Hereditary Angioedema Guide: Pathogenesis, Classification, Diagnosis and Treatment

HEREDITARY ANGIOEDEMA
10th May 2019
Thansinee Saetae, MD.

OUTLINE
• Pathogenesis
• Classification of HAE
• Diagnosis and Approach
• Treatment
• HAE during pregnancy and lactation

ANGIOEDEMA
• Bouts of asymmetric
nondependent swelling involving
cutaneous or mucosal surfaces.
• The affected site typically is non-
pruritic.
• Angioedema most commonly is
mast cell–mediated, often
accompanied by urticaria.
Zuraw BL and Christiansen SC. Middleton’s Allergy 8th edition

Thai Clinical practice guidelines for Urticaria and Angioedema 2014

Maurer et al. World Allergy Organization Journal 2018;11:5
Suspect Mast cell Dependent when
• Urticaria coexists with angioedema
• Response to antihistamines
• Obvious trigger (i.e. drug, food)

Zuraw BL. N Engl J Med 2008;359(10):1027-36

H.H. Walford and B.L. Zuraw. Ann Allergy Asthma Immunol 2014;112:413-418

HISTORY OF HAE
HAE with
C1INH
deficiency
1960s
HAE type I
HAE type II
2000
HAE with
normal C1INH
2006
U-HAE
2018
HAE-PLG
HAE-ANGPT1
HAE-FXII
HAE-C1INH HAE-nl-C1INH HAE-nl-C1INH HAE-nl-C1INH
Cicardi and Zuraw. J Allergy Clin Immunol Pract 2018;6:1132-41

Cicardi M., Clin Rev Allergy Immunol 2016;51:162–169
Plasminogen gene Mutations
HAE-PLG
Angiopoietin-1 gene Mutations
HAE-ANGPT1

Cicardi M. Allergy 2014; 69: 602–616.

HAE WITH C1 INH DEFICIENCY
HAE type 1
HAE type 2

HAE WITH C1INH DEFICIENCY
• Mutation in one of the two alleles of SERPING1 gene located near chromosome 11
• Autosomal dominant
• De novo mutations (sporadic case) 25%
• HAE type I (85%)
• Quantitative
• Very heterogeneous, missense, nonsense, deletion or insertion
• HAE type II (15%)
• Functional
• Missense mutations

• Clinical features
• Recurrent episode of non-pruritic, non-pitting angioedema at extremities, abdomen, face, oropharynx or
a combination without urticaria
• 50% of all attacks à extremities and abdomen
• Gradual worsening over the first 24 hours, followed by an even slower recovery over the next 48 - 72 hrs
• Risk for a potential laryngeal attack
• 50% of the patients have swelling begins before the age of 10 years and worsening of symptoms
around puberty
• The earlier the onset of symptoms the more severe the subsequent course of HAE-1/2.
• All ethnicities and males and females equally effected
• Highly variable in individuals and within families.
ZurawBL and Christiansen SC. Middleton’s Allergy 8th edition

• Sites: face, oropharynx, extremities,
abdomen, genitourinary tract
• Less frequent: brain, kidney, heart, and
joints
• Abdominal swelling can cause nausea,
vomiting and diarrhea and may result in
inappropriate surgery
• Frequency: twice per week to less than 1/yr

• Extremities: temporary inability to carry out normal, compartment
syndrome
• Abdominal attacks: frequent cause of significant morbidity, severe
abdominal pain with intractable nausea and vomiting, and “third
spacing” of fluid can induce hypotension
• Oropharynx: closing the airway, resulting in death from asphyxiation
• Mortality rate due to laryngeal angioedema of approximately 30%
• More than half experience at least one laryngeal attack
• All patients are at risk for potential laryngeal attack irrespective of prior
disease severity
• Genitourinary attack: significant discomfort, temporary inability to
urinate
Shiber JR. N Engl J Med 2005;353:e15

