Newborn levels of thrombin steadily increase after birth to reach normal adult levels, from a level of around 0.5 units/mL 1 day after birth, to a level of around 0.9 units/mL after 6 months of life. Mechanism of action
In the blood coagulation pathway, thrombin acts to convert factor XI to XIa, VIII to VIIIa, V to Va, fibrinogen to fibrin, and XIII to XIIIa. In the conversion of fibrinogen into fibrin, thrombin catalyzes the cleavage of fibrinopeptides A and B from the respective Aα and Bβ chains of fibrinogen to form fibrin monomers.Factor XIIIa is a transglutaminase that catalyzes the formation of covalent bonds between lysine and glutamine residues in fibrin. The covalent bonds increase the stability of the fibrin clot. Thrombin interacts with thrombomodulin.As part of its activity in the coagulation cascade, thrombin also promotes platelet activation and aggregation via activation of protease-activated receptors on the cell membrane of the platelet. Negative feedback
Thrombin bound to thrombomodulin activates protein C, an inhibitor of the coagulation cascade. The activation of protein C is greatly enhanced following the binding of thrombin to thrombomodulin, an integral membrane protein expressed by endothelial cells. Activated protein C inactivates factors Va and VIIIa. Binding of activated protein C to protein S leads to a modest increase in its activity. Thrombin is also inactivated by antithrombin, a serine protease inhibitor. Structure
The molecular weight of prothrombin is approximately 72,000 Da. The catalytic domain is released from prothrombin fragment 1.2 to create the active enzyme thrombin, which has a molecular weight of 36,000 Da.
Primary hyperoxaluria is a rare condition (autosomal recessive), resulting in increased excretion of oxalate (up to 600 mg a day from normal 50 mg a day), with oxalate stones being common. Signs and symptoms
Primary hyperoxaluria is an autosomal recessive disease, meaning both copies of the gene contain the mutation. Both parents must have one copy of this mutated gene to pass it on to their child, but they do not typically show signs or symptoms of the disease. A single kidney stone in children or recurrent stones in adults is often the first warning sign of primary hyperoxaluria. Other symptoms range from recurrent urinary tract infections, severe abdominal pain or pain in the side, blood in the urine, to chronic kidney disease and kidney failure. The age of symptom onset, progression and severity can vary greatly from one person to another, even among members of the same family. Some individuals may have mild cases that go undiagnosed well into adulthood; others may develop severe complications during infancy, which may result in early death. Pathophysiology
The buildup of oxalate in the body causes increased renal excretion of oxalate (hyperoxaluria), which in turn results in kidney and bladder stones. Stones cause urinary obstruction (often with severe and acute pain), secondary infection of urine and eventually kidney damage. Primary hyperoxaluria is caused by genetic defects that result in the overproduction of oxalate.