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Hemostatic techniques during laparoscopic partial nephrectomy.

PURPOSE OF REVIEW: To review the current techniques and technologies being used for hemostatic control during laparoscopic partial nephrectomy. RECENT FINDINGS: Laparoscopic nephron-sparing surgery has become more common for the treatment of renal masses. With increasing experience, the indications for nephron sparing are increasing. Despite the increased use of these techniques in high-volume centers, however, more widespread application has been limited because of the need for advanced laparoscopic skills including the laparoscopic control of intraoperative renal bleeding. As a result, many techniques have been developed to achieve hemostasis, including conventional suture repair, tissue sealants, radiofrequency ablation, lasers, water dissection, and microwave tissue coagulation. SUMMARY: Laparoscopic partial nephrectomy is a technically challenging procedure. Many promising techniques are being developed currently, most geared toward improved hemostasis and collecting system repair. These techniques and products have made, and will continue to make, the procedure less demanding and more universally accepted.

Adhesives↗

Coping processes and hemostatic reactivity to acute stress in dementia caregivers.

BACKGROUND: A hypercoagulable stress response might contribute to the increased cardiovascular risk in Alzheimer's caregivers. OBJECTIVES: (1) To evaluate whether coping processes affect hemostatic reactivity to acute psychological stress and (2) whether these effects differ substantially between caregivers and noncaregivers. METHODS: Sixty elderly community-dwelling spousal caregivers of patients with Alzheimer's disease and 33 noncaregiving controls completed the revised Ways of Coping Questionnaire to assess approach/problem-solving versus avoidant coping processes. Participants were administered an acute stress test that required them to deliver a 3-minute speech challenge to the interviewer on an assigned topic. The hypercoagulability marker D-dimer was measured at three time points: baseline, immediately postspeech, and during recovery (15 minutes postspeech). RESULTS: Multivariate analysis of covariance revealed that subjects who endorsed greater levels of approach coping had decreased levels of D-dimer at all time points (p = .048). A significant three-way interaction between planful problem solving, caregiver status, and the temporal pattern of D-dimer was found (p = .004), indicating that caregivers with low levels of planful problem solving exhibited greater increases in D-dimer from baseline to speech and recovery time points relative to controls. No relationship between avoidant coping and D-dimer was found. CONCLUSIONS: These findings suggest the possibility that approach and problem-solving coping processes buffer the impact of acute psychological stressors on procoagulant activity. It remains to be seen whether interventions that increase approach/problem-solving processes might produce salutary effects among caregiving populations.

Adaptation, Psychological↗

Evaluation of FloSeal as a potential intracavitary hemostatic agent.

BACKGROUND: Noncompressible hemorrhage is a major cause of death in combat and civilian trauma. When surgery is unavailable, one potential solution to such hemorrhage might be the introduction of an agent into the closed body cavity to provide hemostasis via a combination of coagulative and tamponade effects. FloSeal is an agent containing collagen and thrombin with proven hemostatic efficacy when applied with manual pressure to a bleeding site. The current studies were conducted to analyze the ability of FloSeal to reduce blood loss and increase survival time when applied directly, immediately, and without additional pressure to a severe liver injury in rats. METHODS: Male rats were anesthetized and catheters were placed in the carotid artery (for measurement of blood pressure) and jugular vein (for resuscitation with lactated Ringers, 3.3 mL/min/kg BW). After midventral laparotomy, the liver was exposed and caudal portions of both medial lobes ( approximately 1% of body weight) were rapidly excised. FloSeal (5 mL, 800 units Thrombin/mL) or vehicle (5 mL, 0.9% NaCl) was directly and immediately applied to the cut liver surface. The abdominal cavity was closed and resuscitation initiated. After hemorrhage-induced death, or after euthanasia at 90 minutes, fluid loss (blood + resuscitation fluid) was measured. RESULTS: Compared with the control group, direct and immediate application of FloSeal was associated with a reduction in the amounts of fluid lost into the abdominal cavity (p < 0.01) (19.2 +/- 1.5 versus 25.1 +/- 1.5 g) and enhanced mean arterial pressure at 5, 20, and 30 minutes after injury (p = 0.02), but neither survival time (p = 0.12) nor percent survival (p = 0.17) differed between treated and control groups. CONCLUSIONS: Reductions in fluid loss after liver injury and hemorrhage in FloSeal-treated rats in the absence of additional applied pressure are encouraging, and provide evidence for the ability of FloSeal to reduce blood loss when applied immediately and directly to a bleeding tissue.

