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A. Tiede et al.
mild or no bleeding. Subcutaneous hematomas are charac- teristic of AHA and can be the first indication of the dis- ease.
Patients with AHA are often elderly; comorbidities and medications, such as antiplatelet agents and anticoagu- lants, may influence the clinical picture and require an individualized therapeutic approach. In contrast to con- genital hemophilia, comparative clinical studies are not available in AHA, largely because of the rarity of the dis- order and the severe clinical condition of patients at pres- entation. Treatment decisions are often based on the expertise and clinical experience of treating physicians, and referral to expert centers is often recommended to provide the best possible care.
In 2009, Huth-Kühne et al. published international rec- ommendations for AHA.1 Since then, other guidance has also been published.6 These documents are recognized as important sources of guidance for hematologists and other specialists. The 2009 recommendations were mainly based on the authors’ collective experience in treating a large number of patients with AHA. Data from several AHA registries have since been published, including the EACH2 (European ACquired Haemophilia),3,5,7,8 SACHA (Surveillance des Auto-antiCorps au cours de l’Hémophilie Acquise)9 and GTH (Gesellschaft für Thrombose- und Hämostaseforschung) registries10-13 in Europe, as well as the HTRS (Hemostasis and Thrombosis Research Society) registry in the USA.14 Moreover, a clinical trial investigat- ing the use of a recently introduced treatment for AHA, recombinant porcine FVIII (rpFVIII), has been reported.15 Here, we provide an updated set of recommendations based on this higher level of recent evidence, which has influenced clinical practices in AHA.
Methods
First, each author independently reviewed the 2009 international AHA recommendations,1 identifying areas in which an update was required based on their personal
Table 1. Recent studies and registries in acquired hemophilia A.
experience and knowledge of current literature. Feedback was consolidated in a single document, and the latest available published evidence was assessed to ascertain the extent to which each proposed statement was justified, with particular emphasis on the results of the AHA reg- istries summarized in Table 1. A PubMed literature search was conducted to identify additional relevant publications published since 2009. The search strategy and a PRISMA diagram are provided in the Online Supplementary Material.
Recommendations were formulated according to Guyatt et al.,16 as detailed in Online Supplementary Table S1. We used GRADE 1 for recommendations (“we recom- mend”) whenever a clear impact on patients’ safety or benefit would outweigh risks and burden. More specifical- ly, GRADE 1B was used when the statement was support- ed by data from at least one observational or intervention- al study, and when the recommendation seemed to apply to most patients in most circumstances without reserva- tion; GRADE 1C was used for recommendations that lacked support from such evidence, but still appeared to be important for patients’ safety or benefit. GRADE 2 (“we suggest”) was used for weaker suggestions (2B for those with support from registries or studies, and 2C without) that may change when new data become avail- able. Table 2 lists our main recommendations in the order in which they are discussed.
Diagnosis
AHA is rare, usually occurring unexpectedly, with physicians of different specialties potentially seeing patients initially. Therefore, a simplified diagnostic algo- rithm to assist physicians who may not have direct expe- rience of AHA is required (Figure 1).
Typically, patients with AHA present with acute or recent bleeding symptoms, without a previous history of bleeding, with laboratory investigations showing an isolat- ed prolonged activated partial thromboplastin time (APTT), reduced FVIII activity (FVIII:C) (<1% in 50% of cases; <5%
Study name
UK surveillance study
EACH2
SACHA
GTH-AH 01/2010 HTRS
OBI-1
Study type
Registry
Registry
Registry Registry Registry Clinical trial
Design
Prospective, consecutive
Retrospective (3 years); prospective (3 years)
Prospective
Prospective
Prospective
Prospective,
single-arm
Collection period
2001−2003
2003−2009
2001−2006 2010−2013 2004−2011 -
Total n. of patients
Treatment/outcome data available information
Survival information (pts)
Reference
Hemostatic therapy (n. of pts)*
Bleeding IST
resolved (n. of pts)** (n. of pts or
episodes)
Remission (n. of pts)
17297-151105113(2)
501 307 288 patients 331 331 331 (3, 5, 7, 8) (1st episodes)
82 38 38patients 77 77 82 (9)
102 166 29
70
68 (rFVIIa only) 28 (rpFVIII only)
162 episodes 139 episodes 28 patients
101 101
- - (14)
102 (10-12, 37)
- -
29 (15)
*Number of patients reported to have received recombinant activated factor VII (rFVIIa), activated prothrombin concentrate complex (APCC), factor VIII (FVIII) and/or recombinant porcine factor VIII (rpFVIII). Differences in the numbers reported vs. the total number of patients may be due to no treatment or lack of reporting. **Number of patients reported to have received immunosuppressive therapy. N: number; IST: immunosuppressive therapy; UK: United Kingdom; EACH2: European ACquired Haemophilia; SACHA: Surveillance des Auto-antiCorps au cours de l’Hémophilie Acquise; GTH: Gesellschaft für Thrombose- und Hämostaseforschung; HTRS: Hemostasis and Thrombosis Research Society; OBI-1: susoctocog alfa.
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