Randomized clinical trial of fibrin sealant in patients undergoing resternotomy or reoperation after cardiac operations. A multicenter study

A multicenter study was conducted to test the efficacy and safety of fibrin sealant as a topical hemostatic agent in patients undergoing either reoperative cardiac surgery (redo) or emergency resternotomy. A total of 333 patients from 11 centers in the United States were included in the study. Patients were randomly assigned to initially receive the fibrin sealant or a conventional topical hemostatic agent when such was required during an operation. The end point used to evaluate the agent's efficacy was local hemostasis, the number of bleeding episodes controlled within 5 minutes. The fibrin sealant group from the prospective study was compared with historical matched control subjects for postoperative blood loss, need for resternotomy, blood products received, and hospital stay. It was also compared with historical nonmatched control subjects for the incidence of resternotomy and mortality. The results showed a 92.6% success rate for fibrin sealant in controlling bleeding within 5 minutes of application, compared with only a 12.4% success rate with conventional topical agents (p less than 0.001). Fibrin sealant also rapidly controlled 82.0% of those bleeding episodes not initially controlled by conventional agents. High-volume postoperative blood loss was significantly less (p less than 0.05) in the fibrin sealant group than in the matched controls. Additionally, resternotomy rates after redo operations were significantly lower in the fibrin sealant group (5.6%) than in the nonmatched historical control group (10%) (p less than 0.0089). There were no significant differences in hospital stay or blood products received between the fibrin sealant group and matched historical controls and no difference in mortality between the fibrin sealant group and nonmatched historical controls. There were no documented instances of adverse reactions, transmission of viral infection (hepatitis B, non-A/non-B hepatitis), or human immunodeficiency virus seroconversion. This study shows that fibrin sealant is safe and highly effective in controlling localized bleeding in cardiac operations. Fibrin sealant reduces postoperative blood loss and decreases the incidence of emergency resternotomy. These findings make fibrin sealant a valuable hemostatic agent in cardiac surgery.     

Management of massive operative blood loss

Coagulopathy associated with massive operative blood loss is an intricate, multicellular and multifactorial event. Massive bleeding can either be anticipated (during major surgery with high risk of bleeding) or unexpected. Management requires preoperative risk evaluation and preoperative optimization (discontinuation or modification of anticoagulant drugs, prophylactic coagulation therapy). Intraoperatively, the causal diagnosis of the complex pathophysiology of massive bleeding requiring rapid and specific coagulation management is critical for the patient's outcome. Treatment and transfusion algorithms, based on repeated and timely point-of-care coagulation testing and on the clinical judgment, are to be encouraged. The time lapse for reporting results and insufficient identification of the hemostatic defect are obstacles for conventional laboratory coagulation tests. The evidence is growing that rotational thrombelastometry or modified thrombelastography are superior to routine laboratory tests in guiding intraoperative coagulation management. Specific platelet function tests may be of value in platelet-dependent bleeding associated e.g. with extracorporeal circulation, antiplatelet therapy, inherited or acquired platelet defects. Therapeutic approaches include the use of blood products (red cell concentrates, platelets, plasma), coagulation factor concentrates (fibrinogen, prothrombin complex, von Willebrand factor), pharmacological agents (antifibrinolytic drugs, desmopressin), and local factors (fibrin glue). The importance of normothermia, normovolemia, and homeostasis for hemostasis must not be overlooked. The present article reviews pathomechanisms of coagulopathy in massive bleeding, as well as routine laboratory tests and viscoelastic point-of-care hemostasis monitoring as the diagnostic basis for therapeutic interventions.     

Autologous fibrin sealant preparing system in coronary artery bypass grafting

Autologous fibrin sealant (AFS) which is not based on the conventional method of co-administering fibrinogen, thrombin and aprotinin was prepared by Vivostat system, and was used in coronary artery bypass grafting (CABG). The purpose of this study was to investigate the safety and efficacy of the AFS prepared by the Vivostat system. In 6 of 68 cases of CABG, normal AFS was not prepared due to device failures. AFS was prepared and sprayed in 62 cases. There were the total of 230 anastomosis sprayed AFS and the bleeding could not seen in 225 anastomosis. Surgical hemostatic procedures (4 cases) were or other sealant usage (1 case) was performed 5 bleeding anastomosis sites. The rate of hemostasis at the anastomosis using AFS was 97.8%. This study was conducted in patients undergoing CABG. In this group of patients, a number of commercial available fibrin sealant products are routinely used. The usefulness of Vivostat as medical device to prepare and administer AFS was confirmed in this study.     

