Acquired hemophilia A caused by factor VIII inhibitors: report of a case

We report a case of acquired hemophilia A (AHA) after esophageal resection. The patient was an 80-year-old woman whose preoperative activated partial-thromboplastin time (APTT) was well within the normal range, at 34.9 s. She underwent thoracic esophagectomy and gastric pull-up for superficial esophageal cancer (operative time, 315 min; intraoperative blood loss, 245 ml). Intrathoracic and subcutaneous bleeding occurred spontaneously on postoperative day (POD) 39. The APTT was prolonged, at 140 s, and factor VIII inhibitor was 36 Bethesda U/ml. Treatment with recombinant activated factor VII, prednisolone, and cyclophosphamide resulted in remission within 2 months. This case supports an association between surgery and the triggering of factor VIII inhibitors. The diagnosis of AHA requires clinical acumen and must be considered in any patient with bleeding and a prolonged APTT.     

Acute renal failure as a complication of acquired hemophilia due to autoantibody to factor VIII

A 53-year-old Japanese woman, without any specific medical or family history, was admitted to our hospital for acute renal failure with macrohematuria. Routine blood analysis, including blood coagulation test, revealed azotemia accompanied by prolonged activated partial thromboplastin time (aPTT). Computed tomography revealed bilateral kidney swelling with dilatation of the renal pelvis. An extensive coagulation analysis revealed that the concentration of factor VIII had decreased to 1.8% and the level of factor VIII inhibitor was markedly elevated to 19 BU/ml. The final diagnosis was acquired hemophilia induced by autoantibodies against factor VIII, which was complicated by postrenal acute renal failure due to the obstruction of urinary tracts by renal bleeding and clots. The patient was treated with a combination of prednisolone at a dose of 50 mg/day (1 mg/kg body weight) and cyclophosphamide. The levels of factor VIII inhibitor decreased gradually, and the activity of factor VIII was improved after treatment. The levels of aPTT and concentrations of factor VIII and factor VIII inhibitor were monitored during the subsequent follow-ups.     

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.     

Acquired hemophilia A as a cause of postoperative bleeding

Acquired spontaneous hemophilia is a rare but potentially life-threatening disease, which poses a major challenge to intensive care medicine. We report a case in which the disease occurred postoperatively in a patient following uncomplicated lumbal discectomy. The clinical sequelae involved hemorrhagic shock (cHb 4.1 g/dl; hct 17 %; systolic BP 60 mmHg; HR 130/min; saO2 73 %) due to retroperitoneal hematoma eight days after neurosurgical intervention. While lesions of the retroperitoneal vessels were not found during emergent angiography and laparotomy, the laboratory results showed a slightly prolonged activated prothrombin time (aPTT; 47 s). However, application of fresh frozen plasma (FFP) even prolonged the aPTT (53 s). Analysis of clotting factors proved a deficiency of factor VIII with a reduced activity of about 20 %, which was resistant against therapy with desmopressin (DDAVP) and substitution of factor VIII. Thus, the plasma-mix-test was performed, showing complete inactivation of the factor VIII-activity of the pooled plasma. This evidenced the presence of acquired inhibitors against factor VIII. Hemostasis was successfully and immediately restored with the application of recombinant factor VIIa (rFVIIa), including boluses of 60 - 80 microg/kg every 6th - 8th hour (supplemented with tranexamic acid, 3 x 1 g/d), leading to a continuous infusion of 12 microg/kg per hour. With prednisolone (1 mg/kgBW/d) over the ensuing 8 weeks, the antibodies were sufficiently suppressed and no additional substitution of factor VIII was necessary to maintain normal hemostasis.     

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.     

