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.     

Spontaneously acquired anti-factor VIII antibodies: report of a patient with adenocarcinoma of the prostate

Anti-factor VIII antibodies, inherited or acquired inhibitors of the factor VIII molecule, have not been reported previously in the urological literature. Although more common in hemophiliac patients who have received multiple transfusions, this anticoagulant may be the cause of severe hemorrhage in nonhemophiliac patients. We describe a patient with carcinoma of the prostate and an unsuspected anti-factor VIII antibody, who experienced excessive postoperative bleeding and prolonged hospitalization following a vesicolithotomy and bilateral orchiectomy. A prolonged partial thromboplastin time and a significant decrease in measurable factor VIII clotting activity in a patient with no history of bleeding problems are essential clues in making the diagnosis of a factor VIII inhibitor. This coagulation defect is treated best with prothrombin complex concentrates, which contain vitamin K dependent clotting factors.     

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.     

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.     

A case of acquired hemophilia A discovered by right renal bleeding

An 81-year-old man was referred to our hospital with a chief complaint of asymptomatic macrohematuria. Cystoscopy revealed bleeding from the right ureteral orifice. Various examinations, including ureteroscopy, failed to find any abnormalities. As gingival bleeding followed the macrochematuria, further examinations of blood coagulatory function were undertaken. Decreased factor VIII coagulant activity accompanied by the presence of factor VIII inhibitor was revealed, leading to a final diagnosis of acquired hemophilia A. Macrohematuria and gingival bleeding immediately disappeared with oral administration of prednisolone at 30 mg per day, and the titer of factor VIII inhibitor decreased to an undetectable level by the 45th day of treatment. We emphasized the importance of blood coagulation testing in the examination of patients with macrohematuria.     

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.     

Inherited Bleeding Disorders in Dermatologic Surgery

BACKGROUND: A patient referred for Mohs micrographic surgery of a basal cell carcinoma had a history of a congenital clotting factor IX deficiency requiring recombinant factor IX replacement. OBJECTIVE: To examine the management and problems associated with cutaneous surgery in patients with inherited clotting factor deficiencies. METHODS: Case report and review of the medical literature. RESULTS: Reconstructive options must be carefully chosen to minimize bleeding in patients with clotting factor deficiencies. Preoperative consultation with a hematologist and coagulation factor replacement both before and after cutaneous surgery prevent excessive hemorrhage. CONCLUSION: Meticulous attention to hemostasis, careful preoperative assessment, and postoperative follow-up minimize complications in patients with known coagulation deficiencies who require cutaneous surgery.     

Unusual postoperative hemorrhage in a patient with ruptured aneurysm and hemophilia B

A case of ruptured cerebral aneurysm with hemophilia B is reported, and discussion is made concerning the management of mild type hemophilia in surgical operations. A 41-year-old male came to our hospital with complaints of severe headache, vomiting, and transient consciousness disturbance. His dentist said the patient had a mild bleeding tendency when he was 30 years old, however no postoperative hemorrhage was repeated in appendectomy in his childhood. He also had had no episodes of spontaneous bleeding. CT scan on admission showed subarachnoid hemorrhage, and angiography revealed a ruptured aneurysm at the trifurcation of the left middle cerebral artery. His coagulation screening tests (bleeding time, clotting time, prothrombin time, and activated partial thromboplastin time) were normal. An aneurysmal neck clipping was carried out, and operators did not detect any bleeding tendency during the surgery. CT scan on the next day showed no remarkable finding. On the third postoperative day, right hemiparesis occurred. Left putaminal hemorrhage took place. His coagulation tests and FDP were also normal. The hematoma was partially evacuated. After the second operation his condition was good, and rehabilitation program started. On the 15th hospital day his consciousness deteriorated suddenly, and CT scan showed a massive epidural hematoma on the left. His prothrombin time elongated mildly, but other tests were normal. Coagulation factors VIII and IX were examined and the factor IX was 22.5% of control. He was thought to be a patient with mild type hemophilia B. Despite a third operation for hematoma removal he died on the 20th hospital day. Mild type hemophilia B does not bleed spontaneously.(ABSTRACT TRUNCATED AT 250 WORDS)     

