手术中应用局部止血药后发生血栓栓塞、急性右心衰竭和弥散性血管内凝血

局部止血药通常用于脊柱外科手术以控制或减少出血。目前市场上有多种局部止血药可选用，我院使用的局部止血药是加入牛凝血酶的可吸收明胶粉剂（Surgifoam^TM）。我们报道一例脊柱侧凸畸形患者进行后路椎体融合矫形术，手术中发生可能是由于血管内误入局部止血药诱发的血栓栓塞，导致急性右心衰竭、心脏停搏以及弥散性血管内凝血（DIC）。临床医生必须警惕局部止血药引起的潜在的致命性并发症。     

Hematologic causes of intracerebral hemorrhage and their treatment.

Spontaneous ICH is an unusual and potentially disastrous event that may complicate primary and secondary hemostatic abnormalities. Among the primary abnormalities, deficiencies of coagulation factors I, VII, VIII, IX and XIII as well as von Willebrand factor have been clearly associated with ICH. Specific factor replacement or supportive management to normalize the hemostatic defect is indicated in each case. Among secondary alterations in hemostasis, thrombocytopenia, platelet function abnormalities, or factor consumption contribute to the risk of ICH in patients with ITP, TTP, disseminated intravascular coagulation, myeloproliferative or myelodysplastic disorders, and exposure to certain medications. The precise incidence of spontaneous hemorrhage among these disorders is unknown but low. Platelet transfusion and fibrinogen replacement are appropriate in specific cases; however, treatment of the underlying cause is usually required. The association of hemorrhage with antithrombotic agents in several settings is better defined. Cessation of the medication is required in each instance. Fibrinogen replacement may be required after the use of fibrinolytic agents. In all cases, an assessment of the precise hemostatic defect is recommended.     

Gerinnungsmanagement beim Polytrauma

Hemorrhage after traumatic injury results in coagulopathy which only worsens the situation. This coagulopathy is caused by depletion and dilution of clotting factors and platelets, increased fibrinolytic activity, hypothermia, metabolic changes and anemia. The effect of synthetic colloids used for compensating the blood loss, further aggravates the situation through their specific action on the hemostatic system. Bedside coagulation monitoring permits relevant impairment of the coagulation system to be detected very early and the efficacy of the hemostatic therapy to be controlled directly. Administration of fresh frozen plasma (FFP), platelet concentrates and antifibrinolytic agents is essential for restoring the impaired coagulation system in trauma patients. Clotting factor concentrates should be administered if coagulopathy is based on diagnosed depletion of clotting factors, if FFP is not available and if transfusion of FFP is insufficient to treat the coagulopathy. Recombined FVIIa is frequently employed during severe bleeding which could not be treated by conventional methods but the results of on-going clinical trials are not yet available.     

Coagulation management in trauma patients

Hemorrhage after traumatic injury results in coagulopathy which only worsens the situation. This coagulopathy is caused by depletion and dilution of clotting factors and platelets, increased fibrinolytic activity, hypothermia, metabolic changes and anemia. The effect of synthetic colloids in compensating the blood loss further aggravates the situation. Bedside coagulation monitoring permits relevant impairment of the coagulation system to be detected very early and the efficacy of the hemostatic therapy to be controlled directly. Administration of fresh frozen plasma, platelet concentrations, clotting factors and probably antifibrinolytic agents is essential in restoring the impaired coagulation system in trauma patients.     

Current concepts of hemostasis: implications for therapy

The revised model of coagulation has implications for therapy of both hemorrhagic and thrombotic disorders. Of particular interest to anesthesiologists is the management of clotting abnormalities before, during, and after surgery. Most hereditary and acquired coagulation factor deficiencies can be managed by specific replacement therapy using clotting factor concentrates. Specific guidelines have also been developed for perioperative management of patients using anticoagulant agents that inhibit platelet or coagulation factor functions. Finally, recombinant factor VIIa has been used off-label as a hemostatic agent in some surgical situations associated with excessive bleeding that is not responsive to conventional therapy.     

