Study of 11-dehydro-thromboxaneB2 as a marker of thromboembolic events in beta-thalassemia patients

A range of laboratory tests had provided solid evidence for the existence of a chronic hypercoagulable state in thalassemia particularly in splenctomized patients and TI.Several etiologic factors may play a role in the pathogenesis of that hypercoagulable state in thalassemia. The specific changes in the platelets function contribute to the activation of the coagulation process.In our study we tried to evaluate the role of platelets activation by measuring the level of 11 dehydroTXB2 in beta-thalassemic patients either beta thalassemia major (TM) or beta thalassemia intermedia (TI).This study was carried out in at thalassemia out patient clinic at Zagazig university hospitals. The study included a total number of 35 patients, classified into:Group I: Included 10 healthy and haematologically normal subjects as a control group.Group II: Included 10 non-splenectomized -thalassemia major (NSTM) patients.Group III: Included 8 -thalassemia intermedia (NSTI) patients.Group IV: Included 7 splenectomized -thalassemia major (STM) patients.All the subjects were subjected to the following:1- History taking and clinical examination.2- Laboratory investigations to confirm the diagnosis:•Complete blood count.•Haemoglobin electrophoresis on cellulose acetate strips.• Prothrombin time (PT).• Partial thromboplastin time (PTT).• Urine creatinine: in spot urine sample was done by Jaffe reaction.(Vasilliades ,1976)• Reticulocyte count: by Suravital stain e.g. brilliant cresyl blue.3- Specific investigations include:• D-dimer: by minividas from biomoruex.• Fibrinogen: by clauss method.• Brain MRI.• Doppler ultrasound on the abdomen.• Estimation of 11 dehydro-thromboxane B2 level by ELISA from DRG international company provided by clinilab.• Results were reported as pg urinary 11dhydroTxB2 per ml urinary creatinine in order to normalize results for the concentration of the urine sample tested.from our study we found that the hypercoagulability markers; 11 dehydro-thromboxane B2, D-dimer and Fibrinogen showed very highly significant difference between groups (P<0.001).Age had no significant difference between all groups and it did not correlate with any of the hypercoagulability markers (P>0.05).In our study a very highly significant difference was obtained between groups for the mongoloid features (P<0.001).Hb concentration shows very highly significant decrease in groups NSTM, TI and STM (P<0.001) when compared to that of the control group.RBCs count showed very highly significant decrease in groups II&IV compared to the control group (P<0.001) but there was significant decrease in groups III in comparison with that of the control, P< 0.05.MCV and MCHC showed very highly statistically significant decrease in all patients groups (II, III and IV) compared to the control (P<0.01).HbF % very highly significantly increased in all patients groups compared to the control group (P<0.001) and all the patients groups and each other (P<0.001), except between groups III&IV, there were no statistical significant increase, P>0.05.STM only had statistically significant increase in WBCs counts than all the studied groups, P<0.05. While no significant differences were obtained between all other groups (P > 0.05).Platelets counts revealed significant decrease in NSTM and significant increase in STM when compared to the control group but no significant difference between NSTI and the control group as Plt counts are normal or mildly increased.There were no statistical significant differences between studied groups as regard PT (F=2.436 and P>0.05) and PTT (F=2.586 and P>0.05).In our study Urinary 11 dehydroTXB2 pg/ mg creatinine revealed very high significant increase in the all groups compared to that of the control group. In addition, there were significant difference between all the patients groups and each other (P<0.05), while there were no significant increase between group III & IV, P>0.05. This reflects the more platelet activation and hypercoagulable state in both groups compared with group II.Fibrinogen level showed very highly statistical significant decrease in all patients groups compared to the control group, P<0.001. No statistical significant decrease between group III & IV and II&IV, P>0.05.D-dimer very highly statistical significant increase in all patients groups compared to the control group, P<0.001. No significant difference was obtained between group III & IV and II&IV, P>0.05.There was strong positive correlation in our study between 11 dehydroTXB2 and D-dimer level in groups II, III and IV. On the other hand there were strong negative correlation between 11 dehydroTXB2 and fibrinogen level in groups II, III and IV. There was strong negative correlation between D-dimer and fibrinogen level in groups III and IV.In our results, no significant correlations were found between platelets counts and hypercoagulability markers (11 dehydroTXB2, D-dimer and fibrinogen) in all studied groups (P>0.05).Serum ferretin level showed very highly statistical significant increase in all patients groups compared to the control group, P<0.001 except group III no statistical significant increase, P>0.05.A strong positive correlation was found between serum ferretin and treatment regularity irrespective type of treatment in both group II (r = 0.77) and IV(r =0.88). On the other hand no significant correlations were found between serum ferretin and hypercoagulability markers (11 dehydroTXB2, D-dimer and fibrinogen) in all studied groups (P>0.05).A strong inverse correlation was found between HB F and both 11 dehydro TXB2 and D dimer in group II, III and IV.Platelets counts, PT and PTT did not correlate with any of the hypercoagulability markers (11 dehydroTXB2, D-dimer and fibrinogen) in all the study groups, P>0.05.from all the previous we concluded that platelet activation has a main role in hypercoagulable state of -thalassemic patients by elevated urinary 11-dehydro-TXB2 level derived from platelets. The results of this study are consistent with increase of D-dimer and decrease of fibrinogen levels.This hypercoagulable state is more marked in splenectomized patients than none splenectomized that reflects the role of spleen in eliminating those abnormal RBCs.Incidence of thromboembolism is higher in thalassemia intermedia than in thalassemia major patients. This reflects the role of regular blood transfusion in decreasing the hypercoagulability.That hypercoagulable state is age independent so it is not related to organs damage by iron over load but it mostly due to the original mutation of the disease.The hypercoagulable state is worsening with increasing the anemia and decreasing by high level of HbF which protect against the development of marked anemia.