Factor prothrombin

Haematopoietic Blood tests Complete blood count (red and white blood cell indices and platelets) measurement of clotting factors, prothrombin time, partial thromboplastin time... 

A protein called Stuart factor cleaves prothrombin, turning it into active thrombin that can then cleave fibrinogen to fibrin to form the blood clot.3 Unfortunately, as you may have guessed, if Stuart factor, prothrombin, and fibrinogen were the only blood-clotting proteins, then Stuart factor would rapidly trigger the cascade, congealing all... 

Activity D. inhibits vitamin K epoxide reductase and thus the synthesis of the blood clotting factor prothrombin. D. acts as an anticoagulant (vitamin K antagonist). D. and its analogues (e.g., warfarin, pben-procoumon) are used clinically for thrombosis thnsqry. It causes tissue and skin hemorrhages in rodents and thus finds use as a rat poison. For the mechanism of action, see L/r.. LD50 (rat p.o.) 541.6 mg/kg. lit . Am. Chem. Soc. 1 3.3910-3915 (1981) Nat Plod. Rep. 11,591-606(1994). 

In contrast, in 40 patients with INRs over 5.0, of whom 29 were bleeding and 11 were at high risk of bleeding, who were treated with a three-factor prothrombin complex concentrate and were compared with 42 historical controls treated with plasma alone, the prothrombin complex concentrate did not satisfactorily reduce the INR, because of a low factor VII content [69. Treatment with plasma alone lowered the INR to below 3.0 in 63% of the controls, while low-dose (25 U/kg) and high-dose (50 U/kg) prothrombin complex concentrate alone lowered the INR to below 3.0 in 50% and 43% of patients respectively. Additional transfusion of a small amount of plasma improved these rates to 89% and 88%. 

Holland L, Warkentin TE, Refaai M, Crowther MA, Johnston MA, Sarode R. Suboptimal effect of a three-factor prothrombin complex concentrate (Profil-nine-SD) in correcting supratherapeutic intemational normalized ratio due to warfarin overdose. Transfusion 2009 49(6) 1171-7. 

Haematologic In a study of rapid warfarin reversal for intracerebral haemorrhage using 3-factor prothrombin complex concentrate (PCC) and recombinant FVIIa, authors report that 2 of the 46 patients experienced thrombotic complications [124 J. Both patients experienced non-ST-elevated myocardial infarction. Notably, one of these occurred with a 2.4-mg dose of recombinant FVIIa and the study protocol was changed to all subsequent patients getting l.Omg of recombinant FVIIa. 

Sarode R, Matevosyan K, Bhagat R, Rutherford C, Madden C, Beshay JE. Rapid warfarin reversal a 3-factor prothrombin complex concentrate and recombinant factor Vila cocktail for intracerebral hemorrhage. J Neurosurg 2012 116(3) 491-7. 

Switzer JA, Rocker J, Mohorn P, Waller JL, Hughes D, Bruno A, et al. Clinical experience with three-factor prothrombin complex concentrate to reverse warfarin anticoagulation in intracranial hemorrhage. Stroke 2012 43(9) 2500-2. 

Gastrointestinal An 80-year-old woman presented as an emergency case after 2 weeks of vomiting, abdominal pain and diarrhoea. She had commenced warfarin use 3 weeks prior for paroxysmal atrial fibrillation. An X-ray revealed concentric mural thickening of the proximal jejunum, extending distally from the duodenal-jejxmal flexure and the provisional diagnosis was a spontaneous intramural jejunal haematoma. Warfarin was withheld and with Vitamin K, 3-factor prothrombin complex concentrate and fresh frozen plasma treatment, she recovered and tire abnormality resolved [3 ]. 

Thrombin, the two-chain derivative of the prothrombin molecule, has a molecular weight of approximately 37,000 daltons. Its proteolytic properties induce the conversion of fibrinogen to fibrin to produce the initial visible manifestation of coagulation, the soluble fibrin clot. In addition, thrombin influences the activity of Factors V, VIII, and XIII and plasmin. Thrombin affects platelet function by inducing viscous metamorphosis and the release reaction with subsequent aggregation. 

