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Hypoprothrombinemia Clinical Presentation

  • Author: J Nathan Hagstrom, MD; Chief Editor: Robert J Arceci, MD, PhD  more...
Updated: Apr 08, 2016


The most common initial presentations of hypoprothrombinemia include mucosal bleeding, soft tissue bleeding, and hemarthrosis. Severe prothrombin deficiency can result in deep hemorrhages[5] , including muscle hematomas, intracranial bleeding, pulmonary hemorrhage, umbilical bleeding, postoperative bleeding, and menorrhagia. Severe bleeding can result in anemia with associated symptoms.

Patients with lupus anticoagulant-hypoprothrombinemia syndrome (LAHS) may have other symptoms of autoimmune disease. As an alternative, they may have a history of a preceding viral infection, usually an upper respiratory infection or gastroenteritis.[6]

Symptoms associated with hypoprothrombinemia include the following:

  • Easy bruising
  • Epistaxis
  • Prolonged bleeding with injury, tooth extraction, or surgery
  • Oral mucosal bleeding
  • Melena
  • Hematochezia
  • Hematuria
  • Intracranial hemorrhage
  • Hemarthroses
  • Menorrhagia


The most common physical findings are ecchymoses, bleeding from mucosal surfaces, and pallor secondary to blood loss. Petechiae are uncommon because platelet numbers and function are not affected. Other physical findings are specifically related to the hemorrhage site.



Hypoprothrombinemia may be inherited or acquired. Acquired hypoprothrombinemia may be an isolated factor deficiency or a condition associated with several factor deficiencies.

Acquired causes that are usually associated with isolated factor II deficiency include autoantibodies to prothrombin associated with the lupus anticoagulant or spontaneous formation of an inhibitor to prothrombin (autoantibody not associated with lupus anticoagulant). Lupus anticoagulant–hypoprothrombinemia syndrome may be the initial manifestation of systemic lupus erythematosus or may be postviral. Adenovirus is the viral pathogen most commonly involved, and it is associated with 50% of postviral cases.

Inherited prothrombin deficiency is autosomal recessive. Type I prothrombin deficiency is usually the result of a missense or nonsense mutation that decreases the production of prothrombin. Type II prothrombin deficiency is the result of a missense mutation in the cleavage sites for factor Xa and the serine protease region of prothrombin, which creates a protein with reduced activity.

Prothrombin deficiency can also be seen as part of a rare inherited deficiency of the vitamin K–dependent clotting factors. The disorder is the result of dysfunction in the vitamin K–dependent enzyme pathway that is common to factors II, VI, IX, and X. Inheritance is autosomal recessive, and fewer than 20 cases have been reported worldwide. Presentation and severity of bleeding symptoms widely vary. Some patients have responded to treatment with vitamin K.

Causes usually associated with multiple-factor deficiencies include vitamin K deficiency, severe liver disease, disseminated intravascular coagulation (DIC), and warfarin overdose.

Reports describe antibiotic-induced hypoprothrombinemia, which is usually due to beta-lactam antibiotics. Antibiotic-induced hypoprothrombinemia is thought to be related to decreased availability of vitamin K (due to loss of gut flora) or is caused by direct interference with the vitamin K cycle in the liver by thiol group–containing antibiotics.

Contributor Information and Disclosures

J Nathan Hagstrom, MD Division Head and Director, Hematology-Oncology, Connecticut Children's Medical Center; Associate Professor of Pediatrics, University of Connecticut

J Nathan Hagstrom, MD is a member of the following medical societies: American Society of Hematology, American Society of Pediatric Hematology/Oncology, International Society on Thrombosis and Haemostasis

Disclosure: Nothing to disclose.


