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PubMed1991

[Therapy-refractory primary intestinal lymphangiectasis].

A 20-year-old man with severe physical weakness (from which he soon recovered spontaneously) was found to have hypoproteinaemia and lymphocytopenia (768/microliters). Ten years later, after having been free of symptoms in the meantime, oedema, ascites and abdominal pain occurred, associated with loss of physical capacity. Enteric loss of protein (alpha 1-antitrypsin clearance increased about thirtyfold) with a total serum protein concentration of only 3.7 g/dl, as well as histological evidence of lymphangiectasia of the small and large intestines provided the diagnosis of primary intestinal lymphangiectasia. In the course of the disease cholelithiasis and (after treatment with tranexamic acid) thrombosis of the axillary vein occurred. No treatment has been of any avail and the patient has been unable to work for three years.

Adult↗
PubMedDate not supplied

Gastric angiodysplasia in a child with Bernard-Soulier syndrome: efficacy of octreotide in long-term management.

Gastrointestinal angiodysplasia in association with Bernard-Soulier syndrome has been previously described in adults. The authors report on a 14year-old boy presenting with massive upper gastrointestinal bleeding due to a large gastric angiodysplasia, in whom medical history and laboratory investigations were consistent with Bernard-Soulier syndrome. The vascular lesion was so widespread that surgical or endoscopic therapy was not considered. Therefore, treatment with octreotide, a somatostatin analog, was commenced, following a short course of tranexamic acid and proton pump inhibitor. During the 16-month follow-up with octreotide therapy, no occult or gross bleeding occurred. This case illustrates the utility of using octreotide for the long-term treatment of children with bleeding disorders and angiodysplasia.

Adolescent↗
PubMed1989

Activation of pro-urokinase and plasminogen on human sarcoma cells: a proteolytic system with surface-bound reactants.

Human HT-1080 fibrosarcoma cells produce urokinase-type plasminogen activator (u-PA) and type 1 plasminogen activator inhibitor (PAI-1). We found that after incubation of monolayer cultures with purified native human plasminogen in serum-containing medium, bound plasmin activity could be eluted from the cells with tranexamic acid, an analogue of lysine. The bound plasmin was the result of plasminogen activation on the cell surface; plasmin activity was not taken up onto cells after deliberate addition of plasmin to the serum-containing medium. The cell surface plasmin formation was inhibited by an anticatalytic monoclonal antibody to u-PA, indicating that this enzyme was responsible for the activation. Preincubation of the cells with diisopropyl fluorophosphate-inhibited u-PA led to a decrease in surface-bound plasmin, indicating that a large part, if not all, of the cell surface plasminogen activation was catalyzed by surface-bound u-PA. In the absence of plasminogen, most of the cell surface u-PA was present in its single-chain proenzyme form, while addition of plasminogen led to formation of cell-bound two-chain u-PA. The latter reaction was catalyzed by cell-bound plasmin. Cell-bound u-PA was accessible to inhibition by endogenous PAI-1 and by added PAI-2, while the cell-bound plasmin was inaccessible to serum inhibitors, but accessible to added aprotinin and an anticatalytic monoclonal antibody. A model for cell surface plasminogen activation is proposed in which plasminogen binding to cells from serum medium is followed by plasminogen activation by trace amounts of bound active u-PA, to form bound plasmin, which in turn serves to produce more active u-PA from bound pro-u-PA. This exponential process is subject to regulation by endogenous PAI-1 and limited to the pericellular space.

Cell Line↗
PubMed1997

Bone matrix degradation by the plasminogen activation system. Possible mechanism of bone destruction in arthritis.

