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Three Part Question

In [patients with dabigatran-associated haemorrhage] do [coagulation factor concentrates] improve [haemostasis and survival]?

Search Strategy

Medline (1966/01/01 to 2014/11/01) was searched using the Pubmed database.

"Blood Coagulation Factors/therapeutic use"[Mesh] OR "Blood Coagulation Factors/therapy"[Mesh] ) AND (dabigatran OR pradaxa)

Filters: Humans, English

Search Outcome

48 items returned, of which 5 were relevant.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Schulman S et al. 2013 Canada	4 patients (ages: 81-85) with daibagtran-associated bleeding (gastrointestinal; pericaridal; subdural; intraxial) treated with aPCC (FEIBA)	Case series	Resolution of bleeding	4/4	Limited case series.
			Survival	4/4
Díaz MQ et al. 2013 Spain	5 patients (ages: 77-88) with daibagtran-associated gastrointestinal bleeding treated with PCC (Octaplex), one of whom also received Vitamin K.	Case series	Resolution of bleeding	4/5	Limited case series.
			Survival	4/5
Lillo-Le Louët A et. al. 2012 France	4 patients (ages: 72-86) with dabigatran-associated bleeding, 3 of whom recevied FFP and CFC preparations (PCC (Kaskadil) & rFVIIa; rFVIIa; PCC (Kanokad) & rFVIIa). Of these 3, one patient also received haemodiafiltration.	Case series.	Resolution of bleeding	0/2	Limited case series. The contribution of coagulation factor concentrates could only be assessed in 2 of 3 patients, as one patient also received haemodiafiltration.
			Survival	0/2
Dumkow LE et al. 2012 USA	85 year-old man with dabigaran-associated gastrointestinal bleeding treated with FFP and PCC (Factor IX complex)	Case study	Resolution of bleeding	1/1	Limited case study.
			Survival	0/1
Dager et al. 2013 USA	67 year-old man with dabigatran-associated bleeding secondary to a transseptal perforation during cardiac ablation was treated with aPCC (FEIBA)	Case study	Resolution of bleeding	1/1	Limited case study.
			Survival	1/1

Comment(s)

Currently, there is no antidote available for dabigatran. The role of several coagulation factor concentrates in reversing dabigatran has been investigated, but the evidence for their efficacy in acute haemorrhage is limited to case series and studies.

Clinical Bottom Line

There is insufficient clinical evidence at present for the efficacy of any coagulation factor concentrate in the treamnent of dabigatran-associated bleeding.

References

1. Schulman S, Ritchie B, Goy JK, Nahirniak S, Almutawa M, Ghanny S. Activated prothrombin complex concentrate for dabigatran-associated bleeding.
2. Díaz MQ, Borobia AM, Núñez MA, Virto AM, Fabra S, Casado MS, García-Erce JA, Samama CM. Use of prothrombin complex concentrates for urgent reversal of dabigatran in the Emergency Department.
3. Lillo-Le Louët A, Wolf M, Soufir L, Galbois A, Dumenil AS, Offenstadt G, Samama MM. Life-threatening bleeding in four patients with an unusual excessive response to dabigatran: implications for emergency surgery and resuscitation.
4. Dumkow LE, Voss JR, Peters M, Jennings DL. Reversal of dabigatran-induced bleeding with a prothrombin complex concentrate and fresh frozen plasma.
5. Dager WE, Gosselin RC, Roberts AJ. Reversing dabigatran in life-threatening bleeding occurring during cardiac ablation with factor eight inhibitor bypassing activity.