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What happens to hemostatic agents in contact with urine? An in vitro study.

BACKGROUND AND PURPOSE: As the indications for topical hemostatic agents increase in urology, the question arises: what happens to these agents when they enter the urinary collecting system? To answer this question, we performed a series of in-vitro experiments mixing three hemostatic agents with normal and sanguineous urine. MATERIALS AND METHODS: Four commercially available topical hemostatic products: oxidized regenerated cellulose (Surgicel; Ethicon, Somerville, NJ), fibrin sealant (Tisseel VH Kit; Baxter Health Care Corporation, Irvine, CA), gelatin matrix hemostatic sealant (FloSeal; Baxter Health Care), and polyethylene glycol (CoSeal; Cohesion Technologies, Palo Alto, CA) were studied. Human urine (10 mL) was added to samples of each substance; this was done in triplicate. The 12 sample tubes were then capped and placed on a tube shaker at slow speed and 37 degrees C. Observations regarding consistency of the material were made at 6, 12, 24, 48, 72, 96, and 120 hours (5 days). Gelatin matrix hemostatic sealant was further tested in urine with various amounts of blood or blood clot; observations were again recorded out to 5 days. RESULTS: Surgicel maintained its solid form when it initially came in contact with urine, but over a period of 5 days, it transformed into a mucoid substance with visible free-floating fibers. It did not dissolve completely in urine within 5 days. Gelatin matrix was immediately transformed by urine into a fine colloidal suspension that did not change over the 5 days of the study. Fibrin glue, after mixing of the two components (fibrinogen and thrombin) directly in the urine, and polyethylene glycol immediately formed a solid clot at the bottom of the test tube on contact with the urine. When the mixture of fibrin sealant was allowed to form for 15 minutes and then added to urine, it again maintained a solid form. After 72 hours, the fibrin glue became a semisolid gelatinous plug. On analysis at 5 days, the fibrin sealant clot had transformed into a cohesive mucoid gel, and the polyethylene glycol clot had not changed. The gelatin matrix hemostatic sealant, when in contact with blood or blood clot, appeared to either become part of a clot or to remain in a colloidal suspension. At 5 days, all clots had dissolved to fine particulate suspensions, and the gelatin matrix appeared as a fine suspension. CONCLUSION: Fibrin glue and oxidized regenerated cellulose maintain a solid form when initially placed in direct contact with urine and then assume a semisolid gelatinous state, which is still present at 5 days. Polyethylene glycol forms a solid clot initially and does not change after 5 days. Only hemostatic gelatin matrix remained as a fine particulate suspension in both normal and sanguineous urine. The implications of these findings with regard to sealing the renal parenchyma or small violations of the collecting system after percutaneous or laparoscopic surgery await in-vivo testing.

Blood Loss, Surgical↗

Hemostatic mouthwashes in anticoagulated patients undergoing dental extraction.

OBJECTIVE: To evaluate the efficacy and safety of local acting hemostatic agents in patients who are undergoing dental extraction(s) and are taking oral anticoagulants. DATA SOURCES: A search of MEDLINE (1966-July 2006), International Pharmaceutical Abstracts (1970-July 2006), and EMBASE (1966-July 2006) was conducted using the key terms anticoagulation, warfarin, hemostatic mouthwashes, epsilon aminocaproic acid, tranexamic acid, dental extraction, and oral surgery. Bibliographies of relevant papers were reviewed for additional references. STUDY SELECTION AND DATA EXTRACTION: English-language literature, including abstracts, clinical trials, and review articles, were reviewed. Clinical trials were included if they evaluated hemostatic mouthwashes in patients receiving continued anticoagulation and undergoing dental extractions or various oral surgeries including dental extraction. Eight clinical trials met study selection criteria for evaluation of hemostatic mouthwashes in anticoagulated patients undergoing dental extraction. Eight studies evaluated tranexamic acid; one assessed epsilon aminocaproic acid. All studies were reviewed for efficacy and safety of hemostatic mouthwashes and intensity of continued anticoagulation therapy. DATA SYNTHESIS: Eight small studies enrolled populations that varied in the indications for oral anticoagulation (OA), target INR ranges, and oral surgeries performed. Patients receiving uninterrupted OA and using hemostatic mouthwashes had no greater and, in some cases, lesser bleeding incidence compared with various other treatment groups (including interrupted OA, uninterrupted OA, autologous fibrin glue with uninterrupted OA, and reduced OA with heparin bridge). No severe adverse effects were reported. No studies assessed the risk of thromboembolism between the different treatment strategies. CONCLUSIONS: Findings in recent studies indicate that dental extractions in anticoagulated patients can be performed without temporary discontinuation of oral anticoagulant therapy with the use of hemostatic mouthwashes to control localized bleeding. This practice should be more widely adopted due to minimized bleeding and thromboembolic risks.