The observed increase in urokinase-type plasminogen activator (u-PA) and its receptor (u-PAR) in synovial tissue of patients with rheumatoid arthritis (RA) suggests pathophysiological involvement of the plasminogen activation (PA) system in inflammatory joint disease. In the present study, we investigated the capacity of the PA system to degrade non-mineralized and mineralized bone-like matrix in vitro as a model for bone destruction. Transfected mouse LB6 cell lines, that expressed either human u-PA or u-PAR, were cultured separately and simultaneously on radiolabelled bone matrix in the presence of plasminogen. Osteoblast-like murine calvarial MC3T3-E1 cells were used to produce a well-characterized, highly organized bone-like matrix, that could be mineralized in the presence of beta-glycerol phosphate. Bone matrix degradation was followed by the release of radioactivity in the culture medium. u-PA-producing cells, in contrast to u-PAR-producing cells, degraded both non-mineralized and mineralized bone matrix. This effect could be inhibited by anti-u-PA antibodies, as well as by tranexamic acid and by aprotinin, indicating that the degrading activity is u-PA mediated and plasmin dependent. Co-cultivation of a small portion of u-PA-producing cells with u-PAR-expressing cells resulted in a marked increase in degradation activity. Reduction of this potentiating effect by suramin or the amino-terminal fragment of u-PA, both competitive inhibitors of u-PA receptor binding, shows that this synergistic effect is due to binding of u-PA to u-PAR. u-PAR must be cell associated, as binding of u-PA to a soluble u-PAR prevented this enhancement. The capability of the PA system to degrade bone matrix in vitro, and the previously demonstrated increased expression of u-PA and u-PAR in synovial tissue of patients with RA, further support a role for the PA system in the development of bone erosions.

3T3 Cells↗
PubMed2004

Evaluation of early detection and management of disseminated intravascular coagulation among Alexandria University pediatric intensive care patients.

This prospective study over 24 months aimed to evaluate the outcome of early management of disseminated intravascular coagulation (DIC) among high-risk patients (n = 50) admitted to a pediatric intensive care unit (PICU). It also included all cases presenting with overt DIC (OD) concomitantly (n = 30). The high-risk group (pre-DIC) was subdivided, according to their D-dimer assay, into negative (n = 14) and positive (n = 36) D-dimer groups. All three groups were evaluated, on admission, for their prothrombin time (PT), activated partial thromboplastin time (APTT), plasma fibrinogen level (Fi), fibrinogen degradation products (FDP), platelet count, and presence/absence of schistocytes in peripheral blood. The combination of D-dimer and FDP assay showed the best correlation for early pre-DIC diagnosis (r = 0.9048). FDP assay was the best parameter for followup of progress of DIC condition in the PICU. The lowest mortality was among negative D-dimer, followed by positive D-dimer and OD groups (28.6 per cent, 77.8 per cent, and 93.3 per cent, respectively). Among the positive D-dimer group the lowest mortality was encountered in the subgroup treated with plasma, heparin and tranexamic acid (33 per cent) while those treated with non-specific therapy, plasma only, or plasma and heparin showed higher mortality (100 per cent, 80 per cent, and 100 per cent, respectively). The deceased subgroup, among positive D-dimer cases showed a significantly higher number of patients presenting with multiple organ failure on admission compared with the discharged group. In summary, early diagnosis and proper management of pre-DIC, before overt bleeding, in high-risk patients admitted to a PICU using combined D-dimer and FDP assays had a positive impact on their prognosis.

Blood Coagulation Tests↗
PubMed1991

Calcium-dependent and calcium-independent gelatinolytic proteinase activities of the rat ventral prostate and its secretion: characterization and effect of castration and testosterone treatment.

