A fibrinogen concentrate Haemocomplettan (Riastap) or a Factor XIII concentrate Fibrogammin combined with a mini dose of tranexamic acid can reverse the fibrin instability to fibrinolysis induced by thrombin- or FXa-inhibitor.
To assess whether Haemocomplettan(®) (fibrinogen concentrate) or Fibrogammin(®) (Factor XIII concentrate) can be used to manage bleeding complications of antithrombotic treatment, we examined a normal plasma pool spiked with AR-H067637 (thrombin inhibitor) or rivaroxaban (activated factor X-inhibitor), to which one of the concentrates was added. Fibrin network permeability (Ks), images of Scanning Electron Microscopy (SEM) and Clot Lysis Time (CLT) were examined. Both inhibitors increased the Ks levels, which could be fully or partly reversed by Haemocomplettan(®) or Fibrogammin(®) respectively. However, these modified clots with tightened network remained non-resistant to fibrinolysis, shown as unaffected CLT. Tranexamic acid at a very low concentration (0·4 mg/ml) aided the two concentrates to stabilize the clots, where the prolongation of CLT was more pronounced for a lower dose than a higher dose of Haemocomplettan(®) while Fibrogammin(®) brought the greatest delay to CLT out of all additions. These observations were partly supported by SEM images, displaying alterations of fibrin fibre arrangement known to influence fibirinolysis. The in vitro data suggest that Haemocomplettan(®) or Fibrogammin(®) given in combination with a mini dose of tranexamic acid may slow down the natural clearance of fibrin clot by plasmin and thus prevent patients from haemorrhagic complications during antithrombotic therapy.
Department of Molecular Medicine and Surgery/Clinical Chemistry/Coagulation Research, Karolinska Institutet, Stockholm, Sweden. heshu9999@gmail.com
Shu
S
He
Hans
H
Johnsson
Michal
M
Zabczyk
Kjell
K
Hultenby
Honglie
H
Cao
Margareta
M
Blombäck
D005176:Factor XIII / Q000008:administration & dosage / Q000378:metabolism; D005260:Female; D005337:Fibrin / Q000037:antagonists & inhibitors / Q000378:metabolism; D005340:Fibrinogen / Q000008:administration & dosage* / Q000378:metabolism*; D005341:Fibrinolysin / Q000008:administration & dosage*; D005342:Fibrinolysis / Q000187:drug effects*; D005343:Fibrinolytic Agents / Q000009:adverse effects*; D006470:Hemorrhage / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D006801:Humans; D008297:Male; D013917:Thrombin / Q000037:antagonists & inhibitors / Q000378:metabolism; D014148:Tranexamic Acid / Q000008:administration & dosage*
D005343:Fibrinolytic Agents; D014148:Tranexamic Acid; D005337:Fibrin; D005340:Fibrinogen; D005176:Factor XIII; D013917:Thrombin; D005341:Fibrinolysin