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PubMed2004

Management of bleeding in patients with advanced cancer.

Bleeding occurs in up to 10% of patients with advanced cancer. It can present in many different ways. This article provides a qualitative review of treatment options available to manage visible bleeding. Local modalities, such as hemostatic agents and dressings, radiotherapy, endoscopic ligation and coagulation, and transcutaneous arterial embolization, are reviewed in the context of advanced cancer, as are systemic treatments such as vitamin K, vasopressin/desmopressin, octreotide/somatostatin, antifibrinolytic agents (tranexamic acid and aminocaproic acid), and blood products. Considerations at the end of life are described.

Antifibrinolytic Agents↗
PubMed2004

Benefits and risks of pharmacological agents used for the treatment of menorrhagia.

Menorrhagia affects the lives of many women. The assessment of menstrual flow is highly subjective and gauging the severity of the condition by objective assessment of menstrual blood loss is impractical. In treating menorrhagia, the primary aim should be to improve quality of life. Women are willing to undergo quite invasive treatment in order to achieve this. Drug therapy is the initial treatment of choice and the only option for those who wish to preserve their reproductive function. Despite the availability of a number of drugs, there is a general lack of an evidence-based approach, marked variation in practice and continuing uncertainty regarding the most appropriate therapy. Adverse effects and problems with compliance also undermine the success of medical treatment. This article reviews the available literature to compare the efficacy and tolerability of different medical treatments for menorrhagia. Tranexamic acid and mefenamic acid are among the most effective first-line drugs used to treat menorrhagia. Despite being used extensively in the past, oral luteal phase norethisterone is probably one of the least effective agents. Women requiring contraception have a choice of the combined oral contraceptive pill, levonorgestrel-releasing intrauterine system (LNG-IUS) or long-acting progestogens. Danazol, gestrinone and gonadotropin-releasing hormone analogues are all effective in terms of reducing menstrual blood loss but adverse effects and costs limit their long-term use. They have a role as second-line drugs for a short period of time in women awaiting surgery. While current evidence suggests that the LNG-IUS is an effective treatment, further evaluation, including long-term follow up, is awaited. Meanwhile, the quest continues for the ideal form of medical treatment for menorrhagia--one that is effective, affordable and acceptable.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1993

Current management of bleeding peptic ulcer. A review.

In the United Kingdom, acute bleeding from peptic ulcer is estimated to account for 25 admissions to hospital per 100,000 population annually. Overall mortality has been reported at around 10%. Accurate initial assessment for the identification of high risk groups, prompt resuscitation, close monitoring and timely intervention for rebleeding improves survival. In patients not responding to initial resuscitation and those who rebleed, emergency endoscopy identifies the source of bleeding in the majority and is essential to enable endoscopic therapy. Injection of a vasoconstrictor and/or sclerosant into a visible or bleeding vessel, or thermal coagulation, reduces the incidence of rebleeding and probably decreases mortality. In general terms, 'early' surgical intervention is indicated for those aged over 60 years in whom bleeding recurs or continues despite endoscopic measures. The low mortality (< 5%) reported from specialist units and units adhering to strict protocols of management should become the norm. The use of antacids, histamine H2-receptor antagonists or omeprazole does not influence mortality or the incidence of early rebleeding in patients with acute haemorrhage from peptic ulcer. Although not used routinely, tranexamic acid has been shown to have significant benefit.

Anti-Ulcer Agents↗
PubMed1997

A practical guide to the management of bleeding ulcers.

In patients with acute haemorrhage from peptic ulcers, emergency endoscopy should be performed as soon as safely possible after resuscitation to detect the bleeding lesion, to define stigmata of recent haemorrhage, and to perform endoscopic therapy when required. Subsequent management will be determined by the results of diagnostic endoscopy. Ulcers with a clean base or with flat blood spots will not require endoscopic therapy: the patient can be discharged early after resuscitation and the institution of treatment to promote ulcer healing. Ulcers in which endoscopy discloses active arterial bleeding or a nonbleeding visible vessel should be treated, as these signs denote a high risk of an unfavourable outcome, and the efficacy of endoscopic therapy has been demonstrated when these signs are identified. In keeping with the available data, antisecretory therapy, vasoconstrictor drugs and tranexamic acid cannot be recommended as treatment for an acute ulcer bleeding episode. On the other hand, it has been shown in controlled trials that endoscopic therapy significantly reduces the incidence of further bleeding and the requirement for emergency surgery in patients with ulcers with active arterial bleeding or a nonbleeding visible vessel. Meta-analyses of these studies have also shown a significant decrease in mortality with endoscopic therapy. Among the available endoscopic methods for haemostasis, injection therapy is a valid choice since its efficacy has been similar to that of thermal methods in comparative studies, while its simplicity, tolerability and low cost are great advantages. A second endoscopic treatment can be attempted in patients with further haemorrhage after the initial endoscopic therapy, and permanent haemostasis can be achieved in half of these cases. However, the decision to perform this second endoscopic treatment should be taken individually, as the routine use of such a procedure could increase mortality by delaying surgery.