Anticoagulants↗

Absorbable hemostatic agents.

PURPOSE: The pharmacology, clinical efficacy, adverse effects and toxicities, drug interactions, dosage and administration, and safety issues related to the use of absorbable hemostatic agents are reviewed. SUMMARY: Absorbable hemostatic agents exert their pharmacologic effects at various points within the coagulation cascade. These agents are indicated for use during surgical procedures as adjunctive therapy when bleeding is not controlled by conventional methods. Early clinical data on absorbable hemostatic agents revealed a beneficial effect with regard to controlling capillary bleeding, achieving hemostasis during vascular surgery, and controlling bleeding from fistula-puncture sites. Few randomized controlled clinical trials have directly compared available agents, but case reports describing the efficacy of absorbable hemostatic agents in specific situations, especially unlabeled uses of thrombin, abound. Existing trials have compared the efficacy of established agents with newer agents, including fibrin sealants, with varying results. A variety of rarely occurring adverse effects have been reported with the administration of absorbable hemostatic agents; some of these rare effects, such as paralysis, are quite severe. No standardized dosing regimens are available for these agents, although surgeons may have a preference for a particular regimen based on their own clinical experience. No drug interactions involving absorbable hemostatic agents have been published; however, the use of these agents with other medications that affect hemostasis may disrupt clot formation. CONCLUSION: Absorbable hemostatic agents are useful as adjunctive therapy during surgical procedures when conventional methods do not control bleeding. Although rare adverse effects have occurred with these agents, their careful administration will prevent serious adverse outcomes.

Absorption↗

Hemostatic activation in spontaneous intracerebral hemorrhage.

BACKGROUND AND PURPOSE: There is no in-depth information available on the changes in hemostatic systems in patients in the acute phase of spontaneous intracerebral hemorrhage (ICH). This study was conducted to assess the relationships between the changes in hemostatic systems and clinical parameters in patients in acute-phase ICH. METHODS: The records of 358 patients admitted within 6 hours of onset of ICH were reviewed to examine the relationships between changes in hemostatic systems and computed tomographic findings and clinical parameters. RESULTS: -The white blood cell counts and the levels of thrombin-antithrombin complex, plasmin-antiplasmin complex, and D-dimer in patients with intraventricular extension (IVE) or subarachnoid hemorrhage (SAH) were significantly (P<0.05) higher than those in patients without IVE or SAH. Most of the hemostatic system parameters in patients without IVE or SAH showed no significant differences compared with normal subjects. Multiple linear regression analysis revealed that the levels of thrombin-antithrombin complex significantly increased with an increase in the amount of SAH (P<0.001) and IVE (P<0.001). The levels of thrombin-antithrombin complex were not significantly associated with the volume of intraparenchymal hematoma. The level of the complex, however, was significantly (P<0.001) and independently associated with the presence of IVE or SAH (multiple logistic regression analysis). CONCLUSIONS: The systemic activation of hemostatic systems in ICH patients seems to take place only when blood reaches the subarachnoid space. The intraparenchymal hematoma itself seems unlikely to activate hemostatic systems in peripheral blood, although the hematoma is expected to cause local activation of hemostatic systems.