PRODROMAL SYMPTOMS
• Frequently Proceed an Attack of HAE
• Several hours or up to a day in up to 50% of patients
• Flu-like feelings
• Erythema marginatum
• an erythematous non-urticarial rash à most common
• more frequent in the pediatric population (42% - 58%)
• Parathesias, Fatigue, Indigestion, Non-specific rashes
• Other non-specific symptoms
• Localized tingling, and a sense of skin tightness

COMMON TRIGGERS
Craig TJ. WAO Journal 2012; 5:182–199
URI, H. pylori
Hormonal,
Pregnancy,
Puberty
Even minimal
Esp. oral cavity,
aerodigestive system
Emotional, anxiety

• Level of C1-INH in HAE patients do not reflect disease activity nor
predict the disease course
• Varying in frequency and severity from patient to patient and even in
the same patient throughout life
• Inter-individual variation in frequency and location of attacks, possible
due to different polymorphismor environmental factors
• Some patients with C1-INH-HAE (14%) can remain asymptomatic

HAE WITH NORMAL C1 INH
HAE-FXII
HAE-ANGPT1
HAE-PLG
HAE-UNK

Riedel. J Allergy Clin Immunol In Practice 2013;1:427-32

Zuraw. J Allergy Clin Immunol 2018;141(3):884-885

• HAE-FXII: mutation in exon 9 of the F12 gene.
• HAE-ANGPT1, HAE-PLG à recently found mutations
• HAE-UNK à most common
• Its clinical appearance largely resembles that of HAE1/2.
• Similar triggers
• Highly variable and penetrance of the disease.

HAE-NL-C1INH: HAE-FXII
• Mutation in exon 9 of the F12 gene
• The most common form of HAE-FXII, p.Thr309Lys
• Enhance susceptibility of the contact system to become activated ex vivo and in vivo
• Enhance susceptibility of FXII to activation by plasmin
De Maat et al. J Allergy Clin Immunol 2016;138:1414-23

HAE-NL-C1INH: HAE-PLG
• The mechanism of angioedema in patients with HAE-PLG is not yet known.
• The putative role of plasmin in HAE-FXII, an early target of investigation will be the
ability of the mutant plasmin protease to activate the contact system.
Bork et al. Allergy. 2018;73:442–450
The mutation c.9886A>G was located in exon 9 leading to the missense
mutation p.Lys330Glu (K330E) in the kringle 3 domain of the PLG
protein.

HAE-ANGPT1
• ANGPT1-Tie2 signaling is known to
stabilize the vasculature and diminish
vascular permeability.
• The p.Ala119Ser mutation was shown
to interfere with the ability of mutant
ANGPT1 to assume a multimeric form.
• This mutation may put patients at
greater risk of developing angioedema
from multiple mediators, including
bradykinin.
Bafunno et al. J Allergy Clin Immunol 2018;141:1009-17

ACQUIRED ANGIOEDEMA
C1 INH-AAE
ACEI-AAE

SUSPECT ACQUIRED ANGIOEDEMA
• Angioedema similar to HAE, but later onset (over 40 years)
• Constitutional symptoms
• Low C1q
• Lymphoma or monoclonal gammopathy
• Anti-C1INH antibody

ACQUIRED ANGIOEDEMA WITH
C1 INH DEFICIENCY
• Consequences of increased catabolism of C1INH
• Continuous activation of classical pathway complement
• Autoantibodies to C1INH
• No mutations in C1-INH gene (SERPING1)
• No family history of angioedema (90%)
• Presented above fourth decade of life
• Facial edema is the most frequent location
• Clinically similar to C1-INH-HAE but differ in comorbidities
• More than 50% of C1-INH-AAE patients have or will develop
hematological disorder (B cell malignancy)
Cicardi M., Clinic Rev Allerg Immunol 2016;51:162–169

Zingale LC, et. al. Immunol Allergy Clin North Am 2006;26:669-90
Underlying diseases; malignancy
or immune dysregulation
• Lymphoma
• CLL
• MGUS
• Multiple myeloma
• W. macoglobinemia
• Cryoglobulinemia
• Echinococcus granulosus
• SLE
• Rheumatoid arthritis
• AIHA
• Gastric tumor
• Carcinoma of breast, pancreas,
bladder, colon, rectum
Low C1q level and anti C1-INH
Treatment of underlying diseases à resolution of acquired angioedema