Humans↗
PubMed2002

Pharmacological strategies to decrease transfusion requirements in patients undergoing surgery.

Surgical procedures are inevitably associated with bleeding. The amount of blood loss may vary widely between different surgical procedures and depends on surgical as well as non-surgical factors. Whereas adequate surgical haemostasis may suffice in most patients, pro-haemostatic pharmacological agents may be of additional benefit in patients with (diffuse) surgical bleeding or in patients with a specific underlying haemostatic defect. In general, surgical haemostasis and pharmacological therapies can be complementary in controlling blood loss. The use of pharmacological therapies to reduce blood loss and blood transfusions in surgery has historically been restricted to a few drugs. Antifibrinolytic agents (aprotinin, tranexamic acid and aminocaproic acid) have the best evidence supporting their use, especially in cardiac surgery, liver transplantation and some orthopaedic surgical procedures. Meta-analyses of randomised, controlled trials in cardiac patients have suggested a slight benefit of aprotinin, compared with the other antifibrinolytics. Desmopressin is the treatment of choice in patients with mild haemophilia A and von Willebrand disease. It has also been shown to be effective in patients undergoing cardiac surgery who received aspirin up to the time of operation. However, overall evidence does not support a beneficial effect of desmopressin in patients without pre-existing coagulopathy undergoing elective surgical procedures. Topical agents, such as fibrin sealants have been successfully used in a variety of surgical procedures. However, only very few controlled clinical trials have been performed and scientific evidence supporting their use is still limited. Novel drugs, like recombinant factor VIIa (eptacog alfa), are currently under clinical investigation. Recombinant factor VIIa has been introduced for the treatment of haemophilia patients with inhibitors, either in surgical or non-surgical situations. Preliminary data indicate that it may also be effective in surgical patients without pre-existing coagulation abnormalities. More clinical trials are warranted before definitive conclusions can be drawn about the safety and the exact role of this new drug in surgical patients. Only adequately powered and properly designed randomised, clinical trials will allow us to define the most effective and the safest pharmacological therapies for reducing blood loss and transfusion requirements in surgical patients. Future trials should also consider cost-effectiveness because of considerable differences in the costs of the available pro-haemostatic pharmacological agents.

Administration, Topical↗
PubMed1986

Conization by carbon dioxide laser or cold knife in the treatment of cervical intra-epithelial neoplasia.

In a randomized trial concerning 123 women with CIN, 59 were treated with laser conization under colposcope without further hemostatic remedy and 64 with cold knife conization guided by Schiller's iodine dyeing supported by side sutures, vaginal packing and postoperative oral administration of tranexam acid. Follow-up with colposcopy and cytology was done 3 and 12 weeks post-conization and then every 6 months. The average follow-up period was 36 months (28-48). Peroperative bleeding was rather less pronounced in the laser group. Postoperatively, however, bleeding requiring treatment was significantly less common in the laser group (5%) than in the cold knife group (17%). The recurrence rate of CIN was 7% in the laser group and 10% in the knife group. Stenosis of the cervical canal developed in 7% of the patients in the laser group and in 3.5% in the knife group. After 12 weeks the squamocolumnar junction was visible in its full extent in 66% of the laser treated patients compared with 38% of the cold knife treated patients. It is concluded that laser conization is a safe procedure even without hemostatic procedures other than the coagulation abilities of the laser beam itself, as used in this work.

Adult↗
PubMed1986

Prevention of recurrent ulcer bleeding, a multicentre study of the effect of ranitidine and trimipramine over one year.

Short term studies of the prevention of bleedings from peptic ulcers and erosions have been reported by a number of authors following treatment with antacids (1), H2-receptor blockers, cimetidine (2-15), a combination of cimetidine and tranexamic acid (16), cimetidine and somatostatin (17), cimetidine and sucralfate or secretion (18, 19, 20), cimetidine compared to antacid (21), and cimetidine compared to antacid and pirenzepine (22). The H2-blocker rantitidine has been compared to placebo (24, 25, 26). An uncontrolled study has been performed using proglumide (27), a controlled study with vasopressin (28) and with secretin versus somatostatin (28). In the studies with H2-receptor antagonists conflicting results have been obtained. No report has been published concerning the effect over more than a few days or weeks.

