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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 clinical manifestations of the disorder.

1.  What are vaso-occlusive pain crises?
2.  What is responsible for the "anemia" of sickle cell disease?
3.  What organs are at risk for ischemia in sickle cell diseaese?
4.  Are patients with sickle cell disease at greater risk of infection?

本周我们讨论镰状细胞病的临床表现：

1、什么是血管闭塞性痛危象？
2、镰状细胞病“贫血”的原因？
3、镰状细胞病时哪些器官有缺血的危险？
4、镰状细胞病患者是否有更高的感染机会？

参考答案：

1、什么是血管闭塞性痛危象（VPC）？

VPC是指四肢、背部、腹部、胸部或头部出现疼痛，持续两小时以上，且不能为镰状细胞病以外的疾患所解释[1]。VPC最常发生在骨部，常由气温下降、较高的血红蛋白浓度、脱水、感染、运动、潮湿、缺氧、酸中毒、应激和疲劳所诱发[2]。有趣的是，10%的VPC病例发作有两个高峰，分别为下午2点和9点，相比之下，有1%的病例在早上5点发作[3]。

除了与VPCs相关的发病率较高外，死亡率也增加。大于20岁的镰状细胞患者，每年VPC发作次数小于或大于3次的年死亡率分别为1.8%和3.7%[1]。

2、镰状细胞病“贫血”的原因？

随着镰（状细胞贫血）珠蛋白中氧的去除，红细胞变形成镰状，红细胞膜受到破坏，破裂的可能性增加，从而导致贫血。事实上，据观察，镰状细胞病红细胞的寿命只有10-12天，而正常红细胞的寿命为120天[4]。这种红细胞的慢性破坏使机体产生代偿机制，包括骨髓增生、肝肿大（由于髓外造血）。

3、镰状细胞病时哪些器官有缺血的危险？

因为镰（状细胞贫血）珠蛋白有凝聚趋势，降低血流，因此一些器官有缺血的危险。一些特定的器官特别危险，包括脾脏、肾脏、肝脏、骨骼，甚至中枢神经系统。研究表明中风多发生在疾患早期，8%的镰状细胞性贫血患者发生在14岁时，而这些中风的80%造成了至少一条重要脑血管完全堵塞[5]。器官损害呈逐渐加重，发病率也有所不同，最终导致器官功能完全障碍。

4、镰状细胞病患者是否有更高的感染机会？

阻塞再发和不可逆最终可导致脾脏完全失去功能。随着脾脏功能、抗体形成、补体调理作用和交替产生作用的失去，机体感染几率增加，特别是对有夹膜的生物如肺炎球菌、脑膜炎球菌、沙门氏菌。这种状态对机体影响很大，因为即使机体很小的创口或感染也可成为威胁生命的全身感染。

What are vaso-occlusive pain crises?

Vaso-occlusive pain crises (VPC) have been defined as the occurrence of pain in the extremities, back, abdomen, chest, or head that lasts 2 or more hours and cannot be explained except by the presence of sickle cell disease (1). VPC most commonly occurs in bone, and has been known to be precipitated by cold weather, relative high hemoglobin concentrations, dehydration, infection, exercise, dampness, hypoxia, acidosis, stress and fatigue (2). Of interest, VPC have a cricadian pattern, with bimodal peaks occuring at 2pm and 9pm with 10% of cases occurring at each peak; by contrast, a trough occurs at 5 am, with only 1% of cases occuring at this time (3).

In addition to the morbidity associated with VPCs, mortality is increased as well. In sickle cell patients older than 20 years of age, 1.8 and 3.7 deaths/100 patient years occur in those who have less and more than 3 VPC episodes per year, respectively (1).

What is responsible for the "anemia" of sickle cell disease?

With the removal of oxygen from sickle hemoglobin, the red blood cell deforms into a sickled shape. This sickling damages the RBC membrane and increases the likelihood of rupture and anemia. In fact, the lifespan of erythrocytes in sickle cell disease has been observed to be only 10-12 days, compared to the normal 120 days (4). This chronic destruction leads to compensatory mechanisms, including hyperplastic marrow and hepatomegaly (due to extramedullary hematopoiesis).

What organs are at risk for ischemia in sickle cell diseaese?

As the sickled hemoglobin molecules tend to aggregate and reduce blood flow, any organ is at risk for ischemia. Certain organs are at particular risk, including the spleen, kidneys, liver, bone, and even the central nervous system. Strokes have been noted to occur at an early age, with 8% of patients with sickle cell anemia affected by age 14, with 80% of these strokes resulting in complete occlusion of at least 1 major cerebral vessel (5). Organ damage is progressive, occurs at different rates, and can ultimately result in complete organ dysfunction.

Are patients with sickle cell disease at greater risk of infection?

Recurrent and irreversible infarcts eventually result in complete destruction of the spleen. With the loss of spleen function, antibody formation, opsonization and alternate complement production are all affected, producing an increased risk of infections, especially to encapsulated organisms (pneumococci, meningococci, salmonella). This vulnerability is particularly concerning, as it allows small peripheral cuts or infections to become life threatening systemic infections.

References:

1.  Platt OS, Thorington BD, Brambilla DJ, et al. Pain in sickle cell disease. Rates and risk factors. N Engl J Med 1991;325:11-6.
2.  Behrens RJ, Cymet TC. Sickle Cell Disorders: Evaluation, Treatment, and Natural History. Hosp Phys 2000;17-28.
3.  Auvil-Novak SE, Novak RD, el Sanadi N. Twenty-four-hour pattern in emergency department presentation for sickle cell vaso-occlusive pain crisis. Chronobiol Int 1996;13(6):449-56.
4.  Sergeant GR. Sickle cell disease. Lancet 1997;350:725-30.
5.  Adams RJ. Lessons from the Stroke Prevention Trial in Sickle Cell Anemia (STOP) study.J Child Neurol 2000;15:344-9.


编辑：ache