Гипопротромбинемия: причины, симптомы и механизмы развития

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.

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.

Hypoprothrombinemia is found to present itself as either inherited or acquired, and is a decrease in the synthesis of prothrombin. 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. 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. 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:
Vitamin K deficiency: In the liver, vitamin K plays an important role in the synthesis of coagulation factor II. Body's capacity in the storage of vitamin K is typically very low. Vitamin K dependent coagulation factors have a very short half life, sometimes leading to a deficiency when a depletion of vitamin K occurs. The liver synthesizes inactive precursor proteins in the absence of vitamin K (liver disease). Disseminated intravascular coagulation (DIC): Involving abnormal, excessive generation of thrombin and fibrin within the blood. Relative to hypoprothrombinemia, due to increased platelet aggregation and coagulation factor consumption involved in the process. Anticoagulants: warfarin overdose: Used as a treatment for prevention of blood clots, however, like most drugs, side effects have been shown to increase risk of excessive bleeding by functioning in the disruption of hepatic synthesis of coagulation factors II, VII, IX, and X. Vitamin K is an antagonist to warfarin drug, reversing its activity, causing it to be less effective in the process of blood clotting. Warfarin intake has been shown to interfere with Vitamin K metabolism.

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. 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. A known treatment for hypoprothrombinemia is menadoxime. Menatetrenone was also listed as an antihemorrhagic vitamin. 4 Amino 2 methyl 1 naphthol (Vitamin K5) is another treatment for hypoprothrombinemia. Vitamin K forms are administered orally or intravenously. Other concentrates include Proplex T, Konyne 80, and Bebulin VH. Fresh frozen plasma infusion (FFP) is a method used for continuous bleeding episodes, every 3–5 weeks for mention. Used to treat various conditions related to low blood clotting factors. Administered by intravenous injection and typically at a 15 20 ml/kg/dose. Can be used to treat acute bleeding. 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. With proper treatment and care, most people go on to live a normal and healthy life. With more severe cases, a hematologist will need to be seen throughout the patient's life in order to deal with bleeding and continued risks.