Assessment of topical hemostats in a renal hemorrhage model in heparinized rats

Various topical hemostatic agents or devices have been employed to address the challenges associated with hemorrhage from parenchymal organs during surgery or trauma. Their relative efficacy, however, has not been assessed in a single animal model. The objective of this study was to develop a small animal renal hemorrhage model for comparing hemostatic efficacy of various topical agents, and then to compare fibrin sealant (FS) to an existing standard of care for topical hemostasis. A left heminephrectomy was performed in anesthetized adult male Sprague-Dawley rats. Animals were anticoagulated with 2000 IU/kg heparin IV and various topical hemostatic agents were applied to the injury. Treatment groups included FS applied as a spray; FS applied through a cannula; gelatin sponge (GS) soaked in 1000 IU/mL thrombin solution; GS soaked in 300 IU/mL thrombin; dry GS; and fibrinogen without thrombin applied as a spray. The main endpoints of the study were incidence of hemostasis, blood loss, acute survival trends, and maintenance of mean arterial pressure (MAP). Three treatment groups, the two FS groups and the GS soaked in 1000 IU/mL thrombin, afforded significant hemostasis compared to the controls (P < 0.01). Both FS groups had significantly less blood loss, longer survival times, and maintained higher MAPs than the GS-treated groups. Quantitative dose effects and functional deficiencies in topical hemostatic products could be assessed using this animal model. The study demonstrated that liquid FS was significantly more efficacious than a GS soaked in thrombin for abating hemorrhage from a renal excision in a heparinized rat.     

Fibrin tissue adhesive in otolaryngology-head and neck surgery

In otolaryngology-head and neck surgery, fibrin tissue adhesive (FTA) is primarily used for fixation of tissues, for attaining hemostasis, or for drug delivery. It can be used for positioning implants or ossicles in the middle ear or as a sealant in closure of cerebrospinal fluid leaks. FTA is an excellent hemostatic agent and can be used for controlling capillary bleeding along the cut surface of muscle or in a previously operated site. As a delivery system, FTA can be used to administer antibiotics, chemotherapeutic agents, or growth factors. New technology is providing safer homologous products, stronger autologous products with higher fibrinogen levels, and better applicators.     

Comparison of a new fibrin sealant with standard topical hemostatic agents

BACKGROUND: Bleeding following liver resection continues to be a significant morbidity of the procedure. Fibrin sealants represent an improvement over conventional topical hemostatic agents, because they contain components that actively form clot. However, most available agents contain nonhuman protein, which represents an immunologic risk. HYPOTHESIS: An investigational surgical fibrin sealant (Crosseal; American Red Cross, Washington, DC) composed of human clottable proteins and human thrombin is more effective than standard topical hemostatic agents in reducing the time required to achieve hemostasis after liver resection. DESIGN: Prospective, randomized, controlled trial. SETTING: Fifteen major referral centers in the United States and the United Kingdom. METHODS: After liver resection using standard surgical techniques, 121 patients seen between May 1999 and May 2000 were randomized to treatment with a 2-component fibrin sealant (n=58) or to standard topical hemostatic agents, used singly or in combination (n=63). Up to 10 mL of Crosseal was administered by a spray applicator, as recommended by the manufacturer, whereas agents used in the control group were applied according to their instructions for use. MAIN OUTCOME MEASURES: The primary outcome measured was time to hemostasis. Secondary outcomes measured included blood loss between application of the hemostatic agent and closure of the abdomen, duration of postoperative biliary drainage, and the occurrence of complications, defined a priori as reoperation for any reason, development of abdominal fluid collections, or bilious appearance of drained fluid for at least 1 day postoperatively. RESULTS: The mean time to hemostasis was 282 seconds with Crosseal, compared with 468 seconds with standard agents (2-sided; P =.06), for the 116 efficacy-evaluable patients. Hemostasis was achieved within 10 minutes in 53 patients (91.4%) treated with the study fibrin sealant and in 44 control patients (69.8%) (2-sided; P =.003). Intraoperative blood loss was similar in the 2 groups. In the Crosseal group, the percentage of patients developing postoperative complications was 17.2%, compared with 36.5% in the control group (2-sided; P =.02). CONCLUSIONS: Compared with the use of standard topical hemostatic agents, Crosseal fibrin sealant significantly reduced the time to achieve hemostasis following liver resection. Patients treated with the new fibrin sealant also experienced significantly fewer postoperative complications.     

