A clinical evaluation of patients with known mutations (plasminogen and factor XII) with a focus on prophylactic treatment

Figures & data

Figure 1. A simplified overview of the presumed pathomechanism and mode of action of drugs approved for HAE-1 and HAE-2, acute and prophylactic treatment. The drugs are marked in yellow, pink lightnings mark known mutations leading to HAE-nC1-INH.

Figure 2. The highly significant negative correlation between the year of birth and the age of initial diagnosis (Spearman correlation; p = <.0001).

Table 1. All study patients (n = 18) with HAE-nC1-INH and the family members with a history of angioedema, the mutations and clinical information are listed.

Patients evaluated in the study and age (years)	Age at first onset of symptoms (years)	Other family members with a history of angioedema	Mutation	Attack frequency and burden of disease at first presentation
Female, 28 Female, 32 Female, 62	16 No attack until today No attack until today	None	Factor XII: c.983C > A	Abdominal edema and edema of the limbs under estrogen intake No attacks, sister with angioedema, mutation was detected No attacks, daughter with angioedema, mutation was detected
Female, 21 Female, 44 Female, 46	18 19 30	1 Female, 1 male	Factor XII: c.983C > A	Recurrent edema of the limbs, lips, face, abdomen, lasting approx. five days Recurrent edema of the limbs, larynx, lips, face, abdomen, lasting approx. five days Recurrent edema of the lips and eyes, lasting approx. five days
Female, 21	17	1 Female, 1 male	Plasminogen: c.988A > G	Recurrent edema of the lips, lasting approx. one day
Female, 32 Female, 42 Female, 57 Female, 62	19 Unspecific symptoms 47 35	1 Female	Plasminogen: c.988A > G	Edema of the lips, upper airway, abdomen, lasting approx. two days, 2–3x/year Rare episodes of abdominal pain, possibly due to HAE Recurrent edema of the tongue and face, lasting approx. one day, 2–3x/year Recurrent edema of the lips, tongue, face, lasting approx. three days, >20x/year
Male, 77	50	1 Female, 1 male	Plasminogen: c.988A > G	Edema of the lips, upper airway, lasting approx. two days, 4–6x/year
Female, 26 Male, 58	20 53	2 Females	Plasminogen: c.988A > G	Edema of the lips, abdomen, lasting approx. two to three days, 1–3x/year Edema of the lips and face after intake of ACE inhibitor
Male, 61	48	2 Females	Plasminogen: c.988A > G	Edema of the lips and upper airway, one time requiring intubation
Female, 28 Female, 58	Unspecific symptoms 52	1 Female	Plasminogen: c.988A > G	Rare episodes of edema of the upper airway Edema of the lips and abdomen, lasting approx. two days
Female, 62	19	1 Female	Plasminogen: c.988A > G	Recurrent edema of the lips, tongue, face, lasting approx. three days, 2-5x/year

Figure 3. (a) The course of all three patients with HAE-nC1-INH (factor XII: n = 2, PLG: n = 1) under long-term prophylaxis with lanadelumab 300 mg SC measured with AECT (Angioedema Control Test). Ten and more points in AECT reflect a sufficiently controlled disease situation. (b) The course of all three patients with HAE-nC1-INH (Factor XII: n = 2, PLG: n = 1) under long-term prophylaxis with lanadelumab 300 mg SC measured with AE-QoL (Angioedema Quality of Life Questionnaire). In AE-QoL (0–100), a high score reflects a low quality of life. (c) AECT results, before and after comparison, *= p < .05; one-tailed Kruskal–Wallis test.