Factor II. Prothrombin is a vitamin K-dependent compound synthesized by the Hver. When prothrombin is activated it is cleaved at two sites, resulting in a two-chain molecule linked by a disulfide bond that has a molecular weight of 37,000 daltons. Thrombin is the serine protease that initiates the conversion of soluble fibrinogen into fibrin. 

Factor V. High in sialic acid content. Factor V is a large asymmetric single-chain glycoprotein that becomes an active participant in the coagulation cascade when it is converted to its active form by a-thrombin. Approximately 25% of human Factor V is found in the whole blood associated with platelets. Factor V is an essential cofactor along with Factor Xa plus phosphohpid plus Ca " in the conversion of prothrombin to thrombin. 

Antihemophilic factor [9001-28-9] (AHF) is a protein found in normal plasma that is necessary for clot formation. It is needed for transformation of prothrombin to thrombin. Administration of AHF by injection or infusion can temporarily correct the coagulation defect present in patients with hemophilia. Antihemophilic factor VIII (Alpha Therapeutic) has been approved by the FDA as replacement therapy in patients with hemophilia B to prevent bleeding episodes, and also during surgery to correct defective hemostasis (178). 

Prothrombin (Factor II, from equine blood plasma) [9001-26-7] 72,000. Purified by two... 

Prothrombin time (PT) is a coagulation assay, which measures the time for plasma to clot upon activation by thromboplastin (a mixture of tissue factor and phospholipids). 

Zymogen is a precursor protein that is converted to an active protease when one or more of its peptide bonds are cleaved. Zymogens involved in coagulation include factors II (prothrombin), VII, IX, X, and XI. 

In the case of prothrombin and related clotting factors, interruption of the vitamin K cycle leads to the production of nonfunctional, undercarboxylated proteins, which are duly exported from hepatocytes into blood (Thijssen 1995). They are nonfunctional because there is a requirement for the additional carboxyl residues in the clotting process. Ionized carboxyl groups can establish links with negatively charged sites on neighboring phospholipid molecules of cell surfaces via calcium bridges. 

Prothrombin and several other proteins of the blood clotting system (Factors VII, IX and X, and proteins C and S) each contain between four and six y-carboxygluta-mate residues which chelate calcium ions and so permit the binding of the blood clotting proteins to membranes. In vitamin K deficiency or in the presence of warfarin, an abnormal precursor of prothrombin (preprothrombin) containing little or no y-carboxyglutamate, and incapable of chelating calcium, is released into the circulation. 

Fibrinogen -i These factors are usually referred Prothrombin J to by their common names. Tissue factor -i These factors are usually not re-Ca + J ferred to as coagulation factors. 

Proconvertin, serum prothrombin conversion accelerator (SPCA), cothromboplastin Antihemophilic factor A, antihemophilic globulin (AHG)... 

Activated by thrombin factor Va is a cofactor in the activation of prothrombin by factor Xa. 

In the final common pathway, factor Xa, produced by either the intrinsic or the extrinsic pathway, activates prothrombin (factor II) to thrombin (factor Ila), which then converts fibrinogen to fibrin (Figure 51-1). 

The activation of prothrombin, like that of factor X, occurs on the surface of activated platelets and requires the assembly of a prothrombinase complex, consisting of platelet anionic phospholipids, Ca, factor Va, factor Xa, and prothrombin. 

Figure 51-2. Diagrammatic representation (not to scale) of the binding of factors Va, Xa, Ca +, and prothrombin to the plasma membrane of the activated platelet. The sites of cleavage of prothrombin by factor Xa are indicated by two arrows. The part of prothrombin destined to form thrombin is labeled prethrombin.The Ca " is bound to anionic phospholipids of the plasma membrane of the activated platelet.

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