FRAGMIN VS HEPARIN AT RECYCLING OE HUMAN BLOOD IN HEART-LUNG MACHINE (HLM)
L Bagge, E Holmer, S Nystroöm, H Tydeén, T Wahlberg
FACTORS XII AND XI
During cardio-pulmonary bypass (CPB), Heparin inhibits EXa (EXal), thrombin and platelet activity and is also reported to induce fibrinolysis. Eragmin (Erag) has 25% thrombin inhibition capacity as related to that of Heparin (Hep). An in_vitro study was performed to compare Frag with Hep by circulating blood in a pure artificial system. In 20 experiments, 400 ml of freshly collected blood with Frag or Hep were recycled for 2 h. HLM was primed with 400 ml of Ringeracetate. Blood sampling: donor,
... blood pack and every 20 min from the oxygenator. V_a£i£ble£/jassay/:ACT/Hemochron/5 APTT , TT and NT/Nyegaard/;FXaI, FVIII and ATIiT t"ATA)/amydolytic/; AT 111 (ATAg) and vWF/IEP/;Plasminogen (Pig) and albumine/immuno-diffusion/;FDP/Wellcome/;Platelet function/Adeplat S/;Fibrinogen (Fbg)/clottable/;Hemolysis (HL)/photometric/; (β -Thromboglobulin ((βTG)/RTA/;EVF, Hb, platelet count (PC) and Leucocyte count (LC)/ conventional). Corrections for hemo-/plasma dilutions were calculated. Dosages (n): Frag: 750 (1), 1500 (3), 2100 (4), 2500 (4) FXal-U (U); Hep: 1000 (3), 1500 (6) IU clinical level. Clotting only occurred at Frag 750 (1) and 1500 (2) U, when ACT, APTT, FVIII, Fbg and ATA were significantly lowered. Generally, PC fell 75% during the recycling, while PF was constant'∼20% and (βTG increased. Neither presence of FDP nor Pig consumption were detected. FXal, ACT, APTT, TT and NT were dose dependent for both drugs. ATA was directly dose-related to Frag but inversely to Hep. LC decreased with the Frag-dose but inversely to that of Hep. HL increased generally. Several proteins increased (clotting excl): Fbg 30%, ATAg 25%, ATA 45?o and vWF 60%. Conclusions. Prevention of clotting required about the double dosage of Frag. Shortened ACT and APTT predicted clotting while the levels of FXal, TT and NT did not. Thus, an effective thrombin inhibition is needed under this conditions. Consumptions of FVIII, Fbg and ATA but no further drop in PC at clotting, indicate weak platelet aggregation involvement. Absence of fibrinolytic signs supports that the fibrinolysis seen at CPB, is not a genuine effect of Hep (or Frag). Increases in some proteins may be caused by cytolysis. The rise in vWF is probably due to release from platelet surfaces.