Key Points

  • Patients with AHA have a high risk of recurrent bleeding until they achieve partial remission of their disease.

  • Residual FVIII activity and clinical performance status are associated with recurrent bleeding.

Abstract

Acquired hemophilia A (AHA) is due to autoantibodies against coagulation factor VIII (FVIII) and most often presents with unexpected bleeding. In contrast to congenital hemophilia, the patient’s residual FVIII activity does not seem to correlate with the risk of bleeding as suggested from previous studies. Risk factors for bleeding have not been described. We used data from the prospective GTH-AH 01/2010 study to assess the risk of bleeding and the efficacy of hemostatic therapy. FVIII activity was measured at baseline and weekly thereafter. Bleeding events were assessed by treating physicians. A total of 289 bleeds were recorded in 102 patients. There were 141 new bleeds observed starting after day 1 in 59% of the patients, with a mean rate of 0.13 bleed per patient-week in weeks 1 to 12, or 0.27 bleed per patient-week before achieving partial remission. Weekly measured FVIII activity was significantly associated with the bleeding rate, but only achieving FVIII activity ≥50% abolished the risk of bleeding. A good World Health Organization performance status assessed at baseline (score 0 vs higher) was associated with a lower bleeding rate. Hemostatic treatment was reportedly effective in 96% of bleeds. Thus, the risk of new bleeds after a first diagnosis of AHA remains high until partial remission is achieved, and weekly measured FVIII activity may aid in assessing the individual risk of bleeding. These results will help to define future strategies for prophylaxis of bleeding in AHA.

