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Activation of the hemostatic process in patients with unruptured aortic aneurysm before and in the first week after surgical repair.

BACKGROUND AND OBJECTIVE: It has been previously suggested that activation of coagulation and fibrinolysis may sometime occur in patients with unruptured aortic aneurysm. However, the incidence of this complication and the effect of surgical repair are unknown. The objective of our study was to gain further information on this topic. METHODS: We investigated activation of the hemostatic process in 20 consecutive patients with unruptured abdominal aortic aneurysm. We then evaluated the effect of surgical repair of the vascular abnormalities. RESULTS: Both before and in the first week after surgery, the large majority of patients showed clear signs of activation of coagulation (increased plasma levels of prothrombin fragment 1 + 2 and fibrin peptide A), and many had low levels of the natural anticoagulant antithrombin III. Platelets were activated in all cases (high levels of plasma beta-thromboglobulin), and signs of platelet consumption (thrombocytopenia and/or increased mean platelet volume) were present in most of them. INTERPRETATION AND CONCLUSIONS: Activation of the hemostatic process occurs in nearly all patients with abdominal aortic aneurysm and could play a role in the hemorrhagic and thrombotic events that can complicate the clinical development of these subjects.

Aged↗

Hemostatic alterations accompanying sickle cell pain crises.

Three patients with sickle-cell disease (SSD) were followed, weekly, for 1 1/2 to 2 years, during which time they experienced one or more episodes of crisis. Crisis was associated with reproducible sequential hemostatic alterations indicating intravascular fibrin formation and a marked disturbance in platelet economy. With crisis onset, or possibly before, there was an increase in plasma high-molecular-weight fibrinogen complexes and a transient fall in platelet count, with a subsequent rise in both fibrinogen concentration and platelet count; plasma fibrinogen peaked 1 week after crisis onset and platelet count approximately 2 weeks after onset. Subsidence of crisis was associated with a fall in high-molecular-weight fibrinogen complexes and a subsequent increase in fibrinogen first derivative, an early fibrinogen breakdown product. Hemostatic findings and patient clinical status were generally correlated, the findings during asymptomatic periods being essentially normal. Agents affecting platelet function (aspirin alone or in combination with dipyridamole) appeared to reduce the extent of laboratory abnormality, suggesting potential clinical usefulness in this disorder.

Acute Disease↗

Platelet agonists and calcium homeostasis in endothelial cells: possible role in the interaction of endothelium with hemostatic system.

BACKGROUND AND OBJECTIVE: The endothelium is complex tissue that modulates a vast array of biological functions and Ca++ transients are critically important to these endothelium-dependant functions. We addressed the hypothesis that some platelet agonists and products of activation of the hemostatic system could determine Ca++ transients in a bovine pulmonary artery endothelial cell line (CPA-47). DESIGN AND METHODS: The effect of thrombin, collagen, ADP, PAF, PDGF, GRGDS, and the TxA2 mimetic U46619 on CPA-47-cytoplasmic Ca++ transients was evaluated using a Platelet ionized Calcium Aggregometer, after cells were loaded with the photoprotein aequorin. RESULTS: ADP, GRGDS, PAF, U46619 and collagen were able to induce rapid Ca++ transients in CPA-47 endothelial cells and the response was stable after repeated additions, while thrombin acted slightly differently, as cells became refractory to this agonist after the first response, but they remained sensitive to the other inducers. Only PDGF was completely ineffective. Furthermore, calcium-channel blockers verapamil and flunarizine (but not nifedipine) caused a reduction only of thrombin-induced cytoplasmic Ca++ transients, while the addition of depolarizing concentration of KCl suggests the presence also of voltage-operated channels on endothelial cell membrane. Finally, EGTA caused the complete suppression of Ca++ transients induced by all the tested agonists but collagen. INTERPRETATION AND CONCLUSIONS: Our study demonstrated that the different agents tested are able to induce Ca++ transients on bovine endothelial cultured cells, similarly to that observed in platelets and other non excitable cells, including tumor cells, and that calcium channel blockers had only a limited inhibitory effect on these changes; these results may help more thorough understanding of the biochemical basis of the interaction between endothelium and the hemostatic system.

