Pathophysiology, diagnosis and treatment of anemia

Anemia can result from deficient erythropoiesis [aplastic anemia, myelodysplastic syndromes (MDS), iron deficiency anemia, anemia of chronic disease (ACD), thalassemia, megaloblastic anemia, chronic renal failure, hematological malignancies, etc.], excessive RBC destruction [hereditary spherocytosis, inherited enzyme deficiency, hemoglobinopathies, autoimmune hemolytic anemia (AIHA), paroxysmal nocturnal hemoglobinuria (PNH), etc.], and blood loss. Based on the measured red cell size(MCV), anemia is classified as microcytic, normocytic, or macrocytic. Iron parameters (serum iron, serum ferritin, etc.), reticulocyte count, bone marrow examination, Coombs test, serum vitamin B12 level, and Ham test are also useful in the differential diagnosis of anemia. Novel treatment of anemia includes lenalidomide for 5q(-)MDS, azacitidine for high-risk MDS, and eculizumab for PNH. Oral iron chelator(deferasirox) developed for the treatment of transfusional iron overload is also very useful for the management of patients with bone marrow failure syndromes.     

Improved approach to patients with normocytic anemia

A precise cause for normocytic anemia can be determined through applied pathophysiology. Examination of the peripheral blood smear may yield evidence of renal disease, liver disease, hemolysis or megaloblastic anemia. A reticulocyte count is performed next; then the creatinine clearance is determined. Bone marrow aspiration with iron stain should further narrow the cause. Physical examination and family history remain important in determining the etiology of normocytic anemia.     

Anemia in children.

Anemia in children is commonly encountered by the family physician. Multiple causes exist, but with a thorough history, a physical examination and limited laboratory evaluation a specific diagnosis can usually be established. The use of the mean corpuscular volume to classify the anemia as microcytic, normocytic or macrocytic is a standard diagnostic approach. The most common form of microcytic anemia is iron deficiency caused by reduced dietary intake. It is easily treatable with supplemental iron and early intervention may prevent later loss of cognitive function. Less common causes of microcytosis are thalassemia and lead poisoning. Normocytic anemia has many causes, making the diagnosis more difficult. The reticulocyte count will help narrow the differential diagnosis; however, additional testing may be necessary to rule out hemolysis, hemoglobinopathies, membrane defects and enzymopathies. Macrocytic anemia may be caused by a deficiency of folic acid and/or vitamin B12, hypothyroidism and liver disease. This form of anemia is uncommon in children.     

Normocytic anemia

Anemia is a common problem that is often discovered on routine laboratory tests. Its prevalence increases with age, reaching 44 percent in men older than 85 years. Normocytic anemia is the most frequently encountered type of anemia. Anemia of chronic disease, the most common normocytic anemia, is found in 6 percent of adult patients hospitalized by family physicians. The goals of evaluation and management are to make an accurate and efficient diagnosis, avoid unnecessary testing, correct underlying treatable causes and ameliorate symptoms when necessary. The evaluation begins with a thorough history and a careful physical examination. Basic diagnostic studies include the red blood cell distribution width, corrected reticulocyte index and peripheral blood smear; further testing is guided by the results of these studies. Treatment should be directed at correcting the underlying cause of the anemia. A recent advance in treatment is the use of recombinant human erythropoietin.     

Anemia in the elderly

Anemia should not be accepted as an inevitable consequence of aging. A cause is found in approximately 80 percent of elderly patients. The most common causes of anemia in the elderly are chronic disease and iron deficiency. Vitamin B12 deficiency, folate deficiency, gastrointestinal bleeding and myelodysplastic syndrome are among other causes of anemia in the elderly. Serum ferritin is the most useful test to differentiate iron deficiency anemia from anemia of chronic disease. Not all cases of vitamin B12 deficiency can be identified by low serum levels. The serum methylmalonic acid level may be useful for diagnosis of vitamin B12 deficiency. Vitamin B12 deficiency is effectively treated with oral vitamin B12 supplementation. Folate deficiency is treated with 1 mg of folic acid daily.     

Iron deficiency anemia. How to diagnose and correct

The prevalence of iron deficiency anemia has decreased in recent years because of improved dietary habits. Yet, iron deficiency anemia is still the most common anemia. Among mature adults, anemia of chronic disease is probably more common. Mean corpuscular volume and red cell distribution width, along with a peripheral smear examination, can often distinguish iron deficiency anemia from other common microcytic anemias, such as thalassemia minor. A normal serum iron level excludes iron deficiency anemia and indicates other causes for microcytic anemia. Often, a low serum iron level and total iron-binding capacity are due to chronic disease, and measurement of serum ferritin or a bone marrow stain for hemosiderin will be necessary to diagnose iron deficiency. Iron therapy to restore the red cell mass should be continued until iron stores are replenished.     

