fibrin and Menorrhagia

The mechanism of dysfunctional uterine bleeding remains unknown. Recent studies suggest that the majority of cases of dysfunctional uterine bleeding are due to local endometrial, or myometrial, dysfunction. Changes in the pattern of production of prostaglandins PGE2, PGF2 alpha, prostacyclin and thromboxane and increased fibrinolytic activity in the endometrium have been implicated in this disorder. Successful treatment of excessive menstrual bleeding with the prostaglandin synthetase inhibitor mefenamic acid and the fibrinolytic inhibitors epsilon amino caproic acid and tranexamic acid further substantiates the role of prostaglandins and fibrinolysis in pathological menstruation. The relationship between uterine mast cells, heparin-like activity and menstrual bleeding still needs to be elucidated. Further studies are required to improve our understanding of the pathogenesis of dysfunctional uterine bleeding, so that advances can be made in a specific treatment to restore normal menstrual function.

Topics: Blood Platelets; Dinoprost; Dinoprostone; Endometrium; Female; Fibrin; Fibrinolysis; Hemostasis; Heparin; Humans; Mast Cells; Menorrhagia; Menstruation; Prostaglandins E; Prostaglandins F

Topics: Blood Coagulation; Blood Coagulation Tests; Blood Platelets; Cesarean Section; Estradiol; Factor VIII; Female; Fibrin; Fibrinogen; Fibrinolysis; Hemagglutination Tests; Humans; Hydrogen-Ion Concentration; Immunoassay; Immunoelectrophoresis; Labor, Obstetric; Menorrhagia; Menstruation; Methods; Plasminogen; Postpartum Period; Pregnancy; Progesterone; Thromboplastin; Time Factors; Uterus

To study the effects of adenomyosis on the coagulation and fibrinolysis system during menstruation and the relationship between dysfunction of the coagulation and fibrinolysis system and the symptoms and complications of adenomyosis.. Concentrations of thrombin-antithrombin complex (TAT) and soluble fibrin (SF) as markers of coagulation, D-dimer (DD) as a marker of both coagulation and fibrinolysis, and plasmin-alpha 2-plasmin inhibitor complex (PIC) as a marker of fibrinolysis in the peripheral blood of eight patients with adenomyosis were measured daily from the first to fifth day of menstruation. Associations between levels of these markers during menstruation and patient characteristics, history of thrombotic disorder, and hemoglobin loss during menstruation were investigated.. TAT, SF, DD and PIC increased in 5, 2, 3 and 1 of the 8 patients, respectively. TAT increased in 5 of the 6 patients with an adenomyotic uterus ≥100 cubic centimeters. Patients with elevated DD, SF and/or PIC were among patients with elevated TAT. DD was only increased in 3 patients with a past history of small cerebral infarction or pulmonary thromboembolism and/or hemoglobin loss >2.0g/dl during menstruation. SF was increased only in 2 patients with a past history of cerebral infarction or pulmonary thromboembolism. PIC increased in 1 of the 2 patients with hemoglobin loss >2.0g/dl during menstruation.. Adenomyosis patients with a uterus volume ≥100 cubic centimeters are at risk of having an activated coagulation system. These patients, particularly those with elevated SF and DD, may be at risk of thrombotic disorders. Fibrinolysis is activated in a portion of patients with activated coagulation during menstruation. Activated fibrinolysis during menstruation may contribute to menorrhagia in patients with adenomyosis, as only patients with activated fibrinolysis suffered menorrhagia, even though patients with an adenomyotic uterus ≥100 cubic centimeters without activated fibrinolysis did not. These results suggest extensive adenomyosis confers a potential risk of infarction and thrombosis and exacerbates menorrhagia via activation of coagulation and fibrinolysis during menstruation.

Topics: Adenomyosis; Adult; alpha-2-Antiplasmin; Antithrombin III; Blood Coagulation; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinolysin; Fibrinolysis; Humans; Menorrhagia; Peptide Hydrolases; Thrombosis