Management of surgical hemostasis: topical agents

Intraoperative control of bleeding during any surgical procedure is vital for achieving a positive patient outcome. Hemostasis can be achieved through practical and effective systemic or topical approaches. A variety of hemostatic methods can be employed, ranging from simple manual pressure application with one finger to electrical tissue cauterization, systemic administration of blood products, and systemic administration or topical application of procoagulation agents. The key to surgical success is critically dependent on knowledgeable use of a method appropriate for the level of bleeding experienced by the patient. Topical agents can be effective as adjuncts to aid in hemostasis when bleeding is not controllable with pressure application, vessel ligation, or electrocautery. Such adjunctive hemostatic treatments include topical gelatins, collagens, oxidized celluloses, thrombin and fibrin sealants, synthetic glues, and glutaraldehyde-based glues. As with the use of systemically delivered hemostatic agents, topical treatments also carry risks with their use, and their efficacy has not been extensively studied in large randomized, placebo-controlled prospective studies. The effective use of topical agents is highly dependent on the surgeon's experience or preference and their availability in the surgical setting. In this article, we review the currently available topical hemostatic agents, compare their efficacy, and give general recommendations for their use in the operating room.     

Comparative study of the hemostatic efficacy of a new human fibrin sealant: is an antifibrinolytic agent necessary?

BACKGROUND: Sustained hemostasis by fibrin sealant (FS) is critically important when it is used in trauma surgery. To purportedly delay fibrin degradation and prevent premature hemostatic failure, some FS products added an antifibrinolytic agent (e.g., bovine aprotinin). The purpose of this study was to compare the overall hemostatic efficacy of a new inhibitor-free FS obtained from the American Red Cross (ARC-FS) to a clinically available aprotinin-containing FS preparation (Tisseel). The need for addition of an antifibrinolytic agent was assessed under normal and high-fibrinolytic conditions. METHODS: The abdominal aortas of anesthetized rabbits were transected and anastomosed, end-to end, using only four interrupted sutures. The suture line was covered with approximately 2 mL of either type of FS and blood flow was restored. Blood loss was absorbed by gauze and measured. All rabbits were recovered and underwent histologic examination 4 weeks after operation. The efficacy of FS was also tested under a high-fibrinolytic state by treating the rabbits with human recombinant tissue plasminogen activator (0.15 mg/kg, 3-hour infusion). The investigators were blinded to the treatment groups. RESULTS: The majority (11 of 12) of deaths occurred because of bleeding at the suture line within 7 days of surgery. Sustained hemostasis by FS (>1 week) was required for normal tissue healing and long-term survival of animals. Application of ARC-FS to the suture line produced immediate hemostasis in 43% of animals (three of seven), with mean blood loss of 4.8 +/- 1.8 mL, and 86% long-term survival. Tisseel application produced immediate hemostasis in 13% of animals (one of eight), with mean blood loss of 26.9 +/- 7.0 mL (p < 0.05 vs. ARC-FS) and survival rate of 37% (three of eight). Under high-fibrinolytic conditions, ARC-FS produced immediate and complete hemostasis in seven of eight animals (88%), whereas the Tisseel demonstrated complete hemostasis in one of seven (p < 0.01). The ARC-FS rabbits had a blood loss of 1.9 +/- 1.9 mL and survival rate of 75% (six of eight), whereas the Tisseel animals had a mean blood loss of 30 +/- 6.0 mL and survival rate of 43% (three of seven) (p < 0.01). No detrimental effect on healing was noted with either product. CONCLUSION: ARC-FS provides effective and secure hemostasis against high-pressure arterial bleeding under both normal and high-fibrinolytic conditions. Addition of an antifibrinolytic agent such as aprotinin is not required to sustain the hemostatic function of this fibrin sealant.     