Anemia in the elderly. Common causes and suggested diagnostic approach

Anemia is a frequent finding in the elderly. Hypochromic microcytic anemia, usually secondary to iron deficiency, is the most common type. Macrocytic anemia, usually caused by folic acid or vitamin B12 deficiency, is the next most common. Both iron and vitamin B deficiencies are easy to treat with supplements, but the clinician must make a careful search for the cause of the deficiency. Normochromic normocytic anemia can be caused by a number of conditions. The only effective treatment is arrest or cure of the underlying disorder.     

铁粒幼细胞性贫血伴急性心肌梗死1例报告并文献复习

目的：报告1例铁粒幼细胞性贫血伴急性心肌梗死的少见病例的诊治过程。方法：病例分析及文献复习。结果：患者面色苍白、疲乏头晕2a余，一直误诊为“缺铁性贫血”，服用“补血药”无效，后出现急性心肌梗死急诊入院。经骨髓铁染色、铁蛋白等检查，确诊为铁粒幼细胞性贫血，给予低分子肝素抗凝、硝酸甘油及大剂量维生素B6等治疗病情稳定痊愈出院。结论：铁粒幼细胞性贫血属少见病，很容易与同为低血色素贫血的缺铁性贫血、地中海贫血相混而误诊，如果误补铁过多则更容易加重心脏铁负荷。所以，对低血色素贫血患者要及时做骨髓铁染色．对冠心病合并铁粒幼细胞性贫血患者，除扩冠、抗凝外还需祛铁治疗。     

A three-point approach to anemia

Anemia is a sign of underlying disease that is causing blood loss, sequestration of red blood cells (RBCs), impaired RBC production, or primary marrow dysfunction. The most efficient clinical approach to a patient with anemia is to ask the following three questions: Is the anemia microcytic, macrocytic, or normocytic? Is pancytopenia present? Is the marrow response appropriate for the anemia as determined by the reticulocyte count? Answers to these questions focus laboratory evaluation on a logical progression and avoid a costly shotgun approach.     

THE ANEMIA OF SCURVY : EFFECT OF VITAMIN C DIET ON BLOOD FORMATION IN EXPERIMENTAL SCURVY OF GUINEA PIGS

1. Weight loss, progressive anemia, and a moderate increase in reticulated red blood cells occurred in seventeen guinea pigs on a diet deficient in vitamin C. 2. The histological changes of the bone marrow removed from guinea pigs with scurvy showed large numbers of erythrogenic cells, but scant evidence of active maturation to the adult erythrocyte. 3. A reticulocyte response was induced in guinea pigs with scurvy when fed orange juice daily. 4. The histological changes of the bone marrow removed from guinea pigs during the reticulocyte response showed large numbers of mitotic figures and relatively more adult red blood cells than in the bone marrow from guinea pigs with scurvy that had not been treated with orange juice. 5. It is concluded from this study that the anemia of experimentally induced scurvy in the guinea pig is largely dependent upon vitamin C deficiency resulting in retarded maturation of the red blood cell.     

Characteristics of marrow production and reticulocyte maturation in normal man in response to anemia

Erythropoiesis in normal man was studied during periods of phlebotomy-induced anemia of varying severity. This study permitted a comparison of marrow production measurements over a wide range of marrow production levels. As long as the serum iron remained above 50 mug/100 ml, measurements of plasma iron turnover provided an excellent index of marrow production at all levels of red cell production. In contrast, the absolute reticulocyte count demonstrated a poor correlation with the other measurements. This was shown to be the result of a prolongation of the time required for circulating reticulocytes to lose their reticulum, which correlated with the severity of the anemia. For the clinical application of the reticulocyte count as a measurement of marrow production, an adjustment must be made for this alteration in the circulating reticulocyte maturation time.     

Microcytic anemia. Differential diagnosis and management of iron deficiency anemia.

Microcytic anemia is defined as the presence of small, often hypochromic, red blood cells in a peripheral blood smear and is usually characterized by a low MCV (less than 83 micron 3). Iron deficiency is the most common cause of microcytic anemia. The absence of iron stores in the bone marrow remains the most definitive test for differentiating iron deficiency from the other microcytic states, ie, anemia of chronic disease, thalassemia, and sideroblastic anemia. However, measurement of serum ferritin, iron concentration, transferrin saturation and iron-binding capacity, and, more recently, serum transferrin receptors may obviate proceeding to bone marrow evaluation. The human body maintains iron homeostasis by recycling the majority of its stores. Disruptions in this balance are commonly seen during menstruation, pregnancy, and gastrointestinal bleeding. Although the iron-absorptive capacity is able to increase upon feedback regarding total body iron stores or erythropoietic activity, this physiologic response is minimal. Significant iron loss requires replacement with iron supplements. The vast majority of patients respond effectively to inexpensive and usually well-tolerated oral iron preparations. In the rare circumstances of malabsorption, losses exceeding maximal oral replacement, or true intolerance, parenteral iron dextran is effective. In either form of treatment, it is necessary to replete iron stores in addition to correcting the anemia.     

