Endothelial Activation Hemostasis Disturbances and Severe Bleeding Events in Hyperleukocytic Acute Myeloid Leukemia

Study Overview
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Brief Summary
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Hyper-leukocytosis > 50.109/L is observed in 15% of acute myeloid leukemia (AML). Level of hyper-leukocytosis is linearly associated with the incidence of life threatening complications that lead to the early death in 25% of these patients. The HEAL project is a prospective, uni-centric, observational study that plans to include a cohort of 50 patients presenting de novo AML with hyper-leukocytosis (HL) (> 50.109/L) and 10 controls. The aim of the study is to describe the relative proportion of various hemostasis components disturbances, endothelium alterations, platelet dysfunction and to calculate cumulative incidence of hemorrhagic and thrombotic complications as well as overall survival of patients presenting with HL AML.

Official Title
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Characterization of Endothelial Activation Hemostasis Disturbances and Severe Bleeding Events in Hyperleukocytic Acute Myeloid Leukemia

Conditions
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Leukemia, Myeloid, Acute

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: De novo AML GB counts > 50 G/L Eligible for intensive chemotherapy no previous AML treatment Exclusion Criteria: secondary AML relapse of AML Acute promyelocytic leukemia Previous antiplatelet or anticoagulant treatment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cases<br>Patients with acute myeloid leukemia, associated to hyper leukocytosis | |
| Control<br>Patients with acute myeloid leukemia, without hyper leukocytosis | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hemostasis / platelet and endothelial dysfunction assessed by plasma concentration of ICAM- | plasma concentration of ICAM- | 12hours after chemotherapy initiation | 
| Hemostasis / platelet and endothelial dysfunction parameter assessed by plasma concentration of Syndecan-1 | plasma concentration of Syndecan-1 | 12hours after chemotherapy initiation | 
| Hemostasis / platelet and endothelial dysfunction parameter assessed by plasma concentration of vWF Ag | plasma concentration of vWF Ag | 12hours after chemotherapy initiation | 
| Hemostasis / platelet and endothelial dysfunction assessed by vWF activity | vWF activity | 12hours after chemotherapy initiation | 
| Hemostasis / platelet and endothelial dysfunction assessed by plasma concentration of Fg | plasma concentration of Fg | 12hours after chemotherapy initiation | 
| Hemostasis / platelet and endothelial dysfunction assessed by plasma concentration of t-PA | plasma concentration of t-PA | 12hours after chemotherapy initiation | 
| Hemostasis / platelet and endothelial dysfunction assessed by plasma concentration of u-PA | plasma concentration of u-PA | 12hours after chemotherapy initiation | 
| Hemostasis / platelet and endothelial dysfunction assessed by plasma concentration of e-Selectin | plasma concentration of e-Selectin | 12hours after chemotherapy initiation | 
| Hemostasis / platelet and endothelial dysfunction assessed by plasma concentration of sCD40L | plasma concentration of sCD40L | 12hours after chemotherapy initiation | 
| Hemostasis / platelet and endothelial dysfunction parameter assessed by plasma concentration of IL6 | plasma concentration of IL6 | 12hours after chemotherapy initiation | 
| Hemostasis / platelet and endothelial dysfunction assessed by plasma concentration of AT | plasma concentration of AT | 12hours after chemotherapy initiation | 
| Hemostasis / platelet and endothelial dysfunction assessed by plasma concentration of Fragments thrombin 1+2 | plasma concentration of Fragments thrombin 1+2 | 12hours after chemotherapy initiation | 
| Hemostasis / platelet and endothelial dysfunction assessed by plasma concentration of TAT complex | plasma concentration of TAT complex | 12hours after chemotherapy initiation | 
| Hemostasis / platelet and endothelial dysfunction assessed by plasma concentration of plasmin-antiplasmin complex | plasma concentration of plasmin-antiplasmin complex | 12hours after chemotherapy initiation | 
| Hemostasis / platelet and endothelial dysfunction assessed by plasma concentration of PAI-1 Ag | plasma concentration of PAI-1 Ag | 12hours after chemotherapy initiation | 
| Hemostasis / platelet and endothelial dysfunction assessed by plasma concentration of PAI-1 activity | plasma concentration of PAI-1 activity | 12hours after chemotherapy initiation | 
| Hemostasis / platelet and endothelial dysfunction assessed by plasma concentration of t-PA-PAI-1 complex | plasma concentration of t-PA-PAI-1 complex | 12hours after chemotherapy initiation | 
| Hemostasis / platelet and endothelial dysfunction assessed by plasma concentration of ADAMTS13 Ag | plasma concentration of ADAMTS13 Ag | 12hours after chemotherapy initiation | 
| Hemostasis / platelet and endothelial dysfunction assessed by ADAMTS13 activity | ADAMTS13 activity | 12hours after chemotherapy initiation | 
| Hemostasis / platelet and endothelial dysfunction assessed by plasma concentration of vWF:CB | plasma concentration of vWF:CB | 12hours after chemotherapy initiation | 
| Hemostasis / platelet and endothelial dysfunction assessed by plasma concentration of Fibrin monomers | plasma concentration of Fibrin monomers | 12hours after chemotherapy initiation | 
| Hemostasis / platelet and endothelial dysfunction assessed by Prothrombine Time | Prothrombine Time | 12hours after chemotherapy initiation | 
| Hemostasis / platelet and endothelial dysfunction assessed by Activated Partial Thromboplastin Time [APTT] | Activated Partial Thromboplastin Time [APTT] | 12hours after chemotherapy initiation | 
| Hemostasis / platelet and endothelial dysfunction assessed by plasma concentration of Factor IX | plasma concentration of Factor IX | 12hours after chemotherapy initiation | 
| Hemostasis / platelet and endothelial dysfunction assessed by plasma concentration of Factor II | plasma concentration of Factor II | 12hours after chemotherapy initiation | 
| Hemostasis / platelet and endothelial dysfunction assessed by plasma concentration of Factor VIII | plasma concentration of Factor VIII | 12hours after chemotherapy initiation | 
| Hemostasis / platelet and endothelial dysfunction assessed by plasma concentration of Factor XII | plasma concentration of Factor XII | 12hours after chemotherapy initiation | 
| Hemostasis / platelet and endothelial dysfunction assessed by plasma concentration of Factor X | plasma concentration of Factor X | 12hours after chemotherapy initiation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative incidence of serious bleeding events | Time from inclusion to first serious bleeding event | 1 month | 
| Cumulative incidence of thrombotic events | Time from inclusion to first thrombotic event | 1 month | 
| Overall survival | Time from inclusion to death of any cause | 1 month | 
| ICU length of stay | duration of stay in ICU within the first month | 1 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hemostasis