Animals↗

[The clinical significance of disorders in the hemostatic system in infectious endocarditis].

AIM: Study of blood clotting to evaluate hemostatic disorders in infectious endocarditis (IE). MATERIALS AND METHODS: The trial included 124 patients with IE (61 males and 63 females aged 15-70 years). Primary and secondary IE was in 38 and 62% of patients, respectively. RESULTS: Clinically evident hemostatic disorders were observed in 93(74.2%) cases. They manifested as intravascular platelet activation with development of hypercoagulatory status and chronic DIC-syndrome. CONCLUSION: A differentiated approach is advisable to correction of thrombotic disorders in IE basing on the severity of blood coagulation impairment.

Adolescent↗

[Markers of hemostatic activation in the coronary sinus versus peripheral circulation in coronary artery disease. Effects of percutaneous transluminal coronary angioplasty].

BACKGROUND: To evaluate haemostatic changes in coronary sinus (CS) and peripheral circulation (PC) in patients with cardiovascular disease (CAD) following PTCA. PATIENTS AND METHODS: We studied 12 patients scheduled for elective PTCA. Blood samples were obtained from CS and PC before angioplasty and after each balloon dilation. Expression of P selectin and several haemostatic parameters were determined. RESULTS: D-Dimers (DD) plasma levels were significantly increased in samples from CS. No significant differences were found in other haemostatic parameters. A significant decrease of thrombin-antithrombin III levels after PTCA was assessed. CONCLUSIONS: Intracoronary and peripheral hemostatic activation does not occur during and immediately following PTCA. No major differences in hemostatic parameters between CS and PC were observed in patients with CAD.

Adult↗

The use of microfibrillar collagen hemostat for control of renal bleeding.

Microfibrillar collagen hemostat was used in 23 patients with renal injuries owing to multiple causes in an attempt to control small vessel bleeding from raw renal surface areas. Minimal complications have occurred with the use of this substance. Control of bleeding has been prompt and no late bleeding has occurred.

Animals↗

Addition of a propyl gallate-based procoagulant to a fibrin bandage improves hemostatic performance in a swine arterial bleeding model.

Fibrin bandages manufactured by Nycomed Austria (TC-S) were modified by the addition of Hemostyptin (HS), a proprietary platelet-activating reagent containing propyl gallate. HS was added as an additional layer to TC-S fibrin bandages and the bandages were tested for hemostatic efficacy in a swine femoral artery bleeding model. Injuries were treated with a TC-S+HS bandage preparation using HS lyophilized onto a bandage surface that was then attached to the fibrin dressing. This preparation qualitatively and quantitatively exhibited more robust blood clotting at the surgical site than the control bandages. TC-S+HS bandages were more effective than control bandages with a difference in blood loss of 251.8+/-66.5 g for TC-S bandage alone, n=12 vs. 121+/-40.7 g, n=13 for the TC-S+HS bandage, P=0.05. Bleeding times were shortened for animals treated with the HS fortified bandages and residual platelets counts in these animals were higher.

Animals↗

Use of a collagen hemostatic closure device to achieve hemostasis after arterial puncture: a cost-effectiveness analysis.

PURPOSE: To evaluate whether a collagen hemostatic closure device is a safe, cost-effective alternative to manual compression for achieving hemostasis at arterial puncture sites. MATERIALS AND METHODS: A cost-effectiveness analysis, based on a meta-analysis of published data, was performed from the perspective of the health-care system. The gain in effectiveness was expressed as the decrease in rate of puncture-site complications that required treatment. Costs associated with achieving hemostasis and treating complications were included. RESULTS: Use of a collagen closure device decreased the number of puncture-site complications from 31:1,000 to 16:1,000. The average cost of using the device was $177 per patient compared with $42 per patient for manual compression. The incremental cost of averting one complication exceeded $9,000. CONCLUSION: Use of a collagen closure device to achieve hemostasis after an arterial puncture may reduce the complication rate, but the additional cost per complication averted is very high.

