| Synonyms: | Congenital factor II deficiency[1] |
Hypoprothrombinemia is a rare blood disorder in which a deficiency in immunoreactive prothrombin (Factor II), produced in the liver, results in an impaired blood clotting reaction, leading to an increased physiological risk for spontaneous bleeding. This condition can be observed in the gastrointestinal system, cranial vault, and superficial integumentary system, affecting both the male and female population. Prothrombin is a critical protein that is involved in the process of hemostasis, as well as illustrating procoagulant activities. This condition is characterized as an autosomal recessive inheritance congenital coagulation disorder affecting 1 per 2,000,000 of the population, worldwide, but is also attributed as acquired.
There are various symptoms that are presented and are typically associated to a specific site that they appear at. Hypoprothrombinemia is characterized by a poor blood clotting function of prothrombin. Some symptoms are presented as severe, while others are mild, meaning that blood clotting is slower than normal. Areas that are usually affected are muscles, joints, and the brain, however, these sites are more uncommon.
The most common symptoms include:
Other reported symptoms that are related to the condition:
Type I: Severe hemorrhages are indicators of a more severe prothrombin deficiency that account for muscle hematomas, intracranial bleeding, postoperative bleeding, and umbilical cord hemorrhage, which may also occur depending on the severity, respectively.
Type II: Symptoms are usually more capricious, but can include a variety of the symptoms described previously. Less severe cases of the disorder typically do not involve spontaneous bleeding.
Hypoprothrombinemia can be the result of a genetic defect, may be acquired as the result of another disease process, or may be an adverse effect of medication. For example, 5-10% of patients with systemic lupus erythematosus exhibit acquired hypoprothrombinemia due to the presence of autoantibodies which bind to prothrombin and remove it from the bloodstream (lupus anticoagulant-hypoprothrombinemia syndrome).[4] The most common viral pathogen that is involved is Adenovirus, with a prevalence of 50% in postviral cases.[5]
Autosomal recessive condition in which both parents must carry the recessive gene in order to pass the disease on to offspring. If both parents have the autosomal recessive condition, the chance of mutation in offspring increases to 100%. An individual will be considered a carrier if one mutant copy of the gene is inherited, and will not illustrate any symptoms. The disease affects both men and women equally, and overall, is a very uncommon inherited or acquired disorder.
There are two types of prothrombin deficiencies that occur depending on the mutation:
Type I (true deficiency), includes a missense or nonsense mutation, essentially decreasing prothrombin production. This is associated with bleeding from birth. Here, plasma levels of prothrombin are typically less than 10% of normal levels.
Type II, known as dysprothrombinemia, includes a missense mutation at specific Xa factor cleavage sites and serine protease prothrombin regions. Type II deficiency creates a dysfunctional protein with decreased activity and usually normal or low-normal antigen levels. A vitamin K-dependent clotting factor is seldom seen as a contributor to inherited prothrombin deficiencies, but lack of Vitamin K decreases the synthesis of prothrombin in liver cells.
Acquired underlying causes of this condition include severe liver disease, warfarin overdose, platelet disorders, and disseminated intravascular coagulation (DIC).
It may also be a rare adverse effect to ceftriaxone.[6]
Hypoprothrombinemia is found to present itself as either inherited or acquired, and is a decrease in the synthesis of prothrombin.[7] In the process of inheritance, it marks itself as an autosomal recessive disorder, meaning that both parents must be carriers of the defective gene in order for the disorder to be present in a child. Prothrombin is a glycoprotein that occurs in blood plasma and functions as a precursor to the enzyme, thrombin, which acts to convert fibrinogen into fibrin, therefore, fortifying clots. This clotting process is known as coagulation.[8]
The mechanism specific to prothrombin (factor II) includes the proteolytically cleaving, breakdown of proteins into smaller polypeptides or amino acids, of this coagulation factor in order to form thrombin at the beginning of the cascade, leading to stemming of blood loss. A mutation in factor II would essentially lead to hypoprothrombinemia. The mutation is presented on chromosome 11.[9]
Areas where the disease has been shown to present itself at include the liver, since the glycoprotein is stored in this area.
Acquired cases are results from an isolated factor II deficiency. Specific cases include:
Diagnosis of inherited hypoprothrombinemia, relies heavily on a patient's medical history, family history of bleeding issues, and lab exams performed by a hematologist. A physical examination by a general physician should also be performed in order to determine whether the condition is congenital or acquired, as well as ruling out other possible conditions with similar symptoms. For acquired forms, information must be taken regarding current diseases and medications taken by the patient, if applicable.
Lab tests that are performed to determine diagnosis:
Treatment is almost always aimed to control hemorrhages, treating underlying causes, and taking preventative steps before performing invasive surgeries.
Hypoprothrombinemia can be treated with periodic infusions of purified prothrombin complexes.[14] These are typically used as treatment methods for severe bleeding cases in order to boost clotting ability and increasing levels of vitamin K-dependent coagulation factors.
Fresh frozen plasma infusion (FFP) is a method used for continuous bleeding episodes, every 3–5 weeks for mention.
Invasive options, such as surgery or clotting factor infusions, are required if previous methods do not suffice. Surgery is to be avoided, as it causes significant bleeding in patients with hypoprothrombinemia.
Prognosis for patients varies and is dependent on severity of the condition and how early the treatment is managed.