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Year : 2015  |  Volume : 16  |  Issue : 1  |  Page : 5-8

Antiphospholipid antibody syndrome in pediatric population: An overview

1 Department of Dermatology, Venereology and Leprosy, Bangalore Medical College and Research Institute, Bengaluru, Karnataka, India
2 Department of Paediatric Dermatology, Institute of Child Health, Talegaon Dabhade, Pune, Maharashtra, India
3 Department of Dermatology, Venereology and Leprosy, M.I.M.E.R. Medical College, Talegaon Dabhade, Pune, Maharashtra, India
4 Pediatric Dermatology Unit, Rita Skin Foundation, Kolkata, West Bengal, India

Date of Web Publication16-Jan-2015

Correspondence Address:
Samipa S Mukherjee
Department of Dermatology, Venereology and Leprosy, Bangalore Medical College and Research Institute, Bangalore, Karnataka
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2319-7250.149401

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The antiphospholipid (APL) antibody syndrome is an autoimmune conditions characterized by recurrent thromboembolic events. The exact incidence of its occurrence in the pediatric age group in Indian population is not known. Due to the higher incidence of infections in this age group there is a higher incidence of APL antibodies (APLAs) while the patients are asymptomatic, thereby making the establishment of diagnosis challenging. Secondary APL antibody syndrome is associated with underlying systemic lupus erythematosus. Due to the higher incidence of positivity of APLAs in children it is advised to conduct the diagnostic tests twice. Varying cutaneous features and lack of adequate awareness regarding the presenting signs and symptoms in pediatric population makes the diagnosis difficult. There are no guidelines for the management of this condition in children and it is extrapolated from the guidelines used in the adults. Early detection of this condition helps in reducing morbidity and improving the care and management of the patient.

Keywords: High positivity of antiphospholipid antibodies, lack of management guidelines, varying cutaneous manifestations

How to cite this article:
Mukherjee SS, Dhar S, Gaikwad RP, Saha A. Antiphospholipid antibody syndrome in pediatric population: An overview. Indian J Paediatr Dermatol 2015;16:5-8

How to cite this URL:
Mukherjee SS, Dhar S, Gaikwad RP, Saha A. Antiphospholipid antibody syndrome in pediatric population: An overview. Indian J Paediatr Dermatol [serial online] 2015 [cited 2022 May 20];16:5-8. Available from: https://www.ijpd.in/text.asp?2015/16/1/5/149401

  Introduction Top

The antiphospholipid syndrome (APS) is an autoimmune condition characterized by recurrent thromboembolic phenomenon and pregnancy morbidities associated with fetal loss. Antiphospholipid (APL) antibodies (APLAs) are defined as a group of antibodies directed against epitopes on plasma proteins that are uncovered by binding of these proteins to anionic phospholipids on plasma membranes. The most commonly used tests, to detect APL, include lupus anticoagulant (LAC), anticardiolipin (ACL) antibodies, and anti-β2 -glycoprotein I (GPI) antibodies. [1] An accurate data on the incidence of the true prevalence of the APS is unavailable due to the paucity of guidelines and disease detection criteria. The prevalence of the disease among the different patient populations in India has been reported to be between 25.5% and 51.5%. [2] The Indian data on the prevalence of this syndrome in the pediatric population is lacking. However the Canadian Registry of 137 children identified prospectively, the incidence of venous thromboembolism was 5.3/10,000 hospital admissions or 0.07/10,000 children. [3] An incidence of 1.2/10,000 admissions for thrombosis was noted at the Children's Hospital of Denver between 1952 and 1972. [4] A prospective study in Germany (ESPED) reported an incidence of thrombosis in children to be 5.1/1,00,000 live births. [5]

  Antiphospholipid antibodies and its detection tests Top

Phospholipids present in the blood are important for the clotting process. However at ties due to the autoimmune process the body identifies these phospholipids as foreign and generates antibodies against them thus giving rise to APLAs. The paucity of this clotting agent gives rise to a thrombophilic state leading to the manifestations of APS. The various APL includes ACL, antiβ2 -GPI, antiphosphatidyl-ethanolamine, antiphosophatidyl-inositol and antiprothrombin. Of clinical importance amidst these are LAC, ACL and anti-β2 -GPI. The ways of detecting these antibodies include direct assessment of the levels of the antibodies in the blood or the effect of the antibodies on clotting. The tests most frequently employed in LA testing are the activated partial thromboplastin time, the dilute Russell's viper venom time and the kaolin clotting time while the ACL assay is performed using the ELISA test. [6]