Perioperative use of recombinant activated factor VII (rF VIIa) in a patient with hemophilia A having inhibitors

We experienced the perioperative management of a patient with hemophilia A having inhibitors using recombinant activated factor VII (rF VIIa). A 55-year-old man was scheduled for right total hip arthroplasty. Since he developed high titer of VIII inhibitor, rF VIIa was utilized for the hemostatic control for "bypass therapy". Dosage and interval for perioperative rF VIIa administration were determined before the surgery with a trial injection. Just before anesthesia induction, rF VIIa (9.6 mg) was given and repeated every 2 hrs during surgery till the 2nd post operative day (POD). Thereafter, rF VIIa was repeatedly given in decremental steps till 5th POD. Although intraoperative bleeding was 2500 g and 1200 ml of RBC was transfused, post surgical bleeding was minimal and no adverse effect was observed. He was discharged on 46th POD without any trouble. Perioperative rF VIIa administration is safe and useful for hemostatic control in a patient with hemophilia A having inhibitor.     

Elective cardiac operation in a patient with severe hemophilia and acquired factor VIII antibodies

This paper describes a successful cardiac operation in a young boy with hemophilia, congenital heart disease, severe factor VIII deficiency, and an acquired high titer antibody to factor VIII. To our knowledge, there have been no published cases of elective cardiac operations in a person with severe hemophilia and an accompanying complex problem. Utilizing the team approach, we administered a megadose bolus of factor VIII concentrate preoperatively (eight times the calculated dose), followed by a continuous intravenous infusion at 500 units/hr throughout the procedure and at a reduced dose for the first 5 postoperative days. With the anamnestic rise in factor VIII antibody on day 5, activated prothrombin complex concentrates were substituted for factor VIII and provided continued adequate hemostasis during the remaining 9 postoperative days. The rapid infusion of large quantities of factor VIII was effective in neutralizing the low titer inhibitor and providing normal hemostasis during the procedure. In addition, activated prothrombin complex concentrates were substituted for factor VIII coagulant without recurrent bleeding or thromboembolic phenomena.     

Cholecystectomy and acquired factor VIII inhibitor coagulopathy

The purpose of this study was to describe the outcome of patients undergoing surgery with recognized and unrecognized factor VIII inhibitor. The setting was a tertiary care center with a community-based general surgery training program. Two patients with acquired factor VIII inhibitor coagulopathy required cholecystectomy. Interventions included intravenous immunoglobulin (IVIG) and factor VIII transfusions. An elderly patient undergoing urgent open cholecystectomy for acute cholecystitis exsanguinated despite postoperative recognition and treatment of factor VIII inhibitor. A second patient with known factor VIII inhibitor underwent laparoscopic cholecystectomy with perioperative transfusions of factor VIII and IVIG. No hemorrhage occurred, but cost to the patient exceeded 50,000 dollars. Acquired factor VIII inhibitor coagulopathy is rare and potentially lethal. Preoperative recognition and appropriate hematologic intervention is crucial to achieve a successful outcome.     

Factor XII Deficiency Acquired by Orthotopic Liver Transplantation: Case Report and Review of the Literature

Transmission of congenital clotting factor deficiencies after orthotopic liver transplantation is rare. There are published reports of liver donor-to-recipient transmission of protein C deficiency with dysfibrinogenemia, protein S, factor VII and factor XI deficiencies. We report a case of transmission of factor XII deficiency with liver transplantation in a patient with Budd-Chiari syndrome. There was a persistent elevation of the activated partial thromboplastin time (aPTT), but no evidence of bleeding while the patient was maintained on warfarin. The presence of a persistently abnormal aPTT may raise suspicion for the presence of a clotting factor deficiency; however, deficiencies of other clotting factors may not be readily apparent on routine blood tests performed in a donor. Being aware of the possibilities of transmission of these inherited deficiencies of coagulation factors will aid in their early detection and management in the transplant donor and recipient.     

Surgery and the acquired inhibitor of factor VIII coagulant

A case is reported of an 80 year old woman with old sarcoidosis and acquired factor VIIIc inhibitor undergoing orthopaedic surgery. This was successfully carried out after she had been given a total of 48,420 units of factor VIII concentrate: there were no haemorrhagic complications. The main pathological states in which acquired factor VIIIc inhibitor may be found are related: principal treatments available nowadays are discussed: immunosuppressors, human factor VIII, animal factor VIII, prothrombin complex concentrate, plasma exchange.     

