Sickle cell anemia is the most common familial hemolytic anemia. In parts of Africa, where malaria is endemic, the gene frequency approaches 30% as a result of a protective effect against Plasmodium falciparum malaria. Much more serious are vaso-occlusive crises, which are characteristically associated with pain and often lead to tissue damage and significant morbidity and mortality. Among the most common and serious of these vasoocclusive crises are the following:Hand-foot syndrome, resulting from infarction of bones in the hands and feet, is the most common presenting symptom in young children.  Acute chest syndrome, in which sluggish blood flow in inflamed lung (e.g., an area of pneumonia) leads to sickling within hypoxemic pulmonary beds. This exacerbates pulmonary dysfunction, creating a vicious circle of worsening pulmonary and systemic hypoxemia, sickling, and vaso-occlusion. Acute chest syndrome may also be triggered by fat emboli emanating from infarcted bone. Patients with sickle cell disease also are predisposed to Salmonella osteomyelitis, possibly in part because of poorly understood acquired defects in complement function. Robin’s Textbook of pathology 10th ed Page 446-447