Antifibrinolytic Agents↗

Preoperative hemostatic assessment of the adenotonsillectomy patient.

Intraoperative or postoperative hemorrhage in the patient who has undergone an adenotonsillectomy because of an unrecognized hemostatic defect may increase morbidity and can be potentially life-threatening to the patient in what should be a "routine" procedure. Preoperative identification of occult hemostatic abnormalities, coupled with perioperative management directed at correcting the effects of the defects, should serve to reduce the incidence of this distressful complication. Routine use of preoperative laboratory screening tests for this purpose has been discouraged recently as a result of concerns over cost-effectiveness and the low predictiveness of the tests for bleeding. Our experience with the routine use of a comprehensive hemostatic laboratory screening panel--which includes a bleeding time test--in the adenotonsillectomy patient population demonstrated that 11.5% of our patients had abnormal initial screening laboratory tests; these results were ultimately attributable to occult hemostatic defects. Clinical history, the universally recommended method of preoperative hemostatic assessment, failed to detect any previously unrecognized coagulation disorder. Laboratory screening improved preoperative detection of occult hemostatic defects and allowed for appropriate alterations in perioperative care. Our results with this approach are presented, along with illustrative case histories and a discussion of the current recommendations for preoperative laboratory screening of the hemostatic system, as found in a review of the literature.

Adenoidectomy↗

Dynamic variability of hemostatic and fibrinolytic factors in young women.

This prospective study was designed to characterize the time course and variability of hemostatic and fibrinolytic risk factors over the course of a menstrual cycle in normal premenopausal women. Plasminogen activator inhibitor (PAI-1), tissue plasminogen activator, von Willebrand factor, fibrinogen, and fibrin D-dimer predict risk of coronary heart disease. Yet there is limited information describing the status of endogenous hormone concentrations and hemostatic and coagulation factors in premenopausal women. Twenty premenopausal women, mean age 34 +/- 7 yr, underwent testing over a cycle to measure endogenous hormones and hemostatic factors: estradiol and progesterone, FSH, LH; PAI-1, tissue plasminogen activator, von Willebrand factor, fibrin D-dimer, and fibrinogen as well as lipids: total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, and triglycerides. There was cyclical variability in estradiol (P < 0.01) and progesterone (P < 0.001) during the follicular and luteal phases. Moreover, there was intra- and interindividual cyclical variation in hemostatic risk factors. Measures of PAI-1 (P < 0.01) and D-dimer (P < 0.05) differed during the follicular and luteal phases. As estradiol concentration increased, PAI-I decreased. There was a significant correlation between total cholesterol and PAI-1 (r = 0.56, P < 0.05), low-density lipoprotein-cholesterol and PAI-1 (r = 0.50, P < 0.05) as well as between total cholesterol and fibrinogen (r = 0.61, P < 0.05). There is significant cyclical variability in estradiol, FSH, and progesterone as well as the hemostatic factors, PAI-1 and fibrin D-dimer. Characterization of emerging hemostatic risk factors enhances understanding of normal physiology, provides insight into the relation between estrogen and hemostatic factors, and raises the potential for predicting coronary heart disease even in relatively young women.

Adult↗

Maturation of the hemostatic system during childhood.

