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Hypoprothrombinemia Clinical Presentation

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

History

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
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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, 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; 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.

Acknowledgements

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.

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