Antithrombotic Therapy in Children: Antiplatelet Agents

Antiplatelet Agents: One level III study reported no difference in survival or thromboembolic events in children treated with coumadin to maintain a PT of 1.5 X control (n = 48), or aspirin (5 to 6 mg/kg) and dipyridamole (6 mg/kg) (n = 16). The linearized thromboembolic event rates were 2.6 and 1.7/% pa-tient-year, respectively (p = 0.6). Bleeding linearized event rates were 1.5/% patient-year in the coumadin group and 0 in the antiplatelet group (p = 0.09). Numerous level V studies have reported the use of empiric low doses of aspirin (6 to 20 mg/kg/d) and/or dipyridamole (2 to 5 mg/kg/d) for the prevention of thromboembolic complications in the absence of oral anticoagulants. With antiplatelet agents alone, thromboemboli occurred at rates of 1.1 to 68/% patient-years, with 3 of 8 studies having thromboembolic rates over 5/% patient-years (Table 15). There was only one major bleed. It was not fatal, and it did not result in long-term morbidity (Table 15). There were eight deaths due to thromboembolic complications for which therapy could not be determined.
Oral Anticoagulation Therapy: With oral anticoagulants, the incidence of thromboembolic events were uniformly less than 5/% patient-years (Table 16). There were five deaths due to thromboembolic events and two due to bleeding. Three of the five patients had discontinued oral anticoagulants, and the anticoagulant status of the other two could not be determined. With one exception, the rate of major bleeding was less than 3.5/% patient-years (Table 16). In one study, two patients required blood transfusions (rate of 8.2/% patient-years) and recovered uneventfully 50 Adjuvant therapy with antiplatelet agents was used in one study.46 Based on information available for adults and children, it seems reasonable to consider aspirin in combination with oral anticoagulants for high risk patients. High risk patients include those with prior thromboembolic events, atrial fibrillation, large left atrium, left atrial thrombi, ball valves, and mitral valves. flovent inhaler

Conclusion: The available data support the recommendation of oral anticoagulation in children with mechanical prosthetic heart valves. Problems of effectively monitoring oral anticoagulants can be addressed through anticoagulation clinics for children1 and through the use of whole blood monitors in the clinic and at home.

Table 15—Thromboembolic and Hemorrhagic Complications of Mechanical Prosthetic Heart Valves Treated With Antiplatelet Agents

Source, yr Level No. Dose Age Valve Type Position TE/% pt-yr HEM/% pt-yr Deaths
Serra et al, 1987 V 24 ASA 6 mg/kg/d 5-20 yr St. Jude Ao 68 NR 0
DIP 25 mg/kg M 19 NR 0
McGrath et al, 1987 V 30 ASA 900 mg/d 4-20 yr St. Jude Ao, M 32 0$ 0
DIP 150 mg/kg/d >2 NRf NR 1
Ao + M
El Makhlouf et al, 1987 V 150 ASA 20 mg/kg/d 2-16 yr Various Ao, M NR NR 0
DIP 5 mg/kg/d >2 NR NR 0
overall 2.3 0.1 0
Bradley et al, 1985 V 10 ASA 6.1 mg/kg/d <19 yr Various Ao 0 ot 0
DIP 1.9 mg/kg/d M 12 0* 0
Solymar et al, 1991 V (186)H ASA 12 mg/kg/d 1-20 yr Various Ao 1.8 NR 0
DIP 3 mg/kg/d M 2.5 NR 2 CVA
>2 NR NR 0
Borkon et al, 1986 V 8 Not provided 3 wk-17 yr Various Ao 0 ot 0
M 1.1 ot 1 M§
LeBlanc et al, 1993 V 20 ASA 10 mg/kg/d 1-17 yr Various Ao 0 Ot 0|
DIP 3 mg/kg/d M 1.7 01 ot
Bradley et al, 1997 III 16 ASA 5-6 mg/kg/d 3-16 yr St. Jude Ao, M 1.7 0 2
DIP 6 mg/kg/d >2

Table 16—Thromboembolic and Hemorrhagic Complications of Mechanical Prosthetic Heart Valves Treated With Warfarin

Source, yr Level No. Age Valve Type Position TE/% pt-yr HEM/% pt-yr Deaths
Spevak et al, 1986 V 56 <5 yr Various Ao, M 1.6 0.8
el Makhlouf et al, 1987 V 83 2-16 yr Various Ao, M 2.3 0 4f
Harada et al, 1990 V 40 4 mo-15 yr St. Jude Ao 0 1 M\
M 1.3
Stewart et al, 1987 V 30 6-17 yr Various Ao, M 2.30 0.5
>2
Bradley et al, 1985 V 20 <19 yr Various Ao 0 8.2
M 0
Milano et al, 1986 V 71 <15 yr Various Ao 0.7 0
M 4.0 0 1 M|
>2 1.4 0
Schaffer et al, 1987 V 33 9-48 mo St. Jude Ao 0.13 0
M 0.38 0
Solymar et al, 1991 V (186)1 1-20 yr Various Ao 2.1 2.1
M 3.2 3.2 1 M j
>2 5.0 2.6
Schaff et al, 1984 V 48 6 mo-18 yr Starr-Edwards Ao 5.3
M 2.0
Borkon et al, 1986 V 22 3 wk-17 yr St. Jude Ao 0
M 1.1 0
Pulm 0
Human et al, 1982 V 56 2-12 yr Various M n = 3 0
Antunes et al, 1989 V 352 <20 yr Various Ao 0.8
M 0.5
<2 1.7
Woods et al, 1986 V m 5 mo-16 yr Various Ao, M 1.8 0.9 1
>2 0 0
Champsaur et al, 1997 V 54 1-17 yr Various Ao >2 0.3 0.3 1 bleeding
1 valve clot
Bradley et al, 1997 III 48 6 mo-18 yr St. Jude Ao, M 2.6 1.5 1 bleeding
1 valve clot