The hemostatic system is assumed to be similar in children and adults and reference ranges established for adults are commonly used to evaluate children suspected of having congenital or acquired hemostatic problems. However, we know that the hemostatic system is not fully mature by 6 months of age and comprehensive studies of healthy older children have not been published. Therefore, we conducted a prospective cohort study of the hemostatic system in healthy children having minor, elective day surgery. After obtaining informed consent, a 3-mL blood sample was obtained at the time routine preoperative blood work was drawn. The plasma was fractioned and stored at -70 degrees C for batch assaying. We measured the concentration of 33 components of the hemostatic system (functional and immunologic assays) and the bleeding time (automated pediatric device) in 246 children aged 1 to 16 inclusive (a minimum of four subjects at each age). Eleven components of hemostasis (fibrinogen, prekallikrein, high-molecular weight kininogen, factors VIII and XIII, antithrombin III [ATIII], heparin cofactor II [HCII], alpha 1-antitrypsin [alpha 1AT], protein S, plasminogen, alpha 2-antiplasmin [alpha 2AP]) had mean values and ranges of normal that were similar to adults. Mean values of seven coagulants (II, V, VII, IX, X, XI, XII) were significantly lower than adult values and varied with age. Values for three inhibitors, alpha 2-macroglobulin (alpha 2M), protein C, and protein C1-inhibitor (C1-Inh) also differed from adults. Alpha 2M and C1-Inh inhibitor levels were elevated throughout childhood, whereas protein C levels were low, with a lower limit of normal of 0.40 U/mL until the age of 11. Finally, the upper limit of normal for the bleeding time was longer in children during the first 10 years of life, but decreased to adult values in the teenage years. In summary, there are important physiologic differences in the hemostatic system in children compared with adults. The decreased levels of several critical coagulants and increased levels of alpha 2M may contribute in part to the lower risk of thrombotic events in childhood. Age-matched controls should be used for evaluation of the hemostatic system in children with suspected congenital or acquired defects.

Adolescent↗

[Preliminary evaluation on seroma prevention and treatment with transposition of tissue flaps and arista hemostatic powder].

OBJECTIVE: To investigate and evaluate prevention and treatment of seroma by transposition of tissue flaps and Arista hemostatic powder after regional lymph node resection in patients with malignant tumors. METHODS: Twelve patients (6 males, 6 females; aged 31-81 years, with metastatic tumors underwent prevention and treatment of seroma with the tissue flaps and Arista hemostatic powder spray after regional lymph node resection. The metastatic tumors involved the axilla in 1 patient with breast carcinoma, the iliac and inguinal regions in 2 patients with carcinomas of the uterine cervix and the rectum, and the inguinal region in 9 patients, including 4 patients with malignant fibrous histiocytoma(3 in the thigh, 1 in the leg), 2 patients with squamous carcinomas in the leg, 1 patient with synovial sarcoma in the knee, 1 patient with epithelioid sarcoma in the leg, and 1 patient with malignant melanoma in the foot. As for the lymph node removal therapy. 1 patient underwent axillary lymph node removal, 2 patients underwent lymph node removal in theiliac and inguinal regions, and 9 patients underwent lymph node removal in the inguinal region. Meanwhile, of the 12 patients, 6 patients underwent transposition of sartorius flaps with Arista hemostatic powder, 3 patients underwent transposition of the rectus abdominis myocutaneous flaps (including 2 patients treated with Arista spray befor the wound closure and 1 patient treated by transposition of local skin flaps with Arista spray used again),and 3 patients underwent only the suturing of the wounds combined with Arista. At the same time, of the 12 patients,only 4 patient underwent the transplantation of artificial blood vessels. RESULTS: The follow-up for 2-10 months after operation revealed that 10 patients, who had received the transposition of tissue flaps and the spray of Arista hemostatic powder, had the first intention of the incision heal with seroma cured. Nine patients were given a preventive use of Arista hemostatic powder and therefore no seroma developed. The combined use of the transposition of tissue flaps and Arista hemostatic powder spray achieved a success rate of 100% in the prevention or treatment of seroma. However, 1 patient developed microcirculation disturbance 24 hours after operation and underwent disarticulation of the hip; 1 patient developed pelvic cavity hydrops and died 10 months after operation. CONCLUSION: The combined use of transposition of tissue flaps and Arista hemostatic powder spray can effectively prevent or treat seroma after regional lymph node removal in a patient with malignant tumor.

Adult↗

Comparative study of the efficacy of the common topical hemostatic agents with fibrin sealant in a rabbit aortic anastomosis model.

