Essential thrombocythemia

Introduction to essential thrombocytosis Primary thrombocytosis (primary throbocythemia) is a myeloproliferative disorder characterized by hemorrhagic tendency and thrombosis. It means that the number of platelets in the peripheral blood exceeds the upper limit of normal platelet count by 400×109/L, and the function is not normal. The cells proliferate excessively. Because this disease often has repeated bleeding, it is also called hemorrhagic thrombocytosis, the incidence is not high, more common in those over 40 years old, the main pathophysiological characteristics are: clonality, reactive or secondary, familial or hereditary Sex, treatment remains to be resolved. basic knowledge The proportion of illness: 0.0005% Susceptible people: no special people Mode of infection: non-infectious Complications: venous thrombosis thrombosis

Causes of essential thrombocythemia

(1) Causes of the disease

Thrombocytopenia

Essential thrombocytopenia is a disease caused by clonal proliferation of a single abnormal pluripotent stem cell. The number of pathogenic megakaryocytes, the average megakaryocyte capacity increases, and platelet growth can reach 15 times the normal rate.

Stem cell disease

G6PD isoenzyme test confirmed that the disease is also a clonal disease of pluripotent stem cells, leading to the proliferation of bone marrow megakaryocytes, increased platelet production, and the release of platelets stored in the spleen and liver, but the platelet life is mostly normal.

Platelet function defect

Adhesion and aggregation function decreased, platelet third factor decreased, serotonin decreased and release function was abnormal. Some patients still had abnormal blood coagulation mechanism, increased capillary fragility, and excessive thrombocytosis, activated platelets produced thromboxane, easily caused The aggregation and release of platelets can form thrombi in the microvessels, and extramedullary hematopoiesis in the spleen and other organs in the late stage.

(two) pathogenesis

The nature of cloning was established because an isoenzyme of glucose-6-phosphate dehydrogenase (G-6-PD) was found in the red blood cell line of a female case of this disease, which was expressed as two types of G-6-PD "A". Heterozygous with "B", the same abnormality was found in the erythroid and granulocyte progenitor cells of another patient. The main phenotype of this disease is expressed in the megakaryocyte-platelet system. The cause may be abnormal. - The regulatory factors of the platelet system are related to the dominant reaction, and the mutation may occur in pluripotent stem cells whose differentiation is mainly megakaryocyte-platelet. The histological examination and in vitro culture of megakaryocytes indicate abnormal expansion of megakaryocyte progenitor cells in the bone marrow of the disease. Increased, the megakaryocyte colony forming unit (CFU-MEG) in patients with bone marrow and blood increased significantly compared with normal or secondary thrombocytopenia, which may be accompanied by abnormal CFU-MEG clonal size and nuclear nuclear replication. CFU-MEG growth is also common when no exogenous growth factors are added, and a few cases are accompanied by an increase in granulocyte-monocyte colony forming units and erythrocyte colony forming units.

When the number of megakaryocytes, the average megakaryocyte capacity increased, platelet production reached 15 times the normal rate, platelet life is usually normal, a small number of cases may be caused by spleen destruction of platelets, a large number of platelets increase the mechanism of bleeding and thrombosis Certainly, it is generally believed that abnormal platelet function is the main cause of bleeding. Some patients may have one of the causes of clotting factor reduction. The significant increase in the number of platelets leads to high-aggregate thrombosis. The intrinsic defects of platelets are characterized by a decrease in serotonin in platelets. Decreased adhesion function, decreased ADP and adrenaline-induced platelet aggregation, etc., the megakaryocyte proliferation of this disease is not only in the bone marrow, but also may involve extramedullary tissue, liver, spleen and other tissues may appear megakaryocyte-based hyperplasia, Due to the low degree of malignancy, the growth rate is slow, the liver and spleen are often moderately enlarged, and no external pathogenic factors related to the disease have been found so far.

Prevention of essential thrombocytosis

Patients need to visit frequently, monitor peripheral blood changes, adjust medications in time, understand the evolution of the disease, pay attention to self-protection, prevent traumatic bleeding, and take small doses of enteric-coated aspirin to reduce platelet and platelet aggregation.

Essential thrombocytopenia complications Complications, venous thrombosis, thrombosis

About 30% of patients with arterial or venous thrombosis, often involving limb veins, can also occur in the liver, spleen, kidney, mesentery and portal vein, etc., embolism of heart, brain, kidney and other organs may have corresponding clinical symptoms, 20% asymptomatic Spleen infarction, leading to spleen atrophy.

