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.     

蛇毒血凝酶(巴曲亭)在骨科手术中的止血作用

目的研究国产蛇毒血凝酶(巴曲亭)在骨科手术围术期应用的止血作用。方法选择40例不同种类的骨科手术病人,随机分为巴曲亭组和生理盐水对照组,比较两组病人的术中出血量、术后24h引流量、血红蛋白浓度、输血量、血小板浓度、纤维蛋白原浓度、凝血酶原时间和激活部分凝血酶时间。结果围术期应用蛇毒血凝酶可以显著减少骨科手术的出血量和输血量,但并不影响凝血状态。结论蛇毒血凝酶(巴曲亭)可以作为一种安全、有效的止血剂用于骨科手术。     

Use of hemostatic forceps as a preoperative rescue therapy for bleeding peptic ulcers

Standard endoscopic management of bleeding peptic ulcers includes injection, thermal coagulation, or mechanical clipping. The use of hemostatic forceps has increased with the widespread use of endoscopic submucosal dissection to control bleeding. However, there are few reports on the use of hemostatic forceps to control bleeding peptic ulcers. From January to October 2010, four hundred twenty-seven patients received endoscopic therapy at our institution for bleeding peptic ulcers. In 5 patients hemostasis was achieved with hemostatic forceps as a rescue therapy after standard endoscopic therapy had failed. In 4 patients successful hemostasis was achieved, whereas 1 patient had to undergo emergency surgery. We found that hemostatic forceps are a useful alternative for the control of bleeding peptic ulcers after standard endoscopic treatment has failed. This treatment may help in avoiding the necessity of surgery. Further large-scale studies are required to confirm our observations.     

On-site coagulation monitoring does not affect hemostatic outcome after cardiac surgery

BACKGROUND: Rapid coagulation tests are now available for monitoring of bleeding patients after cardiac surgery. As inappropriate blood use in these patients may be due to lack of timely coagulation data, we studied the effect of an algorithm with on-line coagulation monitoring on transfusions in these patients. METHODS: Prospectively, patients bleeding (>1.5 ml kg(-1) 15 min(-1)) after cardiac surgery were randomly assigned to two groups: in group A (n=28), hemostatic treatment during the immediate recovery period (1 h after surgery) was based on an algorithm with on-site hemostasis monitoring, whereas during the same period group B patients (n=30) were managed solely according to the clinician's judgement; laboratory tests other than activated clotting time after heparin neutralization were prohibited. RESULTS: Cumulative chest tube drainage up to 16 h and total transfusion requirements did not differ between the groups. Using a platelet transfusion trigger of 100x10(9)/l, significantly more patients received platelets during the immediate recovery period in the algorithm group than in the control group (14 vs. 3 patients, P=0.001). Desmopressin acetate was administered more often in group A than in group B (8 vs. 2 patients, P=0.04). CONCLUSIONS: Algorithm-based therapy increased utilization of hemostatic interventions during the immediate recovery period without any obvious benefit to the hemostatic outcome. Re-evaluation of the platelet transfusion trigger seems warranted.     

Monitoring of Perioperative Dilutional Coagulopathy Using the ROTEM Analyzer: Basic Principles and Clinical Examples

Recent changes in quality of transfusion supply, transfusion triggers as well as fluid therapy promote the development of dilutional coagulopathy. Nevertheless, up to now guidelines generally assume presence of hypocoagulability when more than one individual circulating blood volume is lost. This might be true for some patients under some conditions but is not necessarily true for every patient. Routine coagulation tests are insufficient in predicting increased bleeding and, moreover, available after an unacceptable time delay. Therefore the occurrence of diffuse microvascular bleeding is often used as clinical sign to start hemostatic therapy. However, such severe derangement of hemostasis might lead to the development of secondary tissue damage and frequently is unresponsive to conventional treatment. Coagulopathy occurring during extensive surgery or after polytrauma can be detected and treated early when using the ROTEM monitoring. Recent data showing a direct beneficial effect of hemostatic therapy on blood loss and final outcome are scarce. However, evidence exists that the amount of blood loss, presence of coagulopathy and number of transfusions needed are associated with poor outcome in bleeding patients. Although manifold articles have been published already using thrombelastography for various indications (medline research "thrombelastography", 2022 articles), further data are needed to confirm the clinical experience that this technique is an excellent tool for safe patient management.     

