Pregnancy with thrombotic thrombocytopenic purpura
Introduction
Introduction to pregnancy with thrombotic thrombocytopenic purpura Thrombotic thrombocytopenic purpura (TTP) is a rare microvascular thrombosis-hemorrhagic syndrome characterized by fever, thrombocytopenic purpura, microvascular hemolytic anemia, central nervous system and kidney involvement, etc. The first three are called triad, the disease is mostly dangerous, the mortality rate is as high as 54%, young women are slightly more, and occur in the childbearing age, so they can be concurrent in pregnancy. It can also occur after a few days of therapeutic abortion, especially after childbirth. It is also caused by oral contraceptives and after hysterectomy. basic knowledge The proportion of sickness: 0.002%-0.003% Susceptible population: pregnant women Mode of infection: non-infectious Complications: systemic lupus erythematosus rheumatoid arthritis
Cause
Pregnancy with thrombotic thrombocytopenic purpura
(1) Causes of the disease
The etiology of TTP is unknown, and the cause of the disease is called primary. Some patients may be related to drug allergy, immune rheumatic diseases, pregnancy, various infections and heredity. In recent years, TTP related to HIV (human immunodeficiency virus) infection has been reported. With severe anemia and thrombocytopenia and mild renal insufficiency, one or more platelet aggregation factors (PAF) are present in the plasma of patients, or lack of PAF inhibitors present in normal plasma, causing platelet aggregation, and some people are in TTP The vWF macromultimer is isolated from the patient's plasma and can aggregate platelets in vitro. It is believed that the abnormal metabolism of vWF may also be related to the pathogenesis of TTP.
(two) pathogenesis
The pathogenesis has not yet been elucidated, and there are currently several possibilities:
1. Small vessel disease In the capillaries with obvious lesions, the pathological changes of the endothelium before thrombosis can be seen under electron microscope. Microscopic erythrocyte lysis can occur due to lesions in the microcirculation, which can aggravate local thrombosis. If the lesion is more extensive, it can lead to thrombocytopenia. TTP can be associated with systemic lupus erythematosus, rheumatoid arthritis, multiple nodular arteritis, Sjogren's syndrome, etc. Vasculitis lesions.
It has been found that the lack of a plasminogen activator in vascular endothelial cells of patients with TTP causes local fibrinolytic function to impede thrombosis in small blood vessels. Studies have confirmed that local platelet activation may play a role in the pathogenesis of TTP. In some patients with TTP, the aging plasma can gradually decrease the platelet aggregation activity. Therefore, it may be considered that there may be some platelet activating factor (PAF) in the plasma of the patient, or it may also lack the inhibition of platelet activating factor (PAFI) and cause disease. Significant aggregation of platelets requires binding of the polymeric VWF polymer to the GPIb in the platelet surface structure, followed by binding of plasma proteins [probably lyophilized human fibrinogen, thrombinmodulin (TM) and fibronectin] to GPIIb /IIIa complex goes up.
It is currently believed that vascular endothelial cell injury is one of the pathogenic factors of TTP. TM is a high-affinity thrombin receptor in vascular endothelial cells, placental syncytium trophoblasts and platelets. In 1991, Takahashi et al measured 13 cases of acute TTP. The patient's TM showed that the concentration of TM in 8 patients increased; the concentration of TM in patients with SLE was higher than that in patients without SLE, and the concentration of TM was significantly correlated with tissue plasminogen activator (t-PA) and vWF: Ag, but Regardless of the number of platelets, patients with acute TTP had no significant difference in TM concentration regardless of the condition. The authors believe that the vascular endothelial cells of TTP patients are damaged, but the degree is different, and the TM concentration has a certain relationship with the severity of the lesion.
