatric data for this recommendation in the 2024 update
28 observational studies from original guidelines + 2 new (1 on neonates with RAT; 1 on RAT in paediatric patients on haemodialysis)
No randomised trial for thrombolysis in paediatric CSVT
Adult RCT: endovascular treatment did NOT show benefit vs anticoagulation alone — higher mortality in endovascular arm
Certainty: very low

Implementation Notes

Thrombolysis is NOT routinely recommended — reserve for select cases with neurologic deterioration
Access to paediatric interventional radiology is needed for catheter-directed thrombolysis
Document careful risk-benefit discussion with patient/family before considering thrombolysis

Rec 7a/b

Right Atrial Thrombosis (RAT) — Anticoagulation vs No Anticoagulation (Risk Stratification)

Conditional ⊕○○○ Very Low

PICO QuestionFor neonatal and paediatric patients with RAT, should anticoagulation vs no anticoagulation be used?

Rec 7a (High-Risk Features Present): For neonates and paediatric patients with RAT, the ASH/ISTH guideline panel suggests anticoagulation rather than no anticoagulation for patients with high-risk features and low perceived risk of bleeding (conditional recommendation based on very low certainty ⊕○○○).

Rec 7b (High-Risk Features Absent): For neonates and paediatric patients with RAT and the absence of high-risk features or with unacceptable perceived risk of bleeding, the ASH/ISTH guideline panel suggests no anticoagulation over anticoagulation (conditional recommendation based on very low certainty ⊕○○○).

RAT Risk Stratification — Quick Guide

HIGH-RISK features (any = consider anticoagulation if bleeding risk acceptable):

Large size (>2 cm or >50% of right atrium)
Snake-shaped or pedunculated morphology
Mobile thrombus
Involving tricuspid valve / restricting blood flow
Intracardiac right-to-left shunt / patent foramen ovale
Associated CVAD
Symptoms: arrhythmias, haemodynamic compromise, emboli
Increasing size despite therapeutic anticoagulation

NO high-risk features → NO anticoagulation + close radiological reassessment within 3 days

High-Risk Features of RAT (from Guideline)

Any of the following should prompt consideration of anticoagulation (if bleeding risk acceptable):

Large size (>2 cm in any dimension or >50% of right atrium)
Snake-shaped morphology
Pedunculated morphology
Mobile thrombus
Location involving tricuspid valve or restricting blood flow
Presence of intracardiac right-to-left shunt or patent foramen ovale
Concomitant cardiac anomalies (decreased function, abnormal rhythm, pacemaker/ICD)
Presence of CVAD and location of thrombus relative to catheter
Symptoms: arrhythmias, emboli, haemodynamic compromise
Age of thrombus (fresh vs chronic)
Increasing size despite therapeutic anticoagulation

NEOCLOT high-risk criteria: Size >50% of right atrium; restricting tricuspid valve; extension through tricuspid valve or PFO; haemodynamic instability; pedunculated/mobile/snake-shaped; increasing despite therapeutic anticoagulation

Without high-risk features: Wait-and-see approach with close radiological reassessment (<3 days) — not associated with higher risk of adverse outcomes

Action Steps

Confirm RAT diagnosis by echocardiography
Characterise morphology: size, shape (pedunculated/mobile/snake-shaped), location relative to tricuspid valve
Assess for cardiac shunts (PFO, ASD, etc)
Assess haemodynamic status and symptoms
Determine bleeding risk
If high-risk features present AND bleeding risk acceptable → initiate anticoagulation (agent per Recs 17–20)
If no high-risk features OR unacceptable bleeding risk → withhold anticoagulation; arrange echocardiographic reassessment within 3 days
If increasing despite anticoagulation → reassess urgently; may trigger step-up therapy

Harms & Cautions

Resolution rates: 32/42 (76.2%) anticoagulation vs 23/25 (92.0%) no anticoagulation — no clear benefit of anticoagulation in low-risk RAT
Recurrence: 1/16 (6.3%) anticoagulation vs 1/25 (4.0%) no anticoagulation — similar
Bleeding: 9/31 (29%) in anticoagulation group; 2 deaths deemed related to anticoagulation; 0/4 (0%) in no-anticoagulation group died
Major bleeding/unspecified: 3/41 (7.3%) and 7/46 (15.2%) anticoagulation; 0/25 (0.0%) no anticoagulation
Evidence is sparse, non-randomised, and subject to significant bias

Evidence Summary

No new data for recommendation 7 in this update
28 observational studies from original guidelines + 2 additional (1 on neonates with RAT; 1 on RAT in paediatric patients on chronic haemodialysis)
Studies are non-randomised, small, and subject to significant bias
Insufficient data for formal risk stratification of RAT and bleeding from anticoagulation
Certainty: very low (serious risk of bias and very serious imprecision)

Implementation Notes

Echocardiographic characterisation is essential before treatment decision
Decisions should be individualised and made with the paediatric cardiology team
Radiological reassessment within 3 days is required for conservatively managed patients
Document rationale for treatment vs no treatment clearly

Rec 8

RAT Requiring Treatment — Anticoagulation Alone vs Thrombolysis + Anticoagulation

Conditional ⊕○○○ Very Low

PICO QuestionFor neonatal and paediatric patients with RAT, should thrombolysis followed by anticoagulation vs anticoagulation alone be used?

For neonates and paediatric patients with RAT requiring antithrombotic treatment, the ASH/ISTH guideline panel suggests using anticoagulation alone over thrombolysis followed by anticoagulation (conditional recommendation based on very low certainty in the evidence about effects ⊕○○○).

Quick Action Steps

For RAT requiring treatment (high-risk features per Rec 7a): use anticoagulation alone as first-line
Do NOT routinely add thrombolysis
Reserve thrombolysis for exceptional cases where haemodynamic status, size, and mobility of thrombus dictate more aggressive therapy
If considering thrombolysis: assess feasibility and patient/family acceptability of risks and benefits

Key Remarks

In most cases, anticoagulation alone is adequate for RAT requiring treatment
Individual cases may exist where haemodynamic status, size, and mobility dictate more aggressive therapy
Choice to use thrombolysis depends on: feasibility of intervention; patient and family acceptability; anticipated risks and benefits
Thrombolysis data for RAT: resolution 16/17 (94.1%) thrombolysis vs 25/27 (92.6%) anticoagulation alone — no benefit of thrombolysis
Thrombolysis deaths: 2/11 (18.2%) patients; bleeding 3/10 (30.0%) and 1/6 (16.7%)

Harms & Cautions

Thrombolysis bleeding: 3/10 (30.0%) and 1/6 (16.7%)
Thrombolysis mortality: 2/11 (18.2%) patients treated with thrombolysis followed by anticoagulation died
Resolution rates similar between thrombolysis and anticoagulation alone — no clear benefit
Neonates particularly vulnerable to intracranial haemorrhage with thrombolysis

Evidence Summary

No new data for recommendation 8 in this update
From original 28 observational studies: thrombolysis 2/11 (18.2%) patients died; resolution: 16/17 (94.1%) thrombolysis vs 25/27 (92.6%) anticoagulation alone
Bleeding for thrombolysis: 3/10 (30.0%) and 1/6 (16.7%)
Certainty: very low

Implementation Notes

Document rationale carefully if thrombolysis is considered for RAT
Paediatric cardiology input is essential
Surgical thrombectomy: not addressed in this recommendation but may be considered in extreme circumstances — refer to specialist centre

Rec 9

Neonatal RVT — Anticoagulation vs No Anticoagulation

Conditional ⊕○○○ Very Low

PICO QuestionFor neonates with RVT, should anticoagulation vs no anticoagulation be used?

