scholarly journals Bismuth Subgallate as a Local Hemostatic Agent

Author(s):  
Poerwati Soetji Rahajoe ◽  
Cahya Yustisia Hasan ◽  
Amelia Elizabeth Pranoto

Abstract Background: Patients on clopidogrel increased bleeding risk after surgery. This drug prolonged bleeding time, increased bleeding volume and induced secondary bleeding because its active metabolite inhibited platelets aggregation and interfered with haemostatic plug stabilization. Conventional methods, such as pressing sterile gauze on the surgery site, showed less effective to stop bleeding in patients on clopidogrel. This research aims to prove the haemostatic effect of bismuth subgallate both on normal and delayed platelet aggregation due to clopidogrel.Methods: Twenty-eight Wistar rats were equally and randomly administered with clopidogrel (10 mg/kgBW) or NaCl 0.9% (saline) via oral gavage. After anesthetizing, we amputated transversely their tail 10 mm from the distal tip. Bleeding after amputation was controlled with pressing gauze soaked in saline or bismuth subgallate solution. After 60 seconds, bleeding assays (bleeding time, bleeding volume, and secondary bleeding) have been observed, recorded, and analysed both in normal and clopidogrel groups.Results: Clopidogrel groups had significantly longer bleeding time, greater bleeding volume, and had more secondary bleeding rather than saline groups (p <.05). Using bismuth subgallate as local haemostatic agent decreased bleeding time and bleeding volume significantly (p <.05) both in normal and clopidogrel groups. Conclusions: Bismuth subgallate has a haemostatic effect on both clopidogrel and normal rat tail bleeding models.

Phlebologie ◽  
2008 ◽  
Vol 37 (06) ◽  
pp. 287-297 ◽  
Author(s):  
P.-M. Baier ◽  
Z. T. Miszczak

Summary Background: Platelet function inhibitors (PFI) are used for prophylaxis of atherothrombosis. These drugs cause a prolongation of the bleeding time and should eventually be stopped before an elective operation. However, there is a risk that a perioperative pause of PFI lead to acute atherothrombosis. Objective: Our aim was to study whether a discontinuation of PFI therapy is necessary to avoid bleeding complications in patients undergoing varicose vein surgery. Methods: Selective review of the literature and retrospective analysis of clinical data of our own patients. Results: In the years 2002 to 2007 a total of 10 827 patients have been operated on varicose veins, 673 (6.2%) of these aged 32–86 years (67 ± 7.9) receiving permanent PFI therapy: 256 male patients (38.0%) and 417 female (62.0%), 39.1% categorized as ASA III patients: male 11.6%, female 27.5%. 38 patients who continued PFI therapy did not demonstrate haemorrhagic complications and none of those pausing anti-platelet medication experienced thromboembolic complications. The literature survey confirmed our finding that it is not necessary to suspend PFI medication for varicose vein surgery as the bleeding risk can be controlled for by technical means. Conclusion: Discontinuation of PFI therapy prior to interventions on varicose veins does not seem to be necessary, further studies are essential though.


1988 ◽  
Vol 59 (02) ◽  
pp. 225-230 ◽  
Author(s):  
J P Maffrand ◽  
A Bernat ◽  
D Delebassée ◽  
G Defreyn ◽  
J P Cazenave ◽  
...  

SummaryThe relative importance of ADP, arachidonic acid metabolites and serotonin as thrombogenic factors was evaluated in rats by comparing, after oral administration, the effects of two inhibitors of ADP-induced platelet aggregation (ticlopidine and PCR 4099), three cyclo-oxygenase inhibitors (aspirin, triflusal and indobufen) and a selective serotonin 5HT2 receptor antagonist (ketanserin) on platelet aggregation, in four platelet-dependent thrombosis models and on bleeding time. Platelet aggregation induced by ADP and collagen was completely inhibited by ticlopidine and PCR 4099 whereas only the collagen aggregation was reduced by the cyclo-oxygenase inhibitors. Ketanserin or a depletion of platelet serotonin by reserpine did not affect platelet aggregation. Ticlopidine and PCR 4099 greatly prolonged rat tail transection bleeding time. This is probably related to their known ability to inhibit ADP-mediated platelet aggregation. In contrast, the cyclooxygenase inhibitors did not affect bleeding time at all. Reserpine and ketanserin prolonged bleeding time by interfering with the action of serotonin on the vascular wall. Ticlopidine and PCR4099 were very potent antithrombotics in all the models. Aspirin, only at a high dose, inhibited poorly thrombus formation on a silk thread in an arterio-venous shunt, suggesting that the inhibition of cyclo-oxygenase was not responsible. Triflusal was inactive in all models while indobufen slightly reduced thrombus formation in the silk thread and metallic coil models. Ketanserin and reserpine reduced thrombus only in the metallic coil model. Thrombus formation was greatly reduced in fawn-hooded rats, which lack ADP in their platelet dense granules because of a genetic storage pool deficiency. Taken together, the results obtained with the drugs and with the fawn-hooded rats support the concept that ADP plays a key role in thrombogenesis in rats.


