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Morphology of menstrual hemostasis in essential menorrhagia.

We performed a morphologic and morphometric study with light and electron microscopy on early menstrual hemostasis in five menorrhagic uteri and one control uterus, related the data to measured menstrual blood loss and compared the data with our previous study on normal menstruation. Menstrual blood loss ranged from 39 to 234 ml. Menorrhagic uteri contained large hemostatic plugs, protruding with a large part into the extravascular space. These plugs often consisted of loosely packed, poorly degranulated platelets with few fibrin fibers. Recanalized plugs, consisting of fibrin fibers and platelet remnants at the periphery of the vessel, were also observed in menorrhagic uteri. Using morphometry, we demonstrated a positive correlation between menstrual blood loss and the number of occlusive and nonocclusive hemostatic plugs, but not with other aspects of hemostatic plug formation such as the vessel area occluded by the plug, plug transformation, or intra- or extravascular localization of the plug. Vasodilation or endometrial height were not correlated with the amount of menstrual blood loss. These data suggest that essential menorrhagia is associated with fragile hemostatic plugs or with more extensive vessel damage.

Adult↗

Hemostasis in Glanzmann's thrombasthenia (GT): GT platelets interfere with the aggregation of normal platelets.

The transfusion requirements for a 6-year-old Glanzmann's thrombasthenia (GT) patient undergoing tonsillectomy and adenoidectomy were studied. Transfusion of pheresed platelets from a single normal donor increased the platelet count by 63 x 10(9)/L but did not correct the bleeding time. Since the ratio of normal:GT platelets in vivo was approximately 1:5, it was possible that GT platelets interfered with the function of normal platelets. To test this hypothesis, mixtures of platelet-rich plasma (PRP) from a normal donor and the patient were studied to determine a ratio of normal:GT platelets that would yield acceptable in vitro aggregation. Normal:GT ratios of 1:4 and 3:2 resulted in 25% and 59% aggregation, respectively. Mixtures of normal and nonfunctional ethylene glycol tetra-acetic acid-treated platelets gave similar results. Aggregates from mixtures of normal and patient platelets were also examined morphologically by light microscopy and were proportional in size to the normal:GT platelet ratio. Transfusion of platelets from the pheresis of four donors increased the patient's platelet count by greater than 300 x 10(9)/L (normal:GT ratio 1:1), produced 53% aggregation, and resulted in satisfactory postoperative hemostasis. The platelet transfusion requirement for this GT patient was much greater than would have been expected in the absence of aggregation-defective platelets.

Antibodies, Monoclonal↗

Effects of ketorolac tromethamine on hemostasis.

Ketorolac tromethamine is a potent prostaglandin synthetase inhibitor useful in the treatment of postoperative pain. Since it is also known to have antiplatelet properties, we determined the effect of ketorolac, alone and in combination with low-dose heparin, on hemostasis. Each of 12 healthy male volunteers received the following drug combinations on a double-blind, crossover basis: ketorolac dummy/heparin dummy, ketorolac active/heparin dummy, ketorolac active/heparin active, and ketorolac dummy/heparin active. Ketorolac significantly prolonged bleeding time, and inhibited platelet aggregation and platelet thromboxane production. Heparin had no effect on bleeding time or platelet function, but significantly prolonged the kaolin-cephalin clotting time and increased anti-Xa levels. Ketorolac had no effect on the kaolin-cephalin clotting time or anti-Xa levels, and no interaction was found between ketorolac and heparin. The modest prolongation of bleeding time with ketorolac is unlikely to be of any major clinical significance, as the value remained within the normal range in almost all subjects. However, because of its antiplatelet properties, the drug should be used with caution in persons with hemostatic disorders.

Administration, Oral↗

[State of coagulation hemostasis and fibrinolysis processes in dynamics of rapidly progressing forms of botulinal intoxication].

Phase disturbances of coagulation blood potential were revealed in experiments on white rats in dynamics of rapidly progressing form of botulinic intoxication, intoxication being caused by intraperitoneal injection of type C toxin. In preclinical period of intoxication activation of procoagulant and anticoagulant parts of hemostasis system, as well as fibrinolysis system, was noted. Similar shifts were revealed in the developmental period of generalized pareses of skeletal musculature. Only in the terminal stage of intoxication insufficiency of mechanism in formation of prothrombinase activity developed by simultaneous activation of anticoagulant mechanism and fibrinolysis system.

