Introduction to polycythemia vera

Brief introduction: Polycythemia vera (referred to as true red) is a kind of chronic myeloproliferative disease with erythrocytosis and white blood cells and thrombocytosis. The total blood volume is absolutely increased, the blood is thick, and the clinical manifestation is red and purple. Dizziness, dizziness, headache, high blood pressure, hepatosplenomegaly, severe blood vessels, bleeding complications, infarction, etc. Etiology: 1. PV is a pluripotent stem cell disease. According to stem cell proliferation and differentiation theory, abnormal stem cells can directly lead to abnormalities of hematopoietic cells in various lines. Since PV manifests as a whole blood cell in peripheral blood and three lines of cell proliferation in bone marrow histology, it is speculated that PV is a stem cell disease in the 1950s. In 1976, Adamson et al. performed a glucose-6-phosphate dehydrogenase (G-6-PD) isozyme analysis on two women with PV, and found that their skin fibroblasts and lymphocytes contain two types of G-6- PD isoenzyme (GdA/GdB), while peripheral red blood cells, granulocytes, and platelets all contain the same type A G-6-PD (GdA). This suggests that they are derived from stem cells of type A isozyme, thus confirming that PV is an inference of stem cell disease. Using molecular biology techniques such as Southem hybridization and PCR, X-linked gene polymorphism and inactivation pattern analysis confirmed the above conclusions and found that about 80% of female PV patients had peripheral blood neutrophils as monoclonal. T lymphocytes are polyclonal. 2. Cellular and molecular level defects of PV In semi-solid medium, bone marrow cells cultured in PV patients can form spontaneous CFU-E and BFU-E colonies, while normal and secondary hyperplasia patients are none or very There are few spontaneous colonies. Unlike secondary polycythemia, the plasma and urine erythropoietin (EPO) levels in PV patients do not increase, so it is speculated that EPO may be abnormal with EMO signaling, perhaps EPO receptors (EPO-R). It is related to its abnormality, but studies on the structure of EPOY-R in PV patients indicate that there is no abnormal structure of EPO-R gene in PV patients. Recent studies have found that PV-derived progenitor cells are highly sensitive to EPO, insulin-like growth factor 1 (1GF-1), resulting in an uncontrolled production of erythroid cells. As PV patients progress, the increasing number of fibroblasts in the bone marrow is the result of reactive proliferation of platelet-derived growth factor (PDGF) released by megakaryocytes. Pv itself does not involve fibroblasts. 3. A large series of PV cytogenetic studies have shown that about 40% of patients have karyotypic abnormalities. Del(20)(q11), +8 and +9 are common abnormalities at the time of initial diagnosis. These abnormalities can be seen in the course of PV. It has little impact on clinical performance and disease duration and may be related to the disease itself. The chromosomal abnormalities that are currently thought to be associated with PV are del(1)(P11), del(3)(P11;p14), t(1;6)(q11;p21) and t(1;9)(q19; Q14). Since del(20)(q11) is the most common chromosomal abnormality in PV, people are looking for a target gene for PV. A common deletion fragment has been identified and an artificial yeast chromosome spanning this fragment has been constructed. This work is being further studied. Among them. Familial PV found in Jews of European descent suggests that there may be genetic predispositions in PV. In addition, some people think that PV is caused by the Friend virus variant "erythrocyte proliferative virus" infection. Injecting mouse spleen filtrate containing this virus into normal mice can cause red blood cell volume increase and splenomegaly, but It has not been fully confirmed in humans. (1) Causes of the disease The cause of this disease is still unclear. In most patients, the plasma and urine EPO levels did not increase, but decreased significantly. Cell culture showed that the number, affinity and expression of EPO receptors in erythroid progenitor cells of PV patients were not different from those in normal subjects. No abnormality was found in the sequence analysis of EPO gene. The above results showed that there was no EPO receptor in the pathogenesis of the disease. . Modern studies have shown that PV is not an excessive proliferation of normal stem cells, but is caused by abnormal clonal proliferation of single cell origin. (B) the pathogenesis of the bone marrow erythrocyte lineage significantly increased the pathogenesis of peripheral blood cell volume may be related to the following factors. 1. Formation of "endogenous" red blood cell clones When stem cells are cultured in vitro, normal bone marrow cells form late erythroid progenitor colonies (CFU-E), and EPO is added to the culture medium, while bone marrow cells of PV patients do not add EPO. It can grow, suggesting that this patient's red blood cell clone that does not rely on EPO production has "tumor" properties. If the bone marrow culture of PV patients is also supplemented with EPO, in the formed CFU-E, there are both PV cells and normal red blood cells, indicating that in addition to PV cell clones, PV patients still have normal stem cells, but their proliferation is affected. Inhibition of PV cloning. It is currently believed that abnormal clones of PV originate from a single cell, continue to proliferate, have the advantage of inhibiting normal clones, and have cytogenetic instability. Clinically, cases of PV conversion to acute leukemia can be found. 2. Erythroid progenitor cells are more sensitive to EPO. When the bone marrow cells of PV patients and normal humans are cultured in stem cells, the same concentration of EPO is added. The number of early erythroid progenitor colonies (BFU-E) and CFU-E in PV patients are normal. The number of people increased significantly, and the growth of CFU-E was significantly higher than that of patients without EPO. When EPO antibodies were added to the culture, the number of CFU-E production in PV patients decreased. These results suggest that erythroid progenitor cells in PV patients have increased sensitivity to EPO, which is one of the causes of erythrocytosis. 3. Apoptosis of pluripotent stem cells is normal. Normal red blood cells contain isoforms of two kinds of glucose 6-phosphate dehydrogenase (G-6-PD) of type A and type B, while red, granulocytes and platelets of PV patients only contain A. Type I, fibroblasts and lymphocytes still contain A and B type G-6-PD isoenzymes, indicating that the disease is a single clonal disease originating from the same pluripotent stem cell level. 