U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Congenital prothrombin deficiency

MedGen UID:
124425
Concept ID:
C0272317
Disease or Syndrome
Synonyms: Congenital factor II deficiency; Factor II deficiency; Hereditary factor II deficiency disease; HYPOPROTHROMBINEMIA; Inherited hypoprothrombinemia; Inherited prothrombin deficiency
SNOMED CT: Hereditary factor II deficiency disease (33297000); Hereditary hypoprothrombinemia (33297000)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): F2 (11p11.2)
 
Monarch Initiative: MONDO:0013361
OMIM®: 613679
Orphanet: ORPHA325

Definition

Prothrombin deficiency is an extremely rare autosomal recessive bleeding disorder characterized by low levels of circulating prothrombin; it affects about 1 in 2,000,000 individuals. There are 2 main types: type I deficiency, known as true prothrombin deficiency or 'hypoprothrombinemia,' is defined as plasma levels of prothrombin being less than 10% of normal with a concomitant decrease in activity. These patients have severe bleeding from birth, including umbilical cord hemorrhage, hematomas, ecchymoses, hematuria, mucosal bleeding, hemarthroses, intracranial bleeding, gastrointestinal bleeding, and menorrhagia. Type II deficiency, known as 'dysprothrombinemia,' is characterized by normal or low-normal synthesis of a dysfunctional protein. Bleeding symptoms are more variable, depending on the amount of residual functional activity. Variant prothrombin gene alleles can result in 'hypoprothrombinemia' or 'dysprothrombinemia,' and individuals who are compound heterozygous for these 2 types of alleles have variable manifestations. Heterozygous mutation carriers, who have plasma levels between 40 and 60% of normal, are usually asymptomatic, but can show bleeding after tooth extraction or surgical procedures (review by Lancellotti and De Cristofaro, 2009). [from OMIM]

Additional descriptions

From MedlinePlus Genetics
Prothrombin thrombophilia is an inherited disorder of blood clotting. Thrombophilia is an increased tendency to form abnormal blood clots in blood vessels. People who have prothrombin thrombophilia are at somewhat higher than average risk for a type of clot called a deep venous thrombosis, which typically occurs in the deep veins of the legs. Affected people also have an increased risk of developing a pulmonary embolism, which is a clot that travels through the bloodstream and lodges in the lungs. Most people with prothrombin thrombophilia never develop abnormal blood clots, however.

Some research suggests that prothrombin thrombophilia is associated with a somewhat increased risk of pregnancy loss (miscarriage) and may also increase the risk of other complications during pregnancy. These complications may include pregnancy-induced high blood pressure (preeclampsia), slow fetal growth, and early separation of the placenta from the uterine wall (placental abruption). It is important to note, however, that most women with prothrombin thrombophilia have normal pregnancies.  https://medlineplus.gov/genetics/condition/prothrombin-thrombophilia
From MedlinePlus Genetics
Prothrombin deficiency is a bleeding disorder that slows the blood clotting process. People with this condition often experience prolonged bleeding following an injury, surgery, or having a tooth pulled. In severe cases of prothrombin deficiency, heavy bleeding occurs after minor trauma or even in the absence of injury (spontaneous bleeding). Women with prothrombin deficiency can have prolonged and sometimes abnormally heavy menstrual bleeding. Serious complications can result from bleeding into the joints, muscles, brain, or other internal organs. Milder forms of prothrombin deficiency do not involve spontaneous bleeding, and the condition may only become apparent following surgery or a serious injury.  https://medlineplus.gov/genetics/condition/prothrombin-deficiency