Surgical hemostatic agents: assessment of drugs and medical devices

Surgical hemostatic agents are indicated to improve hemostasis when conventional techniques (compression, sutures or electrocoagulation) are inadequate. The National French Authority for Health (Haute Autorité de santé [HAS]) set out to assess these products (medical devices and agents) to determine their optimal utility. This evaluation included one class of products containing some form of human fibrinogen and thrombin and eight classes of medical devices and automated devices to prepare autologous fibrin. The assessment was based on a systematic review of the literature and expert opinion of health care professionals. The main measures of effectiveness of hemostatic agents were the success rate as expressed in terms of the time necessary to obtain adequate hemostasis, the volume of intra and/or postoperative blood loss, the need for blood transfusions, complication rate, duration of operations and hospital stay. A meta-analysis and 52 controlled randomized studies were selected involving cardiac or vascular surgery (19), ENT surgery (11), gastrointestinal surgery (5), urology (4), orthopedic surgery (4). Approximately half of the studies retained in this analysis evaluated blood derived agents (fibrin sealants) while the other half evaluated medical devices. The working group considered that there is not any evidence that these surgical hemostatic agents decrease the rates of transfusion, complications, reoperation, mortality, duration of operation and/or hospital stay. The working group considered that the use of surgical hemostatic agents to improve the safety of hemostasis in the absence of identified bleeding as an alternative to adequate conventional hemostasis was not justified. Surgical hemostatic agents can be used in ad hoc settings, as a complement to conventional methods to control persistent bleeding after conventional hemostatic techniques, or when abundant bleeding has led to biologic hemostatic disorders. The working group also distinguished several particular settings (mouth and dental care in patients under antiagregant or anticoagulation therapy, central nervous system surgery or acute aortic dissection). Comparative data are insufficient to determine if one product is superior to another for a specific use. To evaluate the clinical value of these products, methodologically sound clinical studies are necessary.     

Applications of fibrin sealant in surgery

Fibrin sealant has been used with increasing frequency in a variety of surgical field for its unique hemostatic and adhesive abilities. Fibrin sealant mimics the last step of the coagulation cascade and takes place independently of the patient's coagulation status. With rapid advances in minimally invasive surgery, the potential uses for this type of biologic and synthetic material are expanding exponentially. This article reviews the data associated with the application of fibrin sealant in various surgical procedures. From reinforcing gastrointestinal anastomosis to repair perforated duodenal ulcers to mesh fixation in laparoscopic inguinal hernia repair, fibrin sealant is gaining increasing acceptance among surgeons. The applications of fibrin sealant are expanding, and new preparations of fibrin sealant are currently being evaluated.     

Hydrophilic Polymers with Potassium Salt and Microporous Polysaccharides for Use as Hemostatic Agents

BACKGROUND Postoperative bleeding can lead to complications such as hematoma, infection, dehiscence, and an unscheduled office visit. Topical hemostatic agents can be used to aid in hemostasis.
OBJECTIVE The objective is to familiarize physicians with topical hemostatic agents—hydrophilic polymers with potassium salts (Urgent QR powder) and microporous polysaccharide hemispheres (Bleed-X).
METHODS Two hemostatic agents, microporous polysaccharide hemospheres and hydrophilic polymers with potassium salt, are discussed. The literature is reviewed.
RESULTS Numerous types of hemostatic agents exist. Topical hemostatic agents are safe, cost-effective, and efficient.
CONCLUSION Microporous polysaccharide hemospheres and hydrophilic polymers with potassium salts can be an adjunct to hemostasis after cautery and ligation. Patients can apply hemostatic agents if they experience any bleeding leading to decreased office visits. Hemostatic agents used intraoperatively shorten bleeding time and enable the physician to use less cautery. Using hemostatic agents can lead to fewer hematomas, infections, and office visits.     

Heparinase-modified thrombelastography in term and preterm neonates

Thrombelastography (TEG) appears to be a promising test to assess coagulation in infants and children. TEG enables a rapid assessment of hemostatic function with only 300 microL of whole blood and provides information about plasmatic coagulation, platelet function, and fibrinolysis. In this study, we used TEG to assess the coagulation system of preterm and term neonates to determine the effects of their deficient coagulation factor levels on global hemostatic function. Heparinase-modified TEG, platelet and red blood cell count, plasma fibrinogen, and prothrombin time were assessed in four groups of clinically stable infants: severely preterm (gestational age [GA], 27-31 wk), moderately preterm (GA, 32-36 wk), term (GA, 36-40 wk), and former preterm (corrected GA, 34-40 wk). Healthy adult volunteers served as a control group. When compared with the adult group, thromboelastography revealed no defects in coagulation from groups of clinically stable infants, documenting the functional integrity of coagulation despite, in part, decreased conventional coagulation variables. Because clinically stable preterm and term infants show a relatively small incidence of bleeding, despite prolonged conventional coagulation tests, TEG may better reflect the hemostatic potential of these patients compared with conventional coagulation tests. IMPLICATIONS: This study assessed the coagulation of preterm and term infants by thrombelastography and found functional integrity of coagulation despite, in part, decreased conventional coagulation variables.     

