myeloproliferative disease
Introduction
Introduction to myeloproliferative diseases Myloproliferative disorders are a collective term for a group of diseases caused by the constant abnormal proliferation of certain or multi-lineage bone marrow cells. Clinically, there are one or more abnormalities in blood cytoplasm and quantity, splenomegaly, bleeding tendency, and thrombosis. Disease characteristics 1 lesions occur in pluripotent stem cells, but the source of fibroblasts has not been elucidated, may be a secondary response to abnormal proliferation of bone marrow stem cells. 2 each disease is often accompanied by one and two other cell proliferation, such as polycythemia vera can be associated with granulocyte and platelet hyperplasia. 3 can be transformed between the various diseases, and sometimes transitional, such as polycythemia vera can be converted to myelofibrosis. 4 cell proliferation can also occur in extramedullary tissues such as the spleen, liver, and lymph nodes. basic knowledge The proportion of sickness: 0.003%-0.005% Susceptible people: good for middle-aged men Mode of infection: non-infectious Complications: myelofibrosis systemic vasculitis recurrent polychondritis anemia
Cause
Causes of myeloproliferative diseases
Polycythemia vera (34%):
This disease is a myeloproliferative disease with clonal erythrocytosis. The JAK2V617F gene mutation can be found in 90% to 95% of patients. The course of disease is divided into: 1 red blood cell and hemoglobin increasing period: sustainable for several years. 2 myelofibrosis: usually occurs 5 to 13 years after diagnosis. 3 anemia period: there are giant spleen, extramedullary metaplasia and complete blood cell reduction.
Primary myelofibrosis (20%):
The cause of this disease is unknown, spleen, young red blood cell anemia, teardrop-shaped red blood cells. The bone marrow is often dry, and the biopsy confirms the proliferation of bone marrow fibrous tissue, and has a myeloid metaplasia in the spleen, liver, and lymph nodes.
Essential thrombocytosis (15%):
For hematopoietic stem cell clonal disease, about 50% to 70% of patients have JAK2V617F gene mutation. Also known as hemorrhagic thrombocytosis.
Prevention
Myeloproliferative disease prevention
Polycythemia vera: can survive for 10 to 15 years. Bleeding, thrombosis, and embolism are the leading causes of death. Individuals can evolve into acute leukemia, mostly dying within 2 to 3 years.
Essential thrombocytosis: Progress is slow and remains benign for many years. About 10% of patients are likely to be converted to other types of myeloproliferative diseases.
Primary myelofibrosis: a median survival of 5 years after a positive diagnosis. Nearly 20% of patients eventually evolved into acute leukemia. Most of the causes of death are severe anemia, heart failure, bleeding or repeated infections.
Complication
Myeloproliferative complications Complications, myelofibrosis, systemic vasculitis, recurrent polychondritis anemia
1. Marrow fibrosis
Nearly 50% of patients with MDS have mild to moderate reticular fibers in the bone marrow, of which 10% to 15% have significant fibrosis. Different from primary myelofibrosis, MDS with myelofibrosis in patients with peripheral blood often complete cytopenia, abnormal and broken red blood cells are rare; bone marrow often shows obvious three-line dysplasia, collagen fiber formation is very rare. And often no hepatosplenomegaly. MDS with myelofibrosis can be seen in various subtypes, which is considered by the author to be one of the factors suggesting poor prognosis. Another rare condition is called acute myelodysplasia with acute myel fibrosis (acutemyelodysplasia with myelofibrosis, AMMF). The patient has acute onset, symptoms and signs such as anemia, hemorrhage, infection, and no hepatosplenomegaly. The whole blood cells in the peripheral blood are reduced, and the morphology of mature red blood cells is lightly changed. Only a few broken red blood cells can be seen, and primitive cells, immature granulocytes or nucleated red blood cells can be seen. The area of hematopoietic tissue in bone marrow tissue sections increased, and the three lines of hematopoietic cells developed abnormally and became fibrotic. The number of megakaryocytes is increased and the abnormal morphology is very prominent. The primordial cells are moderately increased, but large fragments and clusters are not formed. In a few cases, there is an increase in focal crude collagen fiber deposition and focal osteogenesis. The patient is in serious condition and often dies of bone marrow failure or conversion to leukemia within a few months.
