Determination of the activity of complement factor C1 inhibitor (C1INH). Everyone needs to know about HAE (hereditary angioedema)


A C1 inhibitor is an inhibitor whose main function is to inhibit the complement system to prevent spontaneous activation. It is an acute phase protein circulating in the blood. It also inhibits fibrinolytic, kinin pathways and the cascade of reactions in the blood coagulation system. Increased or decreased activity of complement factor C1 inhibitor may indicate a number of diseases immune system.

Synonyms Russian

C1-inhibitor, C1-INH test.

English synonyms

C1-inh, C1 esterase inhibitor.

Research method

Enzyme-linked immunosorbent assay (ELISA).

Units

cu/ml (arbitrary units in milliliter).

What biomaterial can be used for research?

Venous blood.

How to properly prepare for research?

  • Eliminate fatty foods from your diet for 24 hours before the test.
  • Avoid physical and emotional stress for 30 minutes before the test.
  • Do not smoke for 30 minutes before the test.

General information about the study

The complement system is part of the innate immune system. It consists of nine proteins - from C1 to C9. They help the body recognize foreign cells that may cause disease. Some health problems can cause deficiencies in these proteins. Blood tests are needed to check complement protein levels. One such test is the C1INH inhibitor activity test. This will help determine whether your body has enough C1-INH protein.

Hereditary angioedema is a rare autosomal dominant disease caused by mutations in the C1 inhibitor gene (C1INH), leading to decreased plasma C1 inhibitor levels or impaired protein function. The cause of the disease as a biochemical defect is a deficiency of the C1-esterase inhibitor. This vascular reaction deep layers of skin and mucous membranes, accompanied by local expansion and increased permeability blood vessels, resulting in tissue swelling. The swelling is asymmetrical; when pressed, there is no trace left on it; disappears without a trace. It is caused by a temporary increase in blood vessel permeability, mediated by the release of one or more neurotransmitters. The C1 inhibitor disrupts the binding of C1q to C1r2s2, thereby limiting the time during which C1s catalyzes the activation cleavage of C4 and C2. In addition, C1inh limits the spontaneous activation of C1 in the blood plasma. At genetic defect dinh develops hereditary angioedema. Its pathogenesis consists of chronically increased spontaneous activation of the complement system and excess accumulation anaphylactins (C3a and C5a), which cause edema.

The C1INH activity test can be used to screen for hereditary angioedema. Symptoms:

  • swelling in the legs, face, arms, respiratory tract and gastrointestinal wall;
  • abdominal pain;
  • nausea and vomiting.

The study can help you learn how a person responds to treatment for autoimmune diseases such as systemic lupus erythematosus (SLE).

When is the study scheduled?

  • In the presence of angioedema;
  • if you suspect the presence of a systemic autoimmune disease, in particular systemic lupus erythematosus (although the study itself, determining the activity of the complement factor C1 inhibitor, does not allow one to unambiguously verify a particular diagnosis; additional laboratory and instrumental research is required).

What do the results mean?

Reference values: 0.7 - 1.3 cu/ml.

Reasons for increased activity of complement factor C1 inhibitor:

  • infectious diseases.

Reasons for decreased activity of complement factor C1 inhibitor:

  • systemic lupus erythematosus;
  • recurrent bacterial infections;
  • angioedema;
  • sepsis.


Important Notes

  • Increased complement factor C1 inhibitor activity may occur in the presence of infectious disease. However, this test is not routinely performed to detect infections.
  • A change in complement factor C1 inhibitor activity is not a diagnosis. A number of laboratory and instrumental studies, specialist consultation.
  • Antinuclear factor on Hep2 cells
  • Immunological test for determining monospecific agglutinins in hemolytic anemia

Who orders the study?

Doctor general practice, therapist, infectious disease specialist, hematologist, rheumatologist, immunologist, allergist, neurologist, dermatologist.