For neonates with renal vein thrombosis (RVT), the ASH/ISTH guideline panel suggests using anticoagulation rather than no anticoagulation (conditional recommendation based on very low certainty in the evidence about effects ⊕○○○).

Quick Action Steps

Confirm neonatal RVT diagnosis (ultrasound +/− Doppler)
Assess laterality (unilateral vs bilateral) — critical for Rec 10 decision
Assess gestational age, IVH, comorbidities, degree of thrombocytopenia
Initiate anticoagulation (weigh against bleeding risk)
Plan long-term follow-up: blood pressure, renal function, kidney atrophy

Remarks & Clinical Rationale

Panel considers anticoagulation to have potential beneficial effect on long-term outcomes: avoiding hypertension, chronic kidney disease, and renal failure
Anticoagulation likely more important with bilateral renal vein involvement compared with unilateral (with or without IVC extension)
Individual bleeding risk assessment required: gestational age, presence of IVH, underlying comorbidities, thrombocytopenia
Outcomes of interest: renal function, blood pressure, kidney atrophy, renal failure

Harms & Cautions

Neonates have highest bleeding risk in the paediatric spectrum
Gestational age affects pharmacokinetics and bleeding risk significantly
Intraventricular haemorrhage (IVH): if present, markedly increases risk of anticoagulation-related intracranial bleeding
Thrombocytopenia: increases bleeding risk; assess before anticoagulation
Short half-life agent (UFH) preferred if high bleeding risk (GPS 2)

Evidence Summary

Evidence derived from observational studies only
Critically ill patients who received thrombolysis cannot be adequately compared to those who received anticoagulation alone due to selection bias
Certainty: very low

Rec 10a/b

Neonatal RVT — Thrombolysis + Anticoagulation vs Anticoagulation Alone (Non-life-threatening vs Life-threatening)

⬛ STRONG (10a) Conditional (10b) ⊕○○○ Very Low

PICO QuestionFor neonates with RVT, should thrombolysis followed by anticoagulation vs anticoagulation alone be used?

✓

Rec 10a is the ONLY STRONG recommendation in the entire guideline. For non-life-threatening neonatal RVT — STRONG recommendation AGAINST thrombolysis (anticoagulation alone).

Rec 10a — Non-Life-Threatening RVT (unilateral or unilateral + IVC extension): For neonates with non–life-threatening RVT, the ASH/ISTH guideline panel recommends anticoagulation alone vs thrombolysis followed by anticoagulation (strong recommendation based on very low certainty in the evidence of effects ⊕○○○).

Rec 10b — Life-Threatening RVT (bilateral thrombosis): For neonates with life-threatening RVT, the ASH/ISTH guideline panel suggests using thrombolysis followed by anticoagulation, rather than anticoagulation alone (conditional recommendation based on very low certainty in the evidence about effects ⊕○○○).

RVT Classification & Treatment Decision

Type of RVT	Definition	Treatment	Strength
Non-life-threatening	Unilateral, or unilateral + IVC extension	Anticoagulation alone — NO thrombolysis	STRONG
Life-threatening	Bilateral thrombosis	Thrombolysis → anticoagulation	Conditional

Classification & Rationale

Non-life-threatening RVT (Rec 10a — STRONG against thrombolysis):

Unilateral RVT
Unilateral RVT with IVC extension
Rationale: High value placed on avoiding thrombolysis bleeding risks, especially in neonates. High-quality evidence for HARM from thrombolysis; high costs; very low quality evidence for benefit.
Note: A strong recommendation can be made even with very low certainty evidence when evidence for harm is of high quality

Life-threatening RVT (Rec 10b — Conditional, thrombolysis):

Bilateral RVT (bilateral thrombosis)
Rationale: When RVT is life-threatening, beneficial effects of thrombolysis may outweigh undesirable consequences
Assess: gestational age, IVH, comorbidities, thrombocytopenia — affect bleeding risk

Action Steps

Confirm RVT diagnosis and laterality (unilateral vs bilateral)
Assess IVC extension
Assess gestational age, IVH, comorbidities, platelet count
Unilateral or unilateral + IVC (non-life-threatening): Use anticoagulation alone — STRONG recommendation against thrombolysis
Bilateral (life-threatening): Consider thrombolysis followed by anticoagulation — weigh bleeding risks carefully
Long-term monitoring: blood pressure, renal function, kidney size
Paediatric nephrology input recommended

Harms & Cautions

Thrombolysis carries substantial bleeding risk in neonates — particularly intracranial haemorrhage
Evidence from observational studies where thrombolysis patients were critically ill — causation difficult to assess
Thrombolysis in neonates: avoid unless truly bilateral life-threatening disease
Gestational age: premature neonates at much higher bleeding risk
IVH: absolute relative contraindication to thrombolysis
Thrombocytopenia: significant relative contraindication

Evidence Summary

Evidence derived from observational studies — critically ill patients treated with thrombolysis, studies did not adjust for this bias
Panel placed high value on avoiding bleeding risks of thrombolysis in neonates
Strong recommendation 10a: high-quality evidence for harm + high costs despite very low quality evidence for benefit = basis for strong recommendation
Certainty: very low for both 10a and 10b

Rec 11a/b

Portal Vein Thrombosis (PVT) — Anticoagulation vs No Anticoagulation

Conditional ⊕○○○ Very Low

PICO QuestionFor neonates and children with PVT, should anticoagulation vs no anticoagulation be used?

Rec 11a: For neonates and children with occlusive PVT and for children with non-occlusive PVT, post–liver transplant PVT, or unprovoked PVT, the ASH/ISTH guideline panel suggests using anticoagulation rather than no anticoagulation (conditional recommendation ⊕○○○).

Rec 11b: For neonates with nonocclusive PVT, and for children who have already developed portal hypertension (PHTN) secondary to PVT, the ASH/ISTH guideline panel suggests no anticoagulation rather than using anticoagulation (conditional recommendation ⊕○○○).

PVT Treatment Summary

Scenario	Recommendation
Neonates — occlusive PVT	Anticoagulate (Rec 11a)
Children — non-occlusive PVT	Anticoagulate (Rec 11a)
Children — post–liver transplant PVT	Anticoagulate (Rec 11a)
Children — unprovoked PVT	Anticoagulate (Rec 11a)
Neonates — nonocclusive PVT	No anticoagulation (Rec 11b)
Children — PHTN established secondary to PVT	No anticoagulation (Rec 11b)

Population

Rec 11a — Anticoagulate:

Neonates with occlusive PVT
Children with non-occlusive PVT
Children with post–liver transplant PVT
Children with unprovoked PVT

Rec 11b — No anticoagulation:

Neonates with nonocclusive PVT
Children who have already developed PHTN secondary to PVT (risk of oesophageal variceal bleeding)

⚠

Panel recognises increased risk of bleeding in paediatric patients with PHTN and oesophageal varices — therefore does NOT recommend anticoagulation in established PHTN.

