Factor XIII deficiency, with an estimated incidence of 1 in 1-2 million, is an extremely rare congenital bleeding disorder with autosomal recessive inheritance and often with a history of consanguinity [1]. It can present with myriad bleeding manifestations in different age groups, with varying severity. This is partly due to multiple possible mutations of the two subunits of Factor XIII (subunit A mutations are associated with severe manifestations than those of subunit B) and partly because factor XIII is a multifunctional protein (required in wound healing, maintenance of pregnancy, angiogenesis and hemostasis). Umbilical cord bleeding, present in 73% of patients, is highly suggestive of this condition [1,2]. Pubertal menorrhagia was present in nearly 31% patients as per an Indian study [1].

A14-year-old girl presented with severe anemia and menorrhagia, refractory to antifibrinolytic therapy, during the third menstrual cycle, with significant past history of having menorrhagia in every cycle after the onset of menarche. These episodes were being treated with blood transfusions, antifibrinolytics, hematinics and oral contraceptive pills. She was born as a third issue of third degree consanguineous couple with no relevant family history and bleeding diathesis. Ultrasound of pelvis, thyroid profile, platelet counts and morphology, coagulation profile (PT-12.1sec, PTT-28sec, INR-1) and clot retraction tests were normal. With this background, qualitative assay for factor XIII was considered and clot solubility test was positive. Quantitative assay, platelet function test, von Will ebrand factor assay and molecular genetic test were not performed because of affordability issues.

Although, coagulopathy is the second most common cause of pubertal menorrhagia [3] with congenital factor XIII deficiency being the commonest amongst the ‘rare congenital factor deficiencies’, it stays under diagnosed due to its rarity, heterogeneity and absence of diagnostic facilities [1]. Qualitative assay with clot solubility in 5M urea detects only severe form, but quantitative functional assay detects all forms and it is the recommended first line screening method as it has no false positivity [4]. The available treatment options include replacement and prophylactic therapy with cryoprecipitate, fresh frozen plasma and factor XIII concentrates [5].

Awareness about all possible features of factor XIII deficiency is essential among clinicians while managing cases for prompt diagnosis, appropriate treatment, improving quality of life, decreasing the burden of further medical catastrophes, follow up and genetic counseling to prevent morbidity in affected children.

Acknowledgments: Dr Spoorthi SM and Dr Lingaraja Gowda C Patil for help in data analysis and drafting the manuscript.

1. Shetty S, Shelar T, Mirgal D, Nawadkar V, Pinto S, Shabhag S, et al. Rare coagulation factor deficiencies: A countrywide screening data from India. Haemophilia. 2014;20:575-81.

2. Naderi M, Dorgalaleh A, Alizadeh S, Taibibian S, Hosseini S, Shamsizadeh M, et al. Clinical manifestations and management of life threatening bleeding in the largest group of patients with severe factor XIII deficiency. Int J Hematol. 2014;100:443-9.

3. Karaman K, Ceylan N, Karaman E, Akbayram S, Akbaryram HT, Garipardic M, et al. Evaluation of the hemostatic disorders in adolescent girls with menorrhagia: Experiences from a tertiary referral hospital. Indian J Hematol Blood Transfus. 2016;32:356-61.

4. Kohler HP, Ichinose A, Seitz R, Ariens RAS, Muszbek L. Diagnosis and classification of factor XIII deficiencies. J Thromb Haemost. 2011;9:1404-06.