Literature

  • Davis AE (September 2004). "Biological effects of C1 inhibitor". Drug News Perspective. 17 (7): 439–46.
  • Cicardi M, Zingale L, Zanichelli A, Pappalardo E, Cicardi B (November 2005). "C1 inhibitor: molecular and clinical aspects". Springer Semin. Immunopathol. 27 (3): 286–98.
  • Davis AE (January 2008). "Hereditary angioedema: a current state-of-the-art review, III: mechanisms of hereditary angioedema." Ann. Allergy Asthma Immunol. 100(1 Suppl 2): ​​S7–12.
  • Zuraw BL, Christiansen SC. Hereditary angioedema and bradykinin-mediated angioedema. Middleton's Allergy: Principles and Practice, 37, 588-601.

Cl-inhibitor (CI) deficiency leads to the appearance of characteristic clinical syndrome- hereditary angioedema (HAE). The main clinical manifestation of hereditary angioedema is recurrent edema, which can threaten the patient’s life if it develops in vital locations.

Pathogenesis of Cl-inhibitor deficiency

The cause of the deficiency is a mutation in the Cl inhibitor gene - a serine protease that inactivates the C1r and Cls components of complement, as well as the kallikrein-kinin system and activated factors XI and XII of the coagulation cascade. Although the C1 inhibitor is not a significant inhibitor of plasmin, it is consumed by plasmin, and in its absence, activation of plasmin is one of the most important triggers for edema episodes. The main reason for increased vascular permeability in HAE is an excess of bradykinin, which is a consequence of excessive proteolysis of the high-molecular-weight kininogen by kallikrein.

Congenital C1I deficiency is an autosomal dominant disorder with equal racial and gender distribution and is the most common of all complement system defects. In patients with hereditary angioedema, three main types of defects are distinguished: in 85% of cases, there is a decrease or absence of Cl-inhibitor due to impaired transcription; in the presence of a missense mutation in the active site, the concentration of Cl-inhibitor may be normal or even increased, but the protein is nonfunctional. Type 3 HAE is caused by the presence of autoantibodies to the C1 inhibitor.

Symptoms of Cl-inhibitor deficiency

Signs of the disease in patients with hereditary angioedema are observed mainly in the first years of life. In most cases described in the literature, the manifestation of the disease occurred before the patient was 18 years of age, although there are cases of primary detection of the disease at the age of 52 years. Clinically, hereditary angioedema is characterized by edema various parts bodies. Swelling occurs rapidly, reaches a maximum within 1-2 days and resolves spontaneously after 3-4 days. Edema is usually not accompanied by rash, itching, or discoloration skin, pain symptoms. However, swelling of the intestinal wall can manifest as severe abdominal pain. In this regard, patients with these types of manifestations of hereditary angioedema are frequent subjects surgical interventions. In some patients, loss of appetite, vomiting and cramping abdominal pain are the only clinical manifestations hereditary angioedema, with complete absence edema subcutaneous tissue. Laryngeal edema is often fatal, especially among children. younger age. The factors that provoke edema have not been determined, although patients often associate attacks with stress or minor trauma, usually with swelling of the extremities. Facial swelling and respiratory tract may occur after tooth extraction or tonsillectomy.

Diagnosis of Cl-inhibitor deficiency

The normal level of Cl-I is 0.15-0.33 g/l for adults and 0.11-0.22 g/l for children. The functional activity of Cl-I in children of the first year of life is 47-85% of that in adults. Decreased concentration of C1I or significant reduction functional activity S1I is diagnostic. During an acute attack of hereditary angioedema, there is a significant decrease in the hemolytic titers of C4 and C2, and, unlike patients with systemic lupus erythematosus and other immune complex diseases, the level of C3 remains normal. Due to the autosomal dominant pattern of inheritance, patients with hereditary angioedema often have a positive family history.