Studies show that the pediatric population has an increased incidence of APLAs, and most of them could be asymptomatic. The reason attributed towards the development of these antibodies is the presence of frequent infections in childhood. [7] APL positivity should be confirmed twice in children since the postinfectious elevation of APL levels may only be transient. There have been reports showing increased levels of β2 -GPI in cases of atopic dermatitis without any increase in the risk for APS. A meta-analysis of the published studies that investigated the prevalence and clinical significance of APL in pediatric systemic lupus erythematosus (SLE) showed a global prevalence of 44% for ACL, 40% for antiβ2 -GPI and 22% for LAC. [8] In the study by Makhija et al. in 2008 the prevalence of APS was 25% of the 36 pediatric patients with stroke being the commonest presentation. [9] In 2001 Singh et al. showed that the most common presentation in young patients was myocardial infarction and stroke with 18.18% patients in the stroke subgroup and 4.16% patients in myocardial infarction subgroup had raised ACL titers. [10]

  Antiphospholipid antibody syndrome Top

Antiphospholipid syndrome is an autoimmune disorder with a thrombophilic tendency leading to recurrent thrombosis and pregnancy morbidity with fetal loss. Based on whether there is an underlying cause or not it can be divided into primary and secondary form. The primary form of this condition is not associated with any underlying disorder while the secondary form is generally associated with an underlying SLE.

The onset has been reported in children as young as 8 months. Studies have shown that patients with associated rheumatic disease were older and had a higher frequency of venous thrombotic events associated with hematologic and skin manifestations. A female predilection exists for secondary APS most likely due to the increased incidence of SLE in them.

  Pathogenesis Top

The formation of the clot in APS can be explained by a two-hit hypothesis which triggers the process of clotting. Experimental models as well as in clinical observations demonstrated that infections, surgical intervention or other procoagulant factor may precipitate the thrombosis. [10],[11],[12] Singh et al. demonstrated the presence of activated platelets have several altered functions in the in vivo and in vitro studies. The literature and evidences suggest the role of altered platelet function to be important irrespective of the triggering factors. Detailed study on the pathogenic mechanism, if possible using individualized antithrombotic strategies will help to elaborate on the pathogenetic mechanisms of APS. [13]

  Clinical features Top

Noncutaneous features include thrombotic events in the form of pulmonary thromboemolism, strokes, retinal vein and artery thrombosis. Hematological abnormalities include thrombocytopenia, autoimmune hemolytic anemia and leukocytopenia. Neurologic manifestations include headaches, seizures and chorea.

Thrombosis has been attributed as the major clinical feature of APS with recurrence of thrombosis occurring in almost 20% of patients. [14] A very small group of people with APLAs develop multiple clots in different organ systems throughout the body within a matter of days. This is called catastrophic APLA syndrome. [15]

Antiphospholipid syndrome manifesting in children with only cutaneous manifestation is generally rare. Cutaneous manifestations include gangrene, ulceration, livedo reticularis, thrombophlebitis, necrotic purpura, Raynaud phenomenon, leukocytoclastic vasculitis, Degos-like ulceration and pyoderma gangrenosum like ulceration. Although Raynaud phenomenon and livedo reticularis represent the most common skin manifestation, each amounting to 6% of the affected patients, cutaneous necrosis was the sole manifestation in one report from India. [16]

 Sneddon syndrome More Details, characterized by the triad of livedo reticularis, hypertension, and cerebrvascular disease is rare in children. However, there have been reports of the same in the past. [17],[18],[19]

  Diagnosis Top

The diagnosis of this condition can be done using revised Saporro criteria which include at least one clinical criteria and one laboratory criteria.

  Management Top

There is a paucity of data regarding the guidelines for the management of APS and most of the times it is extrapolated from the adult guidelines and recommendations. As reports suggest, most patients require international normalized ratio (INR) of 3-4 like that of adults to prevent recurrent events. [6] There were no reports of any adverse events experiences by the Canadian study group when they used anticoagulants for their patients. [3] However the safety of anticoagulants in children has not been studied adequately. Aspirin at low dose is used as prophylaxis in children with autoimmune diseases such as SLE along with APL. [6] Low molecular weight heparin and enoxaparin have been both used for the acute management of thromboembolic events. A study of 14 patients treated for active thrombosis and five treated prophylactically showed that low molecular weight heparin (LMWH) were at least as effective and safe as unfractionated heparin in pediatric patients immediately after a thrombotic event. [20] Albisetti and Andrew concluded that LMWH is an efficient and safe alternative to standard anticoagulation therapy with unfractionated heparin and oral anticoagulants for treatment and prevention of thromboembolic phenomenon in children of varying ages and with different underlying disorders. [21]

Children with catastrophic APS are managed with intravenous anticoagulation and plasmapheresis. The long-term management of APS has been advised with oral warfarin. An intermediate intensity anticoagulation treatment with a target INR of 2.0-2.5 has been suggested in children with APS by Uysal et al. and Manco-Johnson and Nuss [22],[23]

  Conclusion Top

Although the main clinical features of APS include noncutaneous manifestations with occasional cutaneous manifestation in children, it is worthwhile to have knowledge regarding the varied cutaneous features of this condition along with work up guidelines of these patients. Early suspicion of this condition based on the clinical characteristics will help in effective detection and management of these cases.