4. Apoptosis abnormalities It has been found that the survival time of nucleated red blood cells in PV patients is significantly longer than that in normal people. PV colonies are highly sensitive to IL-3 and SCF, and these factors can delay the apoptosis of erythroid progenitor cells. Cell culture showed that PV patients and normal controls developed apoptosis in the absence of cytokine culture conditions, but PV patients had less apoptosis than normal controls, and this difference may be related to high expression of bcl-2 in PV patients. 5. Other experiments suggest that there may be a glycoprotein in the serum of PV patients, which can stimulate the formation of red blood cells and stimulate the granulocytes and platelets, called bone marrow stimulating factor. The antigenicity of this factor is different from that of EPO, but requires a small amount of EPO to participate. Its nature needs further study. Symptoms: The disease is insidious, often in the asymptomatic period of several months to several years, often found during blood tests. In some cases, the diagnosis is confirmed after thrombosis and bleeding symptoms. Many symptoms and signs are associated with increased blood volume and blood viscosity. The earliest symptoms are often related to blood circulation disorders and nervous system symptoms. The main clinical manifestations are as follows. 1. Skin changes are characteristic. It is characterized by reddening of the skin, especially on the face, neck and extremities. The mucosa is congested and is light blue. Osler described the symptoms as "summer as rose red, winter as indigo blue". Common telangiectasia, bleeding gums and nasal discharge. See also skin blemishes, cyanosis, sputum, hemosiderin deposition, rosacea and spoon-shaped nails. 50% of patients have watery itching. It can cause itching, burning or itching by shower or shower. Usually lasts for 30 to 60 minutes, regardless of water temperature. Itching can also occur irrespective of water. Histamine is elevated in the blood and in the skin. 2. Nervous system headache is the most common, 50% of patients have this performance, can be associated with dizziness, dizziness and tinnitus, fatigue, forgetfulness, limb numbness, sweating and so on. In severe cases, visual abnormalities such as blind spots, diplopia, and blurred vision may occur. There may also be angina and intermittent claudication. A small number of patients presented with a cerebrovascular accident as the first manifestation. This group of symptoms is mainly caused by increased erythrocyte count, increased blood volume and increased blood viscosity, vasodilation, slow blood stasis and tissue hypoxia. 3. The incidence of bleeding <10%, mainly due to vascular congestion, endovascular damage, reduction of platelet factor 3, etc., platelet dysfunction and abnormal blood coagulation mechanism lead to bleeding tendency. Common are nosebleeds, bleeding gums and stagnant spots and ecchymoses on the skin mucosa. It can also show gastrointestinal bleeding, bleeding after tooth extraction, and more menstrual flow. 4. The manifestation of elevated histamine The disease is accompanied by an increase in granulosa cells and an increase in basophils, which are rich in histamine. Increased histamine release can cause peptic ulcer, so the incidence of peptic ulcer in this disease patients is 10% to 16%, 4 to 5 times higher than normal people. Upper gastrointestinal bleeding caused by ulcers is more common and can be life-threatening. Itching is also common, with 40% occurring after a hot bath and 10% with urticaria. 5. Other causes of excessive proliferation of bone marrow cells, nucleic acid metabolism is too high, blood uric acid concentration is elevated, a small number of patients may develop uric acid nephropathy, manifested as urinary stones and renal colic or gouty arthritis symptoms. Some patients may have gallstones, obstructive jaundice and biliary colic. The most common signs are congestion of the face, nose, ears, lips, palms, and conjunctiva caused by multiple blood, which are crimson, such as drunkenness. The retina and oral mucosa also showed hyperemia. About 70% of patients have elevated arterial blood pressure. About 75% of patients may have splenomegaly, usually moderate to severe swelling, and have certain differential diagnosis significance with secondary polycythemia. About 40% of patients may have large liver, and with the development of the disease, the swelling is gradually obvious. [Diagnostic Criteria] The most important basis for diagnosing PV is erythrocytosis, leukopenia, thrombocytosis, and splenomegaly. Most patients have only two or three of the above characteristics at the time of presentation. Some patients even have only erythrocytes, and occasionally Only with increased thrombocytopenia or leukocytosis or splenomegaly, PV diagnosis is sometimes difficult to establish. In 1975, the PV Research Group (PVSC) proposed “diagnostic criteria, but the diagnostic criteria have been proposed for more than 20 years. Some of these contents have gained some new understanding, so there are constantly authors to supplement and revise them. Since PV has been Still a diagnostic diagnosis, only after the exclusion of secondary polycythemia (secondary polycythemia) and relative polycythemia (apparent polycythemia) can be diagnosed, the differential diagnosis points are listed in the table below. Laboratory tests can be carried out in two stages : The first stage includes complete blood count, urine routine, serum ferritin, VitB12 and folic acid levels analysis, inosine, liver function tests, blood picture analysis, COHb, abdominal ultrasound, after the exclusion of common secondary polycythemia, Perform a second phase of examination, including bone marrow biopsy, karyotype analysis, serum EPO level determination, oxygenation curve, lung function test, chest X-ray, electrocardiogram, etc. for further identification and diagnosis. Index PV secondary polycythemia relativeivity Polycythemia splenomegaly with or without leukocytosis with or without thrombocytosis with or without adrenaline The first wave of abnormal platelets with or without red blood cell volume increased normal arterial oxygen saturation normal decreased normal normal serum vitamin B12 increased normal normal neutrophil alkaline phosphatase increased normal normal bone marrow hyperplasia hyperplasia erythrocytosis Normal EPO level decreases and normal Read more...