Hemophilia-What is hemophilia?
Hemophilia is a hereditary bleeding disorders, hemophilia is due to the lack of certain clotting factors in the blood caused by severe coagulation disorders. Most of the hemophiliacs were male, typical patients often since childhood, the annual incidence of spontaneous or mild trauma, coagulation disorders, bleeding not spontaneously stop; resulting in trauma, surgery is often bleeding, severe cases, the more intense activity may be spontaneous bleeding.
Hemophilia - ProfileHemophilia is a group of hereditary coagulation factor deficiency, is a hemorrhagic disease caused by a single coagulation factor deficiency, is rare. Based on the lack of clotting factor can be divided into three categories A, B, C,. Severity of the disease and the lack of proportional to the plasma level of clotting factor. The vast majority of hemophilia patients were male, as yet, no final solution. However, by increasing the activity of coagulation factor levels, can effectively eliminate the symptoms of the patients. Each year since 1989, was designated as the "World Hemophilia Day on April 17.
Hemophilia - the cause ofHemophilia normal blood clotting in the blood platelets and some plasma proteins result of the role. Those related to the coagulation of plasma proteins, clotting factors. Clotting factor in blood clotting process, with the effect of accelerating and strengthening the response to the lack of clotting factor to assist may occur coagulation dysfunction, resulting in prolonged bleeding. Clotting factors for hemophiliacs less than normal, after the rupture of blood vessels, the blood does not coagulation, resulting in bleeding difficult to stop.
According to the type of patients the lack of clotting factor, the most common hemophilia divided into alpha, beta, gamma, or Type A, Type B, C-type (alpha = Type A, B = B-type C = C type). Lack of other coagulation factors in hemophilia, there was no special classification to confirm the lack of clotting factor.
Hemophilia - genetic characteristicsInfluenza A and hemophilia B are X-linked recessive inheritance. The women are generally not the disease, but can carry disease-causing gene. Carry disease-causing gene in women with normal male offspring, males have 50% probability of disease, women have 50% probability of carrying the disease-causing gene. The prevalence of male and normal female offspring, all normal men and women all carry disease-causing gene. Therefore, these two of hemophilia performance atavistic. Female offspring of the sick men and carry disease-causing gene for the sick woman, but because women have menstruation, so in general very low survival rate after the prevalence of female adolescence.
C hemophilia for the autosomes (autosomal) incomplete recessive inheritance.
About 10,000 have a hemophilia patients, about 35,000 have a hemophilia B patients, hepatitis C patients with hemophilia is very rare
Hemophilia - clinical performanceChange of hemophilia joint bleeding is the main clinical manifestations of this disease, patients with life-long spontaneous minor injuries, post-operative long bleeding tendency in patients with severe disease, after the birth of both later in the incidence of the light by.
Mucocutaneous bleedingProne to injury due to the site of the subcutaneous tissue, gums, tongue and oral mucosa, so the bleeding site. Children hemorrhage more common in the forehead after the collision, skin and mucous membrane bleeding is not characteristic of this disease.
HemarthrosisIs a common clinical manifestations of patients with hemophilia A often occurs in trauma, the line through the long, synovial bleeding caused after exercise, more common in the knee, followed by the ankle, hip, elbow, shoulder and wrist and other places.
Joint bleeding can be divided into three phases:
1, the acute phase: the organization of intra-articular and periarticular bleeding lead to joint local heat, swelling, pain, followed by muscle spasms, limited mobility, joint more in flexion position.
2, full-arthritis of: the majority of cases because of repeated bleeding so that blood can not be fully absorbed, white blood cells release enzymes and other components of the blood to stimulate joint organization, the formation of chronic inflammation of synovial thickening.
Late: arthrofibrosis tough deformity, joint, muscle atrophy, bone destruction, joint contracture lead to loss of function. Knee, often caused by repeated bleeding knee flexion valgus fibular subluxation, the formation of the pace of the characteristic of hemophilia.