2. Disseminated intravascular coagulation (DIC) The main pathological change of this disease is scattered thrombus in the microcirculation. Some people think that the essence of this disease is DIC. Takahashi et al detected plasma thrombin in 10 patients with acute TTP. Blood enzyme III complex (TAT) and plasmin-2-antiplasmin complex (PAP), patients with TAT, PAP values were higher than the normal control, but there was no correlation between the two, 5 patients After remission, the PAP and TAT values were significantly decreased, but the other end, the coagulation index was not abnormal. The authors believe that TTP patients do have increased thrombin and plasmin production, but most patients have no consumptive coagulation.
3. Prostatin (PGI2) synthesis is reduced or there is a lack of certain factors in the plasma to prevent PGl2 degradation. About 60% of patients with TTP can be relieved with whole blood or plasma, and if treated with 5% human albumin, the study is found to be worse. PGI, normal production, but its degradation rate is accelerated, suggesting that there is a factor in normal plasma that can prevent the rapid degradation of PGI2. It is not present in albumin. The half-life of this factor is 2 weeks, which can prolong the biological activity of PGI2. Lack of PGI2 reduction associated with microvascular thrombosis, Hensby et al (1979) reported a decrease in plasma 6-keto-PGFI in patients with TTP, further evidence of this doctrine.
Some people think that this disease is caused by a lack of vascular endothelial cells to promote the formation of PGl2. The use of dipyridamole can promote its formation and play a therapeutic role. It has also been reported that -TG released from agglutinated platelets can further prevent PGI2 synthesis. .
4. Immunology Some people believe that vascular lesions in TTP patients are caused by immune damage. The data show that IgG in TTP serum can kill endothelial cells by 70%, compared with 16.8% in the control group.
Bums incubated 3 serum-purified IgGs from TTP patients with cultured human umbilical vein endothelial cells. Immunofluorescence confirmed that IgG antibody was bound on the surface of endothelial cells. This specific antibody can induce endothelial cell lysis and vascular endothelial cell damage. It can cause PGI2 formation to be low, plasminogen activator to decrease, and finally lead to microthrombus formation.
Some reports indicate that TTP platelet surface-associated immunoglobulin (PAIgG) is increased, and the treatment is improved when it is improved. When IgG is attached to the surface of platelets, it is easily destroyed by the mononuclear macrophage system, resulting in a decrease in the number of platelets in the blood circulation.
Prevention
Pregnancy with thrombotic thrombocytopenic purpura prevention
Actively treat the primary disease, avoid or reduce the use of sulfa drugs, oral contraceptives, to prevent poisoning and infection.
Complication
Pregnancy with thrombotic thrombocytopenic purpura complications Complications systemic lupus erythematosus rheumatoid arthritis
It can be associated with systemic lupus erythematosus, rheumatoid arthritis, multiple nodular arteritis, and Sjogren's syndrome. These diseases are characterized by a certain degree of vasculitis.
Systemic lupus erythematosus (SLE) related to node symptoms, kidney damage, neurological symptoms, and hemolytic anemia, skin damage, LE cells are positive, no abnormalities in the peripheral blood and broken red blood cells.
Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic aggressive arthritis. Rheumatoid arthritis is characterized by synovitis, and the resulting articular cartilage and bone destruction, which ultimately leads to joint deformities.
Multiple arteritis refers to chronic non-specific inflammation that mainly affects the wall of the aorta, which can cause stenosis or even blockage of the lumen. The disease mainly involves the aorta and its main branches, so the blood supply to the head, upper limbs, lower limbs and internal organs may be affected, and the cause of the disease is unknown. Because this disease can cause the pulse of the upper or lower extremity arteries to weaken or disappear, it is also called "no pulse disease."
Sjogren's syndrome is a chronic inflammatory autoimmune disease that primarily affects exocrine glands. Because its immune inflammatory response is mainly manifested in epithelial cells of exocrine glands, it is also known as autoimmune exocrine gland epithelial cell inflammation or autoimmune exocrine disease. In addition to the loss of salivary gland and lacrimal gland damage, dry mouth and dry eyes, there are other symptoms of multiple systemic damage caused by other exocrine glands and other organs in the gland. There are various autoantibodies and high immunoglobulins in their serum.