Analysis of Variance↗

Hemostatic and inflammatory markers as risk factors for coronary disease in the elderly.

Inflammation has been recognized as an integral component of atherothrombotic disease, and inflammatory markers are strongly related to future cardiovascular disease risk in elderly men, and to a certain extent in elderly women. The association is complicated by the prevalence of hormone replacement therapy among older women, and the variety of the underlying vascular disease. For fatal events, inflammation markers exhibit a time-to-event dependency in the elderly that has not been noted to the same degree in younger people. Hemostatic markers that represent inflammatory processes or coagulation activation also predict future risk in older individuals, but there is little evidence for associations between cardiovascular disease risk and ambient levels of coagulation or fibrinolytic factors.

Age Factors↗

Allergic urticaria and angioedema caused by a hemostatic sponge of bovine fibrin used in tooth extraction.

We report the case of a 54-year-old woman with no history of atopic diseases or drug allergies who developed a generalized anaphylactic reaction with urticaria and angioedema a few hours after tooth extraction. The skin scratch and RAST tests demonstrated IgE-mediated hypersensitivity to the product Hémofibrine, a hemostatic sponge made of bovine fibrin. Of all RAST controls, only one serum with known positivity to bovine serum albumin (BSA) showed a low degree of positivity to Hémofibrine. Bovine fibrin should be added to the list of medical products that can elicit allergic reactions following dental treatment.

Anaphylaxis↗

Extended monitoring of hemostatic activation after varicose vein surgery under general anesthesia.

BACKGROUND: Postoperative heparin prophylaxis after stripping of the long saphenous vein is a matter of controversial discussion, and practices vary by surgeon and country. OBJECTIVE: The aim of this study was to assess the extent of hypercoagulability by continued monitoring of activation markers of coagulation and fibrinolysis for a period of 3 weeks after stripping of the long saphenous vein and concomitant phlebectomy. METHODS: Including 21 patients, the following markers were measured preoperatively and on postoperative day 1, 2, 3, 7, 14, and 21: Activation products of coagulation: thrombin-antithrombin complex (TAT), thrombus precursor protein (TPP), and prothrombin-fragment F1+2 (F1+2), and markers of fibrinolysis: plasmin-alpha(2)-antiplasmin complexes (PAP), D-Dimer, tissue plasminogen activator (t-PA) antigen, and plasminogen activator inhibitor 1 (PAI-1) antigen. RESULTS: TAT levels increased significantly until day 3 (p=.008) and normalized within 14 days. TPP levels increased significantly until day 7 (p=.02), decreasing to initial values within 21 days. PAP complexes increased significantly until day 2 (p=.02) reducing to baseline within the observation period. D-Dimer levels increased immediately after surgery (p<.001) until day 14 (p<.001) and returned to baseline until day 21. CONCLUSIONS: Significant hemostatic activation after varicose vein surgery was observed and persisted until 3 weeks postoperatively, indicating that heparin prophylaxis for 2 to 3 weeks is advisable for at-risk patients.

Adult↗

Hemostatic abnormalities in two patients implanted with total artificial hearts.

Patients implanted with total artificial hearts (TAH) suffer frequent thromboembolic complications. The authors report results of continuous monitoring of multiple hemostatic parameters and autopsy findings in two patients implanted with TAH. Case 1 who used a TAH for 10 days and then underwent orthotopic transplantation died of fungal infection 7 days later. At autopsy, mycotic and nonmycotic thrombi were found in the brain, kidneys, spleen, and large bowel. Case 2, who survived 396 days with a TAH, suffered multiple thrombotic episodes despite adequate anticoagulation with warfarin. Autopsy revealed widespread thrombotic lesions mostly in the brain and lungs. Both patients had markedly elevated plasma beta-thromboglobulin and fibrinopeptide A levels throughout their survival, indicating sustained activation of platelets and coagulation secondary to blood contact with artificial surface. Other factors such as infection, liver damage, and acute pancreatitis might have also contributed to activation of hemostasis. As used in the authors two patients, antiplatelet drugs and warfarin seem to be ineffective in preventing artificial heart-related thromboembolic complications.

