Pregnancy with polycythemia
Introduction
Introduction to pregnancy with polycythemia Polycythaemia refers to the number of red blood cells per unit volume of peripheral blood. The hemoglobin and hematocrit are higher than normal, but not the number of white blood cells and platelets. In the past, it was called polycythemia in foreign countries. It is a whole blood cytosis, including an increase in the number of white blood cells and platelets. The correct English name should be erythrocytosis. Polycythemia is a group of symptoms that are caused by any cause that can cause erythrocytosis. Like anemia, it is not a diagnostic disease name. Pregnancy with erythrocytosis is mainly seen in relative polycythemia. basic knowledge The proportion of illness: 0.0035% Susceptible population: pregnant women Mode of infection: non-infectious Complications: hypertension, kidney stones, gallstones, myelofibrosis, gouty arthritis, myelodysplastic syndrome, acute leukemia
Cause
Causes of pregnancy complicated with polycythemia
(1) Causes of the disease
Polycythemia is a group of blood diseases caused by abnormal increase in red blood cells due to various reasons.
1. The etiology of polycythemia vera The etiology of this disease is still unclear. In most patients, the EPO levels in plasma and urine are not increased, but are significantly reduced. Cell culture shows the number of EPO receptors in erythroid progenitor cells of PV patients, affinity. There was no difference between the expression and the normal expression, and no abnormality was found in the sequence analysis of the EPO gene. The above results showed that the pathogenesis of the disease was free of EPO receptors. Modern studies showed that PV is not excessive proliferation of normal stem cells, but a single Abnormal clonal proliferation of cell origin.
2. The cause of secondary polycythemia:
(1) Compensatory increase in erythropoietin:
1 neonatal polycythemia: normal full-term neonatal hemoglobin at 180 ~ 190g / L, red blood cells at (5.7 ~ 6.4) × 10 12 / L, hematocrit 53% ~ 54%, this is due to the fetus in the mother In a physiological hypoxic state, after birth, the newborn can directly absorb oxygen from the air, and the number of red blood cells gradually decreases. For example, neonatal hemoglobin >220g/L, hematocrit >60%, can be diagnosed as neonatal red blood cells. Hyperplasia, which may be caused by:
A. Excessive bleeding from the placenta, transfer between twins (fetal transfer syndrome) or between mother and fetus.
B. Insufficient placenta, such as over-mature, pregnancy-induced poisoning, placenta previa, etc.
C. Endocrine and metabolic abnormalities, such as congenital adrenal hyperplasia, neonatal hyperthyroidism, maternal diabetes, etc.
2 high altitude polycythemia: the disease is due to lower atmospheric pressure in the plateau, in the absence of oxygen, secondary erythrocytosis occurs, the higher the altitude, the lower the atmospheric pressure, the lower the alveolar oxygen pressure, the number of red blood cells, hemoglobin and The hematocrit is also higher. At an altitude of 3500m or above, with the increase of altitude, the incidence of high altitude polycythemia is correspondingly increased. Some of the patients are first to the plateau, and some are residents who move to the plateau. Both men and women can be ill, and the age of onset is not special.
3 chronic lung diseases: emphysema, long-term bronchial asthma, severe spine of the spine, lateral process, affecting heart, lung function, pulmonary heart disease and multiple pulmonary embolism, due to insufficient oxidation of circulating blood transpulmonary, often followed Erythroblastia, about 50% of patients with chronic lung disease produce increased red blood cell volume; in addition, Ayerza syndrome clinical manifestations of chronic progressive bronchial asthma, bronchitis, patients with cyanosis, accompanied by erythrocytosis, can be combined with right ventricle Hypertrophy and expansion, and the development of chronic congestive heart failure.
The main pathological changes are the hardening of the pulmonary artery and its branches, and some are congenital stenosis or hypoplasia of the pulmonary artery.