Use of activated recombinant Factor VII (NovoSeven) during neurosurgery

Diffuse bleeding during neurosurgical operations is a major complication that can be difficult to control. In extreme circumstances, it may be necessary to clamp cerebral blood vessels or resect additional tissue. Both of these procedures can result in brain damage and, ultimately, in disability for the patient. We report on the use of recombinant activated blood coagulation Factor VII (rFVIIa) to control bleeding during neurosurgical procedures in three patients undergoing neurosurgery for brain tumors who received intravenous rFVIIa 4.8 mg (NovoSeven, NovoNordisk, Copenhagen, Denmark) for diffuse intracranial bleeding after conventional hemostatic techniques had been exhausted. All patients (one man and two women, age range 23-40 years) were otherwise somatically healthy with a mean weight of approximately 50 kg. Bleeding ceased 12 to 20 minutes after administration of rFVIIa. All three patients recovered with no further bleeding. In our initial experience, rFVIIa appears to be efficacious for terminating bleeding during neurosurgical procedures. The use of rFVIIa made it unnecessary to resort to procedures carrying a risk of long-term sequelae.     

Desmopressin and antifibrinolytics

Desmopressin appears to be a safe and effective hemostatic agent for use during surgery in patients with mild to moderate hemophilia or von Willebrand disease. Uremic patients also benefit from substitution of desmopressin for cryoprecipitate to control bleeding. The highly variable response to desmopressin by individual patients with hemophilia or von Willebrand disease dictates that each patient receive a trial administration prior to surgery; surgery should proceed only following verification of a therapeutically effective increase in Factor VIII and vWF after desmopressin. Use of desmopressin in patients with normal baseline hemostatic function is not clearly advantageous, although certain patient subgroups might benefit, and prospective studies have documented the drug's safety in these cases. Data are lacking to clarify a role for desmopressin during surgery in patients taking aspirin. Antifibrinolytic therapy appears to decrease bleeding without increased risk after cardiac surgery. In addition, specific use after urological surgery may be beneficial in the absence of upper urinary tract bleeding. In the last ten years, other applications for antifibrinolytic therapy have been found--both surgical (intracranial aneurysms, oral and lacrimal surgery) and nonsurgical (in cancer patients and for gastrointestinal bleeding). Although anecdotal reports have fueled fears of increased thrombosis with antifibrinolytics, controlled studies indicate no increased risk.     

Cryoprecipitate-topical thrombin glue. Initial experience in patients undergoing cardiac operations

The use of fibrin glues as topical hemostatic agents is reported in the European literature. We have composed an analogous compound in our operating rooms using cryoprecipitate and topical thrombin (1000 units/ml) in equal volumes applied directly to the bleeding site. We have used cryoprecipitate-topical thrombin glue in 26 patients undergoing cardiac operations. Severe bleeding not responding to usual methods of control was encountered during or after coronary artery bypass (n = 17), valve replacement (n = 3), bypass plus valve replacement (n = 5), or repair of postinfarction ventricular septal defect (n = 1). Five patients were operated on emergently and four were undergoing their second cardiac operation. The glue was used in four patients while on bypass and fully heparinized and in 17 patients who continued to bleed after separation from bypass and administration of protamine. Hemostasis was achieved in all patients and none required reexploration for bleeding. In five patients undergoing reexploration for postoperative hemorrhage (none having received cryoprecipitate-topical thrombin glue during the initial operation), the glue provided hemostasis when other measures failed, and no additional reexplorations were needed. No patient exhibited hypersensitivity, fibrinolysis, or coagulopathy following the use of this glue. In 16 patients followed for 9 to 12 months postoperatively, no hepatitis has occurred. The highly concentrated fibrinogen in cryoprecipitate is activated by thrombin to form fibrin and bring about rapid hemostasis. Cryoprecipitate-topical thrombin glue is a readily available, reliable, and inexpensive topical hemostatic agent in the patient undergoing a cardiac operation.     

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.     