Serum transferrin receptor is a marker of iron deficiency in patients included in programs for preoperative autologous blood donation.

Recently programs for preoperative autologous blood donation (PABD) have expanded to reduce the need for allogenic blood transfusion. Nevertheless, the ability of the patients's bone marrow to replace the red blood cells (RBCs) mass reduced by phlebotomies determines the efficacy of PABD. In mild anemia, known as iron-deficient erythropoiesis (IDE) or iron deficiency without anemia, precipitated by PABD, the marrow response is suboptimal and needs adjuvant therapy. The aim of this study was to evaluate the use of the serum transferrin receptor (sTfR) for the assessment of IDE in patients undergoing PABD. METHODS: Two autologous blood units from 50 consecutive patients scheduled for elective orthopedic surgery were collected preoperatively. Serial measurements of RBCs, haematocrit (Hct), haemoglobin (Hb), serum iron, serum ferritin, reticulocyte count, reticulocyte maturity index (RMI), endogenous erythropoietin (EPO) and sTfR were performed throughout the phlebotomy program. RESULTS: RBC, Hct, Hb and serum iron significantly decreased although within the normal range. There was no change in serum ferritin levels. Reticulocytes, RMI and EPO significantly increased as did sTfR which significantly exceeds the normal range. CONCLUSIONS: These results demonstrate that the sTfR is a reliable laboratory marker for detecting mild anemia or IDE. In patients undergoing PABD increased sTfR levels may suggest a treatment with recombinant human EPO (rh-EPO) or iron to improve the bone marrow performance.     

新型网织红细胞参数在缺铁性贫血疗效观察中的应用

目的　观察网织红细胞绝对数 (RET #)、网织红细胞内血红蛋白量 (CHr)、平均网织红细胞体积 (MCVr)及网织红细胞内血红蛋白浓度 (CHCMr)等网红参数在缺铁性贫血 (IDA)患者铁剂治疗中的动态变化 ,确定骨髓对铁剂治疗反应的早期指标。方法　用Advia 12 0血细胞分析仪对 13例缺铁性贫血患者在治疗过程中网红参数的变化进行了动态观察。结果　缺铁性贫血患者在铁剂治疗后 ,网红参数RET #、CHr、MCVr于第 4天明显升高 (P <0 0 1) ,第七天恢复正常 ;血红蛋白于第 14天明显升高 (P <0 0 1) ,第 2 8天恢复正常 ;CH、MCV、CHCM于第 2 8天明显升高 (P <0 0 1) ,第 4 9天后恢复正常 ;RDW于第 7天明显升高 (P <0 0 1) ,14天后又逐渐降低 ,第 12 0天恢复正常。结论　网红参数RET #、CHr、MCVr可作为评价缺铁性贫血患者铁剂治疗后骨髓对治疗反应最敏感的指标     

Sideroblastic anemia. A diagnosis to consider in alcoholic patients.

Alcoholic patients who present with anemia can pose a diagnostic challenge. Although deficiencies of iron, vitamin B12, and folate commonly result in anemia, bone marrow suppression of red blood cell production related to the direct toxic effects of alcohol can cause a form called sideroblastic anemia. This case report describes a patient presenting with acute alcohol intoxication and anemia in whom extensive evaluation revealed a hematologic picture compatible with acquired sideroblastic anemia.     

Scope of the problem: epidemiology of anemia and use of blood transfusions in critical care

Anemia is a common problem in critically ill patients. It is caused, in part, by blood loss related to phlebotomy for diagnostic testing, occult gastrointestinal bleeding, renal replacement therapies, surgical intervention, and traumatic injuries. Reduced red cell life span and nutritional deficiencies (iron, folate, vitamin B12) may be other contributing factors. In addition, critically ill patients have impaired erythropoiesis because of blunted endogenous erythropoietin production and the direct inhibitory effects of inflammatory cytokines on red blood cell production by the bone marrow. Blood transfusions are commonly utilized for treatment of anemia in critical care, resulting in high use of blood transfusions in the intensive care unit (ICU). The percentage of patients transfused in the ICU is inversely related to admission hemoglobin and directly related to age and severity of illness. Patients with an increased length of stay in the ICU are also at increased risk for receiving blood transfusions. Studies are needed to improve our understanding of the pathophysiology of ICU-acquired anemia, to determine the efficacy of blood transfusions in critical care, and to investigate alternatives to blood transfusion for the treatment of anemia in the ICU.     

