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Low platelet adhesiveness and other hemostatic abnormalities in hypothyroidism.

Fifteen patients with definite hypothyroidism and two with probable hypothyroidism had extensive hemostatic profiles done. In 12 of the 16 patients tested, the platelet adhesiveness (platelet retention in a glass bead column) was abnormal, and in 1 more it was borderline. In the six patients who were studied repeatedly, hemostatic abnormalities either markedly improved or disappeared after treatment with L-thyroxine. It is concluded that, in addition to the previously reported coagulation factor deficiencies (which we also observed in some of our patients), low platelet adhesiveness occurs frequently in patients with hypothyroidism.

Adolescent↗

[The characteristic of the initial hemostatic status of patients requiring surgical treatment for lung diseases].

Overall 164 patients were examined, who had been assigned to surgical treatment for nonspecific pyo-inflammatory diseases, tuberculosis, and pulmonary neoplasia, with the purpose of assessing the baseline hemostatic abnormalities. The presence of hypercoagulation and of hyperfibrinogenemia was proved to be the case against the background of low activity of fibrinolysis in all patients but the ratio of the above components and the mechanism of origination of abnormalities differed depending on the kind of the underlying disorder. A differentiated approach is recommended towards selecting corrective means for dealing with hemostatic inadequacies in treating the above-named conditions.

Electrocoagulation↗

Evaluation of the effect of storage at -70 degrees C for six months on hemostatic function testing in dogs.

Freezing is a routine method of storage for plasma that is to be used in evaluating certain aspects of hemostatic function in many species. The purpose of this study was to evaluate the effect of storage at -70 degrees C for 6 mo on canine plasma samples. On fresh and frozen plasma from 12 clinically healthy dogs, prothrombin time, activated partial thromboplastin time, thrombin clotting time, fibrinogen determination, antithrombin III activity, fragment D and E assay, and protamine sulfate test were performed. Clinical agreement analysis was utilized to determine the effect of such storage on all assays. Individual differences detected between fresh and frozen samples were all within 2 standard deviations of the mean difference. With the exception of the activated partial thromboplastin time, storing canine plasma at -70 degrees C for 6 mo has no significant effect on hemostatic function, as assessed by these tests.

Animals↗

[Effects on vasomotor tone and hemostatic function of radiologic contrast media used during invasive cardiological procedures].

There are several types of radiologic contrast media which can be used in invasive cardiology: 1) ionic media with high osmolality (2000 mOsm/kg, about 6 times that of plasma), the prototype of which is diatrizoate; 2) ionic media with low osmolality (600-900 mOsm/kg), the prototype of which is ioxaglate; 3) non-ionic monomeric, low-osmolality media, such as iopromide, iopamidol and iohexol; and 4) non-ionic dimeric media, iso-osmolal compared to plasma (290-300 mOsm/kg), among which the most used is iodixanol. Non-ionic media--by far the most expensive--have a generally better tolerability profile for the patient, since they clearly induce a less gastro-intestinal, renal, hemodynamic, electrophysiological and pseudo-allergic side effects. They interfere much less with the physiology of vascular and circulating blood cells, and have lesser negative interference on the hemostatic function. Whether these lesser anti-hemostatic properties become a possible downside in situations at high thrombotic risk, such as in some interventional procedures, has been so far the object of isolated reports, usually with limited numbers of patients, and is presently being verified in adequate clinical trials. Radiologic contrast media also have disparate vasoactive properties on epicardial and myocardial resistance vessels. The knowledge and awareness of such effects is of potential importance for the performance of studies requiring the accurate quantitative evaluation of coronary diameters or of myocardial blood flow.

Angioplasty, Balloon, Coronary↗

Prospective evaluation of hemostatic system activation and thrombin potential in healthy pregnant women with and without factor V Leiden.