Anesthetic management of a patient with acquired factor V inhibitor

A 74-year-old man was scheduled for laparoscopic low anterior resection of rectal cancer. Preoperative blood coagulation test showed his prothrombin time (PT) and activated partial thromboplastin time (APTT) remarkably prolonged. However, he experienced only slight epistaxis. Further examination suggested the presence of acquired factor V inhibitor. Plasmapheresis was carried out before surgery to eradicate inhibitors, but improvement of PT and APTT was temporary. We prepared platelet transfusion and recombinant activated factor VII (rFVIIa) for acute intraoperative bleeding, but there were no abnormal episodes during the surgery. On postoperative day 15, the patient suddenly passed blood in his stool, and received platelet transfusion. For the majority of patients with acquired factor V inhibitor, bleeding is usually mild, but fatal bleeding complications have also been reported. Platelet transfusion was effective in the patient described here.     

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.     

Unforeseen encounter of acquired hemophilia A in a preoperative case of periampullary carcinoma: A case report

IntroductionAcquired hemophilia A (AHA) is a rare disorder characterized by development of antibodies against factor VIII, which can present as paraneoplastic syndrome in various malignancies like periampullary cancer, cancer of lung, prostate, gastrointestinal stromal tumour and non malignant cases like pregnancy, autoimmune disease and medication.Case presentationWe report a case of elderly man presented with paraneoplastic AHA in periampullary carcinoma in preoperative period which was diagnose by mixing study and inhibitor assay and managed with bypass agents like recombinant factor VII, FEIBA and immunosuppresion to eliminate inhibitor with help of steroid, cyclophosphamide and emicizumab. Patient underwent Whipple’s pancreaticoduodenectomy after which coagulation study became normal in immediate postoperative period. Patient was discharged and followed up with chemotherapy.Clinical discussionPeriampullary carcinoma presenting as AHA is rare and rarer in pre-operative settings. The usual mode of presentation is bleeding after biopsy and from minor surgical scars. The pathogenesis is yet to be delineated. It is managed by factor VIII administration and immunosuppressive therapy.ConclusionHigh index suspicion should be there to diagnose AHA as a paraneoplastic manifestation and elective surgery should be delayed till normalization of coagulation parameters.     

Coagulation abnormalities and liver function after hemi-Fontan and Fontan procedures - the importance of hemodynamics in the early postoperative period.

INTRODUCTION: The causes of coagulation abnormalities and thromboembolic complications during staged Fontan approach in patients with single ventricle remain unclear. This study was designed to evaluate the coagulation profile in the early postoperative period after hemi-Fontan and Fontan procedures with relationship to liver function and hemodynamic variables. MATERIALS AND METHODS: The prospective study on 43 patients after hemi-Fontan (group 1) and 37 patients after Fontan procedure (group 2) was carried out. Coagulation profile (factor VII, factor VIII, ATIII, fibrinogen, prothrombin), liver function (total serum protein, albumin, AST, ALT, bilirubin), and hemodynamic variables were assessed on postoperative day 1 and 5 and compared to preoperative measures. RESULTS: Factor VIII concentration was significantly higher on first postoperative day in both groups. On postoperative day 5 the concentration of factor VIII was significantly decreased in group 1 whereas constant in group 2. The concentration of factor VII, ATIII, fibrinogen, and prothrombin was significantly decreased on first and increased on fifth postoperative day after both hemi-Fontan and Fontan procedures. The increase in bilirubin concentration was more distinctive after Fontan operation (p=0.003) with lower AST in this group (p<0.0001). The single ventricle function, pO2 and central venous pressure had significant influence on factor VIII (p=0.034), factor VII (p=0.012), ATIII (p=0.006), and prothrombin (p=0.024) concentrations in group 2 with no significant influence in group 1. CONCLUSIONS: The distinctive causes of coagulation abnormalities during staged Fontan approach are hemodynamic changes and temporary liver dysfunction. Elevated concentration of factor VIII and significant influence of hemodynamics on coagulation profile could contribute to postoperative thromboembolic complications.     

