Hypoprothrombinemia Clinical Presentation
- Author: J Nathan Hagstrom, MD; Chief Editor: Robert J Arceci, MD, PhD more...
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, 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.
Symptoms associated with hypoprothrombinemia include the following:
Prolonged bleeding with injury, tooth extraction, or surgery
Oral mucosal bleeding
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.
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