Normal pregnancy is associated with alterations of the hemostatic system towards a hypercoagulable state and an increased risk of venous thromboembolism. The risk of venous thrombosis is higher in pregnant women with factor V Leiden (FVL) than in those with wildtype factor V. Routine laboratory assays are not useful to detect hypercoagulable conditions. A prospective and systematic evaluation of hemostatic system activation in women with and without FVL during an uncomplicated pregnancy employing more sensitive markers of hypercoagulability, such as prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex (TAT), D-Dimer, or the endogenous thrombin potential (ETP), an indicator of the plasma's potential to generate thrombin, has not been performed. We prospectively followed 113 pregnant women with (n = 11) and without (n = 102) FVL and measured F1+2. TAT, D-Dimer and the ETP at the 12th, 22nd and 34th gestational week as well as 3 months after delivery (baseline) in each subject. None of the women developed clinical signs of venous thromboembolism during pregnancy or postpartum. Pregnant women with and without FVL exhibited substantial activation of the coagulation and fibrinolytic system as indicated by a gradual increase of F1+2, TAT and D-Dimer throughout uncomplicated pregnancy up to levels similar to those found in acute thromboembolic events (p < 0.0001 by analysis of variance for each parameters). Levels of F1+2 and TAT were comparable between women with and without FVL, but levels of D-Dimer were significantly higher in women with FVL than in those without the mutation (p = 0.0005). The ETP remained unchanged in both women with and without FVL at all timepoints. Our data demonstrate a substantial coagulation and fibrinolytic system activation in healthy women with and without FVL during uncomplicated pregnancy. An elevated F1+2, TAT or D-Dimer level during pregnancy is not necessarily indicative for an acute thromboembolic event. The normal ETP in both women with and without FVL suggests that the capacity of the plasma to generate thrombin after in vitro activation of the clotting system is not affected by pregnancy. Higher levels of D-Dimer in women with FVL than in women with wildtype factor V at baseline as well as during pregnancy indicate increased fibrinolytic system activation in carriers of the mutation.

Adult↗

A comparative study of the hemostatic effects of two monophasic oral contraceptives containing 30 mu(g) ethinylestradiol and either 2 mg chlormadinone acetate or 150 mu(g) desogestrel.

OBJECTIVES: To determine the effect of two low-dose monophasic oral contraceptives containing either 2 mg chlormadinone acetate or 150 microg desogestrel on blood clotting and fibrinolysis. METHODS: In vivo markers of intravascular coagulatory and fibrinolytic activity were measured in 45 volunteers randomly assigned to a 6-month treatment with one of the two study preparations. RESULTS: During oral contraceptive use, the procoagulatory activity increased (increased prothrombin fragment 1+2), the anticoagulatory capacity changed (increased protein C activity, decreased activated protein C sensitivity, decreased protein S activity and decreased antithrombin III activity) and the fibrinolytic system was activated (increased concentrations of plasmin-antiplasmin complexes and D-dimer as well as total fibrin degradation products). There were no relevant differences between the two medication groups. CONCLUSION: Our results demonstrate that both oral contraceptive preparations have comparable effects on the hemostatic system. There was a shift towards a new equilibrium of hemostatic activities, both coagulatory and fibrinolytic, at a higher turnover rate. Changes did not exceed the range of normal variation and were comparable to the published effects of other low-dose oral contraceptives. There was no evidence ofa differential risk of deep vein thrombosis between the two preparations.

Adolescent↗

The influence of the degree of cerebral atherosclerosis on the changes in hemostatic system in patients with ischemic brain disease and atherosclerotic encephalopathy.

