Coagulation factor plasma concentration

Coagulation factors are glycoproteins named by roman numbers (the numbers being ascribed at the time of the components definition, not sequence of activation) (Table 1). Besides von Willebrand factor (vWF), the coagulation factors are synthesized in the liver. They have very different half-lifes and different concentrations in the plasma. Several coagulation factors are stored in platelets and endothelial cells and can be released during activation of these cells, which can result in a much higher local concentration of the respective factor (e.g., vWF). 

Coumarins are competitive inhibitors of vitamin K, which is required for the formation in the liver of the amino acid, gamma-carboxyglutamic acid. This is necessary for the synthesis of prothrombin and factors VII, IX and X (Figure 17.1). After starting treatment the anticoagulant effect is delayed until the concentration of normal coagulation factors falls (36-72 h). The effects can be reversed by vitamin K (slow maximum effect only after 3-6 h) or by whole blood or plasma (fast). Gut bacteria synthesise vitamin K and thus are an important source of this vitamin. Consequently, antibiotics can cause excessive prolongation of the prothrombin time in patients otherwise adequately controlled on warfarin. 

The effect of continuously administered low-dose 17-beta-estradiol (E2) + norethisterone acetate (NETA) on coagulation and fibrinolytic factors has been studied in 120 menopausal women, using two dosage variations (1 mg of E2 with 0.25 mg or 0.5 mg of NETA) compared with placebo over a year (53). In either dose, the combination significantly lowered plasma concentrations of factor VII, fibrinogen, antithrombin, and plasminogen activator inhibitor-1 (PAI-1) compared with placebo. These changes appear favorable, since they may lead to increased fibrinolytic activity and could reduce the risk of coronary heart disease. However, antithrombin activity was also reduced, which may increase the risk of venous thromboembolism. 

Freeze-dried concentrates of plasma containing prothrombin, factors IX and X, and varied amounts of factor VII (Proplex, etc) are commercially available for treating deficiencies of these factors (Table 34-3). Each unit of factor IX per kilogram of body weight raises its activity in plasma 1.5%. Heparin is often added to inhibit coagulation factors activated by the manufacturing process. However, addition of heparin does not eliminate all thromboembolic events. 

Prothrombin complex concentrate, cryoprecipitate and fresh frozen plasma, commonly-used coagulation factor products. 

Nagashima et al. (33) developed a model in which the forcing function was modeled as proportional to the logarithm of the warfarin concentration in plasma. However, Pitsiu et al. (34) subsequently found that a sigmoid E ax model (Equation 19.11) is more suitable for modeling the relationship between plasma concentrations of S-warfarin, the active isomer of warfarin, and inhibition of coagulation factor formation. 

Fresh frozen plasma (FFP) 250 ml at six-hour intervals (10-20 ml/kg BW = 1,000-1,500 ml/day). Administration of 10 ml/kg BW (about 600-1,200 rnl) serves to elevate the concentrations of coagulation factors and inhibitors by 15—20%. The half-life of factor VII is only 6 hours, which is why dosage intervals of 6 to 12 hours must be maintained. IgA deficiency is a known contraindication. Adverse transfusion reactions may occur with a frequency of 1-5% of cases. Improvement in coagulopathy generally lasts 1 to 2 days. Caution is called for, since accentuated coagulation entails the danger of thrombosis (if necessary, AT III replacement of up to 60-80%), and an overload of the intra-... 

Piszkiewicz, D. Thomas, W. Lieu, M.Y. Tse, D. Samo, L. Virus inactivation by heat treatment of lyophilized coagulation factor concentrates. In Virus Inactivation in Plasma Products Morgenthaler, J.J., Ed. Curr. Stud. Hematol. Blood Transfus., Basel, Karger, 1989 56, 44—54. 

A (congenital or acquired) and type 1 von Willebrand disease, in which the VWF protein structure is normal but the plasma concentration is reduced (1). By contrast with conventional coagulation factor concentrates, desmopressin is cheap and is free from the risk of transmission of viral infections, which have proved such a problem in the past. It is also very useful in the treatment of carriers of hemophilia A, many of whom have significant reductions in the baseline concentration of factor VIII. By contrast, desmopressin has no effect on the concentration of factor IX, and is thus of no value in hemophilia B (Christmas disease). It is also of little value in type 2 (abnormal VWF structure) von Willebrand s disease, which accounts for about 15-20% of all cases. The administration of desmopressin to patients with type 2B von Willebrand s disease can be hazardous, as it is likely to cause thrombocytopenia (2). The use of desmopressin in bleeding disorders has been reviewed (3). Tachyphylaxis develops if desmopressin is used for prolonged periods to control bleeding disorders, because desmopressin causes release of stored factor VIII and von Willebrand factor, after which it takes time for them to accumulate again. 

Plasma-derived factor VIII concentrates have been implicated in the transmission of the non-enveloped hepatitis A and parvovirus B19 (28). The virus-inactivating procedures now in use (chemical inactivation, wet-heat treatment, and nanofiltration) should provide coagulation factors without risk of transmitting HIV and with a very high safety for hepatitis virus. Nevertheless, recombinant factor VIII is considered a safer alternative. 

The hematological effects of tumor necrosis factor alfa mostly consist of dose-related thrombocytopenia and granulocytopenia, and decreased monocyte or lymphocyte counts (SED-13, 1111) (11,12). Septic episodes are sometimes associated with leukopenia. Coagulopathy with laboratory evidence of disseminated intravascular coagulopathy was found in 30% of patients and was sometimes associated with thromboembolic events (13). Other coagulation disorders include transient alterations in prothrombin time, and a rise in the plasma concentrations of von Willebrand factor was found in healthy volunteers (14). 

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