ACQUIRED ANGIOEDEMA RELATED TO ACEI
Craig TJ et al. Int Arch Allergy Immunol 2014;165:119–127

• 1 in 200 - 1,000 pts treated with ACE-I will develop angioedema
• Risk of angioedema from ACEIs is higher in smokers, African Americans, and women; diabetes has
been associated with lower risk
• Strong predilection for involvement of the face, lips, and tongue.
• Fatalities laryngeal edema have been reported.
• Bowel or extremity angioedema is not commonly.
• Most frequently occurs within the first month of treatment
• 25% of patients experience their first attack of angioedema more than 6 months after beginning the ACE-I
• some patients have been on an ACE-I for years

• Discontinuation of the ACE-I leads to resolution of the problem
• many weeks before the risk of a recurrent attack is gone.
• Patients who remain on an ACE-I despite having experienced an angioedema attack
are at significant risk (greater than 50%) for a recurrent attack within 5 years.
• These patients can be safely switched to an ARB or an alternative class of anti
hypertensives.
• rare reports of ARB-associated angioedema
• it is recommended that introduction be delayed until the window of 6 weeks for recurrent
attacks has passed.

IDIOPATHIC NON-HISTAMINERGIC
ANGIOEDEMA (INH-AAE)

IDIOPATHIC NON-HISTAMINERGIC
ANGIOEDEMA (INH-AAE)
• Recurrent angioedema
• Did not respond to high-dose antihistamine
• Lacked any family history of angioedema
• Plasma bradykinin levels were shown to be elevated during swelling attacks.
• The mechanism has yet to be elucidated.
• Clinical features
• similar to that of mast cell–mediated idiopathic angioedema
• lack of response to the usual treatments for mast cell– dependent angioedema

DIAGNOSIS
• Negative family history does not rule out
• C1-INH-HAE (25% of cases may be a de novo mutation)
• Clinical suspicion of C1- INH-HAE-like symptoms at any age is an indication for screening.
• C1-INH-HAE screening includes
• functional and antigenic C1-INH levels and C4
• If screening is suggestive of C1-INH-HAE, a second test should be performed to confirm the diagnosis.
• If C1-INH-HAE is suggested by testing,
• all first- degree relatives in the ascending line should be screened
• including symptom-free individuals
Farkas H et al. Allergy 2017;72:300-13

INITIAL LAB: C4 à THE BEST FOR SCREENING
• Excellent screening tool for C1INH deficiency in patients > 1 yr
• Reduced C4 level between attacks in at least 95% of patients
• Normal C4 level during an attack strongly suggests a diagnosis other than C1INH deficiency
Low C4 level Normal C4 level
• HAE type 1
• HAE type 2
• Acquired C1-INH HAE
• HAE with normal C1 INH
• Idiopathic AE
• ACEI-associated angioedema

C1INH ANTIGEN AND FUNCTION
After first year of age
• C1 inhibitor antigen concentration <50% of normal values obtained on
2 separate occasions
• C1 inhibitor function <50% (chromogenic assay) or <84% (ELISA assay)
of normal values obtained on 2 separate occasions
• Mutation in C1-inhibitor gene that modifies protein synthesis or
function
Longhurst H. and Cicardi M. Lancet 2012;379:474–81

SPECIAL CONSIDERATION IN
PEDIATRIC PATIENTS
Prenatal diagnosis
• When: Disease-causing mutation has been detected in a C1-INH-HAE family
• By: chorionic villous sampling or amniocentesis
• On the basis of:
• No mutation can be detected in the C1-INH (SERPING1) gene in 8–10% of C1-INH-HAE.
• C1-INH-HAE has a highly variable disease severity within and between families with poor correlation
between gene defect and clinical severity.
• Advances in therapy have significantly improved the health-related quality of life (HRQoL) of patients.
• The decision whether to perform prenatal diagnosis should be made by the parents following appropriate
counseling and the careful evaluation of benefits and risks.