Vascular brain diseases are ranked the third as the cause of morbidity and mortality, in spite of the progress in diagnostic, therapeutic and preventive procedures. In the majority of cases of vascular brain diseases, it is ischemic brain disease, which is the final and the most severe stage of cerebral arteries atherosclerosis. Etiopathogenesis of atherosclerosis is not closer defined yet, but oxidative hypothesis is distinguished among the numerous theories. Within this theory, main place is attached to oxidative modification of LDL and Lp(a), together with numerous physiopathologic facts with the central role of reactive oxidative matters, where endothelial dysfunction is the main disorder responsible for the onset of numerous impairments, such as changes in coagulation-anticoagulation system. Considering these facts, it was established the hypothesis that in patients with IBD existed changes in hemostatic system, which were in positive correlation with the degree of cerebral atherosclerosis. The study comprised 36 patients with acute IBD and 28 patients with atherosclerotic encephalopathy. Control group was comprised of 30 patients with non-vascular diseases of similar characteristics. We investigated the correlation of the changes in hemostatic system (platelet aggregation, anti-thrombin III, D-dimer, protein C, factor VII, factor VIII, PAI-1) compared to the degree of cerebral atherosclerosis (ultrasonographically) and compared to the observed groups of patients. On the basis of all, the results of this study revealed significant increase of procoagulant factors concentration in patients with IBD, and similar changes were observed in patients with atherosclerotic encephalopathy, but less pronounced. All these changes in the total sample of patients, and particularly in patients with the pronounced cerebral atherosclerosis, are of primary and chronic character.

Acute Disease↗

Plasma lipids, lipoprotein Lp(a), apolipoproteins, and hemostatic risk factors distributions in postmenopausal women.

In the present study, the effect of hormone replacement therapy on lipid metabolism, apolipoproteins and hemostatic risk factors for cardiovascular disease was assessed in 216 Croatian postmenopausal women. There were 156 current users divided in to two groups according to the duration of therapy. The short-term study of < 10 months (X +/- SD 5.31 +/- 2.69) included 49 users, and long-term study of > 11 months (X +/- SD 22.06 +/- 10.95) included 107 users of hormone replacement therapy. Sixty nonusers served as a control group. In the short-term study, current users had a significant increase in serum HDL cholesterol, apolipoprotein A-I, A-II and a decrease in total/HDL cholesterol ratio, apoB and antithrombin III (p < 0.05). No significant differences were recorded for total cholesterol, triglycerides, LDL cholesterol, lipoprotein Lp(a) and plasminogen. In the long-term study, a significant increase in HDL cholesterol, apo A-I and total/HDL cholesterol ratio, and a decrease in AT III were observed. Results of the study showed favorable effects of hormone replacement therapy on serum lipid profile and apolipoproteins as a protective regimen from cardiovascular disease in both treatment groups of postmenopausal women. There are conflicting reports regarding increased fibrinolytic activity. The clinical relevance of the observed changes in antithrombin III concentrations as an important coagulation inhibitor is doubtful and should be considered in a more extensive evaluation of the potential hemostatic risk factors for cardiovascular risk and thromboembolism.

Antithrombin III↗

Hemostatic system in early respiratory distress syndrome: reduced fibrinolytic state?

Previous studies suggest that there is a systemic activation of clotting and fibrinolysis in preterm infants with advanced respiratory distress syndrome (RDS). However, there are no data on the hemostatic status in the early stages of the disease; therefore, we studied some of the hemostatic parameters in these patients and made several studies at different times in preterm infants who did or did not develop RDS, using similar protocols. We found normal plasma fibrinogen, protein C, protein S, C4b-binding protein, thrombomodulin, antithrombin III, thrombin-antithrombin III complex, prothrombin fragment 1.2, plasminogen, tissue plasminogen activator, alpha-1 antitrypsin, alpha-2-macroglobulin and protein Z. However, lower D-dimer and higher plasminogen activator inhibitor and von Willebrand factor antigen levels were found within six hours of life in infants who later developed RDS compared to the control group. These findings suggest that disseminated intravascular coagulation is not prominent in the early stages of RDS. Moreover, reduced D-dimer and increased plasminogen activator inhibitor and von Willebrand factor antigen levels are probably related to the abnormalities in the fibrinolytic mechanism due to lung damage in RDS, but further studies are needed to show their pathogenic significance in RDS.