Dibenzazepines↗
PubMed1975

Antimicrobial activity of human seminal fluid.

The antibacterial, antifungal and antimycoplasmal activity of human semen was studied. Gram-positive aerobic bacterial species i.e. staphylococci, but not gram-negative aerobic bacteria, were inhibited by seminal fluid in vitro. Neither were anaerobic gram-positive or gram-negative bacteria, nor Candida or Mycoplasma inhibited. Semen of healthy males had a higher antibacterial effect on S. albus than that of patients with symptoms of chronic prostatitis. There was a positive correlation between the antibacterial power of the semen of the patients studied and their content of zinc and magnesium, while no correlation was found with fructose and lysozyme or the number of spermatozoa in any of the groups. A positive correlation was found between the antibacterial capacity and the volume of the ejaculate in the patients but not among the controls. The antibacterial substance(s) was dialysable, ether-extractable, resistant to boiling and partly to storage at room temperature. The addition of EDTA, tranexamic acid and ammonium reineckate to semen did not influence the antibacterial effect, which was, however, slightly inhibited by sodium polyanethol sulphonate. The nature of possible antibacterial substances in semen is discussed.

Antibiosis↗
PubMed1985

Transurethral versus transvesical prostatectomy. Physiological strain.

The present randomized study evaluated the physiological strain in transurethral (TURP) versus transvesical (TVP) prostatectomy in 75 patients with clinically benign, medium-sized prostatic enlargement. In both groups 5 patients had coincidental prostatic carcinoma. During TURP a suprapubic trocar was inserted for irrigation with 1.5% glycine. Antibiotics were given to patients with preoperative urinary tract infection and postoperatively tranexamic acid was administered to all patients. Coexisting diseases which might increase the operative risk were equally present in TURP and TVP patients. No patient died in connection with the operative procedures. Median duration of anaesthesia for TVP was 95 min and for TURP 60 min (p less than 0.001). Almost identical operative blood loss was seen in the two groups. However, more blood transfusion were given to TVP patients. Following discharge, more episodes of bleeding were registered in the TURP group, but no significant difference was observed in number of secondary operations for bleeding. In the TVP group, more patients had pulmonary complications, elevated rectal temperature as well as antibiotic treatment and 34% of these patients developed wound infection. Secondary operations before discharge were also more frequently undertaken in TVP patients. No differences between the two groups were seen pre- or postoperatively with respect to electrolyte, protein, creatinine and haemoglobin values. In the patients with incidental prostatic carcinoma a TURP was the most gentle procedure. With respect to physiological strain a TURP is clearly to be preferred over a TVP for obstructive clinically benign, medium-sized prostatic hyperplasia.

Aged↗
PubMed1989

Kinetics of pulmonary platelet deposition and clearance during thrombin-induced microembolism in rabbits.

Using 111In-labeled autologous platelets, we studied the kinetics of pulmonary platelet deposition and clearance in relation to hemodynamic and structural events during thrombin-induced pulmonary microembolism in rabbits. Autologous platelets were radiolabeled and returned to animals prior to infusion of thrombin (100 units/kg over 15 min) (n = 20) or saline (n = 6). All animals were pretreated with tranexamic acid, an inhibitor of fibrinolysis. Thrombin-treated animals manifested progressive increases in mean pulmonary platelet activity, reaching a maximum of 38% above baseline (p less than .0001), whereas no change was observed in saline-treated controls. Animals that died during, or immediately following, thrombin infusion manifested significantly greater increases in pulmonary platelet uptake (mean 1.55 +/- 0.47 times baseline), compared to surviving animals (1.14 +/- 0.16; p less than .05 survivors vs. nonsurvivors). In surviving animals, following cessation of thrombin, pulmonary platelet activity cleared gradually, with a half-time of approximately 12 min. Thrombin reduced circulating platelet counts (p less than .001), increased mean pulmonary artery pressure (13 +/- 3 mm Hg to 18 +/- 6 mm Hg; p less than .0001), and reduced mean systemic arterial pressure (55 +/- 10 mm Hg to 44 +/- 7 mm Hg; p less than .001). The time courses of these events approximated that of thrombin-induced pulmonary platelet uptake. Furthermore, the increase in pulmonary artery pressure occurred predominantly in the group of animals in which the increase in pulmonary radiolabeled platelet activity exceeded the median value of 20%. Postmortem histology showed extensive pulmonary thrombus extending from small arterial to capillary levels in animals that died during, or immediately following, thrombin infusion, but not in surviving animals. Our findings suggest that platelet aggregation plays an important role in the pathogenesis of hemodynamic change following thrombin-induced pulmonary embolization.