REFERENCES

REFERENCES
1.
Kruse-Jarres
R
,
Kempton
CL
,
Baudo
F
, et al
.
Acquired hemophilia A: updated review of evidence and treatment guidance
.
Am J Hematol
.
2017
;
92
(
7
):
695
-
705
.
2.
Franchini
M
,
Vaglio
S
,
Marano
G
, et al
.
Acquired hemophilia A: a review of recent data and new therapeutic options
.
Hematology
.
2017
;
22
(
9
):
514
-
520
.
3.
Tiede
A
,
Scharf
RE
,
Dobbelstein
C
,
Werwitzke
S
.
Management of acquired haemophilia A
.
Hamostaseologie
.
2015
;
35
(
4
):
311
-
318
.
4.
Collins
PW
,
Hirsch
S
,
Baglin
TP
, et al;
UK Haemophilia Centre Doctors’ Organisation
.
Acquired hemophilia A in the United Kingdom: a 2-year national surveillance study by the United Kingdom Haemophilia Centre Doctors’ Organisation
.
Blood
.
2007
;
109
(
5
):
1870
-
1877
.
5.
Knoebl
P
,
Marco
P
,
Baudo
F
, et al;
EACH2 Registry Contributors
.
Demographic and clinical data in acquired hemophilia A: results from the European Acquired Haemophilia Registry (EACH2)
.
J Thromb Haemost
.
2012
;
10
(
4
):
622
-
631
.
6.
Janbain
M
,
Leissinger
CA
,
Kruse-Jarres
R
.
Acquired hemophilia A: emerging treatment options
.
J Blood Med
.
2015
;
6
:
143
-
150
.
7.
Tiede
A
,
Amano
K
,
Ma
A
, et al
.
The use of recombinant activated factor VII in patients with acquired haemophilia
.
Blood Rev
.
2015
;
29
(
suppl 1
):
S19
-
S25
.
8.
Tiede
A
,
Giangrande
P
,
Teitel
J
, et al
.
Clinical evaluation of bleeds and response to haemostatic treatment in patients with acquired haemophilia: a global expert consensus statement
.
Haemophilia
.
2019
;
25
(
6
):
969
-
978
.
9.
Collins
P
,
Baudo
F
,
Knoebl
P
, et al;
EACH2 registry collaborators
.
Immunosuppression for acquired hemophilia A: results from the European Acquired Haemophilia Registry (EACH2)
.
Blood
.
2012
;
120
(
1
):
47
-
55
.
10.
Tiede
A
,
Klamroth
R
,
Scharf
RE
, et al
.
Prognostic factors for remission of and survival in acquired hemophilia A (AHA): results from the GTH-AH 01/2010 study
.
Blood
.
2015
;
125
(
7
):
1091
-
1097
.
11.
Borg
JY
,
Guillet
B
,
Le Cam-Duchez
V
,
Goudemand
J
,
Lévesque
H
;
SACHA Study Group
.
Outcome of acquired haemophilia in France: the prospective SACHA (Surveillance des Auto antiCorps au cours de l’Hémophilie Acquise) registry
.
Haemophilia
.
2013
;
19
(
4
):
564
-
570
.
12.
Sun
B
,
Xue
F
,
Feng
Y
, et al
.
Outcome of CARE: a 6-year national registry of acquired haemophilia A in China
.
Br J Haematol
.
2019
;
187
(
5
):
653
-
665
.
13.
Green
D
,
Lechner
K
.
A survey of 215 non-hemophilic patients with inhibitors to factor VIII
.
Thromb Haemost
.
1981
;
45
(
3
):
200
-
203
.
14.
Lottenberg
R
,
Kentro
TB
,
Kitchens
CS
.
Acquired hemophilia. A natural history study of 16 patients with factor VIII inhibitors receiving little or no therapy
.
Arch Intern Med
.
1987
;
147
(
6
):
1077
-
1081
.
15.
Huth-Kühne
A
,
Baudo
F
,
Collins
P
, et al
.
International recommendations on the diagnosis and treatment of patients with acquired hemophilia A
.
Haematologica
.
2009
;
94
(
4
):
566
-
575
.
16.
Collins
PW
,
Chalmers
E
,
Hart
D
, et al;
United Kingdom Haemophilia Centre Doctors’ Organization
.
Diagnosis and management of acquired coagulation inhibitors: a guideline from UKHCDO
.
Br J Haematol
.
2013
;
162
(
6
):
758
-
773
.
17.
Tiede
A
,
Huth-Kühne
A
,
Oldenburg
J
, et al
.
Immunosuppressive treatment for acquired haemophilia: current practice and future directions in Germany, Austria and Switzerland
.
Ann Hematol
.
2009
;
88
(
4
):
365
-
370
.
18.
Delgado
J
,
Jimenez-Yuste
V
,
Hernandez-Navarro
F
,
Villar
A
.
Acquired haemophilia: review and meta-analysis focused on therapy and prognostic factors
.
Br J Haematol
.
2003
;
121
(
1
):
21
-
35
.
19.
Ma
AD
,
Kessler
CM
,
Al-Mondhiry
HA
,
Gut
RZ
,
Cooper
DL
.
Use of recombinant activated factor VII for acute bleeding episodes in acquired hemophilia: final analysis from the Hemostasis and Thrombosis Research Society Registry acquired hemophilia study
.
Blood Coagul Fibrinolysis
.
2016
;
27
(
7
):
753
-
760
.
20.
Den Uijl
IE
,
Mauser Bunschoten
EP
,
Roosendaal
G
, et al
.
Clinical severity of haemophilia A: does the classification of the 1950s still stand?
Haemophilia
.
2011
;
17
(
6
):
849
-
853
.
21.
Napolitano
M
,
Siragusa
S
,
Mancuso
S
,
Kessler
CM
.
Acquired haemophilia in cancer: a systematic and critical literature review
.
Haemophilia
.
2018
;
24
(
1
):
43
-
56
.
22.
Baudo
F
,
Collins
P
,
Huth-Kühne
A
, et al;
EACH2 registry contributors
.
Management of bleeding in acquired hemophilia A: results from the European Acquired Haemophilia (EACH2) Registry
.
Blood
.
2012
;
120
(
1
):
39
-
46
.
23.
Tiede
A
,
Worster
A
.
Lessons from a systematic literature review of the effectiveness of recombinant factor VIIa in acquired haemophilia [published correction appears in Ann Hematol. 2018;97(12):2531]
.
Ann Hematol
.
2018
;
97
(
10
):
1889
-
1901
.
24.
Sumner
MJ
,
Geldziler
BD
,
Pedersen
M
,
Seremetis
S
.
Treatment of acquired haemophilia with recombinant activated FVII: a critical appraisal
.
Haemophilia
.
2007
;
13
(
5
):
451
-
461
.
25.
Hay
CR
,
Negrier
C
,
Ludlam
CA
.
The treatment of bleeding in acquired haemophilia with recombinant factor VIIa: a multicentre study
.
Thromb Haemost
.
1997
;
78
(
6
):
1463
-
1467
.
26.
Sallah
S
.
Treatment of acquired haemophilia with factor eight inhibitor bypassing activity
.
Haemophilia
.
2004
;
10
(
2
):
169
-
173
.
27.
Ingerslev
J
,
Sørensen
B
.
Parallel use of by-passing agents in haemophilia with inhibitors: a critical review
.
Br J Haematol
.
2011
;
155
(
2
):
256
-
262
.
28.
Zanon
E
,
Pasca
S
,
Santoro
C
, et al
.
Activated prothrombin complex concentrate (FEIBA®) in acquired haemophilia A: a large multicentre Italian study—the FAIR Registry
.
Br J Haematol
.
2019
;
184
(
5
):
853
-
855
.
29.
Jennings
I
,
Kitchen
DP
,
Woods
TA
,
Kitchen
S
,
Walker
ID
,
Preston
FE
.
Laboratory performance in the World Federation of Hemophilia EQA programme, 2003-2008
.
Haemophilia
.
2009
;
15
(
2
):
571
-
577
.
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