Formation of compact and poorly lysable clots has been reported in thromboembolic disorders. Little is known about clot properties in bleeding disorders.. We hypothesized that more permeable and lysis-sensitive fibrin clots can be detected in women with heavy menstrual bleeding (HMB).. We studied 52 women with HMB of unknown cause and 52 age-matched control women. Plasma clot permeability (Ks), turbidity and efficiency of fibrinolysis, together with coagulation factors, fibrinolysis proteins, and platelet aggregation were measured.. Women with HMB formed looser plasma fibrin clots (+16% [95%CI 7-18%] Ks) that displayed lower maximum absorbancy (-7% [95%CI -9 - -1%] ΔAbsmax), and shorter clot lysis time (-17% [95%CI -23 - -11%] CLT). The HMB patients and controls did not differ with regard to coagulation factors, fibrinogen, von Willebrand antigen, thrombin generation markers and the proportion of subjects with defective platelet aggregation. The patients had lower platelet count (-12% [95%CI -19 - -2%]), tissue plasminogen activator antigen (-39% [95%CI -41 - -29%] tPA:Ag), and plasminogen activator inhibitor-1 antigen (-28% [95%CI -38 - -18%] PAI-1:Ag) compared with the controls. Multiple regression analysis upon adjustment for age, body mass index, glucose, and fibrinogen showed that decreased tPA:Ag and shortened CLT were the independent predictors of HMB.. Increased clot permeability and susceptibility to fibrinolysis are associated with HMB, suggesting that altered plasma fibrin clot properties might contribute to bleeding disorders of unknown origin.

Topics: Adult; Blood Coagulation; Blood Coagulation Tests; Body Mass Index; Case-Control Studies; Female; Fibrin; Fibrin Clot Lysis Time; Fibrinogen; Fibrinolysis; Glucose; Humans; Menorrhagia; Middle Aged; Permeability; Plasma; Plasminogen Activator Inhibitor 1; Platelet Function Tests; Thrombin; Tissue Plasminogen Activator

Fibrinogen St. Gallen I was detected in an asymptomatic Swiss woman. Routine coagulation tests revealed a prolonged thrombin and reptilase time. Functionally measured fibrinogen levels were considerably lower than those determined immunologically. Polymerization of fibrin monomers derived from purified fibrinogen was delayed in the presence of either calcium or EDTA. Normal fibrinopeptide A and B release by thrombin was established. An abnormal degradation of fibrinogen St. Gallen I by plasmin was observed. Fragment D1 of normal fibrinogen was fully protected against further proteolysis in the presence of 10 mM calcium, whereas fibrinogen St. Gallen I was partially further degraded to fragments D2 and D3. In the presence of 10 mM EDTA, the conversion of variant fragment D1 to D2 was accelerated whereas the degradation of fragment D2 to D3 was delayed in comparison to degradation of fragments D1 and D2 of normal fibrinogen. Three high-affinity calcium binding sites were found in both normal and variant fibrinogen. Mutation screening with SSCP analysis suggested a mutation in exon VIII of the gamma-chain gene. Cycle sequencing of this gene portion revealed a single base substitution from G to T of the base 7527, leading to replacement of gamma 292 glycine by valine. The same mutation has already been described for the fibrinogen variant Baltimore I. Molecular modeling was performed of a part of the gamma-chain containing the mutation site, based on recently published X-ray crystal structures of human fibrinogen fragment D and of a 30 kD C-terminal part of the gamma-chain. Significant structural alterations due to the substitution of glycine by valine at gamma 292 were observed, e.g. spreading of the protein backbone, probably leading to a modified accessibility of the plasmic cleavage sites in the gamma-chain at 356 Lys and 302 Lys. A shift of gamma 297 Asp that is involved in interactions of fragment D with the Gly-Pro-Arg-Pro-peptide was noted by molecular modeling. The latter observation is compatible with delayed polymerization of fibrin monomers.

Topics: Abortion, Spontaneous; Afibrinogenemia; Amino Acid Substitution; Binding Sites; Biopolymers; Blood Protein Electrophoresis; Calcium; DNA Mutational Analysis; Exons; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogens, Abnormal; Fibrinolysin; Humans; Menorrhagia; Middle Aged; Models, Molecular; Mutation, Missense; Nephelometry and Turbidimetry; Point Mutation; Polymerase Chain Reaction; Polymorphism, Single-Stranded Conformational; Pregnancy; Protein Conformation; Thrombin Time; Uterine Hemorrhage

The effect of the intrauterine contraceptive device (IUCD) on uterine haemostasis was studied at various stages of the menstrual cycle in a series of 46 patients by light- and electron-microscopy and by following the distribution of an infusion of 51Cr-labelled autologous platelets. The endometrium in contact with the IUCD in the majority of cases showed grooving with atrophy and mild chronic inflammation in the surrounding tissues. The adjacent stroma also showed increased vascularity and occasional foci of haemorrhage but the increased blood loss associated with the presence of the IUCD could not be attributed to mechanical erosion or stromal blood vessels by the device. During menstruation the presence of an IUCD does not appear to inhibit the formation of fibrin/platelet thrombi although both in control and IUCD patients there was a striking paucity of platelet/fibrin thrombi in circumstances where their formation should be enhanced. In contrast to other workers we have not observed that gaps or breaks in the endothelial lining of endometrial blood vessels occur with any greater frequency in patients fitted with an IUCD. The principal mechanism by which uterine haemostasis is achieved remains to be established.

