Severe Congenital Factor VII Deficiency with Normal Perioperative Coagulation Profile Based on ROTEM Analysis in a Hepatectomy.

BACKGROUND Factor VII (FVII) deficiency is the most common autosomal-recessive bleeding disorder. FVII activity level (FVII: C) of 10-20% is often used as the threshold for administering activated recombinant FVII (rFVIIa) for patients undergoing major surgery. However, rFVIIa is expensive and carries the risk of a thromboembolic event, and thus should only be administered when truly indicated. CASE REPORT A 22-year-old woman with 8% FVII: C underwent a hepatectomy. Although there were no clinical signs of bleeding, peri-operative administration of rFVIIa was recommended by the hematologist (first dose at surgical incision, then 4 h later, then every 12 h until 48 h postoperatively). Intraoperatively, serials of ROTEM analysis were performed to evaluate the effect of rFVIIa administration. No significant effect of rFVIIa was seen on NATEM. Surgery was unremarkable, without any significant blood loss. The patient developed radial artery thrombosis 24 h postoperatively, the arterial line was removed, and rFVIIa was discontinued (PT: 14.6, FVII: C 36%). On POD 3, INR was elevated (3.15, FVII: C 3%). To correct INR, the patient was transfused 8 units of FFP, despite any signs of clinical bleeding. However, INR and FVII: C did not correct and the patient was discharged on POD 7 in a stable condition. CONCLUSIONS Even with FVII: C of 8%, the ROTEM analysis revealed a normal coagulation status. The administration of rFVIIa did not improve the already normal baseline coagulation profile, but rather potentially led to an accelerated coagulation or hypercoagulable state and may have led to the radial artery thrombosis. We endorse the use of viscoelastic testing for hemostasis assessment and factor replacement in congenital FVII deficiency.

Successful Splenectomy Management in a Patient With Moderate Factor VII Deficiency and Concomitant Severe Hereditary Spherocytosis.

By the advent of the effective therapies for many coagulation diseases and hereditary spherocytosis (HS), patient's survival has been improved significantly; however, if patients are diagnosed late or left untreated, both diseases could ominously be life threatening. Concurrent occurring of factor VII (FVII) deficiency and HS is extremely rare and there is no literature report that explain this condition, thus far. In this study, we confronted a 9-year-old female patient diagnosed with HS and enlarged spleen as a result of this blood disorder. Given to her sever signs and symptoms of splenomegaly, she was candidate for emergent splenectomy. However, assessment of coagulation tests revealed a prolonged prothrombin time, suggesting the moderate FVII deficiency. With a multidisciplinary consultation, we decided to performed total splenectomy with prophylaxis administration of totally 6 doses of active recombinant FVII, initiated 1 hour before surgery and followed until 30 hours postoperation. As a result of cautious undertaken in Mofid Children's Hospital, the patient did not experience any hemostatic defect. Patient is now 14-year-old, generally well-being under regular surveillance of FVII deficiency.

Point-of-Care Thromboelastography for Intrathecal Drain Management in Patients With Coagulopathy and Thoracic Aorta Surgery: A Case Report.

Spinal drain placement to prevent spinal cord ischemia during thoracic aorta surgery is a necessary yet complex undertaking in patients with coagulopathies. Thromboelastography (TEG) can be used as a point-of-care management tool to monitor coagulation status before drain placement and removal. We present 2 cases: a case of a patient with factor VII deficiency and a case of a patient with thrombocytopenia for whom TEG was an important procedural adjunct during coagulopathy reversal. TEG parameters are also discussed to encourage more frequent TEG use as an adjunct during these complex cases.

Surgical procedures in patients with severe haemophilia 1997­2014. / Kirurgiske inngrep hos pasienter med alvorlig blødersykdom 1997­2014.

BACKGROUND: As a result of good medical treatment, the life expectancy of patients with severe haemophilia is now approaching normal. This implies a growing need for treatment of lifestyle- and age-related disease. This article describes surgery in patients with severe haemophilia in the period 1997-2014. MATERIAL AND METHOD: Data were retrieved from the registry linked to the national treatment service for surgery, intervention and advanced diagnostics for haemophilia. The patients were categorised according to type of haemophilia and type of intervention in orthopaedic and non-orthopaedic surgical procedures. RESULTS: A total of 825 surgical procedures were undertaken in 286 patients. The number of procedures increased from 21 in 1997 to 66 in 2014. This increase was associated with non-orthopaedic interventions: altogether 4 such procedures were undertaken in 1997 and 45 in 2014. The number of orthopaedic interventions varied somewhat from year to year, but no clear trend was evident. INTERPRETATION: With increased life expectancy, we are seeing a growing need for treatment of diseases that are not causally related to haemophilia. Doctors with little experience of patients with severe haemophilia will need to deal with lifestyle- and age-related disease in this patient group.

Surgery in patients with congenital factor VII deficiency - a single center study.

