Thrombophilia Due To Protein S Deficiency, Autosomal Dominant

Alternative Names

  • THPH5
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WHO-ICD-10 version:2010

Diseases of the blood and blood-forming organs and certain disorders involving the immune mechanism

Coagulation defects, purpura and other haemorrhagic conditions

OMIM Number

612336

Mode of Inheritance

Autosomal dominant

Gene Map Locus

3q11.1

Description

Heterozygous protein S deficiency, like protein C deficiency, is characterized by recurrent venous thrombosis. Protein S deficiency can be classified into 3 clinical subtypes based on laboratory findings. Type I refers to deficiency of both free and total protein S as well as decreased protein S activity; type II shows normal plasma values, but decreased protein S activity; and type III shows decreased free protein S levels and activity, but normal total protein S levels. Approximately 40% of protein S circulates as a free active form, whereas the remaining 60% circulates as an inactive form bound to C4BPA. Under normal conditions, the concentration of protein S exceeds that of C4BPA by approximately 30 to 40%. Thus, free protein S is the molar surplus of protein S over C4BPA. Mild protein S deficiency will thus present with selective deficiency of free protein S, whereas more pronounced protein S deficiency will also decrease the complexed protein S and consequently the total protein S level. These findings explained why assays for free protein S have a higher predictive value for protein S deficiency. 

Epidemiology in the Arab World

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Other Reports

Egypt

[See also: Kuwait > Mohanty et al., 1996].

Iraq

[See also: Kuwait > Mohanty et al., 1996].

Jordan

Awidi et al. (1993) conducted a four-year prospective study on patients admitted or referred with thromboembolic disease to Jordan University Hospital or to the Thrombosis/Haemostasis Laboratory at the University of Jordan. There were a total of 217 patients (102 males and 115 females) with confirmed thromboembolic disease. A total of 49 patients (26 males and 23 females) fulfilled the criteria of hereditary thrombophilia. There were 17 cases of protein C deficiency (PC), 15 protein S deficiency (PS), 10 antithrombin III deficiency (ATIII), 3 dyfibrinogenemia, 2 heparin cofactor II deficiency, and 2 plasminogen defects. Twenty-seven additional relatives with deficiency were identified upon family studies.

Eid (2002) studied 602 (265 female, 337 male) patients with suspected thrombosis, arterial or venous. The prevalence of hereditary deficiencies of antithrombin (AT), protein S (PS), and protein C (PC) were studied over a seven-year period (1993-2000). A diagnosis was established in 22.4% (n = 135) of the subjects (20.3% venous, 2.1% arterial). Protein C deficiency was found in 3.8%, protein S deficiency in 2.3% and antithrombin deficiency in 1.4% of the sample group.

[See also: Kuwait > Mohanty et al., 1996].

Kuwait

Mohanty et al. (1996) conducted a 4-year (1986-1990) retrospective study on 130 unrelated patients with recurrent deep venous thrombosis in order to determine the possible etiology. The study group consisted of only ethnic Arab patients from Kuwait, Palestine, Jordan, Egypt, Sudan, Iraq, and Syria. Fifteen patients were found to have hereditary protein C deficiency (11.52%). Family studies revealed autosomal recessive inheritance in one patient and a dominant pattern in the remaining 14 patients. Protein S deficiency was found in eight cases (6.1%), AT-III deficiency was established in five cases (3.8%) and a fibrinolytic defect in 33 cases (25.4%). Thrombosis of visceral and cerebral vessels and a positive family history were more frequently found among patients who had hereditary deficiency of one or the other antithrombotic factor. Thrombophlebitis of superficial veins was found to be very common in patients with protein C and protein S deficiency and virtually absent in AT-III deficiency.

Oman

Pathare et al. (2006) studied the prothrombotic risk factors in Omani patients who presented with their first thrombophilic event. All Omani patients (39 patients: 24 females and 15 males), who were admitted between 2001 and 2003 with a first episode of deep venous thrombosis (DVT) with or without pulmonary embolism (PE) or with thrombosis in an unusual site, were included in the study. Only two patients (5.12%) were found to have low levels of protein S. Pathare et al. (2006) had suggested conduction of a larger study to relate the hereditary markers for thrombophilia to the actual event.

Palestine

Inbal et al. (1997) described two children from two unrelated Arab families with purpura fulminans who were double heterozygotes for factor V Leiden inherited from their fathers and protein S deficiency inherited from their mothers. No previous thrombotic events have occurred in either patient or their respective family members. In one patient sepsis accompanied by disseminated intravascular coagulation appeared to be the trigger of purpura fulminans. In the other patient varicella infection preceded purpura fulminans and was also associated with disseminated intravascular coagulation.

[See also: Kuwait > Mohanty et al., 1996].

Saudi Arabia

Al-Jaouni (2003) conducted a retrospective analysis in 179 consecutive Saudi patients (74 males, 105 females) that were screened between October 1997 and January 2002 at the King Abdul-Aziz University Hospital (KAUH) and King Fahd Armed Forces Hospital (KFAFH), Jeddah, Kingdom of Saudi Arabia. All patients had at least one of the following features: history of recurrent venous thromboembolism (VTE), first episode of unprovoked VTE, thrombosis in unusual site or thrombosis at young age with or without positive family history. Thrombotic workup included protein C, protein S, antithrombin (AT), APCR, prothrombin mutation, lupus anticoagulant (LA), and anticardiolipin (ACL). Functional assays were carried out in 179 patients. Protein S deficiency was the most common, identified in 26/179 (14.5%) followed by protein C in 15/179 (8.4%), while AT was not deficient in all 179 tested patients. Activated protein C resistance was present in only 4 patients (2.2%).

Sudan

[See also: Kuwait > Mohanty et al., 1996].

Syria

[See also: Kuwait > Mohanty et al., 1996].

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