Calcium-dependent and calcium-independent proteinase activities were detected in extracts of rat ventral prostate and its secretion by use of gelatin-containing SDS-PAGE zymography. Ca(2+)-independent proteinase activities of 22, 26, and 73-79 kDa and Ca(2+)-dependent activities of 58, 63, and 66 kDa were found in the adult gland. The 26- (most intense activity of gland) and 22-kDa activities were present in secretion and were not expressed in the undifferentiated gland of the 10-day-old animal. The Ca(2+)-dependent activities were also present in the secretion, where the 63-kDa form was more prominently expressed than the 58- and 66-kDa bands. The Ca(2+)-dependent and Ca(2+)-independent proteinase activities both responded to a broad range of pH values in the incubation media. The 73-79-kDa Ca(2+)-independent activities were sensitive to benzamidine and the Ca(2+)-dependent activities were inhibited by EDTA and EGTA. Both Ca(2+)-dependent and Ca(2+)-independent proteinase activities responded to androgenic manipulations. Castration was followed by the appearance of a 35-kDa Ca(2+)-independent proteinase (at 2 days) and a 43-kDa Ca(2+)-dependent proteinase (at 4 days). In the Ca(2+)-independent proteinase group, the 73-79-kDa activities were increased somewhat and the 22- and 26-kDa activities decreased after castration. The Ca(2+)-dependent proteinases of 58, 63, and 66 kDa increased in activity with castration, but activity of the 58-kDa form decreased again at 7 days after castration. Treatment of animals upon castration for 4 days with hydrocortisone prevented these changes in proteinase activities whereas treatment with actinomycin D or tranexamic acid did not. Testosterone propionate replacement therapy of rats castrated for 16 days stimulated the activities of the 22- and 26-kDa and 73-79-kDa Ca(2+)-independent and the 58- and 63-kDa Ca(2+)-dependent proteinases with 4 days of therapy. The activities of the 35-kDa Ca(2+)-independent and the 43-kDa Ca(2+)-dependent proteinases were repressed with 8 days of testosterone treatment. Thus, individual proteinases show differential changes in activity during development and in response to androgenic manipulation: this suggests that in addition to proteinases which are secreted, others may be involved in intracellular functions or in mediating tissue organization changes.

Animals↗
PubMed2002

von Willebrand's disease: an important cause of dysfunctional uterine bleeding.

We assessed the prevalence of von Willebrand's disease (VWD) in patients with objectively confirmed dysfunctional uterine bleeding. A case-control study was designed to include 38 patients with objectively confirmed dysfunctional uterine bleeding and 38 age-matched controls with normal menstrual blood loss (MBL). Menorrhagia was defined as a mean MBL of greater than 80 ml on three consecutive menses as measured by the alkali haematin method. von Willebrand factor antigen, von Willebrand factor activity (VWF:Ac) and factor VIII:C were measured on three serial venous blood samples 1 week apart. VWD was diagnosed in five of 38 (13%) patients with menorrhagia and one of 38 (2.6%) patients with normal menstrual blood loss. The mean VWF:Ac value was significantly reduced in patients with menorrhagia (mean +/- standard deviation, 84.5 +/- 26.7 IU/dl versus 103.9 +/- 34.5 IU/dl; P < 0.01) and this effect persisted after exclusion of patients diagnosed with VWD. Failure to investigate patients for VWD will limit the potential benefits of medical therapies such as tranexamic acid or nasal desmopressin [1-desamino-8-D-arginine vasopressin, (DDAVP)] and, in addition, will lead to an increased risk associated with surgical intervention in patients with undiagnosed VWD.

Adult↗
PubMed2003

Safety of dental extraction among consecutive patients on oral anticoagulant treatment managed using a specific dental management protocol.

We found no prospective studies on dental extraction in anticoagulated patients in the literature, even though most authors suggest that there is no need to change anticoagulant treatment and to utilize a local haemostatic measure after extraction. In the present study, we have verified the incidence of bleeding complications after dental extraction in a group of 250 consecutive anticoagulated patients. Two hundred and fifty non-anticoagulated subjects requiring dental extraction represented the control group. In all patients, anticoagulant treatment was not changed (International Normalized Ratio, 1.8-4) and local haemostatic measures (fibrin sponge, silk suture and a gauze saturated with tranexamic acid) were used. All procedures were performed in an outpatient clinic setting. We registered four bleeding complications in the group of anticoagulated patients and three in the control group. The difference of bleeding complications in the two groups was not statistically different (relative risk, 1.14; 95% confidence interval, 0.29-6.04; P = 0.7). None of the post-operative late bleeding required hospitalization and/or blood transfusions, and further local measures were sufficient to stop the bleeding. The protocol proposed in the present study makes dental extractions in anticoagulated patients possible on an outpatient basis with a cost reduction for the community and minor discomfort for the patients.