Anemia in cirrhosis: An underestimated entity

Anemia in a patient with cirrhosis is a clinically pertinent but often overlooked clinical entity. Relevant guidelines highlight the algorithmic approach of managing a patient of cirrhosis presenting with acute variceal hemorrhage but day-to-day management in hospital and out-patient raises multiple dilemmas: Whether anemia is a disease complication or a part of the disease spectrum? Should iron, folic acid, and vitamin B complex supplementation and nutritional advice, suffice in those who can perform tasks of daily living but have persistently low hemoglobin. How does one investigate and manage anemia due to multifactorial etiologies in the same patient: Acute or chronic blood loss because of portal hypertension and bone marrow aplasia secondary to hepatitis B or C viremia? To add to the clinician’s woes the prevalence of anemia increases with increasing disease severity. We thus aim to critically analyze the various pathophysiological mechanisms complicating anemia in a patient with cirrhosis with an emphasis on the diagnostic flowchart in such patients and proposed management protocols thereafter.     

贫血病因待查患者骨髓细胞学检查187例结果分析

目的 分析贫血病因、探讨骨髓细胞学检查在贫血患者病因诊断中的临床应用价值。方法回顾分析187例贫血待查患者的骨髓细胞学检查结果及临床资料。结果187例贫血患者在不同年龄组的分布随年龄段的增长而增长,60岁以上老年患者占58．8％。有159例（85．0％）患者确诊了病因：其中缺铁性贫血40例（21．4％）;慢性病贫血26例（13．9％）;急性白血病21例（11．2％）;巨幼贫21例（11．2％）;多发性骨髓瘤11例（5．9％）;感染性贫血1】例（5．9％）;血小板减少7例（3．7％）;骨髓增生异常综合征4例（2．1％）;再生障碍性贫血3例（1．6％）;溶血性贫血3例（1．6％）;慢性淋巴细胞白血病3例（1．6％）;脾功能亢进3例（1．6％）;淋巴瘤2例（1．0％）;慢性粒细胞白血病2例（1．0％）;纯红再障2例（1．O％）;骨髓纤维化1例（0．5％）。不明原因28例（15．0％）。结论骨髓细胞学检查对贫血的确诊、贫血类型的确定具有重要的临床应用价值;老年患者发病率较高,应引起医务工作者的重视。     

老年与青少年巨幼细胞性贫血的临床特点比较

目的探讨老年与青少年巨幼细胞性贫血的临床特点。方法选择129例巨幼细胞性贫血患者,分为老年组(n=83)和青少年组(n=46),分析两组患者贫血的原因和误诊情况。比较骨髓象、外周血象等检查资料。结果老年和青少年患者贫血原因中均以摄入不足比率最高(老年31例,37.35%;青少年29例,63.04%)。老年患者的骨髓象以活跃、明显活跃的比率较高,而青少年患者以极度活跃和明显活跃为主。老年组患者外周血的血红蛋白、白细胞、血小板水平均显著低于青少年组,全血细胞减少患者比率显著高于青少年组(P均0.05)。老年患者中误诊27例,误诊率为32.53%,显著高于青年组的6.52%。两组治疗后血常规均回复正常,但老年组患者的血红蛋白水平恢复正常的时间(29.3±3.8 d)显著长于青少年组(19.9±2.1 d)。结论老年巨幼细胞性贫血患者因临床症状非特异而易误诊,其主要病因在于维生素B12、叶酸的摄入不足,表现为全血细胞水平下降者的比率更高,临床上需要积极掌握老年巨幼细胞性贫血临床特点,对降低误诊率、提高治愈率具有重要意义。     

Anemia in pregnancy.

In evaluating pregnant women with anemia, it is essential to do a complete history and physical examination, as well as a complete blood count with indices and a blood smear examination. Based on these findings, other tests such as ferritin and serum or red cell folate may be ordered. Because of the normal physiologic changes in pregnancy that affect the hematocrit, indices, and some other parameters, diagnosing true anemia, as well as the etiology of anemia, is challenging. Because of the increased nutritional requirements of the mother and fetus, the most common anemias are iron deficiency anemia and folate deficiency megaloblastic anemia. These anemias are more common in women who have inadequate diets and who are not receiving prenatal iron and folate supplements. Other less common causes of acquired anemia in pregnancy are aplastic anemia and hemolytic anemia associated with preeclampsia. In addition, congenital anemias such as sickle cell disease can impact on the health of the mother and fetus. Obviously, severe anemia has adverse effects on the mother and the fetus. There is also evidence that less severe anemia is associated with poor pregnancy outcome. The cause of this association has yet to be elucidated. It is important, however, to diagnose and treat anemia in pregnancy to provide for optimal health of the mother and infant.