Preoperative hemostatic activity and excessive bleeding after cardiopulmonary bypass

The rationale for predicting the risk of excessive postoperative bleeding by assessing the hemostatic status of a patient before cardiopulmonary bypass was investigated. A novel, rapid, overall test (hemostatometry) consisting of a physiologically relevant test of platelet function (shear-induced hemostasis) and coagulation was performed using nonanticoagulated blood and compared with the routine coagulation screen. Two hundred five patients undergoing elective coronary revascularization were studied 3 to 4 days before operation. Forty-nine bled excessively for nonsurgical reasons; none were predicted by the routine coagulation tests. Using a stepwise discriminant analysis, hemostatometry correctly predicted 31 of 49 (63%). Thirty of 156 predicted as bleeders by hemostatometry did not bleed. Thus, preoperative hemostatometry predicted 77% of the true outcome. The false predictions suggest, however, that certain bleeding abnormalities probably acquired during cardiopulmonary bypass cannot be predicted. These findings do not justify the routine use of preoperative tests in assessing the bleeding risk in patients undergoing cardiopulmonary bypass.     

腹腔镜胆总管探查取石术中出血的原因及对策

目的探讨腹腔镜胆总管探查取石术中出血的原因及处理办法。方法回顾分析2003年11月～2007年12月153例腹腔镜胆总管探查取石术发生29例术中出血的临床资料。结果1例中转开腹止血,6例钛夹夹闭,余22例经纱布压迫止血、Foley气囊胆管压迫、止血海绵填塞压迫、电凝、缝扎等方法,成功地控制了出血。结论术中出血的原因主要是结石长期压迫胆管壁形成感染、水肿、溃疡及不当操作。止血可采用纱布压迫、Foley气囊胆管压迫、止血海绵填塞压迫、电凝、钛夹夹闭、缝扎等方法,必要时中转开腹。     

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.     

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.     

Clopidogrel-related refractory bleeding after coronary artery bypass graft surgery: a rationale for the use of coagulation factor concentrates?

Clopidogrel, an irreversible ADP-receptor antagonist, inhibits platelet aggregation mediated by reduced activation of glycoprotein receptor IIb/IIIa. Clopidogrel in combination with aspirin has been shown to be superior to aspirin alone for treating unstable angina, but clopidogrel recipients have shown increases in blood loss, transfusion requirements, and rate of reoperation after cardiac surgery. We describe a patient who had taken clopidogrel 75 mg daily until the day prior to coronary artery bypass graft surgery. Severe postoperative bleeding developed and was refractory to conventional hemostatic therapy consisting of 19 units of packed red blood cell concentrates, 16 of fresh frozen plasma, 8 of platelet apheresis concentrates plus high-dose treatment with aprotinin (500.000 kallikrein-inhibiting units/h) and administration of 0.3 microg/kg 1-deamino-8-D-arginine vasopressin (DDAVP). Two reoperations were performed, but surgical hemostasis was not achieved, so 100 microg/kg recombinant activated factor VII was applied to generate sufficient thrombin to stop the bleeding. This treatment approach reduced the bleeding. Then, to promote clot formation and firmness, 2 g of fibrinogen and 1250 IU of factor XIII were administered, and the bleeding finally stopped. No further transfusions were required, and the patient was discharged from the hospital on day 10 after the operation. This case suggests that in clopidogrel-related bleeding refractory to conventional hemostatic therapy, hemostasis may be achieved by a stepwise administration of coagulation factor concentrates.     

阿加曲班与肝素在维持性血液透析患者抗凝治疗中的比较

目的 比较两种不同的抗凝方法在维持性血液透析(hemodialysis,HD)患者中的抗凝效果以及对患者凝血功能的影响.方法 选取40例维持性血液透析患者,先后采用不同的抗凝剂,一次使用肝素抗凝(肝素组),一次使用阿加曲班抗凝(阿加曲班组).监测患者治疗前血路管动脉端、治疗中2h血路管动、静脉端、治疗结束后1h活化部分凝血活酶时间(activated partial thromboplastin time,APTT),治疗过程中管路和透析器凝血情况,治疗后穿刺点压迫止血平均时间及组织器官24h内有无出血情况(包括鼻出血、牙龈出血、结膜出血、皮下出血点和黑便等).结果 阿加曲班组HD治疗中APTT明显延长,达到HD抗凝治疗要求,与HD治疗前相比,差异有统计学意义(P＜0.01);阿加曲班组与肝素组相比,治疗中2h及治疗后1h的APTT差异有统计学意义(P＜0.01);阿加曲班组与肝素组治疗中管路和透析器凝血情况比较差别不大,两组差异无统计学意义(P＞0.05);阿加曲班组与肝素组治疗后穿刺点压迫止血平均时间比较差异有统计学意义(P＜0.01);阿加曲班组治疗后组织器官出血较肝素组明显减少,两组比较差异有统计学意义(P＜0.05).结论 阿加曲班在HD抗凝治疗中抗凝效果确切,出血风险较普通肝素少,安全性高,尤其适用于有出血倾向的HD患者.     