Adult↗

Hemostatic alterations caused by ventricular assist devices for postcardiotomy heart failure.

The hemostatic alterations in two adult patients who were supported by left ventricular assist devices (LVADs) because of postcardiotomy heart failure were evaluated. In both patients, fibrinopeptide A and thrombin-antithrombin III complex increased markedly during the first several days, and thereafter decreased moderately but remained above normal over the entire procedure. Furthermore, fibrinopeptide B beta 15-42 and alpha 2 plasmin inhibitor-plasmin complex were also markedly increased over the entire course of LVAD treatment. These data show that the LVAD system strongly activates both the coagulation and the fibrinolytic system, even when thromboembolic or bleeding complications are not clinically evident. Furthermore, the decrease in physiological coagulation inhibitors, especially protein C, indicates that these factors are activated and consumed during LVAD treatment. Because protein C is important in regulating the coagulation cascade during LVAD treatment, exhaustion of this system might result in thromboembolic complications during LVAD treatment.

Aged↗

Evaluation of canine-derived fibrin sealant as a hemostatic agent.

The purpose of this study was to determine whether canine-derived fibrinogen concentrate applied with bovine thrombin was a safe and effective topical hemostatic agent. A canine liver biopsy model was selected to test this product. Cryoprecipitate was prepared from frozen canine plasma using two freeze/thaw/centrifugation cycles. Six healthy adult dogs (weighing more than 18 kg) were used in the fibrin sealant study, and an additional three dogs were used as controls for the liver biopsy. A 1 x 3 cm liver biopsy specimen was obtained, digital pressure was applied to reduce bleeding, and the fibrinogen concentrate was immediately sprayed on the bleeding surface simultaneously with bovine thrombin (1,000 IU/mL). The mean +/- standard error of the mean (SEM) blood pressure at time of biopsy was 98 +/- 9 mm Hg, and the rate of hemorrhage from the cut liver edge was 8.0 +/- 1.1 mL/min. The total blood loss during fibrin sealant application was 37 +/- 9 mL and total time for hemostasis was 5.5 +/- 1.3 minutes. There was no additional hemorrhage after application of the fibrin sealant. In the three control dogs, fibrin sealant was not applied and only digital compression was used to decrease hemorrhage. Before digital compression, the rate of hemorrhage from the cut liver edge was 13.1 +/- 3.1 mL/min. Bleeding had not stopped after 10 minutes of compression and the mean postcompression rate of hemorrhage was 4.0 +/- 2.6 mL/min. Signs of secondary bleeding after fibrin sealant was applied were not evident during the immediate postoperative period or over the next 14 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of cephalothin, cefazolin, and cefmetazole on the hemostatic mechanism in normal dogs: implications for the surgical patient.

Twenty-six female beagles were used to evaluate the effects of intravenous and long-term subcutaneous administration of cephalothin, cefazolin, and cefmetazole on platelet function and the coagulation cascade. Platelet aggregation in response to an adenosine diphosphate (ADP) agonist, bleeding time, platelet count, platelet size, prothrombin time (PT), and activated partial thromboplastin times (aPTT) were evaluated before and 90 minutes after two intravenous doses (22 mg/kg) of cephalothin, cefazolin, and cefmetazole given at 90-minute intervals. Dogs given saline injections were used as controls. Platelet count, platelet size, PT, and aPTT were evaluated after 7 days of subcutaneous administration of saline, cefazolin, and cefmetazole (22 mg/kg every 8 hours). A significant decrease in platelet aggregation in response to ADP was detected 90 minutes after intravenous administration of cephalothin. Bleeding time was increased significantly 90 minutes after intravenous administration of cefmetazole. Platelet size was decreased significantly 24 hours after onset of the study in all animals, including controls. No significant changes in platelet count, platelet size, PT, or aPTT were detected after 7 days of subcutaneous administration. Cefazolin had no adverse effects on platelet aggregation in response to ADP, bleeding time, platelet count, platelet size, PT, or aPTT. Therefore, cefazolin should be considered as a perioperative antibiotic in dogs with conditions predisposing to hemostatic complications.

