Apixaban for the Treatment of Chronic Disseminated Intravascular Coagulation: A Report of Two Cases

Snjezana Janjetovic; Katharina Holstein; Christina Dicke; Carsten Bokemeyer; Florian Langer

doi:10.1055/s-0038-1675386

Hämostaseologie, Table of Contents

Hamostaseologie 2019; 39(03): 294-297
DOI: 10.1055/s-0038-1675386

Case Report

Georg Thieme Verlag KG Stuttgart · New York

Apixaban for the Treatment of Chronic Disseminated Intravascular Coagulation: A Report of Two Cases

Snjezana Janjetovic

¹Department of Oncology and Hematology, BMT with Section of Pneumology, Hubertus Wald Tumorzentrum – University Cancer Center Hamburg, University Medical Center Eppendorf, Hamburg, Germany

,

Katharina Holstein

¹Department of Oncology and Hematology, BMT with Section of Pneumology, Hubertus Wald Tumorzentrum – University Cancer Center Hamburg, University Medical Center Eppendorf, Hamburg, Germany

,

Christina Dicke

¹Department of Oncology and Hematology, BMT with Section of Pneumology, Hubertus Wald Tumorzentrum – University Cancer Center Hamburg, University Medical Center Eppendorf, Hamburg, Germany

,

Carsten Bokemeyer

¹Department of Oncology and Hematology, BMT with Section of Pneumology, Hubertus Wald Tumorzentrum – University Cancer Center Hamburg, University Medical Center Eppendorf, Hamburg, Germany

,

Florian Langer

¹Department of Oncology and Hematology, BMT with Section of Pneumology, Hubertus Wald Tumorzentrum – University Cancer Center Hamburg, University Medical Center Eppendorf, Hamburg, Germany

› Author Affiliations

Abstract

Characteristic features of disseminated intravascular coagulation (DIC) are the opposing risks of bleeding (due to consumptive coagulopathy and hyperfibrinolysis) and organ failure (due to widespread microvascular thromboses). The purpose of anticoagulation in DIC is to attenuate excessive thrombin generation and fibrin deposition. While heparins have been shown to be beneficial in this context, the safety and efficacy of direct oral anticoagulants have not yet been sufficiently addressed. Here, we report two patients in whom chronic DIC was stabilized upon administration of apixaban: an elderly male with aortic dissection presenting with significant mucocutaneous bleeding and a younger female with Klippel–Trénaunay–Weber syndrome presenting with multiple superficial vein thromboses (SVTs). In addition to an improvement in DIC parameters, both patients benefited clinically with resolution of bleeding symptoms and prevention of further SVTs, respectively. Oral apixaban thus showed promising safety and efficacy in the management of DIC caused by vascular abnormalities; still further investigations are needed to support these findings.

Zusammenfassung

Zu den charakteristischen Komplikationen der disseminierten intravasalen Gerinnung (disseminated intravascular coagulation, DIC) gehören sowohl ein erhöhtes Blutungsrisiko (bedingt durch eine Verbrauchskoagulopathie mit sekundärer Hyperfibrinolyse) als auch das Multiorganversagen (als Folge von Mikrothrombosen in den Organendstrombahnen). Mit Hilfe einer antikoagulatorischen Therapie soll die durch die DIC induzierte exzessive Thrombingenerierung mit konsekutiver Fibrinablagerung reduziert werden. Während sich der Einsatz von Heparinen zur symptomatischen Behandlung der DIC bereits bewährt hat, konnten die Sicherheit und Wirksamkeit von direkten oralen Antikoagulantien bislang noch nicht ausreichend belegt werden. Wir berichten über zwei Patienten, bei denen eine chronische DIC jeweils durch die Einnahme von Apixaban stabilisiert werden konnte: ein älterer männlicher Patient mit Aortendissektion und ausgeprägten mukokutanen Einblutungen sowie eine jüngere Patientin mit Klippel-Trénaunay-Weber-Syndrom, welche mit multiplen oberflächlichen Venenthrombosen vorstellig wurde. Neben einer Verbesserung der laboranalytischen DIC-Parameter kam es bei beiden Patienten unter Einnahme von Apixaban zu einem deutlichen Rückgang der klinischen Beschwerdesymptomatik: Blutungssymptome sistierten und ein Auftreten weiterer oberflächlicher Venenthrombosen konnte verhindert werden. In beiden Fällen stellte die Einnahme von Apixaban somit eine wirksame und sichere Therapie der vaskulär bedingten DIC dar. Weitere Untersuchungen sind jedoch erforderlich, um diese Beobachtungen zu bestätigen.

