Thrombotic thrombocytopenic purpura in children
Introduction
Introduction to thrombotic thrombocytopenic purpura in children Thrombotic thrombocytopenic purpura is also known as Moschcowitz syndrome, Baehr-Schiffrin syndrome, Thrombotic thrombocytopenic purpura, Thrombocyticangiothrombosis, thrombotic hemolytic purpura. The symptoms include thrombocytopenic purpura, hemolytic anemia, varying degrees of neurological symptoms, fever and kidney damage, and the typical pathological changes are caused by extensive thrombus obstruction of small blood vessels. basic knowledge The proportion of illness: 0.001% Susceptible people: children Mode of infection: non-infectious Complications: jaundice, acute renal failure
Cause
Pediatric thrombocytopenic purpura etiology
(1) Causes of the disease
The etiology of this disease is unknown, mainly due to small vascular disease, may have toxins, drug allergy, bacterial or viral infection, autoimmune, collagen disease and other theories, but have not been confirmed, common in diseases with small vascular disease, such as Lupus erythematosus, polyarteritis, Sjogren's syndrome and rheumatoid arthritis, due to small vessel disease, diffuse lesions of microvessels, so that intravascular hemolysis promotes thrombosis.
(two) pathogenesis
1. Pathophysiology: vWF is an essential component in the process of normal hemostasis. In the high-shear blood flow state, there is interaction between the surface of endothelial cells, platelet surface receptors and vWF multimers, leading to platelets and endothelial cells. Cell adhesion, vWF deficiency or abnormal molecular structure can lead to a more common hereditary hemorrhagic disease, von Willebrand disease (vWD). On the other hand, excessive vWF levels can cause chronic endothelial cell damage, which can lead to thrombosis. In sexually transmitted diseases, vWF is subjected to enzymatic hydrolysis after being secreted into plasma. The cleavage site is Tyr842-Met843 of its A2 domain, and the VWF cleavage protein (vWFCP) is performed by this cleavage. The thrombin-sensitive protein 1 motif of lysintegrin and metalloproteinase with thrombospodin type 1 motif 13, ADAMTS13, the greater the vWF multimer, the stronger the hemostatic activity, and the oversize TTP patients are prone to large The molecular weight of vWF multimers is more strongly combined with platelets under high shear conditions than usual, thus forming a wide range of microthrombus. Moake et al believe that the super large vWF is more The appearance of the polymer may be due to the lack of endothelial system to secrete vWF or the lack of an enzyme system that degrades vWF, a hypothesis confirmed by later studies.
In 1996, Furlan and Tsai demonstrated that a metalloproteinase cleaves vWF under divalent metal ion conditions, and its deficiency can lead to the formation of super-large vWF multimers. This metalloproteinase is vWFCP, and further studies have confirmed vWFCP structural defects and families. Sexual TTP is closely related, and acquired vWFCP autoantibodies cause non-familial TTP. Endothelial cell damage is considered to be a key trigger in the pathogenesis of TTP, leading to platelet aggregation and formation in the microvasculature of brain, kidney and other organs. Platelet thrombosis, in general, the microvascular endothelium is anticoagulated under normal conditions, but once destroyed or activated, endothelial cells will lose their anticoagulant activity and become procoagulants. Hamilton et al found that they are exposed to the complement complex C5b-9. Within a few minutes, human umbilical vein endothelial cells can release endothelial microparticles (EMPs). EMPs can express tissue factor, structural antigens CD31 and CD51 in the presence of TNFa for 24 to 48 hours, and exhibit procoagulant activity. Jimenez et al found TTP. The patient's plasma can induce brain and kidney EMPs levels to increase by 5 times, procoagulant activity by 2 to 3 times, and make fine Intercellular adhesion molecules (ICAM-1) expression increased 3-fold, VCAM-1 increased 13 times, while the control group of patients with ITP plasma and plasma does not have this effect.
It indicated that the occurrence of TTP may be mainly related to endothelial cell activation. It was found that the level of EMP in the acute phase of TTP was significantly increased. The level of EMP in the recovery phase was comparable to that in the control group. Therefore, they concluded that the plasma of TTP patients can be seen from the level of EMP and the expression of activating markers. Activation and induction of microvascular endothelial cell injury, recently they found that EMP overexpressing the relevant markers CD62E and CD54 released by plasma-induced microvascular endothelial cells in TTP patients, further supporting the role of endothelial cell activation in the pathogenesis of TTP, procoagulant EMP Release may play a major role in TTP. EMP may be a promising marker for TTP and other thrombotic disease activation and endothelial damage. EMP may trigger or expand the formation of platelet microthrombus, which is helpful for in-depth study of EMP. To deepen the understanding of TTP or thrombotic microangiopathy.