Aneurysm, False↗

Hand-assisted laparoscopic partial nephrectomy in the porcine model using gelatin matrix hemostatic sealant without hilar occlusion.

BACKGROUND AND PURPOSE: Gelatin matrix hemostatic sealant (GMHS) has been used for hemostasis during partial nephrectomy with hilar clamping. The objective of this study was to determine the ability of GMHS to achieve hemostasis without hilar clamping in the porcine model. MATERIALS AND METHODS: In this feasibility study, eight farm pigs underwent a left-hand-assisted laparoscopic partial nephrectomy (HALPN). The lower fourth of the kidney was removed with cold scissors, and GMHS was applied laparoscopically. Samples were collected for measurement of serum hemoglobin (Hb) and creatinine (Cr) prior to surgery and at 4 and 30 days after HALPN. The kidneys were harvested at 30 days, and retrograde pyelograms and pathologic analysis were performed. RESULTS: Application of GMHS achieved complete hemostasis in all eight animals. The mean estimated blood loss was 40 mL, and the operating time was short (mean 92.5 minutes). In three kidneys, a significant collecting system opening was noted but not repaired. At harvest, there were no hematomas, infections, or urine leaks in any animals. In one animal, a 2-cm contained fluid collection was identified. There was no difference in the preoperative and harvest Hb (9.63 v 9.21 g/dL; P = 0.49), but there was a slight increase in Cr (1.21 v 1.46 mg/dL; P = 0.01) possibly because of the decreased renal mass after partial nephrectomy. CONCLUSION: Even without hilar occlusion, GMHS was 100% safe and effective in controlling bleeding after HALPN in the porcine model. Avoidance of hilar occlusion may reduce the risk associated with warm renal ischemia and the extra dissection required to isolate the hilum in preparation for clamping.

Animals↗

Initial experience with hemostatic fibrin glue as adjuvant during tubeless percutaneous nephrolithotomy.

PURPOSE: To report our initial experience with hemostatic fibrin glue as an adjuvant during tubeless percutaneous nephrolithotomy (PCNL). PATIENTS AND METHODS: Seventeen consecutive patients underwent tubeless PCNL with injection of 2 mL of Tisseel Vapor Heated Sealant (Baxter AG, Vienna, Austria) into the percutaneous tracts at the conclusion of the procedure. The perioperative outcomes of these patients were compared retrospectively with those of a control group of 25 consecutive patients who underwent tubeless PCNL without the use of fibrin glue. The safety and efficacy of the new approach was evaluated by comparing operative time, hemoglobin drop, transfusion requirement, length of hospitalization, postoperative pain, analgesic use, and postoperative complications in the two groups. RESULTS: There was no difference in the mean drop in hemoglobin, transfusion requirement, or complications in the two groups. However, patients undergoing Tisseel tubeless PCNL required less analgesia postoperatively (P=0.05), and they were discharged an average of 7 hours earlier than the patients in the control group. There were no major postoperative complications. CONCLUSIONS: Use of fibrin glue was safe and was associated with less analgesic requirement and a shorter hospital stay. Randomized studies are needed to evaluate its clinical role in the future.

Adult↗

Application of the poly-N-acetyl glucosamine-derived rapid deployment hemostat trauma dressing in severe/lethal Swine hemorrhage trauma models.

BACKGROUND: The Rapid Deployment Hemostat (RDH) Bandage was developed for the rapid control of bleeding caused by trauma. METHODS: An extremity wound involving skin, muscle, bone, and femoral arterial injury and a 1-cm vertical incision in the abdominal aorta in swine were studied to compare the RDH Bandage, a fibrin sealant dressing and gauze to restore hemostasis. The total blood loss was determined and the survival of animals was measured. RESULTS: In the extremity injury model, the RDH Bandage reduced blood loss by 63% compared with the gauze control. In the aorta arterial incision model, the RDH Bandage required a significantly lower compression time to control bleeding compared with gauze and TachoComb. The RDH Bandage was able to stop bleeding from this injury in 100% of the tests. CONCLUSION: The RDH Bandage was superior to a commercially available fibrin bandage in controlling hemorrhage, decreasing blood loss, and increasing survival.

