Diagnostic value of hemostatic parameters in bone marrow transplant-associated thrombotic microangiopathy

Abstract

Summary:We investigated hemostatic parameters in a prospective study of 16 patients who received bone marrow transplants (BMT). We found a significant rise in the levels of fibrinogen, plasmin-␣ 2 antiplasmin inhibitor complex, tissue-plasminogen activator·plasminogen activator inhibitor complex (t-PA·PAI), von Willebrand factor antigen, and thrombomodulin on day 14 after transplant compared with values before transplant. Protein C and thrombin-antithrombin III levels did not change significantly. No significant changes in prothrombin time ratio, activated partial thromboplastin time, or protein S were detected. Patients who had grades II-IV graft-versus-host disease (GVHD) (n = 6) showed a significantly higher level of t-PA·PAI on day 14 compared with those with grades 0-I GVHD (n = 10) (P = 0.0062). Three patients with grades II-IV GVHD developed thrombotic microangiopathy (TMA) on days 19, 19 and 62. In these patients, we noted significantly lower levels of fibrinogen (P = 0.0383), and significantly higher levels of t-PA·PAI (P = 0.0008) and thrombomodulin (P = 0.0001) on day 14 compared with those patients who did not develop TMA. These results suggest that prothrombotic states and endothelial damage may be caused by the conditioning regimen and/or acute GVHD during BMT; thrombomodulin values on day 14 post BMT may be useful in surveillance for TMA because of endothelial cell injury.

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

“…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 This is of importance as CsA is withdrawn in patients with TAM in many centers; others switch treatment to alternative drugs.…”

“…To further test these hypotheses, measures of endothelial damage may be helpful. 2,3,41 Plasma exchange has been used extensively to treat TAM but is now not considered to be effective. Plasma exchange is used in classical TTP and this use is in accordance with today's understanding of its pathophysiology.…”

“…[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.…”

Endothelial damage caused by cytomegalovirus and human herpesvirus-6

“…1 Immunosuppressants, acute graft-versus-host disease (GVHD), viral infection, and steroids have been reported as possible risk factors for secondary clinical manifestations of TMA after BMT, but the pathogenesis is still unknown. [2][3][4][5][6] However, some information concerning possible secondary clinical manifestations of TMA [7][8][9][10] and an association between vascular endothelium damage and increased levels of cytokines 11 as well as chemokines 12,13 has been reported.…”

Sensitive measurement of fragmented red cell population using flow cytometry, and its application for estimating thrombotic microangiopathy after stem cell transplantation

“…The level of plasminogen activator inhibitor type 1 is another marker for TMA (17). The level of tissueplasminogen activator/plasminogen activator inhibitor complex was elevated in patients with high-grade acute GVHD and was part of the background in the development of severe TMA (18). Among these markers, red cell fragmentation was often the earliest sign of TMA and was found in most patients in the first month of the clinical course after SCT (19).…”