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Thrombophilia due to protein S deficiency, autosomal dominant(THPH5)

MedGen UID:
479841
Concept ID:
C3278211
Disease or Syndrome
Synonym: THPH5
Modes of inheritance:
Not genetically inherited
MedGen UID:
988794
Concept ID:
CN307044
Finding
Source: Orphanet
clinical entity without genetic inheritance.
 
Gene (location): PROS1 (3q11.1)
 
Monarch Initiative: MONDO:0012868
OMIM®: 612336
Orphanet: ORPHA26349

Definition

Heterozygous protein S deficiency, like protein C deficiency (176860), is characterized by recurrent venous thrombosis. Bertina (1990) classified protein S deficiency 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 (120830). Zoller et al. (1995) observed coexistence of type I and type III PROS1-deficient phenotypes within a single family and determined that the subtypes are allelic. 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. See also autosomal recessive thrombophilia due to protein S deficiency (THPH6; 614514), which is a more severe disorder. [from OMIM]

Additional description

From MedlinePlus Genetics
Protein S deficiency is a disorder that increases the risk of developing blood clots. People with protein S deficiency are at risk of developing a type of clot called a deep vein thrombosis (DVT) that occurs in the deep veins of the arms or legs. A DVT can travel through the bloodstream and lodge in the lungs, causing a life-threatening clot called a pulmonary embolism (PE). Both DVTs and PEs are a type of venous thromboembolism, a general term for blood clots that form in a vein. Factors such as age, surgery, immobility, or pregnancy can increase the risk of clotting in people with protein S deficiency. In addition, people who have protein S deficiency and another inherited blood clotting disorder may have a higher risk of developing blood clots. Venous thromboembolism occurs in approximately fifty to sixty percent of people with protein S deficiency. 

In rare cases, individuals have a severe form of protein S deficiency with signs and symptoms that develop soon after birth. Affected infants typically develop a life-threatening blood clotting disorder called purpura fulminans. Purpura fulminans is characterized by the formation of blood clots within small blood vessels throughout the body. These blood clots disrupt normal blood flow and can lead to the death of tissues (necrosis). Widespread blood clotting uses up all available blood clotting proteins. As a result, the body can no longer create clots, and bleeding occurs in various parts of the body. This abnormal bleeding often appears as large, purple skin lesions. Affected individuals who survive the newborn period may experience recurrent episodes of purpura fulminans.  https://medlineplus.gov/genetics/condition/protein-s-deficiency

Clinical features

From HPO
Pulmonary embolism
MedGen UID:
11027
Concept ID:
C0034065
Pathologic Function
An embolus (that is, an abnormal particle circulating in the blood) located in the pulmonary artery and thereby blocking blood circulation to the lung. Usually the embolus is a blood clot that has developed in an extremity (for instance, a deep venous thrombosis), detached, and traveled through the circulation before becoming trapped in the pulmonary artery.
Arterial thrombosis
MedGen UID:
56253
Concept ID:
C0151942
Pathologic Function
The formation of a blood clot inside an artery.
Cerebral venous thrombosis
MedGen UID:
57743
Concept ID:
C0151945
Disease or Syndrome
Formation of a blood clot (thrombus) inside a cerebral vein, causing the obstruction of blood flow.
Thrombophilia
MedGen UID:
98306
Concept ID:
C0398623
Disease or Syndrome
An abnormality of coagulation associated with an increased risk of thrombosis.
Superficial thrombophlebitis
MedGen UID:
266934
Concept ID:
C1510431
Disease or Syndrome
Inflammation of a superficial vein associated with venous thrombosis (blood clot formation within the vein).
Reduced protein S activity
MedGen UID:
892328
Concept ID:
C4025284
Finding
An abnormality of coagulation related to a decreased concentration of vitamin K-dependent protein S. Protein S is a cofactor of protein C.
Purpura
MedGen UID:
19584
Concept ID:
C0034150
Disease or Syndrome
Purpura (from Latin
Warfarin-induced skin necrosis
MedGen UID:
356820
Concept ID:
C1867638
Finding

Term Hierarchy

Recent clinical studies

Etiology

Okada K, Tamura S, Suzuki N, Odaira K, Mukaide M, Fujii W, Katsuragi Y, Suzuki A, Kanematsu T, Okamoto S, Suzuki N, Katsumi A, Matsushita T, Kojima T, Hayakawa F
Thromb Res 2022 Feb;210:26-32. Epub 2021 Dec 21 doi: 10.1016/j.thromres.2021.12.014. PMID: 34968852
Bona R
Oral Maxillofac Surg Clin North Am 2016 Nov;28(4):491-495. doi: 10.1016/j.coms.2016.06.002. PMID: 27745619
Wypasek E, Undas A
Adv Clin Exp Med 2013 Jul-Aug;22(4):459-67. PMID: 23986205
García de Frutos P, Fuentes-Prior P, Hurtado B, Sala N
Thromb Haemost 2007 Sep;98(3):543-56. PMID: 17849042
Kutteh WH, Triplett DA
Semin Reprod Med 2006 Feb;24(1):54-66. doi: 10.1055/s-2006-931801. PMID: 16418978

