Disorders with Defective Platelet Release Function in Children
Introduction
Brief introduction of pediatric platelet release dysfunction Defects in platelet release function are a group of heterogeneous diseases, which are also hereditary diseases. Some of the genetic methods are still not fully understood. Clinical manifestations of mild, moderate bleeding, such as nosebleeds, ecchymosis, excessive menstruation and postpartum hemorrhage, excessive bleeding after surgery and extraction of tonsils, occasionally severe bleeding caused by death. Most of the bleeding time in the laboratory examination was prolonged; the platelet count was normal or slightly reduced, and the morphology was normal; the coagulation factor was normal, and platelet adhesion was reduced. The key to the diagnosis of this group of diseases is that the first wave of platelet aggregation test for ADP or adrenaline is normal, the second wave is significantly reduced or absent; the aggregation of collagen is also reduced, but it is normal at high concentration. basic knowledge Sickness ratio: 0.0001% Susceptible people: children Mode of infection: non-infectious Complications: lymphoma
Cause
Pediatric platelet release function deficiency disease etiology
(1) Causes of the disease
Defects in platelet release function are hereditary diseases, and some of the hereditary methods have not yet been fully understood. This group of diseases is further divided into two categories, one is storage pool disease (SPD), and the other is platelet release disorder disease. As the dense particles of platelets, the latter is normal for platelet contents, but release disorders, including arachidonic acid release defects, cyclooxygenase deficiency, thromboxane A2 synthetase deficiency, etc., the final diagnosis should be excluded Sexual platelet release dysfunction, and then by means of detecting platelet granule contents, electron microscopy, etc. to confirm the diagnosis,
(two) pathogenesis
1. storage pool disease storage pool disease (-SPD), also known as primary dense body deficiency, the basic defect is the dense particle content of platelets ATP, ADP, calcium ion, pyrophosphate, serotonin The reduction of ADP is more significant than that of ATP. The platelet of -SPD lacks two-phase aggregation wave for the induction of ADP or adrenaline, the collagen-induced aggregation reaction is reduced or absent, and the arachidonic acid causes the aggregation reaction to decrease. Electron microscopy shows that dense particles are reduced, and and particles are simultaneously deficient. They are called storage pool disease (-SPD), in which the content of particles is often more severe, and the content of particles is reduced to moderate to moderate. Clinical and laboratory tests are similar to -SPD, which is part of other hereditary diseases such as Hermansky-Pudlak syndrome, Chédiak-Higashi syndrome, Wiskott-Aldrich syndrome, osteogenesis imperfecta and thrombocytopenia with humeral defects Such as syndrome (TAR syndrome), etc.
(1) Hermansky-Pudlak syndrome: This disease is autosomal recessive, characterized by whitening of the eye and skin, accumulation of lipid-like substances in the mononuclear-macrophage system, and tendency to hemorrhage in the absence of platelets. Reduced or practically absent, due to the low levels of serotonin, calcium and adenine nucleotides, platelets lack a two-phase aggregation wave for the induction of ADP, adrenaline and thrombin,
(2) Chédiak-Higashi syndrome: This disease is autosomal recessive, characterized by abnormal granule formation in neutrophils, monocytes, fibroblasts and melanocytes, and increased susceptibility to bacteria and fungi. Clinically, there are eye and skin albinism, and hemorrhagic disease is mild. Examination of abnormal particles in granulocytes can often help to confirm the diagnosis.
(3) Wiskott-Aldrich syndrome: the disease is associated with recessive genetic disease, characterized by repeated infections caused by cellular immunodeficiency, eczema and thrombocytopenic hemorrhage, small platelets in children, small morphology and reduced dense particles, clinical Most of the time in the infants and young children, hemorrhage, and more deaths from repeated infections and bleeding,
(4) TAR syndrome: this disease is autosomal recessive, the child has multiple malformations such as bone, heart, kidney, etc., more common bilateral humeral abscess, platelet often reduced with the number of bone marrow megakaryocytes decreased or absent ,
2. Alpha storage pool disease storage pool disease (-SPD), also known as gray platelet syndrome, is due to the gray platelets on the Wright's stain smear, electron microscopic observation of the patient's megakaryocytes and platelet-specific deficiency Alpha particles, biochemical studies found that patients with platelet alpha granule proteins such as platelet factor IV (PF4), platelet globulin (-TG) vWF, platelet prothrombin sensitive protein, fibronectin, factor V, high molecular weight kininogen , decreased or lack of platelet growth factor, further studies revealed that -granule protein synthesis is normal, but storage disorders; this disease also has conduction defects, patients with mild platelet count reduction, bleeding time and bleeding tendency, platelet to coagulation Enzyme-mediated aggregation and release reactions are abnormal, but the aggregation reaction induced by collagen and ADP is unchanged. Gray platelets on Wright's stained blood tablets often indicate diagnosis, and the diagnosis depends on electron microscopy.
Prevention
Prevention of pediatric platelet release dysfunction
The genetic pattern of the disease is not yet clear, so the preventive measures are not known. Patients with this disease should be banned from drugs that affect platelet function.