Treatment of Cl-inhibitor deficiency

Various types of drugs have been proposed for the treatment of hereditary angioedema. They can be divided into the following groups:

Androgens. In I960, he first showed that methyltestosterone has a striking preventive effect on the severity and frequency of HAE attacks. In 1963, a synthetic analogue of methynyltestosterone, Danazol, was obtained. Primary pharmacological actions The drug is inhibition of gonadotropin, suppression of the synthesis of sex hormones, competitive binding to progesterone and androgen receptors. Danazol is used in the treatment of endometriosis, gynecomastia, increased blood loss associated with menstruation, hemophilia A and B to reduce bleeding and in idiopathic thrombocytopenia, where the drug can help increase the number of platelets. Danazol has been shown to increase Cl-I concentrations in most patients with hereditary angioedema. Although Danazol is one of the most commonly used agents in the prophylactic therapy of hereditary angioedema, its mechanism of action remains unknown. Unfortunately, with prolonged prophylactic use, the presence of androgens typical of drugs is observed. side effects. There is a tendency towards obesity, amenorrhea, decreased libido, increased aminotransferases and cholesterol, muscle spasms, myalgia, increased fatigue, headache. The use of the drug in children and pregnant women is especially limited.

Antifibrinolytic drugs. The first successful use of antifibrinolytic drugs in hereditary angioedema was described by Swedish doctors. Alpha-aminocaproic acid, which is a plasmin inhibitor, as well as tranexamic acid can be used with partial success to prevent attacks of hereditary angioedema, especially if danazol cannot be used. In acute attacks of hereditary angioedema, therapy with these drugs is ineffective. Alpha-aminocaproic acid has the following side effects: nausea, headaches, diarrhea, myositis, and a tendency to develop thrombosis.

Transfusion of fresh plasma and purified Cl-I. As a rule, during an attack of hereditary angioedema, transfusion of fresh frozen plasma reduces the intensity of edema within minutes. However, fresh frozen plasma containing C1-I also contains all other complement components, the presence of which in the transfused drug can worsen the patient’s condition. Moreover, fresh frozen plasma is a possible source of such viral infections like HIV, hepatitis B and C. For last years Cryoprecipitate Cl-I is used successfully in many countries. From all points of view, C1-I is an ideal drug for patients with a high risk of developing edema of the upper respiratory tract and for patients in whom the use of Danazol does not lead to an increase in the concentration of C1-I or is contraindicated.

Summarizing the above, it is necessary to take into account a three-phase approach to the treatment of hereditary angioedema: long-term preventive therapy, short-course preventive therapy before elective intervention, and therapy acute attacks hereditary angioedema. Currently, long-term preventive therapy is carried out with androgens and antifibrinolytic drugs. Preventive therapy short courses, mainly in patients with hereditary angioedema undergoing dental and surgical procedures, as well as therapy for life-threatening edema is carried out with fresh frozen plasma and, if available, C1-I cryoconcentrate.

Human blood contains proteins that provide immunity. A group of these proteins is called the complement system. They contain a C1-esterase inhibitor. It controls the synthesis of another protein, bradykinin, which is responsible for vasodilation to lower blood pressure.

Disturbances in the functioning of the C1 inhibitor are associated with the mutated C1NH gene. As a result, control over the production of the bradykinin protein is lost. Because of this, a person can develop very rare disease– hereditary angioedema, abbreviated as HAE.

Description and symptoms of the disease

HAE – recurring edema associated with the work of peripheral vascular system. Uncontrollably produced bradykinin causes dilation of blood vessels and a decrease in the permeability of their walls. The result is the accumulation of fluid in the deep layers of the skin or submucosal layer.

In 60% of patients, the first attack of the disease occurs in childhood or adolescence. For many, the first swelling appears in mature age, for a few – in the elderly.

The reasons that provoke the first angioedema are as follows.

  1. Hormonal surge of adolescence.
  2. Prolonged stressful situation.
  3. Any injury, no matter how small.
  4. Surgical intervention.
  5. Dental treatment.
  6. Chronic infection.
  7. Hypothermia.
  8. Taking certain medications ( oral contraceptives, ACE inhibitors).

Locations:

  • with angioedema of soft tissues, tumors appear on the face, arms, legs, abdomen, back;
  • on the mucous membranes of the upper respiratory tract, gastrointestinal tract.

