Acquired circulating anticoagulant hyperplasia

Introduction to acquired circulating anticoagulant Acquired circulating anticoagulant hyperplasia is an acquired clotting factor inhibitor that can be directly affected by a specific clotting factor. The coagulability of blood causes a tendency to bleed. basic knowledge The proportion of sickness: 0.0001% - 0.0002% Susceptible people: no specific population Mode of infection: non-infectious Complications: intracranial hemorrhage

Acquired circulating anticoagulant hyperplasia

(1) Causes of the disease

1. Some patients with hemophilia A, due to hereditary factor VIII deficiency, repeated infusion of fresh plasma, whole blood, frozen plasma or anti-hemophilic globulin concentrated preparation due to clinical replacement therapy, due to the effect of similar allogeneic antigen An antibody against Factor VIII was produced.

2. Healthy women develop factor VIII inhibitors during pregnancy, or inhibitors appear several days to several years after delivery, usually 2 to 4 months after delivery, possibly due to autoimmunity.

3. Some healthy elderly spontaneously produce factor VIII inhibitors, both men and women can be ill, the mechanism is unknown.

4. Rheumatoid diseases such as systemic lupus erythematosus, rheumatoid arthritis and other immune-related diseases such as ulcerative colitis, bronchial asthma, drug allergies, etc., in the course of illness, factor VIII inhibitors, in addition, vascular blood AIDS, systemic lupus erythematosus, abnormal globulinemia, lymphoma, and diabetes may present with factor VIIIR: WF inhibitor.

Factor VIII inhibitor is an antibody, most of which are IgG, and some are IgM, and there are also a mixture of the two. IgG is usually X-ray light chain (ie, IgGX strong type), and X and human-chain mixed type. The Factor VIII inhibitor of individual patients is an IgG heavy chain type, and most of them are classified into the IgG4 subtype according to the antigenicity of the immunoglobulin and the number of disulfide bonds, and also the IGg4 and IgG1 mixed type, and the IgG4 and IgG2 mixed type.

5. Factor IX inhibitors A small number of hemophilia B patients, due to the lack of hereditary factor IX, clinical treatment of repeated infusion of plasma factor IX concentrate after the emergence of factor IX inhibitors, Cohn fractionation method to determine the inhibitor is gamma sphere The protein was mostly determined to be IgG by immunoneutralization, and a small amount was IgG4 human type.

6. Factor V inhibitors This disease is rare. It has been seen in patients with streptomycin and healthy people after surgery. It also occurs in patients with hereditary factor V deficiency.

(two) pathogenesis

1. Immunological factors According to a study by Allain et al, there are two kinds of immune responses to hemophilia A-producing factor VIII inhibitors: one is a "hish responder", which is characterized by accepting allogeneic factor VIII. High titers exceeding 10 Bethesda units (BU) inhibitors, if factor VIII is no longer infused, the inhibitors are often slowly reduced over time; if factor VIII is administered again, inhibitors can occur after 5-7 days These high-responders account for about 75% of hemophilia A with inhibitors, and the other is "low-responders". The inhibitor titers that occur after replacement therapy are low (about 5BU or less). Not every inhibitor is produced after each factor VIII is received. It is also reported that a small number of patients can be converted from a low responder to a high responder. The main immunogen determinant for the formation of hemophilia A factor VIII inhibitor may be in the immune sphere. The heavy and light chain subunits of the protein.

2. Characteristics of inhibitors Most of the current studies are immunobiochemical methods. Most of the hemophilia A factor VIII inhibitors are polyclonal IgG; a few are IgM or IgA, or coexist with IgG, and a few factors VIII has a high affinity immunoglobulin, IgG4, which is currently thought to be associated with an immune response stimulated by chronic antigens; IgG4 is a monovalent antibody that inactivates clotting factors without antigenic antibody precipitation and does not fix complement components. However, endogenous factor VIII and exogenous factor VIII may be inhibited, so no complications of kidney and blood vessels may occur. In addition, some patients have inhibitors of IgG4 with IgG1, occasionally IgG3-based inhibitors, and factors for individual postpartum women. The inhibitor of VIII is mainly IgM, which later evolved into IgG type. The mechanism is unknown. It is concluded that most anti-Factor VIII heterotype antibodies are mostly restricted to the type of light chain, while autoantibodies are mostly light chain heterogeneous components.

According to Gawry and Hoyer's experimental studies, there are two main ways to inactivate inhibitors on factor VIII:

Type 1I antibodies can directly inactivate factor VIII at high concentrations and express inhibitor strength.

2 type II antibody needs to dissociate factor VIII from vWF, and then inactivate factor VIII. The residual activity of factor VIII in plasma is not proportional to the inhibitor concentration. Generally, the allogeneic antibody of hemophilia A shows type I reaction, and itself Antibodies usually show type II inactivation, so scholars speculate that factor VIII inhibitors may act on phospholipids in coagulation reactions, or may act on thrombin-mediated activator VIII and inhibitors that block factor VIII and The binding of vWF, thereby inhibiting the clotting activity of factor VIII.

Acquired circulation anticoagulant hyperplasia prevention

There is no effective preventive measure for this disease. Early detection and early diagnosis are the key to the prevention and treatment of this disease.

Acquired circulating anticoagulant complications Complications intracranial hemorrhage

Severe cases can be complicated by intracranial hemorrhage.

Acquired circulating anticoagulant symptoms symptoms Common symptoms Bleeding tendency nosebleed joint swelling intra-articular bleeding

The primary disease is mainly manifested, the degree of bleeding tendency and the irreversible inactivation of anti-Factor VIII antibody in the blood circulation to factor VIII, severe cases of typical hemophilia-like bleeding symptoms, such as spontaneous joint bleeding, deep Soft tissue hematoma, nosebleeds, bleeding after trauma, etc.

Examination of acquired circulating anticoagulant hyperactivity

1. Activated partial thromboplastin time, clotting time and plasma recalcification time are prolonged.

2. Normal whole blood and plasma cannot correct abnormal coagulation caused by increased circulating anticoagulant substances.

3. Anti-Factor VIII, IX, XI and XIII antibodies enhance the inactivation of factors VIII, IX, XI and XIII.

4. Anticoagulant substance is measured to increase the titer.

5. The antibody neutralization assay showed a decrease in the activity of factors VIII, IX, XI and XIII, which may be as low as about 1%.

According to the condition, clinical manifestations, symptoms, signs, ECG, B-ultrasound, X-ray, CT, MRI, biochemistry, liver and kidney function tests.

Diagnosis and differentiation of acquired circulating anticoagulant

Confirmed according to clinical manifestations and laboratory tests.

This disease is generally not confused with other diseases.

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