James L Harper, MD Associate Professor, Department of Pediatrics, Division of Hematology/Oncology and Bone Marrow Transplantation, Associate Chairman for Education, Department of Pediatrics, University of Nebraska Medical Center; Associate Clinical Professor, Department of Pediatrics, Creighton University School of Medicine; Director, Continuing Medical Education, Children's Memorial Hospital; Pediatric Director, Nebraska Regional Hemophilia Treatment Center

James L Harper, MD is a member of the following medical societies: American Society of Pediatric Hematology/Oncology, American Federation for Clinical Research, Council on Medical Student Education in Pediatrics, Hemophilia and Thrombosis Research Society, American Academy of Pediatrics, American Association for Cancer Research, American Society of Hematology

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Gary D Crouch, MD Associate Professor, Program Director of Pediatric Hematology-Oncology Fellowship, Department of Pediatrics, Uniformed Services University of the Health Sciences

Gary D Crouch, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Hematology

Disclosure: Nothing to disclose.

Chief Editor

Robert J Arceci, MD, PhD Director, Children’s Center for Cancer and Blood Disorders, Department of Hematology/Oncology, Co-Director of the Ron Matricaria Institute of Molecular Medicine, Phoenix Children’s Hospital; Editor-in-Chief, Pediatric Blood and Cancer; Professor, Department of Child Health, University of Arizona College of Medicine

Robert J Arceci, MD, PhD is a member of the following medical societies: American Association for the Advancement of Science, American Association for Cancer Research, American Pediatric Society, American Society of Hematology, American Society of Pediatric Hematology/Oncology

Disclosure: Nothing to disclose.


Gary R Jones, MD Associate Medical Director, Clinical Development, Berlex Laboratories

Gary R Jones, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Pediatric Hematology/Oncology, and Western Society for Pediatric Research

Disclosure: Nothing to disclose.

Sara E Tisdale, MD Resident Physician, Creighton University Joint Pediatric Residency Program, Department of Pediatrics, University of Nebraska Medical Center

Disclosure: Nothing to disclose.

  1. Meeks SL, Abshire TC. Abnormalities of prothrombin: a review of the pathophysiology, diagnosis, and treatment. Haemophilia. 2008 Nov. 14(6):1159-63. [Medline].

  2. Xue J, Wu Q, Westfield LA, et al. Incomplete embryonic lethality and fatal neonatal hemorrhage caused by prothrombin deficiency in mice. Proc Natl Acad Sci U S A. 1998 Jun 23. 95(13):7603-7. [Medline]. [Full Text].

  3. Acharya SS, Coughlin A, Dimichele DM, et al. Rare Bleeding Disorder Registry: deficiencies of factors II, V, VII, X, XIII, fibrinogen and dysfibrinogenemias. J Thromb Haemost. 2004 Feb. 2(2):248-56. [Medline].

  4. Pasmant E, Dumont B, Lacapere JJ, Dautzenberg MD, Bezeaud A. A severe neonatal presentation of factor II deficiency. Eur J Haematol. 2011 Nov. 87(5):464-6. [Medline].

  5. Kim JS, Kim MJ, Bae EY, Jeong DC. Pulmonary hemorrhage in pediatric lupus anticoagulant hypoprothrombinemia syndrome. Korean J Pediatr. 2014 Apr. 57(4):202-5. [Medline]. [Full Text].

  6. Appert-Flory A, Fischer F, Amiral J, Monpoux F. Lupus Anticoagulant-Hypoprothrombinemia syndrome (HLAS): report of one case in a familial infectious context. Thromb Res. 2010 Aug. 126(2):e139-40. [Medline].

  7. Sarker T, Roy S, Hollon W, Rajpurkar M. Lupus anticoagulant acquired hypoprothrombinemia syndrome in childhood: two distinct patterns and review of the literature. Haemophilia. 2015 Nov. 21 (6):754-60. [Medline].

  8. Akhavan S, Luciani M, Lavoretano S, Mannucci PM. Phenotypic and genetic analysis of a compound heterozygote for dys- and hypoprothrombinaemia. Br J Haematol. 2003 Jan. 120(1):142-4. [Medline].