SPECIAL CONSIDERATION IN
PEDIATRIC PATIENTS
• Before the age of 1 year
• The antigenic and functional C1- INH levels may be lower than in adults, with the lowest levels in umbilical
cord blood.
• Both antigenic and functional C1-INH cord blood levels correspond to 70% and 61.8% of adult normal
values increasing to normal adult levels by the age of one year
• Genetic testing increases the diagnostic reliability in children and may be helpful in cases in which
biochemical measurements are inconclusive and the genetic mutation of the parent is known.
• All early complement testing performed in offspring of HAE-1/2 patients should be repeated after
the age of 1 year.
Longhurst H. and Cicardi M. Lancet 2012;379:474–81

OTHER LAB TESTS
• Autoantibodies to C1q, C1q level
• Dx à Acquired angioedema with C1INH deficiency
• Usually not indicated for testing in the pediatric ages
• C2, C3, and CH50 testing are not indicated for C1-INH-HAE diagnosis.
• SERPING1 or Factor XII gene sequencing may be helpful to confirm the
C1-INH-HAE.

TREATMENT OF HAE
• Acute treatment of attacks (on demand)
• Short term prophylaxis (pre-procedural)
• Long term prophylaxis (suppression of attacks)

Castelli R et al. Immunopharmacology and Immunotoxicology, 2013; 35(1): 181–190

ACUTE TREATMENT (ON DEMAND THERAPY)
• All attacks are considered for on-demand treatment
• Treat as early as possible
• Either C1-INH, ecallantide, or icatibant
• If not available, attacks should be treated
• solvent detergent-treated plasma (SDP) > fresh frozen plasma (FFP)
• Not advise; antifibrinolytics (tranexamic acid), androgens (danazol)
• no or only minimal effects
• All patients have sufficient medication for on demand treatment of two attacks and carry
on-demand medication at all times.

PLASMA-DERIVED C1-INH CONCENTRATE
(PDC1-INH)
• Cryodepleted human plasma by adsorption and precipitation, purification,
pasteurization, and virus filtration.
• Berinert (CSL Behring) and Cinryze (Shire HGT).
• The mean plasma half-life of pdC1-INH is longer than 30 hrs
• The safety and tolerability of all available pdC1-INH are good, and few adverse events
have been reported.
• The risk of allergic reactions is negligible.
• not associated with transmission of HBV, HCV, HIV

RECOMBINANT C1-INH
• Ruconest (Pharming)
• Recombinant human C1-INH (rhC1-INH)
• It is derived from the milk of transgenic rabbits
• 3-step purification procedure including cation exchange chromatography, anion exchange
chromatography, and affinity chromatography.
• Plasma half-life to approximately 3 hrs
• It is contraindicated in patients with known or suspected allergy to rabbits or
rabbit-derived products.
• favorable safety profile
• Transmission of human viruses is not a concern

https://www.ruconest.com/about-ruconest/

KALLIKREIN-INHIBITOR
• Ecallantide(Kalbitor; Shire), > 12 yrs in US
• 60-amino acid recombinant protein produced by expression in the yeast Pichia pastoris
• Plasma half-life of 2 hrs
• Serious hypersensitivity reactions, including anaphylaxis, which was reported in 3% to
4% of treated patients.
• Only be administered by a health care professional with appropriate medical support to
manage anaphylaxis

BRADYKININ-RECEPTOR ANTAGONIST
• Icatibant (Firazyr; Shire HGT), > 18 years
• 10-amino acid synthetic peptide, is a specific and selective competitive antagonist of
the bradykinin B2 receptor.
• plasma half-life of 1 to 2 hrs
• The safety and tolerability of icatibant are good
• transient local injection site reactions
• self-administered