Animals↗
PubMed1986

Prognosis in subarachnoid hemorrhage of unknown etiology.

Thirty-two patients with subarachnoid hemorrhage of unknown etiology were followed for periods from 1 to 6 1/2 years. Two more patients had normal initial angiograms, but were excluded when repeat angiography revealed an aneurysm. The mortality rate in this series was 6%. There was one possible early and no late episode of rebleeding. One patient developed epilepsy. Five patients developed communicating hydrocephalus and underwent a shunting procedure. A complete recovery was observed in 12 patients. An additional eight had minimal disability, seven were more severely disabled, and three patients were totally disabled. Antifibrinolytic treatment (tranexamic acid) was given in a nonstandardized regimen to 14 patients who showed a poorer result than did the 18 untreated patients.

Adolescent↗
PubMed1988

Meningiomas and hemorrhagic diathesis.

The physical act of operating on 13 patients with meningiomas was studied for its effect on the fibrinolytic system. Fibrinolytic abnormalities, mainly due to an increase of plasma fibrinolytic activity, appeared in three patients prior to, during, or after surgery. These patients demonstrated hemorrhagic diathesis in the operative wounds which was associated with a consumptive coagulopathy, namely, an increase of fibrin/fibrinogen degradation product concentration and a decrease of fibrinogen concentration in plasma. Antiplasmin agents (gabexate and tranexamic acid) were effective in minimizing loss of blood during and after the operation. Abnormal hyperfibrinolysis seems to play a role in hemostatic difficulties in patients undergoing surgery for meningioma.

Adult↗
PubMed1999

Women and inherited bleeding disorders: menstrual issues.

Von Willebrand, who described a bleeder family from Aland in 1926 in whom the index patient died at the fourth menses, stated, "the trait seems to be seen among women." Menorrhagia is defined objectively as a menstrual blood loss of at least 80 mL. However, even though 5% of women aged 30 to 49 years consult their general practitioner and 12% of gynecologic referrals are for menorrhagia, the diagnosis is difficult. A pictorial bleeding assessment chart (PBAC) has a specificity and sensitivity of more than 80%, with a score of > or = 100 being equivalent to more than 80 mL of blood loss. Using this chart to screen 150 women with menorrhagia who attended a gynecology clinic, an inherited bleeding disorder was diagnosed in 17%. Menorrhagia with onset at the menarche was predictive of an inherited bleeding disorder in 65% of von Willebrand's disease (vWD) and 67% of factor XI (FXI)-deficient patients. A retrospective survey in patients with inherited bleeding disorders using the PBAC showed menorrhagia in 74% of patients with vWD, 57% of carriers of hemophilia A or B, and 59% of FXI-deficient patients, compared with 29% of control individuals. Menorrhagia was the most common symptom in 60% of patients with FVII deficiency studied. Menorrhagia in women with bleeding disorders can be controlled with tranexamic acid with good effect. More recently, a desmopressin acetate (DDAVP) spray has been shown to achieve good FVIII and von Willebrand factor (vWF) levels and is efficacious for women with these deficiencies. The oral contraceptive pill may be useful. Since bleeding disorders are found in a substantial number of women with menorrhagia, it is important that such patients are investigated for these disorders before invasive procedures are done; hysteroscopy and hysterectomy in these patients are associated with a high rate of postoperative bleeding.

Family Health↗
PubMed1999

Bleeding tendency: a practical approach in dentistry.

The dental profession faces the problems of exaggerated bleeding on a daily basis. The hemostatic, as well as the fibrinolytic processes are better understood today, and the dentist should be familiar with them. The activation of coagulation factors and their clinical expression in the circulation are both described. The most frequently used blood coagulation tests are explained. Antithrombotic medications are frequently used and their implications in dentistry are accentuated. Protocols of prevention and treatment of exaggerated bleeding following dental procedures are included. Among them, the transfusion of clotting factors and the administration of antifibrinolytic medications (tranexamic acid) are recommended for both congenital or acquired bleeding tendencies.

Anticoagulants↗
PubMed2000

[A homozygous quantitative defect of alpha 2-antiplasmin in a family from central Slovakia].

