Hypoprothrombinemia Medication

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

Medication Summary

The treatment of hypoprothrombinemia depends on the underlying etiology. Numerous products that provide prothrombin are available.


Hemostatic agents

Class Summary

Vitamin K can be administered intravenously or orally. Slowly administer intravenous infusions over 10-20 minutes. In addition, premedicating the patient with diphenhydramine (Benadryl) may be helpful. The only current oral formulation of vitamin K available in the United States is in tablet form; however, a liquid formulation has been developed and is currently being used in Europe and Japan.

Acquired hypoprothrombinemia due to vitamin K deficiency is treated with vitamin K1 (phytonadione). In the presence of severe or life-threatening bleeding, frozen plasma or prothrombin-complex concentrates are administered to immediately increase the levels of vitamin K–dependent coagulation factors. Other clotting factors (eg, concentrate of clotting factors II, VII, IX, and X [Proplex T]) may also be required. Solvent-detergent–treated frozen plasma is now available.

Epsilon aminocaproic acid (Amicar) can be used to minimize the severity of mucosal bleeding and enhances hemostasis when fibrinolysis contributes to bleeding. Amicar is especially useful in acquired hypoprothrombinemia secondary to anti–factor II circulating antibodies because of the immediate neutralization of prothrombin upon infusing plasma or prothrombin-complex concentrates.

For inherited hypoprothrombinemia, concentrates of prothrombin complex (eg, Autoplex T) are used. No recombinant factor II product is available.

Aminocaproic acid (Amicar)


A 6-aminohexanoic acid that inhibits fibrinolysis by inhibiting plasminogen activator substances and, to some degree, antiplasmin activity.

Anti-inhibitor coagulant complex (Feiba VH Immuno)


Prothrombin-complex concentrates contain vitamin K–dependent clotting factors. Prepared from pooled normal human plasma. Some products contain more activated factors than others. Presence of activated factors increases risk of thromboembolic complications.

Phytonadione (AquaMEPHYTON, Mephyton)


Promotes liver synthesis of clotting factors. Aqueous colloidal solution of vitamin K1 for parenteral injection. This form has same activity as naturally occurring vitamin K. Vitamin K is essential cofactor for microsomal enzyme that catalyzes posttranslational carboxylation of several specific peptide-bound glutamic acid residues in inactive hepatic precursors of vitamin K–dependent factors. Results in gamma-carboxyglutamic acid residues necessary for calcium-dependent phospholipid membrane binding.

Fresh frozen plasma


Plasma is fluid compartment of blood that contains soluble clotting factors. For use in patients with deficiencies of blood products. Indications include bleeding in patients with congenital coagulation defects and deficiencies of multiple coagulation factors (severe liver disease).

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].

Medscape Consult
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.