Action Steps

Confirm PVT diagnosis and characterise as occlusive or nonocclusive
Assess for PHTN (portal hypertension) — if established, recommend no anticoagulation
Assess for liver transplant status
In neonates: assess occlusive (treat) vs nonocclusive (do not treat)
In children: treat if non-occlusive, post-transplant, or unprovoked
If not treated: arrange close follow-up monitoring for extension or organ dysfunction
If treated: select agent per Recs 17–20
Paediatric hepatology/gastroenterology input recommended

Harms & Cautions

PHTN with oesophageal varices: significantly increased bleeding risk with anticoagulation — do NOT anticoagulate (Rec 11b)
Observational studies show PVT resolution in both treated and untreated patients — benefit of anticoagulation uncertain
Patients who did not receive anticoagulation: warrant follow-up monitoring — extension or organ dysfunction may require reconsideration
Evidence: very low certainty (observational studies only)

Evidence Summary

Evidence from observational studies only
PVT resolution described in both anticoagulated and non-anticoagulated patients
Panel valued avoiding long-term complications of persistent occlusive thrombus → favoured treatment in most settings
Panel recognised bleeding risk with PHTN/varices → recommends against treatment in that setting
Certainty: very low

Rec 12a/b

Superficial Vein Thrombosis (SVT) — Anticoagulation vs No Anticoagulation

Conditional ⊕○○○ Very Low

PICO QuestionFor paediatric patients with SVT, should anticoagulation vs no anticoagulation be used?

Rec 12a — IV Cannula-Related Upper Limb SVT: For paediatric patients with SVT secondary to IV cannulation in the upper limb, the ASH/ISTH guideline panel suggests no anticoagulation rather than using anticoagulation (conditional recommendation ⊕○○○).

Rec 12b — Non-Cannula Upper Limb or Cancer/Varicose Vein-Related Lower Limb SVT: For paediatric patients with SVT in the upper limb which is not cannula related, or in the lower limbs associated with cancer or varicose veins, the ASH/ISTH guideline panel suggests anticoagulation rather than no anticoagulation (conditional recommendation ⊕○○○).

SVT Decision Guide

SVT Type	Recommendation
Upper limb — IV cannula related (PIV, PICC)	No anticoagulation (Rec 12a)
Upper limb — NOT cannula related	Anticoagulate (Rec 12b)
Lower limb — cancer related	Anticoagulate (Rec 12b)
Lower limb — varicose veins	Anticoagulate (Rec 12b)
Symptomatic SVT with progression	Consider anticoagulation

Population

Rec 12a (No anticoagulation):

SVT secondary to IV cannulation in the upper limb (PIV, PICC)
Most peripheral IV/CVAD-related events in upper extremity

Rec 12b (Anticoagulate):

SVT in upper limb — NOT cannula related
SVT in lower limbs associated with cancer
SVT in lower limbs associated with varicose veins

Consider anticoagulation for:

Symptomatic SVT (non-PIV/PICC-related)
SVT with symptom progression
Scenario: PIV/long-term PICC with progression

ℹ

When anticoagulation is prescribed for SVT, there is uncertainty about optimal intensity (prophylactic vs full dose) and duration of therapy.

Action Steps

Confirm SVT diagnosis and characterise: location (upper/lower limb), aetiology (cannula vs non-cannula, cancer, varicose vein)
Upper limb cannula-related: no anticoagulation; remove or replace cannula if no longer needed
Upper limb non-cannula-related: anticoagulate — select agent per Recs 17–20
Lower limb cancer/varicose vein-related: anticoagulate
Monitor for symptom progression — reconsider anticoagulation if progression

Harms & Cautions

No direct and only limited indirect data available for this recommendation
Panel experience-based recommendation for most cases
Optimal intensity and duration of anticoagulation for SVT uncertain in paediatric patients

Evidence Summary

No direct and only limited indirect data upon which to base this recommendation
Panel experience: most peripheral IV/CVAD-related upper extremity events do not require anticoagulation
Certainty: very low

Rec 13

Proximal DVT — Anticoagulation Alone vs Thrombolysis + Anticoagulation

Conditional ⊕○○○ Very Low

PICO QuestionFor paediatric patients with proximal DVT, should thrombolysis followed by anticoagulation vs anticoagulation alone be used?

For paediatric patients with proximal DVT, the ASH/ISTH guideline panel suggests using anticoagulation alone rather than thrombolysis followed by anticoagulation (conditional recommendation based on very low certainty in the evidence about effects ⊕○○○).

Quick Action Steps

Confirm proximal DVT
Initiate anticoagulation alone as first-line (agent per Recs 17–20)
Consider extent and clinical impact of VTE in risk-benefit assessment for thrombolysis
Reserve thrombolysis for individuals where benefit clearly outweighs risk
If thrombolysis considered: assess feasibility of catheter-directed vs systemic; refer to paediatric interventional radiology if available

Key Remarks

In most cases, risks of thrombolysis seem higher than potential benefit for proximal DVT
However, there may be individuals for whom the risk-benefit ratio favours thrombolysis (e.g., extensive thrombosis, threatened limb)
Extrapolation from adult data was difficult for this recommendation
Insufficient data to compare catheter-directed vs systemic thrombolysis in paediatric patients
Centres with access to paediatric interventional radiology may have different perspectives — local resources relevant
Extent and clinical impact of VTE: important in determining risk-benefit ratio of thrombolysis

Harms & Cautions

Thrombolysis carries substantial bleeding risk including intracranial haemorrhage
No RCT data for thrombolysis in paediatric proximal DVT
Risk-benefit assessment must consider: age, comorbidities, thrombus extent, access to paediatric IR

Rec 14

Submassive PE (RV Dysfunction, No Haemodynamic Compromise) — Anticoagulation Alone vs Thrombolysis

Conditional ⊕○○○ Very Low

PICO QuestionFor paediatric patients with submassive PE (right ventricular dysfunction without haemodynamic compromise), should thrombolysis followed by anticoagulation vs anticoagulation alone be used?

For paediatric patients with PE and echocardiographic or biochemical evidence of right ventricular dysfunction but without haemodynamic compromise, the ASH/ISTH guideline panel suggests using anticoagulation alone rather than thrombolysis followed by anticoagulation (conditional recommendation based on very low certainty in the evidence about effects ⊕○○○).

⚠

Adult data extrapolation: Minimal paediatric data available. Recent international adult guideline panels have recommended anticoagulation alone rather than thrombolysis for submassive PE (based on low certainty evidence).

Quick Action Steps

Confirm submassive PE: RV dysfunction (echo or biomarkers) WITHOUT haemodynamic compromise
Initiate anticoagulation alone — do NOT routinely add thrombolysis
Monitor closely for haemodynamic deterioration (progression to massive PE)
If haemodynamic compromise develops → escalate to thrombolysis (Rec 15)

Definition — Submassive PE

PE with both or either of:

Echocardiographic evidence of right ventricular dysfunction: right ventricular dilation OR intraventricular septal bowing to the left ventricle
Biochemical evidence: elevated troponin OR brain natriuretic peptide (BNP/NT-proBNP)

WITHOUT haemodynamic compromise (no systemic hypotension or signs of shock)

ℹ

Adult guidelines suggest thrombolysis may be reasonable to consider for younger patients with submassive PE at low risk of bleeding who have evidence of BOTH echocardiographic AND biochemical RV dysfunction. This may extrapolate to select paediatric patients — use clinical judgement and specialist input.

