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

Abstract

Summary:Organ dysfunction following hematopoietic stem cell transplantation (HSCT) may be a manifestation of a systemic inflammatory response. We speculate that part of the platelet transfusion requirement in HSCT patients results from this systemic inflammatory response, and increased transfusion requirement would be associated with, or precede, organ dysfunction. We studied 199 adults undergoing autologous (n = 173) or allogeneic (n = 26) HSCT. Patients with CNS (P = 0.008) or pulmonary (P = 0.002) dysfunction, or with VOD (P = 0.05) received a higher mean number of platelet transfusions per week than patients who did not have these dysfunctions. Furthermore, a higher number of platelet transfusions during any 1 week period was significantly associated with development of pulmonary (P = 0.0002) or renal (P Ͻ 0.0001) dysfunction in the following week. This predictive value was strongest early in the HSCT course, but remained significant over all 4 weeks. In multivariate analysis the number of platelet transfusions during the previous week was independently predictive for development of pulmonary dysfunction in week 2 (P = 0.01) and week 3 (P = 0.055). We believe that occurrence of increased platelet transfusion requirement prior to onset of dysfunction is consistent with the concept that an antecedent inflammatory response results in both platelet consumption and various organ dysfunctions. Increased platelet transfusion requirement may act as an early marker of subsequent organ dysfunction. Additionally, there may be a direct role of platelets in the development and progression of organ dysfunction in HSCT patients. Keywords: thrombocytopenia; multiple organ dysfunction; syndrome; VOD; transfusion Thrombocytopenia following high-dose therapy and hematopoietic stem cell transplantation (HSCT) is an almost universal phenomenon. The duration of thrombocytopenia is probably related to both quantity and quality of stem cells reinfused, 1

Organ dysfunction following stem cell transplantation: relationship to plasma cytokine concentrations

“…6,12,13,15 As previously stated, subtle changes in pulmonary, CNS, or liver function identifies a group of patients with high risk for death. Patients with pulmonary dysfunction or CNS changes had a 4.9-and 18-fold increased risk of dying after stem cell transplantation, respectively.…”

“…Patients developing OD may be identified by a decline in pulmonary, central nervous system, or hepatic function and often have corresponding laboratory abnormalities including a drop in antithrombin III and protein C concentrations and an increased platelet utilization. 6,12 Regardless of which of these abnormalities is the first to be recognized, affected patients are at risk of progressing to MODS and death. 1,13 The importance of developing these clinical abnormalities is difficult to overestimate, with one study reporting no mortality in patients without signs of early OD compared to 46% mortality in patients who showed signs of early OD.…”

“…For example, the observation that patients whose early OD progresses to MODS have high platelet transfusion requirements suggests there may be damaged endothelium leading to increased platelet binding. 6 Apoptosis can be induced in vascular endothelium by TNF-␣ and IL-6 and apoptotic endothelial cells have very potent procoagulant activity. 7 The preparative regimen is one potential etiology of OD.…”

Safety of low-dose low-molecular-weight-heparins in thrombocytopenic stem cell transplantation patients: a case series and review of the literature

“…1 Platelet engraftment can be impeded by the occurrence post transplant of complications of veno-occlusive disease (VOD) and GVHD in allogeneic HSCT. 2 Indeed, in the presence of GVHD, recovery of platelet count is a slow and gradual process, with 50% of patients remaining thrombocytopenic at day 50. 3 The incidence of major bleeding owing to prolonged thrombocytopenia ranged between 14 and 17% in one series evaluating platelet transfusion threshold in HSCT recipients.…”

Avoiding hepatic veno-occlusive disease: what do we know and where are we going?

“…7 Increased platelet transfusion requirement is usually associated with VOD. Gordon et al 8 retrospectively reviewed platelet requirements in 199 patients who underwent transplant at the University of Nebraska. They found that patients with dysfunction of a single organ (VOD, pulmonary or CNS) received more platelet transfusions per week compared to patients without organ dysfunction.…”