Abstract 2298

The prevalence of prothrombotic markers and their association with thrombosis in pediatric solid tumor patients is not well defined. This study was aimed to discern the value of the following laboratory measures in assessment of thrombotic risk in pediatric patients with solid tumor: Prothrombin and activated partial thromboplastin times (PT and aPTT), D-dimer level, fibrinogen level, inherited and acquired hypercoagulability risk factors and soluble pro-inflammatory cytokines.

Forty pediatric patients with newly-diagnosed malignancy and same number of age and sex-matched normal healthy controls were enrolled in the study. The median age was 7.5 and 8 years, respectively. Exclusion criteria included: history of autoimmune, hematologic, or chronic disease; history of chemotherapy administration; anticoagulant or anti-platelet therapy within 2 weeks of enrollment. Control subjects were selected from children undergoing elective surgery who had no known coagulation disorder and had not received anticoagulant or anti-platelet therapy within the previous 7 days.

The following laboratory parameters were measured at the time of initial diagnosis: thromboelastography (TEG), thrombin generation assay (TGA), PT and aPTT, D-dimer level, fibrinogen level, lupus anticoagulant (LA) and anticardiolipin antibodies (ACA), interleukin (IL)-1b, IL-6, IL-8, and tumor necrosis factor (TNF)-α. Two years after completion of the laboratory component of the study, the patient cohort was retrospectively reviewed for the occurrence of thrombosis. Comparisons were made between patients vs. controls and patients with thrombosis vs. patients without thrombosis.

As compared to controls, pediatric patients with newly diagnosed solid tumors demonstrated significantly higher prothrombotic markers, including TEG parameters, proinflammatory cytokines, and endogenous thrombin potentials assessed by TGA (Table 1).

Among the 40 cancer patients, 4 (10%) experienced following thrombotic complications: cerebral sigmoid sinus thrombosis; right subclavian vein thrombosis; left internal jugular vein thrombosis; inferior vena cava thrombosis. All 4 patients had a hypercoagulable TEG profile as shown by increased maximum amplitude and elevated fibrinogen level at initial presentation.

PT, fibrinogen level, and maximum amplitude of TEG were further predictive of thrombosis development in cancer patients (Table 2). Further studies are needed to support recommendations for prophylaxis of thrombosis in this vulnerable patient population.

Table 1:

Statistically significant parameters in cancer patients compared to controls

ParameterN=40 Patients Median (range)N=40 Controls Median (range)P Value
Fibrinogen (mg/dL) 342 (202–734) 266 (183–456) 0.00 
D-dimer (μg/mL) 1.4 (0.2–13.7) 0.2 ((0.0–3.9) 0.00 
Factor VIII (%) 145 (59–361) 100 (50–173) 0.00 
ACA IgM (MPL) 1.5 (0.0–7.4) 1.2 (0.0–3.8) 0.03 
Maximum amplitude (mm) 66.9 (52.0–82.0) 61.4 (55.0–68.0) 0.00 
Coagulation index 2.1 (−1.0–4.0) 1.3 (0.0–3.0) 0.00 
G (k d/sec) 10.2 (5.4–23.1) 8.0 (6.1–10.7) 0.00 
AUC/ETP 5300 (1970–6501) 4864 (2300–5832) 0.03 
IL-1β 0.8 (0.1–6.5) 0.5 (0.1–1.1) 0.01 
IL-6 0.8 (0.1–18.8) 0.2 (0.1–0.6) 0.00 
TNF-α 0.1 (0.0–2.3) 0.1 (0.1–0.3) 0.02 
ParameterN=40 Patients Median (range)N=40 Controls Median (range)P Value
Fibrinogen (mg/dL) 342 (202–734) 266 (183–456) 0.00 
D-dimer (μg/mL) 1.4 (0.2–13.7) 0.2 ((0.0–3.9) 0.00 
Factor VIII (%) 145 (59–361) 100 (50–173) 0.00 
ACA IgM (MPL) 1.5 (0.0–7.4) 1.2 (0.0–3.8) 0.03 
Maximum amplitude (mm) 66.9 (52.0–82.0) 61.4 (55.0–68.0) 0.00 
Coagulation index 2.1 (−1.0–4.0) 1.3 (0.0–3.0) 0.00 
G (k d/sec) 10.2 (5.4–23.1) 8.0 (6.1–10.7) 0.00 
AUC/ETP 5300 (1970–6501) 4864 (2300–5832) 0.03 
IL-1β 0.8 (0.1–6.5) 0.5 (0.1–1.1) 0.01 
IL-6 0.8 (0.1–18.8) 0.2 (0.1–0.6) 0.00 
TNF-α 0.1 (0.0–2.3) 0.1 (0.1–0.3) 0.02 
View Large
Table 2:

Statistically significant parameters in cancer patients with thrombosis compared to those without thrombosis

ParameterN=4 Thrombosis (+) Median (range)N=36 Thrombosis (−) Median (range)P Value
PT (sec) 15.8 (15.6–18.2) 13.9 (12.3–16.7) 0.00 
Fibrinogen (mg/dL) 579 (430–724) 333 (202–734) 0.00 
Maximum amplitude (mm) 72.2 (67.3–74.8) 66.4 (46.4–56.3) 0.03 
G (k d/sec) 13.3 (4.3–23.1) 9.1 (10.3–14.8) 0.03 
ACA IgM (MPL) 4 (1–5) 0 (0–16) 0.04 
ParameterN=4 Thrombosis (+) Median (range)N=36 Thrombosis (−) Median (range)P Value
PT (sec) 15.8 (15.6–18.2) 13.9 (12.3–16.7) 0.00 
Fibrinogen (mg/dL) 579 (430–724) 333 (202–734) 0.00 
Maximum amplitude (mm) 72.2 (67.3–74.8) 66.4 (46.4–56.3) 0.03 
G (k d/sec) 13.3 (4.3–23.1) 9.1 (10.3–14.8) 0.03 
ACA IgM (MPL) 4 (1–5) 0 (0–16) 0.04 
View Large

Disclosures:

No relevant conflicts of interest to declare.

Topics:
cancer, thrombosis, antibodies, anticardiolipin, fibrinogen assay, activated partial thromboplastin time measurement, fibrin fragment d substance, tumor necrosis factors, anticoagulants, antiplatelet agents, cytokine

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2011 by The American Society of Hematology
2011
Sign in via your Institution