Harms & Monitoring

Monitor submassive PE closely for development of haemodynamic compromise — if it occurs, escalate to thrombolysis (Rec 15)
Thrombolysis risks outweigh benefits in most submassive PE cases without haemodynamic compromise
Consider intensive monitoring (PICU setting) for submassive PE
No paediatric RCT data — recommendation based on adult guidelines + clinical reasoning

Rec 15

Massive PE (With Haemodynamic Compromise) — Thrombolysis + Anticoagulation

Conditional ⊕○○○ Very Low

PICO QuestionFor paediatric patients with massive PE (with haemodynamic compromise), should thrombolysis followed by anticoagulation vs anticoagulation alone be used?

For paediatric patients with PE and haemodynamic compromise the ASH/ISTH guideline panel suggests using thrombolysis followed by anticoagulation rather than anticoagulation alone (conditional recommendation based on very low certainty in the evidence about effects ⊕○○○).

⚠

Adult data extrapolation + limited paediatric data: This recommendation is based predominantly on extrapolation from recent adult guidelines AND 3 small paediatric studies suggesting a trend toward decreased mortality with thrombolysis in massive PE.

Quick Action Steps

Confirm massive PE: haemodynamic compromise (systemic hypotension, signs of shock)
Immediate thrombolysis followed by anticoagulation — life-threatening emergency
Involve paediatric intensivist and haematologist urgently
Consider local thrombolytic agent availability and protocol
Post-thrombolysis: initiate anticoagulation per Recs 17–20

Definition — Massive PE

PE with haemodynamic compromise that may be life threatening, with limited time to respond to standard anticoagulation

Systemic hypotension
Signs of shock (altered consciousness, cold extremities, reduced urine output)
Life-threatening situation — requires immediate intervention

Harms & Cautions

Thrombolysis carries substantial bleeding risk — including fatal intracranial haemorrhage
Risk-benefit: in haemodynamically compromised massive PE, benefit likely outweighs risk
3 small paediatric studies suggest trend toward decreased mortality (not definitive evidence)
Assess for contraindications to thrombolysis before administering
Post-thrombolysis: delay initiation of full-dose anticoagulation until bleeding risk acceptable

Rec 16

CVAD Removal — Immediate vs Delayed Removal (Symptomatic CVAD Thrombosis, No Longer Required or Nonfunctioning)

Conditional ⊕⊕○○ LOW

PICO QuestionFor paediatric patients with symptomatic CVAD-related thrombosis who no longer require venous access or whose CVAD is nonfunctioning, should immediate or delayed removal of the CVAD be used?

For paediatric patients with symptomatic CVAD-related thrombosis who no longer require venous access or whose CVAD is nonfunctioning, the ASH/ISTH guideline panel suggests either immediate removal or delayed removal of the CVAD (conditional recommendation based on low certainty in the evidence about effects ⊕⊕○○).

ℹ

This recommendation has LOW certainty (⊕⊕○○) — slightly higher than the very low certainty of most other recommendations in this guideline.

CVAD Management Summary

Clinical Scenario	2024 Recommendation	Basis
CVAD no longer required OR nonfunctioning	Either immediate OR delayed (≥48h anticoagulation) removal	Rec 16 (2024) — ⊕⊕○○
CVAD still required + functioning (2018 Rec 9)	No removal — continue anticoagulation with CVAD in situ	2018 guideline — conditional
CVAD nonfunctioning or unneeded (2018 Rec 10)	REMOVE — strong recommendation	2018 guideline — STRONG
Large clot burden or right-to-left shunt	Anticoagulate a few days before removal	Rec 16 remarks

Population & Context

Applies to: Paediatric patients with symptomatic CVAD-related thrombosis who:

No longer require venous access, OR
CVAD is nonfunctioning

Delayed removal preferred for:

Large thrombotic burden
Right-to-left cardiac shunts (risk of paradoxical embolism)

2018 Rec 9 (unchanged): CVAD still required and functioning → NO removal; continue anticoagulation with CVAD in situ

2018 Rec 10 (unchanged): CVAD nonfunctioning or unneeded → STRONG recommendation for removal

Action Steps

Assess: does patient still require venous access? Is CVAD functioning?
If still required + functioning: keep CVAD in situ; continue anticoagulation (2018 Rec 9)
If no longer required OR nonfunctioning: plan removal
Assess for large thrombotic burden or right-to-left cardiac shunt
If large burden or right-to-left shunt: anticoagulate for a few days before removal to reduce embolisation risk
If no high-risk features: immediate removal is acceptable
Document rationale for timing of removal

Harms & Cautions

Recent observational studies: >48 hours anticoagulation before CVAD removal vs immediate removal were comparable for risk of PE or paradoxical stroke
Large thrombotic burden: may benefit from anticoagulation prior to removal to reduce embolisation risk
Right-to-left cardiac shunts: risk of paradoxical embolism on removal
Certainty: low (⊕⊕○○) — highest certainty of any recommendation in this guideline

Evidence Summary

Recent observational studies provided data: >48 hours anticoagulation before removal vs immediate removal — comparable risk of emboli leading to PE or paradoxical stroke
Certainty: LOW (⊕⊕○○) — slightly higher than most recommendations

Rec 17

DOACs (Rivaroxaban/Dabigatran) vs SOC Anticoagulants

Conditional ⊕○○○ Very Low

PICO QuestionFor paediatric patients with VTE, should DOACs vs SOC anticoagulants be used?

For paediatric patients with VTE, the ASH/ISTH guideline panel suggests using DOACs (rivaroxaban/dabigatran) over SOC anticoagulants (LMWH, UFH, VKAs, and fondaparinux; conditional recommendation based on very low certainty in the evidence about effects ⊕○○○).

✓

DOACs are now the preferred first-line agents over SOC (LMWH/UFH/VKA/fondaparinux) for most paediatric patients with VTE in these updated guidelines.

DOAC vs SOC — Key Summary

Favours DOACs: Reduced thrombus recurrence; improved thrombus resolution; reduction in major bleeding vs LMWH/UFH; oral — no injections; no routine monitoring; better QOL
Concerns: Increase in CRNMB; heavier menstrual bleeding (rivaroxaban); GI side effects (dabigatran); limited data for age <6 months (rivaroxaban) and <2 years low body weight (dabigatran)
NOT included: Apixaban and edoxaban — phase 3 paediatric trial data not yet published

Important Exclusions — Where DOAC Evidence Does NOT Apply

Rivaroxaban (EINSTEIN-Junior) excluded:

Age <6 months
Low birth weight
Severe liver impairment
Severe renal impairment

Dabigatran (DIVERSITY) excluded:

Age <2 years with low body weight
Severe liver impairment
Severe renal impairment

⚠

Use of DOACs in excluded populations is NOT supported by trial evidence. Use SOC (LMWH/UFH) for these patients.

⚠

Apixaban and edoxaban: NOT considered in these guidelines — phase 3 paediatric trial data not yet published at time of guideline development.