PRE-PROCEDURAL (SHORT-TERM)
PROPHYLAXIS
• Swellings; near the site of intervention, usually occur within 48 h
• Pre-procedural prophylaxis reduces the risk of angioedema after interventions.
• Indication
• surgical trauma, dental surgery and other interventions associated with mechanical impact to the
upper aerodigestive tract (e.g. endotracheal intubation, bronchoscopy or
esophagogastroduodenoscopy)
• Although pre-procedural prophylactic treatments, break-through attacks can occur.
• The patients should remain under observation
• on demand treatment needs to be available

PRE-PROCEDURAL (SHORT-TERM)
PROPHYLAXIS
• C1-INH concentrate : Berinert, Cinryze
• 1st line treatment
• as close as possible to the start of the procedure
• 1000 units or a dose of 20 units/kg of pdC1-INH
• Fresh frozen plasma (FFP)
• 2nd line treatment
• greater risk of blood borne disease transmission
• Attenuated androgens : Danazol
• used for 5 days before and 2 to 3 days post event
• 2.5-10 mg/kg/day, maximum 600 mg/day
• Antifibrinolytic drugs : Tranexamic acid à not recommended by most experts

LONG TERM PROPHYLAXIS
• Long-term prophylaxis should be individualized
• activity of the disease, frequency of attacks, quality of life, availability of health-care
resources and failure to achieve adequate control by appropriate on-demand therapy
• Assessed regularly for efficacy and safety of the therapy, and dosage and/or treatment
interval should be adapted according to the clinical response.
• Upper airway edema and other attacks may occur despite the use of long-term prophylaxis.
• All patients using long-term prophylaxis should also have on-demand medication
(C1-INH concentrate, ecallantide, or icatibant)

LONG TERM PROPHYLAXIS
• C1-INH concentrate : Berinert, Cinryze
• 1st line treatment
• 1000 U IV twice a week or 40-60 U/kg SC twice a week (recent papers)
• Dose and/or frequency may need adjustment for optimum efficacy
• Attenuated androgens : Danazol
• 2nd line treatment
• 100 mg every other day and 200 mg of danazol 3 times a day (not exeed200 mg/day)
• The minimal effective dose should be used.
• Antifibrinolytic drugs : Tranexamic acid
• not recommended due to less efficacy and side effect
• Except in children à more prefer to Danazol
• 30 to 50 mg/kg to 6 g daily

ANDROGEN
• Side effects are numerous and involve the majority of patients.
• Side effects appear to be dose related.
• Virilization, menstrual disorders, diminished libido, hirsutism
• weight gain, headache, myalgia, depression, and acne.
• Absolutely contraindicated during pregnancy à virilization of the female fetus
• Children and adolescents
• interfere with the natural growth and maturation process.
• Drug interaction with statins
• Hepatotoxicity à hepatic adenomas and hepatic carcinoma
• Careful surveillance
• semiannual blood and urine tests (standard urine test strip)
• ultrasound of the liver once a year Maurer et al. World Allergy Organization Journal 2018;11:5

TRANEXAMIC ACID
• Data for their efficacy are largely lacking.
• Side effects are usually minor.
• GI upsets, myalgia/creatine kinase elevation, and a theoretical risk of
thrombosis.
• Contraindications/precautions
• the presence of thrombophilia or increased thrombotic risk or acute
thrombosis à deep venous thrombosis, pulmonary embolism.

• Study design: international, prospective, multicenter, randomized, double-blind,
placebo-controlled, dose-ranging, phase 3 trial
• Aim: evaluate the efficacy and safety of self-administered subcutaneous CSL830
• Participants:>/= 12 years of age, HAE 1-2, >/=4 attacks requiring immediate
treatment or medical attention or causing clinically significant functional impairment
over a 2-month period within 3 months before screening
Longhurst H. et al. N Engl J Med 2017;376:1131-40

Primary end points: the number of attacks of angioedema
Secondary end points: the percentage of patients who had a response (≥50% reduction vs.
placebo in the number of attacks) and the number of times that rescue medication was used.
Exploratory end points: the number of days of angioedema symptoms, severity of attacks, and
proportion of patients in whom the number of attacks was reduced to less than one attack per 4-
week period from one attack or more per 4-week period with placebo.

