Endocrine Abstracts (2015) 38 P158 | DOI: 10.1530/endoabs.38.P158

Clot structure analysis in survivors of acute lymphoblastic leukaemia: the role of growth hormone deficiency

Nikolaos Kyriakakis1,2, Satish S Kumar1, Julie Lynch1, Natalie Oxley2, Fladia Phoenix2, Ramzi Ajjan2 & Robert D Murray1,2


1Leeds Centre for Diabetes and Endocrinology, St James’s University Hospital, Leeds, UK; 2Division of Cardiovascular and Diabetes Research, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK.


Introduction: Childhood-onset cancer survivors demonstrate increased mortality rates due to cardiovascular and cerebrovascular events. Studies suggest that leukaemia and brain tumour survivors have a relative risk of 6.4 and 29.0 respectively for stroke. Adverse lipid profile, body composition, insulin resistance and hypertension have been implicated to the increased cardiovascular risk in these patients, however little is known about procoagulant factors and markers of vascular inflammation in these cases.

Methods: We undertook a pilot cross-sectional study in 6 patients with acute lymphoblastic leukaemia (ALL), compared with 6 age and gender-matched controls. Measurements included plasma fibrinogen using the Clauss method, high-sensitivity CRP using in-house ELISA and clot structure analysis, using turbidimetric analysis to measure ex-vivo fibrin polymerization and fibrinolysis speed.

Results: patients (mean age 27.5±7 years), diagnosed with ALL at 6.7±3.1 years of age, were assessed. All patients received cranial radiotherapy, while three patients had additional total body irradiation for bone marrow transplantation (total mean cranial radiation dose 28.6±8.3Gy). All patients had severe GHD and 3 of them were on stable GH replacement at the time of the study. Fibrinogen levels were significantly higher in the ALL group compared with controls (2.96±0.38 mg/ml vs. 2.45±0.27 mg/ml, P=0.022). All controls had undetectable CRP, while mean CRP level for patients was 1.8±2.1mg/L; however difference failed to reach statistical significance (P=0.065). Patients had raised clot maximum absorbance (0.42±0.08 vs 0.31±0.03 arbitrary units (AU), P=0.009), longer lysis time (1336.8±653.1 s vs. 893.8±65.22 s, P=0.009) and larger lysis area (915.4±578.9 vs 521.1±71.1 AU, P=0.04) compared with controls.

Conclusions: Our results demonstrate more compact clots and resistance to fibrinolysis ex-vivo in patients with ALL, which may contribute to the increased cardiovascular risk in these individuals. Similar changes in clot structure/lysis have previously been found in GHD, which may constitute the underlying mechanism responsible for the clotting abnormalities observed in ALL patients.

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