Table 1.

Example terms specific to the SCDO phenotype upper-level class that may also be important for other ontologies, such as HPO and DO

SCDO ID	SCDO term	Definitions or description
SCDO:0000162	Breakthrough pain	Originally used to describe patients with cancer pain who were maintained on a stable dose of analgesics, breakthrough pain was defined as a flair-up of sudden pain unresponsive to usual therapy. Such a flare-up is usually sudden and incidental and can last from a few seconds to a few hours. There are currently no data that clearly describe or can be used to define breakthrough pain in SCD.
SCDO:0006461	Acutely severe anemia	Aplasia or haemolysis may be precipitated by another illness/infection in patients with sickle cell disease. Acutely severe anaemia is defined as Hb < 5 g/dl or a recent acute drop in HB > 2 g/dl below the individual’s steady state value. If no steady state value is available, it can be detected by the presence of acutely symptomatic anaemia (i.e. tachycardia, cardiac failure, shock).
SCDO:0007900	Embryonic hemoglobin	The type of haemoglobin present within an embryo in the first 8 weeks of gestation. Two haemoglobins, Gower 1 and Gower 2, are found in embryos of up to 8 weeks of gestation, and Haemoglobin Portland is a third normal embryonic haemoglobin found at lower levels in an embryo.
SCDO:0007161	Acute splenic sequestration crisis	Significant change in blood picture characterized by a precipitous fall in the haemoglobin level of at least 2 g/dl and accompanied by a rapidly enlarging spleen or liver (greater than 2 cm from the steady state level) and reticulocytosis above the steady state level for each individual patient. Signs of acute circulatory insufficiency, such as tachypnoea, tachycardia and hypotension, may or may not be present. It is the earliest life-threatening complication seen in patients with SCD besides pneumococcal infections.
SCDO:0006847	Aplastic crisis	An acute form of acquired red cell aplasia. A significant change in blood picture is observed, characterized by a precipitous fall in the haemoglobin level (>2 g/dl beyond steady state level) and reduced (<1%) or absent reticulocytes in the peripheral blood. The total white blood cell or platelet counts may or may not be affected. In addition, there is no significant increase in the unconjugated fraction of serum bilirubin.
SCDO:0009664	Abdominal vaso-occlusive crisis	Abdominal distension with generalized abdominal tenderness (no rebound tenderness) and reduced bowel sounds. Abdomen moves with respiration. Vomiting/diarrhoea is not common. It is thought to occur secondary to the occlusion of mesenteric vessels.
SCDO:0000812	Non-specific acute lower respiratory tract episode	Includes acute respiratory episodes with lower respiratory tract signs that do not meet the criteria for other diagnoses. May include episodes that would have been diagnosed as ACS were radiographic facilities available.
SCDO:0008625	Right upper quadrant syndrome	Characterized by pain and discomfort in the right upper quadrant (RUQ) of the abdomen caused by a number of possible aetiologies in sickle cell disease. Causes of RUQ pain may be divided into pain originating from the liver or gall bladder versus other origins of abdominal pain in that region.
SCDO:0006909	Hyperhemolytic Crisis	Significant change in blood picture characterized by a precipitous fall in the haemoglobin level associated with jaundice, marked reticulocytosis and polychromasia on the blood smear, increased unconjugated hyperbilirubinemia and increased urobilinogen content in urine above the steady state level for each individual patient.
SCDO:0002039	Zinc deficiency	A deficiency of the essential metal zinc; an essential cofactor for many enzymes. Zinc deficiency is caused by a lack of zinc in the diet, loss of zinc after absorption, for example through loss through burns, inability to absorb zinc or increased loss through exercise.
SCDO:0008623	Vaso-occlusion	The obstruction of blood vessels by altered erythrocytes that can result in pain, anaemia and tissue ischemia.
SCDO:0004888	Functional hyposplenism	An acquired disorder caused by several haematological and immunological diseases and characterized by impairment of splenic function.
SCDO:0006835	Normal hemoglobin	Haemoglobins that present no inherited health condition phenotype susceptible to undergo alterations in the red blood cells.
SCDO:0004187	Hemolytic crisis	May be caused by an acute VOC, malarial infection or oxidant drug exposure in individuals with concomitant glucose-6-phosphate dehydrogenase (G6PD) deficiency. Haemolytic crisis may be distinguished from aplastic crisis by the finding of a reticulocytosis as opposed to a reticulocytopenia.
SCDO:0001229	Vaso-occlusive crisis	Pain resulting from tissue ischemia as a result of blockage of blood vessels, occurring in a variety of vascular beds, but most commonly in the bone or bone marrow and requiring analgesic medication.
SCDO:0004576	Chronic hypersplenism	Chronic splenic sequestration associated with enlarged spleen and cytopenia with anaemia and reduction in white blood cells and platelets. The anaemia is usually chronic in nature and patients rarely present with signs of heart failure.
SCDO:0000225	Chronic complications of sickle cell disease	A condition that co-exists or follows from sickle cell disease and that has a slow, creeping onset, slow progress and long continuance of disease manifestations.
SCDO:0000895	Phenotype of sickle cell disease	A (combination of) quality(ies) of some or all sickle cell disease individuals, determined by the interaction of the genetic make-up of these individuals (with regard to sickle cell disease) and their environment.
SCDO:0001135	Acute sickle cell crisis	Refers to a worsening, over a short period of time, of the symptoms and signs of SCD; usually associated with pain and/or shortage of blood (anaemia). Can be suspected in a person with sickle cell disease who presents with a sudden onset of pain, infection, anaemia or other symptoms such as stroke or priapism. Acute pain frequently occurs spontaneously, but may be precipitated by infections, skin cooling, dehydration or stress.
SCDO:0001023	SCD related pain	Pain resulting from the presence of sickle cell disease (SCD). Such pain can be acute, chronic or a mixture of the two.
SCDO:0000233	Chronic sickle cell pain	Pain that does not resolve and lasts for more than 3 months.
SCDO:0001604	Steady state	This is a period when the patient with sickle cell anaemia is free of infection, pain or other disease processes.
SCDO:1000061	Altered level of normal hemoglobin present in SCD	An altered level of normal haemoglobin (Haemoglobin A (Hb A), Haemoglobin A2 (Hb A2) or Haemoglobin F (Hb F, fatal haemoglobin) in the blood, which may be seen in those suffering with sickle cell disease (SCD).
SCDO:0000007	Abnormal hemoglobin structure present in SCD	A structurally abnormal haemoglobin that occurs in one or more forms of sickle cell disease (SCD).