  References Top

Saigal R, Kansal A, Mittal M, Singh Y, Ram H. APLA syndrome. J Assoc Phy Ind 2010;58:176-84.  Back to cited text no. 1
Chandrashekhara S, Kirthi R, Varghese J. Prevalence of anticardiolipin antibodies in various thrombotic conditions: A hospital-based study. J Assoc Physicians India 2003;51:359-62.  Back to cited text no. 2
Andrew M, David M, Adams M, Ali K, Anderson R, Barnard D, et al. Venous thromboembolic complications (VTE) in children: First analyses of the Canadian Registry of VTE. Blood 1994;83:1251-7.  Back to cited text no. 3
Wise RC, Todd JK. Spontaneous, lower-extremity venous thrombosis in children. Am J Dis Child 1973;126:766-9.  Back to cited text no. 4
Nowak-Göttl U, Koch HG, Aschka I, Kohlhase B, Vielhaber H, Kurlemann G, et al. Resistance to activated protein C (APCR) in children with venous or arterial thromboembolism. Br J Haematol 1996;92:992-8.  Back to cited text no. 5
Kamat AV, D'Cruz DP, Hunt BJ. Managing antiphospholipid antibodies and antiphospholipid syndrome in children. Haematologica 2006;91:1674-80.  Back to cited text no. 6
Cabiedes J, Trejo-Hernández J, Loredo-Abdalá A, Castilla-Serna L, López-Mendoza AT, Cordero-Esperón HA, et al. Anti-cardiolipin, anti-cardiolipin plus bovine, or human beta (2) glycoprotein-I and anti-human beta (2) glycoprotein-I antibodies in a healthy infant population. Arch Med Res 2002;33:175-9.  Back to cited text no. 7
Avcin T, Cimaz R, Silverman ED, Cervera R, Gattorno M, Garay S, et al. Pediatric antiphospholipid syndrome: Clinical and immunologic features of 121 patients in an international registry. Pediatrics 2008;122:e1100-7.  Back to cited text no. 8
Makhija S, Aneja S, Tripathi RP, Narayan S. Etiological profile of stroke and its relation with prothrombotic states. Indian J Pediatr 2008;75:579-84.  Back to cited text no. 9
Singh K, Gaiha M, Shome DK, Gupta VK, Anuradha S. The association of antiphospholipid antibodies with ischaemic stroke and myocardial infarction in young and their correlation: A preliminary study. J Assoc Physicians India 2001;49:527-9.  Back to cited text no. 10
Kaneria MV, Vishwanathan C. A preliminary study of antiphospholipid antibodies in 50 cases of bad obstetric history. J Assoc Physicians India 1999;47:669-72.  Back to cited text no. 11
Chakrabarti S, Bhunia C, Bhattacharya DK. The prevalence of antiphospholipid antibodies in cases of recurrent pregnancy loss. J Assoc Physicians India 1999;47:496-8.  Back to cited text no. 12
Misra R, Chandrashekara S. Pathogenesis of antiphospholipid antibody syndrome needs further exploration. Internet J Rheumatol Clin Immunol 2013;1:E2.  Back to cited text no. 13
Tong M, Viall CA, Chamley LW. Antiphospholipid antibodies and the placenta: A systemic review of their in vitro effects and modulation by treatment. Human Reproduction Update 2014;21:97-118.  Back to cited text no. 14
Misita CP, Moll S. Antiphospholipid antibodies. Circulation 2005;112:e39-44.  Back to cited text no. 15
Bapat SS, Pulikot AM, Naik P, Chinchankar N. Antiphospholipid antibody syndrome. Indian Pediatr 2001;38:1413-6.  Back to cited text no. 16
Heesen M, Rossaint R. Anaesthesiological considerations in patients with Sneddon's syndrome. Paediatr Anaesth 2000;10:678-80.  Back to cited text no. 17
Gottlöber P, Bezold G, Schaer A, Stolz W, Friesecke I, Peter RU, et al. Sneddon's syndrome in a child. Br J Dermatol 2000;142:374-6.  Back to cited text no. 18
Zaccariotti VA, Martins LF, da Costa V, Silva NA, da Casas AA, de Melo-Souza SE. Sneddon syndrome. Report of 3 cases. Arq Neuropsiquiatr 1995;53:82-7.  Back to cited text no. 19
Punzalan RC, Hillery CA, Montgomery RR, Scott CA, Gill JC. Low-molecular-weight heparin in thrombotic disease in children and adolescents. J Pediatr Hematol Oncol 2000;22:137-42.  Back to cited text no. 20
Albisetti M, Andrew M. Low molecular weight heparin in children. Eur J Pediatr 2002;161:71-7.  Back to cited text no. 21
Uysal Z, Dogu F, Kürekçi AE, Culha VK, Deda G, Ekim M, et al. Recurrent arterial thrombosis in a child: Primary antiphospholipid antibody syndrome. Pediatr Hematol Oncol 2002;19:59-66.  Back to cited text no. 22
Manco-Johnson MJ, Nuss R. Lupus anticoagulant in children with thrombosis. Am J Hematol 1995;48:240-3.  Back to cited text no. 23


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