4 pulmonary dyspnea syndrome (Pickwickian syndrome): due to respiratory center affecting patients with poor alveolar ventilation, its clinical features are obesity, hypercapnia, erythrocytosis, patients with lethargy, convulsions, cyanosis, periodic breathing, Eventually, it leads to right heart failure. After weight loss in individual cases, the alveolar ventilation can be normal and the symptoms disappear.
5 cardiovascular disease: congenital heart disease such as tetralogy of Faro, complete displacement of large blood vessels, often secondary to erythrocytosis, the pathogenesis is due to short circuit of blood circulation, reduce arterial oxygen saturation, stimulate erythropoiesis Increased in erythropoiesis, non-cyanotic congenital heart disease patients with chronic heart failure, pulmonary congestion and pulmonary ventilatory dysfunction, leading to long-term hypoxia, erythrocytosis can also occur, the second point in acquired heart disease Valve disease and chronic pulmonary heart disease are often accompanied by erythrocytosis due to systemic circulatory disturbance and obstruction of pulmonary ventilation, but the degree of erythrocytosis is milder than that of congenital heart disease. In addition, pulmonary arteriovenous fistula, jugular vein and pulmonary vein Blood vessel traffic, etc.
6 hemoglobin disease: due to the increased oxygen affinity of abnormal hemoglobin, it closely binds with oxygen, maintains the state of oxyhemoglobin, and does not easily release oxygen to tissues, causing tissue hypoxia, which can increase erythropoietin and erythrocytosis. In this group of cases, the oxygen affinity increased, the oxygen dissociation curve shifted to the left, the tissue could be reduced by oxygen, and the tissue oxygen tension was reduced.
7 abnormal hemorrhagic disease: This group of diseases, including some damage or pathological conditions, hemoglobin oxygen uptake or release abnormalities, according to the absorption band and characteristics, can be divided into methemoglobinemia, thiohemoglobinemia and carbon monoxide hemoglobin Hemoglobin, etc., because hemoglobin loses its ability to bind to oxygen, can not carry oxygen to the tissue, can also cause mild secondary polycythemia. The red blood cell increase caused by smoking is due to the large number of people smoking, long-term exposure to high concentrations of carbon monoxide. Inhaled carbon monoxide has a strong affinity for hemoglobin. Carbon monoxide combines with hemoglobin to replace oxygen, causing hypoxia. It can cause mild erythrocytosis in the future. Hematocrit has a certain relationship with smoking consumption. Stop smoking. After the plasma can be recovered.
(2) Non-compensatory increase of erythropoietin:
1 Kidney disease: Kidney disease secondary erythrocytosis is the most common in kidney cancer, followed by polycystic kidney, hydronephrosis, benign renal adenoma, renal sarcoma, kidney tuberculosis, etc. Secondary kidney tumors and kidney transplants are also available. Reported by secondary erythrocytosis, the mechanism of erythrocytosis is due to tumors, cysts or stagnant water compressing kidney tissue, obstructing blood flow, causing hypoxia in local tissues, increasing erythropoietin production in the kidney, leading to erythropoietin production. Increased, in addition to the presence of erythropoietin RNA in the leachate of the cyst wall and the fluid of the cyst and the renal cancer tissue of the tumor. If the crude leachate of the tumor tissue is injected into the animal, the erythropoiesis may be stimulated, and the patient of the kidney transplant may The cause of erythrocytosis may be related to an increase in erythropoietin caused by kidney damage in the recipient itself.
2 other tumors: hepatocellular carcinoma has been confirmed to have erythrocytosis, erythropoietin antigen has also been confirmed in liver cancer cells, erythrocytosis can be improved after liver cancer resection, metastatic liver cancer, hepatic hemangioma, hepatic angiosarcoma and other visible red blood cells Increased, cirrhosis patients occasionally see erythrocytosis, may be associated with hepatocellular carcinoma, in addition to liver tumors, there are cerebellar hemangioblastoma, uterine fibroids, pheochromocytoma, ovarian cancer, etc., individual reports of gastric cancer, prostate cancer , lung cancer, Hodgkin's disease, esophageal tumors, etc. can affect the secretion of erythropoietin and then erythrocytosis.
