Background: A successful outcome of pregnancy depends on proper placental formation. In the very beginning of this process, trophoblast invasion and fibrin deposition into the wall of the decidual veins play an important part. Two polymorphisms, coagulation factor XIII (FXIII) Val34Leu and plasminogen activator inhibitor 1 (PAI-1) 4G/5G, interfere with fibrin cross-linking and regulation of fibrinolysis and may therefore contribute to early pregnancy loss. Methods: We enrolled 49 unrelated Caucasian women with a history of two consecutive or three to six nonconsecutive early pregnancy losses and 48 unrelated parous healthy controls without a history of pregnancy loss and evaluated them for the following genetic variants: the factor V Leiden and prothrombin G20210A gene mutations, the methylenetetrahydrofolate reductase C677T and A1298C polymorphisms, and the PAI-1 4G/5G and FXIII Val34Leu polymorphisms. Results: For the isolated occurrence of PAI-1 4G/5G or FXIII Val34Leu, we found no statistically significant difference between cases and controls. For homozygosity of either or compound carrier status of both mutations, the overall relative risk for early pregnancy loss was significantly increased (odds ratio ‫؍‬ 2.4; 95% con-

We investigated the effects of an ultra-marathon on cell-free plasma DNA as well as on mRNA expression of pro-apoptotic (Bax, Bad), anti-apoptotic (Bcl-2) and cell-protective (Hsp70, Hsp27 and Hsp32) genes in mononuclear blood cells (MNCs). Blood samples were drawn from 14 athletes before and immediately after 6-h run. In addition, blood samples were also collected and analyzed 2 and 24 h after the end of the run. Levels of plasma DNA were significantly increased immediately after the marathon (P < 0.001) and were still higher 2 h later (P < 0.005), but significantly lower than those immediately after the race (P < 0.05). Cell-free plasma DNA returned to pre-race levels 24 h after the run. mRNA expressions of Hsp70, Hsp32 and Bax significantly increased in MNCs after the race, whereas Hsp27 and Bad mRNA expression levels showed no significant changes. Bcl-2 expressions decreased immediately after the race (P < 0.001), but increased in the 24 h later (P < 0.05). We conclude that apoptotic ladders of cell-free DNA following exhaustive exercise originate from apoptotic cells and that not only skeletal muscle cells but also leukocytes contribute to this phenomenon.

Inherited and acquired thrombophilia are associated with recurrent pregnancy loss. Recently, an increased risk for thromboembolic disease was described for patients with elevated coagulation factor VIII, but it is unknown whether there is also an association to early pregnancy loss. We therefore evaluated the relation between recurrent early pregnancy loss and levels of coagulation factor VIII. We enrolled 49 unrelated Caucasian women with a history of 2-6 early pregnancy losses and 48 healthy controls, who had delivered at least one term infant and had never experienced pregnancy loss. We determined factor V Leiden-, G20210A prothrombin-, MTHFR C677T- and A1298C-gene mutations, levels of antithrombin, protein C, protein S, factor VIII, C-reactive protein and antiphospholipid antibodies. There was a significantly higher rate of pregnancy losses in women with Antiphospholipid Syndrome (p = 0.043). Furthermore, plasma levels of coagulation factor VIII were significantly higher in cases than in controls (130.5 IU/dl +/- 25.4 vs 119.5 IU/dl +/- 24.1; p = 0.032) and appeared independent of C-reactive protein (R = 0.146, p = 0.323 in cases; R = -0.028, p = 0.850 in controls). The relative risk for recurrent pregnancy loss in women with factor VIII levels above 151 IU/dl (90(th) percentile of controls) was 2.5 (0.7 - 8.9, 95 percent confidence interval), for levels above 156 IU/dl (95(th) percentile of controls) 3.9 (0.8 - 20.0, 95 percent confidence interval). Elevated maternal plasma levels of coagulation factor VIII tend to be associated with an increased risk for recurrent early pregnancy loss.

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Beriplex P/N reverses severe warfarin-induced over anticoagulation immediately and completely in patients presenting with bleeding. British Journal of Haematology, 115, 998-1001.