Animals↗

Dementia in subjects with atrial fibrillation: hemostatic function and the role of anticoagulation.

BACKGROUND: Atrial fibrillation (AF) is associated with cognitive impairment and dementia, perhaps through encouraging a prothrombotic state and cardioembolism. OBJECTIVES: We wished to test the hypotheses that hemostatic function is altered in subjects with AF who develop dementia, and that long-term warfarin anticoagulation is protective against this complication. PATIENTS AND METHODS: Recruitment was from an observational cohort study of AF. Baseline assessment included measurement of plasma fibrinogen, fibrin D-dimer, prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complexes (TAT), von Willebrand factor and tissue plasminogen activator. We assessed cognitive function after 3 years' follow-up using the 13-item modified Telephone Interview for Cognitive Status (TICSm) and the short form of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). RESULTS: Of the 218 subjects assessed, 145 (66%) were prescribed warfarin. Forty-nine (22%) met TICSm/IQCODE criteria for dementia. D-dimer, F1+2 and TAT levels were higher in AF subjects with dementia compared with those without (medians 81 vs. 60 ng mL(-1), P = 0.008; 0.76 vs. 0.49 nmol L(-1), P = 0.006; and 1.78 vs. 1.44 microg L(-1), P = 0.003, respectively). These associations became of borderline statistical significance following adjustment for age. Logistic regression showed a trend towards warfarin use being independently associated with reduced prevalence of dementia (odds ratio 0.52, P = 0.08). CONCLUSIONS: We found evidence of increased thrombin generation and fibrin turnover in subjects with AF and dementia compared with those without dementia. Long-term warfarin use may be protective against the development of dementia in subjects with AF.

Aged↗

Identifying novel genetic determinants of hemostatic balance.

Incomplete penetrance and variable expressivity confound the diagnosis and therapy of most inherited thrombotic and hemorrhagic disorders. For many of these diseases, some or most of this variability is determined by genetic modifiers distinct from the primary disease gene itself. Clues toward identifying such modifier genes may come from studying rare Mendelian disorders of hemostasis. Examples include identification of the cause of combined factor V and VIII deficiency as mutations in the ER Golgi intermediate compartment proteins LMAN1 and MCFD2. These proteins form a cargo receptor that facilitates the transport of factors V and VIII, and presumably other proteins, from the ER to the Golgi. A similar positional cloning approach identified ADAMTS-13 as the gene responsible for familial TTP. Along with the work of many other groups, these findings identified VWF proteolysis by ADAMTS-13 as a key regulatory pathway for hemostasis. Recent advances in mouse genetics also provide powerful tools for the identification of novel genes contributing to hemostatic balance. Genetic studies of inbred mouse lines with unusually high and unusually low plasma VWF levels identified polymorphic variation in the expression of a glycosyltransferase gene, Galgt2, as an important determinant of plasma VWF levels in the mouse. Ongoing studies in mice genetically engineered to carry the factor V Leiden mutation may similarly identify novel genes contributing to thrombosis risk in humans.

ADAM Proteins↗

Proteolytic cleavage of protein S during the hemostatic response.