Animals↗

[The role of the thrombocyte and erythrocyte components of hemostasis in the development of thrombohemorrhagic complications in patients with systemic lupus erythematosus].

The authors evaluated changes of plasma, thrombocytic and erythrocytic links of hemostasis in 15 patients with thrombotic and in 30 with hemorrhagic complications in lupoid nephritis. Marked changes of thrombocytes, erythrocytes were caused by autoimmune processes with signs of thrombohemorrhagic syndrome requiring therapeutic correction using heparin and deaggregants under careful coagulographic control.

Blood Platelets↗

[Hemostasis of the Santorini plexus].

The surgical approach in radical retropubic prostatectomy is facilitated by precise hemostasis of the dorsal vein complex (Santorini plexus). The authors technic is described.

Hemostasis, Surgical↗

[Preparations of alpha-lipoic acid: the dynamics of their content in the blood and their effect on hemostasis in lesions of the human liver].

The changes in blood coagulating activity before and after treatment with alpha-lipoic acid drugs as compared with blood lipoic acid content were studied in 130 patients with chronic diffuse diseases of the liver of the virus and alcohol etiology. A moderate correlation between the increase in blood alpha-lipoic acid concentration in patients with the liver diseases during the replacement therapy with alpha-lipoic acid drugs and a number of parameters of thrombelastogram was established. It was shown that relief of coenzyme deficit against the background of treatment with lipoic acid is associated with relief of hypocoagulative syndrome and an elevation of the blood ATP level. It is suggested that the ability of the coenzyme to stimulate the bioenergetic protection of hemostasis processes plays the important role in the mechanism of action of alpha-lipoic acid drugs.

Adolescent↗

The influence of coronary angiography and angioplasty on parameters of hemostasis and fibrinolysis.

The influence of invasive investigations on parameters of hemostasis and fibrinolysis is generally unknown, although this has consequences for the design of prospective studies on the association between those parameters and regression or progression of atherosclerosis. We therefore determined hemostatic and fibrinolytic factors in 12 patients who were admitted to the hospital for coronary angiography (CAG; n = 5) or percutaneous transluminal coronary angioplasty (PTCA; n = 7). Blood samples were drawn under basal circumstances on the day before, the day of and the day after CAG or PTCA. Significant changes occur in the concentrations of platelets and white blood cells, hematocrit (Ht), von Willebrand factor antigen (vWF:ag), antithrombin III-activity (AT III-ag), antithrombin III-antigen (AT III-ant), fibrinogen, plasminogen, alpha2-antiplasmin (alpha2-AP), histidine-rich glycoprotein (HRG), and plasminogen activator inhibitor (PAI)-activity. Mean values of beta-thromboglobulin, platelet factor 4, factor VIII:C, tissue-type plasminogen activator activity (t-PA act) and euglobulin clot lysis time (ECLT) do not differ significantly. After correction for Ht, no significant differences exist between the day before and the day of the procedure; but on the day after CAG and PTCA significant differences occur in white blood cells, factor VIII:C, AT III-ag, alpha2-AP and PAI-act. It is concluded that principally blood samples for investigations on fibrinolysis may be taken on the day before or the day of CAG or PTCA without a loss of quality, if the values are corrected for Ht. Samples taken on the day after the procedure are not useful for such purposes.

Angina Pectoris↗

Fibrin polymerization and its regulatory role in hemostasis.

Proteolytic conversion of fibrinogen to fibrin results in self-assembly to form a three-dimensional clot matrix that subsequently becomes cross-linked by fXIIIa to form the central structural element of the in vivo thrombus. The process of fibrin formation and assembly leads to new properties that serve to regulate the rate and extent of clotting, cross-linking, and fibrinolysis. These are brought about by the ability of fibrin (1) to bind thrombin at a noncatalytic site, thus limiting its diffusability but at the same time preserving its catalytic potential; (2) to bind fXIII, regulate its activation to fXIIIa, and limit further activation of fXIII once fibrin cross-linking has occurred; and (3) to bind alpha 2-PI, tPA, and plasminogen and regulate the initiation and propagation of fibrinolysis. Additional interactions not covered in this review between fibrin(ogen), and other plasma proteins, cells or matrix components suggest other functions for fibrin that, along with those discussed above, define a critical role in modulating hemostasis, inflammation, and the wound healing process.

