Sickle Cell Disease
Sickle cell disease is a common genetic disorder. This week we'll discuss the disease and its implications for anesthesia. Today we'll discuss the treatment of the disorder.
1. How does hydration assist patients with sickle cell disease?
2. Is supplemental oxygen beneficial for patients with sickle cell disease?
3. What is hemoglobin F, and how does it affect sickle cell disease?
4. Are there other novel ways of treating sickle cell disease?
本周我们讨论镰状细胞病的治疗：
1、水合作用（液体治疗）用于镰状细胞病治疗的原因？
2、辅助供氧对镰状细胞病患者是否有益？
3、何谓血红蛋白F？其对镰状细胞病有何作用？
4、治疗镰状细胞病有没有其它新方法？
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水合作用（液体治疗）用于镰状细胞病治疗的原因？
由于镰状细胞在感染、发热、脱水、酸中毒、低血氧、暴露于冷的环境、脱水的条件下，容易沉积堵塞小血管，这种堵塞可能是不可逆的，造成血管闭塞危象。适当的液体治疗可以对镰状细胞起到稀释的作用，降低它的浓度，防止血管闭塞的发生。同时也应输注正常红细胞，使镰状细胞约占总红细胞30％左右。
2、辅助供氧对镰状细胞病患者是否有益？
多数学者认为辅助供氧对镰状细胞对患者无益，甚至有害，被认为是禁忌，他们认为氧治疗会抑制红细胞的生成，加重病情。但有学者认为在低血氧时，给予适当氧疗对患者是有力的。
3、何谓血红蛋白F？其对镰状细胞病有何作用？
血红蛋白F就是胎儿血红蛋白，主要是靠绒毛膜促性腺激素和雌激素刺激产生。胎儿血红蛋白能够防止镰状细胞基因的表达来治疗镰状细胞病。
4、治疗镰状细胞病有没有其它新方法？
治疗镰状细胞有以下几种新的方法：增加胎儿血红蛋白合成、应用作用于血红蛋白和红细胞膜的抗镰状细胞的药物、抗氧化剂治疗、降低红细胞血红蛋白的浓度、骨髓移植、基因治疗等。
参考答案：
1、水合作用（液体治疗）用于镰状细胞病治疗的原因？
许多传统方法已成功用于镰状细胞病的治疗，包括水合、氧合、身体保温和减轻疼痛等。液体治疗可使红细胞内自由水增加，从而阻止镰状变形。特别是口服轻度低渗性液体（钠浓度130-135 meq/L）、静脉使用half normal saline solutions（生理盐水？）或5%葡萄糖可促使红细胞摄取水[1]。
2、辅助供氧对镰状细胞病患者是否有益？
辅助供氧对镰状细胞病导致的缺氧有益，虽然这种情况很罕见。但是辅助供氧对缺乏血流的血管阻塞部位作用甚微，因为氧气不能有效到达这些部位[1]。然而，供氧治疗效果较好，可提高氧张力，从而阻止阻塞部位周围的镰状化。
3、何谓血红蛋白F？其对镰状细胞病有何作用？
血红蛋白F，也就是胎儿血红蛋白，其作用主要取决于其浓度。可阻止血红蛋白S的β-链变化，并减轻镰状细胞病的程度。出生后第一个月血红蛋白F较正常为高，后逐渐下降至一较低但稳定的水平，保持终生。羟基脲有增加血红蛋白F水平的功能，并被成功地用于部分镰状细胞病患者的治疗，减低了死亡率[2]。此外，羟基脲减少了附着于血管壁的粒细胞、血小板和网织红细胞的数量，从而促进血流恢复[2]。
4、治疗镰状细胞病有没有其它新方法？
最近研究表明，再灌注损伤可能加重血管阻塞性危象患者曾经出现的缺血改变。Osarogiagbon等[3]研究发现，与正常大鼠相比，镰状病大鼠的脂质过氧化和羟基形成程度更高，导致低氧血症发生，从而导致缺血的发生。有趣的是，当使用别嘌呤醇时，脂质过氧化程度显著降低。该研究表明，即使在呼吸空气情况下，镰状细胞病产生大量的自由基，有助于阻止以上反应的发生。
最近，通过使用单克隆抗体发现，可阻止镰状细胞在内皮周围的聚集[4]。通过对血管阻塞性疾患形成的初步步骤的影响，微循环得到改善。这些抗体证实有效现尚处于实验室研究，未来有望用于临床以证实其有效性。
How does hydration assist patients with sickle cell disease?
A number of traditional methods have been employed with some success for the treatment of sickle cell disease including hydration, oxygenation, preserving body temperature and pain relief. Fluids may increase intra-erythrocyte free water and hinder the formation of sickling. More specifically, the use of mild hyponatremic fluids (sodium concentration 130-135 meq/L) via oral free water, intravenous half normal saline solutions, or 5% dextrose in water may promote erythrocyte water uptake (1).
Is supplemental oxygen beneficial for patients with sickle cell disease?
While supplemental oxygen may be benefit the extremely rare entity of sickle cell induced pulmonary hypoxia, it serves of little benefit at vaso-occlusive sites as these areas are devoid of blood flow, and thus oxygen cannot reach these areas effectively (1). However, the use of oxygen is a benign intervention which, by raising oxygen tension, may prevent sickling in peri-occlusive sites.
What is hemoglobin F, and how does it affect sickle cell disease?
Depending on its concentration, hemoglobin F (also known as fetal hemoglobin) prevents the crossbridging of hemoglobin S beta chains and has been noted to mitigate the effects of sickle cell disease. Normally high during the first few months of life, hemoglobin F levels decrease gradually to a low, but constant level, throughout life. Hydroxyurea has been observed to increase the level of hemoglobin F, and has been used with some success in reducing the morbidity of sickle cell disease (2). In addition, hydroxyurea reduces the number of leukocytes, platelets and reticulocytes which adhere to the vascular walls and promote a reduction in blood flow (2).
Are there other novel ways of treating sickle cell disease?
More recently, it has been noted that reperfusion injury may be as harmful as the preceding ischemia in patients with sickle cell induced vaso-occlusive crises. Osarogiagbon et al. (3) noted that sickle mice had higher markers of lipid peroxidation and hydroxyl radical formation than normal mice with both ambient and hypoxic oxygen concentrations. This was especially true following an ischemic event. Of interest, when allopurinol was given, a significant decrease in lipid peroxidation was observed. This work suggests that sickle disease produces excessive free-radicals even with ambient air concentrations, and may benefit from agents which prevent these reactions.
Most recently, the use of monoclonal antibodies has been noted to block the adhesion of the sickling cells to the surrounding endothelium (4). By preventing this initial step of vaso-occlusive disease, improvements in microcirulation were noted. While these antibodies have proven effective in the laboratory, future investigation will hopefully prove their worth in the clinical setting.
References:
1. Behrens RJ, Cymet TC. Sickle Cell Disorders: Evaluation, Treatment, and Natural History. Hosp Phys 2000;17-28.
2. Loukopoulos D, Voskaridou E, Kalotychou V, et al. Reduction of the clinical severity of sickle Cell/beta-thalassemia with hydroxyurea: the experience of a single center in Greece. Blood Cells Mol Dis 2000;26:453-66.
3. Osarogiagbon UR, Choong S, Belcher JD, et al. Reperfusion injury pathophysiology in sickle transgenic mice. Blood 2000;96(1):314-20.
4. Hebbel RP. Blockade of adhesion of sickle cells to endothelium by monoclonal antibodies. N Engl J Med 2000;342:1910-2.