Severe thrombotic microangiopathy: an infrequent complication of bone marrow transplantation

Abstract

Summary:Thrombotic microangiopathy (TMA) usually occurs during the first weeks following transplantation in the setting of systemic infections or graft-versus-host reaction. However, some cases without any evidence of other complications or after autologous transplantation have been reported. Transplant-associated TMA (BMT-TMA) incidence ranges from 0% to 74%, possibly due to different diagnostic criteria. The GITMO Group provided the opportunity to retrospectively study 4334 consecutive Italian patients who received bone marrow transplants (1759 allogeneic and 2575 autologous BMT), during the 1985-1995 period. The present report focuses on patients with severe TMA requiring specific treatment. We identified nine cases of TMA as a complication of allogeneic BMT (0.51%), whereas three patients developed the syndrome after ABMT (0.13%); four of the 12 patients were not receiving CsA at the time of TMA onset. Finally, it is noteworthy that TMA occurred in seven patients as a late complication (up to 90 days after BMT). Despite intensive treatment, five of the seven patients with thrombotic thrombocytopenic purpura died. One death was observed among the five cases with hemolytic uremic syndrome.

Transplant-associated microangiopathy (TAM) in recipients of allogeneic hematopoietic stem cell transplants

“…33 The higher risk of TAM observed among female patients has also been observed in other studies. 6,11,12,16 This present study confirms this gender effect but the pathophysiology remains unresolved, hypotheses include a role of hormones, oral contraceptives, sensitization by pregnancy or other hitherto unknown factors. The increased risk for TAM was only observed with female patients, whereas stem cell transplants from female donors were not associated with a higher risk for TAM suggesting that it is not an effect of the donor stem cells, but rather of the host environment.…”

“…We could not detect any difference in TAM incidence in patients with high or low trough levels of CsA. 2,3,11,17 This does not exclude a causative role of CsA in susceptible patients, but there is no obvious relationship with plasma levels. This is of importance as CsA is withdrawn in patients with TAM in many centers; others switch treatment to alternative drugs.…”

“…11 We could not analyze CsA use vs none, as all patients analyzed had CsA (with the exception of twins). We could not detect any difference in TAM incidence in patients with high or low trough levels of CsA.…”

“…[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] Thrombotic microangiopathy is characterized by systemic or intrarenal platelet aggregation and a microangiopathic hemolytic anemia, with red blood cell (RBC) fragmentation and a negative direct antiglobulin test. Increased platelet consumption leads to thrombocytopenia.…”

Transplantation-associated thrombotic microangiopathy: effect of concomitant GVHD on efficacy of therapeutic plasma exchange

“…[1][2][3][4][5][6][7] This uncertainty in diagnosis has led to wide variations in the reported incidence of TA-TMA, a lack of consensus regarding clinical approach to management, and poor understanding of prognostic factors with respect to therapeutic response and survival. [1][2][3][4][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] To address this issue of diagnostic clinical uncertainty, two new diagnostic criteria for TA-TMA have recently been proposed; the Bone Marrow Transplant Clinical Trials Network (BMT-CTN) and the IWG (International Working Group) TA-TMA criteria. 24,25 However, neither criterion has been rigorously evaluated clinically, and issues remain with respect to the diagnostic sensitivity of both.…”