Hémarthroses et hémophilie acquise : à propos de 2 observationsHémarthrosis in acquired hemophilia: 2 case-reports

The many causes of hemarthrosis include acquired hemophilia due to production of auto-antibodies to factor VIII. We report 2 very different cases.Case 1. – This woman experienced onset of juvenile idiopathic arthritis at 8 years of age. Her first child was born when she was 28-years-old. Three months after delivery, vaginal bleeding and recurrent hemarthrosis led to a diagnosis of acquired hemophilia (isolated APTT prolongation, 1% VIIIc activity, and 58 U of antifactor VIII antibody). Treatment included glucocorticoid therapy, prothrombin complex, and intravenous immunoglobulins. She achieved a full recovery within a year.Case 2. – In this 84-years-old woman, spontaneous recurrent hemarthrosis with hematomas revealed idiopathic acquired hemophilia. Treatment included prothrombin complex, factor VIII concentrates, and intravenous immunoglobulins, followed by cyclophosphamide and glucocorticoid therapy. Recovery was complete within a year. The diagnosis, etiology, prognosis, and treatment of acquired hemophilia are discussed.Conclusion. – Although rare, acquired hemophilia should be considered among the causes of hemarthrosis, particularly as a favorable outcome can be expected with early diagnosis and appropriate treatment.     

Subarachnoid hemorrhage associated with von Willebrand's disease--case report

A 59-year-old woman with type IIA von Willebrand's disease (VWD) presented with subarachnoid hemorrhage (SAH). Computed tomography showed SAH in the right sylvian fissure and intracranial hemorrhage in the right temporal lobe. Angiography demonstrated an aneurysm at the bifurcation of the right middle cerebral artery. Neck clipping was performed on the 3rd day after the onset with intra- and postoperative administration of factor VIII/von Willebrand factor concentrate. No excessive bleeding occurred. Patients with prolonged bleeding time should be screened for VWD before surgery. This is a rare case of VWD presenting with SAH secondary to ruptured intracranial aneurysm. The clinical characteristics and the management of SAH in a patient with VWD are discussed.     

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.     

Successes and failures of the activated partial thromboplastin time in the preoperative evaluation

In a prospective study assessing haemostatic functions, the activated partial thromboplastin time was prolonged in 134 out of 10,229 patients studied, without an increase in the prothrombin or thrombin times; this abnormality persisted in only 37 of them on a new blood sample. A retrospective analysis was made of 265 patients who had such an isolated prolongation of the activated partial thromboplastin time on two successive blood samples: the causal abnormality remained unexplained in 135 patients; a well defined coagulation disorder without abnormal bleeding tendency was present in 110 patients (1 severe factor XII deficiency, 58 partial factor XI or XII deficiencies and 51 lupus anticoagulants); a bleeding disorder was diagnosed in 20 patients (8 haemophilias, 8 Von Willebrand's diseases, 4 factor VIII inhibitors). The well-iron efficacy of the activated partial thromboplastin time for detecting coagulation abnormalities is counter-balanced by some disadvantages such as the delay for biologic conclusions. In the preoperative assessment of haemostatic functions, rather than taking a routine approach, it would seem better to determine for each patient the need and the extent of biological testing according to the type of planned surgery, the clinical status of the patient and possible bleeding symptoms.     