Benefits vs Harms of DOACs vs SOC

Outcome	DOACs vs SOC
Thrombus recurrence	Small reduction with DOACs
Thrombus resolution	Improved with DOACs
Major bleeding	Reduced with DOACs
CRNMB	Increased with DOACs
Mortality	Uncertain (small event numbers)
PTS	Uncertain (insufficient follow-up)
QOL	Better with DOACs (oral, no monitoring)
Menstrual bleeding (rivaroxaban)	Heavier menstrual bleeding reported
GI side effects (dabigatran)	Increased GI side effects

*Note: Evaluation at 3–6 months considered too soon for accurate PTS and recurrence data. Panel acknowledged limitations of small event numbers.

Monitoring

Rivaroxaban: No routine monitoring required per current approvals
Dabigatran: Monitoring and dose adjustment required per DIVERSITY trial protocol; current approvals do NOT require monitoring — panel concern about efficacy/safety of routine use per current approvals
LMWH: Anti-Xa levels; weight-based dosing
UFH: Standard monitoring protocols
VKA: INR monitoring

Evidence Summary

EINSTEIN-Junior (n=500): rivaroxaban vs SOC (LMWH or VKA) — small benefit in reduced recurrence and improved resolution; reduced major bleeding; increased CRNMB; heavier menstrual bleeding
DIVERSITY (n=267): dabigatran vs SOC — small benefit; fewer major bleeds; equivalent CRNMB; GI side effects; monitoring/dose adjustment in trial raised concern for routine use
Panel acknowledged limitations: small event numbers, evaluation at 3–6 months
QOL, cost-effectiveness, acceptability of oral agent without monitoring: important factors
Certainty: very low

Rec 18

Rivaroxaban vs SOC Anticoagulants (EINSTEIN-Junior)

Conditional ⊕○○○ Very Low

PICO QuestionFor paediatric patients with VTE, should rivaroxaban vs SOC anticoagulants be used?

For paediatric patients with VTE the ASH/ISTH guideline panel suggests using rivaroxaban over SOC anticoagulants (LMWH, UFH, VKA, and fondaparinux; conditional recommendation based on very low certainty in the evidence about effects ⊕○○○).

Rivaroxaban Key Points

Key trial: EINSTEIN-Junior (n=500; age >37wk GA to 17y)
Benefits: reduced thrombus recurrence; improved resolution; reduced major bleeding
Harms: increased CRNMB; heavier menstrual bleeding in adolescent females
Excluded: age <6 months; low birth weight; severe liver/renal impairment
No routine monitoring required

EINSTEIN-Junior Key Data

Design: Randomised; rivaroxaban vs LMWH or VKA (SOC)
Population: n=500; birth >37wk GA to age 17 years
Benefits: Small benefit in reduced thrombus recurrence rate; increased rate of thrombus resolution
Major bleeding: Reduced with rivaroxaban vs SOC
CRNMB: Increased with rivaroxaban
Menstrual bleeding: Heavier menstrual bleeding reported in adolescent females
Limitation: Small number of outcome events; 3–6 month evaluation may underestimate PTS

Exclusions & Cautions

Age <6 months: excluded — do NOT use rivaroxaban (insufficient evidence)
Low birth weight: excluded — insufficient evidence
Severe liver impairment: excluded — avoid rivaroxaban
Severe renal impairment: excluded — avoid rivaroxaban
Adolescent females: counsel regarding increased menstrual bleeding
No routine drug level monitoring required

Rec 19

Dabigatran vs SOC Anticoagulants (DIVERSITY)

Conditional ⊕○○○ Very Low

PICO QuestionFor paediatric patients with VTE, should dabigatran vs SOC anticoagulants be used?

For paediatric patients with VTE, the ASH/ISTH guideline panel suggests using dabigatran over SOC anticoagulants (LMWH, UFH, VKA, and fondaparinux; conditional recommendation based on very low certainty in the evidence about effects ⊕○○○).

⚠

Important monitoring concern: Monitoring and dose adjustment of dabigatran was required during the DIVERSITY trial. Current approvals do NOT require such monitoring. The panel raised concern about the potential effect on efficacy and safety of routine use per current approvals.

Dabigatran Key Points

Key trial: DIVERSITY (n=267; age >37wk GA to <18y)
Benefits: reduced thrombus recurrence; improved resolution; fewer major bleeds
Harms: equivalent CRNMB; gastrointestinal side effects
Excluded: age <2 years with low body weight; severe liver/renal impairment
Monitoring concern: required in trial but not in current approvals

DIVERSITY Key Data

Design: Randomised; dabigatran vs SOC
Population: n=267; birth >37wk GA to age <18 years
Benefits: Small benefit in reduced thrombus recurrence; improved thrombus resolution
Major bleeding: Fewer major bleeds with dabigatran
CRNMB: Equivalent to SOC
GI side effects: Increased with dabigatran
Monitoring concern: Monitoring and dose adjustment required during trial; current approvals do not require — potential concern re efficacy/safety

Exclusions & Cautions

Age <2 years with low body weight: excluded — insufficient evidence for dabigatran
Severe liver impairment: excluded — avoid
Severe renal impairment: excluded — avoid
GI side effects: counsel patients; may affect adherence
Dabigatran capsules: contents can be sprinkled on food for younger children — check local guidance
Consider jurisdictional availability and regulatory approval status

Rec 20

Rivaroxaban vs Dabigatran — No Preference; Agent Selection Factors

Conditional ⊕○○○ Very Low

PICO QuestionFor paediatric patients with VTE, should either rivaroxaban or dabigatran be preferentially used?

For paediatric patients with VTE, the ASH/ISTH guideline panel suggests using either rivaroxaban or dabigatran, although there may be individual populations or jurisdictional availability that would lead clinicians to choose 1 agent over the other (conditional recommendation based on very low certainty in the evidence about effects ⊕○○○).

ℹ

The panel was unable to distinguish one DOAC as preferred over the other after a formal review of the evidence-to-decisions (EtDs) for rivaroxaban vs SOC and dabigatran vs SOC.

Factors That May Favour One Agent Over the Other

Factor	Consideration
Age <6 months	Neither rivaroxaban nor dabigatran — use SOC (LMWH/UFH)
Age <2 years, low body weight	Dabigatran not supported — prefer rivaroxaban if age ≥6m, or SOC
Adolescent females	Rivaroxaban: heavier menstrual bleeding — consider dabigatran
GI tolerance	Dabigatran: more GI side effects — consider rivaroxaban
Liver/renal impairment	Both excluded from trials — use SOC
Local availability	Check jurisdictional approval and formulary access
Drug monitoring concern	Dabigatran: monitoring required in trial; rivaroxaban: no monitoring

⚠

Apixaban and edoxaban are NOT included in these guidelines — phase 3 paediatric trial data were not yet published at the time of guideline development.

Agent Selection Factors

Local/jurisdictional availability and approval status
Patient age and weight (exclusion criteria of each trial)
GI tolerability (dabigatran: GI side effects; rivaroxaban: menstrual bleeding)
Need for monitoring (dabigatran dosing adjustment in trial raises concern; neither required per current approvals)
Liver/renal function
Patient/family preference (oral formulation, palatability)

⚠

Apixaban and edoxaban: NOT considered in these guidelines — phase 3 paediatric trial data yet to be published.

