Polycythemia vera in the elderly

Introduction to acute polycythemia in the elderly Polycythaemia vera is a clonal, chronic myeloproliferative disorder of unknown etiology characterized by a marked increase in red blood cells. It is characterized by a marked increase in total red blood cell count and total blood volume, usually accompanied by increased granulocytes and thrombocytosis; increased blood viscosity; bone marrow hyperplasia, advanced bone marrow fibrosis and extramedullary hematopoiesis; splenomegaly, skin and mucous membranes It has a unique reddish purple color and a variety of blood vessel and nervous system symptoms. basic knowledge Sickness ratio: 0.05% Susceptible people: the elderly Mode of infection: non-infectious Complications: thrombosis, jaundice, myelofibrosis, leukemia

The cause of polycythemia in the elderly

(1) Causes of the disease

The etiology is unknown. The hypoxic stimulation of red blood cells by bone marrow hypoxia; the increase of erythropoietin; the prolongation of red blood cell life has been overturned. In recent years, studies have shown that red blood cell life is not prolonged, but excessive autologous red blood cell production; The disease is a clonal disease that occurs at the level of pluripotent stem cells. The patient's red blood cells, granulocytes and platelets contain only glucose-6-phosphate dehydrogenase (G-6-PD) isoenzyme A, while fibroblasts. And lymphocytes still contain (G-6-PD) isoenzyme A, B type, indicating that red blood cells, granulocytes and megakaryocytes originate from the same abnormal pluripotent stem cells, and the possible mechanisms of hematopoietic cell proliferation are:

1 Stem cell tumor proliferation is out of control;

2 There is an abnormal myeloid growth factor;

3 Stem cells have increased sensitivity to erythropoietin and other hematopoietic factors. It has been reported that patients with bone marrow and mononuclear cells in semi-solid culture, even in the absence of exogenous erythropoietin, have erythroid ancestors Cell clone forming unit (CFU-E), called endogenous CFU-E. If erythropoietin is added to the above culture system, not only CFU-E is increased, but also occurs in G-6-PD isoenzyme A and The cloning of type B B showed that there were two kinds of cell clones, normal and abnormal. It was envisaged that normal stem cell clones in the bone marrow were inhibited by an unknown mechanism and caused the proliferation of abnormal cell clones. The generated red blood cells could not be produced by red blood cells. The erythropoiesis is increased by the hormone or erythropoiesis, and the production of erythropoietin is also inhibited, so that the normal red blood cell line is in a relatively rest state. In addition, it is suggested that there may be a factor stimulation in the patient's serum. The effects of can and erythroid stem cell production, and experiments have shown that erythroid progenitor cells can spontaneously differentiate in various culture systems. Growth, abnormally sensitive to erythropoietin, the addition of anti-erythropoietin antibody to the culture system can inhibit the formation of erythroid clones, but can not be eliminated, however, it has also been mentioned that in normal humans and patients in cell culture, red blood cells There was no difference in the shape of the pheromone dose response curve, indicating that the cells did not significantly change the sensitivity to erythropoietin.

(two) pathogenesis

The pathogenesis is still not fully understood. MeCulloch summarizes the clonal hyperplasia data and considers that the abnormal clone of polycythemia has the following three characteristics: 1 from a single cell origin, sustained proliferation; 2 abnormal clones have the advantage of inhibiting normal clones, late normal clones Disappeared; 3 abnormal clones have cytogenetic instability, and occasionally see cases of true red conversion to acute leukemia, similar phenomena can be seen in chronic myeloid leukemia, essential thrombocytosis and primary myelofibrosis Myeloid metaplasia, McCulloch called it "clonal blood disease."

Elderly erythrocytosis prevention

Because the cause of this disease is unclear, its prevention is mainly in early diagnosis and early treatment.

1. Pay attention to the early detection of risk factors: for patients with facial and limbs often purple, do not mistakenly believe that facial telangiectasia or emotional agitation, for frequent dizziness, headache, dizziness, limb numbness and other neurological symptoms are not simple Considering hypertension or cerebral insufficiency, if the patient is not cured by systemic treatment, blood routine and blood rheology should be checked to detect the abnormal increase of red blood cells at an early stage.

2. For patients who have been diagnosed, they should be treated reasonably to prevent serious complications. For patients who have had movements, venous thrombosis and major organ infarction, control the development of the disease, strengthen the function recovery of the organs, and improve the quality of life of patients. .

Elderly erythrocytosis complications Complications, thrombosis, jaundice, myelofibrosis, leukemia

The most common complications include hemorrhage, thrombosis, obstructive jaundice, biliary colic, myelofibrosis, and leukemia.

Symptoms of polycythemia in the elderly Common symptoms Tired erythrocytosis Skin itching Freckle cysts Sclerotherapy Hemorrhagic tendency Angina pectoris Hemorrhoids bleeding Congestion

Insidious onset, often found in blood routine examination, some cases are diagnosed after thrombosis and bleeding symptoms, the main clinical manifestations are as follows:

1. The performance of blood vessels and nervous system

In the early stage, there may be headache, dizziness, dizziness and tinnitus, fatigue, forgetfulness, numbness of the limbs, excessive sweating, etc. In severe cases, blind spots, diplopia and blurred vision may be present, and angina and intermittent claudication may also occur. Mainly due to increased red blood cell count, increased blood volume and increased blood viscosity, vasodilation, slow blood stasis and tissue hypoxia.

