Structurally, it is a member of the large PA clan of proteases. Prothrombin is composed of four domains; an N-terminal Gla domain, two kringle domains and a C-terminal trypsin-like serine protease domain. Factor Xa with factor V as a cofactor leads to cleavage of the Gla and two Kringle domains (forming together a fragment called fragment 1.2) and leave thrombin, consisting solely of the serine protease domain.As is the case for all serine proteases, prothrombin is converted to active thrombin by proteolysis of an internal peptide bond, exposing a new N-terminal Ile-NH3. The historic model of activation of serine proteases involves insertion of this newly formed N-terminus of the heavy chain into the β-barrel promoting the correct conformation of the catalytic residues. Contrary to crystal structures of active thrombin, hydrogen-deuterium exchange mass spectrometry studies indicate that this N-terminal Ile-NH3 does not become inserted into the β-barrel in the apo form of thrombin. However, binding of the active fragment of thrombomodulin appears to allosterically promote the active conformation of thrombin by inserting this N-terminal region. Gene
The thrombin (prothrombin) gene is located on the eleventh chromosome (11p11-q12).There are an estimated 30 people in the world that have been diagnosed with the congenital form of Factor II deficiency, which should not be confused with the prothrombin G20210A mutation, which is also called the factor II mutation. Prothrombin G20210A is congenital.Prothrombin G20210A is not usually accompanied by other factor mutations (i.e., the most common is factor V Leiden).
The mainstay diagnosis of the presenting DVT symptom is an ultrasound with venous Doppler. Ultrasound with venous Doppler rarely identifies the inferior vena cava anomalies present from birth. Difficulties in identifying the congenital stenosis of the vena cava makes diagnosis uncommon. Diagnosis of congenital stenosis of the inferior vena cava can be rarely discovered through abdominal CT examinations, and may present with an array of clinical findings dependent on the drainage patterns of the individuals. Further diagnostic tools such as a transthoracic echocardiogram can reveal the narrowing of the vena cava showing a low velocity of flow. Congenital stenosis of the vena cava can also present as acute respiratory failure and effusion of the right lung on chest X-rays. Treatments
Treatments may not be necessary for the congenital heart defect. If required, treatments can include medication, catheter procedures, corrective surgery and heart transplants dependent on the severity of the defect, age of the patient and patients general health. Symptomatic relief of venous hypertension, associated with the congenital heart defect, can be achieved through surgery as it reduces the likelihood of hepatic vein thrombosis. Intravascular stents are a treatment method for Congenital Stenosis of the Vena Cava. Expandable metallic stents have been used as part of a procedure to dilate and maintain stenotic vena cava. Experiments carried out on mongrel dogs resulted in some failures for dilation and early migration, and occlusion complications in patients. Immediate relief of persisting symptoms occurred in two patients. Double balloon dilation is another technique used to treat stenosis of the vena cava.