3. The cause of relative polycythemia:
(1) Temporary polycythemia: persistent vomiting, severe diarrhea and excessive sweating: can cause significant loss of body fluids, insufficient water intake, can cause a decrease in plasma volume, and a relative increase in erythrocytes.
(2) Pseudo-erythrocytosis (relative or stress erythrocytosis, Gaisbock syndrome): The cause is unknown, some people think it is not an independent disease; others think it is a benign disease, there are reports that may be excessive smoking , drinking, emotional, chronic anxiety, high blood pressure, etc.
(two) pathogenesis
Under normal circumstances, the amount of red blood cells is maintained in a state of dynamic equilibrium, which is regulated by erythropoietin, a relatively stable glycoprotein hormone with a relative molecular mass of 46,000 and a gene located on chromosome 7. The long arm is produced by the renal tubulointerstitial cells, which is also the oxygen sensor. This sensing site is a hemoprotein that controls the expression of erythropoietin mRNA when hypoxia or anemia. Stimulates the production of erythropoietin; after anemia or hypoxia correction, the production of erythropoietin tends to be normal, which is related to the regulation of gene expression levels. Animal experiments have shown that the concentration of erythropoietin in the kidney is close to that of plasma erythropoietin. Relationship; erythropoietin can also be produced in adult liver, but the latter has only minimal response to hypoxia and anemia. Normal erythropoietin is 4-26 U/L, when hemoglobin drops to 105 g/L. Under the stimulation of hypoxia, there is a change in erythropoietin. After the amount of red blood cells increases, the level of peripheral blood erythropoietin is restored. Often; under hypobaric hypoxia, there is an increase in peripheral blood erythropoietin, especially in the case of persistent hypoxia, and erythropoietin can mediate an increase in the amount of red blood cells, which may be accompanied by hypoxia. The reduction in plasma volume is not only in the high altitude but also in hypoxic congenital heart disease, and there is an increase in red blood cells in smokers.
Prevention
Pregnancy with polycythemia prevention
Mainly for anticoagulation and antiplatelet therapy, it can prevent retrograde thrombosis and prevent recurrence of embolized blood vessels, and at the same time treat the primary disease, correct arrhythmia, and focus on valvular heart disease and related diseases that cause endocardial lesions. Effective treatment to eradicate the source of the embolus and prevent recurrence. Care should be taken to ensure that patients should stay in bed during the acute phase to prevent embolization from embolism. At the same time, due to long-term bed rest, attention should also be paid to swallowing function and oral care to prevent aspiration pneumonia, urinary tract infection, hemorrhoids, and deep vein thrombosis of lower extremities.
Complication
Pregnancy with complications of polycythemia Complications hypertension kidney stones gallstones bone marrow fibrosis gouty arthritis myelodysplastic syndrome acute leukemia
Common complications include high blood pressure, bleeding, thrombosis (cerebral blood vessels, upper and lower extremity blood vessels, coronary artery, mesenteric artery, hepatic vein, spleen blood vessels, etc.), gastroduodenal ulcer, kidney stones, gallstones, gout Arthritis, myelofibrosis, leukemia, etc., simple venous bloodletting complicated with embolism and myelofibrosis, with 32P or chemotherapeutic patients with acute leukemia, including acute granulocyte and acute granulocyte-monocytic leukemia, There are also a small number of lymphocytic leukemias. The cause of death is thrombosis, followed by leukemia, tumor, hemorrhage and myelofibrosis. Leukemia often occurs 5 to 12 years after treatment, and some cases first turn into myelodysplastic syndrome. Then converted to acute leukemia, the response to treatment is poor, in some cases after a few years, the hematocrit is normal, and the spleen gradually increases, called the spent phase (spent phase); some cases develop into myelofibrosis.