Acetylglucosamine↗

Comparison of poly-N-acetyl glucosamine with commercially available topical hemostats for achieving hemostasis in coagulopathic models of splenic hemorrhage.

BACKGROUND: The hemostatic quality of the poly-N-acetyl glucosamine (p-GlcNAc) patch was compared with a fibrin sealant, fibrin bandage, and cellulose patch. METHODS: A 2 x 2-cm capsular strip to a depth of 3 mm of the swine spleen was used as a source of bleeding. Splenic lacerations were created in hemophilia B dogs and treated with p-GlcNAc and Surgicel. Wounds were created in rabbits and treated with p-GlcNAc at 37degreesC and after keeping body core temperature at 29degreesC. RESULTS: Poly-N-acetyl glucosamine was able to achieve hemostasis with greater efficacy than either of the fibrin-based bandages. In the hemophilia B dog study, p-GlcNAc significantly outperformed Surgicel, with p-GlcNAc achieving hemostasis in 75% of the treated wounds compared with 17% for the cellulose patch. The hypothermia study demonstrated that p-GlcNAc is equally effective at 29degreesC and at 37degreesC. CONCLUSION: Poly-N-acetyl glucosamine was effective at controlling bleeding in animals with experimentally induced or genetic coagulopathic disorders.

Acetylglucosamine↗

New hemostatic agents in general open and laparoscopic surgery.

F ollowing tissue disruption, whether operative or traumatic, the priorities of any organism are cessation of hemorrhage, prevention of infection, and restoration of tissue integrity and function. Several hemostatic techniques achieve the goal of hemorrhage cessation. One evolving technique is the use of fibrin sealants (FSs) as a surgical tissue adhesive. The different and most common applications of fibrin glue in open and laparoscopic surgery are reviewed.

Animals↗

[Hemostatic provision of surgical treatment of juvenile angiofibromas of the skull base in children].

For three years we operated sixty two 7-16-year-old children for angiofibroma of the base of the skull. To reduce the risk of massive intra- and postoperative bleeding, we used preoperative endovascular occlusion of the vessels carrying blood to the tumor. In addition to preventive administration of vicasol, ethamsilate, dicinon and transamine, we used highly effective hemostatic drugs tahocomb and novo-seven intraoperatively in case of massive blood loss. Neither lethal outcomes nor complications occurred in children during removal of angiofibromas of the base of the skull.

Adolescent↗

[Wound healing in viscera studied using a hemostatic gelatin-starch sponge of Polish manufacture].

The authors studied the reaction of liver, spleen and kidneys in rats to the implantation of Polish made hemostatic gelatin-starch sponge. The sponge under study evoked no disadvantageous tissue reactions in the case of liver; it was readily resorbed and did not inhibit the wound healing. It facilitated the healing of lienal wounds without any suturing and produced neither local nor general disadvantageous results. When dressing renal wounds, the sponge was completely resorbed within 3 weeks and the wound was completely healed. The renal wounds healed without any complications despite of a greater tissue reaction compared with that of liver and spleen.

Animals↗

Antidiuretic effect of desmopressin given in hemostatic dosages to healthy volunteers.

The aim of this study was to characterize the magnitude and duration of the antidiuretic effects elicited by desmopressin given in hemostatic dosage intravenously (i.v.) (0.3 microg/kg) or intranasally (i.n.) (300 microg) both as single or repeated doses (four i.n. doses with 12-hr intervals) to healthy volunteers. Urine osmolality increased to a maximum median value of 1,087 mOsmol/kg after the single i.v. dose, 1,065 after the single i.n. dose, and 1,071 during the repeated i.n. dosing schedule, and did not differ significantly between the three dosage schedules. The increase lasted for 24 hr after single doses, and 12 hr after the last of the repeated i.n. doses. Serum sodium did not decrease more than normal diurnal variation after single doses, but decreased marginally below the normal reference range in three volunteers after repeated doses. Lowest median serum sodium concentrations after single i.v. and i.n. doses were 140 and 141 mmol/l, respectively, and 139 after repeated i.n. doses. Body weight changed only marginally after single doses, but increased 1.3 kg during repeated dosing. In adult healthy volunteers, single desmopressin doses give an antidiuretic effect lasting for about 24 hr. There is no difference in magnitude or duration between i.v. or i.n. doses. The effect is prolonged as long as the doses are repeated. Serum sodium is only marginally affected by single doses, but tends to decrease after four repeated doses with 12-hr intervals. If desmopressin is repeated for a period of up to 48 hr, fluid intake should be restricted to 2 liters per day in adults.

