Protein S Deficiency Clinical Presentation

Updated: Aug 05, 2017
  • Author: Mohammad Muhsin Chisti, MD, FACP; Chief Editor: Perumal Thiagarajan, MD  more...
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Presentation

History

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  • Symptoms related to protein S deficiency are those associated with deep venous thrombosis (DVT), thrombophlebitis, or pulmonary embolus. As noted in Deterrence/Prevention, some women may have fetal loss as their only manifestation of a thrombophilic disorder (eg, protein S deficiency).
  • Venous thrombosis of the lower limbs: Lower limb swelling and discomfort are the usual symptoms. Occasionally, redness or discoloration also is present, with or without associated cellulitis.
  • A family history of thrombosis is an important finding, which suggests inherited thrombophilia.
  • Thrombosis at an early age (eg, usually < 55 y) or recurrent thrombosis is also frequently indicative of an inherited thrombophilic state (eg, protein S deficiency).
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Physical

Direct the examination to identify signs of venous thrombosis or pulmonary embolism. The results of the physical examination are nonspecific and often misleadingly indicate the diagnosis of DVT. Unusual sites of thrombosis (eg, mesenteric vein, [21] cerebral sinuses) are rare (< 5%) but, when observed, characteristically suggest one of the inherited thrombophilias (eg, protein S deficiency)

Deep vein thrombosis

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  • The most common manifestation is venous thrombosis of the lower extremities, whichaccounts for approximately 90% of all events
  • Superficial veins that are obviously thrombosed usually appear distended, firm, and noncompressible (cords), with or without associated redness or pain
  • Superficial thrombophlebitis can be observed in some cases, with or without DVT
  • Suspect DVT if identifying signs of venous obstruction and local inflammation are present on examination
  • The classic presentation of DVT is a triad of calf pain, edema, and pain on dorsiflexion of the foot (ie, Homan sign). However, less than a third of DVT cases exhibit these three findings; physicians observe unilateral leg or calf swelling with mild or moderate pain more often, which suggests DVT; rarely, calf discomfort without swelling is the only sign of DVT
  • Differential diagnoses for DVT include muscle strains and tears, passive swelling of a paralyzed or immobilized limb, Baker cyst, cellulitis, knee trauma or derangement, lymphatic obstruction, and postphlebitic syndrome
  • In postphlebitic syndrome, chronic swelling and pain are present in the limb, and the occurrence of a new venous thrombosis is often impossible to assess without Doppler or venography.

Pulmonary embolism

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  • Some patients may have associated or isolated pulmonary embolism and may experience dyspnea, chest pain, syncope, or cardiac palpitations; dyspnea is the most frequent symptom of pulmonary embolism, and tachypnea is the most frequent sign
  • Some patients with massive pulmonary embolism can present with syncope or cyanosis
  • Classic pleuritic chest pain, cough, or hemoptysis suggests an embolism with pleural involvement
  • Acute right-sided heart failure occurs rarely and is associated with massive embolus
  • Findings of right ventricular dysfunction include bulging neck veins, a left parasternal lift, and an accentuated pulmonic component of the second heart sound; these findings are not specific for pulmonary embolism
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Causes

Hereditary causes of protein S deficiency are described in detail in the Pathophysiology section.

Rarely, an acquired disorder causes protein S deficiency. Acquired deficiencies of protein S occur with liver disease, vitamin K deficiency, or as a result of antagonism with oral warfarin anticoagulants.

Protein S levels decrease in pregnancy and can fall into the abnormal-low laboratory range. These low levels of protein S in pregnancy do not cause thrombosis by themselves.

Another seldom recognized cause for acquired protein S deficiency is sickle cell anemia; however, this condition alone does not produce a thrombophilic state.

Age affects total protein S but not free protein S levels. Generally, the total protein S level increases in persons older than 50 years. This rise is in association with total increases in the complement binding protein, C4BP. Free protein S levels do not increase with age. These factors may explain the observation that families with the same recognized genetic defect in protein S can have both type I and type III deficiencies. Type I deficiency is a reduction in both total and free protein S. Type III deficiency is isolated reduction in free protein S. When families with the same genetic type I defect are surveyed, older individuals even with deficiency in protein S have an increase in total protein S and now appear to have type III deficiency.

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