Rituximab therapy in two children with autoimmune thrombotic thrombocytopenic purpura

Thrombotic thrombocytopenic purpura (TTP) is a rare disease among pediatric patients, in whom it may be mistaken for hemolytic uremic syndrome (HUS) and idiopathic thrombocytopenic purpura (ITP). Familial forms are caused by mutations in the ADAMTS13 gene, whereas acquired forms may result from an inhibitory antibody directed against ADAMTS13, a metalloprotease that cleaves very large multimers of Von Willebrand factor (VWF), thereby preventing platelet aggregation in blood vessels. We report two cases of TTP. The first was a 15-year-old girl with her first episode of TTP that failed to respond after 10 days of plasmapheresis and was treated with rituximab; she has remained in remission at 12 months of follow-up. The second was a 6-year-old boy with acquired relapsing TTP previously managed with plasmapheresis and prednisolone, who presented with a third relapse that was treated with plasmapheresis and rituximab; he remains in remission 17 months after treatment. Rituximab has been used by pediatricians for treating B cell malignancy, autoimmune diseases and antibody-mediated diseases, such as the Factor VIII inhibitors in hemophilia A, and may also have a promising role in children with acute refractory or chronic relapsing TTP.     

Autoantibodies and anti-factor VIII and Chlamydia pneumoniae infection

We report the case of a 64-year-old man without hemorrhagic history experiencing epistaxis. The standard hemostasis assessment including prothrombin index, activated partial thromboplastin time (APTT) and platelet count found an isolated abnormal APTT (105 sec vs 33 sec). Therefore, coagulation factors were explored. An acquired factor VIII deficiency (5%) with anti-FVIII antibody (4.5 Bethesda unit.mL-1) was recognised. This anti-FVIII antibody was related to a Chlamydia pneumoniae pulmonary infection. Treatment consisted of: i) Four successive anterior packing and activated factor VII infusion (Novoseven); ii) steroids injection and bi-antibiotherapy. The time course of the epistaxis was favourable under treatment.     

Successful treatment of collapsing focal segmental glomerulosclerosis with a combination of rituximab, steroids and ciclosporin

We report a case of a 2-year-old boy with steroid- and ciclosporin (CsA)-resistant collapsing focal segmental glomerulosclerosis (FSGS) who went into complete remission with a combination of IV rituximab and methylprednisolone pulse therapy (MPT) while receiving oral CsA. He was initially treated with steroids including MPT, CsA, and plasmapheresis, but his massive proteinuria and severe systemic edema persisted. We treated him with four weekly doses of intravenous rituximab. After the second administration of rituximab, his proteinuria and systemic edema were dramatically improved, but hypoalbuminemia and proteinuria persisted. Eight months after the onset, he was re-treated with two courses of MPT. Thereafter, he finally went into complete remission 1 month after MPT. He continued in remission for 8 months with CsA, but then relapsed. However, he went into complete remission again with 60 mg/m² of oral prednisolone without rituximab and since then, he has been in remission with CsA. This is the first report of the successful treatment of collapsing FSGS with rituximab. Thus, rituximab emerges as a new therapeutic option against refractory collapsing FSGS.     

A case of acquired hemophilia A with massive hemothorax

Acquired hemophilia A (AHA) is an uncommon but potentially life-threatening hemorrhagic disorder caused by the development of an inhibitor against coagulation factor VIII (FVIII). AHA is very rare, affecting approximately 1 in 1 million individuals. However, the incidence may actually be higher, because diagnosis is difficult and the disease can be overlooked. We report a case of an 80-year-old man who presented with sudden onset of severe hemothorax. The patient was diagnosed with presumed AHA based on acute onset of bleeding symptoms and unexplained isolated prolonged activated partial thromboplastin time. Diagnosis was definitely established by demonstrating a decrease in FVIII activity, presence of FVIII inhibitor activity, and normal von Willebrand factor. The patient was successfully treated with recombinant activated coagulation factor VII and transcatheter artery embolization of the intercostal arteries.     

