Prophylactic heparin does not prevent liver veno‐occlusive disease following autologous bone marrow transplantation

Abstract

Veno‐occlusive disease (VOD) is a major cause of toxic death after autologous bone marrow transplantation (ABMT). We studied the potential role of continuous administration of low‐dose heparin for VOD prevention in 234 consecutive patients who underwent ABMT in our institution. The population consisted of 98 patients autografted before October 1984 who did not receive heparin, and a series of 136 patients autografted from October 1984 to March 1989 containing 98 patients included in a randomized trial comparing heparin administration (n = 52) vs no heparin (n = 46), and an additional group of 38 patients who received non‐randomized heparin in view of high‐risk criteria to develop VOD (n = 31) or other reasons unrelated to VOD (n = 7). Overall, 90 patients (38%) received heparin and 144 (62%) did not. The global incidence of VOD was 13/234 (5–5%). Heparin did not reduce the risk of VOD in all subgroups studied. In particular, in the randomized trial, the incidence of VOD was 2.2% in the group without heparin vs 7–7% in the group receiving heparin. We analyzed in depth the 13 patients who developed VOD and we compared them to a control group of 13 patients pair‐matched for age, sex, diagnosis and preparative regimen, who did not develop VOD. We found that abnormal LFT before ABMT predisposed patients to VOD; refractoriness to platelet transfusion was observed in 85% of the patients in the VOD group vs 15% in the control group (p<0.05). VOD patients had an increased requirement for red cells and platelet transfusions, a lower recovery (R<25%) after the second and third platelet transfusion, and shorter intervals separating the first four platelet transfusions. Further, the platelet reconstitution after ABMT in the VOD group was slower in comparison to the control group (p<0.01). Again, in this pair‐matched analysis continuous infusion of low‐dose heparin did not prevent VOD.

Hepatic Veno-Occlusive Disease following Stem Cell Transplantation: Incidence, Clinical Course, and Outcome

“…For studies investigating VOD prophylaxis, incidence and outcome data from historical or contemporary controls only (when available) were considered; however, administration of heparin or ursodiol prophylaxis for VOD during SCT may not have been clearly documented if it was not relevant to the theme of the article. Data are conflicting on the efficacy of heparin or ursodiol prophylaxis in VOD; although authors have reported a possible beneficial effect [21–25], most studies (including the large multicenter European Group for Blood and Marrow Transplantation [EBMT] study of more than 1600 SCT recipients) have found neither form of prophylaxis to be effective in reducing the incidence of VOD [2,16,26–30]. Therefore, rather than exclude such studies from the analysis, the overall incidence of VOD was used, making it impossible to distinguish between patients receiving or not receiving prophylaxis with heparin or ursodiol.…”

Hepatic Veno-Occlusive Disease

“…Ohashi et al [59] suggest that prophylactic administration of ursodeoxycholic acid from the first day of chemotherapy can mitigate endothelial damage by inducing a down-regulation of inflammatory mediators such as the cytokines TNFa and IL-1b. [61] Several studies in adults [62] have assessed the effectiveness of intravenous lowdose heparin administration, with conflicting results. [61] Several studies in adults [62] have assessed the effectiveness of intravenous lowdose heparin administration, with conflicting results.…”

Sinusoidal Obstruction Syndrome (Hepatic Veno-Occlusive Disease)

“…143 Institution of low-dose heparin prophylaxis is a more aggressive approach, as it requires an infusion regime, and the evidence for efficacy of this prophylaxis also is equivocal. [144][145][146] Glutamine supplementation, use of peripheral blood progenitor cells as opposed to those derived from the bone marrow, and T-cell depletion as prophylaxis against graft-versushost disease have been reported as having reduced incidence of SOS. 147,148 In the pediatric population undergoing HSCT, a prophylactic regime of enoxaparin or ursodeoxycholic acid and vitamin E has been of potential value.…”