Complication
Pediatric platelet release dysfunction disorder Complications lymphoma
Children with storage pools often have varying degrees of eye and skin albinism, varying degrees of pulmonary fibrosis, infectious bowel disease and hemorrhagic diarrhea, prone to purulent infections, etc. Wiskott-Aldrich syndrome may be due to intracranial hemorrhage at a young age. Infection and death, 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, etc., can also be concurrent 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, and some children are accompanied by Congenital heart disease can also have small heads, small jaws and other deformities, sometimes severe bleeding, and even intracranial hemorrhage.
Symptom
Symptoms of platelet release dysfunction in children Symptoms Common symptoms diarrhea, nosebleeds, hemorrhage, skin ecchymosis, intracranial hemorrhage, gastrointestinal bleeding, fungal infection, thrombocytopenia, immunodeficiency, pulmonary fibrosis
1. -storage patients with bleeding symptoms are mild, mild to moderate bleeding quality, manifested as skin ecchymosis, bleeding gums, nose bleeding, menorrhagia, bleeding during childbirth, but generally no joints and Gastrointestinal bleeding, some patients with other defects, most commonly in Hermanky-Pudlak syndrome (HPS) and Chédiak-Higashi syndrome (CHS), HPS showed varying degrees of eye and skin albinism, reticuloendothelial system lysozyme In vivo lipid-like pigmentation, varying degrees of pulmonary fibrosis, infectious bowel disease and hemorrhagic diarrhea, CHS manifested as partial whitening of the eye and skin, neutrophils, monocytes, macrophages and fibroblasts Lysosome particles and prone to purulent infections.
2.-storage pond disease The bleeding of this disease is generally mild, mainly manifested as mild skin, mucosal bleeding, such as nosebleeds, skin ecchymoses and so on.
3. Wiskott-Aldrich syndrome clinical manifestations of immunodeficiency, thrombocytopenia and extensive eczema triad, young can be due to intracranial hemorrhage, infection and death, immunodeficiency involving cellular and humoral immunity, patients with this disease on polysaccharide antigen Can not produce antibodies, making the body susceptible to Streptococcus pneumoniae and Haemophilus influenzae; because T cells are abnormally susceptible to viral and fungal infections, bleeding usually occurs within 1 year of age, and later with the increase in bleeding symptoms, except bleeding and infection In addition to complications, about 2% of patients can develop malignant tumors, such as lymphoma and leukemia, in addition, can also be associated with autoimmune diseases such as arthritis, vasculitis and autoimmune hemolytic anemia.
4. TAR syndrome The clinical features of this disease are the reduction of tibia and bone marrow megakaryocytes in both sides of the newborn. The tibia of both sides is missing and the thumb is present. It can also be associated with short limb deformities, such as the loss of arms and legs. The hands and feet are directly connected to the trunk; some children also have humerus and ulna missing; about 1/3 of children may also have congenital heart disease, among which Fallot tetralogy and atrial septal defect are the most common, and a few children may have Small head, small jaw and other deformities, children are often allergic to milk, children usually appear purple cyanosis and ecchymosis at birth, sometimes severe bleeding, and even intracranial hemorrhage.
Examine
Examination of pediatric platelet release dysfunction
1. Blood routine platelet count is normal or slightly reduced, and the shape is normal.
2. The bleeding time is prolonged, it can be normal, the blood clot retraction is poor, and the blood coagulation factor is checked normally.
3. PF3, PF4 detection can be reduced.
4. Platelet aggregation test plus ADP or adrenaline, ADP aggregation first phase is normal, second phase is obviously weakened or no aggregation, a few can still be normal; collagen platelet aggregation is reduced, but high concentration can be normal.
5. Platelet electron microscopy The lack of or the lack of or particles in the platelets, routine B-ultrasound examination, clear whether there is hepatosplenomegaly, other choices depending on clinical necessity.
Diagnosis
Diagnosis and diagnosis of pediatric platelet release dysfunction
diagnosis
Clinical manifestation
(1) Autosomal dominant genetic disease or hereditary pattern is still unclear, with bleeding tendency or family history.
(2) Moderate bleeding: manifested as epistaxis, menorrhagia, excessive bleeding after trauma or surgery, no joint bleeding, a small number of bleeding can be fatal.
2. Experimental examination
(1) The platelet count is normal or slightly reduced, and the morphology is normal.
(2) The bleeding time is prolonged and can be normal.
(3) The clotting factor was checked normally.
(4) Platelet aggregation test: Add ADP or adrenaline, the second phase is normal, the second phase is obviously reduced or no aggregation, and a few can still be normal; collagen platelet aggregation is reduced, but it can be normal at high concentration.
(5) Reduced platelet adhesion.
(6) PF3 is lowered.
(7) Lack of or particles in platelets under electron microscopy or both.
(8) Excluding secondary platelet secretion dysfunction.
Differential diagnosis
1. Giant platelet syndrome This disease is an autosomal recessive disorder. Platelets in peripheral blood can be reduced with platelets with large morphology and platelet adhesion is reduced.
2. Platelet weakness is an autosomal recessive disorder, and platelets do not produce aggregation reactions on ADP, etc.
3. Acquired platelet function defects There is no family history of this disease, there are primary diseases such as uremia, myeloproliferative diseases or a history of drugs affecting platelet function. After the primary disease is cured, platelet function can return to normal.