Conclusion
In patients with HAE, the
prophylactic use of a subcutaneous
C1 inhibitor twice weekly
significantly reduced the frequency
of acute attacks
1st C1 inhibitor subcutaneous route
since July 2017

• Study design: phase 1b, multicenter, double-blind, placebo-controlled, multiple-ascending-dose trial.
• Aim: To assess safety and side-effect profile, characterize the pharmacokinetic and pharmacodynamic
characteristics, and evaluate the immunogenicity of multiple subcutaneous lanadelumab
administrations.
• Participants: >/= 18 years of age, HAE1/2 Patients, Patients must have had two or more attacks of
angioedema per year, with at least one attack in the previous 6 months.
• Intervention: 4 dose groups (30 mg, 100 mg, 300 mg, and 400 mg), with lanadelumab administered in
a staggered, dose-escalating fashion, 2:1 ratio (active drug N=24 or placebo group N=13)
Banerji A. Et al. N Engl J Med 2017;376:717-28

Conclusion
• This phase Ib trial supports the continued investigation of lanadelumab.
• No patients discontinued the trial because of adverse events, and the
low incidence and severity of adverse events and the type of events did
not indicate a safety signal.

1st monoclonal antibody for
prevention HAE attack
since August 2018

• Study design: phase 2, randomized, double-blind, placebo-controlled, parallel-group
• Aim: To evaluate the safety, adverse event profile, pharmacokinetics, pharmacodynamics and efficacy of BCX7353
• Participants: 18 to 70 years of age, HAE1/2 Patients, rate of angioedema attacks of at least 2 attacks/month for 3
consecutive months within the 6 months before the screening visit.
• Intervention: 4 doses of BCX7353 (62.5 mg, 125 mg, 250 mg, and 350 mg once daily) for the prevention of
angioedema attacks over a 28-day period
• Primary end points: the number of confirmed angioedema attacks
• Secondary end points: angioedema attacks according to anatomical location and quality of life
Aygören-Pürsün E. et al. N Engl J Med 2018;379:352-62

Conclusions
• Once-daily oral administration of BCX7353 at a dose of 125 mg or
more resulted in a significantly lower rate of attacks of hereditary
angioedema than placebo.
• Mild gastrointestinal symptoms were the principal side effect.

ADJUNCTIVE TREATMENTS
• Moderate and severe abdominal attack
• Narcotics, anti emetics, hydration
• Oropharyngeal-laryngeal attack
• Admit, Maintain patency of airway
• Observe sign impending airway closure
• change in voice, loss of the ability to swallow and difficult breathing
• Back up tracheostomy
• Genitourinary attack
• Pain control, catheterization

EDUCATION AND COUNSELLING
• Parents should be provided with comprehensible information on specific characteristics and
on management options for all age groups at the time of diagnosis and with each follow-up
• Teachers and child care workers should receive detailed written information on the disease.
• Information card containing a description of emergency procedures along with acute
treatment products
• Alert devices, including identifying wrist or neck bands with emergency contact information,
should also be considered
• All patients who are provided with on-demand treatment licensed for self-administration
should be taught to self-administer.

AVOIDANCE OF TRIGGERS
• The aim of management at all ages should be to normalize activities
and lifestyle whenever possible
• ACEIs and estrogen-containing oral contraceptives
• Avoiding contact sports and other activities involving physical trauma
• Immunizations
• usual schedule vaccination for pediatrics.
• HBV, HAV vaccine à high chance of receiving blood products
• Annual influenza vaccine à URI can trigger upper airway swelling

FAMILY SCREENING
• Family members including grandparents, parents, siblings, children, and grandchildren of HAE-
1/2 patients should be screened for C1-INH function, C1-INH protein, and C4 plasma levels
• Indication base on
• autosomal dominant inheritance
• delayed diagnosis leads to morbidity and decreased quality of life without appropriate therapy.
• risk of the first angioedema event being fatal due to airway involvement without appropriate therapy.

