Clinical experience with antithrombin III concentrate in treatment of congenital and acquired deficiency of antithrombin. The Antithrombin III Study Group.
Phase I clinical studies of antithrombin III (ATIII) concentrate demonstrated a mean in vivo incremental recovery of functional activity of 1.4 percent per unit/kg administered, an initial 50 percent disappearance time of 22 hours, and a biologic half-life of 3.8 days. Based on these observations, a treatment regimen designed to maintain plasma ATIII levels between 75 and 120 percent of normal has been developed. None of 10 subjects with congenital ATIII deficiency treated prophylactically had evidence of thromboembolism, including four pregnant women at the time of delivery. Five subjects treated for acute thrombosis and/or thromboembolism, four of whom were pregnant, recovered without further thrombotic extension or recurrence. Heparin resistance was reversed in two subjects, both pregnant. Nine subjects with acquired ATIII deficiency also received ATIII treatment for venous or arterial thrombosis or disseminated intravascular coagulation, all with low plasma ATIII levels. Two subjects with disseminated intravascular coagulation demonstrated improvement, one clinically, the other biochemically. All patients with congenital ATIII deficiency survived, but only five of nine with acquired deficiency survived, highlighting the importance in acquired ATIII deficiency of the underlying disease in prognosis. Survival rate was especially poor in subjects with arterial thrombosis in the setting of low plasma ATIII. Administration of ATIII concentrate was well tolerated. None of the subjects who received ATIII concentrate demonstrated evidence of an infectious transmissible agent. These studies demonstrate that it is now feasible to safely replace the deficient protein in congenital ATIII deficiency, either prophylactically or therapeutically.
Schwartz
R S
RS
Department of Clinical Research, Cutter Biological, Miles Inc., Berkeley, California 94710.
Bauer
K A
KA
Rosenberg
R D
RD
Kavanaugh
E J
EJ
Davies
D C
DC
Bogdanoff
D A
DA
D000990:Antithrombin III / Q000627:therapeutic use*; D020152:Antithrombin III Deficiency; D004211:Disseminated Intravascular Coagulation / Q000517:prevention & control*; D005260:Female; D006801:Humans; D008297:Male; D011247:Pregnancy; D011250:Pregnancy Complications, Hematologic / Q000517:prevention & control*; D013924:Thrombophlebitis / Q000517:prevention & control*
D000990:Antithrombin III