Administration, Oral↗
PubMed2003

Recombinant activated factor VII combined with local measures in preventing bleeding from invasive dental procedures in patients with Glanzmann thrombasthenia.

Recombinant activated factor VII (rFVIIa), combined with local measures of fibrin glue and a celluloid splint, preventing bleeding from four invasive dental procedures is reported. A single dose of 180-200 micro g/kg was successfully used in three surgical removals of impacted teeth. Four doses of rFVIIa were required in another full mouth treatment of extraction, pulpotomy, filling and the stainless steel crowning of 13 teeth. The repeated dose of rFVIIa was given whenever the bleeding complication was visualized. It is cost-effective for preventing external bleeding. Additionally, an oral rinsing solution of tranexamic acid (25 mg/kg) was given three times a day for 7 days. In conclusion, rFVIIa has been shown to be an effective alternative to platelet concentrate in patients with Glanzmann thrombasthenia.

Adult↗
PubMed1996

Role of granulocyte elastase in the formation of hemorrhagic shock-induced gastric mucosal lesions in the rat.

OBJECTIVE: To investigate the mechanism by which activated leukocytes induce gastric mucosal lesions, we examined whether granulocyte elastase is involved in the formation of such lesions in a rat model of hemorrhagic shock. DESIGN: Prospective, randomized, controlled study. SETTING: Research laboratory at a university medical center. SUBJECTS: Male Wistar rats, weighing 220 to 280 g. INTERVENTIONS: Animals were subjected to hemorrhagic shock by phlebotomy. ONO-5046, a granulocyte elastase inhibitor (300 mg/kg ip), was administered 30 mins before or after phlebotomy. The effects of antithrombotic substances and tranexamic acid on hemorrhagic shock-induced gastric mucosal lesions also were examined. The effects of granulocyte elastase on the thrombomodulin activity and 35S-glycosaminoglycan content of endothelial cells were examined, using cultured human umbilical vein endothelial cells.

Animals↗
PubMed1995

Advances in surgical care of infants and children with congenital heart disease.

Recent important technical developments in the field of surgery for congenital heart disease have included the Ross pulmonary autograft replacement of the aortic valve, video-assisted thoracoscopic surgery, and the double-switch and switch-Rastelli procedure for congenitally corrected transposition. Although the growth potential of the pulmonary autograft has been confirmed, an important incidence of late aortic regurgitation has been noted. Expanding indications for video-assisted thoracoscopic surgery have been described, including division of the vascular ring. Late hemodynamic assessment after the double-switch or switch-Rastelli procedure will encourage increased application of this repair. Both clinical and laboratory studies have focused on neurologic and developmental outcome after cardiac surgery. Perioperative seizures in young infants have been found to be associated with impaired psychomotor development at 1 year of age. In the area of perioperative management, the antifibrinolytic agents tranexamic acid, epsilon-aminocaproic acid, and aprotinin have been found to be useful in reducing postoperative hemorrhage. Nitric oxide is useful in reducing postoperative pulmonary hypertension. Late clinical follow-up studies of patients with single ventricle have revealed an important incidence of pulmonary arteriovenous malformations after a bidirectional Glenn shunt and atrial flutter after a Fontan procedure. Late assessment of patients after the arterial switch procedure for transposition has revealed preservation of ventricular function and an extremely low incidence of late arrhythmias.

Antifibrinolytic Agents↗
PubMedDate not supplied

Safety and efficacy of methods for reducing perioperative allogeneic transfusion: a critical review of the literature.