Symptoms of angioedema:

  1. Tumors of various sizes on the body, usually painless, non-itching, and do not change color. They feel like they are bursting and are quite dense to the touch.
  2. The size of the lips, ears, eyelids, and fingers may increase significantly.
  3. Sometimes, before the onset of swelling, a hives-like rash appears.
  4. With swelling of the upper respiratory tract, the voice changes, a dry cough, wheezing appears, and breathing becomes difficult, even to the point of suffocation.
  5. Tumors of the gastrointestinal tract give severe pain, nausea, vomiting, anorexia, diarrhea.

The appearance of recurring angioedema (or Quincke's edema) is caused not only by the factors that provoked the onset of the disease. Sometimes a little pressure is enough for dental or gynecological examination. But most often, edema develops spontaneously, and antiallergic drugs are ineffective.

If you seem to have the same symptoms as outlined above, but have no idea what it is, the photo in our article shows what it looks like. And if the swelling in the photo is similar to your swelling, it is advisable to consult a specialist.

It is often difficult to determine that a patient has a congenital disease. For decades in a row, doctors can make incorrect diagnoses, suspecting allergic angioedema, anaphylaxis, appendicitis, intestinal obstruction, liver disease, kidney disease, gynecological pathologies, even meningitis. The disease can occur without obvious and external swelling, which further complicates its diagnosis.

The most dangerous is angioedema of the larynx. It blocks the access of air to the lungs, and the person suffocates. Sudden occurrence fast development This condition leads to death in two out of five cases.

Types of congenital angioedema

The disease is inherited. If at least one of the parents suffers from it, then the child with a 50% chance will also receive the mutated gene. But sometimes it happens that healthy family a baby is born with HAE. He becomes the first carrier of a hereditary disease.

Doctors diagnose three types of HAE.

  1. A decrease in the concentration of C1 inhibitor in complement is observed in the vast majority of patients (85%).
  2. The concentration is normal or increased, but at the same time, the functionality of the protein is minimal.
  3. Concentration and functionality are within normal limits, but symptoms of the disease are present.

    4. There are few such cases; experts suggest the presence of a mutation that has not yet been studied.

For accurate diagnosis the doctor finds out how long ago and how often edema appears, and whether there is a hereditary factor. In the acute stage, an examination is carried out. Based on a blood test from a vein, it is determined immune status, and specifically the concentration and functionality of the C1 inhibitor. At the same time, the presence of other similar diseases is excluded.

It is important that immediate family members undergo testing. In its absence, the probability of occurrence critical situation increases to 35%. That is, every third case of edema can affect the larynx and cause death.

Treatment of hereditary angioedema

Medicine does not have a method for correcting mutations. But there are ways to compensate for their influence, thereby controlling the disease. The main methods of treating angioedema are used in the acute stage. At the same time, corticosteroid drugs and antihistamines are ineffective.
Methods used:

  • preventative hormone therapy– used for frequent swelling, is rarely used due to side effects (androgens are synthetic substitutes for male hormones);
  • medications that reduce the effect of bradykinin (administered in the form of solutions, swelling disappears in a maximum of one and a half hours);
  • drugs that replace the missing amount of protein: synthetic (injection solutions) and donor (fresh frozen plasma, aminocaproic acid).

Examples modern drugs from angioedema:

Popular:

Traditional medicine does not know any means that can restore disorders of the primary immune function.

A reader from the Vitebsk region, Regina Kh., called the editor with a request to print information for doctors of various specializations about a rare disease that has been suffering for many years - hereditary angioedema.

“I always warn the dentist and otolaryngologist about my diagnosis,” the woman explained. - I say that manipulations on soft tissues can cause severe swelling, which is difficult to cope with. Some people are perplexed. And some even take me for a malingerer or a hypochondriac.

Tell us about the features of this disease, prevention of manifestations and treatment.”