Should blood coagulation tests be performed before locoregional anesthesia in class 1 ASA patients?

Coagulation testing is warranted before regional anaesthesia to avoid bleeding complications. The most feared is spinal epidural hematoma causing neurologic deficits if epidural or spinal anaesthesia is performed in patients with hemostatic defects. These concepts are submitted to critical appraisal in the special setting of ASA class 1 patients. If patients are correctly assessed by questionnaire and physical examination as having negative history, asymptomatic coagulopathies are very scarce, mainly represented by hemophilia in men and von Willebrand's disease in women. Activated partial thromboplastin time (APTT) is the main test to assess coagulation defects. APTT is not sufficiently sensitive to identify all patients with coagulopathies, especially mild ones and von Willebrand's disease. Medium specificity combined with low prevalence of the disease to be screened incur false positive results and poor predictive value of positive tests as well for diagnostic purpose as for prognostic evaluation of haemorrhagic risk. Neurologic deficits secondary to compression by haematoma are rare and their frequency presently unknown. Epidural or spinal anaesthesia has been shown to be quite safe when performed in patients with various hemostatic abnormalities. Consequently, routine coagulation testing in ASA class 1 patients seems to provide more drawback than benefit. Lack of coagulation testing prior to regional anaesthesia is probably not a factor of increased risk if patients are correctly assessed.     

Hemostatic Changes Induced In Vitro by Hemoperfusion Over Activated Charcoal

The effect of hemoperfusion over charcoal on changes in platelet counts, coagulation factor concentrations and standard coagulation tests were determined during a two-hour in vitro perfusion of normal blood through a column containing 20 gm of activated charcoal, either uncoated or coated with 0.5% acrylonitrile/dimethylaminoethyl methacrylate copolymer (AN/DMAEMA). With citrated whole blood, platelet counts fell by 15% during hemoperfusion over coated or uncoated charcoal and also during passage through an identical empty chamber. On the other hand, with heparinized whole blood, platelet counts fell by 90% during hemoperfusion over uncoated charcoal, and 25% during hemoperfusion over coated charcoal. The concentrations of coagulation factors II, V, IX, X and XII were reduced during hemoperfusion over uncoated charcoal, while those of factors II and X were reduced and that of factor VII increased during hemoperfusion over coated charcoal. Perfusion with heparinized, platelet-rich plasma resulted in small reductions in platelet counts, suggesting that either erythrocyte disruption or the physical effects of intact red cells play a major role in producing the hemostatic abnormalities occurring during whole blood hemoperfusion. The method described may be used to assess the hemocompatibility of polymer coatings for charcoal particles, to investigate the nature of the interaction between platelets and artificial surfaces, and to assess the effect of platelet-active agents in reducing platelet adsorption on charcoal or other sorbents.     

Pathophysiologie des Schocks unter besonderer Berücksichtigung der schockspezifischen Hämostasestörung

Circulatory shock is defined as a syndrome of hemodynamic and metabolic disturbances. Impairment of macro-and microcirculation initiated by different causes is followed by a reversible and later on by an irreversible disturbance of cell metabolism. Breakdown of organ function may be the consequence. The shock specific discomposure of the hemostatic system is characterized by an acitivation of blood coagulation. This leads first to hypercoagulability accompanied by a tendency to thrombosis; later on the impairment of the hemostatic balance is followed by the consumption of coagulation factors and by hypocoagulability with a more or less pronounced bleeding tendency. Treatment of shock is the main prerequisite to avoid and overcome shock induced coagulation disorder. Heparin administration, fresh blood and fresh plasma are adjuvant measures. Substitution of concentrates of clotting factors are indicated only in states of total consumption of the coagulation system.     