INTRODUCTION: Congenital factor VII deficiency is a rare hemorrhagic disorder inherited in an autosomal recessive pattern. Surgical treatment with insufficient diathesis correction is burdened with high risk of bleeding complications. The aim of the study was evaluation of the surgical outcome in patients with congenital factor VII deficiency and assessment of the efficacy and safety of recombinant activated factor VII (rFVIIa) used for perioperative hemostatic coverage in our two schemas of substitutive therapy. MATERIAL AND METHODS: In the years 2002-2017 a total of 22 patients with congenital factor VII deficiency were subjected to surgery. Substitution therapy relied on rFVIIa used in two schemas. One involved 15 patients with factor VII activity of<10% of normal value who were injected rFVIIa at a dose of 30 µg/kg b.w. every12 hours on surgery day, 15 µg/kg b.w. every 12 hours on the first postoperative day and 15 µg/kg b.w. every 24 hours on the following days. The second schema involved 7 patients with factor VII activity of 10-25% of normal value who were given rFVIIa at a dose of 15 µg/kg b.w. every 12 hours on surgery day and the first postoperative day; then the same dose was administered every 24 hours on consecutive days. The treatment continued for 4-10 days. RESULTS: In the 22 patients a total of 26 surgeries were performed; 17 surgeries in 15 patients with factor VII<10% of normal and 9 in 7 patients with factor VII deficiency of 10-25% of normal. The surgeries included: 9 cholecystectomies (8 laparoscopic,1 open), 7 thyroidectomy procedures, 2 exploratory laparotomies, 1 left hemicolectomy, 1 total proctocolectomy, 3 inguinal hernia repairs and 3 excisions of varicose veins. One patient with factor VII activity of 9% required an additional dose of rFVIIa in the intraoperative period due to diathesis bleeding. Intraoperative hemostasis was normal for all other patients; no postoperative hemorrhagic complications were reported. In patients with FVII activity<10% average daily dose of rFVIIa was 31.3(range 20-56) µg/kg b.w., total daily dose 186(136-303) µg/kg b.w., total dose of rFVIIa-15.2(12-112) mg. In patients with FVII activity 10-25% the doses were 21.2(15-31), 117(46-271) µg/kg b.w. and 9.1(6-17) mg respectively. CONCLUSIONS: Surgery in patients with congenital factor VII deficiency can be safely and efficiently performed with rFVIIa as substitutive treatment securing perioperative hemostasis.

Constrictive pericarditis in a patient with inherited factor VII deficiency.

Constrictive pericarditis (CP) is the final stage of a chronic inflammatory process characterized by fibrous thickening and calcification of the pericardium that impairs diastolic filling, reduces cardiac output, and ultimately leads to heart failure. We present a clinical case of CP in a patient with rare inherited bleeding disorder - factor VII deficiency. Heart failure due to CP was suspected based on clinical symptoms, results of ultrasonic and radiological investigations. The diagnosis was verified by the results of cardiac magnetic resonance imaging. Pericardectomy was performed resulting in significant improvement in the patient's condition.

Role of clinical and laboratory parameters for treatment choice in patients with inherited FVII deficiency undergoing surgical procedures: evidence from the STER registry.

Perioperative bleeding is a major concern in patients with factor VII (FVII) deficiency. Evaluating data of 95 FVII-deficient patients undergoing 110 surgical procedures (61 major, 49 minor), we assessed the impact of type of surgery, bleeding phenotype and FVII coagulant activity (FVII:C) levels on perioperative replacement therapy (RT). Compared to those with higher FVII:C levels, patients with <3% FVII:C received a higher number of RT doses (8 vs. 2, P = 0·003) for a longer RT duration (3 days vs. 1 day, P = 0·001), with no difference in RT dose. Similarly, patients with a history of major bleeds received a higher number of RT doses (8·5 vs. 2-3, P = 0·013) for a longer RT duration (2 days vs. 1 day, P = 0·005) as compared to those with a history of minor bleeds or to asymptomatic patients. No difference in RT was found among major and minor surgical procedures. Overall, multivariate analysis showed that history of major bleeding was the only independent predictor of number of RT doses (ß = 0·352, P = 0·001) and RT duration (ß = 0·405, P = 0·018). Overall, a ≈20 µg/kg perioperative RT was efficacious in 95·5% of cases. The infusion should be repeated ≈8 times in high-risk subsets (i.e. patients with a history of major bleeding).

A rare combination: congenital factor VII deficiency with Chiari malformation.

Congenital factor (VII) deficiency is a rare bleeding disorder. We present a patient with congenital FVII deficiency and congenital hydrocephalus who underwent a ventriculoperitoneal shunt operation and needed no prophylaxis after the procedure.

First living-related liver transplant to cure factor VII deficiency.