2. Pathological features: TTP belongs to microangiopathy, systemic arterioles and capillaries can be involved, excessively proliferating endothelial cells and platelet microthrombus block the blood vessels. This incomplete blockage causes red blood cells to form fragmented cells when passing through microvessels. (cleaved cells), microthrombotic granules under light microscopy, PAS and GIEMSA staining positive, immunofluorescence and electron microscopy studies have confirmed that the main components of this thrombus are cellulose and platelets, and occasionally can also find complement and immunoglobulin, due to endothelium Excessive hyperplasia of cells causes some thrombi to appear under the endothelium. Although there is no inflammatory cell infiltration like the usual inflammatory pathology, the endothelial cells of the affected blood vessels still have morphological and functional changes. Under electron microscopy, these cells are swollen and the cytoplasm is microscopic. There are many cellulosic components in the tube. The endothelial cells in the platelet aggregation area contain a large amount of cytoplasmic components, the surface of the endoplasmic reticulum is rough, the mitochondria is increased, the Golgi region is enlarged, and there are a large number of lysosomes. , no specificity, but with kidney, brain, spleen, pancreas, heart and adrenal gland The most common, especially from the heart, kidney, brain, endothelial cells are more susceptible to TTP plasma damage in the body, skin, gums and bone marrow biopsy can be found in 30% to 50% of patients with evidence of injury, the most common bleeding site is In the vicinity of damaged blood vessels, these areas appear as purpura, which is an ideal site for skin biopsy. Although pancreas and kidney bleeding and embolism are the most common, the most extensive bleeding often occurs in the brain, leading to more serious results.
Prevention
Pediatric thrombotic thrombocytopenic purpura prevention
The cause of this disease is unknown, and it can also be secondary to other diseases. It is also found to have familial disease. Common secondary factors include drugs, poisoning and immune diseases, etc., should be actively prevented, such as NO, dye, Paint, bee venom, snake venom, etc., should avoid contact and cause toxic damage.
Complication
Pediatric thrombotic thrombocytopenic purpura complications Complications jaundice acute renal failure
Concurrent infection, retinal hemorrhage, gastrointestinal and urinary tract bleeding, jaundice, causing acute renal failure.
Symptom
Symptoms of thrombotic thrombocytopenic purpura in children Common symptoms Jaundice epilepsy and epileptic seizures Brain nerve palsy Retinal hemorrhage Thrombocytopenia Renal failure Muscle tissue necrosis coma
Most patients with TTP have previous physical health (Idiopathic TTP), and about 15% of patients can be secondary to certain diseases. These patients are called secondary TTP. These common secondary causes are bacterial or viral infections. Pregnancy, collagen vascular disease or pancreatitis, etc., certain drugs can also induce TTP-HUS, such as clopidogrel, quinine, mitomycin C, cyclosporine and FK506 (immunosuppressive drugs), etc. The pathogenesis of TTP is not clear, but it has been found that some patients with TRP who have been taking clopidogrel can detect inhibitory antibodies to ADAMTS13. In most cases, the onset of TTP is sudden, the most common first symptom is bleeding and Abnormal manifestations of the nervous system, rapid development of neurological symptoms can occur headache, drowsiness, stupor, coma, cranial nerve palsy and seizures, fever does not necessarily appear at the beginning of the disease, as the disease progresses
1. Fever: often at 38 ~ 40 ° C, more than 90% of patients have fever, fever can be due to lesions invading the hypothalamus, tissue necrosis, hemolysed substance release, antigen-antibody reaction and concurrent infection.
2. Bleeding: mainly thrombocytopenia, purpura and retinal hemorrhage are the most common, followed by the gastrointestinal tract and urinary tract.
3. Hemolytic anemia: due to fibrin deposition in the capillaries, the lumen is narrowed, and the red blood cells are crushed to break, and different degrees of jaundice may occur due to hemolysis.
4. Symptoms of involvement of the nervous system: The blood vessels of the brain are invaded, and there are various kinds of symptoms, such as light and heavy, temporary or permanent neurological symptoms.
5. Renal lesions: visible renal tubular obstruction, and even renal cortical necrosis caused by acute renal failure.
Examine
Examination of thrombotic thrombocytopenic purpura in children
1. Anemia: often more serious, positive pigmented anemia, reticulocyte and nucleated red blood cells are significantly increased, red blood cell morphology is abnormal and broken, bone marrow red system is active, red blood cell life is shortened to 3 to 6 days, serum bilirubin is increased Indirect reaction.
2. Increased white blood cells: Some cases have leukemia-like reactions.
3. Platelets: thrombocytopenia, normal bone marrow megakaryocytes.
4. Others: There may be proteinuria, hematuria, blood urea nitrogen increased, vascular fragility test is often positive, should do a variety of imaging examinations, such as chest X-ray, gastrointestinal sputum angiography, B-ultrasound, brain CT and EEG Check the graph.
Diagnosis
Diagnosis and diagnosis of thrombotic thrombocytopenic purpura in children
According to the characteristics of clinical hemolysis, anemia, thrombocytopenic purpura, neurological symptoms, renal lesions and laboratory tests, it can be diagnosed.
Must be identified with the following diseases:
1 idiopathic thrombocytopenic purpura.
2 idiopathic autologous hemolytic anemia.
3 symptomatic hemolytic anemia.
4Evens syndrome (idiopathic thrombocytopenic purpura with immunological hemolytic anemia).
5 systemic lupus erythematosus.
