Hypoprothrombinemia

Source: Wikipedia, the free encyclopedia.
Hypoprothrombinemia
Other namesCongenital factor II deficiency[1]
This condition is inherited in an autosomal recessive manner.
SpecialtyHematology Edit this on Wikidata

Hypoprothrombinemia is a rare blood disorder in which a deficiency in immunoreactive

congenital
coagulation disorder affecting 1 per 2,000,000 of the population, worldwide, but is also attributed as acquired.

Signs and symptoms

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.[citation needed
]

The most common symptoms include:

  1. Easy bruising[2]
  2. Oral mucosal bleeding - Bleeding of the membrane mucus lining inside of the mouth.
  3. Soft tissue bleeding.
  4. Hemarthrosis - Bleeding in joint spaces.
  5. nasopharynx
    .
  6. Women with this deficiency experience
    menorrhagia: prolonged, abnormal heavy menstrual bleeding.[3]
    This is typically a symptom of the disorder when severe blood loss occurs.

Other reported symptoms that are related to the condition:

  1. Prolonged periods of bleeding due to surgery, injury, or post birth.
  2. Melena - Associated with acute gastrointestinal bleeding, dark black, tarry feces.
  3. Hematochezia - Lower gastrointestinal bleeding, passage of fresh, bright red blood through the anus secreted in or with stools. If associated with upper gastrointestinal bleeding, suggestive of a more life-threatening issue.

Type I: Severe

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.[2]

Causes

Hypoprothrombinemia can be the result of a

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]

Inheritance

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.[3]

Non-inheritance and other factors

There are two types of prothrombin deficiencies that occur depending on the mutation:[5]

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.[citation needed]

Type II, known as

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.[5]

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]

Mechanism

Hypoprothrombinemia is found to present itself as either inherited or acquired, and is a decrease in the synthesis of

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

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:

  1. synthesizes inactive precursor proteins in the absence of vitamin K (liver disease).[8] Vitamin K deficiency leads to impaired clotting of the blood and in some cases, causes internal bleeding without an associated injury.[10]
  2. coagulation factor consumption involved in the process.[11]
  3. antagonist to warfarin drug, reversing its activity, causing it to be less effective in the process of blood clotting.[12] Warfarin intake has been shown to interfere with Vitamin-K metabolism.[10]

Diagnosis

Diagnosis of inherited hypoprothrombinemia, relies heavily on a patient's medical history, family history of bleeding issues, and lab exams performed by a

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.[citation needed
]

Lab tests that are performed to determine diagnosis:

  1. Factor assays: To observe the performance of specific factors (II) to identify missing/poorly performing factors. These lab tests are typically performed first in order to determine the status of the factor.
  2. Prothrombin blood test: Determines if a patient has deficient or low levels of Factor II.[citation needed]
  3. Vitamin K1 test: Performed to evaluate bleeding of unknown causes, nosebleeds, and identified bruising. To accomplish this, a band is wrapped around the patient's arm, 4 inches above the superficial vein site in the elbow pit. The vein is penetrated with the needle and amount of blood required for testing is obtained. Decreased vitamin K levels are suggestive of hypoprothrombinemia. However, this exam is rarely used as a prothrombin blood test is performed beforehand.[13]

Treatment

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.

  1. A known treatment for hypoprothrombinemia is menadoxime.[15]
  2. Menatetrenone was also listed as an antihemorrhagic vitamin.
  3. 4-Amino-2-methyl-1-naphthol (Vitamin K5) is another treatment for hypoprothrombinemia.
    1. Vitamin K forms are administered orally or
      intravenously
      .
  4. 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.[2]

  1. Used to treat various conditions related to low blood clotting factors.
  2. Administered by intravenous injection and typically at a 15-20 ml/kg/dose.
  3. 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

Prognosis for patients varies and is dependent on severity of the condition and how early the treatment is managed.

  1. With proper treatment and care, most people go on to live a normal and healthy life.
  2. 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.

References

  1. ^ RESERVED, INSERM US14-- ALL RIGHTS. "Orphanet: Congenital factor II deficiency". www.orpha.net. Retrieved 5 June 2019.{{cite web}}: CS1 maint: numeric names: authors list (link)
  2. ^ a b c "Hypoprothrombinemia Clinical Presentation: History, Physical, Causes". emedicine.medscape.com. Retrieved 2017-12-12.
  3. ^ a b "Factor II Deficiency". DoveMed. Retrieved 2017-12-12.
  4. PMID 6403077
    .
  5. ^ a b c "Hypoprothrombinemia Clinical Presentation: History, Physical, Causes". emedicine.medscape.com. Retrieved 2017-12-12.
  6. ^ [ http://www.gene.com/download/pdf/rocephin_prescribing.pdf Archived 2013-08-16 at the Wayback Machine Rocephin proscribing information]. Accessed October 24, 2013.
  7. ^ "hypoprothrombinemia | pathology". Encyclopedia Britannica. Retrieved 2017-12-12.
  8. ^ a b "Hypoprothrombinemia: Background, Pathophysiology, Epidemiology". 2017-03-30. {{cite journal}}: Cite journal requires |journal= (help)
  9. ^ "ortholog_gene_2147[group] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2017-12-12.
  10. ^ a b "nutritional disease - Vitamin K". Encyclopedia Britannica. Retrieved 2017-12-13.
  11. ^ "Disseminated Intravascular Coagulation (DIC) - Hematology and Oncology - Merck Manuals Professional Edition". Merck Manuals Professional Edition. Retrieved 2017-12-12.
  12. PMID 6403077
    .
  13. ^ "Vitamin K Deficiency". labtestsonline.org. Retrieved 2017-12-12.
  14. PMID 10499908
    .
  15. ^ J. Elks, C. R. Ganellin · DoDs page 765.

External links