Similarly, although the goal is not to wait to discuss end-of-life until death is imminent, such discussion may not have the same benefit for young patients who are clinically well with low-risk disease. Thus, it is important to always have and en- courage the option to discuss end-of-life issues, but timing of conversation is individualized. The definition of cyanosis is blueish discoloration of the skin and/or mucous membranes resulting from inade- quate oxygenation of the blood. Generally, for cyanosis to be visible, at least 5 g/L of unsaturated hemoglobin in tissue is needed.S3.16-1 Anemia may result in hypoxe- mia that is not manifest as cyanosis. In this guideline, cyanosis is used as a generic term to identify hypox- emia caused by right-to-left shunting of blood, but not all hypoxemic patients will be visibly cyanotic at all times. Cyanotic heart disease encompasses a widely hetero- geneous group; therefore, an individualized approach is needed for each patient according to the clinical details. Secondary erythrocytosis (a physiological increase in red blood cell mass in response to hypoxemia) and polycythe- mia (a neoplastic proliferation of hematopoietic cells in- cluding the red blood cell line) are fundamentally different conditions that require different treatments. In secondary erythrocytosis, the patient s own homeostatic processes generally direct achievement of an optimal level of red cell mass, estimated by hemoglobin and hematocrit.S3.16-2 Iron deficiency is frequently encountered in cyanotic In addition to contributing to symp- toms, iron deficiency causes a reduction of hemoglobin without a proportional change in hematocrit and thus compromises systemic oxygen transport without lower- Symptoms mimic those of hyperviscos- ity. Consequences of iron deficiency may include stroke and myocardial ischemia,S3.16-4 S3.16-6 although published findings are inconsistent. 