Panel EtD Methodology

Panel undertook a formal evidence-to-decisions (EtD) review comparing rivaroxaban vs SOC and dabigatran vs SOC
Highest weighting: Balance of effects; certainty in the evidence; acceptability and feasibility of implementation
Moderate weighting: Resources required
Lowest weighting: Cost-effectiveness; equity
After applying these weights: panel could not distinguish one agent as preferred over the other

💊 Drug Implementation Guidance

First-Line Preferred: DOACs (Rivaroxaban or Dabigatran)

As per Recommendations 17–20: DOACs preferred over SOC for most paediatric patients with VTE.

Advantages: Oral; no routine monitoring required; better QOL; reduced major bleeding vs LMWH/UFH; small reduction in recurrence and improvement in resolution
Disadvantages: Increase in CRNMB; heavier menstrual bleeding (rivaroxaban); GI side effects (dabigatran); monitoring concern for dabigatran per trial protocol
Evidence base: EINSTEIN-Junior (rivaroxaban, n=500) and DIVERSITY (dabigatran, n=267)

SOC Agents: LMWH / UFH / VKA / Fondaparinux

Still appropriate and may be preferred in the following situations:

Age <6 months (rivaroxaban excluded) or <2 years with low body weight (dabigatran excluded)
Severe liver impairment
Severe renal impairment
High bleeding risk scenarios: CSVT with haemorrhage; post-invasive procedures → use short half-life agent (UFH) for rapid reversal (GPS 2)
Resource-limited settings where DOAC access/cost is a barrier

Short Half-Life Agent (UFH) — High Bleeding Risk Situations

Good Practice Statement 2 (GPS 2): Consider UFH rather than LMWH or DOACs in high bleeding risk patients:

CSVT with haemorrhage secondary to venous congestion
Immediately after or anticipated invasive procedures
To decrease risk of worsening haemorrhage or bleeds
Allows rapid reversal via discontinuation ± protamine

⚠

Apixaban and edoxaban are NOT included in these guidelines. Phase 3 paediatric trial data had not been published at the time of guideline development. Do not extrapolate adult data for apixaban/edoxaban use in paediatric patients without paediatric-specific evidence.

Monitoring Principles

Agent	Monitoring Required	Notes
Rivaroxaban	None required (per current approvals)	No routine monitoring; weight-based dosing
Dabigatran	None required (per current approvals)	Concern: monitoring and dose adjustment was required in DIVERSITY trial; not per current approvals — panel concern re efficacy/safety
LMWH	Anti-Xa levels	Weight-based dosing; dose adjust to target anti-Xa range
UFH	Per standard protocols (APTT or anti-Xa)	IV infusion; adjust per protocol; short half-life for high-risk situations
VKA	INR monitoring	Multiple drug interactions; dietary vitamin K consistency required
Fondaparinux	Anti-Xa (in selected cases)	SOC; limited paediatric data

ℹ

Numeric dosing tables are NOT included in this summary. Dosing information was not provided in the guideline text summarised here. Refer to: (1) the original publication supplementary data; (2) individual drug Summary of Product Characteristics (SPCs); (3) local formularies and pharmacy guidance; (4) BNFc (British National Formulary for Children) or equivalent local resources.

CVAD Removal — Timing Guidance (Rec 16)

Clinical Scenario	Action	Source
CVAD no longer required OR nonfunctioning	Either immediate OR delayed removal (≥48h anticoagulation before removal)	Rec 16 (2024) — ⊕⊕○○
CVAD still required AND functioning	No removal — continue anticoagulation with CVAD in situ	2018 Rec 9 — conditional
CVAD nonfunctioning or unneeded	REMOVE (strong recommendation)	2018 Rec 10 — STRONG
Large thrombotic burden or right-to-left shunt	Anticoagulate for a few days before removal	Rec 16 remarks
Worsening signs/symptoms despite anticoagulation + CVAD still required	Either removal or no removal (individualise)	2018 Rec 12 — conditional

⚡ Special Situations

Click each situation to expand detailed guidance.

1. CSVT with Haemorrhage — Critical Decision Points ▼

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Do NOT withhold anticoagulation for haemorrhage that is secondary to venous congestion from CSVT. Anticoagulation is recommended in this scenario.

Haemorrhage Type	Action
Haemorrhage DUE TO venous congestion (thrombus obstruction)	ANTICOAGULATE — Rec 5
Haemorrhage from other aetiology	Individualise carefully
Intracranial haemorrhage unrelated to CSVT	Do NOT automatically anticoagulate
Premature neonates with IVH	Higher bleeding risk — individual assessment; consider UFH (GPS 2)

Infection-associated CSVT: also treat underlying infection (surgical intervention if needed)
High bleeding risk: prefer short half-life agent UFH (GPS 2)
Neurologic deterioration despite anticoagulation → consider thrombolysis/reperfusion (Rec 6)
Cavernous sinus thrombosis: anticoagulate if no contraindications (pathophysiology may differ)

2. Submassive vs Massive PE — Classification and Treatment ▼

PE Type	Definition	Treatment (Rec)	Monitoring
Submassive PE	RV dysfunction (echo: RV dilation, septal bowing; OR biochemical: elevated troponin/BNP) WITHOUT haemodynamic compromise	Anticoagulation ALONE (Rec 14) — conditional	Close monitoring for haemodynamic deterioration
Massive PE	Haemodynamic compromise — systemic hypotension or signs of shock; life-threatening; limited time to respond to anticoagulation	Thrombolysis → anticoagulation (Rec 15) — conditional	PICU; urgent intervention

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Submassive PE: monitor closely for progression to haemodynamic compromise — if it occurs, escalate to thrombolysis per Rec 15. Adult guidelines may suggest considering thrombolysis for younger patients with submassive PE who have both echocardiographic AND biochemical RV dysfunction at low bleeding risk.

⚠

Rec 15 is based predominantly on adult guideline extrapolation plus 3 small paediatric studies suggesting trend toward decreased mortality. Direct paediatric RCT evidence is absent.

3. Right Atrial Thrombosis (RAT) — Risk Stratification Algorithm ▼

High-Risk Features (any = consider anticoagulation if bleeding risk acceptable):

Large size (>2 cm in any dimension or >50% of right atrium)
Snake-shaped or pedunculated morphology
Mobile thrombus
Location involving tricuspid valve or restricting blood flow through it
Intracardiac right-to-left shunt or patent foramen ovale
Associated CVAD (and location of thrombus relative to catheter)
Symptoms: arrhythmias, haemodynamic compromise, emboli
Increasing size despite therapeutic anticoagulation
Concomitant cardiac anomalies: decreased function, abnormal rhythm, pacemaker/ICD

If NO high-risk features are present:

No anticoagulation (Rec 7b)
Close radiological reassessment within 3 days
Withholding anticoagulation is appropriate for small, mural, asymptomatic thrombi
Wait-and-see approach was NOT associated with higher adverse outcomes in observational data

If HIGH-RISK features present AND bleeding risk acceptable:

Anticoagulation (Rec 7a)
If treatment needed: anticoagulation ALONE preferred over thrombolysis (Rec 8)
Reserve thrombolysis for exceptional cases with haemodynamic compromise or failure of anticoagulation