Pathophysiology of bleeding in surgery

Bleeding is a major surgical complication. Although mortality rates of 0.1% are observed for surgical procedures, it may be 5% to 8% for elective vascular surgery, and increase to 20% in the presence of severe bleeding. In major surgery for liver diseases, as well as in cardiac surgery, excessive blood loss is associated with increased mortality, morbidity, and intensive care stay. Approximately 75% to 90% of intraoperative and early postoperative bleeding is due to technical factors. However, in some cases either acquired or congenital coagulopathies may favor, if not directly cause, surgical hemorrhage. Uncontrolled bleeding leads to a combination of hemodilution, hypothermia, consumption of clotting factors, and acidosis, which in turn worsen the clotting process, further exacerbating the problem in a vicious bloody circle. At present, the standard treatment for surgical bleeding is the rapid control of the source of bleeding by either surgical or radiological techniques. Blood-derived products as well as hemostatic agents, such as aprotinin, tranexamic acid, and DDAVP, are widely used to improve hemostatic balance in bleeding patients. Recombinant activated factor VII (rFVIIa) has been reported to be effective for the treatment of surgical or traumatic massive bleeding unresponsive to conventional therapy. Although most reports are anecdotal, and therefore exposed to a "positive" selection bias, the number of cases is impressive, strongly suggesting that in such patients rFVIIa may afford a hemostatic advantage beyond that of conventional replacement therapy.     

Nd-YAG laser for general surgery

We report here our clinical experiences with Nd-YAG laser on general surgery, and evaluate the results of this procedure. From December 1979 to December 1981, we applied Nd-YAG laser to various operations as a hemostatic and cutting tool. For hemostasis, we used conventional quartz fiber which was covered with sterile tube, and hemostatic efficacy was examined especially in the subcutaneous bleeding and the bleeding from solid organs. For cutting, we used special devices, ie, Medilas YAG surgical probe (noncontact-type probe), and a laser blade (contact-type probe), and performed four liver resections. It is concluded that the hemostatic efficacy of Nd-YAG laser to various bleeders was proved in general surgical procedures, and furthermore this laser can cut tissue if we utilize these devices. When comparing these two devices, we would prefer the contact-type probe.     

Effect of compression with aerosolized fibrin sealant on surgical hemostasis

In order to decrease complications following incomplete hemostasis after surgery, especially in the case of arterial bleeding, we experimentally investigated an effective way of applying fibrin glue as a sealant. Using white rabbits as a model, in which arterial bleeding from the abdominal aorta was induced, fibrin glue and a related hemostatic agent were tested to evaluate the hemostatic effectiveness. Group I (n = 9): Fibrin glue was applied by spraying it on the fingertip and then placing the fingertip on the bleeding part and pressing. Group II (n = 9): Fibrin glue was applied with oxycellulose on the fingertip and then placing the fingertip on the bleeding part and pressing. The results demonstrated that: 1) Although complete hemostasis could not be obtained with finger-pressing alone in 30 second, it could be obtained in 9/9 cases 100%) in Group I but in only 3/9 cases (33%) in Group II. 2) Pressure-resistant force was higher for Group I at an earlier time after hemostasis (p < 0.05). 3) Pathological study reconfirmed the predominance of Group I. We conclude from this study that ideal hemostasis can be obtained with fibrin glue applied simply by spraying it on the fingertip and then placing the fingertip on the bleeding part and pressing.     

Principles of hemostasis in children: models and maturation

Hemostasis is an active process regulating the formation and dissolution of fibrin clot to preserve vascular integrity. The different phases of hemostasis are coordinated so that effective clotting occurs only at the site of vascular injury while maintaining blood flow in other parts of the circulation. Procoagulant processes culminate in thrombin generation and fibrin clot formation to protect the vasculature against uncontrolled bleeding after injury. Conversely, anticoagulant processes limit clot extension to unaffected portions of the vasculature. Lastly, fibrinolysis is responsible for clot dissolution once tissue repair and regeneration permit the return of normal blood flow. A precise and delicate interplay exists among these processes to ensure normal hemostasis. The hemostatic system is incompletely developed at birth and matures throughout infancy. Both full‐term and preterm neonates are born with low levels of most procoagulant proteins including all the contact activation factors and vitamin K‐dependent factors. Similarly, levels of the major anticoagulant proteins are low at birth. Although often characterized as ‘immature’, the neonatal hemostatic system is nevertheless functionally balanced with no tendency toward coagulopathy or thrombosis. In this article, we will review the current models of hemostasis and the maturation of the hemostatic system. Our goal is to help clinicians gain a better understanding of the actions of procoagulant agents and of the disruptive effects of serious systemic illnesses on the precarious hemostatic balance of infants.     