2. Thrombosis and embolism symptoms

Can occur in peripheral arteries, cerebral arteries and coronary arteries, causing severe consequences such as hemiplegia and myocardial infarction. Thrombophlebitis with embolism mainly occurs in the lungs, but mesenteric, liver, spleen and portal veins can also occur, which can cause acute abdomen When accompanied by an increase in platelet count, the chance of this group of symptoms increases.

3. bleeding symptoms

Platelet dysfunction, such as vascular congestion, endovascular damage, and reduction of platelet factor 3, can lead to bleeding tendencies, such as epistaxis, bleeding gums, and blemishes and ecchymoses on the skin's mucosa.

4. The performance of histamine increased

This disease with increased granulosa cells, basophils also increased, the latter is rich in histamine, increased histamine release can cause peptic ulcer, so the incidence of peptic ulcer in this patient is 4 to 5 times higher than normal people, ulcers The resulting upper gastrointestinal bleeding can be life-threatening, and itching is common, with 40% occurring after a hot bath and 10% with urticaria.

The most common signs are bleeding, facial, nasal, ear, lip, palm and conjunctival congestion, dark red, such as drunkenness, retinal and oral mucosa also showed congestion, arterial blood pressure increased, about 3 / 4 patients There may be splenomegaly, because secondary polycythemia usually does not have splenomegaly, so the signs of splenomegaly have certain differential diagnosis significance, splenomegaly is not caused by increased blood volume, so the spleen will not shrink when bloodletting treatment, about One third of patients may have hepatomegaly, and the swelling will gradually become obvious with the disease. Cirrhosis may occur in the advanced stage. The liver and spleen are not swollen in about 10% of cases. Excessive hyperemia and extramedullary hematopoiesis may cause spleen. The main cause of swelling.

Examination of acute polycythemia in the elderly

Blood

Venous blood is characteristic dark, thick red, red blood cell volume increased significantly, male 36ml / kg, female 32ml / kg (normal male 28.27 ± 4.11ml / kg, female 24.21 ± 2.59ml / kg, chromium labeled red blood cell method) The plasma volume of about 2/3 cases is lower than the lower limit of normal value, no more than normal value, blood viscosity is 5-8 times higher than normal, blood specific gravity is increased by 1.070~1.080 (normal 1.052~1.058), arterial blood Oxygen saturation 92%, if > 92%, is helpful to identify the secondary erythrocytosis caused by cardiopulmonary disease, it is worth noting that blood samples should be sent in time to avoid pseudo-hypoxemia.

Blood picture

At the first visit, the red blood cell count is mostly (6 ~ 10) × 1012 / L, and even up to (12 ~ 15) × 1012 / L; hemoglobin concentration can reach (180 ~ 260) g / L (18.0 ~ 26.0g / dl) The hematocrit is 0.600.80, the red blood cells are slightly different in size, occasionally the red blood cells or young red blood cells, the number of reticulocytes is normal, the reticulocytes can be increased after repeated hemorrhage, the red blood cells are easier to see, and the red blood cell state is lacking. When iron anemia is seen, the white blood cell count is mostly higher than normal, and is usually around 25×109/L. A few of them are above 50×109/L. There are also normal or reduced, the number of granulocytes increases, and there is a nuclear left shift phenomenon. Sometimes seeing neutral late-young and myelocytes, eosinophils and basophils; no granulocytes are seen, platelet counts are often increased (domestic data, about 2/5 cases have increased, foreign statistics, Seen in 3/5 to 4/5 cases, usually at (300 ~ 1000) × 109 / L, individual more than 3000 × 109 / L, visible giant and deformed platelets and megakaryocyte debris.

3. Bone marrow examination

Most of the bone marrow smears showed significant proliferation of hematopoietic cells, increased number of megakaryocytes, and volume change; the percentage of nucleated red blood cells increased moderately; granules were more common in neutral late granulocytes and rod nucleated cells, eosinophils and The basophils are slightly increased. About 90% of the patients have reduced or absent iron and blood in the bone marrow cells before and after the bloodletting treatment. The bone marrow cells are also proliferated, and 10% to 20% of the cases are in the bone marrow biopsy. In the early stage of the disease, there is an increase in net hard protein and/or fibrosis. Barrlte et al. suggest that bone marrow biopsy can be divided into four types:

1 Classical three-line cell proliferation accompanied by giant megakaryocytes, almost lacking fat cells;

2 Both red blood cells and megakaryocytes are proliferated, megakaryocytes are clustered, and fat cells can be increased;

3 red blood cells and granulocyte two lines of proliferation with a few atypical megakaryocytes;

4 single-erythroid cell hyperplasia, bone marrow electron microscopy, the original red and early red blood cells have a deep reflex of the nuclear membrane, and there are curtain-like protrusions on the neutrophil nuclear membrane.