Symptom
Symptoms of pregnancy with polycythemia Symptoms Common symptoms Hyperemia Hypertensive pregnancy Hypertension Intracranial hemorrhoids Conjunctival congestion Bloody nose Hemorrhoids Skin itching Memory disorder Visual impairment Drowsiness
Symptoms of polycythemia vary greatly, depending on whether the patient is relative or absolute, primary or secondary; patients with different stages may have different clinical manifestations, except for erythrocytosis caused by blood concentration, most cases develop Slow, often have an asymptomatic period, lasting for several months to several years, some patients can feel a period of weakness and other non-specific symptoms before review; some occasionally found in physical examination or other disease test blood routine, secondary Symptoms of the sexual person are often masked by the symptoms of the primary disease without causing the patient's attention.
Central nervous system
Can cause head swelling, headache, dizziness, dizziness, tinnitus, blurred vision and limb numbness, etc. Others include: nervousness, behavioral changes, impatience, lethargy or sleep disorders, memory loss, depression, etc., in stress or pseudo-erythrocytes More common in the case of increased disease.
2. Circulatory system
Symptoms of the circulatory system are caused by venous thrombosis or thrombophlebitis caused by high blood volume and high viscosity. In the case of polycythemia vera, thrombosis is often formed in different parts to produce corresponding symptoms. The common parts are brain and surrounding. Blood vessels, coronary arteries, portal veins, mesenteric veins, etc., air urgency is more common in erythrocytosis, acute erythrocytosis is not related to fatigue; and secondary to chronic heart and lung disease, shortness of breath is aggravated after exertion, shortness of breath is often due to pulmonary vessels Congestion, there may be most pulmonary small blood vessel embolism.
3. The gastrointestinal tract
Symptoms are more common, may have increased gastric acid and increased gastric activity, and some patients may be combined with stomach, duodenal ulcer, may be related to small blood vessel thrombosis in the stomach or duodenum.
4. Bleeding
More common in polycythemia vera, may have different parts of bleeding, but not serious, such as nosebleeds, bleeding gums, skin purpura or ecchymosis, menorrhagia, etc., secondary is rare, such as surgery must be carried out, it is best When the disease is controlled, hemorrhage and endometrial damage, tissue hypoxia, and abnormal mass and quantity of platelets (abnormal platelet morphology, structural abnormalities, shortened prothrombin consumption time, decreased platelet factor III, poor platelet adhesion and aggregation) , blood clot retraction, serotonin reduction, increased fibrinolytic activity, etc.).
5. High metabolism
Symptoms such as excessive sweating, weight loss, diarrhea, etc., due to hyperuricemia can cause gouty arthritis, complaining of joint pain, which is rare in China, there may be skin itching during polycythemia vera, especially after taking a bath, Some patients complained when they asked carefully, which may be related to hyperhistamine and rare in pseudo and secondary polycythemia.
The most prominent signs and diagnostics are facial, hand, foot and mucous membranes are reddish purple; secondary to chronic heart and lung disease and congenital heart disease, the hair, mouth, lips, membrane and fingers, especially at the end of the toe, Combined with membrane congestion, retinal veins are obviously varicose, the latter is not common in patients with stress erythrocytosis, because the patient's red blood cell volume is normal, secondary to chronic heart and lung disease may have heart enlargement, 3/5 cases of polycythemia patients Hypertension, stress (pseudo) is also common, so it is called erythrocytosis hypertonica, in the case of polycythemia vera, about 80% of cases have splenomegaly, splenomegaly Etc., can be just a few, less than 10cm under the ribs, mostly in 1 ~ 5cm, which has a diagnostic significance in the disease, other causes of polycythemia patients with small spleen, in the course of the disease, spleen progressive enlargement It is often indicated that the disease is transformed into extramedullary metaplasia, myelofibrosis or leukemia, and hepatomegaly is relatively rare, accounting for 50% to 60% of polycythemia vera, mostly within 4cm of the rib, secondary Liver not large.
6. Performance of the primary disease
According to the history of the disease and related symptoms, combined with its characteristics, it can determine the type of polycythemia.