Various local hemostatic agents with different modes of action; an in vivo comparative randomized vascular surgical experimental study.

OBJECTIVES: To evaluate the effects of different local hemostatic agents in a new high flow vascular experimental bleeding model. DESIGN: Bovine thrombin combined with collagen matrix (bTcM), microporous polysaccharide hemospheres (MPH), freeze-dried rFVIIa with and without the combination of MPH were compared to a control group (solely compression) in a randomized fashion (20 animals/group). Primary endpoint was hemostasis, and secondary endpoints were time to hemostasis, blood loss, and blood pressure at hemostasis. METHODS: The common carotid artery of heparinized rats was ligated proximally and transected. Compression was applied for one minute followed by application of the topical hemostatic agent. Compression was maintained for another two minutes followed by re-evaluation of hemostasis: if bleeding continued additional compression was applied and thereafter bleeding was checked every minute until hemostasis. RESULTS: All animals in the bTcM group obtained hemostasis compared to 20% in the control group (p<0.0001). The combination of MPH and rFVIIa (70% hemostasis) also showed a significant hemostatic capacity compared to control group (p<0.001). None of the other active treatment groups differed compared to control group. Animals treated with bTcM had a significantly shorter time to hemostasis compared to animals in the other active treatment groups. No significant difference in blood loss and blood pressure at hemostasis was detected. CONCLUSIONS: The most effective hemostatic agent was bTcM, followed by the combination of rFVIIa and MPH, while neither MPH nor rFVIIa alone displayed any hemostatic capacity compared to compression only.     

Recombinant factor VIIa (NovoSeven) as a hemostatic agent after surgery for congenital heart disease

BACKGROUND: Postoperative bleeding and blood product requirements can be substantial in children undergoing open-heart surgery, and reexploration is required in 1% of cases. Recombinant activated factor VII (rFVIIa, NovoSeven, NovoNordisk, Denmark) is a hemostatic agent approved for the treatment of hemophilic patients with inhibitors to factor VIII or factor IX. It has also been used with success in other conditions. We present our experience with rFVIIa treatment for uncontrolled bleeding after open-heart surgery in five pediatric patients. METHODS: The study group consisted of five patients after open-heart surgery with excessive blood loss. The patients were treated with rFVIIa after failure of conventional treatment to control the bleeding. Blood loss, blood product consumption, and coagulation test results were recorded before and after rFVIIa administration. RESULTS: In all cases, blood loss decreased considerably after rFVIIa administration (mean 7.8 ml x kg(-1) x h(-1)), almost eliminating the need for additional blood products, and the prolonged prothrombin time normalized. In two patients with thrombocytopathy, rFVIIa helped to discriminate surgical bleeding from bleeding caused by a defect in hemostasis. No side effects of rFVIIa treatment were noted. CONCLUSIONS: These cases support the impression that RFVIIa is efficient and safe in correcting hemostasis in children after cardiopulmonary bypass when other means fail. However, the data are still limited, and more extensive research is needed.     

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.     

Control of presacral venous bleeding during rectal surgery

Background

Presacral venous hemorrhage is an uncommon but potentially life-threatening complication of rectal surgery. It is difficult to control presacral venous hemorrhage with conventional hemostatic measures and several alternative methods for hemostasis have been proposed. We described our experience of using the combination of a hemostatic matrix and an absorbable hemostat as an alternative method of hemostasis.

Methods

From September 2007 to March 2009, 83 patients underwent rectal surgery for cancer, ulcerative colitis, or familial adenomatous polyposis. Three patients (3.6%) had severe presacral hemorrhage, which was controlled by the combined use of a hemostatic matrix (FloSeal; Baxter, USA) and an absorbable hemostat (Surgicel Fibrillar; Ethicon, USA).

Results

Intraoperative blood transfusion was required in 1 patient. Postoperative blood loss was minimal and drain was removed on day 4 in all 3 patients.

Conclusions

The use of synthetic hemostatic agents is an effective and simple way to arrest presacral bleeding where conventional methods fail.     