A number of pharmacologic and nonpharmacologic technologies are in current use to minimize perioperative homologous blood use. Clinical trials, many of them randomized controlled trials, have been done evaluating these approaches and have demonstrated their efficacy. However, data on safety has relied mostly on case reports, uncontrolled studies, and, for the pharmacologic agents, extrapolation from the nonsurgical setting. In this review I analyze the data from the randomized trials and the lower-level evidence studies to provide the best estimates in safety with these alternatives. In general, these alternatives are safe with proper dosing and monitoring of effects. With aprotinin, the primary concern is anaphylaxis, and this predominantly with re-exposure. With aprotinin and with the anti-fibrinolytics, increased venous thromboembolic risk has not been a consistent finding. Tranexamic acid use intraoperatively is advantageous, but postoperative use appears to have no advantage and may be associated with renal dysfunction. DDAVP is low-risk, provided it is not overused, which can induce hyponatremia. Autologous predonation probably has similar risks as homologous blood with respect to transfusion errors and bacterial infection. As with most medical interventions, we must be vigilant to prevent human error.

Aminocaproic Acid↗
PubMed2005

Short-course use of recombinant factor VIIa in a haemophilia patient with inhibitor undergoing cataract surgeries.

A 36 year-old patient with severe haemophilia A and high-titre inhibitor underwent cataract surgery under topical anaesthesia. Recombinant factor VIIa was used only three times, once before and twice following surgery. Tranexamic acid was given concomitantly. One month after the first successful procedure on the right eye, a second operation was performed on the left eye in the same manner. Both procedures were uneventful. Neither bleeding complications nor any other side effects occurred.

Adult↗
PubMed2003

Autoantibodies and lymphoproliferative diseases in acquired C1-inhibitor deficiencies.

Angioedema due to acquired C1-inhibitor (C1-INH) deficiency (also referred to as "acquired angioedema") is a rare, life-threatening disease with poorly defined etiology, therapy, and prognosis. To define the profile of acquired C1-INH deficiency and to facilitate the clinical approach to these patients, we report on 23 patients with acquired C1-INH deficiency followed for up to 24 years (median, 8 yr), and review the literature. We measured C1-INH activity with chromogenic assay and detected autoantibodies to C1-INH by enzyme-linked immunosorbent assay (ELISA). Median age at onset of angioedema was 57 years (range, 39-75 yr). All patients had C1-INH function and C4 antigen below 50% of normal. C1q was reduced in 17 patients. Autoantibodies to C1-INH were present in 17 patients. Long-term prophylaxis of attacks with danazol was effective in 2 of 6 patients, and with tranexamic acid, in 12 of 13 patients. Therapy with C1-INH plasma concentrate was necessary in 12 patients: 9 had rapid positive response and 3 became progressively resistant. Associated diseases at the last follow-up were non-Hodgkin lymphomas (3 patients), chronic lymphocytic leukemia (1 patient), breast cancer (1 patient), monoclonal gammopathies of uncertain significance (13 patients). In 4 patients no pathologic condition could be demonstrated. Compared with the general population, patients with acquired C1-INH deficiency present higher risk for B-cell malignancies, but not for progression of monoclonal gammopathies of uncertain significance to malignancy. Antifibrinolytic agents are more effective than attenuated androgens in long-term prophylaxis. Patients with acquired C1-INH deficiency may be resistant to replacement therapy with C1-INH plasma concentrate.

Aged↗
PubMed2006

Von Willebrand disease.

