Menstruation: Extravascular Fibrinolytic Activity and Reduced Fibrinolytic Capacity U. H. WINKLER Unipersity OfEsSen Dcpartmmt OB/GYN Hufih-se 55 4300 Emn 1, G m n y Extravascularfibrinolytic activity is involved in a variety of physiological and pathological proteolytic mechanisms, most of them being of prime clinical interest. Unbrmnately, little is known about how to monitor extravascular plasmin activity. We therefore studied plasmatic coagulation and fibrinolytic regulation in 40 young women at the first day of menstruation and on day 21 of the menstrual cyde. We consider menstruation as an easy accessible physiologic example of localized exmvascular plasmin activity. S u p o n s have long been reluctant to operate during menstruation claiming that mechanisms capable of making the menstrual discharge noncoagulable would impose a high risk of intraoperative bleeding. Blood collection and handling was done according to the Leiden fibrinolysis workshop criteria. The increase in tissue-plasminogen activator concentration (tPA) after 10 min of venous occlusion (A tPA) was calculated without correction b r plasma volume. Kits were purchased fmm KabiVitrum, Germany (KV), Behring Werke AG, Germany (BW), AKZO O w o n , the Netherlands (OR) and Boehringcr Mannheim, Germany (BM). Significance of change was assessed by the Wdcoxon test b r paired samples at p < 0.05. Results are summarized in TABLE 1. At the first day of menstrual discharge we b u n d the fibrin degradation products increased by 30%. This increase could not be explained by a concomitant incrrase of coagulatory activity. Fragment 1+2 (Frag 1+2) is cleaved in the process of prothrombin activation. The lack of difference in Frag 1+2 levels suggested only minor changes in thrombin generation during menstruation. On the other hand, owing to the striking differences in the halflife of thrombin and fibrin, degradation products of intravasculary generated fibrin may be detectable while activation peptides are already back to normal. So in theory, a short increase of coagulatory activity might have been missed by our sampling protocol. We can not completely rule out such hidden peaks of intravascular coagulation, but considering the sample size we should have hit such a peak at least once. It is reasonable to condude that the increase in fibrin degradation products associated with the onset of menstruation reflected at least to a major degree lysis of extravascular fibrin. Intravascular tPA concentration as well as the plasma level of its inhibitor PAL1 ag were not significantly changed at menstruation. The increase of tPA after 10 min of venous occlusion was not increased. In fict, A tPA was 30% lower during menstru289

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TABLE 1. Fibrinolytic and Coagulatory Activity at Menstruation and at Day 21 of the Menstrual Cycle in 40 Women Median (25th-75th Quartilc)

21st Day of the Menstrual Cycle

90 (68-115) 94 (82- 134) 0.52 (0.44-0.65) 1.6 (1.1-2.1)

300

(Auld)

(150480) 36 (22-58) 8.4 (6.3-10.0)

1st Day of Menstruation

Change (25th-75th Quartile)

155 (95-195) 182 (119-198) 0.65 (0.55-0.80) 1.8 (1.3-2.5) 250 (120-380) 46 (32-60) 9.6 (8.4-15.4)

28% (p < 0.05) (13-50) 33% (p < 0.05) (19-45) 12% (n.s.) (-4-26) 6% (n.s.) (-20-33) -30% (p < 0.1) (-93-25) 9% (p < 0.1) (- 12-30) 15% (p < 0.05) (-48-58)

Mean, 25th and 75th quartile arc given for each day and for the individualchanges. Fibrin degradation products were determined as total (FbDP) and cm-linked (DDimer) antigens. These assays are calibrated with Merent fragments ofthe fibrin molecule (accountingfor higher values of D-dimer and lower of the total degradation products). Prothrombin fragment 1+ 2 (Frag 1 + 2) reflects coagulatory activity. Tissue plasminogen activator (tPA), its increase after 10 min of venous occlusion (A tPA) and concentration (PAL1 ag) and activity (PA1 act) of its fast-acting inhibitor regulate the fibrinolytic activity.

ation and PA1 activity increased by 15%.Thus, mechanisms upregulating intravascular fibrinolysis like decreasing PAI activity and increasing fibrinolytic capacity are not associated with extravascular plasminogen activation. We conclude that extravascular fibrinolysis may best be monitored by sequential determinations of fibrin degradation products. Intravascular fibrinolytic activity is not increased during extravascular plasrninogen activation suggesting that surgery during menstruation is not complicated by increased intravascular fibrinolytic activity. REFERENCE 1. KLum, C. & J , H. VERHEIJEN. 1990. Leiden fibrinolysis working party: Blood collection and handling procedures for assessment of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor (PA1 1). Fibrinolysis 4 155-161.