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.     

Successful perioperative management of factor X deficiency associated with primary amyloidosis

Acquired bleeding abnormalities are common in patients with primary amyloid light-chain amyloidosis. Factor X deficiency is the most common coagulopathy associated with life-threatening hemorrhagic complications when surgery is indicated. Fresh-frozen plasma (FFP) or prothrombin complex concentrates (PCCs) are the most frequently used blood products in this disease; however, FFP is often ineffective in controlling bleeding and PCCs have a significant risk of thrombosis when used intraoperatively. This report describes a patient with primary amyloidosis and factor X deficiency who underwent hemicolectomy with preoperative and intraoperative administration of recombinant human factor VIIa and postoperative administration of Bebulin (a PCC that contains the highest concentration of factor X). The management was successful with no signs of bleeding postoperatively. To our knowledge, few reports of successful perioperative management of factor X deficiency have been published to date. This is the first case report using recombinant human factor VIIa and Bebulin in the perioperative management of factor X deficiency associated with primary amyloidosis. Recombinant human factor VIIa and Bebulin may allow for successful perioperative management of bleeding disorders in patients with primary amyloidosis.     

Coronary artery bypass grafting in a patient with hemophilia B: continuous recombinant factor IX infusion as per the Japanese guidelines for replacement therapy

We herein report our experience of successfully managing the hemostatic system by controlling serum factor IX levels throughout the perioperative period in a patient with hemophilia B. Coronary artery bypass grafting with cardiopulmonary bypass was planned for a 52-year-old man with moderate severity of hemophilia B. During surgery, recombinant factor IX (rFIX; BeneFIX^® Pfizer Japan inc., Tokyo, Japan) was administered by bolus infusion followed by continuous infusion as per the guidelines of the Japanese Society on Thrombosis and Hemostasis. The operative course was uneventful without any considerable bleeding or complications.     

Emergency cardiac surgery in patients with acute coronary syndromes: a review of the evidence and perioperative implications of medical and mechanical therapeutics

Patients with acute coronary syndromes who require emergency cardiac surgery present complex management challenges. The early administration of antiplatelet and antithrombotic drugs has improved overall survival for patients with acute myocardial infarction, but to achieve maximal benefit, these drugs are given before coronary anatomy is known and before the decision to perform percutaneous coronary interventions or surgical revascularization has been made. A major bleeding event secondary to these drugs is associated with a high rate of death in medically treated patients with acute coronary syndrome possibly because of subsequent withholding of antiplatelet and antithrombotic therapies that otherwise reduce the rate of death, stroke, or recurrent myocardial infarction. Whether the added risk of bleeding and blood transfusion in cardiac surgical patients receiving such potent antiplatelet or antithrombotic therapy before surgery specifically for acute coronary syndromes affects long-term mortality has not been clearly established. For patients who do proceed to surgery, strategies to minimize bleeding include stopping the anticoagulation therapy and considering platelet and/or coagulation factor transfusion and possibly recombinant-activated factor VIIa administration for refractory bleeding. Mechanical hemodynamic support has emerged as an important option for patients with acute coronary syndromes in cardiogenic shock. For these patients, perioperative considerations include maintaining appropriate anticoagulation, ensuring suitable device flow, and periodically verifying correct device placement. Data supporting the use of these devices are derived from small trials that did not address long-term postoperative outcomes. Future directions of research will seek to optimize the balance between reducing myocardial ischemic risk with antiplatelet and antithrombotics versus the higher rate perioperative bleeding by better risk stratifying surgical candidates and by assessing the effectiveness of newer reversible drugs. The effects of mechanical hemodynamic support on long-term patient outcomes need more stringent analysis.     

Hemostatic matrix application after open synovectomy in a hemophilic patient

Recurrent, spontaneous bleeding is common in patients with hemophilia. The joints are commonly and repeatedly affected, and this can result in chronic synovitis and joint damage. Synoviorthesis or synovectomy are indicated after failure of appropriate medical management. Hemostasis in the perioperative period is paramount in these patients. We report a case study of a patient with hemophilia A inhibitors undergoing open synovectomy complicated by postoperative bleeding. In addition to an infusion of bypassing agents due to the presence of inhibitors, a topical hemostatic agent, FLOSEAL, and absorbable Gelfoam were applied. Hemostasis was achieved rapidly. The patient recovered without complications.     