Administration, Intranasal↗

Polyethylene glycol/microfibrillar collagen composite as a new resorbable hemostatic bone wax.

Although bone wax is effective at achieving hemostasis, it is nonresorbable, causes a foreign body reaction, and inhibits osteogenesis. We report development of a polyethylene glycol/microfibrillar collagen composite (PEG/MFC) that has inherent hemostatic qualities, is biodegradable, and is compatible with bone repair. PEG/MFC composite (n = 42) was placed in 5 mm cranial defects in New Zealand white rabbits. Hemostasis and healing were compared to unfilled defects (n = 32) and defects filled with standard bone wax (n = 10). Both PEG/MFC and bone wax handled well and stopped bleeding. The polyethylene glycol component was resorbed by 8 h, and the microfibrillar collagen was resorbed over 2 months, eliciting only a minor inflammatory response during the first month. Defects filled with the PEG/MFC composite showed similar amounts of bony regeneration as did unfilled control defects. At 4 weeks, healing bone accounted for 43 +/- 13% in those treated with PEG/MFC and 47 +/- 19% defect area in untreated holes. In contrast, less than 1% of the area was bone in defects filled with bone wax (p < 0.05). PEG/MFC composite provided excellent bony hemostasis and did not inhibit bone growth.

Animals↗

Acquired von Willebrand disease--hemostatic management of major orthopedic surgery with high-dose immunoglobulin, desmopressin, and continuous factor concentrate infusion.

Acquired von Willebrand disease (aVWD) is a rare bleeding disorder that mimics congenital VWD in previously healthy individuals; it is most frequently associated with monoclonal gammopathy. Hemostatic therapy of aVWD is challenging due to the extremely shortened half-life of endogenous and exogenous VWF. High-dose intravenous immunoglobulin (ivIG) is recommended as the treatment of choice, usually rapidly normalizing coagulation; but in case of failure, alternative treatment options are not well explored. We report successful major orthopedic surgery in a 61-year-old woman with multiple myeloma IgG lambda and aVWD. IvIG alone failed to correct hemostasis. However, ivIG pretreatment improved the VWF ristocetin cofactor (VWF:RCo) half-life from only 1.5 hr to more than 4 hr, allowing desmopressin infusions twice daily to maintain sufficient VWF:RCo levels. Because of diminishing desmopressin effect, we attempted for the first time in aVWD a continuous VWF/FVIII infusion (Haemate HS), 2.1-2.7 FVIII U/kg/hr or 51-64 U/kg/day, respectively 4.6-6.0 VWF:RCo U/kg/hr or 110-145 U/kg/day) to reach constant factor levels. The steady-state clearance was 2.4 mL/kg/hr for FVIII:C and 13.5 mL/kg/hr for VWF:RCo. During surgery, VWF:RCo, FVIII:C, and PFA-100 closure time were normalized. Until day 5, VWF:RCo was kept above 50%, from day 6 to 10 at least 30% activity were attained. FVIII:C levels were always >70%. The clinical course was uneventful without bleeding. Two weeks after hip surgery the patient was discharged from the hospital without complaints. The therapy described can be recommended as safe and feasible for further evaluation in aVWD patients who are hyporesponsive to ivIG treatment alone. Continuous VWF/FVIII infusion can improve substitution therapy in aVWD.

Arthroplasty, Replacement, Hip↗