TREATMENT OF HAE WITH NORMAL C1INH
• No controlled treatment studies
• May respond to many of the same drugs as in patients with HAE due to reduced C1INH
• Some had improved on long term prophylactic therapy with danazol, progesterone or tranexamic acid
• Corticosteroids and antihistamines ineffective
• Prognosis:
• The frequency of acute attacks varies considerably from patient to patient
• There are many patients with a low clinical disease expression
• Cases of asphyxia have been described

TREATMENT OF ACEI ASSOCIATED
ANGIOEDEMA
• Discontinue of offending drugs time lag up to 6 weeks
• Safely switched ARB
• delayed introduction until the window of 6 weeks
• Icatibant and FFP
• Icatibant and ecallantide may prove useful
TREATMENT OF NONHISTAMINERGIC
IDIOPATHIC ANGIOEDEMA

HAE DURING PREGNANCY
AND LACTATION

COURSE OF DISEASE AND CLINICAL PICTURE
• Pregnancy can mitigate, aggravate, or have no effect.
• Pregnant HAE-1/2 patients require vigilant care and meticulous monitoring by an HAE expert.
• Labour and delivery only rarely induce an attack
• may occur either during labour or within 48 h of delivery.
• Close follow-up is recommended for at least 72 h postpartum after uncomplicated vaginal delivery.
• Breastfeeding may be associated with an increased number of maternal attacks
• abdominal symptoms and facial edema
• still recommended based on benefits provided to the infant
• Care for C-section, especially if intubation is necessary, should proceed as in any other surgical
procedure performed on a patient with HAE-1/2

DIAGNOSIS
• Plasma levels of C1-INH decrease during pregnancy, and return to normal after delivery.
• measurements of levels of C1- INH function, C1-INH protein and C4 for the purpose of
diagnosing HAE-1/2 during pregnancy should be interpreted with caution.
• It is recommended to repeat the measurements after childbirth to confirm the
diagnosis of HAE

THERAPY
• C1-INH concentrateis recommended as first-line therapy.
• Then SDP > FFP
• During pregnancy
• Pre-procedural prophylaxis is recommended, preferably with C1-INH concentrate,
• before chorionic villus sampling, amniocentesis, and induced surgical abortion
• LTP may become indicated during pregnancy with C1-INH concentrate
• Women experiencing an increase of attack frequency.
• Antifibrinolytics may be considered if C1-INH concentrate is unavailable, but efficacy is not proven
• Androgens are contraindicated.

THERAPY
• During labour and delivery
• Few women have developed angioedema
• Routine administration before uncomplicated natural delivery is not mandatory
• For delivery: Vaginal delivery is preferred
• Recommend when
• recurring frequently during the third trimester, patient’s history includes genital edema caused by
mechanical trauma, forceps delivery or vacuum extraction
• Pre-procedural prophylaxis with C1-INH concentrate and epidural anesthesia is recommended before a
caesarean section, and intubation should be avoided if possible.

THERAPY
• During lactation
• Plasma-derived C1-INH concentrate is considered the best therapy for on-demand treatment,
short-term prophylaxis and long-term prophylaxis
• Androgens and antifibrinolytics are secreted in breast milk.
• Tranexamic acid was found to be safe during breastfeeding

Hereditary Angioedema Guide: Pathogenesis, Classification, Diagnosis and Treatment

Recommandé

Recommandé

Contenu connexe

Tendances

Tendances (20)

Similaire à Hereditary Angioedema Guide: Pathogenesis, Classification, Diagnosis and Treatment

Similaire à Hereditary Angioedema Guide: Pathogenesis, Classification, Diagnosis and Treatment (20)

Plus de Chulalongkorn Allergy and Clinical Immunology Research Group

Plus de Chulalongkorn Allergy and Clinical Immunology Research Group (20)

Dernier

Dernier (20)

Hereditary Angioedema Guide: Pathogenesis, Classification, Diagnosis and Treatment