Autologous bone marrow transplantation and factor xii, factor vii, and protein c deficiencies report of a new association and its possible relationship to endothelial cell injury

Abstract

Four patients who underwent treatment with high-dose chemotherapy (HDC) and autologous bone marrow transplantation (ABMT) and in whom posttreatment deficiencies of Factor XII and protein C subsequently developed are reported. Factor VII or Factor X deficiencies also developed in several of these patients. Three of these patients experienced chemotherapy-related cardiac, hepatic, or pulmonary toxicity. It is believed by many that endothelial cell injury may be the underlying lesion responsible for these various organ system toxicities seen in the setting of ABMT, although direct evidence of this is lacking. It is proposed that the factor deficiencies described in this report may be an additional consequence of endothelial cell injury or dysfunction. These coagulation factor deficiencies may therefore serve as both a marker to follow these organ system toxicities with and as a useful tool to better study and understand the mechanisms underlying these events. Additionally, deficiencies of either Factor VII or Factor X developed in several patients that were of a sufficient magnitude such that factor replacement therapy would be indicated before any invasive procedures or in the event of significant hemorrhage.

Catheter-Related Thrombosis in Patients with Lymphoma or Myeloma Undergoing Autologous Stem Cell Transplantation

“…24 We also evaluated basic coagulation parameters and confirmed that most patients have normal baseline levels of INR and PTT, and mildly elevated fibrinogen, reflecting hospitalized population. 25 Conlan et al and others had reported low antithrombin III and protein C levels in AHCT patients 1, 26 , while increased von Willebrand factor and platelet adhesion may also play a role. 6 Presence of inherited thrombophilia was rare and its contribution is difficult to assess.…”

Venous thromboembolism in hematopoietic stem cell transplant recipients

“…12 HSCT recipients have several identifiable risk factors for thrombosis including malignancy, high-dose myeloablative chemotherapy and immune-modulatory drugs, [13][14][15][16] graft versus host disease (GVHD), [17][18][19] infections, 14,20 indwelling vascular catheters and prolonged immobilization. 14 HSCT is also associated with an 'acquired hypercoagulable state' characterized by inflammation, endothelial damage and activation of endothelium-dependent coagulation factors, increase in von Willebrand factor and platelet adhesion, increased thrombin generation, decreased anti-thrombin levels and decreased levels of anticoagulant proteins such as protein C. [21][22][23][24][25][26][27] graft versus host disease (GVHD) is associated with inflammation that leads to endothelial damage and activation. 28 TNF alpha, an essential mediator in the pathogenesis of GVHD, has been shown to enhance pro-thrombotic alterations on the endothelial cell surface.…”

Postoperative bleeding with factor VII deficiency: Case report

“…Endothelial cell injury was believed to be the responsible underlying lesion, causing various organ toxicities leading to a deficiency in various coagulation factors. 7 Factor VII deficiency may also be acquired in various conditions such as liver failure, anticoagulation administrations and vitamin K deficiency.…”