Hepatic artery pseudoaneurysm,bronchobiliary fistula in a patient with liver trauma

Background

A wide variety of hemostats are available as adjunctive measures to improve hemostasis during surgical procedures if residual bleeding persists despite correct application of conventional methods for hemorrhage control. Some are considered active agents, since they contain fibrinogen and thrombin and actively participate at the end of the coagulation cascade to form a fibrin clot, whereas others to be effective require an intact coagulation system. The aim of this study is to provide an evidence-based approach to correctly select the available agents to help physicians to use the most appropriate hemostat according to the clinical setting, surgical problem and patient’s coagulation status.

Methods

The literature from 2000 to 2016 was systematically screened according to PRISMA [Preferred Reporting Items for Systematic Reviews and Meta-Analyses] protocol. Sixty-six articles were reviewed by a panel of experts to assign grade of recommendation (GoR) and level of evidence (LoE) using the GRADE [Grading of Recommendations Assessment, Development and Evaluation] system, and a national meeting was held.

Results

Fibrin adhesives, in liquid form (fibrin glues) or with stiff collagen fleece (fibrin patch) are effective in the presence of spontaneous or drug-induced coagulation disorders. Mechanical hemostats should be preferred in patients who have an intact coagulation system. Sealants are effective, irrespective of patient’s coagulation status, to improve control of residual oozing. Hemostatic dressings represent a valuable option in case of external hemorrhage at junctional sites or when tourniquets are impractical or ineffective.

Conclusions

Local hemostatic agents are dissimilar products with different indications. A knowledge of the properties of each single agent should be in the armamentarium of acute care surgeons in order to select the appropriate product in different clinical conditions.

     

Surgical hemostasis.

Every surgical procedure taxes the hemostatic defenses of the patient. If his hemostatic mechanism is sound, he is unlikely to have a bleeding problem during or after an operation, unless, of course, a suture or clip slips off. Two classes of patients do present bleeding problems to the surgeon. One group has a pre-existing bleeding tendency, the other acquires it during or after the operation. The recognition of patients with severe hemostatic disabilities, such as hemophilia, presents no problem since the patient is aware of the disease. The mild bleeder is less likely to be detected by screening tests than by adroit questioning. The major hemostatic defect that may develop during an operation, or shortly thereafter, is disseminated intravascular coagulation. This syndrome, always secondary, may accompany shock, mismatched blood transfusion, septicemia, or extensive malignancy. Its prevention or early recongnition is much easier than treatment after circulating platelets and some coagulation factors have been consumed and fibrinolysis is destroying fibrin and fibrinogen.     

Severe postoperative hemorrhage caused by antibody-mediated coagulation factor deficiencies: report of two cases

Antibody-mediated coagulation factor deficiencies constitute a rare disorder that may develop in elderly patients without any history of a bleeding diathesis. Patients may present with severe and sometimes catastrophic bleeding. We report two cases of postoperative hemorrhage caused by a coagulation factor deficiency. In Case 1, massive intraabdominal bleeding occurred on day 3 after pancreaticoduodenectomy for bile duct cancer, and was caused by an acquired inhibitor of coagulation factor VIII. Hemostasis was achieved and the factor VIII inhibitor titer decreased to zero with activated prothrombin complex concentrates, prednisolone, and cyclophosphamide. In Case 2, intraabdominal bleeding occurred on day 7 after hepatectomy for hepatocellular carcinoma, and was caused by an acquired inhibitor against factors II (prothrombin) and V. This patient was treated with hemostatic agents containing bovine thrombin during surgery and also with prednisolone. We report these cases to highlight that antibody-mediated coagulation factor deficiencies should be considered when an elderly patient suffers sudden postoperative hemorrhage and to stress the importance of prompt diagnosis because of the risk of potentially life-threatening hemorrhage.     

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.     