2. Combined with low bone marrow hyperplasia
About 10% to 15% of patients with MDS have significantly reduced nucleated cells in the bone marrow smear at the time of diagnosis, and the area of hematopoietic tissue in the bone marrow tissue section is reduced (the hematopoietic tissue area is less than 30% in patients under 60 years old, <20% in patients over 60 years old) . Some authors refer to this condition as hypoplastic MDS (hypoplastic or hypocellular MDS) and consider it to be a special subtype of MDS. In fact, this situation is difficult to distinguish from aplastic anemia. The following findings have helped to establish a diagnosis of MDS with low myeloproliferation: 1 dysplastic neutrophils or type I and type II blasts can be seen in the blood; 2 dysplastic granules can be seen in the bone marrow smear , erythroid cells, can see type I, type II blasts, especially small megakaryocytes; 3 small megakaryocytes can be seen in bone marrow sections, early granulocytes are relatively common or ALIP (), reticular fibers increase; 4 Bone marrow cells have common clonal chromosomal abnormalities in MDS; 5 can prove monoclonal hematopoiesis. Some authors believe that MDS with both myeloproliferative and severe aplastic anemia are the result of immune myelosuppression, but to varying degrees. Immunosuppressive therapy can be used.
3. Concurrent immune disease
In recent years, reports on MDS complicated with immune diseases have been increasing. Immune diseases can occur before, after, or at the same time as the diagnosis of MDS. Enright et al analyzed 221 patients with MDS and 30 patients with immune diseases, accounting for 13.6%. There are also 10 cases of clinical non-immune diseases, but there are serological abnormalities of immune diseases. Immune diseases that have been reported to occur in MDS include cutaneous or systemic vasculitis, rheumatoid osteoarthritis, inflammatory bowel disease, recurrent polychondritis, acute febrile neutrophilic dermatitis (AFND, or Sweet's Syndrome), necrotizing panniculitis, Hashimoto's thyroiditis, Sjogren's syndrome (Sjogren's syndrome), rheumatic polymyalgia, and so on. Immune diseases can be complicated by various subtypes of MDS, but more often in patients with clonal and complex chromosomal abnormalities. When MDS is complicated by certain immune diseases (such as Sweet's syndrome), the condition often deteriorates rapidly or turns white in a short period of time. Immunosuppressive therapy can control the condition and improve hematological abnormalities in some patients.
4. The most common complication is infection, fever
Mainly due to pulmonary infection, anemia, severe cases can be complicated by anemia. Bleeding is mainly found in skin, mucous membranes and internal organs bleeding, joint pain and so on. In acute leukemia MRS, the incidence of RA, RAS type evolved into acute myeloid leukemia was about 13%, and the survival time of this group was 50 months. In MDS, 35%-40% of RAEB and CMML group evolved into acute marrow. In cell leukemia, the median survival time is only 14 to 16 months. RAEB-T evolves into acute leukemia with a median survival of three months. About 20% of patients with MDS have bleeding manifestations, which are common in the skin, respiratory tract, digestive tract, etc., and also have intracranial hemorrhage.
Symptom
Symptoms of myeloproliferative diseases Common symptoms Tinnitus, dizziness, loss of appetite, forgetfulness, visual impairment, erythrocytosis
Polycythemia vera
The incidence of middle-aged and elderly people is more common in men. The onset is hidden, and it is found by accidental blood test. Increased blood viscosity can cause slow blood flow and tissue hypoxia, manifested as headache, dizziness, excessive sweating, fatigue, forgetfulness, tinnitus, vertigo, visual impairment, numbness and tingling of the extremities. With thrombocytosis, there may be thrombosis and infarction. Common in limbs, mesentery, brain and coronary blood vessels, severe convulsions. Basophilic granulocyte, his basophilic granules are rich in histamine, a large amount of release stimulates the gastric gland wall cells, can cause peptic ulcer; irritating skin has obvious pruritus. Endocardial damage, reduction of platelet factor 3, poor blood clot retraction, etc., can cause bleeding. Hyperuricemia can produce secondary gout, kidney stones and kidney damage.
