Thrombocytopenia
Introduction
Introduction to platelet weakness Platelet weakness In 1918, Glanzmann first reported the disease, so this disease is also known as "Glanzmann disease (Glanzmannthrombasthenia, GT)", is an inherited bleeding disease. It is characterized by the low or absent response of blood cells to various physiological attractants, caused by abnormalities in the quality or quantity of platelet membrane glycoprotein IIb (GPIIb) and/or IIIa (GPIIIa). In 1990, the International Committee for Thrombosis and Hemostasis Standardization Committee defined GT as a congenital hereditary non-aggregation or response of platelets to various receptors (such as adenosine diphosphate, thrombin, collagen, etc.) due to defects in GPIIb or GPIIIa genes. reduce. basic knowledge The proportion of illness: 0.03% Susceptible people: good for children Mode of infection: non-infectious Complications: Albinism Lymphoma Leukemia Arthritis Vasculitis Autoimmune hemolytic anemia Congenital heart disease
Cause
Causes of thrombocytopenia
Cause of the disease (35%) :
The disease is caused by abnormalities in the quality or quantity of platelet membrane glycoprotein IIb (GPIIb) and/or IIIa (GPIIIa). The GPIIb-IIIa complex is a calcium-dependent multimer, a fibrinogen receptor, and can also bind. vWF, fibronectin and thrombosensitive protein, mediate platelet aggregation under the action of various physiological attractants such as ADP and TXA2. Therefore, abnormal receptors can cause platelet thrombosis in vascular injury, and bleeding can occur. Or ecchymosis.
The GPIIb-IIIa receptor also helps the platelet alpha particles to take up fibrinogen. Therefore, the platelet fibrinogen level in GT patients is significantly decreased. The GPIIb-IIIa complex is the fibrinogen on the outer side of the membrane and the actin filament on the inside of the membrane. The main attachment point is involved in the blood clot retraction function, so GT patients often have poor blood clot retraction.
Pathogenesis (15%) :
Studies have shown that GPIIb and GPIIIa form a complex rapidly after synthesis in the rough endoplasmic reticulum. The formation of complexes helps prevent glycoproteins from being digested by proteolytic enzymes. Both GPIIb and GPIIIa are required for platelet receptor function. Defects in either of them can lead to the same dysfunction.
GPIIb and GPIIIa are encoded by different genes, which are located on chromosome 17 (17q21~23). After the 1990s, the research on gene defects of GT is progressing rapidly. The types of gene mutations that have been discovered include point mutations and deletions. And insertion, gene mutations can also cause variant GT. Although platelets have sufficient GPIIb-IIIa, GPIIb-IIIa has abnormal quaternary structure, does not have receptor activity, and cannot bind fibrinogen, homozygous for this disease. The platelet membrane GPIIb and GPIIIa levels of patients can be reduced to less than 5% of normal, and the heterozygote content can also be reduced to about 60% of normal people.
In this patient, glyceraldehyde phosphate dehydrogenase, pyruvate kinase, glutathione peroxidase and glutathione reductase are abnormal, and the viability is reduced, thereby making platelet function and blood clot retraction poor.
Prevention
Platelet weakness prevention
1. The preventive measures for this disease are to prohibit the marriage of close relatives, carry out genetic counseling and prenatal examination, avoid trauma and surgery, and avoid using drugs that affect platelet function.
2, premarital physical examination plays a positive role in the prevention of birth defects, the size of the effect depends on the examination items and content, mainly including serological examination (such as hepatitis B virus, treponema pallidum, HIV), reproductive system examination (such as screening for cervical inflammation) ), general physical examination (such as blood pressure, electrocardiogram) and asking about the family history of the disease, personal medical history, etc., do a good job in genetic disease counseling.
3, pregnant women to avoid harmful factors, including away from smoke, alcohol, drugs, radiation, pesticides, noise, volatile harmful gases, toxic and harmful heavy metals.
Complication
Thrombocytopenia complications Complications Albinism Lymphoma Leukemia Arthritis Vasculitis Autoimmune Hemolytic Anemia Congenital Heart Disease
Children with storage pools often have varying degrees of eye and skin albinism, varying degrees of pulmonary fibrosis, infectious bowel disease and hemorrhagic diarrhea, and are prone to purulent infections. Wiskott-Aldrich syndrome can die from intracranial hemorrhage and infection when young, susceptible to infection by Streptococcus pneumoniae and Haemophilus influenzae; susceptible to viral and fungal infections. In addition to complications such as bleeding and infection, malignant tumors such as lymphoma and leukemia can occur. In addition, it can also be complicated by autoimmune diseases such as arthritis, vasculitis and autoimmune hemolytic anemia. Children with TAR syndrome have bilateral humeral loss, some humerus and ulna are missing, short limb deformity, some children with congenital heart disease, small head, small jaw and other deformities. Sometimes bleeding is severe, and even intracranial hemorrhage occurs.