7. The performance of plethora
Skin and mucous membrane congestion is purple-red, with the most obvious skin and mucous membranes on the cheeks, and conjunctival hyperemia, such as drunkenness.
8. Increased blood viscosity
Slow blood flow may occur in peripheral arteries, coronary or cerebral arterial thrombosis, chronic DIC and bleeding tendency, gingival bleeding, nosebleeds and digestive tract, urinary bleeding, and death from intracranial hemorrhage.
9. Poor perfusion of limbs and vital organs causes numbness of hands and feet, visual impairment, dizziness, tinnitus and epileptic seizures.
Clinical type:
1 polycythemia vera (also known as Vaguez disease or Osler disease) is a chronic myeloproliferative disease mainly caused by abnormal erythroid cell proliferation, mainly due to dysregulation of erythrocyte production, causing excessive proliferation of red blood cells, which is characterized by the number of red blood cells and blood. Increased capacity, increased blood viscosity, increased blood oxygen saturation, most patients with congestive splenomegaly, the etiology of this disease is still unknown, studies have shown that its incidence is not excessive proliferation of normal stem cells, but an abnormal origin of single cells Caused by clonal proliferation.
2 Secondary polycythemia is mostly a manifestation of the body's compensatory effects in the absence of oxygen, such as long-term high altitude disease and chronic cardiopulmonary disease, the release and production of red blood cells in the spleen and bone marrow, so that in the blood A large increase in red blood cells causes polycythemia, which is characterized by an increase in red blood cells accompanied by a decrease in oxygen saturation.
3 Relative polycythemia is a stress reaction in the body after the reduction of plasma volume in the blood, such as severe dehydration, a large amount of diuretic, abnormal plasma and red blood cell ratio, relatively increased red blood cells, in the clinical obstetrics Severe hypertensive disorder of pregnancy, hypovolemic bloodemia, blood concentration, severe edema caused by diuretics, or acute dehydration due to other reasons, characterized by normal or decreased number of red blood cells, increased hematocrit, and oxygen saturation Normal.
Examine
Examination of pregnancy with polycythemia
Peripheral blood
Hemoglobin determination, red blood cell count, hematocrit determination is the main experimental method for diagnosing polycythemia. Table 1 lists the diagnostic criteria for hematology of erythrocytosis, in which hematocrit and hemoglobin are more accurate, and the factors affecting red blood cell count are more . The number of white blood cells is mostly higher than normal in polycythemia vera, and more than 10×10 9 /L in stress and secondary, unless the infection is combined; but the number of white blood cells in about 25% of cases of polycythemia No increase, the number of platelets in polycythemia vera is more than half of the cases higher than 400 × 10 9 / L, up to 1000 × 10 9 / L or more, and other factors of polycythemia patients with more platelets in the normal range .
2. Bone marrow examination
Bone marrow smear examination has certain value for the differential diagnosis of true and secondary polycythemia. The difference between the two is not significant, but the ratio of true granules to red blood cell system is almost normal. The granule, red and megakaryocyte 3 lines are all normal. Hyperplasia, sometimes visible immature red blood cells aggregated into small heaps; while secondary people often only have red blood cell system hyperplasia, granulocyte and megakaryocyte system no abnormalities, so the ratio of granulocyte to red blood cell system is reduced, bone marrow biopsy is more meaningful in differential diagnosis Large, true polycythemia bone marrow sections showed that the granules, red, and megakaryocytes were all proliferated. All the fat cells were replaced by hematopoietic cells. In 10% to 20% of cases, the reticular fibers increased. If reticular fibers proliferated, This is an important diagnostic basis; while the secondary section is mainly red blood cell system hyperplasia, adipose tissue can still exist, lack of reticular fibers.
3. Blood volume
In the diagnosis of polycythemia, the determination of red blood cell volume by 51Cr or 99Tc labeling method, simultaneous determination of whole blood volume and determination of plasma volume by 125I or 131I human serum albumin method is an important diagnostic step, red blood cell volume male > 36ml / kg body weight, Women with >32ml/kg body weight can diagnose polycythemia; patients with relative polycythemia have higher hematocrit than normal, while red blood cell volume is normal, and plasma volume is often reduced compared with normal values, which is helpful for diagnosis.
