Hypoprothrombinemia Clinical Presentation

  • Author: J Nathan Hagstrom, MD; Chief Editor: Robert J Arceci, MD, PhD   more...
 
Updated: Feb 29, 2012
 

History

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

Patients with lupus anticoagulant-hypoprothrombinemia syndrome 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.[5]

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
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Physical

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.

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Causes

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.

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Contributor Information and Disclosures
Author

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, and International Society on Thrombosis and Haemostasis

Disclosure: Nothing to disclose.

Coauthor(s)

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; Assistant 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 Academy of Pediatrics, American Association for Cancer Research, American Federation for Clinical Research, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Council on Medical Student Education in Pediatrics, and Hemophilia and Thrombosis Research Society

Disclosure: Nothing to disclose.

Specialty Editor Board

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.

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 and American Society of Hematology

Disclosure: Nothing to disclose.

Samuel Gross, MD  Professor Emeritus, Department of Pediatrics, University of Florida; Clinical Professor, Department of Pediatrics, University of North Carolina; Adjunct Professor, Department of Pediatrics, Duke University

Samuel Gross, MD is a member of the following medical societies: American Association for Cancer Research, American Society for Blood and Marrow Transplantation, American Society of Clinical Oncology, American Society of Hematology, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Chief Editor

Robert J Arceci, MD, PhD  King Fahd Professor of Pediatric Oncology, Professor of Pediatrics, Oncology and the Cellular and Molecular Medicine Graduate Program, Kimmel Comprehensive Cancer Center at Johns Hopkins University School of Medicine

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

Disclosure: Nothing to disclose.

Additional Contributors

The authors and editors of eMedicine gratefully acknowledge the contributions of previous coauthor Sara E Tisdale, MD, to the development and writing of this article.

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