Topics: Adult; Blood Platelets; Endometrium; Female; Fibrin; Hemostasis; Humans; Intrauterine Devices; Menorrhagia; Menstruation; Microscopy, Electron; Uterus

Increased menstrual loss and irregular uterine bleeding are major drawbacks to acceptibility of intrauterine contraceptive devices (IUCDs). Fibrinolytic activity around IUCDs removed from 80 women was measured by embedding the device immediately after removal in a plasminogen-rich fibrin plate. In fifteen of the women an endometrial biopsy was also taken at the time of removal of the IUCD. In women who had the IUCDs removed because of bleeding a much higher fibrinolytic activity was found than in women not complaining of excessive bleeding. The fibrinolytic activity was shown to be due to plasminogen activator and not plasmin. The findings suggest that the excessive menstrual bleeding which occurs with the IUCD may be due to enhancement of fibrinolytic activity in the endometrium which can be modified by fibrinolytic inhibitors such as epsilon aminocaproic acid.

Topics: Aminocaproic Acid; Antifibrinolytic Agents; Female; Fibrin; Fibrinolysin; Fibrinolysis; Humans; Intrauterine Devices; Menorrhagia; Menstruation Disturbances; Plasminogen; Plasminogen Activators

Fibrinogen-fibrin degradation products, FDP, in menstrual blood during the first three days of menstrual blood during the first three days of menstruation have been investigated. Two groups of women were studied, those with normal menstrual blood loss (15 women, mean loss 30 ml, range 8-60 ml) and those with menorrhagia (14 women, mean loss 222 ml, range 107-729 ml). The following results were obtained: 1). The FDP concentrations decreased during menstruation in both groups. 2). The FDP concentrations in the two were compared for each day of the menstrual period. No differences were found between the two groups. A possible explanation of the results is given: there is a higher rate of coagulation and fibrinolysis in the endometrium of women with menorrhagia compared with women with normal blood losses. The hypothesis is supported by results of studies in which tranexamic is supported by results of studies in which tranexamic acid, an inhibitor of fibrinolysis, was given to reduce the menstrual blood loss. 3). The FDP excretion patterns differed from women to women. There were no consistent differences between the menorrhagic and the control group.

Topics: Adult; Female; Fibrin; Fibrinogen; Humans; Menorrhagia; Menstruation; Middle Aged; Time Factors; Tranexamic Acid

As part of a large-scale study of menstrual blood loss in the community serum fibrin degradation products were measured soon after menstruation in 331 women. No significant correlation was found between the amount of blood lost and the serum level of fibrin degradation products. These findings conflict with reports suggesting that excessive intrauterine fibrinolysis, which may play a part in menorrhagia, is associated with raised serum F.D.P. concentrations.

Topics: Adolescent; Adult; Blood; Female; Fibrin; Fibrinolysis; Hemagglutination Inhibition Tests; Humans; Menorrhagia; Menstruation; Uterus

Topics: Female; Fibrin; Humans; Menorrhagia; Menstruation

Serum concentrations of fibrin degradation products were found to be higher during menstruation than in the intermenstrual phase. Higher concentrations were present in cases of menorrhagia as compared with healthy women and women with various gynaecological disorders but with normal menstrual function. Higher serum concentrations of fibrin degradation products in cases of menorrhagia may indicate increased local fibrinolytic activity in the uterus.

Topics: Adolescent; Adult; Female; Fibrin; Fibrinolysis; Genital Diseases, Female; Humans; Menorrhagia; Menstruation; Middle Aged; Uterus

Topics: Decidua; Estradiol; Female; Fibrin; Fibrinolysin; Humans; Menorrhagia; Menstruation; Metrorrhagia; Placenta; Pregnancy; Uterine Hemorrhage

Topics: Female; Fibrin; Hemorrhage; Humans; Menorrhagia; Metrorrhagia; Pregnancy; Syndrome; Thrombosis; Uterine Hemorrhage; Uterus