Tatiana Uglova, head of laboratory clinical trials Scientific Department of the Republican Scientific and Practical Center for Pediatric Oncology, Hematology and Immunology, Candidate of Medical Sciences. Sciences, Associate Professor.

Hereditary angioedema (HAE) is a rare, potentially life-threatening, genetically determined disease with an autosomal dominant inheritance pattern and incomplete penetrance. Diagnosis of HAE is not difficult, but, unfortunately, due to insufficient alertness of doctors, the pathology may remain unrecognized for many years. Patients are observed at different specialists. Often the diagnosis is anaphylaxis, angioedema or allergic angioedema. However, treatment approaches are fundamentally different: antihistamines, glucocorticosteroids, epinephrine, successfully used for allergic angioedema, are ineffective for HAE.

HAE is a primary (congenital) immunodeficiency without infectious syndrome. Key role the pathogenesis is played by a decrease in the amount and/or activity of the esterase inhibitor of the complement component C1 (C1 inhibitor) due to a defect in the SERPING gene (C1 INH), which is mapped on chromosome 11 (11q12-q13.1) and encodes the synthesis of the C1 inhibitor. Approximately 300 gene mutations have been described in patients with HAE, most of which involve exon 8.

The C1 inhibitor is produced in hepatocytes and monocytes. It inactivates the C1 component of complement and the classical pathway of complement activation by binding to C1r and C1s, preventing the transition of prekallikrein to kallikrein, plasminogen to plasmin, and activation of coagulation factor XII. With its deficiency, the content of bradykinin increases with a subsequent increase in permeability vascular wall and the development of edema. Histamine is not involved in the development of edema in HAE.

Women have more swelling

The prevalence of HAE is from 1: 10,000 to 1: 50,000 population. Men and women get sick equally often, although in the fair sex the disease is more severe.

In 40% of patients, the first episode of HAE occurs before the age of 5 years, in 75% - before the age of 15 years. Patients with early onset of HAE attacks have a worse prognosis. In 5% of adults, the disease is asymptomatic; they were diagnosed after identifying the disease in their children.


How to recognize


The dominant manifestation is edema. They are pale, dense (when pressed, there is no depression left), limited. They are provoked by infections, injuries, dental interventions, compression of the limbs, physical stress, tonsillectomies, emotional arousal, stressful situations, sharp drop temperature environment, pregnancy, menstruation, taking certain medications (ACE inhibitors - captopril, enalapril, ramipril, lisinopril, etc.; angiotensin II receptor antagonists - eprosartan, valsartan, telmisartan; drugs containing estrogen hormones). However, most attacks develop spontaneously.

Approximately 33% of patients have attacks more often than once a month, and in 40% - 6–11 times a year. And only 22% have them from time to time.

As a rule, swelling is localized on the skin of the face (lips, eyelids); the genitals are often involved. There is no itching. The patient feels an “increase” and thickening of the skin or tingling in the affected area, in some cases pain.

Swelling increases over 12–24 hours and usually lasts 72 hours. For some, symptoms persist for 5 days, and swelling migrates.

70–80% of patients with HAE complain of abdominal pain. In a quarter it is dominant and is caused by swelling of the mucous membrane of any part of the gastrointestinal tract. The intensity of pain is similar to that of an “acute abdomen”; sometimes accompanied by nausea, vomiting, diarrhea, rarely constipation and intestinal obstruction.

Absence of inflammatory changes in peripheral blood analysis, ultrasound abdominal cavity help in differential diagnosis.

When the urinary system is damaged, pain syndrome, urinary retention or anuria.

IN in rare cases when the meningeal membranes are involved, they are fixed meningeal symptoms(stiff neck, sharp headache, vomiting), diplopia, ataxia. When the labyrinthine systems are damaged, Meniere's syndrome develops. Very rarely - epileptic seizure, Raynaud's syndrome.

