Antithrombin-III for the treatment of chemotherapy-induced organ dysfunction following bone marrow transplantation

Abstract

Summary:with lethal organ dysfunction in the renal, pulmonary and cardiac systems. 5-8A hypercoaguable state has been demonstrated to occur A hypercoaguable state has been shown to follow highdose chemotherapy for bone marrow transplantation in many patients following bone marrow transplantation (BMT). 6,7,[9][10][11][12][13][14][15][16] Specifically, the natural anticoagulants (BMT). Deficiency of the natural anticoagulants, antithrombin III (AT-III), protein C and protein S cor-(antithrombin-III (AT-III), protein C and protein S) have been reported to be decreased in BMT patients, while prorelate with organ dysfunction following BMT. We treated 10 patients with severe post-BMT organ dyscoagulants (fibrinogen and factor VIII) were increased. The resulting imbalance between procoagulants and the natfunction with AT-III concentrate. Indications for treatment included AT-III anticoagulant level less than 88% urally occurring anticoagulants has been implicated in the development of VOD. and life-threatening single or multiorgan dysfunction. All patients were loaded with 50 units/kg AT-III every Fibrinolytics (tissue plasminogen activator, tPA) and anticoagulants (heparin) in addition to fluid restriction, 8 h for three doses followed by 50 units/kg/day each day for 3-12 days. Clinical improvement was seen within 1-diuretics, and supportive care have been used to treat VOD. 1,4,[17][18][19][20][21][22] The use of tPA and heparin in this patient 5 days of start of therapy in all patients. Patients with veno-occlusive disease (VOD) showed a decrease in platpopulation has been reported to have a high risk of bleeding and low response rate. 21elet consumption in nine of nine patients, resolution of hepatic tenderness in six of eight patients, and reduction Low levels of AT-III have correlated with the development of organ dysfunction during BMT in previously pubof severe ascites and weight gain in four of five patients. The probability of death due to VOD and life-threatenlished reports. 6,7,9,16 In addition, VOD or other single organ dysfunction has been associated with progression to fatal ing organ dysfunction was significantly less in the AT-III-treated group when compared to a historical control multiorgan failure. 5-8 Based on these reports, we hypothesized that correction of the AT-III deficit with AT-III congroup receiving the same preparative regimen (P ‫؍‬ 0.047 and P ‫؍‬ 0.034, respectively). Significant centrate might prevent progression to lethal organ dysfunction. Patients who developed organ dysfunction following improvements in organ dysfunction following AT-III treatment in this small study supports a causal relationhigh-dose chemotherapy for BMT and who also had low AT-III activity levels were treated with AT-III concentrate. ship between AT-III deficiency and post-BMT chemotherapy-induced organ dysfunction.This paper reports the outcome of our AT-III-treated patients compared to historical control patients treated at Keywords: bone marrow transplantation; antithrombin III; veno-occlusive disease; orga...

Hepatic veno-occlusive disease after hematopoietic stem cell transplantation: update on defibrotide and other current investigational therapies

“…[86][87][88] However, concordant with prior studies in adults, a recent large pediatric transplant trial in which 91 children received preemptive ATIII replacement (ATIII given when plasma ATIII activity p70%) demonstrated that ATIII administration did not reduce the incidence of VOD compared to the control group of 71 children who received no VOD prophylaxis. 89 Prostaglandin E1 (PGE1) is a vasodilator with a cytoprotective effect on endothelium as well as being an inhibitor of platelet aggregation with prothrombolytic activity.…”

A Successful Liver Transplantation for Refractory Hepatic Veno‐Occlusive Disease Originating from Cord Blood Transplantation

“…As prophylaxis against hepatic VOD, UDCA, LMWH and PGE1 have been favorably reported (18)(19)(20), while conservative treatments of hepatic VOD include rt-PA, DF, AT-III and PGE1 (6,7,21). In this case, we tried all of the above -except for rt-PA -and all failed.…”

Increased platelet transfusion requirement is associated with multiple organ dysfunctions in patients undergoing hematopoietic stem cell transplantation

“…30,31 There is already evidence suggesting a role of this agent in transplant-related organ dysfunction. 32,33 Alternatively, or in addition, there may be a direct role of platelets in the development and progression of multiorgan dysfunction. It has been shown that consumption of platelets on the endothelial cell surface has adverse clinical consequences.…”