A Jehovah’s Witness child with hemophilia B and factor IX inhibitors undergoing scoliosis surgery

PURPOSE: To describe the successful perioperative hemostatic management of a Jehovah's Witness patient with hemophilia B and anaphylactic inhibitors to factor IX, undergoing scoliosis surgery. CLINICAL FEATURES: A 14 (1/2)-yr-old boy with severe hemophilia B who had a history of anaphylactic inhibitors to factor IX was scheduled to undergo corrective scoliosis surgery. He was initially started on epoetin alfa and iron supplementation to maximize preoperative red cell mass. Additionally, he was placed on a desensitization protocol of recombinant coagulation factor IX (rFIX) and was then treated with activated recombinant coagulation factor VII (rFVIIa) during the postoperative period. Tranexamic acid was given concomitantly. The intraoperative blood loss was approximately 350 mL. The nadir hemoglobin concentration was 111 g.L(-1) on postoperative days one and two. On postoperative day 11, the patient was stable and discharged home with a hemoglobin of 138 g.L(-1). He did not require blood transfusion and no adverse events were observed. CONCLUSIONS: The use of rFIX, rFVIIa, erythropoetin, iron, and tranexamic acid before, during and after scoliosis surgery may be a viable and safe option for hemophilia patients with inhibitors, who refuse blood products.     

A novel hemostatic agent: the potential role of recombinant activated factor VII (rFVIIa) in anesthetic practice.

PURPOSE: To review the role of recombinant factor VIIa in anesthetic practice. SOURCE: A review of the published literature. MAIN FINDINGS: The mechanism of action of rFVIIa suggests enhancement of hemostasis limited to the site of injury without systemic activation of the coagulation cascade. In addition to its indication for use in patients with hemophilia, use of rFVIIa for treatment of uncontrolled massive hemorrhage in various peroperative settings appears to be rational, safe, and effective. Published results suggest that in trauma patients rFVIIa may play a role as an adjunctive hemostatic measure in addition to surgical hemostatic techniques There is preliminary evidence that hemorrhagic complications (eg. epistaxis, vaginal bleeding) associated with profound thrombocytopenia can be reversed with rFVIIa even at platelet counts below 10,000 per microL. Various case reports outlining the successful treatment with recombinant factor VIIa of patents experiencing intractable bleeding after valve replacement surgery, and with severe hemorrhage during therapy with left ventricular assist device, indicate the potential therapeutic efficacy of this agent in cardiac surgical procedures. Additionally, rFVIIa has been used successfully for treatment of massive postoperative bleeding following general surgery. CONCLUSIONS: rFVIIa is a novel hemostatic agent that shows promise in non-hemophiliac patents of a significant therapeutic role in variety of coagulopathic and hemorrhagic conditions in clinical situations ranging from thrombocytopenia, disseminated intravascular coagulation and transfusion-related coagulopathy, as well as in patients experiencing massive blood loss undergoing orthotopic liver transplantation, cardiac, orthopedic and genitourinary surgery.     

Management of postoperative hemorrhage associated with factor VIII inhibitor: report of a case

This report presents a case that was successfully treated for acquired factor VIII inhibitor after extensive visceral surgery. A 71-year-old male who underwent surgery for bile duct cancer had active bleeding in the abdominal drainage tube on postoperative day (POD) 5, and prolonged activated partial thromboplastin time (aPTT) was detected (83.1 s) on POD 7. An extensive coagulation work-up revealed factor VIII deficiency (1 %), and a diagnosis of an acquired factor VIII deficiency was established when a factor VIII inhibitor of 8 Bethesda units was demonstrated. The patient was treated with activated prothrombin complex concentrate (aPCCs) and bloody discharge was stopped within 3 days. Inhibitor elimination was started using prednisolone on POD 20; rituximab, was administered on POD 74 and 81. Factor VIII inhibitor had disappeared by POD 124, and factor VIII (72 %) and aPTT recovered to 45.9 s. This case report demonstrated the efficacy of aPCCs and rituximab in the treatment of acquired hemophilia associated with visceral surgery.     