Congenital factor VII deficiency is an autosomal recessive serious disorder of blood coagulation with wide genotypic and phenotypic variations. The clinical presentation can vary from asymptomatic patients to patients with major bleedings in severe deficiency (factor VII <1%). Investigations show prolonged PT and low factor VII. Treatment modalities include FFP and repeated recombinant factor VII infusions. We hereby report the first successful LRLT for factor VII deficiency in an infant, the first-ever youngest baby reported worldwide. A six-month-old male child presented with easy bruisability, ecchymotic patches, hematuria, and convulsions. CT of the head showed subdural hemorrhage, which was treated conservatively. He had markedly increased PT (120 s) with normal platelets, and aPTT with factor VII level <1%. Despite the treatment by rFVIIa administration weekly, which was very expensive, he still had repeated life-threatening bleeding episodes. LRLT was performed with mother as the donor, whose factor VII level was 57%. A factor VII infusion plan for pre-, intra- and postoperative periods was formulated and TEG followed. Postoperatively, his factor VII started increasing from third day and was 38% on 24th day with PT <14 s. He had uneventful intraoperative and postoperative courses. LT is a safe and definite cure for factor VII deficiency.

Liver transplant for congenital factor VII deficiency.

Congenital factor VII (FVII) deficiency is a rare, autosomal recessive bleeding disorder with a spectrum of phenotypes ranging from asymptomatic to life-threatening intra-cranial hemorrhage (ICH). Orthotopic liver transplantation has been described for definitive treatment in a few patients with severe manifestations. We report a patient with congenital FVII deficiency and recurrent ICH, despite twice-weekly prophylaxis with recombinant activated FVII. At 17 months of age, he underwent an orthotopic liver transplant. He is now 1-year post-transplant, on maintenance immunosuppression with no hemorrhage or other complications.

Management of factor VII-deficient patients undergoing joint surgeries--preliminary results of locally developed treatment regimen.

Inherited factor VII (FVII) deficiency is a rare coagulation disorder with variable haemorrhagic manifestations. In severely affected cases spontaneous haemarthroses leading to advanced arthropathy have been observed. Such cases may require surgery. Therapeutic options for bleeding prevention in FVII deficient patients undergoing surgery comprise various FVII preparations but the use of recombinant activated factor VII (rFVIIa) seems to be the treatment of choice. To present the outcome of orthopaedic surgery under haemostatic coverage of rFVIIa administered according to the locally established treatment regimen in five adult patients with FVII baseline plasma levels below 10 IU dL(-1). Two patients required total hip replacement (THR); three had various arthroscopic procedures. Recombinant activated factor VII was administered every 8 h on day of surgery (D0) followed by every 12-24 h for the subsequent 9-14 days, depending on the type of surgery. Factor VII plasma coagulation activity (FVII:C) was determined daily with no predefined therapeutic target levels. Doses of rFVIIa on D0 ranged from 18 to 37 µg kg(-1) b.w. and on the subsequent days--from 13 to 30 µg kg(-1) b.w. Total rFVIIa dose per procedure ranged from 16 to 37.5 mg, and the total number of doses per procedure was 16-31. None of our patients developed excessive bleeding including those in whom FVII:C trough levels returned nearly to the baseline level on the first post-op day. Preliminary results demonstrate that rFVIIa administered according to our treatment regimen is an effective and safe haemostatic agent for hypoproconvertinaemia patients undergoing orthopaedic surgery.

Managing incidentally diagnosed isolated factor VII deficiency perioperatively: a brief expert consensus report.

While isolated factor VII (FVII) deficiency is being more frequently diagnosed owing to improved preoperative screening procedures, there is no specific guideline for perioperative management of such patients. To complicate the issue, FVII activity levels seem to correlate less well with the risk of hemorrhage than the patient's past and family bleeding history do. We have devised expert consensus recommendations for managing such patients perioperatively, taking into consideration the personal and family bleeding history, the FVII activity level and the inherent bleeding risk of the procedure itself. We hope that clinicians will find this a useful tool in the decision-making process, thereby limiting the use of recombinant factor VIIa to those who need it most, and preventing possible thrombotic complications in those without a strong indication for its use.

The use of recombinant activated factor VII in neurosurgery.

BACKGROUND: Bleeding complications in neurosurgery often take alarming proportions without major hemodynamic effect or impairment of coagulation physiology because severe neurologic deficits are to be expected. Any measures used to stabilize or normalize coagulation are therefore of great interest. Administration of packed red cells, fresh frozen plasma, and platelet concentrates is associated with volume loading, which is suspected to multiply the secondary brain damage, for example, by the development of an edema. In this respect, the administration of rFVIIa may develop into a new option associated with low-volume administration. CASE DESCRIPTIONS: We report on 5 neurosurgical patients to whom rFVIIa was given at doses of 51 to 202 microg/kg of body weight for the treatment of severe intraoperative bleeding (n = 3) or as prophylaxis of bleeding (n = 2). The operation was completed successfully in all patients after administration of rFVIIa, with stabilization of the coagulation status. CONCLUSION: Therefore, reported cases constitute an approach in treatment and prophylaxis of bleeding complications in neurosurgery. There are reports of thromboembolic events in use of rFVIIa, particularly in unlabeled use. But according to our findings and current literature, there is no evidence of higher risk of thromboembolic adverse events in treatment with rFVIIa. However, the number of patients presented does not allow any final assessment to be made as to whether the properties of rFVIIa are of particular benefit for neurosurgical patients. Further studies with appropriate study design are required to verify effects observed in this investigation.