Muscle bleeding and hematomaOften occur in patients with severe hemophilia A, multi-trauma, muscle activity for too long, more common in the forced muscles.
HematuriaSevere hemophilia A patients with microscopic hematuria or gross hematuria, no more pain, no history of trauma. But if it ureter formation of blood clots symptoms of renal colic.
PseudotumorHemophilia hemophilic blood cysts can occur at any site, more common in the thigh, pelvis, leg, foot, arm and hand, but also sometimes occur in the eye.
Bleeding after trauma or surgeryVarious degrees of trauma minor surgery can cause lasting and slow oozing or bleeding.
Other parts of the bleeding1, gastrointestinal bleeding can be manifested as hematemesis melena, bloody diarrhea or abdominal pain, most patients with primary lesions such as gastric ulcer;
2, hemoptysis, and pulmonary tuberculosis, bronchiectasis and other primary lesions related;
3, epistaxis, sublingual hematoma is usually the oral lesions in patients with hemophilia A due to sublingual hematoma can be caused by tongue displacement. If the hematoma to the neck, often caused by difficulty in breathing;
Intracranial hemorrhage is often the cause of death in patients with hemophilia.
Hemophilia - complications1, hemophilia clotting factor antibodies
Hemophiliacs during treatment, repeated a large number of antibody infusion, is likely to clotting factor antibodies, these antibodies and clotting factors, loss of coagulation of the blood clotting factor.
Patients with hemophilia A, for example, almost all severe hemophilia A Ⅷ factor treatment, will produce the inhibitory IgG antibodies against factor Ⅷ Ⅷ factor antibody. Coagulation factor antibodies are one of the most severe hemophilia concurrent symptoms seriously affect the treatment of hemophilia.
2, AIDS
Hemophiliacs the risk of HIV infection, due to reasons of patients with plasma products, quality problems, according to statistics, in 1978-1985, AIDS, hemophilia leading cause of death.
3, hepatitis
And AIDS, hepatitis is caused by quality problems because plasma products, the probability of hemophilia patients with liver cancer is 30 times higher than the general population, liver failure has become one of the reasons for the hemophiliacs death can not be ignored.
4, hemophilic arthritis
Hemophilic arthritis is caused by the joints in patients with recurrent bleeding is difficult to dissipate congestion causes inflammatory stimuli. Almost all hemophiliacs have symptoms of joint bleeding, severe hemophilia arthritis cause joint contracture or deformity is the main reason of disability of patients with hemophilia.
5, other complications
The floor of the mouth, pharynx posterior wall of the throat and neck bleeding can cause breathing difficulties and even suffocation. Hematoma may compress the deep tissue near the blood vessels causing tissue necrosis, nerve of a limb or localized pain, numbness and muscle atrophy, pressure vessels can be caused by the corresponding blood supply to parts of the ischemic necrosis or congestion, edema.
Hemophilia - diagnosisRFLP diagnosis of typical cases the diagnosis based on history, family history and laboratory tests is not difficult. FIX: C, determination of diagnostic significance. Easily missed some light cases or subclinical cases no significant bleeding history, often in abnormal bleeding after trauma, tooth extraction and surgical diagnosis.
Diagnostic criteria1, mostly for male patients (female homozygous rare), or no family history, family history of the x linked recessive inheritance law;
2, joint and muscle, deep tissue bleeding, or no activity for too long, the force trauma or after surgery, history of abnormal bleeding, and severe cases, visible joint deformities;
3, a positive laboratory test results.
Genetic diagnosis
Determine the causative gene for carrier detection and prenatal diagnosis, and can predict the generation of inhibitors.A direct genetic diagnosis: the molecular biology methods (PCR, DGGE to SSCP, DNA sequencing, etc.) direct determination of the causative gene defects. FVIII 22 intron inversion analysis can be used as a screening test of heavy HA is currently (March 2012) only used for clinical diagnosis of direct genetic testing methods. Inversion of FVIII 22 introns and other gene mutation is often accompanied by the inhibitor occurred, thus contributing to the generation of forecast inhibitor.