BACKGROUND: Protein S is a vitamin K-dependent protein with anticoagulant properties. It contains a so-called thrombin-sensitive region (TSR), which is susceptible to cleavage by coagulation factor Xa (FXa) and thrombin. Upon cleavage, the anticoagulant activity of protein S is abolished. OBJECTIVE: The aim of the present study was to determine whether protein S is cleaved within the TSR during activation of the coagulation system under near physiological conditions. RESULTS: In a reconstituted coagulation system containing apart from protein S only procoagulant constituents and synthetic phospholipid vesicles, protein S was cleaved at Arg60 by the FXa generated (3 mol min(-1) mol(-1) enzyme). FXa-catalyzed cleavage of protein S, however, was inhibited by factor Va and prothrombin by more than 70%. During clotting of recalcified citrated plasma in the presence of a synthetic lipid membrane, no FXa-catalyzed proteolysis of protein S was observed. Substituting platelets for phospholipid vesicles resulted both in the reconstituted system and in plasma in cleavage of the TSR. Cleavage was at Arg60 and was observed upon platelet activation, irrespective of the presence of FXa (13 pmol min(-1) 10(-8) platelets). No cleavage by thrombin was observed in either the reconstituted coagulation system or clotting plasma. CONCLUSION: These findings suggest that in vivo the anticoagulant activity of protein S is not down-regulated by FXa or thrombin during activation of coagulation. Our results rather suggest a role for a platelet protease in down-regulating the anticoagulant activity of protein S during the hemostatic response.

Binding Sites↗

The effect of levonorgestrel-releasing intrauterine system use on menstrual blood loss and the hemostatic, fibrinolytic/inhibitor systems in women with menorrhagia.

BACKGROUND: Menorrhagia is known to be associated with uterine fibroids, adenomyosis, pelvic infections, endometrial polyps and clotting defects. A viable alternative therapy to hysterectomy should alleviate heavy menstrual blood flow and consequently improve the quality-of-life measures in women presenting with menorrhagia. The levonorgestrel-releasing intrauterine system (LNG-IUS) ranks higher than medical treatments in terms of efficacy, comparable improvements in quality of life and psychological well-being. OBJECTIVE: The purpose of the study was to determine the effects of 6 months of LNG-IUS use on menstrual blood loss and the hemostatic, fibrinolytic/inhibitor systems in blood and the endometrium in women with menorrhagia with known pathologic causes. PATIENTS AND METHODS: Samples from 41 women were analyzed. Hemoglobin, hematocrit, thrombelastography, tissue-type plasminogen activator (t-PA), urokinase plasminogen activator (u-PA), u-PA receptor (u-PAR), plasminogen activator inhibitor-1/2 (PAI-1/2), D-dimer and von Willebrand factor (VWF) were determined, and t-PA, u-PA and PAI-1/2 were also determined in endometrial tissue extracts. RESULTS: Menorrhagia was reduced in 89% of women by 3 months; by 6 months all women had no menorrhagia, and 39% of women had become amenorrhoeic. Hemoglobin and hematocrit levels showed improvement, and reached normal reference levels by 6 months. There were no systemic changes in the fibrinolytic/inhibitor systems and VWF, except for a decreased u-PAR level. However, in the endometrium, significant elevations in PAI-1/2 together with u-PAR levels were seen at 6 months. CONCLUSIONS: The slow levonorgestrel-release intrauterine device use results in high expression of fibrinolytic inhibitors (PAI-1/2) and upregulated u-PAR expression in the endometrium. Systemic hemostasis was not significantly altered. The study demonstrated that LNG-IUS is highly effective in the treatment of menorrhagia with known pathologic causes.

Adult↗

Reduced fibrinolysis and increased fibrin generation can be detected in hypercoagulable patients using the overall hemostatic potential assay.