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.     

重组活化凝血因子Ⅶ治疗心血管手术后渗血的临床探讨

目的 总结重组活化凝血因子Ⅶ(rFⅦa)治疗常规止血措施无效的心血管手术后渗血的初步经验.方法 回顾性分析2006年5月至2007年12月16例接受rFⅦa治疗的患者资料,其中男性15例,女性1例,年龄36～77岁,平均52岁.手术包括主动脉手术8例.瓣膜置换术6例,肺动脉内膜剥脱术1例和房间隔缺损修补术1例.应用rFⅦa治疗心血管外科术后渗血.结果 rFⅦa首次剂量27.6～54.5 ug/kg,平均40.2ug/kg,给药后6例达到止血效果.9例因出血持续于30 min内第2次给药,累计剂量59.3～90.9 ug/kg,平均80.3 ug/kg,8例获得止血,1例开胸探查.1例7 h内给药4次,累计剂量203.4 ug/kg后止血.给药后患者胸腔引流量明显下降,红细胞悬液、新鲜冰冻血浆、冷沉淀、血小板输注量明显减少.术后12 h内总引流量及红细胞悬液、冷沉淀输注量与给药距转流停机时间呈正相关.给药后凝血功能指标改善,全组患者在观察期间未发生血栓性并发症.结论 中小剂量rFⅦa应用于其他止血处理无效的心血管手术后渗血,可以减少引流量,降低血制品输注量.     

A case of heel reconstruction with a reverse sural artery flap in a hemophilia B patient

Hemophilia B is a rare blood coagulation disorder. Complications such as bleeding and hematoma can cause necrosis of flaps, wound disruption, and the disturbance of wound healing. In particular, guidelines for flap operations in hemophilia B patients have still not been defined, and case reports are rare. We reconstructed the heel of a 41-year-old male hemophilia B patient using a reverse sural artery flap operation. The patient presented with mild hemophilia, having 27% of the normal value of coagulation factor IX. Coagulation and the changing value of the coagulation factor were regularly measured, and 70% of the normal value of coagulation factor IX was maintained through the injection of recombinant coagulation factors and antihemorrhagics. Hematoma developed twice (postoperative day [POD] 5 and POD 7) and in each case the hematoma was removed. Injections of recombinant coagulation factors and antihemorrhagics were continuously administered until postoperative week 2. When the coagulation factors were within normal ranges. In this article, a hemophilia B patient underwent reverse sural artery flap surgery and the healing progress was analyzed. We conclude that higher than baseline levels of coagulation factors are needed for successful healing in reverse sural artery flap surgery.     

Bilateral percutaneous nephrolithotomy in a patient with hemophilia A disorder

A 50-year-old man with hemophilia A presented with recurrent hematuria due to renal stone disease. He was receiving approximately 50,000 units of recombinant factor (rF) VIII concentrate every year due to hematuria. Between 1996 and 2002, his serum creatinine level increased from 0.7 to 1.2 ng/ml. In an effort to resolve the problems of excessive blood loss with transfusions, recurrent rF VIII replacements and deteriorating renal function, he was offered treatment with percutaneous nephrolithotomy (PNL) in conjunction with rF VIII administration. He underwent left PNL for left staghorn calculi in November 2002 with administration of 52,000 units rF VIII, and another PNL for the right kidney in April 2004 with the administration of 90,500 units rF VIII. A pneumatic lithotriptor was used in both operations. The serum creatinine level was 0.8 ng/ml upon completion of treatment and the patient was symptom and stone free at 10-month follow-up. He has not suffered from hematuria since that time. We conclude that bleeding disorders may not be a contraindication for PNL if corrected and monitored appropriately.     