Symptoms of essential thrombocytosis common symptoms erythrocytosis insomnia fatigue sensory venous thrombosis spleen embolism

Slow onset, clinical manifestations vary, about 20% of patients, especially young people with asymptomatic onset, occasional blood test or splenomegaly confirmed. Lighter people only have dizziness and fatigue; in severe cases, there may be bleeding and thrombosis. Bleeding is often spontaneous, recurrent, about 2/3 of the disease, common gastrointestinal bleeding, but also nasal, gingival bleeding, hematuria, skin and mucous membranes, but purpura is rare. The incidence of thrombosis is less than that of bleeding. Domestic statistics show that 30% have arterial or venous thrombosis. After limb embolism, it can show limb numbness, pain, and even gangrene, as well as erythematous limb pain. Spleen and mesenteric vascular embolization can cause abdominal pain and vomiting. Lung, brain and kidney embolism cause corresponding clinical symptoms. Splenomegaly accounts for 80%, usually mild to moderate. A small number of patients have hepatomegaly.

Examination of essential thrombocytosis

(1) Blood image

The platelet count is mostly between 1 million and 3 million/mm ³ , and the highest is 20 million/mm ³ . The blood platelets are aggregated into piles. The size varies, and there are huge deformities. Occasionally, megakaryocyte fragments and naked nuclei, white blood cells are also seen. The number can be normal or increased, mostly in the range of 10,000 to 30,000/mm ³ , generally not more than 50,000/mm ³ , classified as neutral lobular granulocytes, occasionally young cells, 30% of patients with red blood cells Normal or slightly increased, the shape is different, more staining, can also appear Hao-gel body and basophilic spot color, a small number of patients with repeated bleeding leading to hypopigmentation anemia, may have mild anemia, hemoglobin Rarely less than 100g / L, some patients can increase hemoglobin, but the red blood cell capacity is normal, neutrophil alkaline phosphatase score is generally normal, occasionally reduced or increased.

(2) Bone marrow

The nucleated cells, especially the megakaryocytes, proliferated significantly, the original and young megakaryocytes increased, the platelets aggregated into the heap, the alkaline phosphatase activity of neutrophils increased, the proliferation was active or significantly active, the megakaryocyte cell line increased significantly, and the primitive and naive megakaryocytes In the latter case, megakaryocytes can be clustered, platelets are often aggregated into a large number of cells, most patients have no cytogenetic abnormalities, and some cases have abnormal chromosomes. If Ph chromosome or bcr/abl fusion gene is present, Chronic myeloid leukemia, although these reported cases do not have a significant increase in leukocyte counts and other features of chronic myeloid leukemia, but the development of the course is more prone to chronic myeloid leukemia, most cases die from accelerated or acute changes.

(three) out, blood coagulation test

Prolonged bleeding time, shortened consumption time of thrombin principle, poor blood clot retraction, prolonged prothrombin time, thromboplastin production disorder, platelet adhesion function and aggregation function induced by adrenaline and ADP, but the collagen aggregation reaction is generally normal. .

(four) platelet life

Generally normal, sometimes mildly shortened, platelet function may be reduced, especially adrenaline-induced platelet aggregation is more obvious, platelet aggregation function may also be enhanced and spontaneous aggregation occurs.

(5) Others

Bleeding time can be normal or mildly prolonged, coagulation test is normal, in some cases plasma von Willebrand factor levels are reduced or subunit structure is abnormal, other platelet defects have a dense body number reduction and its contents ADP, ATP and serotonin decrease ( Acquired storage pool disease), decreased -adrenergic receptors, impaired membrane coagulation activity, decreased cyclooxygenase activity, abnormal membrane glycoprotein, enhanced Fc receptor, and decreased prostaglandin D2 receptor. However, these defects have not been linked to the complications of hemostasis. The chromosome examination has a long arm loss of 21 (21q-), and there are also variations in the size of the long arm of chromosome 21.

Blood uric acid and vitamin B12 are often increased. In some patients, pseudohyperkalemia is associated with potassium release from a large number of platelets.

According to the condition, clinical manifestations, symptoms, choose to do ECG, B-ultrasound, X-ray, CT, MRI, biochemical, liver, kidney function tests.

Diagnosis and diagnosis of essential thrombocytosis

Diagnostic points

Inspection

Blood routine and platelet count examination should pay attention to observe the abnormality of platelet morphology, clotting time, platelet function measurement, neutrophil alkaline phosphatase score, bone marrow aspiration and biopsy help to rule out secondary thrombocytosis, Ph Negative chromosomes help to differentiate from chronic myeloid leukemia.

