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Chapter: Paediatrics: Haematology

Paediatrics: Thrombophilia

These haemostatic disorders predispose to venous or arterial thrombo-sis.



These haemostatic disorders predispose to venous or arterial thrombo-sis.

·  May be inherited or acquired.


·  Most inherited thrombophilias are asymptomatic or present in adult life. In children, most present in the newborn period or following thrombogenic events (trauma, surgery or pregnancy).


·  Newborns requiring intensive support often have multiple thrombotic risk factors including sepsis, dehydration, polycythaemia, and central vascular lines.


·  Inherited thrombophilia should be considered when there is an unexplained arterial or venous thrombosis, neonatal venous thrombosis, or positive family history.


Inherited causes


Activated protein C resistance or factor V Leiden deficiency


Commonest inherited form of venous thrombophilia. Activated protein C (APC) is an anticoagulant formed in the vascular epithelium and limits haemostasis with cofactor protein S. Over 90% of APC resistance is due to factor V Leiden (FVL) deficiency (a polymorphism present in 2–5% of pop-ulation). Adults heterozygotes for FVL deficiency have 5–10 × increased risk of venous thrombosis, and homozygotes ×30. Whilst homozygous FVL deficiency will often present in children, heterozygous children are unlikely to experience a significant risk unless an additional prothrombotic risk factor is also present.


Prothrombin G20210A mutation 

Similar incidence to FVL deficiency. It results in a higher average prothrombin level. Heterozygotes have a two-fold risk of thrombosis in adults.


Protein C deficiency 

Thromboembolism is rare in childhood, but severe deficiency can cause life-threatening massive thrombosis in newborns, resulting in skin bruises that may become necrotic (purpura fulminans).


Protein S deficiency 

Autosomal dominant. This condition is clinically similar to protein C deficiency; less likely to cause thromboembolism in children.


Antithrombin (III) deficiency 

Very rare. Autosomal dominant. Associated with high thrombotic risk, generally venous.



May be s to a genetic defect or vitamin B12 or folate deficiency. Congenital homocystinuria is associated with thromboem-bolism, e.g. stroke, mental retardation, and, in later life, arteriosclerosis.



Familial homozygous hypercholestrolemia can result in myocardial infarction in childhood, causing adult like atherosclerosis

Acquired causes


Acquired thrombophilia is most commonly associated with:



·Use of central lines;


·Takayasu’s arteritis;


·Kawasaki disease;






·SLE, anti-phopholipid antibody;


·s to development of anti-protein S antibodies post-Varicella zoster virus (VZV) infection; can cause (as with congential deficiency) necrotic skin bruises.


Newborns, especially if preterm, are most at risk. In the newborn arterial or aortic thrombosis s to a UAC may lead to bowel infarction, NEC, buttock or leg infarction, renal arterial thrombosis. Most common venous thrombosis involves the renal vein.


Investigation of thrombophilia


·FBC (polycythaemia or infection).


·ESR/CRP (infection or inflammation).


·LFTs (protein C and S, and prothrombin are vitamin K-dependent factors).

·Standard coagulation screen.


·Thrombophilia ‘screen’. Under guidance by your local laboratory, this usually includes APC resistance, with FVL, prothrombin G20210A variant testing, as well as protein C, protein S, antithrombin III, and homocystine levels.



·Acute venousthrombosis: anticoagulate with SC low molecular weight (LMW) heparin (or sometimes IV unfractionated heparin) and then warfarin, if prolonged anticoagulation required. In neonatal purpura fulminans secondary to homozygous protein C or S deficiency, treat with FFP or protein C concentrate for 6–8wks until skin lesions have healed.


·Recurrent thrombosis: treatment depends on severity, presentation, coagulation defect, and risk factors. Long-term anticoagulation with warfarin may be appropriate (aim for INR of 3–4).


·Major vessel or catheter-related thrombosis: can be treated with fibrinolytic agents, e.g. tissue plasminogen activator (TPA), urokinase.


·Prophylaxis: give SC heparin during surgery or trauma in patients with established prothrombotic defects.


·positive personal history. Alternatively, antithrombin III or protein C concentrate may be given if relevant.

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