Diagnosis

Wypasek E, Undas A
Adv Clin Exp Med 2013 Jul-Aug;22(4):459-67. PMID: 23986205
Joshi A, Jaiswal JP
JNMA J Nepal Med Assoc 2010 Jan-Mar;49(177):56-8. PMID: 21180223
Agoşton-Coldea L, Rusu LD, Bobar C, Rusu ML, Mocan T, Procopciuc LM
Rom J Intern Med 2008;46(3):261-6. PMID: 19366087
Wilkerson DK, Burrell L, Cisar LA, Graham AM, Kim H
J Vasc Surg 1993 Dec;18(6):932-7; discussion 937-8. PMID: 8264049
Earls JP, McAdams HP, Colon E, Jelinek JS
AJR Am J Roentgenol 1993 Dec;161(6):1283-7. doi: 10.2214/ajr.161.6.8249743. PMID: 8249743

Therapy

Lou J, Yin L, Ke X, Zhang L, Xu F, Liu Z
Blood Coagul Fibrinolysis 2020 Sep;31(6):405-409. doi: 10.1097/MBC.0000000000000929. PMID: 32815916
Wypasek E, Undas A
Adv Clin Exp Med 2013 Jul-Aug;22(4):459-67. PMID: 23986205
Joshi A, Jaiswal JP
JNMA J Nepal Med Assoc 2010 Jan-Mar;49(177):56-8. PMID: 21180223
Agoşton-Coldea L, Rusu LD, Bobar C, Rusu ML, Mocan T, Procopciuc LM
Rom J Intern Med 2008;46(3):261-6. PMID: 19366087
Petersen EJ, Allaart RC, Meuwissen OJ
Neth J Med 1989 Jun;34(5-6):243-50. PMID: 2528077

Prognosis

Okada K, Tamura S, Suzuki N, Odaira K, Mukaide M, Fujii W, Katsuragi Y, Suzuki A, Kanematsu T, Okamoto S, Suzuki N, Katsumi A, Matsushita T, Kojima T, Hayakawa F
Thromb Res 2022 Feb;210:26-32. Epub 2021 Dec 21 doi: 10.1016/j.thromres.2021.12.014. PMID: 34968852
Lou J, Yin L, Ke X, Zhang L, Xu F, Liu Z
Blood Coagul Fibrinolysis 2020 Sep;31(6):405-409. doi: 10.1097/MBC.0000000000000929. PMID: 32815916
Jang MA, Kim SH, Kim DK, Kim HJ
Blood Coagul Fibrinolysis 2015 Mar;26(2):223-4. doi: 10.1097/MBC.0000000000000217. PMID: 25255242
Wypasek E, Undas A
Adv Clin Exp Med 2013 Jul-Aug;22(4):459-67. PMID: 23986205
Hirsh J, Piovella F, Pini M
Am J Med 1989 Sep 11;87(3B):34S-38S. doi: 10.1016/0002-9343(89)80529-7. PMID: 2679068

Clinical prediction guides

Okada K, Tamura S, Suzuki N, Odaira K, Mukaide M, Fujii W, Katsuragi Y, Suzuki A, Kanematsu T, Okamoto S, Suzuki N, Katsumi A, Matsushita T, Kojima T, Hayakawa F
Thromb Res 2022 Feb;210:26-32. Epub 2021 Dec 21 doi: 10.1016/j.thromres.2021.12.014. PMID: 34968852
Lou J, Yin L, Ke X, Zhang L, Xu F, Liu Z
Blood Coagul Fibrinolysis 2020 Sep;31(6):405-409. doi: 10.1097/MBC.0000000000000929. PMID: 32815916
Jang MA, Kim SH, Kim DK, Kim HJ
Blood Coagul Fibrinolysis 2015 Mar;26(2):223-4. doi: 10.1097/MBC.0000000000000217. PMID: 25255242
Wypasek E, Undas A
Adv Clin Exp Med 2013 Jul-Aug;22(4):459-67. PMID: 23986205
Joshi A, Jaiswal JP
JNMA J Nepal Med Assoc 2010 Jan-Mar;49(177):56-8. PMID: 21180223

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