Immunologic impact and clinical outcomes after surgical exposure to bovine thrombin

OBJECTIVE: To determine prospectively the immunologic response and adverse clinical events in surgical patients exposed to bovine thrombin during cardiac surgical procedures. SUMMARY BACKGROUND DATA: Topical bovine thrombin is used extensively as a hemostatic agent during cardiovascular surgery. Antibodies developing after exposure to bovine thrombin have been anecdotally associated with hemorrhagic complications. METHODS: One hundred fifty-one patients undergoing cardiac surgical procedures were prospectively recruited for this study before surgical exposure with topical bovine thrombin. Immunoassays were used to determine antibody levels against both bovine and human coagulation proteins before and after exposure to bovine thrombin. Alterations in coagulation assay parameters and adverse clinical events were followed in all patients enrolled in the study. RESULTS: Baseline elevated antibody levels to one or more bovine coagulation proteins were observed most frequently in patients with a prior history of a surgical procedure during which bovine thrombin is frequently used. More than 95% of patients developed a seropositive response to bovine coagulation proteins, and 51% manifested elevated antibody levels to the corresponding human coagulation proteins after bovine thrombin exposure. Postoperative coagulation abnormalities were more common in patients with antibodies to human coagulation proteins. Patients with multiple elevated antibody levels to bovine proteins before surgery were more likely to sustain an adverse clinical outcome after surgery. Using a logistic regression model, the adjusted odds ratio for sustaining an adverse event with multiple elevated antibody levels to bovine proteins before surgery was 5.40. CONCLUSIONS: Bovine thrombin preparations are highly immunogenic and appear to be associated with an increased risk for adverse clinical outcomes during subsequent surgical procedures. The clinical safety of these commonly used preparations needs to be reassessed, and reexposure to these agents should likely be avoided.     

Thermal injury resulting from application of a granular mineral hemostatic agent

BACKGROUND: Uncontrolled hemorrhage accounts for the majority of deaths in combat. Effective topical hemostatic agents suitable for use on the battlefield may be valuable in controlling hemorrhage until definitive surgical intervention is possible. In an effort to identify a hemostatic agent suitable for battlefield use, we evaluated several potential hemostatic agents in a swine injury model and noted thermal injury to tissues with a granular mineral hemostatic agent (QuikClot). METHODS: Anesthetized swine were maintained with a mean arterial pressure in excess of 60 mm Hg. Cutaneous, muscular, hepatic, splenic, venous, and arterial wounds were created in a standardized fashion. Topical hemostatic agents were immediately applied to the wounds and the amount of bleeding and time to hemostasis were noted. RESULTS: The results reported here are part of a larger study in which a variety of hemostatic agents were evaluated. Only the findings related to the granular mineral hemostatic agent are discussed here. Application of the agent resulted in elevated tissue surface temperatures in excess of 95 degrees C and internal tissue temperatures exceeding 50 degrees C, 3 mm deep to the bleeding surface. Necrosis of fat and muscle were noted as well as full and partial thickness cutaneous burns. CONCLUSIONS: Topical administration of a granular mineral hemostatic agent to a variety of wounds in an experimental swine model resulted in thermal tissue injury and necrosis. Suggestions for reducing the extent of injury with this product are offered.     

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普通外科病人凝血功能障碍主要有高凝状态、血栓栓塞和低凝状态、止血障碍。可通过常规实验室检查对其进行检测,包括活化部分凝血活酶时间(APTT)、凝血酶原时间(PT)、凝血酶时间(TT)、纤维蛋白原(FIG)以及血小板(PLT)。血栓弹力图可以连续全程监测止血功能。中、重度危险的病人推荐采取药物或器械性措施,预防静脉血栓栓塞。对于出血病人,应根据床边、即时、快速试验结果和合理指征计算输入量,有针对性地输注浓缩凝血因子和新鲜冷冻血浆等血液制品。     

Trauma-induced coagulopathy

Hemorrhage is the leading cause of death in trauma patients who arrive alive at hospital. This type of hemorrhage has a “coagulopathic” component, specific to major trauma and associated with poor outcomes. Over the last decade, a better understanding of this trauma-induced coagulopathy lead to a new therapeutic approach requiring earlier and more aggressive management. This hemostatic resuscitation includes early activation of massive transfusion protocols with: 1) immediate delivery of blood packs with high ratios for RBC units: fresh frozen plasma: platelet-concentrates; 2) antifibrinolytics; 3) substitution of coagulation factors. However, early identification of coagulopathic patients requiring aggressive hemostatic resuscitation remains challenging, with an increasing role of point of care devices for hemostatic diagnosis and monitoring. Efforts have to be focused on the early diagnosis of coagulopathy for immediate delivery of blood products and coagulation factors to the right, accurately screened patients through pre-established protocols within the golden hour.