Alpha2-antiplasmin is the main inhibitor of plasma fibrinolytic system. An inborn defect of alpha2-antiplasmin was first described by Koie et al. in 1978 in connection with severe haemorrhage syndrome. The authors present a case report of 45 years old woman living in middle Slovakia with severe haemorrhagic syndrome started in childhood (epistaxis, skin and muscle hematomas, appendectomy with 6 weeks recovery, hardly manageable haemorrhage after teeth extractions, menorrhage, metrorrhage). Laboratory tests were negative for platelet function defects and coagulation system defects. Low level of alpha2-antiplasmin activity (10%) was detected with use of synthetic chromogenic substrate method and low amount (2%) with ELISA method. In asymptomatic daughter was decreased level of alpha2-antiplasmin (activity 51%, quantity 32%) detected. On the basis of patient history, laboratory investigations and comparison with published cases the haemorrhagic syndrome is considered to be an inborn homozygous quantitative defect of alpha2-antiplasmin. Detection of the defect in further haemorrhagic and risk situations (including laparotomy, multiple teeth extractions, obstetric surgery) led to following therapeutic measures: careful local care [by procedures], tranexamic acid in sufficient dose [4 g/day in continual i.v. infusion, or 4 x 1 g in 1/hour infusions, 4 x 1 g perorally], in sufficient duration [14 days by procedures]. Therapeutic approach after detection of the defect is efficient. (Tab. 2, Ref. 13.)

Female↗
PubMed1979

Cold activation of complement and kinin.

Differences between serum and plasma complement, which now is called as the cold activation of complement, was investigated in relation with the phenomenon reported as the cold promoted activation of factor VII, to which kallikrein and Hageman factor are known to participate. Despite the presence of several similarities in these two phenomena, it is concluded that the cold activation of complement is not related to the coagulation nor the kinin system. Evidence that tranexamic acid, a potent antiplasmin compound, provided an inhibitory effect on the cold activation of complement, suggested that the phenomenon could not be explained by a single mechanism, and plasmin might be involved in the phenomenon in a limited case.

Cold Temperature↗
PubMedDate not supplied

Oral surgery in patients undergoing oral anticoagulant therapy.

UNLABELLED: There is an evident need for procedural protocol for oral surgery patients who undergo oral anticoagulant treatment (OAT) because of: 1) the possible severity of complications and 2) the growing demand for OAT, which in some cases may be as much as 8% of the oral surgery patients that are referred to the hospital from primary care centers. In this study, the authors define the parameters for creating a proto- col applicable to this group of patients. The conclusion is that it is not necessary to suspend OAT before surgery; rather, these procedures should be performed under multidisciplinary medical control. OBJECTIVE: The authors demonstrate that it is possible to perform oral surgery on OAT patients, without having to sus- pend treatment beforehand. STUDY DESIGN: A longitudinal study was performed in OAT patients that required some type of oral surgical procedures. After an INR control, the patient underwent surgery and afterwards the patient was given tranexamic acid as a mouth rinse. Postoperative hemorrhage was classified as slight when it lasted less than 5 minutes, moderate when it lasted longer than five minutes, and severe when it required blood transfusion. RESULTS: The study was performed over a 5-year period (1996-2000), by the maxillofacial surgery department. In that time period, 125 patients with OAT were treated; 90 of them were males and 35 were females. Tooth extraction was per- formed in 229 sessions and a total of 367 teeth were extracted, with an average of 1.6% per session. With regards to postoperative hemorrahage, it was slight in 210 cases (91.7%), moderate in 18 (7.9%) and severe only in one case (0.4%). All the variables were compared and no statistically significant differences were found. CONCLUSIONS: We believe that OAT should not be suspended before oral surgery, but it surgery should be performed under multidisciplinary control-especially in the case of the elderly (over 65) or with those patients that have other concomitant illnesses such as renal insufficiency or anemia or other medical treatments.

Administration, Oral↗
PubMed1995

[Aspirin, a risk factor for bleeding at dental procedures].

Aspirin is widely used as an antithrombotic drug in the prevention of cardiovascular events. It causes a usually mild bleeding tendency. When used before dental or surgical procedures, aspirin increases the risk of bleeding, contrary to the postoperative administration of aspirin, which has not been associated with increased risk of bleeding. To estimate the risk of bleeding, a history on bleeding tendency and information on the recent use of aspirin is worthwhile. It is recommended to delay procedures for at least one week after the last ingestion of aspirin, if possible. In case of urgent surgical procedures or in patients who suffer from serious bleeding due to the use of aspirin, a single preoperative transfusion of a suspension of platelets is usually sufficient to antagonize the effects of aspirin. Tranexamic acid can be given alternatively. The preferred policy depends on the type of the procedure to be performed, or the nature of the bleeding.

Antifibrinolytic Agents↗