Combined factor V and VIII deficiency and pregnancy – Need for an early protocol-based multidisciplinary management

We report the medical management of a 32-year-old primigravida, after she was found to have a combined factor V (FV) and factor VIII (FVIII) deficiency during pregnancy. A routine coagulation profile performed during the 6th month of pregnancy showed a prolonged activated partial thromboplastin time (aPTT) of 78 seconds, giving a patient/control ratio of 2.29, combined with a prothrombin time (PT) of 28 seconds. An investigation of the coagulation factors showed a combined FV and FVIII deficiency of 29% and 21% respectively. The bleeding risk was considered to be high. A multidisciplinary approach permitted a specific and individualized FVIII substitution protocol. At 39 weeks of amenorrhea, the patient was admitted to the labor room. An infusion of 2000 IU of FVIII was implemented over 5 minutes; soon thereafter, PT was 17 seconds, aPTT patient/control ratio had decreased to 1.9 and FV and FVIII reached 38% and 36% respectively. Six hours later, the patient delivered an infant weighing 2850 g who had an Apgar score of 10. No bleeding was detected. The patient was then closely monitored for 2 hours in the recovery room. Twelve hours after administration of the first dose of FVIII, another infusion of 2000 IU of FVIII was administered. This substitution treatment was continued every 12 hours in ever-decreasing doses, allowing maintenance of FVIII level > 50% for 5 days. At D7 post-partum, the patient was discharged uneventfully.     

Intramural Hematoma of the Cecum as the Lead Point of Intussusception in an Elderly Patient with Hemophilia A: Report of a Case

Hemophilia A is a congenital bleeding disorder characterized by a deficiency of coagulation factor VIII. Intramural hematoma of the colon is a very rare complication of this disease. We report a case of intramural hematoma of the cecum serving as the lead point of intussusception in a 65-year-old man with hemophilia A. The patient presented with right-sided abdominal pain and bloody stool. Palpation of his abdomen revealed a fist-sized mass. Abdominal computed tomography (CT) showed a circular mass with concentric rings, consistent with an intussuscepted intestine. Because his activated partial thromboplastin time (APTT) was prolonged, we gave him a continuous infusion of factor VIII during and after surgery. Laparotomy revealed an irreducible colo-colic intussusception and we identified a cecal hematoma as the lead point. After an unsuccessful attempt at Hutchinson's maneuver, we performed right colectomy. We report this case to illustrate the necessity of monitoring APTT in patients with hemophilia A who undergo surgery.     

Postsurgical coagulopathy in a hemophilia A patient with inhibitors: efficacy of recombinant factor VIIa

Perioperative hemostatic management in patients with hemophilia A who develop the coagulation factor VIII (FVIII) inhibitor is challenging, because exogenous FVIII is neutralized, which boosts the inhibitor to provoke postoperative coagulopathy. Recombinant activated factor VII (rFVIIa) has become available for this type of patient, although FVIII is sometimes required. We treated a 56-year-old male patient with hemophilia A with FVIII inhibitor scheduled for total hip arthroplasty (THA) and total knee arthroplasty (TKA). We used rFVIIa for THA; however, the amount of bleeding was 2,500 ml and blood transfusion was required, which boosted FVIII inhibitor after surgery. The TKA was then scheduled for 19 months later, after the level of the inhibitor had reduced to the preoperative level. Unfortunately, rFVIIa failed to improve PT/APTT, and thus we used recombinant factor VIII (rFVIII). The amount of bleeding during TKA was 1,340 ml, while the level of the inhibitor increased to a greater level than that after THA, provoking uncontrollable bleeding. For anesthetic management in hemophilia A patients with FVIII inhibitor, anesthesiologists must pay attention to postoperative coagulopathy, and every effort should be used to minimize exposure to FVIII. Furthermore, when rFVIIa is ineffective, postponement of surgery until rFVIIa regains its efficacy may be beneficial as compared to an operation with FVIII.     

Clinical efficacy of rituximab for acute rejection in kidney transplantation: a meta-analysis

Objectives

This meta-analysis was undertaken to compare the efficacy and safety of pretransplant treatment with rituximab in sensitized patients receiving kidney transplantation.

Methods

PubMed, EMBASE, and Cochrane databases were searched to identify studies that used pretransplantation rituximab in eligible patients. The major outcomes included antibody-mediated rejections (AMR) after kidney transplantation and one-year graft survival rate. The meta-analysis was performed using fixed-effects model.