OBJECTIVE: The purpose of this study was to compare the hemostatic efficacy of the common surgical hemostatic agents with fibrin sealant (FS) and to assess their functional strength to secure hemostasis in lieu of placing additional sutures. METHODS: End-to-end anastomosis of transected abdominal aorta was performed in moderately anticoagulated rabbits using 4 or 6 interrupted sutures. The suture line was covered either with gauze alone ("untreated") or with gauze plus Gelfoam, Avitene, Surgicel, FloSeal, or FS, following which blood flow was restored. Blood loss was absorbed by gauze and measured. The surviving rabbits were recovered and the repaired vessel was examined histologically 4 weeks after operation. The investigators were blinded to the treatment groups. Aortic anastomoses using 8 or 12 sutures (untreated) were also performed. RESULTS: Untreated 4-suture anastomosis of aorta resulted in a profuse hemorrhage with an average 108.0 +/- 19.2 (mean +/- SD) ml blood loss and 100% mortality (n = 4). FS application sealed the anastomoses, prevented blood loss (P < 0.01 vs untreated) and exsanguination of the rabbits (n = 4). Other hemostatic agents reduced the bleeding to varying degrees compared to the untreated animals (Gelfoam 66.4 +/- 17.6, Avitene 80.6 +/- 34, Surgicel 66.7 +/- 16.7, FloSeal 44.2 +/- 8.5 ml blood loss, n = 4/group), but the changes were not statistically significant. One to three rabbits in each group survived the operation. Six-suture aortic anastomoses, untreated, resulted in 67.7 +/- 21.8 ml blood loss and 100% survival (n = 6). Application of FS produced immediate and sustained hemostasis in all the animals (P < 0.01 vs untreated). Other hemostatic agents also reduced the bleeding (Gelfoam 42.5 +/- 10, Avitene 50.9 +/- 12.4, Surgicel 32.1 +/- 14, FloSeal 33.9 +/- 5.4 ml blood loss, n = 6/group), but the changes were not statistically significant. The 8- and 12-suture aorta repairs resulted in a moderate blood loss (43.9 +/- 19 and 21.3 +/- 14.9 ml, respectively), followed by a stable hemostasis that precluded the need to use any hemostatic agent. The aortic cross-clamping time of the 12-suture and time to hemostasis for both the 8- and the 12-suture techniques were significantly longer than those of the 4-suture plus FS application (P < 0.01, P < 0.01 and P < 0.05, respectively). CONCLUSION: In a moderate coagulopathy, FS was proven to be the most efficacious hemostatic agent, producing immediate and sustained hemostasis at the arterial anastomotic site. This high efficacy is in part attributed to the strong tissue adhesive property of this agent. FS application may potentially ease the anastomosis and shorten the duration of timely critical vascular procedures.

Anastomosis, Surgical↗

Biocompatibility and bioabsorption of microfibrillar collagen hemostat in experimental animals.

The effects of Microfibrillar Collagen Hemostat (MCH) and Gelfoam after surgical implantation into incision sites of the liver, kidney, and brain were studied in beagle dogs, rabbits, and beagle dogs, respectively. The results of these experimental animal studies suggest that MCH is comparable to Gelfoam with respect to biocompatibility, rate of bioassimilation, and a lack for adverse systemic effects. The brain, liver, and kidney tissues responded comparably to MCH and Gelfoam with a mild to moderate infiltration of macrophages and mononuclear cells. Most of the hemostatic compound had disappeared from the incision sites by Day 28 and completely disappeared by Day 84. The tissue degree response was interpreted as a factor in the process of bioassimilation of the two hemostatic materials. Both hemostatic compounds contributed to adhesion formation in the experimental models. The incidence of adhesions was somewhat lower for MCH than for Gelfoam, but both produced more adhesions than were found at the control sites. The adhesions were only to the adjacent structures and always localized to the surgical site. When MCH or Gelfoam is used under conditions similar to those in the present experimental study, where tissue approximation is impaired, and where growth of granulation tissue is stimulated by the physical presence of the hemostatic compound, there is the possibility for increased incidence of adhesion formation. However, when an intraperitoneal absorbable hemostatic compound is desired, the present studies in experimental animals suggest that MCH will be safe by exhibiting minimal tissue reaction.