ESR
The blood erythrocyte sedimentation rate is usually 1~2mm/h, the blood viscosity is higher than normal, and the ratio of blood relative viscosity to water is 8:110:1 (normal person is 3.5:15.4:1) (Oswald or Hess) According to the viscosity meter, the relative density of whole blood increased between 1.061 and 1.083 (normal male 1.055 to 1.065, female 1.048 to 1.059).
5. Arterial oxygen saturation
In patients with polycythemia vera and secondary polycythemia, arterial oxygen saturation is normal due to increased non-physiologic erythropoietin; whereas arterial oxygen saturation secondary to increased erythropoietin is lower than normal (< 88%), such as cardiovascular disease, arteriovenous fistula, carbon monoxide hemoglobinemia, methemoglobinemia and other patients due to changes in oxygen affinity, resulting in increased erythropoietin, arterial oxygen saturation decreased.
6. Blood oxygen separation curve
This curve shows the relationship between oxygen saturation and oxygen partial pressure. When normal, the curve is S-shaped. In the standard state, the oxygen half-saturation partial pressure (p-50) of normal red blood cell hemoglobin is 3.54 kPa, so the value is reduced, p -50 left shift, indicating increased affinity of hemoglobin for oxygen; conversely, p-50>3.54kPa is right shift, indicating that hemoglobin has reduced affinity for oxygen, and blood oxygen separation curve may indicate abnormal hemoglobin or red blood cell when p-50 is increased. The 2,3-diphosphoglycerate content is reduced.
7. Determination of erythropoietin
Since polycythemia vera is a clonal disease, the differentiation of erythroid progenitor cells is autonomic and independent of erythropoietin, so the serum of patients is detected by enzyme-linked immunosorbent assay (ELISA) or immunoradiometric assay (IRMA). The hormone is often reduced or normal (normal value: 6 ~ 32U / L); and secondary polycythemia is due to excessive production of erythropoietin, due to abnormal oxygen transport mechanism, compensatory erythropoiesis; or due to benign or malignant tumors As a result of the formation of exogenous erythropoietin, which is the formation of non-compensatory erythropoietin, the detection of serum erythropoietin is increased or normal, and the determination of erythropoietin has reference value.
8. Erythrocyte colony forming unit culture
Since 1974, Prchal and Axelrad proposed that the red blood cell colony-forming unit (SFU-E) in patients with polycythemia vera is not dependent on erythropoietin in vitro, this spontaneous erythroid colony is called endogenous erythroid endogenous colonies. , EEC); and patients with secondary polycythemia do not have this EEC characteristic, erythroid colony formation must add a certain amount of erythropoietin in the medium, so the in vitro erythroid colony formation unit culture test helps with two The identification of the person is now considered to be highly specific for the diagnosis of polycythemia vera.
B-ultrasound or CT examination of abdominal and lumbar kidneys, uterus, liver and brain with or without cysts or tumors; determination of hemoglobin electrophoresis, 2,3-diphosphoglycerate, methemoglobin, hemoglobin, etc. contribute to secondary polycythemia The reason for the determination.
Diagnosis
Diagnosis and differentiation of pregnancy complicated with polycythemia
The exact diagnosis of polycythemia depends mainly on laboratory tests. The first step is to determine if there is an increase in erythrocytes, and secondly to determine what causes it.
Mainly differentiated from chronic myeloid leukemia (CML). Patients with PV often have splenomegaly and granulocytes, and advanced peripheral blood immature granulocytes can be increased, so it must be differentiated from CML. Neutrophil alkaline phosphatase score in PV patients. Elevated, Ph1 chromosome and bcr/abl mRNA are negative, while slow granules are just the opposite. Recently, it has been found that chronic granule patients can also spontaneously form CFU-E, so endogenous CFU-E cannot be used to identify PV and slow granules.
