Relevant bleeding diathesis due to acquired factor XIII deficiency

Summary

Background

Acquired factor XIII (FXIII) deficiency is associated with reduced clot firmness and increased bleeding in patients undergoing major surgery. In contrast, only limited information is available on the haemostatic relevance of acquired FXIII deficiency in non-surgical patients.

Case report

An 81-year-old patient, who had experienced acute type-A dissection of the aorta eight years earlier, presented with a 3-year history of progressive mucocutaneous and softtissue bleeding. Diagnostic work-up was unremarkable for global coagulation tests, but FXIII and alpha2-antiplasmin were decreased to 33% and 27%, respectively, while plasma D-dimer was elevated to > 35 mg/l. A FXIII inhibitor was excluded by mixing studies. CT scanning revealed a massively elongated and progressively dilated aorta with a false lumen reaching from the left carotid artery to the iliac bifurcation. Bleeding control was achieved by single doses of FXIII at 20-30 IU/ kg body weight and tailored oral tranexamic acid.

Conclusion

Acquired FXIII deficiency with activity levels of 30–35% may confer a severe bleeding tendency in non-surgical patients, especially in the context of increased thrombin an fibrin generation.

Zusammenfassung

Hintergrund

Bei größeren chirurgischen Eingriffen ist der erworbene Faktor XIII(FXIII)Mangel mit einer verminderten Gerinnselstabilität und einem erhöhten Blutverlust assoziiert. Im Gegensatz dazu ist die Bedeutung dieser Hämostasestörung für nichtchirurgische Patienten noch weitgehend unklar.

Fallbericht

Bei einem 81-jährigen Patienten, der vor acht Jahren eine akute Typ A-Aortendissektion erlitten hatte, war es zuletzt zu vermehrten (Schleim)Haut- und Weichteilblutungen gekommen. Bei unauffälligen Globaltests waren die Werte für FXIII und Alpha2-Antiplasmin mit 33% und 27% deutlich vermindert. Die D-Dimere lagen bei > 35 mg/l. Ein FXIII-Inhibitor wurde durch einen Plasmatauschversuch ausgeschlossen. Das CT zeigte eine massiv elongierte und im Verlauf zunehmend dilatierte Aorta mit einem falschen Lumen von der linken Karotis bis zu den Beckenarterien. Eine suffiziente Blutungsbehandlung war mit Einzelgaben von FXIII (20–30 IE/kg Körpergewicht) und oraler Tranexamsäure möglich.

Schlussfolgerung

Insbesondere unter Bedingungen einer vermehrten Thrombin- und Fibrinbildung kann ein erworbener FXIII-Mangel auch bei nichtchirurgischen Patienten mit einer schweren Blutungsneigung einhergehen.

Keywords

Faktor XIII - aortic aneurysm - DIC - fibrinolysis - tranexamic acid

Schlüsselwörter

Faktor XIII - Aortenaneurysma - DIC - Fibrinolyse - Tranexamsäure

• References

• 1 Hsieh L, Nugent D. Factor XIII deficiency. Haemophilia 2008; 14: 1190-1200.
• 2 Dufner GS, Marbet GA. [Factor XIII in man: a review]. Hämostaseologie 2002; 22: 11-19.
• 3 McDonagh J. Structure and function of factor XIII. In: Colman RW. Hemostasis and Thrombosis: Basic Principles and Clinical Practice. 3rd 1994 ed. Philadelphia: Lippincott Company; 1994
• 4 Mosesson MW, Siebenlist KR, Hernandez I. et al. Evidence that alpha2-antiplasmin becomes covalently ligated to plasma fibrinogen in the circulation: a new role for plasma factor XIII in fibrinolysis regulation. J Thromb Haemost 2008; 06: 1565-1570.
• 5 Siebenlist KR, Meh DA, Mosesson MW. Plasma factor XIII binds specifically to fibrinogen molecules containing gamma chains. Biochemistry 1996; 35: 10448-10453.
• 6 Wolpl A, Lattke H, Board PG. et al. Coagulation factor XIII A and B subunits in bone marrow and liver transplantation. Transplantation 1987; 43: 151-153.
• 7 Anwar R, Miloszewski KJ. Factor XIII deficiency. Br J Haematol 1999; 107: 468-484.
• 8 Egbring R, Kroniger A, Seitz R. Factor XIII deficiency: pathogenic mechanisms and clinical significance. Semin Thromb Hemost 1996; 22: 419-425.
• 9 Trappe R, Budde U, Zimmermann H. Haemorrhage due to proteolysis of FXIII and hyperfibrinolysis under vemurafenib treatment of metastatic melanoma. Thromb Haemost 2012; 108: 798-800.
• 10 Gerlach R, Tolle F, Raabe A. et al. Increased risk for postoperative hemorrhage after intracranial surgery in patients with decreased factor XIII activity: implications of a prospective study. Stroke 2002; 33: 1618-1623.
• 11 Wettstein P, Haeberli A, Stutz M. et al. Decreased factor XIII availability for thrombin and early loss of clot firmness in patients with unexplained intraoperative bleeding. Anesth Analg 2004; 99: 1564-1569.
• 12 Langer F, Spath B, Haubold K. et al. Tissue factor procoagulant activity of plasma microparticles in patients with cancer-associated disseminated intravascular coagulation. Ann Hematol 2008; 87: 451-457.
• 13 Korte W. Fibrin monomer and factor XIII: a new concept for unexplained intraoperative coagulopathy. Hämostaseologie 2006; 26: S30-S35.
• 14 Korte WC, Szadkowski C, Gahler A. et al. Factor XIII substitution in surgical cancer patients at high risk for intraoperative bleeding. Anesthesiology 2009; 110: 239-245.
• 15 Godje O, Gallmeier U, Schelian M. et al. Coagulation factor XIII reduces postoperative bleeding after coronary surgery with extracorporeal circulation. Thorac Cardiovasc Surg 2006; 54: 26-33.
• 16 Deleplanque G, Kraimps JL, Rouffineau J. et al. Abdominal aortic aneurysm detected by a consumption coagulopathy. J Chir (Paris) 1990; 127: 325-329.
• 17 Miyata T, Tada Y, Takagi A. et al. Disseminated intravascular coagulation caused by abdominal aortic aneurysm. J Cardiovasc Surg (Torino) 1988; 29: 494-497.
• 18 Fine NL, Applebaum J, Elguezabal A. et al. Multiple coagulation defects in association with dissecting aneurysm. Arch Intern Med 1967; 119: 522-526.
• 19 Disdier P, Harle JR, Aillaud MF. et al. Disseminated intravascular coagulation and chronic aortic dissection. Ann Cardiol Angeiol (Paris) 1991; 40: 547-549.
• 20 Sadhwani D, O’Mara K. Acute dissecting thoracic aortic aneurysm presenting with stroke, consumptive coagulopathy, and gastrointestinal hemorrhage. J Emerg Med 1999; 17: 631-635.