Absorption↗

Microfibrillar collagen hemostat during laparoscopically directed liver biopsy.

Meticulous hemostasis is a necessity during laparoscopic procedures in maintaining a clear visual field and avoiding the need for an extended laparotomy to secure hemostasis. Methods of hemostasis available to laparoscopic surgeons include direct pressure, suture/clip ligation, conventional monopolar or argon-enhanced coagulation, and application of topical hemostatic agents. The effectiveness of topical hemostatic agents for open surgical procedures has been demonstrated; however, to date, laparoscopic utilization of topical hemostatic agents has been hampered by lack of compatible forms for laparoscopic instillation. Endo-Avitene is a 15 x 50 mm rolled sheet of microfibrillar collagen hemostat, available in an applicator capable of placement through standard laparoscopic trocar. The use of Endo-Avitene during laparoscopically-directed liver biopsies in a porcine model is reported. The effective hemostatic properties of microfibrillar collagen hemostat were reaffirmed and the clinical utility of Endo-Avitene for laparoscopic use is demonstrated.

Animals↗

Arterial puncture site management after percutaneous transluminal procedures using a hemostatic wound dressing (Clo-Sur P.A.D.) versus conventional manual compression: a randomized controlled trial.

PURPOSE: To investigate the efficacy and safety of a novel hemostatic wound dressing designed for rapid hemostasis at arterial puncture sites. METHODS: Over a 15-month period, 209 consecutive patients were randomized to conventional manual compression (n=105) or the use of the Clo-Sur P.A.D. hemostatic device (n=104) after removal of the sheath. Puncture-related and device-related complications, time to hemostasis, time to ambulation, and patient and physician discomfort were recorded. RESULTS: In 209 patients, 21 (10.0%) puncture-related complications were observed, including 11 (5.3%) pseudoaneurysms, 9 (4.3%) hematomas, and 1 (0.5%) major bleeding complication. There was no significant difference (p=0.36) in complications between the hemostatic device (9/104, 8.7%) and the conventional group (12/105, 11.4%). In the hemostatic device group compared to the conventional group, respectively, the average time to hemostasis (13.6 versus 20.3 minutes; p<0.001), time to ambulation (6.5 versus 17.4 hours, p<0.001), patient discomfort (VAS 2.1 versus 4.7, p<0.001), and physician discomfort (VAS 3.8 versus 5.2, p<0.001) were significantly lower. Twenty (19%) sheath removals in the hemostatic device group were classified as a technical failure of the device. CONCLUSION: The use of this hemostatic wound dressing for arterial access site management after percutaneous vascular procedures significantly reduced the time to hemostasis, enabled early mobilization, and reduced patient discomfort without increasing the risk for complications compared to conventional manual compression. A high rate of technical failures, however, warrants further improvement before routine use can be recommended.

Aged↗

[Experimental study on the hemostatic properties of collagen sponge].

OBJECTIVE: To validate the hemostatic properties of collagen sponge made in China. METHODS: The experimental model of superficial cut of liver was established in 20 Sprague-Dawley adult rats, which were divided into two groups randomly. Collagen sponge or gelatin sponge was used to cover the cut respectively. Hemostatic result was observed. Afterwards, standard liver trauma model by resection left front liver lobe was made, wound was treated with collagen sponge or gelatin sponge respectively. Hemostatic result was observed. Concurrent hemostatic time and bleeding amount were noted. At 7, 14 and 20 days after operation, intra-abdominal adhension, infection and healing state of liver were observed by exploratory laparotomy. The histological changes of regenerate liver tissue were observed by microscopy. RESULTS: Collagen sponge adhered to wound well. Concurrent hemostatic time and bleeding amount in collagen sponge group were superior to those of gelatin sponge (P < 0.05). The histological examination showed that collagen sponge was absorbed and degraded rapidly, regenerative hepatocytes could be induced. CONCLUSION: Collagen sponge has fine hemostatic properties and can induce regeneration of hepatocytes effectively. It is worth popularizing for its convenience in clinical application and its properties of rapid degradation and absorption.

