Hypoprothrombinemia is a term describing reduced levels of prothrombin, or factor II. Its deficiency may result from either inherited or acquired pathologies. The clinical presentation ranges from mild bleeding episodes to severe and life-threatening hemorrhage. Clinical and laboratory studies are needed to make the diagnosis of this very rare coagulation disorder.
Prothrombin is an essential vitamin K-dependent zymogen that is synthesized in the liver and forms thrombin, with its principal function being the conversion of fibrinogen to fibrin, which is essential for the creation of a stable blood clot  . In the literature, hypoprothrombinemia (factor II deficiency) can occur due to both inherited and acquired pathophysiological mechanisms     . Inherited factor II deficiency is considered to be the rarest hereditary disorder of coagulation, with estimated incidence rates of 1 in 2,000,000 individuals    . The autosomal recessive pattern of inheritance is the mode of its transfer and two types have been identified - type 1, also known as true hypoprothrombinemia, is characterized by very low levels of prothrombin and its functional activity; and type II (dysprothrombinemia), where the synthesis of a dysfunctional protein is observed   . Both phenotypes arise from mutations in the gene coding for prothrombin (located on chromosome 11), and the clinical presentation is proportional to the severity of deficiency  . Heterozygotes are often asymptomatic, whereas homozygotes and compound heterozygotes may present with excessive bleeding after trauma and surgical procedures, bruising, hemarthrosis and menorrhagia in women  . Furthermore, a much higher risk of thrombosis and thromboembolic disease is evident in a certain subtype . In rare cases, chronic musculoskeletal disorders, anemia, and intracerebral hemorrhage have been reported . On the other hand, the pathogenesis of acquired hypoprothrombinemia almost always involves the formation of prothrombin antibodies, principally seen in systemic lupus erythematosus (SLE), but certain viral infections and malignancies are reported as possible etiologies as well . Hence, the term lupus anticoagulant-hypoprothrombinemia syndrome (LA-HPS) is used to describe this rare disorder that is most frequently diagnosed in the pediatric population, with a slight female predominance  . The clinical presentation is similar to hereditary hypoprothrombinemia, and patients who develop a severe inflammatory reaction might suffer from sudden and life-threatening hemorrhagic episodes in the absence of adequate treatment  .
Entire Body System
- Easy Bruising
Common clinical signs include epistaxis, menorrhagia, oral cavity bleedings, mucosal bleeding, soft tissue bleeding, hemarthroses, easy bruising, and prolonged bleeding after tooth extraction, trauma or surgery. [orpha.net]
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: Easy bruising Epistaxis Prolonged bleeding with [emedicine.medscape.com]
bruising, postoperative bleeding, epistaxis, menorrhagia, miscarriage, postpartum hemorrhage, hemarthroses and intracranial bleeding (if severe deficiency) Laboratory Prolonged PT and PTT that correct with mixing study (1:1 mixture of patient and normal [pathologyoutlines.com]
Jaw & Teeth
- Bleeding Gums
Specifically, when the bloodstream has insufficient levels of prothrombin, a patient develops hypoprothrombinemia, a condition characterized by the following symptoms: an increased susceptibility to bruising bleeding gums excessive or prolonged bleeding [checkorphan.org]
Mild symptoms might include: bruising and soft tissue bleeding longer bleeding time from wounds or dental extractions bleeding in joints nosebleeds bleeding gums heavy menstrual periods In more severe cases, symptoms can include: destruction of cartilage [healthline.com]
Infants and babies within the first year of life who have homozygous protein S deficiency characteristically have purpura fulminans. [ihtc.org]
Clinically, catastrophic APS (CAPS) may resemble thrombotic thrombocytopenic purpura and hemolytic uremic syndrome.30 Recurrent thromboembolic events tend to have consistency with respect to site (ie, arterial-arterial, venous-venous). [the-medical-dictionary.com]
Disorders affecting the vessel walls Henoch-Schonlein purpura : supportive care Thrombotic thrombocytopenic purpura : prompt plasma exchange therapy (see TTP for details) Disorders of secondary hemostasis Disorders of the intrinsic pathway Hemophilia [amboss.com]
A case of congenital prothrombin deficiency and idiopathic thrombocytopenic purpura in a pregnant female. Blood Coagul Fibrinolysis. 2016 Feb 15. [Medline]. Watson H, Perez A, Ayesu K, Musa F, Sarriera J, Madruga M, et al. [emedicine.medscape.com]
The rare nature of hypoprothrombinemia suggests that a thorough workup is necessary for the physician to raise clinical suspicion. Firstly, a detailed patient history that will cover the course of symptoms and their progression, but also the presence of similar findings within the family (given the autosomal recessive pattern of inheritance) must be obtained, followed by a complete physical examination. A presumptive diagnosis toward bleeding disorders must be made in the presence of typical signs and symptoms, particularly in the pediatric population, in which case a complete laboratory workup must be conducted immediately . Both partial thromboplastin time (APTT) and prothrombin time (PT) are prolonged in hypoprothrombinemia, while the functional activity of factor II through assay testing is a more specific method to confirm hypoprothrombinemia  . Usually, the activity of factor II in hereditary forms will be 10% of normal in homozygotes, and between 40-60% in heterozygotes . Furthermore, genetic testing can be done, both in adults and even prenatally, to yield a solid diagnosis  . On the other hand, detection of antiprothrombin antibodies is suggestive for acquired forms of hypoprothrombinemia  .
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