4. Discussion
Looking at the map illustrating the geographical distribution of
C1-INH-HAE patients in Belarus, it is evident as most of them live in
Minsk, where the Research Centre of Borovlyani is located. This
indicates that patients living in or near Minsk can more easily reach
the centre in order to undergo the necessary examinations and / or to
have easier access to care. Also, Minsk and neighbouring areas have in
their disposition a greater pathology knowledge base, access to relevant
trainings and better developed health services. As a result, the
remaining parts of Belarus report the lack of knowledge about HAE as
well as ability to timely diagnose. This situation results in lower
prevalence and increased diagnostic delay compared to data from surveys
conducted in other countries [10-22].
Despite this situation, a high number of patients have been diagnosed in
the last three years. The collaboration with Italian HAE centre of
Milan, marked a significant improvement in the management of HAE.
Genetic data indicate that, although numerous and variousSERPING1 variants have been already reported in C1-INH-HAE, given
the high number of novel variants identified in our study, the spectrum
of variants responsible for this rare pathology is not completely
characterized yet. Moreover, splicing defects amounted to 25%, which
differs from the word data (about 10%) [29].
Data extrapolated from the answers to the questionnaire regarding
therapeutic possibilities, suggest a serious deficiency in Belarus in
accessing preventive therapy with Danazol: only 9 patients, indeed,
declared to carry on a prophylactic treatment with such drug.
Evaluating the number of attacks reported by patients in the
questionnaire, at least 5 out of 15 patients without prophylaxis had a
number of attacks greater than 2 per month [23], above which the
attenuated androgen therapy is indicated. Furthermore, no patient
reported short-term prophylactic therapy with attenuated androgens
before surgical intervention, particularly in the oral cavity.
Regarding ODT for acute attacks, it is important to consider how half of
the patients (21 out of 38) did not answer the question about drugs used
during acute attacks. This could be a result of inadequate patient
training about the effective drugs for the treatment of HAE. Analysing
17 answers of the patients, it becomes obvious the poor adherence to
guidelines for therapeutic management of acute attacks in Belarus. In
fact, as many as 11 patients were treated with ineffective drugs for
HAE: antihistamine, steroid, tranexamic acid. Only 6 patients were
treated with appropriate drugs, 2 with icatibant or i.v. C1-INH
concentrate and 5 with fresh frozen plasma infusion.
Icatibant or i.v. C1-INH concentrate are not available even at the
national hospitals and not refunded by Belarusian Health System. Hence,
the patients have to import the drugs from abroad on their own expense.
Therefore, danazol, tranexamic acid and fresh frozen plasma infusion are
used as the primary maintenance treatment in Belarus.
Our data show a lack of knowledge of on-demand HAE effective drugs both
by patients and by health personnel. Lack of proper knowledge and
education on patients’ pathology lead to a condition of extreme
vulnerability of the patients even in protected settings such as
hospitals. Twelve patients, that are not included in this study, died of
attacks before being diagnosed. One patient, out of 64 presented in this
study, died of angioedema in the hospital, because the provided therapy
was not effective due to the lack of necessary medications.
Belarus is an independent State formed in 1991. This is the first report
of a HAE patients from Belarus, here well characterized from a genetic
point of view. The lack of access to effective drugs (mainly for ODT)
raises a major concern about the risks to have life-threatening
laryngeal attacks, known to be the main disease specific cause of death
in HAE patients [2]. The young Belarusian Health System have now
other priorities such as control of infectious diseases and improvement
of cancer and cardiovascular disease, before approaching rare diseases
like HAE. Despite that, HAE management has improved, as seen from the
high number of new diagnosis in the last 3 years. Next steps will be
reducing the diagnostics delay, broader use of prophylactic and
on-demand therapy as indicated in HAE guidelines [10].
Table 1 . Epidemiology of the 64 C1-INH-HAE patients
identified in Belarus. Data about mean age of patients, symptom’s
onset, diagnosis and diagnostic delay (expressed in years), and
laboratory assessments. Antigenic C1-INH normal range: 0.21–0.39 g/l,
antigenic C4 normal range: 0.1-0.4 g/l 1-11 years and 0.2-0.5
g/l> 11 years. Functional C1-INH normal range: 77.3-128.8%