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Hypoprothrombinemia Workup

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

Laboratory Studies

Hypoprothrombinemia is determined by performing a specific assay for factor II activity.

The prothrombin time (PT), usually indicated as an international normalized ratio (INR), and the activated partial thromboplastin time (aPTT) are elevated in hypoprothrombinemia. However, both the PT and the aPTT can be elevated in numerous single-factor and multiple-factor deficiencies; therefore, their elevation is not specific for hypoprothrombinemia.

First, determine if the prothrombin deficiency is isolated or associated with other factor deficiencies. Determine this status by performing assays for factors VII, IX, and X, which are the other vitamin K–dependent procoagulants.

Performing assays for factor V and VIII activity may also be helpful. Factor V activity is decreased in liver disease and DIC. Factor VIII activity is decreased in disseminated intravascular coagulation (DIC) but not often in liver disease.

If other vitamin K–dependent factors are decreased, rule out vitamin K deficiency, liver disease, or both. Vitamin K and vitamin K epoxide levels can be determined by select clinical laboratories. Warfarin levels can also be directly measured by some commercial clinical laboratories.

If multiple-factor deficiencies include factors other than vitamin K–dependent factors, evaluate the patient for DIC, liver disease, or both.

If isolated factor II deficiency is present, test for an inhibitor by performing a mixing study. In the presence of an inhibitor, the PT is not corrected when the patient's plasma is mixed 1:1 with normal pooled plasma. If an inhibitor is detected, suspect a lupus anticoagulant, which can be detected by using the dilute Russell viper venom test (DRVVT) or the tissue thromboplastin inhibition test. Anticardiolipin antibodies are found in about 60-70% of patients with a lupus anticoagulant. The presence of these antibodies helps to confirm the diagnosis of an antiphospholipid antibody syndrome as well.

In cases of suspected inherited prothrombin deficiency, assessment of factor II activity in family members may be helpful. Numerous research laboratories across the United States can perform tests for factor II antigen levels and screen for mutations in the prothrombin gene.


Imaging Studies

Neonates found to have a severe inherited bleeding diathesis should undergo head CT scanning to evaluate for intracranial hemorrhage, regardless of their symptoms or signs.

Head ultrasonography may be used but is not as sensitive as CT scanning.


Other Tests

The bleeding time is not a useful test for evaluating hypoprothrombinemia. The bleeding time may or may not be elevated. Although it is certainly elevated in severe platelet function disorders, the degree of elevation is not predictive of bleeding risk, and its sensitivity for milder forms of platelet dysfunction is poor.

Other means of testing platelet function, such as platelet function assay (PFA) or platelet aggregation testing, are also not helpful in evaluating hypoprothrombinemia. Their use in screening for platelet function disorders has not been fully defined.

Thromboelastography and thrombin generation testing is abnormal in hypoprothrombinemia.

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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