UNLABELLED: Von Willebrand disease (VWD), the most common inherited bleeding disorder, results from a deficiency of von Willebrand factor (VWF), a protein required for the normal adhesion of platelets to the site of injured endothelium and for preservation of factor VIII in the circulation. The prevalence of VWD has been reported to be as high as 1.3%. Among women with VWD, menorrhagia is the most common symptom, affecting 32% to 100%. Treatments that have been reported to control menorrhagia in these women include combined oral contraceptives, 1-deamino-8-D-arginine vasopressin (DDAVP), tranexamic acid, and the levonorgestrel-releasing intrauterine system. With the exception of nonsteroidal antiinflammatory drugs, any treatments effective in the treatment of menorrhagia, including hysterectomy, may be suitable. Besides menorrhagia, women with VWD appear to be at an increased risk of developing hemorrhagic ovarian cysts and possibly endometriosis. As they grow older, they may be more likely to manifest conditions that present with bleeding such as fibroids, endometrial hyperplasia, and polyps. During pregnancy, they may be at greater risk of miscarriage and bleeding complications, particularly delayed or secondary postpartum hemorrhage. Vaginal or vulvar hematomas, extremely rare in women without bleeding disorders, are not uncommon. Although women with VWD are at risk for the same obstetric and gynecologic problems that affect all women, they appear to be disproportionately affected by conditions that manifest with bleeding. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader should be able to recall that Von Willebrand Disease (VWD) is a common inherited disease, especially in women with menorrhagia; state that prophylaxis therapies against bleeding in pregnant and nonpregnant women are available; and explain that, despite prophylaxis, miscarriage and bleeding complications can still occur.

Endometrial Hyperplasia↗
PubMed1976

Diagnosis and treatment of acute gastrointestinal haemorrhage in a small district hospital.

Ninety-eight consecutive patients admitted to a small district hospital because of acute gastrointestinal haemorrhage have been studied. Patients with haematemesis and/or melaena were treated with antacids and tranexamic acid from the very beginning and were examined with early panendscopy. All patients were closely observed in an ordinary medical ward by a staff especially trained to handle acute gastrointestinal bleeding. Seven patients required acute surgery. The overall mortality was 4.1%. It is concluded that acute gastrointestinal haemorrhage can be successfully handled with modern diagnosis and treatment in a small hospital.

Adult↗
PubMed1992

An improved method for the serotyping of free coagulase from Staphylococcus aureus.

The serotyping of free coagulase, one of the most reliable ways to identify strains of Staphylococcus aureus, and widely employed in Japan, has been improved by adding magnetite sand to the reaction mixture. Culture medium supernatant and a type-specific antibody are mixed in a well of a microtiter plate, and plasma-enriched bovine fibrinogen is treated with magnetite sand. The use of tranexamic acid and gum arabic in the reaction mixture also increases the sensitivity of the reaction. Finally, the plate is placed on a magnetic stirrer. If the type of the coagulase corresponds to that of the antibody, no clot formation will occur, and this is easily confirmed by the movement of the sand. Although the amount of reaction mixture required is much less than that for the conventional tube method, our new method is able to detect slight increases in viscosity of the reaction mixture due to fibrin formation even before complete clotting occurs, thus providing very high sensitivity. Clot formation can also be judged by observing a turbid mass of fibrin in the well (Hwang's method), but this approach is a little slower than our method involving immobilization of magnetite sand.

Coagulase↗
PubMed1984

Plasmin-alpha 2-antiplasmin complexes in bleeding disorders characterized by primary or secondary fibrinolysis.

A two-dimensional immunoelectrophoresis (2DIEP) method detects plasmin complexed to its major inhibitor, alpha 2-antiplasmin, in plasma in the blood of patients during (a) thrombolytic therapy with urokinase, (b) episodes of disseminated intravascular coagulation (DIC) with active fibrinolysis, and (c) episodes of fibrinolytic haemorrhage without evidence of DIC. Clearance of the complexes from the blood is rapid and their detection thus implies active plasmin generation at the time of blood sampling or within the preceding 24 h. Abolition of the complexes using tranexamic acid therapy allowed surgery without bleeding in two previously grossly haemorrhagic patients in group (c). Antithrombin III complexed with activated procoagulants was detected using a similar 2DIEP method in only two of four patients with DIC. Abnormalities of alpha 2-macroglobulin were detected on 2DIEP of plasma in the patients studied with proteolytic disorders; these did not appear to reflect complex formation.

Abruptio Placentae↗