Keywords

disseminated intravascular coagulation - fibrinolysis - apixaban

Schlüsselwörter

disseminierte intravasale Gerinnung - Fibrinolyse - Apixaban

Full Text

References

References
1 Levi M, Ten Cate H. Disseminated intravascular coagulation. N Engl J Med 1999; 341 (08) 586-592
2 Levi M, Toh CH, Thachil J, Watson HG. ; British Committee for Standards in Haematology. Guidelines for the diagnosis and management of disseminated intravascular coagulation. Br J Haematol 2009; 145 (01) 24-33
3 Wada H, Matsumoto T, Yamashita Y. Diagnosis and treatment of disseminated intravascular coagulation (DIC) according to four DIC guidelines. J Intensive Care 2014; 2 (01) 15
4 Levi M, Scully M. How I treat disseminated intravascular coagulation. Blood 2018; 131 (08) 845-854
5 Taylor Jr FB, Toh CH, Hoots WK, Wada H, Levi M. ; Scientific Subcommittee on Disseminated Intravascular Coagulation (DIC) of the International Society on Thrombosis and Haemostasis (ISTH). Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation. Thromb Haemost 2001; 86 (05) 1327-1330
6 Wada H, Asakura H, Okamoto K. , et al; Japanese Society of Thrombosis Hemostasis/DIC subcommittee. Expert consensus for the treatment of disseminated intravascular coagulation in Japan. Thromb Res 2010; 125 (01) 6-11
7 Di Nisio M, Baudo F, Cosmi B. , et al; Italian Society for Thrombosis and Haemostasis. Diagnosis and treatment of disseminated intravascular coagulation: guidelines of the Italian Society for Haemostasis and Thrombosis (SISET). Thromb Res 2012; 129 (05) e177-e184
8 Wada H, Thachil J, Di Nisio M. , et al. Guidance for diagnosis and treatment of disseminated intravascular coagulation from harmonization of the recommendations from three guidelines. J Thromb Haemost 2013; 11: 761-767
9 Kwaan HC, Cull EH. The coagulopathy in acute promyelocytic leukaemia--what have we learned in the past twenty years. Best Pract Res Clin Haematol 2014; 27 (01) 11-18
10 Janning M, Holstein K, Spath B. , et al. Relevant bleeding diathesis due to acquired factor XIII deficiency. Hamostaseologie 2013; 33 (Suppl. 01) S50-S54
11 Byon W, Sweeney K, Frost C, Boyd R. Population pharmacokinetic analysis of apixaban in venous thromboembolism treatment patients. . Presented at the 5th International Society of Pharmacometrics. October 12–15, 2014 ; Las Vegas, Nevada. Poster no. T-060
12 Yamahira N, Frost C, Fukase H. , et al. Safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple doses of apixaban in healthy Japanese male subjects. Int J Clin Pharmacol Ther 2014; 52 (07) 564-573
13 Beyer-Westendorf J, Schellong SM, Gerlach H. , et al; SURPRISE investigators. Prevention of thromboembolic complications in patients with superficial-vein thrombosis given rivaroxaban or fondaparinux: the open-label, randomised, non-inferiority SURPRISE phase 3b trial. Lancet Haematol 2017; 4 (03) e105-e113
14 Kadohira Y, Yamada S, Matsuura E. , et al. Aortic aneurysm-associated disseminated intravascular coagulation that responded well to a switch from warfarin to rivaroxaban. Intern Med 2017; 56 (21) 2913-2917