Swelling of the mucous membranes of the larynx, nose, and tongue is potentially life-threatening (risk of asphyxia). Precursors are difficulty swallowing, hoarseness, dysphonia, aphonia, anxiety, shortness of breath. In this situation, urgent hospitalization and emergency medical interventions, because urgent state develops, as a rule, within 8–12 hours, but can be faster.

Diagnosis of HAE

  1. History: family history of edema various localizations; death of relatives from laryngeal edema; hospitalization for acute abdomen»without subsequently establishing a topical diagnosis; association of edema with trauma, emotional stress, taking ACE inhibitors or angiotensin II receptor blockers; presence of a patient with HAE in the family.
  2. Results of physical examination: pale, dense swelling, no itching, presence of warning signs, clinical picture, inefficiency antihistamines and glucocorticosteroids.
  3. Laboratory examination data:
  • V general analysis blood, hematocrit may increase, eosinophilia and leukocytosis are absent;
  • C4 component of complement in blood serum - less than 14 mg/l;
  • C1q - more than 77 mg/l;
  • C1 antigenic inhibitor - below 199 mg/l;
  • functional activity of the C1 inhibitor - up to 72% of reference values;
  • CH 50;
  • fragments of prothrombin (F1+2) and D-dimers during an attack.
Genetic research.

NAO classification

Type I- characterized by a decrease in the C1 inhibitor in the blood serum and the C4 component of complement (the latter is a screening factor). C1q level is normal. Occurs in 80–85% of patients. Caused by a mutation in the SERPING gene.

Type II- the activity of the C1 inhibitor is reduced at normal or increased concentrations. Complement C4 levels are low. C1q level is unchanged. Occurs in 10–15% of cases. It is caused by point mutations in the SERPING gene.

III type- normal levels C1 inhibitor, C4 and C1q complement components. The reason is mutations in the F12 gene, encoding coagulation factor XII (c.1032C->A, c.1032C->G, Thr309 Lys). Women are affected. Characteristic low level angiotensin I.

C1 inhibitor deficiency can be acquired and is observed in patients with lymphoproliferative diseases (type I), with autoimmune, oncological pathologies, and liver diseases (type II). A sign of acquired forms (as opposed to HAE) is a low level of C1q.

Differential diagnosis it is also necessary to carry out with angioedema, the mediator of which is histamine. Edema in this case is hot, hyperemic, itchy, occurs quickly (from several minutes to an hour), and is often accompanied by urticaria. Precursors are not typical. Serum C4 levels are normal.
Antihistamines are effective.

Therapeutic tactics. Options

Requires ongoing lifelong prevention acute manifestations diseases. If they occur, stop them. At the III International Congress on HAE in Toronto (2010), an international consensus on the diagnosis, treatment and management of HAE was adopted: indications and principles for the treatment of acute attacks, short-term and long-term prevention were determined.

A. Relief of acute attacks
1. Peripheral edema mild degree do not require emergency treatment.
2. In the presence of severe peripheral edema, causing a decrease in functional activity, -
1st line therapy:

  • intravenous
2nd line therapy:
  • antifibrinolytics (tranexamic acid in a dose of 1–1.5 g orally every 3–4 hours, -aminocaproic acid 7–10 g/day.
3. In the presence of abdominal syndrome:
  • hospitalization;
  • consultation with a surgeon to exclude acute surgical pathology;
  • bradykinin inhibitors (icatibant) - contraindicated under 18 years of age;
  • administration of C1 inhibitor concentrate (donor or recombinant) according to the instructions for use;
  • native or fresh frozen plasma.
4. Swelling in the head, neck, tongue with slowly increasing obstruction of the upper respiratory tract:
  • hospitalization;
  • bradykinin inhibitors (icatibant) - contraindicated under 18 years of age;
  • administration of C1 inhibitor concentrate (donor or recombinant) according to the instructions for use;
  • native or fresh frozen plasma;
  • antifibrinolytics (tranexamic acid at a dose of 1–1.5 g orally every 3–4 hours), -aminocaproic acid intravenously at a dose of 5–10 g (100–200 ml of a 5% solution), then at a dose of 5 g (100 ml 5 % solution) every 4 hours;
  • inhalation of β-adrenergic agonists;
  • if ineffective - intubation, conicotomy, tracheostomy.
5. Swelling in the head, neck, tongue with rapidly increasing life-threatening obstruction of the upper respiratory tract:
hospitalization in the department intensive care;
Stage 1: choice of tactics depending on the clinical situation - conicotomy, tracheostomy, intubation;
2nd stage:
  • bradykinin inhibitors (icatibant) - contraindicated under 18 years of age;
  • administration of ε-aminocaproic acid according to the instructions for use;
  • native or fresh frozen plasma;
  • antifibrinolytics (tranexamic acid at a dose of 1–1.5 g orally every 3–4 hours; -aminocaproic acid intravenously at a dose of 5–10 g (100–200 ml of 5% solution), then at a dose of 5 g (100 ml of 5% solution solution) every 4 hours;
  • inhalation of β-adrenergic agonists.
B. Short-term prevention of attacks
Indications: dental procedures, planned surgery, invasive examination methods, upcoming emotional stress (funeral, exams, etc.).
1st line therapy- administration of C1 inhibitor concentrate (donor or recombinant) according to the instructions for use 1–1.5 hours before.
2nd line therapy- danazol 3 days before and 3 days after; antifibrinolytics (-aminocaproic acid 16 g/day in 4 doses - 2 days before and after, tranexamic acid 4 g/day in 4 doses - 2 days before and after manipulation).

B. Long-term prevention of seizures
Indications:
  • exacerbations more than once a month;
  • if you have ever experienced swelling of the larynx;
  • if tracheal intubation or hospitalization in the intensive care unit has ever been required;
  • attacks are accompanied by temporary disability or absence from classes for more than 5 days per month;
  • significant decrease in quality of life;
  • remoteness of place of residence from health care institutions;
  • Seizures are usually rare.
1st line therapy- danazol
(10 mg/kg, but not more than 800 mg/day with a gradual decrease to 2 mg/kg/day), antifibrinolytics.
2nd line therapy- C1 inhibitor concentrate (donor or recombinant) as required.

When preparing women with HAE for pregnancy and the entire gestation period, only C1 inhibitor concentrate (donor or recombinant), native or fresh frozen plasma, and antifibrinolytics can be used (with caution, monitoring the coagulogram once every 2 weeks). Observation by an immunologist is indicated throughout the entire period of pregnancy with the determination of an algorithm for accompanying childbirth.

It is advisable for people with HAE to carry a “HAE patient passport” or a medical bracelet, which contains information about the disease and recommendations for emergency care.

Treatment should be started as early as possible!
  1. C1 inhibitor concentrate (C1-INHIBITOR).
    A) native C1 inhibitor (isolated from plasma): Berinert, Cinryze(in adolescents and adults), Cetor;
    b) recombinant C1-inhibitor (obtained from the milk of genetically modified rabbits): Rhucin.
  2. Bradykinin receptor antagonists: Firazyr (Icatibant) .
    Adults only. In pediatrics, research continues.
  3. Kallikrein inhibitor: Kalbitor (Ecallantide)
  4. Fresh frozen plasma, if it is not possible to use C1 inhibitor drugs and other modern medications.
*according to NAO Consensus 2010

Long-term prevention of Hereditary Angioedema

According to Craig et al. (2009), long-term prophylaxis is required for patients if:

  • frequency of exacerbations of HAE more than one exacerbation per month;
  • ever experienced swelling of the larynx;
  • ever required tracheal intubation or admission to the intensive care unit;
  • attacks of HAE are accompanied by temporary disability or absence from classes for more than 10 days per year;
  • due to attacks of HAE, there is a significant decrease in quality of life;
  • the patient has any drug addiction;
  • patient contact with health centers is limited;
  • the patient experiences a sharp development of exacerbations of HAE;
  • if the so-called is ineffective on-demand therapy(therapy on demand).