Fibrinolysis↗

[The hemostatic potential of the venous and arterial beds in patients with destabilized ischemic heart disease].

Coagulating activity was studied of the arterial and venous blood platelet-rich and platelet-poor plasma in 16 patients with unstable angina (UA). An unusual activation of the hemostatic potential was recordable in the venous and arterial beds, as per changes in the general index of thrombophilia, which fact, along with the presence of FDR and fibrin-monomer complexes, can be regarded as signs of disseminated intravascular coagulation which can cause thrombogenic complications in UA patients. Changes in the system of hemostasis in the above patients (as evidenced by the index of thrombophilia) might suggest the prethrombotic state. The results obtained showed that platelets had an important role in the formation of the hemostatic potential both in the venous and arterial blood in UA.

Adult↗

[Importance of certain hemostatic indicators as cardiovascular risk factors in type 2 diabetes].

BACKGROUND: Abnormal levels of some hemostatic factors in patients with type 2 diabetes mellitus are associated with increased risk of severe cardiovascular complications. OBJECTIVES: For the purpose of clinical practice it is necessary to specify most relevant coagulation factor abnormalities pertaining to a particular patient's risk profile (e.g. diabetes duration, his/her lipoprotein profile), since a routine examination to their full extent is in common ambulatory practice hardly manageable. This information is also needed for aiming the efforts to influence them purposefully. METHODS: The investigated group included 42 out-patients with type 2 diabetes mellitus. Selected hemostatic factors and lipoproteins were measured with standard methods. Patients were stratified into terciles based on supposedly causative factors (diabetes duration for vWF and lipoproteins for F VII), these relations being also examined in the whole group using regression analysis. MAIN RESULTS AND CONCLUSIONS: vWF (antigen) plasma concentration mean value in the whole group (in % of reference plasma: 149.917; 95% CI 134.296 to 165.538) was on the upper limit of the normal value reference range (56 to 140), exceeding it distinctly in the tercile III with the longest diabetes duration (vWF mean was 180.115; 95% CI 151.961 to 208.270). The mean in this tercile was also by 42.187 (95% CI of diff. 10.231 to 74.142; sign. level 0.012) higher than in the tercile I with the shortest diabetes duration. These 2 variables significantly correlated (r = 0.345; p = 0.025) also in the whole group. F VII plasma concentration mean values in terciles III with highest triacylglycerol (TAG) or total cholesterol (TCH) serum levels (in %: 129.286, 95% CI 121.117 to 137.455 or 121.071, 95% CI 109.228 to 132.915, respectively; the normal value reference range being 70 to 130) clearly surpassed the analogous values in tercile I by 35.0 (95% CI of diff. 22.793 to 47.207; sign. level < 10(-5)) or by 26.0 (95% CI of diff. 10.815 to 41.185; sign. level 0.002), respectively. There were also positive significant correlations between lipoproteins (TAG, TCH or LDL) and F VII in the whole group (r = 0.697, r = 0.580, r = 0.397; p < 0.0001, p < 0.0001, p = 0.018, respectively). Therefore the estimation of vWF seems to be useful in all diabetic patients and most elevated values are to be expected in long-duration-diabetics. F VII should be cared for especially in patients with concomitantly elevated TAG, TCH or LDL-cholesterol serum levels. (Tab. 6, Fig. 4, Ref. 24.)

Blood Coagulation Factors↗

Effects of diets containing olive oil, sunflower oil, or rapeseed oil on the hemostatic system.