Critical bleeding in surgery: conventional therapy and new prospects

Perioperative bleeding is one of the most frequent complications of surgery. Management of bleeding consists of local control (surgical or endoscopic hemostasis), measures to retain adequate circulation and proper transfusion procedures. In this review we will discuss various agents with a prohemostatic potential and their efficacy to reduce perioperative blood loss. Desmopressin increase the plasma concentration of Von Willebrand factor giving an augmentation of primary hemostasis. The use of recombinant activated factor VII is based on the evidence that activation of coagulation in vivo predominantly proceeds by the tissue factor/factor VII (a) pathway. Agents that exerts anti-fibrinolytic activity are aprotinin and the group of lysine analogues. The prohemostatic effect is due to inhibition of fibrinolysis and to a protective effect on platelets. Prohemostatic therapy may achieve an improvement of hemostasis, by amelioration of primary hemostasis, stimulation of fibrin formation or inhibition of fibrinolysis and seems to be effective in reducing perioperative blood loss and transfusion requirements.     

Massive transfusion and coagulopathy: pathophysiology and implications for clinical management

PURPOSE: To review the pathophysiology of coagulopathy in massively transfused, adult and previously hemostatically competent patients in both elective surgical and trauma settings, and to recommend the most appropriate treatment strategies. METHODS: Medline was searched for articles on "massive transfusion," "transfusion," "trauma," "surgery," "coagulopathy" and "hemostatic defects." A group of experts reviewed the findings. Principal findings: Coagulopathy will result from hemodilution, hypothermia, the use of fractionated blood products and disseminated intravascular coagulation. The clinical significance of the effects of hydroxyethyl starch solutions on hemostasis remains unclear. Maintaining a normal body temperature is a first-line, effective strategy to improve hemostasis during massive transfusion. Red cells play an important role in coagulation and hematocrits higher than 30% may be required to sustain hemostasis. In elective surgery patients, a decrease in fibrinogen concentration is observed initially while thrombocytopenia is a late occurrence. In trauma patients, tissue trauma, shock, tissue anoxia and hypothermia contribute to the development of disseminated intravascular coagulation and microvascular bleeding. The use of platelets and/or fresh frozen plasma should depend on clinical judgment as well as the results of coagulation testing and should be used mainly to treat a clinical coagulopathy. CONCLUSIONS: Coagulopathy associated with massive transfusion remains an important clinical problem. It is an intricate, multifactorial and multicellular event. Treatment strategies include the maintenance of adequate tissue perfusion, the correction of hypothermia and anemia, and the use of hemostatic blood products to correct microvascular bleeding.     

Möglichkeiten der lokalen und systemischen Blutstillung bei chirurgischen Eingriffen

Surgery inevitably leads to bleeding, and hemostasis aims at reducing the amount of blood loss and the need for transfusion as well as preventing rebleeding, hematoma formation, and the need for repeat surgery. Various locally applicable agents are in use including bone wax, gelatin, collagen, oxidized regenerated cellulose, fibrin sealant glues, and synthetic glues. Some evidence from randomized controlled trials (RCT) exists regarding the use of fibrin sealants on their own or combined with collagen fleece. Systemic hemostasis may be achieved with lysine analogs such as epsilon-aminocaproic acid or tranexamic acid and aprotinin, which are inhibitors of fibrinolysis. There is much albeit sometimes conflicting evidence from RCT regarding the use of these substances in surgery. The role of recombinant activated factor VII in achieving systemic hemostasis is being investigated.     

Coagulation, fibrinolysis and bleeding after open-heart surgery

To investigate the disputed pathogenesis of excessive bleeding after open-heart surgery, variables representing different hemostatic systems were correlated to postoperative blood loss in 29 patients. The general bleeding tendency in the early postoperative phase was probably attributable to depletion of hemostatic agents due to hemodilution, decreased antiplasmin activity, instantaneous but reversible platelet dysfunction following protaminization, and the natural interval to development of complete hemostasis. Heavy bleeding (greater than 800 ml/16 h) occurred in ten patients, who had significantly reduced levels of von Willebrand factor and lower active platelet count than in eight patients with minor bleeding. Defective primary hemostasis thus seemed to be the main cause of increased postoperative bleeding in these patients. Determination of platelet function by glass retention test showed good clinical relevance and gave considerably more reliable diagnosis than conventional platelet count alone. The patient with the greatest blood loss also showed drastic decrease in the plasminogen-binding form of alpha 2-antiplasmin, suggesting that additionally impaired fibrinolysis inhibition may contribute to development of severe hemorrhagic complications.