Clinical experience of urological surgery of the patients with hemostatic disorder or hemolytic disease]

This report deals with clinical experience of urologic surgery of patients with hemostatic disorder or hemolytic disease. In the past 5 years from May 1986, 14 operations were conducted in our clinic on 13 patients, consisting of 4 with von Willebrand disease (vWd), 1 with hemophilia B, 4 who had warfarin administration, 3 with essential thrombocythemia and 2 with spherocytosis. Almost all patients were treated hematologically before the urological operations. Except in 1 case, the post-operative course was favorable and under hematologic control. Massive bleeding in 1 case was obviously attributable to over-dosage of warfarin. It is difficult to determine the optimal dose of warfarin under an unstable hemostatic condition during the operation and recovery periods. However, it is possible to carry out urologic surgery for these patients under appropriate hematologic control, and ESWL was safely performed without medical treatment on 3 patients; 1 with vWd, 1 treated with warfarin and 1 with spherocytosis.     

Management of surgical hemostasis: systemic agents

Despite improvements in surgical techniques, the risk for perioperative bleeding remains significant. Transfusion of allogeneic red blood cells, platelets, and hemostatic factors remains the mainstay of current therapy strategy for management of perioperative bleeding. Transfusions significantly contribute to perioperative adverse events. Pharmacologic strategies to prevent or decrease perioperative bleeding are also important therapeutic approaches to reduce the need for allogeneic transfusions. This article discusses systemic pharmacologic prohemostatic agents (aprotinin, lysine analogues, protamine, desmopressin, and recombinant factor VIIa).     

Elevated prothrombin time on routine preoperative laboratory results in a healthy infant undergoing craniosynostosis repair: Diagnosis and perioperative management of congenital factor VII deficiency

IntroductionCongenital factor VII deficiency is a rare bleeding disorder with high phenotypic variability. It is critical that children with congenital Factor VII deficiency be identified early when high-risk surgery is planned. Cranial vault surgery is common for children with craniosynostosis, and these surgeries are associated with significant morbidity mostly secondary to the risk of massive blood loss.Presentation of caseA two-month old infant who presented for elective craniosynostosis repair was noted to have an elevated prothrombin time (PT) with a normal activated partial thromboplastin time (aPTT) on preoperative labs. The infant had no clinical history or reported family history of bleeding disorders, therefore a multidisciplinary decision was made to repeat the labs under general anesthesia and await the results prior to incision. The results confirmed the abnormal PT and the case was canceled. Hematologic workup during admission revealed factor VII deficiency. The patient underwent an uneventful endoscopic strip craniectomy with perioperative administration of recombinant Factor VIIa.DiscussionImportant considerations for perioperative laboratory evaluation and management in children with factor VII deficiency are discussed. Anesthetic and surgical management of the child with factor VII deficiency necessitates meticulous planning to prevent life threatening bleeding during the perioperative period.ConclusionA thorough history and physical examination with a high clinical suspicion are vital in preventing hemorrhage during surgeries in children with coagulopathies. Abnormal preoperative lab values should always be confirmed and addressed before proceeding with high-risk surgery. A multidisciplinary discussion is essential to optimize the risk-benefit ratio during the perioperative period.     

Surgery and invasive procedures in patients on long-term treatment with oral direct thrombin or factor Xa inhibitors

Direct oral anticoagulants (DOAs), inhibitors of factor IIa or Xa, are expected to replace vitamin K antagonists in most of their indications. It is likely that patients on long-term treatment with DOAs will be exposed to elective or emergency surgery or invasive procedures. Due to the present lack of experience in such conditions, we cannot make recommendations, but only propose perioperative management for optimal safety as regards the risk of bleeding and thrombosis. DOAs may increase surgical bleeding, they have no validated antagonists, they cannot be monitored by simple, standardised laboratory assays, and their pharmacokinetics vary significantly from patient to patient. Although DOAs differ in many respects, the proposals in the perioperative setting need not be specific to each. For procedures with low risk of haemorrhage, a therapeutic window of 48 h (last administration 24 h before surgery, restart 24 h after) is proposed. For procedures with medium or high haemorrhagic risk, we suggest stopping DOAs 5 days before surgery to ensure complete elimination of the drug in all patients. The treatment should be resumed only when the risk of bleeding has been controlled. In patients with a high risk of thrombosis (e.g. those in atrial fibrillation with an antecedent of stroke), bridging with heparin (low molecular weight, or unfractionated if the former is contraindicated) is proposed. In emergency, the procedure should be postponed for as long as possible (minimum 1–2 half-lives) and non-specific anti-haemorrhagic agents, such as recombinant human activated factor VIIa, or prothrombin concentrates, should not be given for prophylactic reversal, due to their uncertain benefit-risk.     