The patient's skin and mucous membranes are markedly reddish purple, especially on the cheeks, lips, tongue, ears, nose, neck and extremities (finger and size). The ocular membrane is markedly hyperemia. Patients can be complicated with cirrhosis in the later stage, called Mosse syndrome. Patients with splenomegaly can develop spleen infarction and cause inflammation around the spleen. About half of the cases have high blood pressure. Gaisbock syndrome refers to the disease with hypertension and spleen.
Essential thrombocytopenia
Slow onset, fatigue, fatigue. The main clinical manifestations are thrombocytosis, splenomegaly, hemorrhage or thrombosis.
Primary myelofibrosis
The median age of onset was 60 years old, the onset was concealed, and the splenomegaly was found by chance. Symptoms include fatigue, weight loss, loss of appetite, pain in the left upper quadrant, anemia, compression symptoms caused by the spleen, and low fever, sweating, and tachycardia caused by increased metabolism. A few have bone pain and bleeding. Severe anemia and hemorrhage are the late manifestations of this disease. A small number of cases can be complicated by gout and kidney stones due to hyperuricemia. There is also a combination of cirrhosis, due to liver and portal vein thrombosis, resulting in portal hypertension.
Examine
Examination of myeloproliferative diseases
Polycythemia vera
(a) blood
The red blood cell capacity is increased and the plasma volume is normal. Red blood cell count (6 ~ 10) × 10 12 / L, hemoglobin 170 ~ 240g / L. Due to iron deficiency, it is a small cell with low pigmentation erythrocytosis. The reticulocyte count is normal and there may be a small number of young red blood cells. Leukocytosis, (10 ~ 30) × 10 9 / L, visible in young and late granulocytes. Neutrophil alkaline phosphatase activity was significantly increased. There may be thrombocytosis, (300 ~ 1000) × 10 9 / L. The blood viscosity is about 5 to 8 times normal. The radionuclide measures the increase in blood volume.
(two) bone marrow
Hematopoietic cells of all lines are significantly proliferated and adipose tissue is reduced. The ratio of grain red often decreases. Iron staining showed a reduction in stored iron. Megakaryocyte proliferation is often more pronounced.
(3) Blood biochemistry
Most patients have increased blood uric acid. May have hyperhisamine and hyperhidrosis. Serum vitamin B12 and vitamin B12 binding increased. Serum iron is reduced. Reduced erythropoietin (EPO) in blood and urine.
Essential thrombocytopenia
(a) blood
Platelets (1000 ~ 3000) × 10 9 / L, platelets in the smear gathered into a pile, the size is different, occasionally megakaryocyte fragments. In the aggregation test, the aggregation reaction induced by collagen, ADP and arachidonic acid decreased, and the disappearance of adrenaline was one of the characteristics of this disease. Between leukocytosis (10 ~ 30) × 10 9 / L, neutrophil alkaline phosphatase activity increased. If the semi-solid cell culture has spontaneous CFU-Meg formation, it is beneficial to the diagnosis of this disease.
(2) Bone marrow
The lines are obviously hyperplasia, mainly megakaryocytes and platelet hyperplasia.
Primary myelofibrosis
(a) blood
Normal cell anemia, a small amount of young red blood cells in the peripheral blood. The shape of mature red blood cells is different, and teardrop-shaped red blood cells are often found, which has the value of auxiliary diagnosis. The number of white blood cells is increased or normal, and young and late myelocytes can be seen, and even a few primary and promyelocytes appear. Neutrophil alkaline phosphatase activity is increased. Increased blood uric acid, no Ph chromosome. Late white blood cells and thrombocytopenia.