BACKGROUND: Routinely available coagulation assays are not capable of detecting clinically defined hypercoagulable states. A number of global coagulation assays have been developed with the potential to evaluate hypercoagulability, which predisposes to the common clinical events of arterial and venous thromboembolism (VTE). OBJECTIVES: We hypothesized that the overall hemostatic potential (OHP) assay would show abnormal fibrin generation and lysis in patients with clinically defined hypercoagulable states. METHODS: We used the OHP assay as described by Blombäck and colleagues [1,2] in 161 clinically hypercoagulable patients with arterial or VTE, pregnancy complications or autoimmune disease. Eighty patients had associated antiphospholipid antibodies (APLA). Ninety-eight normal plasma donors were tested for comparison. RESULTS: We derived three new assay parameters for correlation with hypercoagulable states: the maximum optical density, maximum slope, and delay in onset of fibrin generation. We found significantly different assay results for all patients' parameters examined when compared with controls, indicating both increased fibrin generation and reduced fibrinolysis in hypercoagulable patients. The findings were similar whether samples were collected in association with an acute thrombotic event or not. Estimated assay sensitivity for detection of a clinically defined hypercoagulable state was 96%. CONCLUSIONS: The OHP assay is a simple, inexpensive global test that is useful for assessing patients with hypercoagulable states including APLA. OHP results are significantly abnormal in hypercoagulable groups compared with controls, indicating that both increased fibrin generation and reduced fibrinolysis contribute to hypercoagulable states. The assay may ultimately assist in tailoring clinical management to patients' individual requirements.

Adolescent↗

Stability of hemostatic proteins in canine fresh frozen plasma units.

The stability of hemostatic proteins, including coagulation factors II, VII, VIII, IX, and X and von Willebrand factor (vWf), in canine fresh frozen plasma (FFP) units stored for up to 1 year was studied. Plasma units from 7 donor dogs were subjected to 4 treatments following collection, including storage at -30 degrees C for 3 months, 6 months, and 1 year and storage at -20 degrees C for 6 months. Coagulant factor activity and vWf concentrations were measured at these times. Significant differences between prestorage and poststorage values were noted for factors VIII, IX, and X, and vWf. Differences seemed to be least pronounced for plasma stored for 3 months; however, a significant interaction between prestorage and poststorage differences and the 4 treatment groups could not be demonstrated. On the basis of factor content in the present study, 15-20 mL/kg of FFP stored for up to 1 year was capable of providing approximately 10-15 U/kg of vWf and factors VIII, IX, X, and II, whereas 10 mL/kg FFP provided at least 10 U/kg of factor VII.

Journal Article↗

Hemostatic disorders in cats: a retrospective study and review of the literature.

Hemostasis profiles from 101 cats presented for medical or surgical evaluation to The Ohio State University Veterinary Teaching Hospital from 1986 through 1991 were reviewed retrospectively; 69% were abnormal. Commonly identified abnormalities included a mixed hemostatic defect compatible with disseminated intravascular coagulation, thrombocytopenia, isolated prolongation of the activated partial thromboplastin time (APTT), and prolongation of both the APTT and one-stage prothrombin time. The most common disorders associated with abnormal hemostasis profiles in this study were liver disease, neoplasia, and feline infectious peritonitis.

Animals↗

Hemostatic changes in dogs with naturally occurring sepsis.

Sepsis is a frequent source of morbidity and mortality in critically ill patients. The goal of this case control study was to measure hemostatic changes in dogs with naturally occurring sepsis. Blood was collected within 24 hours of admission from 20 dogs that fulfilled the criteria for sepsis. Sepsis was defined as histologic or microbiological confirmation of infection and 2 or more of the following criteria: hypo- or hyperthermia, tachycardia, tachypnea, or leukopenia, leukocytosis, or > 3% bands. Culture and sensitivities were performed on appropriate samples from all septic dogs. Twenty-eight control dogs were enrolled on the basis of normal results of physical examination, CBC, serum biochemistry, and coagulation profile. Plasma samples were analyzed for prothrombin time (PT), partial thromboplastin time (PTT), fibrin(ogen) degradation products (FDP), D-dimer (DD) concentrations, antithrombin (AT) activity, and protein C (PC) activity. Data were compared between groups by chi-square or independent t-tests. PC (P < .001) and AT (P < .001) activities were significantly lower in dogs with sepsis compared to controls. Dogs with sepsis had significantly higher PT (P = .007), PTT (P = .005), D-dimer (P = .005), and FDP (P = .001) compared to controls. Platelet counts were not significantly different between groups. Ten of the 20 septic dogs (50%) died, but no association was identified between any of the measured variables and outcome. These findings are consistent with previous studies in animals with experimentally induced disease and in clinical studies of humans. On the basis of these results, further investigation of the role of AT and PC in canine sepsis is warranted.

Animals↗