2. Diagnostic criteria

The course of essential thrombocytosis is slow, many patients are asymptomatic for a long time, and the use of automatic blood cell examination equipment increases the chances of diagnosing asymptomatic cases. The increase of platelets without cause should be considered, and other myeloproliferative diseases and secondary diseases should be excluded. Diagnosis can be made after thrombocytopenia, and the diagnostic criteria proposed by Mushy et al.

1 platelet count is above 600 × 10 ⁹ /L.

2 hemoglobin 130g / L or normal red blood cell volume (male <36ml / kg, female <32ml / kg).

3 bone marrow iron staining normal or iron test treatment is ineffective (iron treatment 1 month hemoglobin rise <10g / L).

4 no Ph chromosome.

5 bone marrow pathological examination without collagen fibers, or no spleen, immature granulocytes and red blood cells reaction collagen fibers less than 1/3 of the biopsy area.

6 non-responsive thrombocytosis.

Diagnostic criteria and basis

(1) Clinical manifestations: There may be bleeding, splenomegaly, symptoms and signs caused by thrombosis.

(2) Laboratory inspection:

1 platelet count > 1000 × 10 ⁹ / L.

2 The blood platelets piled up in piles and there were huge platelets.

3 myeloproliferation is active or above, or megakaryocytes are enlarged, large, and cytoplasm rich.

4 white blood cell count and neutrophil increase.

5 platelet adrenaline and collagen aggregation reaction can be reduced.

Where clinically consistent, platelets > 1000 × 10 ⁹ / L, can exclude other myeloproliferative diseases and secondary thrombocytosis, can be diagnosed as essential thrombocytosis.

Diagnostic evaluation: A considerable number of patients with this disease are asymptomatic. Blood tests have found that thrombocytosis is found in patients with thrombocytosis or physical examination. It is found that thrombocytosis is diagnosed. It is obvious that the increase of platelet count is the basic condition for diagnosing this disease. The platelet count was set to >600×109/L, but it was later found to have a large overlap with secondary thrombocytosis, so the widely accepted standard is the platelet count >1000×10 ⁹ /L, but clinically There are indeed platelets that continue to be (600-1000)×10 ⁹ /L without secondary factors. Some patients have embolized in this range. Therefore, platelet count is not the absolute standard for the diagnosis of this disease. Factors such as clinical factors and laboratory tests are considered, that is, secondary thrombocytosis must be ruled out to confirm the diagnosis.

Primary and secondary identification

Primary thrombocytosis should be distinguished from secondary thrombocytopenia, which is seen in association with chronic inflammatory disease, acute infection and recovery, after massive bleeding, hemolytic anemia, malignancy, splenectomy time And adrenal drugs good luck reaction. Secondary because of the mild to moderate increase in platelets, the platelet function is normal. If the cause of the disease can be removed, the sister can be restored in a short period of time. It is also associated with the communication of chronic myeloid leukemia, polycythemia vera, and other acute myeloproliferative diseases. Any clinical manifestations that are consistent with primary thrombocytopenia, platelets greater than 1000 × 10 ⁹ , and can exclude the aforementioned secondary thrombocytosis and other experience of myeloproliferative diseases, can diagnose the disease.

Identification with other diseases:

(1) Other myeloproliferative diseases

Myeloproliferative diseases such as polycythemia vera, chronic myeloid leukemia, and myelofibrosis can be associated with thrombocytosis. However, polycythemia vera is characterized by erythrocytosis. Chronic myeloid leukemia is mainly composed of granulocyte series, white blood cells in blood are significantly increased, immature granulocytes appear, neutrophil alkaline phosphatase score is significantly reduced, and Ph chromosome can be seen on chromosome examination. In the peripheral blood of patients with myelofibrosis, there are young red and young cells, the size of red blood cells is different, and teardrop-like red blood cells are seen. Most of the bone marrow is dry and the bone marrow biopsy has fibrosis.

(two) secondary thrombocytosis

Found after splenectomy, spleen atrophy, acute or chronic blood loss, trauma and surgery. Drug reactions such as chronic infection, rheumatoid arthritis, rheumatism, necrotizing granuloma, ulcerative colitis, malignant tumors, childbirth, and adrenaline can also cause thrombocytosis. Bone marrow cell culture, primary thrombocytosis has spontaneous megakaryocyte colony formation, which can be distinguished from secondary.

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