Various studies have already shown that the fatty acid composition of dietary fat has different effects on hemostasis and platelet function. However, knowledge on this topic is incomplete. In the present study, fifty-eight healthy students received either a 4-week rapeseed oil [high content of monounsaturated fatty acids (MUFA) and high n-3/n-6 PUFA ratio], an olive oil (high content of MUFA, low n-3/n-6 PUFA ratio) or a sunflower oil (low content of MUFA, low n-3/n-6 PUFA ratio) diet. In each group, effects on hemostatic parameters were compared with a wash-in diet rich in saturated fatty acids with respect to intermediate-time effects on the hemostatic system and platelet function. With the olive oil diet, a reduction of coagulation factors VIIc, XIIc, XIIa, and Xc was found, whereas sunflower oil led to lower values of coagulation factors XIIc, XIIa, and IXc. In all study groups levels of plasmin-alpha2-antiplasmin were lower in week 4 than at baseline. Lower fibrinogen binding on platelets was found after the sunflower oil diet, whereas expression of CD62 and spontaneous platelet aggregation were slightly higher after the olive oil diet. However, given the major differences in the fatty acid compositions of the diets, the differences between the groups with respect to hemostasis tended to be small. Therefore, the clinical significance of the present findings remains to be evaluated.

Adult↗

Hemostatic changes associated with normal and abnormal pregnancies.

Routine hemostatic laboratory tests lack sensitivity and are of little value in the detection of the pregnancy associated hypercoagulable conditions. Assays for F 1 + 2, AT levels, TAT complex, APC activity, FPA, D-Dimers, tPA, plasminogen, PAI 1, and PAI 2 are more specific for fibrin formation and lysis. Monitoring these tests along with fibrinogen and platelet counts provides important information for the early detection of hemostatic activation and for monitoring the severity of the condition. Early detection and therapy is essential for limiting the deleterious complications of pregnancy. Advances in research, the development of new tests such as the TM assay and gene analysis, as well as highly skilled personnel, are required for the providing of quality pre and postnatal healthcare.

Blood Coagulation Tests↗

Hemostatic abnormalities associated with acute promyelocytic leukemia and corrective effects of all-trans-retinoic acid or arsenic trioxide treatment.

OBJECTIVE: To study in vivo effect of all-trans-retinoic acid (ATRA) or arsenic trioxide (As2O3) on the expression of tissue factor (TF) and the hemostatic disorders, a series of parameters were measured in bone marrow blasts and plasma from acute promyelocytic leukemia (APL) patients. METHODS: The plasma variables were measured by ELISA or chromogenic study. The TF transcription was assessed using reverse transcription-polymerase chain reaction technique (RT-PCR). RESULTS: The blast cell procoagulant activity (PCA), TF antigen of APL cell lysates, as well as the transcription of APL TF mRNA elevated at diagnosis, were reduced after ATRA or As2O3 therapy. The plasma level of platelet alpha-granular membrane protein-140, soluble fibrinomonomer complex, thrombomodulin, tissue plasminogen activator and D-dimer significantly increased, fibrinogen, antigen level of protein C, plasminogen, alpha 2-plasminogen inhibitor and plasminogen activator inhibitor decreased at diagnosis, were restored to normal after complete remission but protein C activity and protein S remained elevated in ATRA group. CONCLUSIONS: There existed activation of platelets and consumption of anticoagulants as well as activation of coagulation and fibrinolytic system before treatment. Both ATRA and As2O3 therapy down-regulated the expression of TF mRNA, decreased the PCA and TF level in APL cells, inhibited coagulation activation, secondary hyperfibrinolysis and recorrected other hemostatic abnormalities, thus greatly improved the bleeding symptom in early stage of the treatment.

Adolescent↗

[Hemostatic variations associated with acute leukemia: clinical and prognostic significance].

OBJECTIVE: To study the hemostatic abnormalities and their association with bleeding manifestation and prognosis in acute leukemia (AL) patients. METHODS: A series of hemostatic parameters were determined in 93 cases of AL using ELISA or chromogenic assay. RESULTS: At diagnosis, plasma levels of P-selectin, soluble fibrinomonomer complex (SFMC), thrombomodulin (TM), tissue plasminogen activator, D-dimer (D-D) were significantly elevated, but protein C antigen (PC:Ag), plasminogen (PLG), alpha(2)-antiplasmin (alpha(2)-PI) and plasminogen activator inhibitor (PAI) were decreased, and fibrinogen (Fg), PC activity (PC:A) and protein S (PS) were in normal range. All the above abnormalities returned to normal after complete remission (CR) except for PC:A and PC:Ag. Platelet counts, Fg, SFMC, PLG, alpha(2)-PI and D-D were significantly associated with hemorrhagic manifestations. TM, PS and PAI were related to prognosis. CONCLUSION: There existed the consumption of platelets as well as the activation of coagulant, anticoagulant and fibrinolytic systems in AL, which was greatly improved after CR.