Animals↗

Formation and regulation of platelet and fibrin hemostatic plug.

Formation of a hemostatic plug represents one of the earliest responses to vessel wall injury. Platelets react to any discontinuity in the vascular endothelium through initial contact, spreading, and formation of a thrombus (or aggregate). This development of a primary hemostatic plug requires platelet membrane receptors through which the adhesive macromolecules, von Willebrand factor (vWF) and fibrinogen, anchor platelets to the vessel wall and link them to each other. There are two receptor pathways--classic and alternative--for the binding of vWF to platelets; the latter induced by thrombin, and adenosine diphosphate (ADP) is shared with fibrinogen. Synthetic peptides, patterned after known binding domains of adhesive molecules, have been designed to inhibit their interactions with platelet receptors. A secondary hemostatic plug, composed of platelets enmeshed in fibrin, results from the action of thrombin, which is not only essential for formation of fibrin but also for exposure of platelet receptors for adhesive molecules and for "activation" of factors V and VIII. Thrombin generation is greatly enhanced through the activity of the prothrombinase complex formed on the surface of platelets, perturbed endothelial cells, and leukocytes. A pivotal event is activation of factor X through the intrinsic and extrinsic coagulation pathways. Binding of factors IXa and VIIa to the vascular endothelium represents a localized mechanism for factor Xa generation. Formation of a platelet and fibrin thrombus is controlled by regulatory mechanism: prostacyclin, endogenous heparin-antithrombin III complex, thrombomodulin-protein C-protein S system, and the fibrinolytic system. The balance of all components--vessel wall, platelets, adhesive and coagulation proteins, regulatory mechanisms--determines the effectiveness of the hemostatic plug in maintaining the structural and functional integrity of the circulatory system. An approach to detection of hemostatic derangements in patients at risk evolves from a full understanding of inherited and acquired deficiencies affecting each step of hemostatic plug formation and from selective use of laboratory tests.

Blood Coagulation Tests↗

Invasive line placement in critically ill patients: do hemostatic defects matter?

BACKGROUND: Blood components are often given prophylactically before the placement of invasive lines in patients with coagulation defects. Little, however, is known about the epidemiology of defects in these patients. The purpose of this study is to ascertain what proportion of intensive care patients who receive invasive lines have hemostatic defects, what actions are taken by physicians to correct these abnormalities before invasive line insertion, and what the incidence is of bleeding complications after invasive line placement. STUDY DESIGN AND METHODS: Charts were retrospectively reviewed for 490 intensive care patients in whom 938 arterial, pulmonary artery, and central venous lines were placed. RESULTS: At least one defect in hemostasis was documented for 388 patients (41%) before line placement, with 253 (27%) of these patients evidencing severe abnormalities. Seventeen percent of patients had no preprocedure laboratory evaluation. Trauma patients showed the highest numbers of abnormalities in hemostatic testing, but medical patients had more-severe defects. The occurrence of isolated abnormal laboratory values did not predict bleeding, but a score derived from a consideration of multiple defects did. Correction of the abnormalities was attempted in 37 percent of patients with hemostatic defects. Sixteen patients had bleeding complications, but only two had complications that were life-threatening. None of the complications were fatal. CONCLUSION: Invasive lines are used frequently in patients with hemostatic defects, often without any attempt to correct the abnormalities. Nevertheless, rates of hemorrhage are low and appear to be closely related to the level of experience of the physician rather than to defects in hemostasis. These findings suggest that the use of blood components for preprocedure correction of hemostatic defects is not necessary, except in those patients who have the most severe hemostatic abnormalities.

Adolescent↗

Interrelationship between estimates of adiposity and body fat distribution with metabolic and hemostatic parameters in obese children.

