SummaryHeparin enhances the inhibition rate of thrombin by both antithrombin III (AT III) and heparin cofactor II (HC II). We studied the activity of these two plasma proteins in patients with chronic renal failure (CRF) undergoing regular hemodialysis as their heparin requirements varied widely. In 77 normal blood donors, normal ranges (mean ± 2 SD) were 82-122% for AT III and 65-145% for HC II. When compared with these controls 82 dialyzed CRF patients had a subnormal AT III activity and a significantly (p <0.001) lower HC II activity. To evaluate the effect of hemodialysis we compared AT III, HC II and total proteins in plasma before and after dialysis in. 24 patients (12 with normal and 12 with low basal HC II activity). AT III and HC II activities significantly (p <0.001) increased in absolute value. When related to total plasma proteins, in order to suppress the influence of hemoconcentration induced by dialysis, AT III decreased significantly (p <0.01) whereas HC II increased slightly but significantly (p <0.01) in the 12 patients with low initial HC II activity. The decrease of AT III induced by heparin administrated during dialysis is likely to account for this relative decrease of AT III activity. A modification of the distribution of both HC II and heparin between the vascular wall and the circulating blood is evoked to explain the relative increase in HC II activity and the need for higher heparin dosage in patients with low HC II levels.

The etiology of venous thromboembolic disease has been the subject of several recent discoveries, particularly on genetic predisposing factors. The laboratory investigation that may help to evaluate the risk for individual patients includes the measurements of coagulation inhibitors (antithrombin, protein C, and protein S) in plasma assays, the search for the factor V Leiden mutation by the plasma activated protein C resistance test (always to be confirmed by DNA analysis when abnormal), and the search for the prothrombin gene mutation by DNA analysis. Among acquired abnormalities, the most frequently involved are phospholipid-dependent autoantibodies associated or not with a subset of antibodies having an anticoagulant effect in vitro (lupus anticoagulant). Other coagulation abnormalities such as increased FVIII, FIX, or FXI levels or hyperhomocysteinemia have been suggested to be risk factors for thrombosis, although additional studies are required to definitively assess their role.

BCs can be held at 22 degrees C for up to 12 hours, with no detrimental effect on the quality of PCs stored for up to 5 days in plasma. Such a holding time might help overcome logistic problems in blood banks.

Heparin cofactor II (HCII) is a thrombin inhibitor in human plasma which displays similarities with antithrombin III (ATIII). Hereditary HCII deficiency was recently reported to be associated with thrombophilia. Since thromboembolism constitutes one of the main complications of the nephrotic syndrome (NS), both activities and antigen concentrations of HCII and ATIII were measured in the plasma and urine of 33 adult patients with nephrotic syndrome. The mean HCII plasma level was significantly increased whereas the ATIII level was decreased. Plasma HCII was significantly correlated with proteinuria and with the fibrinogen level, suggesting that HCII could act as an acute phase reactant in patients with NS. HCII antigen was detectable in 16 of the 24 available urine samples, whereas ATIII antigen was present in all of them. In addition, functionally active HCII was detected in most of the urine samples containing HCII antigen, while ATIII was only present in the inactive form. In conclusion, these findings suggest that HCII is submitted to a metabolic pathway different from that of ATIII in patients with NS.

We studied the pharmacokinetics of the low-molecular-weight heparin (LMWH) Fraxiparin in 6 patients with the nephrotic syndrome. Maximal plasma anti-Xa activity was obtained 5 h after a subcutaneous injection of 60 IU anti-Xa/kg. Anti-Xa activity was no longer detectable 24 h postinjection. These results are similar to those obtained with the same dosage in other clinical settings. The biological response to a daily subcutaneous injection of 60 IU anti-Xa/kg was studied for 8 days. No cumulative effect was observed. All the patients had an abnormal activation state of hemostasis mechanisms before treatment, as shown by high prothrombin fragment 1 +2 and D-dimer levels, which were not decreased by Fraxiparin. It remains to be determined whether a higher dosage of LMWH might attenuate the hypercoagulability in these patients.