Treatment of bleeding in severe hemorrhagic pancreatitis with recombinant factor VIIa

Recombinant factor VIIa (rFVIIa) has been used to treat bleeding complications in patients with hemophilia. It acts at the site of vessel injury, forming a complex with tissue factor to activate the clotting cascade. Recent reports have shown rFVIIa may be a useful hemostatic agent in patients after obstetrical, urologic, trauma, or transplant procedures. We report the first documented case of bleeding from hemorrhage pancreatitis treated with rFVIIa.     

Uncontrollable hemorrhage and tissue adhesive.

A case is reported of uncontrollable hemorrhage from suture lines in a patient having undergone coronary surgery. Ultimately the bleeding was brought under control by the use of isobutyl-cyanoacrylate. A piece of fascia was affixed to the suture line. Tissue adhesive is a valuable tool in difficult hemostatic situations, and should be available where major surgery is performed.     

Anesthetic management of a hemophilia A patient with HIV infection: a case report

A 40-year-old male with hemophilia A was scheduled for right total knee arthroplasty. He was HIV positive probably due to receiving infected blood products previously. We performed the pharmacokinetic study of factor VIII in advance, which showed the increased factor VIII activity 1.6% by an injection of one unit. kg-1 of factor VIII and the half-life of about 16 hours. To keep the factor VIII activity over 100% in the perioperative period, 3000 units of recombinant factor VIII was injected one hour before the induction of anesthesia followed by continuous infusion at 125 units per hour. The factor VIII activity before the induction was 110.6%. The operation was successful and there was no sign of bleeding tendency. The factor VIII activity after the operation, however, was unexpectedly low (73.1%), and it was necessary to increase the infusion rate to 150 units per hour. The factor VIII activity was kept over 80% until POD 7 with the continuous infusion and over 60% until POD 21 with intermittent administration. Factor VIII was discontinued on POD 21 without any sign of bleeding tendency after the postoperative rehabilitation. Although this patient was HIV positive, his immune system was well controlled with HAART and there was no difficulty in the anesthetic management. To prevent accidental infection to the medical staff, we again recognized the importance of standard precautions.     

Perioperative use of prothrombin complex concentrates

Prothrombin complex concentrates (PCCs) are purified drug products with hemostatic activity derived from a plasma pool. Today, PCCs contain a given and proportional amount of four non-activated vitamin K-dependent coagulation factors (II, VII, IX, and X), a variable amount of anticoagulant proteins (proteins C and S, and in some antithrombin) and low-dose heparin. In some countries PCC products contained only three clotting factors, II, IX, and X. Dosage recommendations are based on IU of F-IX, so that one IU of F-IX represents the activity of F-IX in 1 mL of plasma. Reversion of the anticoagulant effect of vitamin K antagonists (VKAs) in cases of symptomatic overdose, active bleeding episodes, or need for emergency surgery is the most important indication for PCCs and this effect of PCCs appears to be more complete and rapid than that caused by administration of fresh frozen plasma. They may be considered as safe preparations if they are used for their approved indications at the recommended dosage with adequate precautions for administration, and have been shown to be effective for reversing the effect of VKAs. Their adequate use based on decision algorithms in the perioperative setting allows a rapid normalization of International Normalized Ratio (INR) for performing emergency surgery, minimizing bleeding risk. This review aims to propose two algorithms for the use of PCCs in the perioperative setting, one to calculate the PCCs dose to be administered in a bleeding patient and/or immediately before urgent surgery, based on patient's clinical status, prior INR and INR target and another for reversing the action of oral anticoagulants depending on urgency of surgery.