4. CVAD Removal Timing — Decision Algorithm ▼

Step	Question	Action	Source
1	Does patient still require venous access? Is CVAD functioning?	YES → Keep CVAD; continue anticoagulation with CVAD in situ	2018 Rec 9 — conditional
2	Is CVAD nonfunctioning OR no longer needed?	YES → Remove CVAD	2018 Rec 10 — STRONG
3	Timing of removal: immediate vs delayed?	Either acceptable (Rec 16)	2024 Rec 16 — ⊕⊕○○
4	Large thrombotic burden OR right-to-left cardiac shunt?	YES → Anticoagulate for a few days before removal to reduce embolisation risk	2024 Rec 16 remarks
5	Worsening despite anticoagulation, CVAD still needed?	Individualise: consider removal or no removal	2018 Rec 12 — conditional

5. Clinically Unsuspected VTE — Key Principles ▼

No routine screening for clinically unsuspected VTE is recommended
If detected incidentally: decision to treat or not treat must be individualised (Rec 2)
Neither treat nor no-treat is universally recommended — "either/or" conditional recommendation
Natural history: lower risk of acute and long-term sequelae than symptomatic VTE, especially in certain subpopulations

Subpopulations where anticoagulation benefit is particularly uncertain or risk may be higher:

Neonates with CVAD-related VTE
Critically ill neonates
Patients with cardiac disease
Patients who have experienced trauma

ℹ

Use shared decision-making with patient/family. If not treating: arrange follow-up monitoring for thrombus extension or development of symptoms.

6. Provoked VTE — Kids-DOTT 6-Week Eligibility Checklist ▼

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All criteria must be met for 6-week treatment to be appropriate. Any single exclusion criterion directs towards 3 months of anticoagulation.

INCLUDE (must be present):

First episode of provoked VTE

EXCLUDE (must ALL be absent):

PE
Recurrent VTE
Persistent occlusive thrombus at 6-week imaging
Cancer-associated thrombosis
Positive antiphospholipid antibodies (APA) at 6 weeks (re-test if initially elevated)
Major thrombophilia
Ongoing VTE risk factors
Active cancer, SLE, proximal PE, or requiring thrombolysis (Kids-DOTT exclusions)

If ANY exclusion is met → 3 months anticoagulation. For persistent provoking risk factors → longer duration may be considered.

Most common provoking factors in Kids-DOTT: CVAD (52%), infection (34%), surgery/trauma (20%)

7. Neonatal RVT — Laterality and Treatment Algorithm ▼

RVT Type	Classification	Treatment	Recommendation
Unilateral RVT	Non-life-threatening	Anticoagulation ALONE — STRONG AGAINST thrombolysis	Rec 10a — STRONG
Unilateral RVT + IVC extension	Non-life-threatening	Anticoagulation ALONE — STRONG AGAINST thrombolysis	Rec 10a — STRONG
Bilateral RVT	Life-threatening	Thrombolysis → Anticoagulation	Rec 10b — Conditional

Factors affecting bleeding risk in neonatal RVT:

Gestational age (premature neonates: much higher bleeding risk)
Presence of intraventricular haemorrhage (IVH) — major contraindication to thrombolysis
Underlying comorbidities
Degree of thrombocytopenia
Severity of disease

✓

Rec 10a is the ONLY STRONG recommendation in the entire guideline — strong recommendation AGAINST thrombolysis for non-life-threatening neonatal RVT. Use anticoagulation alone.

Long-term monitoring for all neonatal RVT: Blood pressure, renal function, kidney size/atrophy. Paediatric nephrology input recommended.

📋 2018 Recommendations Not Addressed in This 2024 Update

The following recommendations from the 2018 ASH guidelines were reviewed but not updated in this 2024 publication. They remain valid from the 2018 guidelines.

Thrombectomy and IVC Filters

2018 Rec 6 — Thrombectomy for Symptomatic DVT or PE

Suggests AGAINST thrombectomy followed by anticoagulation; rather use anticoagulation alone in paediatric patients with symptomatic DVT or PE (conditional, very low certainty).

Remarks: Panel recognised cardiovascular compromise cases are rare and not without risk; catheter-directed thrombectomy could not be adequately assessed in available data.

2018 Rec 7 — IVC Filters

Suggests AGAINST using IVC filter; rather use anticoagulation alone in paediatric patients with symptomatic DVT or PE (conditional, very low certainty).

Remarks: IVC filters should be temporary with clear plan for removal; absolute contraindication to anticoagulation or failed adequate anticoagulation in whom filter might reduce embolic risk; not feasible to place IVC filters in children with weight <10 kg.

Antithrombin (AT) Replacement Therapy

2018 Rec 8a — AT Replacement: Against Routine Use

Suggests AGAINST AT replacement therapy in addition to standard anticoagulation; rather use standard anticoagulation alone in paediatric patients with DVT/CSVT/PE (conditional, very low certainty).

Remarks: AT use increased dramatically; limited evidence of clinical benefit; perhaps evidence of harm.

2018 Rec 8b — AT Replacement: For Specific Failure Scenarios

Suggests AT replacement therapy in addition to standard anticoagulation rather than standard anticoagulation alone in paediatric patients with DVT/CSVT/PE who have failed to respond clinically to standard anticoagulation AND in whom subsequent measurement reveals low AT concentrations based on age-appropriate reference ranges (conditional, very low certainty).

Remarks: Certain subgroups may justify AT use — documented inherited AT deficiency, children during asparaginase therapy, nephrotic syndrome, after liver transplant, neonates, and in DIC. AT would be commenced if there is continuous thrombus growth and/or failure of clinical response despite adequate anticoagulation.

CVAD-Related Thrombosis (2018 Recommendations)

2018 Rec 9 — Functioning CVAD, Still Required: No Removal

Suggests NO removal rather than removal of a functioning CVAD in paediatric patients with symptomatic CVAD-related thrombosis who continue to require venous access (conditional, very low certainty).

2018 Rec 10 — Nonfunctioning or Unneeded CVAD: REMOVE (STRONG)

RECOMMENDS removal rather than no removal of a nonfunctioning or unneeded CVAD in paediatric patients with symptomatic CVAD-related thrombosis (STRONG recommendation, very low certainty).

2018 Rec 12 — Worsening Despite Anticoagulation, CVAD Still Required: Individualise

Suggests either removal or no removal of a functioning CVAD in paediatric patients with symptomatic CVAD-related thrombosis with worsening signs or symptoms despite anticoagulation who continue to require venous access (conditional, very low certainty).

LMWH vs VKAs

2018 Rec 13 — LMWH vs VKA: Either

Suggests using either LMWH or VKAs in paediatric patients with symptomatic DVT or PE (conditional, very low certainty).

Decision based on: (1) patient values and preferences; (2) health services resources; (3) infrastructure and support; (4) underlying condition, comorbidities, and other medications. Note: 2024 update now recommends DOACs over SOC — this 2018 rec applies when DOACs are not appropriate or available.

Purpura Fulminans due to Homozygous Protein C Deficiency

2018 Rec 24 — Protein C Replacement over Anticoagulation Alone

Suggests protein C replacement rather than anticoagulation alone in paediatric patients with congenital purpura fulminans due to homozygous protein C deficiency (conditional, very low certainty).

2018 Rec 25 — Anticoagulation + Protein C Replacement

Suggests anticoagulation plus protein C replacement rather than anticoagulation alone in paediatric patients with congenital purpura fulminans due to homozygous protein C deficiency (conditional, very low certainty).