Symptom
Pregnancy with thrombotic thrombocytopenic purpura symptoms Common symptoms Nose bleeding micro-thrombosis vaginal bleeding excessive hypertension jaundice coma abdominal pain sudden death arrhythmia
The onset is often rapid, typical cases have fever, fatigue, weakness, a small number of onset is slow, there are muscle and joint pain prodromal symptoms, other symptoms appear quickly, there are also pleurisy, Raynaud's phenomenon, women's vaginal bleeding as the initial complaint, HIV Infected patients 1/2 patients were asymptomatic, patients with fever accounted for 75%, neurological symptoms accounted for 40%, headaches accounted for 61%, typical clinical manifestations have the following characteristics.
1. Thrombocytopenia causes bleeding
Mainly skin mucosa, manifested as blemishes, ecchymosis or purpura, nosebleeds, retinal hemorrhage, genitourinary tract and gastrointestinal bleeding, severe intracranial hemorrhage, mainly due to the consumption of a large number of platelets during microvascular thrombosis To.
2. Microangiopathic hemolytic anemia
Mainly due to the blood flow through the diseased blood vessels (especially small arteries), red blood cells are mechanically damaged and destroyed, causing different degrees of anemia. Normal red blood cells are labeled with 51Cr and the half-life of TTP patients is only 3 days (normal 25 ~ 26 days), about 1/2 of the cases of jaundice, indirect bilirubin increased, 20% have liver and spleen, and in a few cases there is Raynaud.
3. Neuropsychiatric symptoms
The severity determines the prognosis of the disease. It is reported that 151 of 168 patients have neurological symptoms, accounting for 90%. The symptoms are characterized by changes, the initial is transient, 50% can be improved, and recurrent attacks can be made. There are varying degrees of confusion, 30% have headaches and/or aphasia, unclear speech, dizziness, convulsions, paralysis, paresthesia, visual impairment, sensory disturbances, disorientation, confusion, paralysis, lethargy, coma, cranial nerves Paralysis, 45% have convulsions, sometimes hemiplegia, can recover within a few hours.
4. Kidney symptoms
It is characterized by proteinuria, microscopic hematuria and tubular urine, but gross hematuria is not common, 40% to 80% have mild azotemia, and creatinine clearance decreases, which is related to the extensive involvement of renal blood vessels. Renal failure.
5. fever
It can be fever in different stages, often reaching 38~40.5 °C. The reason is unknown and may be related to the following factors:
(1) Secondary infection, but blood culture results were negative.
(2) hypothalamic body temperature regulation dysfunction.
(3) Tissue necrosis.
(4) Release of hemolytic products.
(5) The antigen-antibody reaction damages macrophages and granulocytes and releases an endogenous heat source.
6. Other
Multifocal hemorrhagic necrosis of the myocardium, microthrombus formation in the myocardium, heart failure or sudden death, electrocardiographic repolarization abnormalities or various arrhythmias, pulmonary insufficiency reported, abdominal pain, liver and spleen, A small number of lymph nodes are slightly enlarged, various types of rash, malignant hypertension, extensive necrosis of the skin and subcutaneous tissue, periarteritis and agammaglobulinemia.
Examine
Examination of pregnancy with thrombotic thrombocytopenic purpura
1. 100% of patients with blood have anemia, positive cells are pigmented, 1/3 of patients with hemoglobin <60g / L, blood cells in the deformation of red blood cells and debris accounted for 95%, and can see spherical red blood cells, nucleated red blood cells and Reticulocytes were significantly elevated (>30%), persistent thrombocytopenia accounted for 92%, median (8.0-40.4)×109/L, and elevated white blood cells accounted for 60%. Leukemia-like reactions were rare, but may have Significantly left shift, and immature granulocytes can be seen.
2. The bone marrow-like red blood cell system is significantly proliferated, and the number of megakaryocytes is normal or increased, and most of them are naive megakaryocytes, which are mature obstacles.