Perioperative anesthetic management in a patient with factor XI deficiency undergoing coronary artery bypass graft surgery

Spontaneous bleeding is rare in patients with factor XI deficiency and significant bleeding usually occurs after a trauma or a surgical procedure. It is difficult to maintain hemostatic balance in these patients. In the present case report, a 68-year-old male patient with no chronic disease was scheduled for elective cardiopulmonary bypass surgery. Eight units of fresh-frozen plasma (FFP) were slowly infused and the operation was initiated with the activated partial thromboplastin time (aPTT) of 34.5, which was 108.7 in the preoperative period. Tranexamic acid bolus was administered before the skin incision and continued throughout the operation. Intraoperative aPTT was measured intermittently and a total of six units of FFP were administered. After 76 minutes of cross-clamp time, the patient was separated from cardiopulmonary bypass without any problem. There is no consensus regarding the management of bleeding during cardiac surgery in patients with factor XI deficiency. The common approach includes normalizing the factor levels via FFP infusion or factor concentrates in the preoperative period, proceeding with surgery following the replacement, and close monitoring of perioperative factor levels and aPTT values.     

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。     

Laparoscopic partial nephrectomy and wedge resection

Partial nephrectomy is a more challenging operation than radical or simple nephrectomy, primarily because of the risk of complications such as bleeding. This problem is even more troublesome with minimally invasive approaches because of the dearth of effective hemostatic instruments and supplies. The location of the lesion determines whether a transperitoneal or a retroperitoneal route will be employed. Centrally located or anterior renal lesions generally are approached transperitoneally whereas peripheral lateral or posterior lesions are accessed by retroperitoneoscopy. The Harmonic Scalpel with slow cutting and high coagulation settings is useful for incising the renal capsule and parenchyma. The argon beam coagulator is helpful to stop any persistent bleeding. The few reported series of laparoscopic partial nephrectomy indicate considerably longer operative times than are needed for open surgery and hospitalization of upwards of 5 days, largely to monitor drainage and urine leakage. It is hoped that this advanced laparoscopic technique will become more user friendly with further developments in techniques and instrumentation to provide patients with the expected benefits of minimally invasive surgery.     

The results of the endoscopic diathermy coagulation of hemorrhaging gastroduodenal ulcers]

The authors analysed the results of endoscopic diathermy coagulation of bleeding acute gastroduodenal ulcers in 83 patients; in 47 of them the follow-up period ranged from 12 months to 9 years. A stable hemostatic effect was achieved in the early periods after coagulation of the acute ulcers in 76% of cases. The frequency of recurrent bleeding was found to be directly dependent on the degree of the blood loss. Recurrent bleeding from acute ulcerations of the gastric mucosa in the late-term period was discovered authentically in only one patient. It was linked with medication with brufen for a long duration. Thus, endoscopic diathermy coagulation produced good results in arresting bleeding from acute gastroduodenal ulcers, particularly in patients with a very high operative risk.     

血凝酶注射液在腭裂整复术中的止血效果分析

目的：观察注射用血凝酶（巴曲亭）在腭裂修复术中的止血效果。方法：回顾性分析单侧完全性腭裂整复术患者180例。随机分为实验组和对照组。实验组应用血凝酶术前10min静脉推注0．5～1U；术后连续静点0．5—1U3天，对照组不用血凝酶。记录术中出血量、手术时间、双侧松弛切口完全止血时间；同时观察患儿出院创口愈合情况等各项指标。结果：血凝酶组患者在术中出血量、手术时间以及双侧松弛切口完全止血时间，创口愈合时间少于对照组。两组出院时创口愈合情况无明显差异。结论：血凝酶注射液在腭裂修复中能够减少术中，术后出血，具有明显的止血效果，安全可靠。