  9. Baca V, Montiel G, Meillon L, et al. Diagnosis of lupus anticoagulant in the lupus anticoagulant-hypoprothrombinemia syndrome: report of two cases and review of the literature. Am J Hematol. 2002 Nov. 71(3):200-7. [Medline].

  10. Bhat RV, Deshmukh CT. A study of Vitamin K status in children on prolonged antibiotic therapy. Indian Pediatr. 2003 Jan. 40(1):36-40. [Medline].

  11. Bolton-Maggs PH, Perry DJ, Chalmers EA, et al. The rare coagulation disorders--review with guidelines for management from the United Kingdom Haemophilia Centre Doctors' Organisation. Haemophilia. 2004 Sep. 10(5):593-628. [Medline].

  12. Eberhard A, Sparling C, Sudbury S, et al. Hypoprothrombinemia in childhood systemic lupus erythematosus. Semin Arthritis Rheum. 1994 Aug. 24(1):12-8. [Medline].

  13. Erkan D, Bateman H, Lockshin MD. Lupus anticoagulant-hypoprothrombinemia syndrome associated with systemic lupus erythematosus: report of 2 cases and review of literature. Lupus. 1999. 8(7):560-4. [Medline].

  14. Galli M, Barbui T. Antiprothrombin antibodies: detection and clinical significance in the antiphospholipid syndrome. Blood. 1999 Apr 1. 93(7):2149-57. [Medline]. [Full Text].

  15. Girolami A, Scarano L, Saggiorato G, et al. Congenital deficiencies and abnormalities of prothrombin. Blood Coagul Fibrinolysis. 1998 Oct. 9(7):557-69. [Medline].

  16. Humphries JE, Acker MN, Pinkston JE, Ruddy S. Transient lupus anticoagulant associated with prothrombin deficiency: unusual cause of bleeding in a 5-year-old girl. Am J Pediatr Hematol Oncol. 1994 Nov. 16(4):372-6. [Medline].

  17. Lechler E. Use of prothrombin complex concentrates for prophylaxis and treatment of bleeding episodes in patients with hereditary deficiency of prothrombin, factor VII, factor X, protein C protein S, or protein Z. Thromb Res. 1999 Aug 15. 95(4 Suppl 1):S39-50. [Medline].

  18. Lipsky JJ. Antibiotic-associated hypoprothrombinaemia. J Antimicrob Chemother. 1988 Mar. 21(3):281-300. [Medline].

  19. Rouy S, Vidaud D, Alessandri JL, et al. Prothrombin Saint-Denis: a natural variant with a point mutation resulting in Asp to Glu substitution at position 552 in prothrombin. Br J Haematol. 2006 Mar. 132(6):770-3. [Medline].

  20. Schmugge M, Tolle S, Marbet GA, et al. Gingival bleeding, epistaxis and haematoma three days after gastroenteritis: the haemorrhagic lupus anticoagulant syndrome. Eur J Pediatr. 2001 Jan. 160(1):43-6. [Medline].

  21. Stanchev H, Philips M, Villoutreix BO, et al. Prothrombin deficiency caused by compound heterozygosity for two novel mutations in the prothrombin gene associated with a bleeding tendency. Thromb Haemost. 2006 Jan. 95(1):195-8. [Medline].

  22. Strijks E, Poort SR, Renier WO, et al. Hereditary prothrombin deficiency presenting as intracranial haematoma in infancy. Neuropediatrics. 1999 Dec. 30(6):320-4. [Medline].

  23. Vivaldi P, Rossetti G, Galli M, Finazzi G. Severe bleeding due to acquired hypoprothrombinemia-lupus anticoagulant syndrome. Case report and review of literature. Haematologica. 1997 May-Jun. 82(3):345-7. [Medline].

  24. Yacobovich JR, Uziel Y, Friedman Z, et al. Diffuse muscular haemorrhage as presenting sign of juvenile systemic lupus erythematosus and lupus anticoagulant hypoprothrombinaemia syndrome. Rheumatology (Oxford). 2001 May. 40(5):585-7. [Medline]. [Full Text].

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