Prevalence and Effect of Coagulation Defects in Children Undergoing Bone Marrow Transplantation for Haemoglobinopathies.
Authors: Collier Edward , de la Fuente Josu , Chakravorty Subarna 
Published: October 2019

Abstract
Abstract 3037
Bone marrow transplantation (BMT) is currently the only cure for thalassaemia major (TM) and sickle cell disease (SCD). Due to the myeloablative preparative regimen used for transplants, patients with TM and SCD become thrombocytopenic prior to platelet engraftment and may occasionally suffer from significant haemorrhage. This may be potentially augmented by co-existing coagulopathies, either inherited, or as a result of abnormal synthesis of clotting factors in the liver due to transfusional hepatic siderosis. The frequency and clinical impact of coagulopathies in patients undergoing BMT for these conditions is not known. The aim of this project was to investigate whether coexisting coagulopathy or hepatic siderosis result in an increase in haemorrhagic complications or increased use of blood products.
All patients who underwent BMT for TM or SCD at St Mary's Hospital from 2002 to 2011 were eligible for this retrospective study. Initially, 98 patients were identified, of whom 4 patients were excluded due to lack of adequate data. Of the 94 patients studied, 69 had TM and 25 had SCD with a mean age of 7.7 years (range 2.2– 17.7). There were 50 females and 44 males. Consanguinity data were obtained in 72 patients, of which 33 had consanguineous parents (46%). Donor and recipient ABO blood group mismatch was present in 62 (66%) patients.
Sixteen out of 94 patients had pre-transplant coagulopathies, of which 12 (75%) had TM and 4 (25%) had SCD. See table 1. These patients were generally asymptomatic and their coagulation deficiencies were only identified on pre-transplant screening Mean pre- transplant ferritin levels were 1587μg/l (s.d. 952) in patients with coagulopathies and 1646μg/l (s.d. 896) in patients without (p=0.815). Transfusional hepatic siderosis was assessed by T2* MRI scan of liver in 44 patients, of which 12 had coagulopathies and by dry weight iron estimation by liver biopsy in 53 patients, of which 11 had coagulopathies. There was no significant difference in hepatic siderosis assessed by T2* MRI scan of liver, (12 versus 9 ms in patients with and without coagulopathies, p=0.28) or by dry weight iron in liver biopsy; (2.9 mg/g versus 3.7 mg/g in those with coagulopathies and those without, respectively, p=0.39).
Mean number of platelet units used in patients with pre-existing coagulopathies was 15.3 (standard deviation, s.d. 12.2) compared to 21.7 units in patients with no pre-existing coagulopathies, p=0.18. Similarly, there was no significant difference in the number of red cell units used in patients with coagulopathies (12.1 units, s.d. 7.8) and in patients without (12.6 units, s.d. 6.2), p=0.78.
Five patients (5.3%) in total had major haemorrhages in the first 30 days post transplant, of which 1 patient had a pre-existing coagulation factor deficiency (FXIII deficiency 36.8 IU/dl, normal range 50–150) and 4 patients had normal coagulation screen prior to transplant.
This study concludes that in a cohort of patients being transplanted for haemoglobinopathies, there is a high frequency of coagulopathies (17%) and that at least some of these disorders are likely to have been inherited, as there were no differences in hepatic siderosis in the 2 groups. Furthermore, pre-transplant coagulopathies such as these are not a contraindication to transplant since these patients were not at a higher risk of major haemorrhage during the transplant and their red cell or platelet requirement was not significantly higher than patients with normal pre-transplant coagulation screens. Further studies are needed to clarify the extent to which pre-transplant coagulopathies are familial and increased in frequency due to consanguinity. In such a scenario, family screening for homozygous deficiencies in other family members might then be indicated.
Table 1. Details of coagulation defects in patients identified on screening Patient's Coagulopathy 1. FXI + FXII deficiency 2. Mild Haemophilia A 3. Mild FXI deficiency 4. Mild FVII deficiency and borderline FXI deficiency 5. Type 1 von Willebrand Disease 6. Type 1 von Willebrand Disease 7. Reduced hepatic synthesis of multiple factors 8. FXIII deficiency and hypofibrinogenaemia 9. Reduced hepatic synthesis of multiple factors 10. Borderline FVII 11. Type 1 von Willebrand Disease 12. FXI deficiency 13. FXII and FXIII deficiency 14. Dysfibrinogenaemia 15. Dysfibrinogenaemia 16. FXII deficiency

Disclosures:
No relevant conflicts of interest to declare.