2018 Rec 26 — Liver Transplantation vs Continued Medical Management

Suggests using either liver transplantation or no liver transplantation (anticoagulation or protein C replacement) in paediatric patients with congenital purpura fulminans due to homozygous protein C deficiency (conditional, very low certainty).

🔬 Evidence & Key Trials

Key Outcomes of Interest (All PICO Questions)

Mortality VTE Resolution VTE Recurrence Thrombus Extension Major Bleeding CRNMB Post-Thrombotic Syndrome (PTS) HITT Neurological Outcome (CSVT) Cerebral Infarction (CSVT/RAT) Kidney Function (RVT) Portal Hypertension (PVT) Paradoxical Embolism (CVAD)

EINSTEIN-Junior

Rivaroxaban vs SOC (LMWH or VKA) in Paediatric VTE · n=500 · Randomised Controlled Trial

Population: Birth >37 weeks gestational age to age 17 years with confirmed VTE. Excluded: Age <6 months, low birth weight, severe liver or renal impairment.

Key results: Small benefit in reduced thrombus recurrence rate and improved thrombus resolution with rivaroxaban. Major bleeding reduced vs SOC. Clinically relevant non-major bleeding (CRNMB) increased. Heavier menstrual bleeding reported in adolescent females. 22/651 (3.4%) recurrent VTE; 10/651 (1.5%) radiological thrombus extension; no patient had symptomatic PE.

Limitation: Eligibility criteria restricted enrolment — results not generalisable to all paediatric patients; small number of outcome events; 3–6 month evaluation may underestimate PTS and long-term outcomes.

Informs: Recommendations 1, 17, 18, 20

DIVERSITY

Dabigatran vs SOC in Paediatric VTE · n=267 · Randomised Controlled Trial

Population: Birth >37 weeks gestational age to age <18 years with confirmed VTE. Excluded: Age <2 years with low body weight, severe liver or renal impairment.

Key results: Small benefit: reduced thrombus recurrence and improved thrombus resolution. Fewer major bleeds with dabigatran. CRNMB equivalent to SOC. Gastrointestinal side effects increased. Monitoring and dose adjustment was required per trial protocol — concern raised about routine use per current approvals which do NOT require monitoring.

Limitation: Monitoring concern; small number of outcome events; exclusion criteria limit generalisability.

Informs: Recommendations 1, 17, 19, 20

Kids-DOTT

Duration of Anticoagulation in Paediatric Provoked VTE · n=417 randomised; 297 per-protocol analysis · Randomised Controlled Trial

Design: First RCT evaluating duration of anticoagulation in paediatric patients with first episode of provoked VTE. 6 weeks vs 3 months.

Population: First episode provoked VTE. Most common provoking factor: CVAD (52%), infection (34%), surgery/trauma (20%). >85% received LMWH.

Excluded: Active cancer, major thrombophilia, SLE, proximal PE, patients requiring thrombolysis. APA positive at 6 weeks excluded from randomisation.

Key results: Demonstrated non-inferiority of 6-week vs 3-month anticoagulation for recurrent VTE and clinically relevant bleeding. Symptomatic recurrent VTE: 1/154 (0.6%) 6-week vs 2/143 (1.4%) 3-month. No difference in mortality (4/206 [1.9%] vs 4/206 [1.9%]).

Limitation: Stringent eligibility criteria — many paediatric patients with provoked VTE were excluded. Cannot be extrapolated beyond its specific inclusion criteria. Not powered for small differences in recurrence.

Informs: Recommendation 3

NEOCLOT Study

Neonates/Infants ≤6 months with CVAD-Associated VTE · n=115 · Prospective Multicenter Observational Study

Population: Neonates and infants ≤6 months with CVAD-associated VTE treated per national consensus guideline.

Key results: 21/24 (87.5%) receiving anticoagulation had thrombus resolution vs 11/13 (84.6%) not; 8/25 (32.1%) infants not receiving anticoagulation had radiological thrombus extension. Major bleeding: 2/33 (6.1%) and CRNMB 1/33 (3.0%) receiving anticoagulation; 0 not receiving. Informs exception to Rec 1 for neonatal CVAD-associated VTE.

Informs: Recommendation 1

Retrospective Multicenter Observational Study (Neonates/Infants/Children <2 years)

n=346 · Retrospective Multicenter Observational

Population: Neonates, infants, children <2 years with VTE.

Key results: 7/223 (3.1%) receiving anticoagulation had recurrent VTE vs 4/47 (8.5%) without anticoagulation (RR 0.38; 95% CI 0.12–1.3).

Informs: Recommendation 1

Single-Centre Retrospective — Trauma-Associated VTE

n=753 · Single-Centre Retrospective

Population: Paediatric patients <18 years with trauma-associated VTE.

Key results: Mortality 1/31 (3.2%) anticoagulation vs 0/10 (0%) no anticoagulation; thrombus resolution 13/31 (41.9%) vs 6/10 (60.0%) (RR 0.69; 95% CI 0.36–1.34). No clear benefit of anticoagulation in trauma-associated paediatric VTE. Informs exception in Rec 1.

Informs: Recommendation 1

Adult ASH 2020 Meta-Analysis — Indefinite vs Finite Anticoagulation

Adult Population · Meta-analysis · High Certainty Evidence (in Adults)

Design: Meta-analysis used to inform adult ASH 2020 guidelines on unprovoked VTE treatment duration.

Key results: Indefinite anticoagulation significantly reduces PE (RR 0.29; 95% CI 0.15–0.56) and DVT (RR 0.20; 95% CI 0.12–0.34) — high certainty in adults. Increases major bleeding (RR 2.17; 95% CI 1.20–3.35 — high certainty).

Limitation: Adult data only — extrapolation to paediatric patients is problematic. Impact on QOL and development in younger patients not reflected in adult data. Certainty for paediatric patients: very low.

Informs: Recommendation 4

⚕ Educational Summary Only. This page summarises the ASH/ISTH 2024 Updated Guidelines for Treatment of VTE in Paediatric Patients (Blood Advances 2025;9:2587–2606; DOI: 10.1182/bloodadvances.2024015328). It does not replace local protocols, Summary of Product Characteristics (SPCs), or specialist advice. Always consult a paediatric haematologist or haematology-trained paediatrician for individual patient decisions.

Numeric dosing information is NOT included as it was not present in the provided guideline text — refer to the original publication, drug SPCs, local formularies, and the British National Formulary for Children (BNFc) or equivalent local resources.

All recommendations reflect those in the published guideline. Readers should refer to the full published guideline for complete methodology, evidence tables, and EtD frameworks. Recommendations may change as new evidence emerges. This summary was prepared for educational purposes and does not constitute individual medical or pharmaceutical advice. The preparer accepts no liability for clinical decisions made on the basis of this summary.

Guideline citation: Monagle P et al. American Society of Hematology/International Society on Thrombosis and Haemostasis 2024 updated guidelines for treatment of venous thromboembolism in pediatric patients. Blood Advances. 2025;9(10):2587–2606. https://doi.org/10.1182/bloodadvances.2024015328

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Conceived & Created by

Dr Abdul Mannan

FRCPath · FCPS · Consultant Haematologist

Blood🩸Doctor | blooddoctor.co@gmail.com