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ASSESSMENT OF PLATELET FUNCTIONS IN CHRONIC MYELOID LEUKEMIA PATIENTS TREATED WITH TYROSINE KINASE INHIBITORS
Author(s): ,
Yigit Sener
Affiliations:
Medical Biochemistry,Hacettepe University Faculty of Medicine,Ankara,Turkey
,
Filiz Akbiyik
Affiliations:
Medical Biochemistry,Hacettepe University Faculty of Medicine,Ankara,Turkey
,
Sevda Aydın
Affiliations:
Hematology,Hacettepe University Faculty of Medicine,Ankara,Turkey
,
Yahya Buyukasik
Affiliations:
Hematology,Hacettepe University Faculty of Medicine,Ankara,Turkey
Zeliha Gunnur Dikmen
Affiliations:
Medical Biochemistry,Hacettepe University Faculty of Medicine,Ankara,Turkey
(Abstract release date: 05/19/16) EHA Library. Akbiyik F. 06/09/16; 134739; PB1839
Prof. Filiz Akbiyik
Prof. Filiz Akbiyik
Contributions
Abstract
Abstract: PB1839

Type: Publication Only

Background
Bleeding is observed time to time in chronic myeloid leukemia (CML) patients using tyrosine kinase inhibitors (TKI). It has been suggested  that tyrosine kinase inhibitors can disrupt platelet functions and cause beeding without thrombocytopenia in CML patients.

Aims
In this study, we aimed to evaluate platelet functions of CML patients using tyrosine kinase inhibitors and examine in conjunction with beeding symptoms to find out whether there is a correlation between them.

Methods
In this study, bleeding surveys were performed for 68 CML patients in cronic phase receiving imatinib (n=47), dasatinib (n=15) and nilotinib (n=6). Hematology analyzer LH780 (Beckman Coulter) was used for measurement of complete blood counts. BCS XP coagulation analyzer (Siemens) was used for measurement of  PT, aPTT, TT, fibrinogen and factor assays. In our coagulation laboratory, platelet rich plasma pool was prepared and light transmittance agregometry (Chrono-Log) was used for the evaluation of platelet functions. Platelet agregation was induced in in vitro conditions by different agonists (ADP, epinephrine, collagen, ristocetin) and the agregation percentage / time graph was analyzed to evaluate platelet functions.

Results
The median age was found as 47 years (range, 18-78 years) in CML patients. Complete blood counts and coagulation test results were in normal range; white blood cell count 6.72,5 ×103/µL, hemoglobin 13.0±1,7 g/dL, platelets 234.7±74,5 ×103/µL, PT 12,8±1,4 sn, INR 1,0±0,1, aPTT 27.6±2,8 sec, TT 16.5±2,0 sec, fibrinojen 325.7 mg/dL and Factor VIII levels were 120,8±11,2%. When the bleeding survey results were analysed, the patients who have bleeding score below 3 were accepted as minor bleeding. When the relation between bleeding scores and TKI treatment were evaluated; we observed that 25,6% of the patients who use imatinib and 20% of the patients who use dasatinib have minor bleeding symptoms. In Nilotinib treatment group, no bleeding symptom was observed. In total, 22% of CML patients under TKI treatment have bleeding symptoms; 17,6% with bleeding score 1 and 4,4% with bleeding score 2. In platelet function tests, when aggregation was induced by ADP, epinephrine, collagen and ristosetin, secretion type defect was observed in 26% of the patients. No correlation was observed between platelet function defects and minor bleeding symptoms in these patients.

Conclusion
As a result, platelet agregation disorders can be observed in CML patients treated with tyrosine kinase inhibitors. However, platelet dysfunction is not associated with bleeding disorder. Furthermore, the effect mechanism of tyrosine kinase inhibitors on platelet homeostasis warrants further investigation.

Session topic: E-poster

Keyword(s): Chronic myeloid leukemia, Tyrosine kinase inhibitor
Abstract: PB1839

Type: Publication Only

Background
Bleeding is observed time to time in chronic myeloid leukemia (CML) patients using tyrosine kinase inhibitors (TKI). It has been suggested  that tyrosine kinase inhibitors can disrupt platelet functions and cause beeding without thrombocytopenia in CML patients.

Aims
In this study, we aimed to evaluate platelet functions of CML patients using tyrosine kinase inhibitors and examine in conjunction with beeding symptoms to find out whether there is a correlation between them.

Methods
In this study, bleeding surveys were performed for 68 CML patients in cronic phase receiving imatinib (n=47), dasatinib (n=15) and nilotinib (n=6). Hematology analyzer LH780 (Beckman Coulter) was used for measurement of complete blood counts. BCS XP coagulation analyzer (Siemens) was used for measurement of  PT, aPTT, TT, fibrinogen and factor assays. In our coagulation laboratory, platelet rich plasma pool was prepared and light transmittance agregometry (Chrono-Log) was used for the evaluation of platelet functions. Platelet agregation was induced in in vitro conditions by different agonists (ADP, epinephrine, collagen, ristocetin) and the agregation percentage / time graph was analyzed to evaluate platelet functions.

Results
The median age was found as 47 years (range, 18-78 years) in CML patients. Complete blood counts and coagulation test results were in normal range; white blood cell count 6.72,5 ×103/µL, hemoglobin 13.0±1,7 g/dL, platelets 234.7±74,5 ×103/µL, PT 12,8±1,4 sn, INR 1,0±0,1, aPTT 27.6±2,8 sec, TT 16.5±2,0 sec, fibrinojen 325.7 mg/dL and Factor VIII levels were 120,8±11,2%. When the bleeding survey results were analysed, the patients who have bleeding score below 3 were accepted as minor bleeding. When the relation between bleeding scores and TKI treatment were evaluated; we observed that 25,6% of the patients who use imatinib and 20% of the patients who use dasatinib have minor bleeding symptoms. In Nilotinib treatment group, no bleeding symptom was observed. In total, 22% of CML patients under TKI treatment have bleeding symptoms; 17,6% with bleeding score 1 and 4,4% with bleeding score 2. In platelet function tests, when aggregation was induced by ADP, epinephrine, collagen and ristosetin, secretion type defect was observed in 26% of the patients. No correlation was observed between platelet function defects and minor bleeding symptoms in these patients.

Conclusion
As a result, platelet agregation disorders can be observed in CML patients treated with tyrosine kinase inhibitors. However, platelet dysfunction is not associated with bleeding disorder. Furthermore, the effect mechanism of tyrosine kinase inhibitors on platelet homeostasis warrants further investigation.

Session topic: E-poster

Keyword(s): Chronic myeloid leukemia, Tyrosine kinase inhibitor

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