Factor XIII activity levels in patients with allogeneic haematopoietic stem cell transplantation and acute graft‐versus‐host disease of the gut

Abstract

Summary. Severe graft-versus-host disease (GvHD) of the gut clinically resembles Crohn's disease and ulcerative colitis. As low plasma levels of factor XIII (FXIII) have been described in chronic inflammatory bowel disease (CIBD) and as beneficial effects of FXIII concentrates in CIBD have been reported, we studied the FXIII plasma activity levels in patients undergoing allogeneic stem cell transplantation (SCT). In 20 of 22 patients with an uncomplicated course of SCT, FXIII stayed within the normal range (median 102 iu/dl, range 74-122), but was significantly reduced with the lowest FXIII levels on d 0 and 7 (d 0: median 83 iu/dl, range 55-165, d 7: median 83, range 70-101). In 20 of 22 patients with histologically proven GvHD of the gut, FXIII levels far below the normal range were observed (median 50, range 21-87) with a strong correlation between FXIII activity levels and degree of GvHD (r ¼ )0AE908; P < 0AE001). We conclude that FXIII is consumed in patients with GvHD of the gut. As FXIII plays a a crucial role in haemostasis and wound healing, a study on the potential benefit of FXIII substitution in patients with severe GvHD of the gut might be rewarding.

Recombinant activated factor VII in treatment of bleeding complications following hematopoietic stem cell transplantation

“…The rapid and short‐term effects of rFVIIa in other settings, which have been documented and are clinically quite impressive, might therefore have been missed in this trial. Finally, it has been shown that patients with GVHD of the gut have levels of FXIII that are considerably below normal, correlating to the degree of GVHD [16]. FXIII plays an important role in hemostasis and wound healing, and depletion may contribute to the reduced activity of rFVIIa observed here.…”

Cre/lox Studies Identify Resident Macrophages as the Major Source of Circulating Coagulation Factor XIII-A

“…9–11 In contrast to Wölpl et al, 8 Poon et al 11 observed that conversion from donor to recipient plasma FXIII-A variant occurred over many months after BMT. Further, Inbal et al 9 and Pihusch et al 10 observed that BMT caused a much greater decrease in platelet count than plasma FXIII-A, which led Pihusch et al 10 to suggest that resident macrophages maintain the plasma pool. Notably, alveolar macrophages persist for ≤80 days after BMT.…”

Defective Platelet Activation and Bleeding Complications upon Cholestasis in Mice

“…Atucha and colleagues described increased Ca 2+ responses of platelets from bile duct ligated rats [24]. In contrast to these studies showing platelet hyperactivity, hypoaggregability has been proposed from others with reduced expression of P-selectin, defective aggregation and prolonged bleeding times [15, 18, 23, 25]. Effects of bile acids on platelet activation have also been suggested [26].…”

“…Few studies suggest a hypercoagulable state in patients with cholestatic liver disease [22, 23]. Atucha and colleagues described increased Ca 2+ responses of platelets from bile duct ligated rats [24].…”