Acute Disease↗

[Production and testing of biologically active fibers with hemostatic properties].

The authors presented the method of laboratory elaboration of biologically active surgical sutures with hemostatic and antiiinflammatory properties as developed by the Leningrad S. M. Kirov Memorial Institute of Textile and Light Industry. With the carboxyl groups of the KFM type fibres (addition product of polyvinylfurfural with maleic acid) adrenalin sorbed from aqueous suspensions was linked by ionic bond. The sutures were tested in the A. I. Bakuliev Memorial Institute of Cardiovascular Surgery. Due to the slow release of adrenalin the sutures exert hemostatic effect. In the in vitro tests there were determined the serum calcium level, hemolysis of red blood cells, pH, prothrombin time and plasma protein content changes. The authors showed also preliminary data on the sterilization of the fibres.

Blood Vessels↗

Changes in hemostatic parameters in fish following rapid decompression.

The effect of rapid decompression on the stress-accelerated blood coagulation system of male and fingerling coho salmon (Oncorhynchus kisutch) was examined after simulated 100- and 200-fsw dives. Blood samples taken either through a dorsal aorta cannula or from a severed caudal peduncle were analyzed for total plasma protein and fibrinogen concentrations, prothrombin times (PT), and partial thromboplastin times (PTT). The effect of mild decompression (100-fsw) on the hemostatic mechanism of both adult and fingerling coho salmon indicated an alternating fibrinogen concentration, declining from normal levels 1 min after decompression, followed by an increase 10 to 15 min later with an eventual loss of fibrinogen to one half the original level an hour after decompression. Partial thromboplastin times were found to increase 10 to 15 min after decompression occurred. Prothrombin times showed an increase 1 hour after decompression in adult salmon, whereas in fingerlings, prothrombin times increased almost immediately from normal levels. The effect of severe decompression (200-fsw) showed similar trends, but at an accelerated rate. It was concluded that both mild and severe decompression activates the hemostatic mechanism of fish which may eventually result in consumption coagulopathy at a greater rate than reported for experimental mammals.

Age Factors↗

The effects of postmenopausal hormone replacement therapy on hemostatic variables: a meta-analysis of 46 studies.

The aim of the study was to summarize and reanalyze all available data from the literature to study the overall effect of postmenopausal hormone replacement therapy (HRT) and its various forms on hemostatic variables. Studies were identified from literature searches by Medline and Index Medicus, review articles and personal communications. Reference lists of all articles were checked to find additional studies. Principal investigators were contacted and asked to provide additional data if required. Data were collected separately for each factor of the hemostatic system. Studies written in any language were included. Each collection of studies was analyzed using standard methods for meta-analysis. A total of 76 arms of 48 studies were eligible for analysis. This included 6,119 women using HRT and 24,974 non-users. The age of investigated women was 40-68 years. HRT was associated with significantly decreased levels of fibrinogen, factor VIII, antithrombin III, and proteins C and S, but significantly increased plasminogen levels. HRT with estrogen alone or in combination with progestins, oral vs. transdermal regimens, different estrogen preparations and various progestins induced significantly different changes in many cases. In conclusion, HRT was associated with changes that could explain the increased rate of venous thrombotic events, and also with some changes that could account for beneficial vascular effects. Surprisingly, the addition of progestins induced favorable changes in many cases. Also, transdermal use was associated with more beneficial effects than oral regimens in some cases.

Adult↗