Infusion of DDAVP Does Not Improve Primary Hemostasis in Patients with Cirrhosis
Authors: Arshad Freeha , Stoof Sara C.M. , Leebeek Frank W.G. , Ruitenbeek Karin , Adelmeijer Jelle , Blokzijl Hans , van den Berg Arie P. , Porte Robert J. , Kruip Marieke J.H.A. , Lisman Ton 
Published: October 2019

Rationale: Cirrhosis frequently affects multiple components of hemostasis. Reversal of the coagulopathy of these patients is frequently required in case of bleeding episodes, or as prophylaxis before invasive procedures. A simple and cost-effective way to correct a prolonged bleeding time in patients with cirrhosis is administration of 1-deamino-8-D-arginine vasopressin (DDAVP). Although DD AVP is widely used as a pro-hemostatic agent in patients with cirrhosis, it is unclear whether DDAVP truly enhances the hemostatic potential in these patients. We investigated the hemostatic effects of a single bolus dose of DDAVP in patients with cirrhosis.

Methods: Ten patients with cirrhosis (n=6 Child-Pugh score B, n=4 Child-Pugh score C) and ten patients with mild hemophilia A (FVIII 0.05-0.40 IU/ml) were included in this study. All patients received an intravenous single bolus of 0.3 microgram/kg DDAVP. Plasma was collected prior to and at 1, 3, 6, and 24 hours after DDAVP administration. Levels of Von Willebrand factor (VWF:Ag), VWF propeptide, Factor VIII (FVIII), and ADAMTS13 were measured in all plasma samples, whereas VWF multimers and functional VWF-dependent platelet adhesion were determined in the samples pre- and 1 hour after DDAVP administration. VWF-dependent platelet adhesion was studied under flow conditions in a reconstituted blood model.

Results: The median age of patients with cirrhosis was 55 years (IQR 47-58) and 46 years (IQR 40-55) in patients with haemophilia. Baseline values of coagulation parameters are shown in table 1. Following DDAVP administration, VWF:Ag, FVIII levels and VWF propeptide increased in patients with hemophilia, while patients with cirrhosis only showed a modest increase in VWF propeptide and FVIII levels (figure 1). Only in those patients with low Child-Pugh scores, VWF:Ag slightly increased following DDAVP. The proportion of high molecular weight VWF multimers and VWF-dependent platelet adhesion increased in patients with hemophilia one hour after DDAVP administration, but did not change in the patients with cirrhosis. Levels of ADAMTS13 were unaffected in both patient groups after DDAVP.

Conclusion: DDAVP administration in patients with cirrhosis did not have effect on VWF:Ag and ADAMTS13, but VWF propeptide and FVIII did increase. The lack of relevant hemostatic effects of DDAVP in patients with cirrhosis may be the explanation for the limited value in previous clinical studies in these patients.

Table 1. Baseline levels of VWF:Ag and related proteins Patient group Hemophilia A Cirrhosis p-value VWF:Ag (IU/dl) 114 (94.5-164.3) 521 (238-643.8) <0.001 ADAMTS13 (%) 76.6 (57.3-87.9) 93.9 (59.2-130.4) 0.247 VWF propeptide (IU/dl) 108.5 (97.3-121.3) 284 (236.5-392.8) <0.001 FVIII (IU/dl) 20 (12.3-38) 152.5 (117.3-193.8) <0.001

Data are presented as medians with IQR; VWF:Ag= Von Willebrand factor antigen; ADAMTS13= a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13; FVIII= Factor VIII

Figure 1. Coagulation parameters in patients with hemophilia (panel A) or cirrhosis (panel B) Figure 1. Coagulation parameters in patients with hemophilia (panel A) or cirrhosis (panel B)

Disclosures

No relevant conflicts of interest to declare.