Extracellular Matrix↗

[Parameters of hemostasis during treatments associating fractionated heparin administered subcutaneously to standard and fractionated heparin administered intravenously in the chronic hemodialysis patient].

The hemorrhagic risk of an association of fractioned heparin (Fraxiparine) injected intravenously at the dose of 7500 AXaICU or of unfractionned heparin (UFH) injected intravenously at the usual dose used for a priming dose for hemodialysis (3750 +/- 1280 IU + 1000 IU after 2 hours of dialysis) to the subcutaneous administration of a thrombo-embolism preventive dose of Fraxiparine (7500 AXaICU) was evaluated on the modifications of the following hemostasis parameters: thrombin time, Activated Partial Thrombin Time (APTT), prothrombin time, anti Xa activity in 13 uremic patients on hemodialysis. The association of intravenous and subcutaneous Fraxiparine prevents efficiently the clotting of the extracorporeal circulation without inducing a detectable antithrombinic activity. In contrast, the association of I.V. UFH to subcutaneous Fraxiparine induces a significant increase of the thrombin time and of the APTT. This latter is exclusively explained by the activity of UFH. It is concluded that subcutaneous Fraxiparine at the thromboembolism preventive dose can be associated as well to I.V. Fraxiparine as to UFH without increasing the antithrombinic activity of the plasma.

Aged↗

[Hemostasis, fibrinolysis, proteolysis: interaction with inflammatory reactions].

Many physiological processes are based on the finely regulated interaction between cells and enzymatic reaction cascades. Mainly proteinases are involved in these processes, which are regulated by inhibitors, principally proteins. If this sensitive balance is disturbed, uncontrolled pathophysiological events can be induced, which are often associated with inflammatory reactions. Characteristic for inflammation are events like contact activation of hemostasis, increasing permeability of blood vessels caused by activation of the Kallikrein-Kinin- and the Complement-system and Plasmin-release induced by activation of fibrinolysis. The following uncontrolled proteolysis, leading to tissue destruction, is mainly associated with the degree of illness. Inflammatory cells excrete besides proteinases also mediators maintaining and increasing these processes. Only when the balance between proteinases and inhibitors is restored, inflammation subsides. Afterwards the controlled course of physiological reactions is possible again.

Endopeptidases↗

[Effects of blood coagulating and fibrinolytic activity of tumor on the state of systemic hemostasis in patients with stomach cancer].

Functional status of hemostatic system was assessed in 75 gastric cancer patients and 40 healthy volunteers. Hemostatic potential of blood flowing off tumor was evaluated in 38 patients whereas fibrinolytic activity of tumor tissue samples--in 35. The results showed the degree and pattern of functional disorders occurring in the hemostatic system to depend upon the extent and procoagulant and fibrinolytic activity of tumor. The evaluation of status of hemostasis as functional test elicited depletion of fibrinolytic and antiaggregation activity of the vascular wall in patients with locally advanced and disseminated cancer of the stomach.

Adult↗

[The status of hemostasis in patients undergoing surgery with artificial circulation].

Hemostasis has been assessed in 200 patients during and after cardiopulmonary bypass surgery depending on different protamine sulphate (PS) doses injected for heparin neutralization. It has been demonstrated that the use of 1:1 PS to heparin ratio leads to adequate heparin neutralization and does not cause the appearance of residual heparin in the blood. PS administration at a dose not exceeding that of heparin was accompanied by an intraoperative decrease in platelet count and its more rapid recovery in the early postoperative period.

Cardiac Surgical Procedures↗

[Hemostasis system and immune reactivity in patients with acute pneumonia and chronic alcoholism].

