Background: The pathophysiology of vaso-occlusive crises in sickle cell anaemia (SCA) is multifactorial and hypercoagulability is believed to play a role. The association between hypercoagulabilty and vaso-occlusive disease has been extensively studied in adult SCA patients, there is however paucity of data on the subject regarding paediatric SCA. Objective: This study set out to determine the presence of hypercoagulable states specifically in paediatric SCA subjects through quantification of specific coagulation markers during painful crises and steady state. Methodology: The study was a hospital- based longitudinal study carried out between May and October 2015 at Federal Medical Center, Abeokuta, Nigeria. Fifty SCA subjects were consecutively recruited during painful crises and followed up into their respective steady states. Twenty-five subjects with HbAA phenotype served as controls. Assays of coagulation markers, D-dimer and prothrombin fragment (F1 2) were carried out by sandwich ELISA method using MyBiosource？ D-dimer and F1 2 ELISA kits. Results: Mean D-dimer level was 7358 ± 4354.33 ng/ml in the SCA subjects during painful crises, 5509 ± 3506.2 ng/ml during steady state, and 800 ± 1874.14 ng/ml in HbAA controls. Mean (F1 2) level was 0.84 ± 0.43 nmol/l in the SCA subjects during painful crises, 0.64 ± 0.25 nmol/l during steady state, and 0.41 ± 0.28 nmol/l, in HbAA controls. The mean values of both coagulation markers assayed were significantly higher during painful crises than at steady state (P = 0.002), while steady state values were also significantly higher than that of haemoglobin AA individuals (P = 0.001). Conclusions: This study suggests the presence of hypercoagulable states in paediatric SCA during steady state which is exacerbated during painful crises. The clinical imports of this finding require further elucidation.
Lal, A. and Vinchinsky, E. (2005) Sickle Cell Disease. In: Hoffbrand, A.V., Catovsky, D. and Tuddenham, E., Eds., Postgraduate Hematology, 5th Edition, Blackwell Publishing, USA, 104-108. https://doi.org/10.1002/9780470987056.ch7
Beutler, E. (2010) Disorders of Hemoglobin Structue: Sickle Cell Anemia and Related Abnormalities. In: Kaushansky, K., Lichtman, M., Beutler, E., Kipps, T., Seligsohn, U., Prchal, J., Eds., Williams Hematology, McGraw-Hill Companies Inc.
Ataga, K.I., Cappellini, M.D. and Rachmilewitz, E.A. (2007) Thalassaemia and Sickle Cell Anaemia as Paradigms of Hypercoagulability. British Journal of Haematology, 139, 3-13. https://doi.org/10.1111/j.1365-2141.2007.06740.x
Fakunle, E., Eteng, K. and Shokunbi, W. (2012) D-Dimer Levels in Patients with Sickle Cell Disease during Bone Pain Crises and in Steady State. Pathology and Laboratory Medicine International, 2, 21-25. https://doi.org/10.2147/PLMI.S29393
Francis Jr., R. (1989) Elevated Fibrin D-Dimer Fragment in Sickle Cell Anemia: Evidence for Activation of Coagulation during the Steady State as Well as in Painful Crisis. Pathophysiology of Haemostasis Thrombosis, 19, 105-111. https://doi.org/10.1159/000215901
Bauer, K.A., Weiss, L.M., Sparrow, D., Vokonas, P.S. and Rosenberg, R.D. (1987) Aging-Associated Changes in Indices of Thrombin Generation and Protein C Activation in Humans. Journal of Clinical Investigation, 80, 1527-1534. https://doi.org/10.1172/JCI113238
Cushman, M., Psaty, B., Macy, E., et al. (1996) Correlates of Thrombin Markers in an Elderly Cohort Free of Clinical Cardiovascular Disease. Arteriosclerosis, Throm- bosis, and Vascular Biology, 16, 1163-1169. https://doi.org/10.1161/01.ATV.16.9.1163
Hursting, M.J., Stead, A.G., Crout, F.V., Horvath, B.Z. and Moore, B.M. (1993) Effects of Age, Race, Sex and Smoking on Prothrombin Fragment 1.2 in a Healthy Population. Clinical Chemistry, 39, 683-686.
Chinawa, J.M., Emodi, I.J., Ikefuna, A.N. and Ocheni, S. (2013) Coagulation Profiles of Children with Sickle Cell Anaemia in Steady State and Crisis Attending University of Nigeria Teaching Hospital Ituku-Ozalla, Enugu. Nigerian Journal of Clinical Practice, 16, 159-163. https://doi.org/10.4103/1119-3077.110132
Taiwo, I.A., Oloyede, O.A. and Dosumu, A.O. (2011) Frequency of Sickle Cell Genotype among Yorubas in Lagos: Implication of Level of Awareness and Genetic Counseling for Sickle Cell Dis-ease in Nigeria. Journal of Community Genetics, 2, 13-18. https://doi.org/10.1007/s12687-010-0033-x
Ota, S., Wada, H., Abe, Y. and Yamada, E. (2008) Elevated Levels of Prothrombin Fragment Indicate High Risk of Thrombosis. Clinical and Applied Thrombosis/ Hemostasis, 14, 279-285. https://doi.org/10.1177/1076029607309176
Akinbami, A., Dosunmu, A., et al. (2012) Haematological Values in Homozygous Sickle Cell Disease in Steady State and Haemoglobin Phenotypes AA Controls in Lagos, Nigeria. BMC Research Notes, 5, 396. https://doi.org/10.1186/1756-0500-5-396
Francis, R.B. (1991) Platelets, Coagulation and Fibrinolysis in Sickle Cell Disease: Their Possible Role in Vascular Occlusion. Blood Coagulation & Fibrinolysis, 2, 341-354. https://doi.org/10.1097/00001721-199104000-00018
Chaplin Jr., H., Monroe, M., Malecek, A., Morgan, L., Michael, J. and Murphy, W. (1989) Preliminary Trial of Minidose Heparin Prophylaxis for Painful Sickle Cell Crises. East African Medical Journal, 66, 574-584.
Schnog, J.B., Kater, A.P., MacGillavry, M.R., et al. (2001) Low Adjusted-Dose Acenocoumarol Therapy in Sickle Cell Disease: A Pilot Study. American Journal of Hematology, 68, 179-183. https://doi.org/10.1002/ajh.1175