Thrombophilia is most commonly due to genetic mutation affecting the amount or function of a protein in the coagulation system. Thrombosis can be arterial or venous with the latter being commoner and increasingly reported in children. There are few big studies describing inherited thrombophilia in the paediatric age group nonetheless in countries with high prevalence of consanguinity.
So we assessed all our cohort diagnosed with inherited thrombophilia and correlated clinical data with genetic mutations.
Retrospective study collecting data from the medical records of 52 children diagnosed with inherited thrombophilia and following up in Haematology Outpatient clinic, Cairo University Paediatric Hospital. Collected data was analysed and statistically correlated
Our cohort included 52(30 males,22 females; 23% neonates, 19% < 6 months and 13% >6 months) children diagnosed with inherited thrombophilia .30.7 % are of a consanguineous marriage and 12 % have a have a positive family history of thrombosis .55.7% of patients presented in the first year of life(23% neonates, 19%< 6 months, 13% >6 months);28.8% presented at age 1 to 5years whereas 13.4% at the age of 5 to 10 years and only one child was > 10 years old .Thrombosis was venous in 39/52 (75%) patients, arterial in 12/52 (23.1%) and intra-cardiac in only one(1.9%) patient. 36.5% of our cohort had recurrent thrombosis. Thrombotic events involved the cerebral vessels in 44.2% children, lower limb vessels in 32.7%, upper limbs in 7.7%, head and neck in 11.5% and the heart in 3.8%. 10 patients presented with both bleeding symptoms and thrombotic events. Thrombosis occurred spontaneously in 34.6% while 65.4% of children had risk factors; dehydration(65.4, fever and infection in nine patients (17.3%), surgery and blood sampling each in 7.7%, trauma and CVP insertion each in 3.8%.
44 (84.6%) patients had more than one mutation and only 8 (15.4%). patients had a single mutation. 14(26.9%) had Factor V G1691A(13 heterozygous, 1 homozygous) whereas 10 had heterozygous Factor V 1299R (R2) .3(5.8%)patients had heterozygous Prothrombin 20210A, 9(17.3%) had Factor XIII V34L(7 heterozygous, 2 homozygous). 18 (34.6%), children had B-Fibrinogen -455 G > A (heterozygous in 16, homozygous in 2). Uncommonly reported mutations in the literature but showing a higher prevalence in our cohort included PAI-1 mutation in 24(46.2%, heterozygous in 19 and homozygous in 5); HPA-1 in 15(28.8%, heterozygous in 7, homozygous in 8); ACE in 28(53.8%, heterozygous in (n = 16), homozygous in (n = 12); APO E mutations in 20(38.5%, heterozygous in 6,homozygous in 14). Twenty (38.5%) patients had MTHFR C6777T,heterozygous in 17 and homozygous in 3 whereas and another 20 patients had heterozygous MTHFR 1298C mutation. 3 patients had protein C(PC) deficiency which together with MTHFR C6777T mutation usually present at a very early age.
26 (50%) had complications; amputation (15.4%) blindness and developmental delay each in 7.7%, renal atrophy, hydrocephalus, and death each in 3.8%, and ischemic insult (1.9%).
Egyptian children having more than one heterozygous mutation even if weakly thrombophiliac are prone to develop significant thrombotic events when exposed to minor risk factors or spontaneously