Anaphylaxis Following Human Prothrombin Complex Concentrate in a Child with Lupus Anticoagulant Hypoprothrombinemia Syndrome: A Cautionary Tale

Abstract

A previously healthy 3-year-old girl presented with a short history of mucocutaneous bleeding and a spontaneous left knee hemarthrosis following a nonspecific viral gastroenteritis. Initial investigations for a bleeding disorder revealed a normal platelet count; however, coagulation studies revealed a prothrombin time (PT) of 25 seconds and an activated partial thromboplastin time (APTT) of 66 seconds (both prolonged). The APTT did not correct on mixing with normal plasma, and further testing confirmed the presence of a strong lupus anticoagulant (LA). One-stage assays of factor VIII, VII, and X were normal, but factor II was markedly reduced. Based on this distinct clinicopathological picture, a diagnosis of lupus anticoagulant hypoprothrombinemia syndrome (LAHS) was made. Due to the presence of a hemarthrosis, the patient was treated with clotting factor concentrate. Human prothrombin complex concentrate (PROTHROMBINEX-VF) was used as a source of factor II replacement; however, during the infusion the patient developed anaphylaxis necessitating resuscitation. The patient was observed without further factor replacement, and the bleeding symptoms resolved over several days. Within 3 weeks her PT and factor II had normalized but the APTT remained prolonged. After 6 months the coagulation profile had completely normalized and the LA was negative. It is unusual to require replacement of factor II in paediatric LAHS because bleeding is typically minor and self-limited. Anaphylaxis to clotting factor concentrates has not been previously reported in the context of LAHS, but is well described in patients with congenital factor IX deficiency (hemophilia B). Whilst the potential mechanism for anaphylaxis in our patient is unknown, it is recommended that human prothrombin complex concentrates should be used cautiously in paediatric LAHS.

Keywords

coagulation factors - coagulation inhibitors - factor concentrates

• References

• 1 Keeling D, Mackie I, Moore GW, Greer IA, Greaves M. ; British Committee for Standards in Haematology. Guidelines on the investigation and management of antiphospholipid syndrome. Br J Haematol 2012; 157 (01) 47-58
• 2 Rapaport SI, Ames SB, Duvall BJ. A plasma coagulation defect in systemic lupus erythematosus arising from hypoprothrombinemia combined with antiprothrombinase activity. Blood 1960; 15: 212-227
• 3 Pengo V, Tripodi A, Reber G. , et al; Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibody of the Scientific and Standardisation Committee of the International Society on Thrombosis and Haemostasis. Update of the guidelines for lupus anticoagulant detection. J Thromb Haemost 2009; 7 (10) 1737-1740
• 4 Bajaj SP, Rapaport SI, Fierer DS, Herbst KD, Schwartz DB. A mechanism for the hypoprothrombinemia of the acquired hypoprothrombinemia-lupus anticoagulant syndrome. Blood 1983; 61 (04) 684-692
• 5 Mazodier K, Arnaud L, Mathian A. , et al. Lupus anticoagulant-hypoprothrombinemia syndrome: report of 8 cases and review of the literature. Medicine (Baltimore) 2012; 91 (05) 251-260
• 6 Sarker T, Roy S, Hollon W, Rajpurkar M. Lupus anticoagulant acquired hypoprothrombinemia syndrome in childhood: two distinct patterns and review of the literature. Haemophilia 2015; 21 (06) 754-760
• 7 Castaman G, Bonetti E, Messina M. , et al; Italian Association of Hemophilia Centers. Inhibitors in haemophilia B: the Italian experience. Haemophilia 2013; 19 (05) 686-690
• 8 Baudo F, Redaelli R, Pezzetti L. , et al. Prothrombin-antibody coexistent with lupus anticoagulant (LA): clinical study and immunochemical characterization. Thromb Res 1990; 57 (02) 279-287
• 9 CSL: PROTHROMBINEX®-VF (Internet). Australia: CSL Group Global. Available at: http://www.csl.com.au/productfinder/prothrombinexau . Accessed September 27, 2017