3. Coagulation examination bleeding time is normal, blood clot shrinkage is not good, beam arm test is positive, prothrombin time is prolonged by 20%, partial thromboplastin time is prolonged 8%, FDP positive accounted for 70%, thrombin time prolonged 48%, generally no laboratory changes in typical DIC.
4. The hemolysis index is directly negative in the Coombs test. The secondary ones can be positive, the serum bilirubin is elevated, the mild bilirubinemia is 84% to 100%, the free hemoglobin is elevated, and the haptoglobin is decreased. And hemoglobinuria.
5. Immunological examination 10% to 20% of patients with lupus cells can be positive, anti-nuclear antibodies 50% positive, a few rheumatoid factor positive, most of the complement is normal, LDH100% increased, and parallel with clinical pathology and severity.
6. Cerebrospinal fluid pressure and protein are slightly increased, the number of cells is normal, subarachnoid hemorrhage is rare, EEG is normal, or diffuse bilateral cortical abnormalities or localized rhythm abnormalities.
7. Skin biopsy is the safest pathological diagnosis method. 1/2 case positive in the defect area, 60% positive in the bone marrow clot section, and only 44% positive in the autopsy pathological examination, so the negative can not rule out the disease.
8. Transforming growth factor 1 (TGF1) increased, inhibiting bone marrow hematopoiesis, that is, the clinical observation of the lack of compensatory hematopoiesis, and some inhibition during the clinical remission period, so that platelet activation still exists.
9. ECG showed ST-T changes, and arrhythmia and conduction block were rare.
10. Chest radiographs can be seen in extensive alveolar and interstitial degeneration lesions.
Diagnosis
Diagnosis and diagnosis of thrombotic thrombocytopenic purpura in pregnancy
diagnosis
Most scholars believe that TTP can be diagnosed according to triad (microvascular anemia, thrombocytopenia and psychotic symptoms), but it is also considered necessary to have five signs (plus fever and kidney damage) to diagnose. The diagnostic criteria of Cutterman et al are as follows:
Main performance
(1) Hemolytic anemia, red blood cell debris and abnormal red blood cells can be seen in the peripheral blood.
(2) Platelet count <100×10 9 /L.
2. Secondary performance
(1) Fever, body temperature exceeds 38.3 °C.
(2) Characteristic neurological symptoms.
(3) Kidney damage, including serum creatinine > 177 mol / L and / or urine routine examination found hematuria, proteinuria, tubular urine.
If there are 2 main performances plus any secondary performance, the diagnosis can be established.
Differential diagnosis
1. Disseminated intravascular coagulation (DIC) The patient has no severe hemolytic anemia and transient variability of neuropsychiatric symptoms, but severe bleeding, thrombocytopenia, decreased coagulation factors, evidence of secondary fibrinolysis Protein C measurement was significantly reduced, tissue factor antigen was significantly increased, TTP thrombocytopenia, broken red blood cells, coagulation factors generally did not decrease, protein C was normal, FDP did not increase or slightly increase, 3P was negative, tissue factor antigen was mild Decreased, no significant increase in 1 month after treatment, and its inhibitor (TFPI) increased significantly, but sometimes the identification of TTP and DIC is more difficult.
2. Evans syndrome autoimmune hemolytic anemia with immune thrombocytopenic purpura, may have renal dysfunction, Coombs test positive, no deformity and broken red blood cells, no neurological symptoms.
3. Systemic lupus erythematosus (SLE) related to node symptoms, kidney damage, neurological symptoms, and hemolytic anemia, skin damage, LE cell positive, no abnormalities in the peripheral blood and fragmentation of red blood cells.
4. Hemolytic uremic syndrome (HUS) Currently, TTP and HUS are two different clinical manifestations of the same disease. It is a polygenic disease and belongs to thrombotic microangiopathy (TMA). The lesion of HUS is damaged by the kidney. Mainly, most children under the age of 4, occasionally seen in adults, often have upper respiratory tract infection symptoms and gastrointestinal symptoms, the most prominent manifestations of acute renal failure, in addition to microvascular hemolysis and thrombocytopenia, generally no spirit symptom.
