Severe hereditary thrombophilia due to congenital protein S deficiency is a very rare and serious blood-clotting disorder.1, 2
Symptoms often begin very early in life, sometimes infancy. Some babies develop neonatal purpura fulminans (NPF), a life-threatening condition where blood clots form throughout the small blood vessels of the skin and other parts of the body. This can cause dark purple skin patches, tissue damage, and severe illness. Other babies may experience multifocal thrombosis, which means blood clots form in several areas of the body at the same time. Some infants also develop intracranial hemorrhage, which is bleeding inside the skull. Not all children show symptoms immediately. Some may instead experience repeated blood clots later in childhood.2,3
Severe hereditary thrombophilia due to congenital protein S deficiency is caused by changes (variants) in both copies (alleles) of the PROS1 gene, which lead to a severe lack of (deficiency of) protein S. Protein S is a natural substance in the body that helps prevent dangerous blood clots.2, 4-6 Specifically, protein S is involved in inhibiting coagulation (It helps to prevent the blood from clotting too much.).
This condition is inherited in an autosomal recessive pattern. 1, 2,5, 7 This means a child must inherit two changed copies of the PROS1 gene – one from each parent – to develop the severe form of the disease.
Neonatal purpura fulminans (NPF) is a medical emergency. Treatment requires immediate medical attention and ongoing care from a team of specialists who can monitor clotting risk and guide ongoing treatment.2, 3
Protein “S” deficiency was first identified in Seattle, which is the source of its name.1, 5 Protein S deficiency can also be inherited in an autosomal dominant pattern. This form is more common and usually milder, and it is mainly associated with an increased risk of developing blood clots rather than severe symptoms in infancy. This milder form may also be called “thrombophilia due to protein S deficiency (THPH5)” or “thrombophilia 5 due to protein S deficiency, autosomal dominant” or “autosomal dominant thrombophilia due to protein S deficiency.”1, 2, 5, 8
Occasionally, protein S deficiency is not inherited but develops later in life due to other conditions. These include kidney disease (such as nephrotic syndrome), pregnancy, or the use of oral contraceptives.1, 7, 9
The autosomal recessive form, known as severe hereditary thrombophilia due to congenital protein S deficiency, is the rarest and most severe form of protein S deficiency.1, 2
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