(two) bone marrow
Puncture is often dry pumping. In the early stage of the disease, bone marrow nucleated cells proliferated, especially granulocytes and megakaryocytes, but later showed low regeneration. Bone marrow biopsy showed non-uniform collagen fibrosis.
(three) spleen puncture
The performance is similar to the bone marrow smear smear, especially the megakaryocyte increase is most obvious.
(4) Liver puncture
There are extramedullary hematopoiesis, megakaryocytes and immature cells in the liver sinus.
(5) X-ray examination
Some patients have signs of osteopetrosis in the pelvis, spine, and long bones. The bone density increases, the trabeculae become thick and fuzzy, and there are irregular osteoporosis areas.
Diagnosis
Diagnosis and diagnosis of myeloproliferative diseases
Polycythemia vera
The main diagnostic indicators: 1 red blood cell volume is greater than 25% of the normal average, or hemoglobin amount male> 185g / L, female > 165g / L; 2 no secondary erythrocytosis exists, arterial blood pO2 92%; 3 spleen Large; 4 bone marrow cells have non-ph chromosome or non-BCR-ABL fusion gene clonal genetic abnormalities; 5 endogenous CFU-E, that is, without EPO, CFU-E can occur spontaneously. Secondary diagnostic indicators: 1 platelets greater than 400 × 10 9 / L; 2 white blood cells greater than 12 × 10 9 / L; 3 bone marrow biopsy showed whole myeloid cell proliferation, mainly erythroid and megakaryocytic hyperplasia; 4 serum EPO is low. Polycythemia vera can be diagnosed when there are any other major diagnostic criteria for the primary diagnostic criteria 1+2+ or the primary diagnostic criteria 1+2+ for any two secondary diagnostic indicators.
Need to be excluded: 1 secondary polycythemia, seen in a. chronic hypoxia, such as high altitude living, emphysema, cyanotic congenital heart disease, pulmonary heart disease, chronic rheumatic valvular disease, etc.; b. When a large amount of smoking increases carboxyhemoglobin and abnormal hemoglobin disease, the oxygen ion affinity curve shifts to the left, and the affinity with oxygen increases, causing tissue hypoxia, which can cause erythrocytosis; c. The secretion of EPO increases, such as renal cysts, Renal hydronephrosis, renal artery stenosis, etc. or suffering from liver cancer, lung cancer, cerebellar hemangioblastoma, uterine leiomyoma and other tumors. 2 relative polycythemia, seen in dehydration, burns and chronic adrenal insufficiency caused by blood concentration.
Essential thrombocytopenia
Platelets lasted more than 600 × 10 9 /L, and the bone marrow was dominated by megakaryocytic hyperplasia. Patients with secondary thrombocytosis, myelodysplastic syndrome and other myeloproliferative disorders can be diagnosed. Secondary thrombocytopenia is seen in chronic inflammatory diseases, acute infection recovery, tumors, massive bleeding, splenectomy, or after the use of epinephrine. Myeloproliferative diseases include polycythemia vera, chronic myeloid leukemia, and chronic primary myelofibrosis.
Primary myelofibrosis
In middle-aged and old people, the spleen and peripheral blood have teardrop-shaped red blood cells and immature red blood cell anemia, and the Ph chromosome is negative. Multiple bone marrow "dry pumping". Bone marrow biopsy found that collagen fibrosis can be diagnosed. Liver, spleen and lymph node puncture can be found in hematopoietic foci, suggesting myeloid metaplasia. The disease must be differentiated from the spleen caused by various causes. In addition, malignant tumor bone marrow metastasis, as well as blood system tumors such as chronic granulocyte leukocytes, lymphoma, myeloma, etc., may cause local proliferation of secondary bone marrow fibrous tissue, should also be identified with the disease.