Results

Seven studies were identified including a total of 589 patients, of whom 312 were treated without rituximab, while 277 were treated with rituximab. In our meta-analysis, patients treated with rituximab had significantly fewer AMR after kidney transplantation [odds ratio (OR) 0.52, 95 % CI 0.28, 0.98, P = 0.04] and higher rate of one-year graft survival rates (OR 3.02, 95 % CI 1.14, 8.02, P = 0.03), indicating that rituximab is effective against acute rejection and enhances graft survival in kidney transplantation. No differences were noted in other efficacy and safety parameters in these two patient groups.

Conclusions

We demonstrated that preinduction with rituximab could significantly improve AMR and graft survival rates in sensitized patients undergoing kidney transplantation. Future prospective controlled studies are warranted to further understand rituximab’s role in kidney transplantation.     

The effects of combined epidural and general anesthesia on the autonomic nervous system and bioavailability of nitric oxide in patients undergoing laparoscopic pelvic surgery

Background

Pneumoperitoneum during laparoscopic surgery is known to affect visceral blood flow and result in oxidative stress. Whether epidural anesthesia will effectively reduce visceral ischemia and oxidative stress by blocking the sympathetic nervous system (SNS) during laparoscopic surgery has not been proven.

Methods

Forty-five patients who were to undergo robot-assisted laparoscopic prostatectomy were randomly assigned to the combined general–epidural anesthesia group (group GE, n = 22) or to the general anesthesia group (group G, n = 23). Blood pressure, heart rate, and the balance between sympathetic and parasympathetic nervous system activity as measured by heart rate variability were recorded at 10 min after induction of anesthesia (T1), 60 (T2) and 120 (T3) min after intra-abdominal CO₂ insufflation, and 10 min after returning the patient to the supine position following CO₂ exsufflation (T4). Arterial blood gas analysis and blood sampling for measurements of nitrite (NO^2?) and malondialdehyde (MDA) were performed at all time points.

Results

Intraoperative mean blood pressure was significantly lower in group GE compared with group G. The low-frequency to high-frequency ratio was significantly increased after induction of pneumoperitoneum in group G but was unchanged in group GE. Plasma levels of nitrite decreased after pneumoperitoneum induction in group G while there was no change in group GE. A significant increase in MDA levels was seen in group G after pneumoperitoneum induction and were higher than group GE at T3 and T4. The 24-h urine output was higher in group GE than in group G on POD 1. The 24-h CrCl was higher in group GE on POD 1 but was not different between groups on POD 2.

Conclusions

Combined epidural and general anesthesia effectively blocks SNS stimulation during laparoscopic surgery and reduces NO inactivation and oxidative stress.     

Intraoperative mechanical and chemical pleurodesis with 50 % glucose solution for secondary spontaneous pneumothorax in patients with pulmonary emphysema

Purpose

Secondary spontaneous pneumothorax is life-threatening for patients with pulmonary emphysema. To prevent recurrence, intraoperative pleurodesis is performed in addition to bullectomy. We report the therapeutic process and effectiveness of adding mechanical plus chemical pleurodesis, with a 50 % glucose solution, to bullectomy, for patients with pulmonary emphysema-related pneumothorax.

Methods

The subjects were 20 patients (19 men and 1 woman; mean age 68 years) with pulmonary emphysema-related pneumothorax. After bullectomy was completed, 500 mL of a 50 % glucose solution was injected into the pleural cavity, followed by mechanical pleurodesis performed via ablation of the parietal pleura.

Results

The volume of pleural effusion decreased on postoperative day (POD) 1, and the temperature decreased on POD 2. The blood sugar levels increased on the day of surgery but decreased on POD 1. The mean postoperative follow-up period was 521 days. One patient died of pneumonia on POD 24. All other patients survived without pneumothorax recurrence.

Conclusions

These results demonstrated the effectiveness of our treatment process for pulmonary emphysema-related pneumothorax. The fact that no patient experienced pneumothorax recurrence suggests that mechanical and chemical pleurodesis with 50 % glucose solution might be effective prophylaxis.