Symptom
Symptoms of thrombocytopenia Common symptoms Nasal bleeding Skin mucosal bleeding Gingival bleeding Bleeding intracranial hemorrhage
Heterozygous patients generally have no bleeding, homozygous patients with bleeding, often bleeding in early childhood, such as umbilical cord bleeding at birth, skin ecchymosis, nosebleeds, bleeding gums, trauma, surgery and childbirth can cause severe bleeding, However, without deep hematoma, female patients may have menorrhagia, intracranial hemorrhage, visceral hemorrhage and joint bleeding are rare.
The severity of bleeding in this disease is different. There are reports of hemorrhage death. Some patients have only slight bleeding even if GPIIb-IIIa is not detected. The severity and frequency of bleeding have no significant relationship with the degree of GPIIb-IIIa deficiency. The increase is reduced.
According to the family history, as well as the above clinical bleeding symptoms and laboratory tests are not difficult to diagnose, conditional units can carry out genetic analysis.
Examine
Examination of platelet weakness
1. Platelet count and platelet morphology are normal, and platelet dispersion is not clustered.
2. The bleeding time was significantly prolonged, the blood clot retraction was mostly poor, and the beam arm test was positive.
3. The adhesion of platelets to collagen is normal, while the adhesion to the bead column is significantly reduced.
4. Platelets did not produce aggregation reaction on various concentrations of ADP, adrenaline, thrombin and collagen, but the aggregation reaction induced by ristocetin and vWF was normal or decreased.
5. Platelet factor III (PF3) effectiveness test is reduced.
6. Platelet bead retention test was reduced.
7. Platelet GPIIb-IIIa is reduced, lacking or structurally abnormal.
Diagnosis
Diagnosis and identification of thrombocytopenia
Diagnostic criteria
The diagnostic criteria for the revision of the Fifth National Conference on Thrombosis and Hemostasis are as follows:
Clinical manifestation
(1) Autosomal recessive inheritance.
(2) Hemorrhagic symptoms from childhood: manifested as moderate or severe skin mucosal bleeding, women may have more menstruation, bleeding after trauma.
2. Laboratory examination
(1) The platelet count is normal, and the platelets on the blood smear are scattered and do not aggregate into a heap.
(2) The bleeding time is prolonged.
(3) The blood clot is poorly contracted or normal.
(4) Platelet aggregation test: ADP, adrenaline, collagen, thrombin and arachidonic acid were not caused to aggregate or the aggregation reaction of the latter three inducers was significantly reduced, and the aggregation caused by ristocetin was normal or reduce.
(5) Platelet membrane GPIIb/IIIa is reduced or has a qualitative abnormality.
According to the degree of GPIIb/IIIa reduction or qualitative abnormality, it can be divided into 3 types.
Differential diagnosis
The disease should be differentiated from other platelet counts and normal platelet function-deficient diseases. Some patients with gray platelet syndrome have defects in clot retraction, but platelet aggregation is only mildly abnormal, and platelet alpha-granule secreted protein is absent. Patients with dense particle deficiency Platelet biphasic aggregation was abnormal, but blood clot retraction was normal, hereditary pattern was autosomal dominant, and bleeding time was prolonged in patients with congenital fibrinogenemia, but the coagulation test was abnormal.
The disease should be differentiated from other platelet counts and normal platelet function defects.
1. Great platelet disease.
2. Secondary thrombocytopenia with autoantibodies that inhibit the function of platelet membrane GPIIb/IIIa fibrinogen receptor or chromosome 17 abnormalities can reduce secondary GPIIb/IIIa production, causing secondary thrombocytopenia, multiple underlying diseases Myeloma, Evens syndrome and lymphoproliferative disorders (such as Hodgkin's lymphoma), patients with anti-GPIIb, GPIIIa or GPIIb/IIIa antibodies, while patients with acute promyelocytic leukemia may be translocated with chromosome 17 Reduce or absent GPIIb/IIIa production.
3. Hereditary coagulation factor deficiency such as hemophilia A or B, has some similar clinical manifestations with thrombocytopenia, but patients often have spontaneous bleeding, most joint and muscle bleeding, and even joint deformity; bleeding Severity is associated with levels of factor VIII or IX, which are different from those of platelet weakness.