1975 ◽  
Vol 33 (02) ◽  
pp. 278-285 ◽  
Author(s):  
Şeref Inceman ◽  
Yücel Tangün

SummaryA constitutional platelet function disorder in a twelve-year-old girl characterized by a lifelong bleeding tendency, prolonged bleeding time, normal platelet count, normal clot retraction, normal platelet factor 3 activity and impaired platelet aggregation was reported.Platelet aggregation, studied turbidimetrically, was absent in the presence of usual doses of ADP (1–4 μM), although a small wave of primary aggregation was obtained by very large ADP concentrations (25–50 μM). The platelets were also unresponsive to epinephrine, thrombin and diluted collagen suspensions. But an almost normal aggregation response occurred with strong collagen suspensions. The platelets responded to Ristocetin. Pelease of platelet ADP was found to be normal by collagen and thrombin, but impaired by kaolin. Platelet fibrinogen content was normal.The present case, investigated with recent methods, confirms the existence of a type of primary functional platelet disorder characterized solely by an aggregation defect, described in 1955 and 1962 under the name of “essential athrombia.”


1994 ◽  
Vol 72 (06) ◽  
pp. 874-879 ◽  
Author(s):  
Jean Millet ◽  
Jocelyne Theveniaux ◽  
Neil L Brown

SummaryThe venous antithrombotic profile of naroparcil or (4-[4-cyanoben-zoyl]-phenyl)-1.5-dithio-β-D-xylopyranoside was investigated in the rabbit following single i. v. and oral administration. Naroparcil attenuated thrombus development in a Wessler stasis model of venous thrombosis (jugular vein) employing bovine factor Xa as a thrombogenic stimulus giving ED50 values of 21.9 mg/kg and 36.0 mg/kg after respectively i. v. and oral administration. Venous antithrombotic activity was maximal 2-3 h after i. v. administration and 4-8 h after oral administration. Four hours after the oral administration of maximal antithrombotic (Wessler model, factor Xa) doses (100 and 400 mg/kg), naroparcil had no significant effect on bleeding time. In platelet poor plasma obtained from animals treated 4 h previously with various doses (25 to 400 mg/kg) of naroparcil, there was no detectable anti-factor Xa nor antithrombin activity. Similarly, naroparcil had no effect on APTT nor on thrombin time. A sensitized thrombin time (to about 35 s) was modestly but significantly increased following oral administration of the compound at 400 mg/kg. However, thrombin generation by the intrinsic pathway was reduced in a dose-related manner, maximal reduction being 65% at 400 mg/kg. The same doses of naroparcil enhanced the formation of thrombin/heparin cofactor II complexes at the expense of thrombin/antithrombin III complexes in plasma incubated with (125I)-human a-thrombin and induced the appearance of dermatan sulfate-like material in the plasma of treated rabbits, as measured by a heparin cofactor II-mediated thrombin inhibition assay. The results suggest that naroparcil could have a safe venous antithrombotic profile following oral administration (antithrombotic effect compared to bleeding risk). It is probable that part of the mechanism of action of the β-D-xyloside, naroparcil, is due to the induction of chondroitin sulfate-like glycosaminoglycan biosynthesis, this material being detectable in the plasma.


1991 ◽  
Vol 65 (05) ◽  
pp. 491-496 ◽  
Author(s):  
M Meyer ◽  
C M Kirchmaier ◽  
A Schirmer ◽  
P Spangenberg ◽  
Ch Ströhl ◽  
...  

SummaryA patient with idiopathic thrombocytopenic purpura developed after splenectomy a thrombasthenia-like severe haemor-rhagic diathesis characterized by a normal or subnormal platelet count, prolonged bleeding time, strongly reduced platelet adhesion to glass and defective platelet aggregation in response to ADP and collagen. In contrast to hereditary thrombasthenia membrane glycoproteins (GP) lib and Ilia were normally present in the patient’s platelets. Immunoelectrophoretic analysis revealed an abnormal behaviour of the patient’s GP IIb-IIIa complex. Autoantibodies against GP IIb-IIIa were detected in Triton-extracted washed platelets. Incubation of normal platelets with plasma from the patient resulted in a similar immunoelectrophoretic abnormality of the GP IIb-IIIa complex indicating that bound autoantibodies (IgG) are responsible for the abnormal immunoelectrophoretic behaviour of the patient’s GP IIb-IIIa complex. Platelet fibrinogen was severely reduced similar to classical thrombasthenia suggesting that the GP IIb-IIIa complex is involved in platelet fibrinogen storage.


1996 ◽  
Vol 76 (03) ◽  
pp. 312-321 ◽  
Author(s):  
Diego Mezzano ◽  
Rodrigo Tagle ◽  
Olga Panes ◽  
Marcos Pérez ◽  
Patricio Downey ◽  
...  

