The coagulopathy of childhood leukemia. Thrombin activation or primary fibrinolysis?
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T C Abshire1, S H Gold, L F Odom
1Department of Pediatrics, University of Colorado School of Medicine, Denver.
Insights
Coagulopathy in childhood acute leukemia is often linked to thrombin activation, not primary fibrinolysis. This study investigated coagulation abnormalities in pediatric leukemia patients, finding thrombin activation as the primary driver of bleeding disorders.
Area of Science:
- Pediatric Hematology
- Hemostasis and Thrombosis
- Oncology
Background:
- Coagulopathy is a recognized complication in pediatric acute leukemia.
- The precise prevalence and underlying mechanisms of coagulopathy at diagnosis remain incompletely understood.
- Existing data on coagulation abnormalities in newly diagnosed childhood leukemia are limited.
Purpose of the Study:
- To investigate the prevalence and etiology of coagulopathy in children with newly diagnosed acute leukemia.
- To differentiate between thrombin activation and primary fibrinolysis as causes of coagulopathy.
- To assess specific coagulation parameters and their correlation with leukemia subtypes.
Main Methods:
- Retrospective and prospective study of 102 children with newly diagnosed acute leukemia.
- Coagulation tests included prothrombin time (PT), partial thromboplastin time (PTT), thrombin time (TT), fibrinogen (FIB), and fibrin degradation products (FDP).
- Prospective group (Group B) also underwent D-dimer, B beta 1-42 peptide, coagulation factors (II, V, VII, X), and tissue factor measurements.
Main Results:
- 40% of the prospective group had normal coagulation studies; 10% presented with severe coagulopathy.
- Elevated PT and FDP were common findings in both groups.
- A significant proportion (38%) of the prospective group had positive D-dimer, indicating thrombin activation, while only 4% showed elevated B beta 1-42 peptide, suggesting minimal primary fibrinolysis (P < 0.00001).
Conclusions:
- The coagulopathy associated with acute leukemia in childhood is predominantly mediated by thrombin activation.
- Primary fibrinolysis appears to play a minor role in the hemostatic disturbances observed at diagnosis.
- Findings highlight the importance of assessing thrombin activation pathways in managing bleeding complications in pediatric leukemia.
Abstract:
Little information is available on the prevalence and etiology of the coagulopathy present in some children with acute leukemia at disease presentation. We studied 102 children with newly diagnosed acute leukemia (50 retrospective: Group A; and 52 prospective: Group B) with prothrombin time (PT), partial thromboplastin time (PTT), thrombin time (TT), fibrinogen (FIB), and fibrin degradation products (FDP). All patients in Group B also had assessment of thrombin activation by measurement of the crosslinked fibrin fragment, D-dimer, and of primary fibrinolysis with the B beta 1-42 peptide. Additionally, ten patients from Group B had Factors II, V, VII, and X measured, and eight of these patients had measurement of tissue factor from sonicated bone marrow cells. Thirty-two percent of Group A and 40% of Group B had totally normal coagulation studies, whereas 20% of Group A and 10% of Group B had a severe coagulopathy on disease presentation. A high percentage of both groups had elevated PT (Group A, 52%; Group B, 27%) and increased FDP (Group A, 39%; Group B, 25%). In Group B, 38% of the patients had a positive D-dimer, whereas only 4% of this prospective group had an elevated B beta 1-42 peptide (P less than 0.00001). Nine of ten patients with a positive D-dimer had low levels of one or more of the extrinsic pathway factors. Three of four patients with the highest tissue factor levels were of monocytoid leukemia cell type. These data indicate that the coagulopathy associated with acute leukemia of childhood is usually mediated by thrombin activation.