2, indirect genetic diagnosis: the use of disease-causing genes inside and outside of the restriction fragment length polymorphism (RFLP) as the specific molecular genetic markers, through the chain of relationships between family members to determine the inheritance of the hemophilia gene, DNA polymorphism analysis of genetic diagnosis (RFLP, VNTR, STR and other methods), allows the diagnosis rate of 99%. RFLP analysis of the limitations: it is necessary to have specimens of the proband; mother and heterozygous for the polymorphic loci, combine multiple RFLP before diagnosis.
Prenatal diagnosis: high-risk fetus in 9-12 weeks of gestation by chorionic biopsy; 12-16 weeks of pregnancy amniocentesis to obtain fetal DNA, but also through the early embryo (8 cell) in the preimplantation determine the sex of the fetus, and to further determine whether hemophilia or carriers by DNA genotypes and genetic phenotype. Microscope to take 18-20 weeks of pregnancy in the fetal umbilical cord blood, determination of FVIII: C and FVIII: Ag. The above-mentioned methods have the risk of miscarriage (about 0.5% -1%), required under the guidance and cooperation of the obstetricians and gynecologists. Use of flow cytometry (FACS) Determination of fetal-specific monoclonal antibodies in the maternal venous blood to determine fetal sex, and early non-invasive prenatal diagnosis.
Hemophilia - CheckLaboratory testsCoagulation analysis of blood as: anemia, white blood cell and platelet count normal.
2, coagulation tests: normal bleeding time; coagulation time; normal prothrombin time (PT); activated partial thromboplastin enzyme time (APTT) to extend, can be normal fresh plasma or barium sulfate adsorbed plasma to correct for hemophilia A (A); normal serum can be corrected, but not barium sulfate adsorbed plasma to correct for hemophilia B (B,).
3, Determination of clotting factor activity: factor VIII coagulant activity (VIII: C) Determination of significantly reduced (hemophilia A, sub-type: Heavy <1%, medium-sized 2% to 5% of light from 6% to 25% of subclinical 26% to 49%); Determination of factor IX procoagulant activity (IX: C) to reduce (hemophilia B).
Other laboratory examinationsAccording to the disease, clinical manifestations, symptoms, signs do B, ECG, X-ray, CT, MRI, hematuria will be routine liver and kidney function and biochemical check.
Hemophilia - treatment measuresHemophilia mainly hemostasis:
Available gelatin sponge, thrombin, epinephrine topical hemostatic; such as the occurrence of joint bleeding, should be fixed limb. Jifu aspirin affect blood clotting drugs.
(2) replacement therapy, including lost plasma, cryoprecipitate matter, factor VIII, IX complex concentrated agents and coagulation zymogen;
3.1 - off the amino-8-D-arginine vasopressin intravenously, hemophilia A;
(4) other treatment, such as 6 - aminocaproic acid, corticosteroids, female contraceptives, Peanut preparations can be used;
5 of the patients as much as possible to avoid all kinds of surgery. Severe joint deformity, and affect the normal activities, under the strict replacement therapy, viable orthopedic surgery.
Hemophilia - care measuresHemophilia 1, to avoid intramuscular injection to patients.
2, because this disease is a genetic disease, it is to make the patients themselves and their families know how to prenatal and postnatal care of the truth. If the prenatal amniocentesis confirmed the termination of pregnancy for hemophilia in order to reduce the birth rate of hemophilia.
3, note that the peace of mind: mental stimulation can induce bleeding.
4, caused by trauma or other causes of bleeding should be promptly disposed of the sequelae of such complications is much lighter.
For surgery, before surgery by plasma VIII: C levels and surgical size, location, factor VIII on the alternative treatment.
6, forbidden to take the platelet aggregation inhibition of drugs such as aspirin the Paul Tai Songpan centimes, and prostaglandin E and so on.
