Introduction
hemophiliaDivided into two types, A and B. Hemophilia A is a hemorrhagic disease caused by a deficiency in factor VIII, accounting for about 85% of congenital bleeding disorders. According to the report of the World Health Organization (WHO) and the World Federation of Hemophilia (WHF) 1990 Joint Conference, the incidence of hemophilia A is about 15-20/100,000 people, and the statistics of European and American countries are about 5-10. 100,000 people, the incidence of hemophilia A in China is about 3-4 million people. Hemophilia B, called Factor IX deficiency or Christmas disease, has an incidence of about 1.0 to 1.5/105, accounting for 15% to 20% of hemophilia. Factor IX has a gene length of 34 kb and is located on the long arm of the X chromosome, with 8 exons and 7 introns. Factor IX is a plasma protein dependent on vitamin K with a relative molecular weight of 56,000 and a synthetic site in the liver. Hemophilia A, B treatment is similar, using alternative therapy, plasma, prothrombin complex (PCC), factor IX concentrate and recombinant factor IX products can be used.
Cause
Hemophilia is a group of congenital coagulation factors that cause bleeding disorders. Congenital factor VIII deficiency is a typical sexual recessive inheritance, transmitted by women, male onset, and the gene that controls the synthesis of factor VIII coagulation components is located on the X chromosome. The sick male is married to the normal female, the male is normal in the child, the female is the passer; the normal male and the female in the passer are married, half of the male is the patient, and half of the female is the passer; the male and the female are married and the female is born. Half of the boys have hemophilia, and half of the girls born are hemophilia, and half of them are transmitters. About 30% have no family history, and its onset may be caused by genetic mutations.
Factor IX lacks the same genetic pattern as hemophilia A, but female transmitters have lower levels of factor IX and have a tendency to bleed. The lack of factor X1 leads to the formation of blood thromboplastin. Prothrombin cannot be converted to thrombin. Fibrinogen cannot be converted to fibrin and is prone to bleeding.
symptom
[clinical manifestations]
Bleeding is the main clinical manifestation of this disease. Patients have spontaneous/slight injury/long-term bleeding tendency after surgery. Heavy-duration can occur both after birth and milder.
1. Skin and mucous membrane bleeding is easy to be injured due to subcutaneous tissue, gums, tongue, oral mucosa, etc., so it is a site of frequent bleeding. Children are more likely to have hemorrhage/hematoma after frontal collision, but skin and mucous membrane bleeding is not a feature of this disease.
2. Joint blood is a common clinical manifestation of hemophilia A patients, often occurs after trauma / walking too long / exercise caused by synovial hemorrhage, more common in the knee joint, followed by sputum, hip, elbow, shoulder, wrist joints, etc. At the office. Joint bleeding can be divided into three phases:
A. Acute phase: bleeding in the joint cavity and around the joint tissue, causing local fever, redness and pain in the joint. Following the muscle spasm, limited mobility, the joints are mostly in the flexion position.
B. Total arthritis: In most cases, blood is not completely absorbed due to repeated bleeding. The enzyme released by white blood cells and other components in the blood stimulate joint tissues to form chronic inflammation and thickening of the synovium.
C. Late stage: joint fibrosis / joint stiffness, deformity, muscle atrophy, bone destruction, joint contracture leading to loss of function. Repeated bleeding of the knee joint often causes knee flexion, valgus, and subluxation of the tibia, forming a characteristic hemophilia pace.
3. Muscle hemorrhage and hematoma often occur in severe hemophilia A, which occurs more often after trauma/muscle activity, and is more common in forced muscle groups.
4. Hematuria severe hemophilia A patients may have microscopic hematuria or gross hematuria, no pain, no history of trauma. However, if there is a ureteral clot, there is a symptom of renal colic.
5. False tumors (hemophilic blood cysts) cysts can occur in any part, more common in the thighs, pelvis, calves, feet, arms and hands, and sometimes in the eyes.
6. Post-traumatic or post-surgical bleeding Various degrees of trauma, minor surgery can cause long-lasting and slow bleeding or bleeding.
7. Other parts of the bleeding gastrointestinal bleeding can be manifested as hematemesis, melena, bloody stools or abdominal pain, most patients have primary lesions such as stomach, duodenal ulcer; hemoptysis is related to tuberculosis, branch expansion and other primary lesions; Hemorrhoids and sublingual hematoma are usually caused by oral damage in patients with hemophilia A; sublingual hematoma can cause tongue displacement. If hematoma develops into the neck, it often causes difficulty in breathing; intracranial hemorrhage is often the cause of death of hemophilia patients.