Adiposity in childhood is often associated with metabolic abnormalities and accompanied by a dysregulation of the coagulation and fibrinolytic systems. We studied the interrelationship of metabolic and hemostatic parameters and explored their relationship with measures of adiposity and fat distribution in obese children. In 34 obese boys (mean age, 11.7 years) and 57 obese girls (12.1 years), blood samples were determined for insulin, glucose, triglycerides, fibrinogen, plasminogen activator inhibitor-1 (PAI-1), and tissue-type plasminogen activator-antigen (tPA-Ag). Body composition was assessed by means of impedance. Waist (Wc) and hip circumference were measured. The thickness of subcutaneous adipose tissue-layers (SAT-layers) was measured at 15 different body sites (from 1-neck to 15-calf) by means of the optical device, Lipometer. Overall subcutaneous fatness (SAT) was calculated and SAT-distribution was estimated by means of factor analysis. Significant correlations were found between different measures of adiposity and Wc with metabolic parameters. Fibrinogen was mainly associated with upper body subcutaneous fatness (factor 1) in boys. In girls, hemostatic parameters were associated with nearly all measures of adiposity and also with factor 1 and SAT. Regression analysis showed that factor 1 together with PAI-1 (both P <.0001) contribute to fibrinogen (adjusted [adj], R(2) =.30). PAI-1 together with trigylcerides (both P <.0001) and age (P <.04) were main determinants for tPA-Ag (adj, R(2) =.41). tPA-Ag (P <.0001) together with glucose (P <.001, negative slope), fibrinogen (P <.001, negative slope), and percentage fat mass (%FM) (P <.01) contributed to PAI-1 (adj, R(2) =.54). These results favor the concept of an interrelationship between metabolic and hemostatic parameters resulting from increased adiposity, perhaps influenced by pubertal development of children. Although upper body subcutaneous fatness was found to be a main correlate of metabolic and hemostatic parameters, it remains to be investigated whether this type of subcutaneous fat distribution is involved in the expression of metabolic and hemostatic risk factors and participates in the dysregulation of the hemostatic system in the state of childhood obesity.

Adipose Tissue↗

Changes of hemostatic variables during hormone replacement therapy.

Hormone replacement therapy (HRT) is accompanied by many changes in the hemostatic system. Because several individual hemostatic variables have been suspected to be reasonable indicators of the hemostatic balance and because this balance is thought to play an important role in the pathogenesis of several diseases, careful examination of the changes in this system induced by HRT could be helpful, first to improve HRT and second to improve our understanding of mechanisms of cardiovascular disease. The effects of (several forms of) HRT on individual hemostatic variables are discussed in this article. The pattern that emerges is that HRT stimulates coagulation, inhibits anticoagulation, and stimulates fibrinolysis (partly by inhibition of fibrinolysis). There are, however, few data that give clear insight into the effects of HRT on hemostatic variables. Controlled randomized clinical studies are needed to evaluate further the effects of HRT on the hemostatic system, to understand the interplay between inflammation and coagulation (both pathways being affected by HRT), and to understand how HRT-associated changes are affected by differences in genetic background.

Blood Coagulation Factor Inhibitors↗

Development of the hemostatic system in the neonate and young infant.

Our understanding of the coagulation and fibrinolytic systems (the hemostatic system) in the adult has progressed rapidly in recent years. However, a more complete understanding of the physiology of the hemostatic system in the neonate has lagged behind that of the adult for many reasons. First, the hemostatic system in the newborn exists in a dynamic state and is rapidly evolving toward the adult system. This situation necessitates the generation of not one, but several, reference ranges (or ranges of normal values) in the postnatal period for the various tests and components of the hemostatic system. Also, microtechniques must be used to perform the required assays, both because of the small size of blood samples available and because of the difficulty of obtaining blood from infants. Recently, many of these problems have been resolved, which resulted in a better appreciation of the development of the hemostatic system in the infant. This article reviews our current understanding of the protein components of the coagulation and fibrinolytic systems in the neonate. Reference ranges for normal values of the various tests and components of the hemostatic system have been provided for the premature and full-term infant at birth and during the first 6 months of life.

Aging↗