Hemophilia - prognosisPrognosis depends on the seriousness of bleeding and whether replacement therapy affect the prognosis of treatment of complications such as hepatitis or alloantibody. Generally, replacement therapy to ensure that patients can achieve the same normal life.
Hemophilia - preventionThe establishment of genetic counseling, strict pre-marital check, to strengthen the prenatal diagnosis, thereby reducing the birth of children with hemophilia.
Haemophilia - discovered the history ofIn 1793, the German Kang Sibu for the first time published on the description of the hemophilia.
In 1803, the U.S. Dr. John Conrad Otto published an article on Hemophilia, the article to promote the other doctors of the disease, and papers published.
In 1823, German Scoresby Rennes use of hemophilia for the first time the word of the bleeding problem. In 1828, the term first appeared in a thesis topic Scoresby Rennes students, and has since specifically used to refer to a hereditary coagulation disorder.
In 1840, Samuel Lane, a British physician, for the first time on a hemophilia boy successful postoperative blood transfusion.
In 1853, the British Queen Victoria's son Lyle Pound identified with congenital hemophilia. And her two daughters hemophilia carriers, and hemophilia This is called the "royal disease" spread to the royal families of Europe and Russia.
In 1904, Russian Czar Nicholas II's son, Alix suffering from severe hemophilia.
In 1934, British doctors R · G · Maikefalei found Russell's viper solution to help people with hemophilia stop bleeding. To start production soon after for hemophilia treatment of commercial drugs "the Si Taifen (Stypen). The product to 2012 still in production.
In 1936, plasma was first used to treat hemophilia.
In 1937, the U.S. medical scientists A, J. Pa Yueke, and F. H. L. Taylor found that the intravenous injection of plasma proteins can shorten the clotting time. Later, Taylor to extract called antihemophilic globulin.
In 1939, Dr Keith Breen Hawes confirmed that patients with hemophilia clotting factor defects. Later, he called the anti-von Willebrand factor, now known as factor VIII.
In 1944, biochemist Edwin Kahn invented the plasma was separated into various components of the separation.
In 1944, Conn and his colleagues confirmed that a component of the (Conn composition I) antihemophilic activity in the blood. In the same year, American doctors Armand Quaker reached the same conclusion using different methods.
In 1952, in San Francisco, New York and Oxford researchers found a new type of hemophilia, and now know Ⅸ factor deficiency. Rosemary Biggs from Oxford, England, it is called "Chris" disease, named Shi Difen Christensen, from a patient.
1955, American doctors Robert · Langedaier, Robert Wo Gena, Keith Boolean Hawes invented the intravenous injection of factor Ⅷ. This is the first effective therapy for the treatment of hemophilia.
1957-1958 Ⅷ factor of human blood in the United Kingdom, France, Sweden, one after another.
In 1958, Inger Marie Nielsen, Swedish doctors on patients with severe hemophilia influenza prevention and treatment. Regular preventive treatment until the early 1970s onwards.
In 1961, the first test factor VIII concentrate.
In 1964, Judy Paul, U.S. researchers published papers said, slowly freezing and thawing of the plasma will produce a factor Ⅷ rich byproduct of This purified solid factor VIII has revolutionized the treatment of hemophilia.
The mid-1960s, hip and the knee replacement surgery in the UK first.
In 1968, the first branch of the enrichment factor VIII preparations.
In 1977, Italy Pierre Mannich prove, arginine vasopressin (DDAVP) can increase the level of factor VIII and vW factor in the blood.
1982, first reported in hemophiliacs infected with HIV.
In 1984, the U.S. Centers for Disease Control and Prevention (CDC) first heat-treated blood products. The experiments show that high temperatures can kill the HIV virus. Detection and replication of factor VIII gene.
In 1985, the advent of virus-inactivated factor concentrated preparation. The advent of HIV antibody detection methods.
In 1992, the first branch of the reorganization of factor VIII products.
In 1997, the first branch of the synthesis of the nine-factor products.
In 1998, gene therapy clinical trials
In 2011, the United Kingdom initial success with gene therapy for hemophilia B.
