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MONITORING OF HEPARIN BY SOLUBLE FIBRIN MONOMER (SFM) GENERATION IN PREVIOUSLY INFERTILE WOMEN WHO BECAME PREGNANT AND CARRIED THEIR PREGNANCY TO SUCCESSFUL OUTCOMES ON HEPARIN.(1)
D. E. Berg, L.H. Berg,  S. Ondreyco, J. Couvaras, J. Garbaciak, S. Gunnala, R. Tamis, H. Harrison. HEMEX Laboratories. Phoenix, AZ.

Infertility may be caused at times by a hypercoagulable state which may be due to immune activation of the coagulation system. In baseline studies of women who have two or more documented miscarriages, there is strong evidence supporting this position. Immune activation can be seen in the cascade by increased thrombin generation as measured by increased (   ) F1+2 and T/ATs and or    Soluble Fibrin Monomer (SFM). Platelet activation, as measured by an   Platelet Activity Score (PA   Sc) using aggregometry &/or flow cytometry markers for platelet activation, demonstrates immune activation of these cells. In many women with immune activation, both pathways are increased. This condition has been termed the HOPI Syndrome (Hypercoagulability Of Pregnancy & Infertility). This syndrome consists of increased Fibrinogen, SFM, PA Score, and Clotting Kinetics (Sonoclot). When these women become pregnant, this hypercoagulability increases. Heparin or LMW Heparin (and   aspirin  when platelets are activated) can be used to decrease the hypercoagulable state to a more ‘normal' state (decreasing the SFM level to prevent fibrin deposition) and result in a normal pregnancy outcome. One of the goals of our study is to examine the capability of the quantitative Berichrom FM assay  versus the semi-quantitative  Diagnostica  Stago F.S. test to monitor the physiological efficacy of low levels of heparin for these women with previous fetal loss and documented immune activation of the coagulation system.

Our data suggests the need for a quantitative method for monitoring low level heparin therapy. The quantitative  Berichrom  FM method  gave answers that related to the decreases in  SFM  as heparin doses were increased. The semi-quantitative method of fibrin monomer measurement did not give adequate information for regulating heparin doses based on a  Negative-3+Positive reporting system.  It may be that the two systems use different antibody recognition sites which accounts for the lack of correlation with heparin dosing when using the Diagnostica Stago assay system. The use of F1+2 and T/ATs correlates with the SFM method as proof of increased thrombin generation, but does not quantitate the effectiveness of heparin therapy on SFM generation and fibrin deposition. The SFM method adds value to heparin monitoring even when the aPTT test results remain in the normal range.

1BLOOD: 90 (10) Nov 15, 1997, p 111b.
 

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