Antithrombin-III for the treatment of chemotherapy-induced organ dysfunction following bone marrow transplantation.
A hypercoaguable state has been shown to follow high-dose chemotherapy for bone marrow transplantation (BMT). Deficiency of the natural anticoagulants, antithrombin III (AT-III), protein C and protein S correlate with organ dysfunction following BMT. We treated 10 patients with severe post-BMT organ dysfunction with AT-III concentrate. Indications for treatment included AT-III anticoagulant level less than 88% and life-threatening single or multiorgan dysfunction. All patients were loaded with 50 units/kg AT-III every 8 h for three doses followed by 50 units/kg/day each day for 3-12 days. Clinical improvement was seen within 1-5 days of start of therapy in all patients. Patients with veno-occlusive disease (VOD) showed a decrease in platelet consumption in nine of nine patients, resolution of hepatic tenderness in six of eight patients, and reduction of severe ascites and weight gain in four of five patients. The probability of death due to VOD and life-threatening organ dysfunction was significantly less in the AT-III-treated group when compared to a historical control group receiving the same preparative regimen (P = 0.047 and P = 0.034, respectively). Significant improvements in organ dysfunction following AT-III treatment in this small study supports a causal relationship between AT-III deficiency and post-BMT chemotherapy-induced organ dysfunction.
Morris
J D
JD
Children's Hospital Medical Center, Division of Hematology/Oncology/Stem Cell Transplantation, Cincinnati, OH 45229, USA.
Harris
R E
RE
Hashmi
R
R
Sambrano
J E
JE
Gruppo
R A
RA
Becker
A T
AT
Morris
C L
CL
D000293:Adolescent; D000328:Adult; D000925:Anticoagulants / Q000627:therapeutic use*; D000990:Antithrombin III / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D002066:Busulfan / Q000008:administration & dosage / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006402:Hematologic Diseases / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006504:Hepatic Veno-Occlusive Disease / Q000188:drug therapy* / Q000209:etiology; D006801:Humans; D007223:Infant; D015993:Life Tables; D008297:Male; D009102:Multiple Organ Failure / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control; D009369:Neoplasms / Q000628:therapy; D012720:Severity of Illness Index; D016019:Survival Analysis; D019851:Thrombophilia / Q000188:drug therapy* / Q000209:etiology; D019172:Transplantation Conditioning / Q000009:adverse effects*; D016896:Treatment Outcome
D000925:Anticoagulants; D005047:Etoposide; D003520:Cyclophosphamide; D000990:Antithrombin III; D002066:Busulfan