4. Chromosome examination: Modern studies have shown that some untreated patients have a variety of non-specific autosomal aberrations, the most common abnormalities are 5q-, 20q-, C group additional chromosomes, etc. Certain value.

5. Erythrocyte progenitor cell culture: Erythrocyte progenitor cells can spontaneously differentiate and grow in various culture systems, and are extremely sensitive to erythropoietin. CFU-E can be formed with little or no need. This test has a diagnosis. value.

6. Determination of erythropoietin: The erythropoietin in plasma and urine is significantly reduced or absent by radioimmunoassay, which is different from most of the secondary polycythemia.

7. The binding of serum vitamin B12 and unsaturated vitamin B12: In the untreated patients, the values of these two tests increased, but the two were not parallel, and the binding of unsaturated vitamin B12 increased in about 2/3 cases. The vitamin B12 content is normal. This test is helpful for identification of secondary erythrocytosis and can be used as an indicator of efficacy and disease activity.

8. Other

The erythrocyte sedimentation rate is obviously slow, the neutrophil alkaline phosphatase score is mostly higher than normal, the uric acid content in serum and urine is often increased, and the urine uric acid is labeled with nitrogen-glycine. The rapid peak of the patient is different from the primary gout, and the red blood cell life is mostly Normally, the hemoglobin production rate is about 2.5 times normal, the plasma iron renewal rate is increased, the bleeding and clotting time are normal, and the proliferating cell nuclear antigen (PCNA) of erythroid hematopoietic cells is detected, which can be distinguished from reactive polycythemia. When the number of platelets is significantly increased, there may be pseudohyperkalemia, and high blood and urinary histamine values are common.

The basal metabolism is slightly elevated.

Diagnosis and differentiation of acute polycythemia in the elderly

Diagnostic criteria

It has three major manifestations of skin and mucous membrane rose red, splenomegaly, whole blood cells, especially erythrocytosis, accompanied by typical cases of normal arterial oxygen saturation. The diagnosis is not difficult. The 1968 erythrocytosis research group proposed The diagnostic criteria have been widely adopted, and the diagnostic criteria are as follows:

1 total red blood cell volume, male 36ml / kg, female 32ml / kg (51Cr red blood cell labeling method);

2 arterial oxygen saturation 92%;

3 splenomegaly.

Secondary indicators include:

1 platelet count 400 × 109 / L;

2 white blood cell count>12×109/L (no fever or infection);

3 neutrophil alkaline phosphatase score > 100 (no fever or infection);

4 serum vitamin B12>664.02pmol/L (900pg/ml), unsaturated vitamin B12 binding capacity>1623.12pmol/L (2200pg/ml), all three of the main indicators in the diagnostic criteria or in line with the main indicators 1, 2 items, plus any 2 items of the secondary indicators, the diagnosis is established. If the total red blood cell capacity is temporarily and unconditionally measured, refer to the diagnostic criteria proposed by Modan in 1971: A. Hematocrit male > 55%, female > 50%; B No clear cause of secondary or relative polycythemia; C. Meets any of the following 3 items, ie, white blood cell count >12×109/L (12000/mm3) (no fever, infection); platelet count> 300 × 109 / L (300,000 / mm3); arterial oxygen saturation is normal; neutrophil alkaline phosphate score > 100; whole bone marrow hyperplasia, with megakaryocytes increased; splenomegaly.

Secondary polycythemia is seen in alpine disease, right-to-left shunt congenital heart disease, chronic lung disease, methemoglobinemia, increased oxygen affinity hemoglobin disease, smoking-induced carboxyhemoglobin hyperemia, various Tumors, especially liver, kidney, brain and uterine tumors, hydronephrosis, renal artery stenosis, renal cysts, adrenal hyperfunction, and long-term use of androgen, sleep apnea syndrome may also be associated with erythrocytosis, mostly due to Tissue hypoxia causes an increase in erythropoietin, resulting in a compensatory increase in red blood cells; an abnormal increase in erythropoietin or erythropoietin-like substance causes polycythemia, and relativity and stress erythrocytosis are seen in severe dehydration, scald, adrenal function In middle-aged patients with diminished and neurotic, obese, and mild obesity, most of the above have obvious causes, and the systemic blood volume is reduced. It is not difficult to distinguish from polycythemia vera. If the blood volume is reduced, it is not difficult to identify with polycythemia vera.

Differential diagnosis

If there is swelling of the spleen, the number of cells in the bone marrow and blood increases, but the degree of erythrocytosis is not obvious enough, it is necessary to consider the possibility of early stage of chronic myeloid leukemia or early stage of myelofibrosis, but the early stage of chronic myelogenous leukemia is characterized by mild Erythrocytosis instead of anemia, in addition, 10% to 40% of patients have obvious symptoms similar to chronic myeloid leukemia, so that identification is difficult, detection of Ph chromosome and neutrophil alkaline phosphatase activity is helpful to identify, when the spleen is not When swollen, white blood cells and platelets do not increase, the total red blood cell volume must be determined.

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