Bleeding disorder of unknown cause (BDUC) is a diagnosis of exclusion encompassing patients who have objective clinical symptoms of a mild bleeding disorder, yet negative hemostatic evaluations. Patients with BDUC may have a history of significant postoperative bleeding, and management of subsequent procedures poses a distinct challenge. After reviewing both patient and procedural bleeding risk factors, empiric hemostatic therapies can be considered. Extrapolating from the management of phenotypically similar bleeding disorders, a therapeutic approach may include antifibrinolytic agents (tranexamic acid), desmopressin, and/or platelet transfusion. Patients should be medically optimized prior to procedures and monitored closely for excess bleeding. Education of both patients and providers is central throughout the hemostatic planning process. Primary research in BDUC remains limited; future multisite observational and therapeutic clinical trials in BDUC may help us better understand multifactorial bleeding risk and further define the role of hemostatic therapies.

1.
Baker
RI
,
Choi
P
,
Curry
N
, et al
;
ISTH SSC Von Willebrand Factor, Platelet Physiology, and Women's Health Issues in Thrombosis and Haemostasis
.
Standardization of definition and management for bleeding disorder of unknown cause: communication from the SSC of the ISTH
.
J Thromb Haemost
.
2024
;
22
(
7
):
2059
-
2070
.
2.
Berkowitz
C
,
Ma
A
,
Miller
V
, et al
.
Periprocedural hemostatic prophylaxis and outcomes in bleeding disorder of unknown cause
.
Res Pract Thromb Haemost
.
2024
;
8
(
7
):
102572
.
3.
Gebhart
J
,
Hofer
S
,
Panzer
S
, et al
.
High proportion of patients with bleeding of unknown cause in persons with a mild-to-moderate bleeding tendency: results from the Vienna Bleeding Biobank (VIBB)
.
Haemophilia
.
2018
;
24
(
3
):
405
-
413
.
4.
MacDonald
S
,
Wright
A
,
Beuche
F
, et al
.
Characterization of a large cohort of patients with unclassified bleeding disorder; clinical features, management of haemostatic challenges and use of global haemostatic assessment with proposed recommendations for diagnosis and treatment
.
Int J Lab Hematol
.
2020
;
42
(
2
):
116
-
125
.
5.
Veen
CSB
,
Huisman
EJ
,
Romano
LGR
, et al
.
Outcome of surgical interventions and deliveries in patients with bleeding of unknown cause: an observational study
.
Thromb Haemost
.
2021
;
121
(
11
):
1409
-
1416
.
6.
Mehic
D
,
Neubauer
G
,
Janig
F
, et al
.
Risk factors for future bleeding in patients with mild bleeding disorders: longitudinal data from the Vienna Bleeding Biobank
.
J Thromb Haemost
.
2023
;
21
(
7
):
1757
-
1768
.
7.
Spyropoulos
AC
,
Douketis
JD
.
How I treat anticoagulated patients undergoing an elective procedure or surgery
.
Blood
.
2012
;
120
(
15
):
2954
-
2962
.
8.
Relke
N
,
Chornenki
NLJ
,
Sholzberg
M
.
Tranexamic acid evidence and controversies: an illustrated review
.
Res Pract Thromb Haemost
.
2021
;
5
(
5
):
e12546
.
9.
Kelly
C
,
Thomas
W
,
Baker
RI
,
O'Donnell
JS
,
Sanchez-Luceros
A
,
Lavin
M
.
Examining variability in the diagnosis and management of people with bleeding disorders of unknown cause: communication from the ISTH SSC Subcommittee on von Willebrand Factor
.
J Thromb Haemost
.
2024
;
22
(
10
):
2900
-
2909
.
10.
Lee
SG
,
Fralick
J
,
Wallis
CJD
,
Boctor
M
,
Sholzberg
M
,
Fralick
M
.
Systematic review of hematuria and acute renal failure with tranexamic acid
.
Eur J Haematol
.
2022
;
108
(
6
):
510
-
517
.
11.
Laan
S
,
Del Castillo Alferez
J
,
Cannegieter
S
, et al
.
DDAVP response and its determinants in bleeding disorders: a systematic review and meta-analysis
.
Blood
.
2025
;
145
(
16
):
1814
-
1825
.
12.
Koon
A
,
Perciavalle
K
,
Oleis
J
,
Arnall
J
.
Providing medication alternatives during intranasal desmopressin recall
.
J Oncol Pharm Pract
.
2022
;
28
(
1
):
190
-
193
.
13.
Furqan
F
,
Sham
R
,
Kouides
P
.
Efficacy and safety of half-dose desmopressin for bleeding prophylaxis in bleeding disorder patients undergoing predominantly low to moderate risk invasive procedures
.
Am J Hematol
.
2020
;
95
(
10
):
E285
-
E287
.
14.
Obaji
S
,
Alikhan
R
,
Rayment
R
,
Carter
P
,
Macartney
N
,
Collins
P
.
Unclassified bleeding disorders: outcome of haemostatic challenges following tranexamic acid and/or desmopressin
.
Haemophilia
.
2016
;
22
(
2
):
285
-
291
.
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