Detail Research Data


Data Doctoral/PhD
Research Title Coagulation Activation in Myeloid Leukemia: the Role of Integrin CD11b, Leukocytositosis, Blast Cells and Promyelocytes, and Neutrophil-Platelet/Monocyte-Platelet Aggregates
Kaji Etik Pass Number 3061
Kaji Etik Pass Date 08 Oktober 2007
Focus Others (-)
Principal Investigator SpPD-KHOM Lugyanti Sukrisman DR.dr.
Promotor Karmel L Tambunan
Co Promotor Alida R Harahap
Co Promotor Bambang Sutrisna
Departement Internal Medicine
Category Biomedic
Research Date 08 Oktober 2007
Research Object Others
Fund Source Mandiri
Level Penelitian Doctoral/PhD
Abstract

Background. Venous thromboembolism (VTE) is a complication which is commonly found in cancer patients and is the second leading cause of death due to pulmonary emboli. It can also be found in hematologic malignancies including acute myeloid leukemia (AML), although it is less frequent compared to solid tumors. integrin CD11b/CD18 is an adhesion molecules expressed on leukocytes which mediate the interaction of leukocytes with platelets and endothelial cells and has an important role in endothelial activation by myeloblasts. Activated leukocytes can interact with activated platelets, forming monocyt neutrophil-platelet aggregates, subsequently measurable by flowcytometry to detect the co-expression of CD14 of monocytes or CD11b of neutrophils and CD42b of platelets or CD62p of activated platelets. These leukocyte-platelet aggregates will trigger tissue factor expression and activate coagulation followed by thrombosis. Coagulation activation will increase the levels of F1+2.

Objectives. This study intended to know the odds ratio (OR) or risk of the expression of CD 11b, CD62p, CD11b/CD42b (neutrophil-platelet aggregates), CD14/CD42b (monocyte­platelet aggregates), leukocyte counts as well as blast and promyelocytes to coagulation activation (increased level of F1+2) in myeloid leukemia.

Materials and methods. This was a cross sectional comparative study performed at the Division of Hematology and Medical Oncology, Department of Internal Medicine, Faculty of Medicine University of Indonesia/Cipto Mangukusurno General Hospital and Dharmais Cancer Hospital starting from January 2008 until February 2009. The subjects were myeloid leukemic patients (AML and chronic myelogenous leukemia/CML) based on FAB criteria and WHO classification of tumours 2001. The subjects were recruited consecutively. The expression of CD11b, CD62p, CD11b/CD42b dan CD14/CD42b was measured by flowcytometry method using monoclonal antibodies from Becton-­Dickinson® and Facscalibur® machine with CellQuest Pro program. Leukocyte count was calculated using blood cell counter (ABX Micros 60®) and the amount of blasts/promyelocytes was examined by doing differential count of leukocytes on peripheral blood using Wright-Giemsa stain. The level of F1+2 was measured using ELISA kit of Enzygost F1+2 (Behring®) and Behring ELISA Processor-III®

 

Results. There were 80 subjects (25 AML patients, 14 CML patients and 41 controls) aged 17-71 years. The OR of CD11b ≥91.5% to activation of coagulation (increased level of F1+2) was 7.1. The OR of the expression of CD 1lb/CD42b using cut-off point of ≥55% and CD14/CD42b using cut-off point of ≥50% to the increased level of F1+2 were 1.7 and 1.2 respectively, but these results were not statistically significant. There was no expression of P-selectin found in all subjects. Multivariate analysis showed the adjusted-OR of leukocyte 50.000-100,000/uL and leukocyte >100.000/uL were 13.4 and 11.2, respectively. The adjusted-OR of blast cells + promyelocyte ≥20% was 3.5 for the increased level of F1+2 and 9.6 for blast cells + promyelocytes ≥ 5%

Background. Venous thromboembolism (VTE) is a complication which is commonly found in cancer patients and is the second leading cause of death due to pulmonary emboli. It can also be found in hematologic malignancies including acute myeloid leukemia (AML), although it is less frequent compared to solid tumors. integrin CD11b/CD18 is an adhesion molecules expressed on leukocytes which mediate the interaction of leukocytes with platelets and endothelial cells and has an important role in endothelial activation by myeloblasts. Activated leukocytes can interact with activated platelets, forming monocyt neutrophil-platelet aggregates, subsequently measurable by flowcytometry to detect the co-expression of CD14 of monocytes or CD11b of neutrophils and CD42b of platelets or CD62p of activated platelets. These leukocyte-platelet aggregates will trigger tissue factor expression and activate coagulation followed by thrombosis. Coagulation activation will increase the levels of F1+2.

Objectives. This study intended to know the odds ratio (OR) or risk of the expression of CD 11b, CD62p, CD11b/CD42b (neutrophil-platelet aggregates), CD14/CD42b (monocyte­platelet aggregates), leukocyte counts as well as blast and promyelocytes to coagulation activation (increased level of F1+2) in myeloid leukemia.

Materials and methods. This was a cross sectional comparative study performed at the Division of Hematology and Medical Oncology, Department of Internal Medicine, Faculty of Medicine University of Indonesia/Cipto Mangukusurno General Hospital and Dharmais Cancer Hospital starting from January 2008 until February 2009. The subjects were myeloid leukemic patients (AML and chronic myelogenous leukemia/CML) based on FAB criteria and WHO classification of tumours 2001. The subjects were recruited consecutively. The expression of CD11b, CD62p, CD11b/CD42b dan CD14/CD42b was measured by flowcytometry method using monoclonal antibodies from Becton-­Dickinson® and Facscalibur® machine with CellQuest Pro program. Leukocyte count was calculated using blood cell counter (ABX Micros 60®) and the amount of blasts/promyelocytes was examined by doing differential count of leukocytes on peripheral blood using Wright-Giemsa stain. The level of F1+2 was measured using ELISA kit of Enzygost F1+2 (Behring®) and Behring ELISA Processor-III®

 

Results. There were 80 subjects (25 AML patients, 14 CML patients and 41 controls) aged 17-71 years. The OR of CD11b ≥91.5% to activation of coagulation (increased level of F1+2) was 7.1. The OR of the expression of CD 1lb/CD42b using cut-off point of ≥55% and CD14/CD42b using cut-off point of ≥50% to the increased level of F1+2 were 1.7 and 1.2 respectively, but these results were not statistically significant. There was no expression of P-selectin found in all subjects. Multivariate analysis showed the adjusted-OR of leukocyte 50.000-100,000/uL and leukocyte >100.000/uL were 13.4 and 11.2, respectively. The adjusted-OR of blast cells + promyelocyte ≥20% was 3.5 for the increased level of F1+2 and 9.6 for blast cells + promyelocytes ≥ 5%

Conclusions. The expression of CD11b ≥91,5% had an OR 7.1 to the increased level of F1+2. The neutrophil-platelet aggregates and monocyte-platelet aggregates were not risk factors for coagulation activation and there was no expression of P-selectin found in all subjects. Among those variables, the blast cells + promyelocytes ≥5% and CD1lb >91.5% were the highest risk factors which had 91% and 81% risk for the activation of coagulation in myeloid leukemia, respectively. The conclusion of this study is that the myeloid leukemic patient had higher risk for thrombotic complication if he/she had leukocyte counts ≥50.000/uL, blast cells + promyelocytes ≥5% and/or expression of CD 11 b ≥91,5%.