Hemostasis system and immune reactivity were studied in chronic alcoholics with (92 subjects) and without (65 subjects) acute pneumonia. Activation and antiplasmin activities of blood in the alcoholics were found reduced. In associated alcoholism and pneumonia the two diseases aggravate each other causing a sharp suppression of lymphocytic component of immunity and inhibition of plasminogen activator activity. The majority of patients respond with a compensatory rise in the number of monocytes with active receptors. In coupled lymphocytopenia and monocytopenia the favorable outcome is unlikely. The prognosis is more beneficial in enhanced systemic fibrinolysis observed in elevated count of mononuclears with active Fc-receptors suggesting laboratory evidence for convalescence.

Adult↗

Hemostasis in hypertensive disorders of pregnancy.

We studied parameters of hemostasis reported to be altered with "pure" preeclampsia in hypertensive disorders of pregnancy. Plasma fibronectin, antithrombin, and alpha-2 antiplasmin were measured in normal pregnancies (N = 26) and in pregnancies complicated by preeclampsia (N = 19), hypertension (N = 11), and chronic hypertension with superimposed preeclampsia (N = 11). Preeclampsia, both pure and superimposed, was associated with high fibronectin (P less than .001), low antithrombin III (P less than .001), and low alpha-2 antiplasmin (P less than .05) levels, suggesting endothelial injury, clotting, and fibrinolysis, respectively. Alpha-2 antiplasmin was increased with chronic hypertension (P less than .001), regardless of whether there was superimposed preeclampsia. Fibronectin appeared to be more closely linked with preeclampsia than antithrombin III or alpha-2 antiplasmin and may prove valuable in detecting preeclampsia when evaluating hypertension in pregnancy.

Adult↗

[Regulation of hemostasis: the protein C-protein S system].

Two vitamin K dependent plasma proteins, protein C and protein S, play an actually well known role in the regulation of hemostasis. The importance of a deficiency in one or the other of these proteins in the genesis of thrombotic events justifies its systematic detection in this type of pathology.

Blood Coagulation Disorders↗

The effect of various anticoagulant/antiplatelet mixtures on determination of plasminogen activator inhibitor, platelet proteins and hemostasis parameters.

Blood collected in different anticoagulant/antiplatelet agents (ETP, EDTA, citrate, citrate/citric acid pH 4.5 and CTAD) was compared with respect to determination of PAI-1 activity and PAI-1 antigen. beta TG and PF4 were analysed as markers of platelet release. Both the middle layer and the remaining layer of the plasma were studied. Moreover vWF:Ag, FVII:Ag, ECLT, t-PA:Ag, t-PA activity, APTT, VIII:C and VII:C were assayed in blood collected in citrate and CTAD. PAI-1 activity showed the same level in all citrate based anticoagulants and ETP and no increase was found in blood standing for 2 hours at room temperature. On the contrary quick handling was most important for determination of PAI-1 antigen. In tubes anticoagulated with citrate no significant increase was found if the sample was prepared within 1 hour. EDTA was not suitable as anticoagulant mixture. Tubes containing the antiplatelet mixture CTAD could be used for determination of PAI activity, PAI antigen, vWF:Ag, FVII:Ag, t-PA activity and APTT. For measurement of PAI-1 antigen quick handling of blood anticoagulated with antiplatelet mixtures are preferable, and plasma treated in that manner could also be used to assay some hemostasis parameters.

Anticoagulants↗

A hemostasis study in CAPD patients during fibrinolytic intraperitoneal therapy with urokinase (UK).

Catheter obstruction due to fibrin deposits during CAPD can cause poor outflow of peritoneal fluid and recurrent peritonitis. In order to treat this complication, 75,000 IU of diluted Urokinase (UK) were infused into catheters obstructed by fibrin in 10 CAPD patients (4 of which had peritonitis), without adverse reactions. After 60 minutes, a 2 liter exchange of peritoneal fluid was performed. In all the cases a normal outflow was restored. Hemostasis parameters (PT, PTT, TT, Fibrinogen, FDP, Fibrin monomers, BT, AT III) and blood cells count (RBC, HGB, HCT, WBC, PTL), were assayed before and two hours after the UK infusion, and did not show any significant variation, except for a decrease of white blood cells, which remained, however, within the normal range. No peritonitis episode occurred in the follow-up period. UK fibrinolytic therapy is safe and effective in treating fibrin obstruction of CAPD catheters without catheter removal and prevents recurrent peritonitis.

Catheters, Indwelling↗