SummarySeveral parameters of primary hemostasis and markers of activation of coagulation and fibrinolysis were measured in 48 patients with severe (creatinine clearance <20 ml/min) chronic renal failure (CRF) without dialysis and diseases or drugs affecting hemostasis. Bleeding time (BT) was prolonged in 25/48 patients, and was correlated with age of patients, severity of renal failure, hematocrit, impairment in platelet aggregation-secretion and decrease in platelet ATP content. Defects in von Willebrand factor played no role in the prolongation of the BT. Multivariate analysis showed that only platelet dysfunction and severity of renal disease were independent predictors of the BT in uremia. The platelet functional disorder was significantly correlated with a reduction in platelet ATP and ADP.High levels of plasma thrombin-antithrombin complexes (TAT), prothrombin fragment F1+2, fibrinogen and factor VIIc were observed in patients with CRF, as described in prethrombotic states. Plasmin-antiplasmin complexes (PAP), fibrinogen and fibrin degradation products (FgDP, FnDP) were significantly increased, and the activity of plasminogen activator inhibitor (PAI-1) was slightly reduced, denoting an activation of fibrinolysis.A negative correlation was found between platelet levels of ATP and ADP with plasma TAT, F1+2 and PAP. Furthermore, plasma PAI-1 activity was negatively correlated with the BT and was lower in patients with prolonged BT as compared with controls and patients with normal BT. These links between primary hemostasis and activation of coagulation and fibrinolysis suggest that increased intravascular generation of thrombin and/or plasmin is an important mediator of the defects in primary hemostasis, prolongation of the BT and, probably, bleeding in CRF.


1995 ◽  
Vol 73 (03) ◽  
pp. 478-483 ◽  
Author(s):  
Michael J Mellott ◽  
Denise R Ramjit ◽  
Inez I Stabilito ◽  
Timothy R Hare ◽  
Edith T Senderak ◽  
...  

SummaryCuticle bleeding time (CBT) measurements in anesthetized rabbits were performed to assess the potential bleeding risks which may accompany the administration of tissue-type plasminogen activator (tPA) or vampire bat salivary plasminogen activator (BatPA). The dose of BatPA or tPA used in this study, 42 nmol/kg, was previously shown to be efficacious using a rabbit femoral artery thrombosis model (Gardell et al, Circulation 84:244, 1991). CBT was determined by severing the apex of the nail cuticle and monitoring the time to cessation of blood flow. CBT was minimally elevated (1.6-fold, p<NS) following bolus intravenous administration of BatPA; in contrast, bolus intravenous administration of tPA dramatically elevated CBT (6.2-fold, p<0.05). Rabbits treated with tPA, but not BatPA, displayed profound activation of systemic plasminogen and consequent degradation of Factor VIII and fibrinogen. Elevations in CBT after the administration of tPA were reversed by the replenishment of plasma Factor VIII activity to 40% of control, but were unaffected by complete replenishment of plasma fibrinogen. The results of this study suggest that the administration of BatPA, at a dose that promotes thrombolysis, may evoke a minimal bleeding risk, relative to an equi-efficacious dose of tPA. In addition, the tPA-provoked proteolytic consumption of Factor VIII may be a key contributor to the heightened bleeding risk.


1997 ◽  
Vol 77 (06) ◽  
pp. 1148-1153 ◽  
Author(s):  
Kazuhisa G Minamiguchi ◽  
Keiko T Kitazato ◽  
Eiji Sasaki ◽  
Hideki Nagase ◽  
Kenji Kitazato

SummaryWe studied the use of depolymerized holothurian glycosaminoglycan (DHG) as an anticoagulant in experimental beagle-dog hemodialysis using a hollow-fiber dialyzer compared to that using unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), and nafamostat mesilate (FUT). Effectiveness was based on 5 h hemodialysis and no marked clot deposition in the extracorporeal circuit. At effective doses, UFH and LMWH significantly prolonged template bleeding time, in sharp contrast to FUT and DHG, which scarcely prolonged bleeding time during hemodialysis. DHG prolonged activated partial thromboplastin time (APTT) about 6 times that of normal plasma and prolonged thrombin clotting time (TCT) markedly; FUT showed marked APTT prolongation but hardly prolonged TCT in the hemodialysis circuit at the effective dose. The anticoagulant profile of DHG thus differs completely from that of FUT. These results suggest that DHG may be useful as anticoagulant for hemodialysis with low hemorrhagic risk.


1962 ◽  
Vol 08 (03) ◽  
pp. 511-523
Author(s):  
G. J. H den Ottolander ◽  
A Bleijenberg

SummaryA prolonged bleeding time can be due to a vascular, plasmatic, or thrombocytic cause. On the basis of investigations in 8 patients with a prolonged bleeding time, these different forms are discussed.There appeared to be at least two plasmatic factors one of which is the bleeding factor of Nilsson. The demonstration of a thrombocytic cause is sometimes only possible with transfusions of normal platelet suspensions. A patient is described with a prolonged bleeding time due to an acquired thrombo-pathia, resulting from excessive haemorrhages and exchange transfusions.


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