Management of Venous Thromboembolism in Children: Current Recommendations and Therapeutic Options

Figures & data

Table 1 Comparison of Guideline Recommendations on the Management of Venous Thromboembolism in Children

	Common	ASH	CHEST	UK
CVAD-associated thrombosis	Leave in situ if functional Remove after starting anticoagulation if dysfunctional or no longer needed	Remove CVAD if alternate venous access is available Remove several days after start of anticoagulation	Anticoagulation or radiologic monitoring Anticoagulation if thrombus progresses Remove 3–5 days after start of anticoagulation Therapy duration 6 weeks–3 months Prophylaxis after therapy is completed, until CVAD is removed Right atrial CVAD thrombus: remove CVAD, with or without prior anticoagulation; ± surgical intervention	Remove 2–4 days after start of anticoagulation No primary prevention
Major DVT and PE	Anticoagulation therapy	Asymptomatic: no therapy or therapeutic anticoagulation Therapy duration 3 months or less 6–12 months for unprovoked DVT/PE No thrombolysis, thrombectomy or inferior vena cava filters In massive PE: thrombolysis and subsequent anticoagulation, no thrombectomy	Therapy duration 3 months for provoked VTE 6–12 months for unprovoked DVT/PE Therapeutic or prophylactic anticoagulation beyond the 3-month baseline therapy for provoked DVT/PE, until the risk factors have resolved VKA life-long for idiopathic VTE and antiphospholipid syndrome IVC-filter only in children >10 kg and with contraindication to anticoagulation-therapy	Therapy duration 3 months 6 months for unprovoked DVT/PE Indefinite anticoagulation in idiopathic VTE and antiphospholipid syndrome Consideration of thrombolytic therapy in extensive thrombosis IVC-filters in older children with contraindications for anticoagulation
CSVT	Anticoagulation therapy	Anticoagulation in CSVT with hemorrhage No thrombolysis	Anticoagulation in CSVT with significant hemorrhage, or radiologic monitoring to detect thrombus progression after 5–7 days, then anticoagulation Thrombolysis, thrombectomy or surgical decompression only if UFH-therapy fails	Anticoagulation in CSVT with hemorrhage, no anticoagulation in hemorrhage with mass effect or intraventricular hemorrhage. Radiologic monitoring in CSVT with significant hemorrhage to detect thrombus progression after 5–7 days, then anticoagulation, or no anticoagulation No thrombolysis
Right atrial thrombosis		Anticoagulation therapy, no thrombolysis, no thrombectomy
Portal vein thrombosis		Anticoagulation vs no therapy
Neonatal renal vein thrombosis	Anticoagulation therapy Severe RVT thrombolysis + anticoagulation	Anticoagulation rather than no therapy and rather than thrombolysis In life threatening RVT: Thrombolysis + anticoagulation	Radiologic monitoring or anticoagulation Anticoagulation upon thrombus progression Severe RVT anticoagulation or initial thrombolysis + anticoagulation
Homozygous Protein C deficiency	Protein C replacement therapy	Protein C replacement therapy with or without anticoagulation	FFP or protein C concentrate until lesions clear Lifelong anticoagulation with VKA or LMWH, protein C replacement or liver transplant.

Table 2 Therapeutic Options on Specific Pediatric Venous Thromboembolic Events

	No therapy	UFH/LMWH	VKA	Thrombolysis	Other	Prophylaxis
CVAD-associated thrombosis	Radiologic monitoring (CHEST)	6 weeks–3 months (CHEST)		CVAD-dysfunction: local thrombolysis trial (CHEST)		After CVAD-thrombosis LMWH or VKA until removal (CHEST) Neonates: UFH-continuous infusion (CHEST) VKA prophylaxis in children >1 year of age with parenteral nutrition (CHEST)
Major DVT and PE	Asymptomatic: no therapy or therapeutic anticoagulation (ASH)	UFH if rapid reversal is necessary (UK) UFH/LMWH as therapy (CHEST) LMWH for infants <1 year (UK) Provoked DVT therapy duration: <3 months (ASH); 3 months (CHEST, UK) Unprovoked DVT therapy duration: 6–12 months (ASH, CHEST, UK)	VKA or LMWH as therapy (ASH) Indefinite anticoagulation in recurrent idiopathic VTE and antiphospholipid syndrome (UK, CHEST)	In massive PE or extended thrombosis in large veins (UK) If life/limb/organ is threatened (ASH, CHEST)	IVC filter in children >10 kg and contraindications for anticoagulation (UK, CHEST); no IVC-filter (ASH) No antithrombin replacement, unless clinical treatment failure (ASH) Thrombectomy only in life-threatening thrombosis (CHEST)	Therapeutic or prophylactic anticoagulation beyond the 3-month baseline therapy for provoked DVT/PE, until the risk factors have resolved (CHEST) LMWH prophylaxis and physical methods for children with VTE risk factors (UK)
CSVT	No anticoagulation in hemorrhage with mass effect or intraventricular hemorrhage (UK) Radiologic monitoring after 5–7 days to detect thrombus progression (CHEST, UK)	in CSVT without relevant hemorrhage (ASH, CHEST, UK) for at least 3 months (CHEST, UK)	In CSVT without hemorrhage for children >1-year age (UK)	No thrombolysis (ASH, UK) In severe CSVT or if UFH-therapy fails (CHEST)	Thrombectomy/surgical decompression in severe CSVT or if UFH-therapy fails (CHEST)	Prophylaxis in patients with recurring risk factors (e.g. asparaginase therapy) (CHEST)
Right atrial thrombosis		Anticoagulation therapy (ASH),		No thrombolysis (ASH)	No thrombectomy (ASH)
Portal vein thrombosis	Non-occlusive PVT or portal hypertension (ASH)	Occlusive thrombosis, post liver transplant or spontaneous PVT (ASH)
Neonatal renal vein thrombosis	Radiologic monitoring (CHEST)	Anticoagulation 6 weeks – 3 months (ASH, CHEST) Anticoagulation upon thrombus progression (CHEST)		In life-threatening RVT: Thrombolysis plus anticoagulation (ASH, CHEST)
Homozygous protein C deficiency		Lifelong anticoagulation with VKA or LMWH (CHEST, ASH)	Lifelong anticoagulation with VKA or LMWH (VKA only if >1 year of age) (CHEST, ASH)		Protein C replacement (ASH, CHEST) or liver transplant (ASH, CHEST)