Congenital or acquired control of the clotting
mechanism resulting in a widespread thrombotic tendency. Protein S is a
nonenzymatic, vitamin K-dependent cofactor of activated protein C. It is
either inherited or acquired and leads to liver disease, nephrotic syndrome,
systemic lupus erythematosus, pregnancy, and disseminated intravascular
Protein S alpha Deficiency; Protein S Pseudogene; Purpura fulminans.
Three types of protein S deficiency are described:
- Type I: reduced production
- Type II: abnormality of C4bBP
- Type III: functionally abnormal Protein S.
Protein S deficiency was first identified in 1979 in Seattle,
United States, and arbitrarily named after the city of this discovery.
Unknown; one study found 8% of 179 patients with a
positive family history or who had spontaneous thrombosis to be deficient in
Autosomal dominant inheritance with
male-to-male transmission observed. Gene map locus is 3p11.1-q11.2.
Additional factors are necessary to precipitate thrombosis because some
family members of the affected are asymptomatic even though they have
equally low levels of protein S and because there are instances of a skipped
Protein S is a vitamin K-dependent plasma protein
that inhibits blood clotting by serving as a cofactor for activated protein
C. Deficiency of protein S causes thrombotic disease. Protein S exists in
two forms in plasma: the free, functionally active form (40%) and the
inactive form complexed with C4b-binding protein (C4bBP).
Familial history of thromboembolic events at a young
age. Low plasma protein S levels.
Deficiency of protein S manifests as severe
recurrent thromboembolic disease (leg vein thrombosis, pulmonary embolism,
superficial thrombophlebitis, and thrombosis in uncommon sites—axillary,
mesenteric, and cerebral veins). While patients with homozygous deficiency
present as neonatal purpura fulminans, those with heterozygous forms (30 to
60% of normal) manifest later with venous and, more rarely, arterial
Protein S deficiency does not cause
abnormalities in the routine screening coagulation tests; a high index of
suspicion is necessary in case of familial or personal history of thrombotic
events at a young age and in patients at risk for acquired protein S
deficiency (e.g., nephrotic syndrome). Preventive measures, such as
low-molecular-weight heparin to prevent deep venous thrombosis, should be
instituted before operation and continued postoperatively until the patient
is ambulant. Initiation of oral anticoagulation therapy without antecedent
heparin therapy is fraught with risks of worsening of thrombotic tendencies.
Detailed evaluation of the cardiac and cerebrovascular systems.
Investigations: complete blood count, clotting studies including thromboelastography,
protein S levels.
If a locoregional anesthetic technique
is used, the timing of its performance (and of the withdrawal of the
catheter) should be adapted to the timing of low-molecular-weight heparin
therapy. Use heparin-bonded central venous catheter to reduce the risk of
central venous thrombosis. Arterial catheters should be removed as soon as
The use of antifibrinolytics (e.g.,
ε-aminocaproic acid) is contraindicated because ...