8. Compression symptoms caused by bleeding and its complications Hematoma compression nerves, can lead to numbness, loss of sensation, severe pain, muscle atrophy, etc. in the compressed nerve innervation; tongue, oral bottom, tonsil, posterior pharyngeal wall, anterior neck hemorrhage , can cause upper airway obstruction, leading to difficulty breathing, and even suffocation, local blood vessels are compressed, can cause tissue necrosis.
【Diagnostic criteria】
The criteria for clinical diagnosis are:
A. Mostly male patients (female homozygotes are rare), with or without family history, family history with x-linked recessive inheritance;
B. Joint, muscle, deep tissue hemorrhage, with or without active activity, exertion, trauma or abnormal bleeding history after surgery, severe deformity can be seen;
C. The laboratory test results are positive.
diagnosis
Should pay attention to:
1. Identification between hemophilia A and hemophilia B;
Second, the identification of vascular hemophilia;
Third, the identification of diseases associated with other coagulation factors.
complication
Hematoma in the deep tissue can compress the nearby blood vessels to cause tissue necrosis. Compression of the nerve can cause limb or local pain, numbness and muscle atrophy. Compression of the blood vessels can cause ischemic necrosis or congestion and edema of the corresponding blood supply site. Bleeding at the bottom of the mouth, posterior pharyngeal wall, throat and neck can cause difficulty breathing or even suffocation. Patients may be unable to completely absorb blood due to repeated joint cavity hemorrhage, resulting in chronic inflammation, synovial thickening, fibrosis, cartilage degeneration and necrosis, eventually joint stiffness, deformity, peripheral muscle atrophy, resulting in limited normal activities.
treatment
First, to avoid trauma and surgery, such as joint bleeding, the affected limb should be fixed. Avoid taking aspirin and other drugs that affect blood clotting.
Second, alternative treatment: 1 hemophilia A: cold sediment, fresh frozen plasma or factor VIII concentrate. Dosage: mild joint hemorrhage, deep hematoma: factor VIII activity should be increased to 15% to 30%, infusion of 10 ~ 15U / kg (factor VIII 1 unit is equivalent to the concentration of 1ml of normal plasma); Joint hemorrhage and deep hematoma: Factor VIII activity should be increased to 40% to 50%, infusion of 15 ~ 25U / kg; for major surgery: Factor VIII activity should be increased to 60% ~ 70%, need to be infused 30 ~ 50U / kg. Calculation formula: Infusion of factor VIII dose (U) = expected concentration (U/ml) '40 ml / kg ' patient weight (kg).
For example, to increase the plasma factor VIII activity of 60 kg of severe hemophilia A patients to 50%, the infusion factor VIII dose = 0.5 U / ml '40 ml / kg '60 kg = 1200 (U). The half-life of factor VIII in the circulation is about 10 to 12 hours, and should be infused 2 to 3 times/d.
2 hemophilia B: The principle of treatment is the same as hemophilia A. Fresh frozen plasma, Factor IX concentrate was transferred. Dosage: starting dose 40 ~ 60U / kg, maintenance amount 20U / kg, 1 / d (factor IX half-life longer: 20 ~ 24 / h).
Third, surgical treatment: severe joint deformity, affecting normal activities, in the case of strict alternative treatment, orthopedic surgery is feasible.
Fourth, local bleeding: compression and hemostasis.
prevention
First, avoid intravenous and intramuscular injections of patients.
Second, because the disease is a hereditary disease, it is necessary to make the patient and his family understand the principle of prenatal and postnatal care. If the prenatal amniocentesis is diagnosed as hemophilia, the pregnancy should be terminated to reduce the birth rate of hemophilia.
Third, flirting: due to mental stimulation can induce bleeding.
Fourth, once the bleeding is caused by trauma or other reasons, it should be disposed of in time, so that the complications and sequelae caused by this are relatively light.
5. If surgery is required, the factor VIII must be referred to the alternative treatment effect according to the plasma VIII:C level and the size and location of the operation before surgery.
6. Drugs that inhibit the accumulation of platelets, such as drugs.aspirin, phenylbutazone, dipyridamole and prostaglandin E.
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