For long-term prevention, experts from the International Consensus on the Treatment of HAE (2010) recommend the following groups of drugs:

  1. T.N. "lightweight" androgens: Stanozolol, Danazol, Oxandrolone.
    This group of drugs is quite effective, but has big amount serious side effects. And, if to receive clinical effect(controllable conditions) a dose of more than 200 mg/day is required (according to Danazol), then the expected benefit should be weighed and possible risk development of side effects.
  2. Fibrinolysis inhibitors (antifibrinolytics): ε-aminocaproic And Tranexamic acids.
    These drugs can be effective for long-term prevention, but have numerous side effects, and therefore experts prefer the use of androgens over this group, as they are more effective.
  3. C-1 inhibitor
    a) native (plasma): Cinryze(in adolescents and adults), Berinert, Cetor,
    b) recombinant: Rhucin, Ruconest- while it's passing clinical trials for permission to use as prophylactic). Its effectiveness has been shown in multicenter studies.

Short-term prevention of Hereditary Angioedema

Drugs used to treat exacerbations of HAE are used. In case of prodromal symptoms (precursors), it may be effective Tranexamic acid or Danazol for 2-3 days to prevent the development of exacerbation.

Medicines used to treat and prevent Hereditary Angioedema

  1. "Aminocapronka" most likely will not help. In general, it helps very few HAE patients, but still, sometimes it does help. It is a pity that our doctors (due to the lack of others effective drugs, and also due to lack of knowledge about HAE) it is still prescribed.
  2. It’s better to pay attention to TRANEXAMIC ACID. In Russia and Ukraine there is such a drug as TRANEXAM. However, unfortunately, this medicine is also considered ineffective. But you can try.
  3. Further, from the available there is "Danazol" with trade names Danoval, Danol, Danazol. Typically, HAE patients take this drug 50 mg - 200 mg per day and increase the dose if there is a possibility of an attack (and attacks do occur, but usually much less frequently). Attention! Danazol has a whole range of bad side effects, especially for women, especially if you take the medicine in large doses. But, despite all the “buts,” the drug works for many HAE patients.
  4. There is also a drug called Stanozolol. It is as effective as Danazol, but there are far fewer side effects. Pay attention to him. In children, according to the literature, treatment with low doses of oxandrolone is more preferable.
  5. During acute attacks of edema (larynx, abdomen, face) abroad (there, there) the following drugs are used:
    + C1 inhibitor concentrate (Berinert, Cinryze, Cetor);
    + Recombinant C1 inhibitor concentrate (Ruconest/Rhucin);
    + B2 receptor antagonists (Firazyr).

    All these drugs are very expensive. Patients rarely pay for them themselves. People are helped by the state, insurance organizations, charities, paying either the full cost of the drugs or part of them. Very often such expensive drugs are stored in refrigerators and “wait” for acute attacks of their owners. In order for these medicines to become available in the CIS countries, patients must take an active part in the process of treatment and diagnosis. To optimize partnerships between HAE patients and physicians, many Western countries There are associations or groups of patients with HAE around the world.

    Please note that Firazyr is officially registered in Russia, which means it should be available to patients. At least in clinics in big cities for the relief of acute edema.

    6. If none of the things stated in clause 5 are available, and dangerous swelling is, then urgent hospitalization in the intensive care unit is necessary (it is advisable that the patient is known there, so you should agree in advance) and the introduction of fresh frozen plasma rich in a C1 inhibitor (it is better to select one in advance and store it, for example, in the refrigerator). Caution: Recent studies on the treatment of exacerbations of HAE have shown that in fresh frozen plasma may contain kininogens (precursors of bradykinin), and therefore the patient’s condition may worsen.

    I would like to express special gratitude to Daria Aleksandrovna Yartseva (assistant of the Department of Faculty Pediatrics, Candidate of Medical Sciences, Zaporozhye State Medical University, Department of Faculty Pediatrics) for her help in writing this section.

    Note. Instructions for Berinert P, Cinryze, Ruconest and Icatibant (Firazyr) preparations are reprinted from the website