Clinical features

From HPO
Joint hemorrhage
MedGen UID:
5479
Concept ID:
C0018924
Pathologic Function
Hemorrhage occurring within a joint.
Gastrointestinal hemorrhage
MedGen UID:
8971
Concept ID:
C0017181
Pathologic Function
Hemorrhage affecting the gastrointestinal tract.
Epistaxis
MedGen UID:
4996
Concept ID:
C0014591
Pathologic Function
Epistaxis, or nosebleed, refers to a hemorrhage localized in the nose.
Gingival bleeding
MedGen UID:
42218
Concept ID:
C0017565
Pathologic Function
Hemorrhage affecting the gingiva.
Menorrhagia
MedGen UID:
44358
Concept ID:
C0025323
Pathologic Function
Prolonged and excessive menses at regular intervals in excess of 80 mL or lasting longer than 7 days.
Prolonged bleeding time
MedGen UID:
56231
Concept ID:
C0151529
Finding
Prolongation of the time taken for a standardized skin cut of fixed depth and length to stop bleeding.
Prolonged partial thromboplastin time
MedGen UID:
66815
Concept ID:
C0240671
Finding
Increased time to coagulation in the partial thromboplastin time (PTT) test, a measure of the intrinsic and common coagulation pathways. Phospholipid, and activator, and calcium are mixed into an anticoagulated plasma sample, and the time is measured until a thrombus forms.
Prolonged prothrombin time
MedGen UID:
208879
Concept ID:
C0853225
Finding
Increased time to coagulation in the prothrombin time test, which is a measure of the extrinsic pathway of coagulation. The results of the prothrombin time test are often expressed in terms of the International normalized ratio (INR), which is calculated as a ratio of the patient's prothrombin time (PT) to a control PT standardized for the potency of the thromboplastin reagent developed by the World Health Organization (WHO) using the formula
Ecchymosis
MedGen UID:
8524
Concept ID:
C0013491
Finding
A purpuric lesion that is larger than 1 cm in diameter.
Bruising susceptibility
MedGen UID:
140849
Concept ID:
C0423798
Finding
An ecchymosis (bruise) refers to the skin discoloration caused by the escape of blood into the tissues from ruptured blood vessels. This term refers to an abnormally increased susceptibility to bruising. The corresponding phenotypic abnormality is generally elicited on medical history as a report of frequent ecchymoses or bruising without adequate trauma.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVCongenital prothrombin deficiency

Professional guidelines

PubMed

Qu C, Liu W, Chen L, Zhang L, Xue F, Yang R
Br J Haematol 2023 Feb;200(3):344-352. Epub 2022 Oct 13 doi: 10.1111/bjh.18514. PMID: 36229963
Shetty SD, Ghosh K
Blood Cells Mol Dis 2015 Mar;54(3):275-80. Epub 2014 Nov 25 doi: 10.1016/j.bcmd.2014.11.012. PMID: 25486929
Shetty S, Bhave M, Ghosh K
Autoimmun Rev 2011 Apr;10(6):311-6. Epub 2010 Nov 27 doi: 10.1016/j.autrev.2010.11.005. PMID: 21115138

Recent clinical studies

Etiology

Girolami A, Brunetti A, Patrassi G, Borsato N
Folia Haematol Int Mag Klin Morphol Blutforsch 1976;103(5):746-57. PMID: 64416

Diagnosis

Harel R, Shani D, Donohoe K
Blood Coagul Fibrinolysis 2017 Jan;28(1):100-101. doi: 10.1097/MBC.0000000000000534. PMID: 26886363
Girolami A, Brunetti A, Patrassi G, Borsato N
Folia Haematol Int Mag Klin Morphol Blutforsch 1976;103(5):746-57. PMID: 64416

Therapy

Seki M, Koh K, Inoue T, Tomita Y, Kato M, Shimizu M, Morishita E, Hanada R
Pediatr Blood Cancer 2013 Mar;60(3):503-5. Epub 2012 Nov 14 doi: 10.1002/pbc.24387. PMID: 23152198
Lancellotti S, De Cristofaro R
Semin Thromb Hemost 2009 Jun;35(4):367-81. Epub 2009 Jul 13 doi: 10.1055/s-0029-1225759. PMID: 19598065
Girolami A, Lombardi AM, Candeo N, Scarparo P, Paternoster A
Acta Haematol 2008;119(4):236-40. Epub 2008 Jun 28 doi: 10.1159/000141782. PMID: 18583905

Clinical prediction guides

Girolami A, Ferrari S, Cosi E, Girolami B, Lombardi AM
Hematology 2018 Mar;23(2):105-110. Epub 2017 Aug 1 doi: 10.1080/10245332.2017.1359900. PMID: 28762299
Girolami A, Brunetti A, Patrassi G, Borsato N
Folia Haematol Int Mag Klin Morphol Blutforsch 1976;103(5):746-57. PMID: 64416

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.
    • Bookshelf
      See practice and clinical guidelines in NCBI Bookshelf. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Recent activity

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...