Erworbene Hemmkörperhämophilie

Although autoantibodies against factor VIII or factor IX are a rare phenomenon, they are associated with a high risk of bleeding and high mortality. The condition, termed acquired haemophilia, occurs equally in both sexes and is most frequent in higher age groups. Patients typically present with severe bleedings in muscles and skin. In contrast to patients with congenital haemophilia and inhibitors, joint bleedings are very rare. In approximately half of all cases an associated disease state can be identified as the cause of autoantibody formation. An immediate and comprehensive diagnosis is essential for a rapid initiation of therapy. Equally important are a careful diagnostic differentiation between congenital and acquired factor deficiencies and the exclusion of non-specific inhibitors, which increase the occurrence of thrombolic events. The inhibitor titre, quantified using the Bethesda assay, is an important criterion for selecting the appropriate therapy. A wide range of treatment options is now available for the management of bleedings in patients with acquired haemophilia, namely porcine factor VIII, recombinant factor VIIa, prothrombin complex concentrates, and immunoadsorptions. In addition, immunosuppressive therapies are used to achieve permanent reduction or elimination of inhibitors.     

External counterpressure to control postoperative intra-abdominal hemorrhage

The effectiveness of the G-suit in controlling massive postoperative intra-abdominal hemorrhage was studied in twenty-eight patients whose diffuse bleeding could not be controlled during operation. Most patients had developed deficiencies of platelets and clotting factors due to dilution, and in addition three had documented disseminated intravascular coagulation. After application of the G-suit, hemorrhage stopped in nineteen patients, allowing the replacement of platelets and clotting factors in patients with deficiencies and the administration of heparin to three patients with disseminated intravascular coagulation. After an average of twenty-one hours the G-suit was removed without rebleeding in seventeen patients. The major cause of G-suit failure was an arterial source of intra-abdominal bleeding. Application of the G-suit had no adverse effect on renal function in at least half the patients; urinary output declined in one third. Most patients experienced respiratory impairment and some had ischemic skin lesions. The G-suit is frequently effective in halting postoperative intra-abdominal hemorrhage, allowing correction of acquired coagulopathies with acceptably few complications. Its use does not replace the need for proper surgical hemostasis.     

Massive intra-abdominal bleeding due to injury in the mesenteric artery during late breast reconstruction with a free TRAM flap: a case report

We report on a rare case of major intra-abdominal bleeding that occurred in a patient undergoing late breast reconstruction with a transversus rectus abdominis musculocutaneous (TRAM) flap. During the flap-raising procedure, a small rupture was found at the base of the superior mesenteric artery, probably caused by electric current. The ruptured vessel required immediate laparotomy and suturing, and the final outcome of the patient was good. The massive bleeding, almost 8-fold as compared with three normal cases, caused clear activation of coagulation seen with elevated TAT values at the end of the operation, and remarkably enhanced fibrin turnover with elevated D-dimer, up to 25-fold from baseline, on the first postoperative day. As a result of major bleeding, the fibrinolytic system was also activated: a biphasic elevation of tPA was seen, first immediately after the bleeding event at 2 h, and later on the first postoperative day, followed by fibrinolytic shutdown associated with increased PAI-1 values.     

A rare case of non-traumatic acute intraabdominal hemorrhage: ruptured superior mesenteric artery aneurysm

Introduction: Rupture of superior mesenteric artery aneurysm (SMAA) is a very rare and life-threatening condition, presenting with acute intraabdominal hemorrhage.

Case: The patient was hospitalized upon complaint of nonspecific severe abdominal pain. Diagnosis of SMAA was established by abdominal Doppler ultrasound that showed a pseudo-aneurysmal lesion with size of 76?×?47?mm at the superior mesenteric main branch. Endovascular stenting was not performed because of the wide neck in the segment of the jejunal branches from SMA and the risk of branch loss during treatment. On the second day of hospitalization, the patient developed an acute abdomen. At explorative laparotomy for intraabdominal bleeding, the root of superior mesenteric artery was immediately and temporarily clamped to provide bleeding control. Aneurysmal tissue was resected and affected part was repaired by Dacron prosthetic graft to maintain proximal and distal vascular continuum. Intestinal viability was preserved. The patient survived disease-free as verified by his 18-month postoperative physical examination.

Conclusions: The patient presents a very rare case showing ability to perform emergent intestine-sparing vascular surgery in ruptured SMAA. Surgery or endovascular treatment options should not be delayed especially in pseudo-aneurysms. It is critical to include ruptured SMAA in differential diagnosis of intraabdominal bleeding.