Congenital factor VII deficiency: therapy with recombinant activated factor VII – a critical appraisal

Mariani, Guglielmo; Konkle, Barbara A.; Ingerslev, J.

doi:10.1111/j.1365-2516.2006.01180.x

Cited by 96 publications

(98 citation statements)

References 40 publications

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“…22 Because rhFVIIa has a short half-life, approximately 3 hours in humans, repeated administration, every 4-6 hours, may be necessary to control severe bleeding. 21 Administration of rhFVIIa to FVII-deficient research Beagles at dosages of 5 mg/kg and 30 mg/kg (single IV dose) resulted in transient near normalization of the PT and cuticle bleeding time. n Studies are needed to determine whether rhFVIIa can be used safely and cost effectively (approximately $1,300 per 1.2-mg vial) to supplement or replace plasma components for controlling clinical bleeding in FVII-deficient dogs.…”

Section: Discussionmentioning

confidence: 99%

Hereditary Factor VII Deficiency in the Alaskan Klee Kai Dog

Kaae

Callan

Brooks

2007

Veterinary Internal Medicne

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Background: Hereditary factor VII (FVII) deficiency is characterized as a mild bleeding disorder in Beagles, caused by a missense mutation in exon 5 of the FVII gene. An Alaskan Klee Kai dog with severe bleeding after trauma was diagnosed with FVII deficiency based on coagulation testing. Molecular analyses were undertaken to identify the genetic basis of the defect in this breed. Hypothesis: FVII deficiency in Alaskan Klee Kai dogs is caused by a mutation in the FVII gene. Animals: Eighteen client‐owned Alaskan Klee Kai. Methods: Coagulation screening tests and factor assays were performed to characterize the coagulopathy. All coding regions of the propositus' FVII gene were sequenced. Amplification of exon 5, sequencing, and Mnl I restriction digest experiments were performed to screen for a point mutation in the remaining 17 dogs. Results: FVII deficiency was diagnosed in 6 dogs with a median FVII activity (FVII:C) of 5% (reference range, 50–150%). All FVII‐deficient Alaskan Klee Kai were homozygous for the same mutation as FVII‐deficient Beagles (ie, a G to A transition), resulting in substitution of glycine 96 by glutamic acid. An overlap in the FVII: C values obtained from heterozygote and wild‐type dogs precluded accurate detection of carriers without genetic screening. Conclusions and Clinical Importance: FVII deficiency may be associated with a bleeding tendency and should be considered in Alaskan Klee Kai dogs with prolonged prothrombin times. Plasma FVII:C accurately identifies affected dogs, but deoxyribonucleic acid testing is required for identification of carriers.

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Section: Discussionmentioning

confidence: 99%

Hereditary Factor VII Deficiency in the Alaskan Klee Kai Dog

Kaae

Callan

Brooks

2007

Veterinary Internal Medicne

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“…Each case requires individual management because of the poor correlation between F7 mutations, FVII activity, and phenotype (7 ). The patient's bleeding history, current clinical situation, and an FVII activity assay performed with recombinant human thromboplastin must guide initial management of FVII deficiency (8,9 ) (Fig.…”

Section: Summary and Recommendationsmentioning

confidence: 99%

Evaluation of a Prolonged Prothrombin Time

Hood

Eby²

2008

Clinical Chemistry

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A 47-year-old African American woman was evaluated for a prolonged prothrombin time (PT) result obtained before she underwent right total hip arthroplasty. The patient had no history of gastrointestinal or intracranial bleeding, epistaxis, or hemarthrosis. However, she reported a tendency toward easy limb bruising and menorrhagia, which required iron supplementation. She had a negative family history of abnormal bleeding. Initial laboratory studies included findings within reference intervals for complete blood cell count and activated partial thromboplastin time (aPTT) (30.8 s, reference interval 23-36 s), prolonged PT (20.3 s, reference interval 11.0 -15.0 s), and International Normalized Ratio (INR) (1.78, reference interval 0.9 -1.2). No preanalytical artifacts were identified, and the result of a repeat PT was also prolonged. DISCUSSION LABORATORY EVALUATION OF PROLONGED RESULTS FOR SCREENING COAGULATION TESTSPT and aPTT are commonly requested screening tests. In vivo, the initiation of coagulation depends on tissue factor-mediated factor VII (FVII) activation, and sustained thrombin generation requires activation of factors XI, IX, VIII, X, and V. For the interpretation of PT and aPTT results, however, coagulation factor activation culminating in a fibrin clot can be organized into intrinsic, extrinsic, and common pathways (Fig. 1). An isolated result showing aPTT prolongation suggests a deficiency or inhibitor of one or more of the intrinsic pathway clotting factors (prekallikrein, high molecular weight kininogen, factors XII, XI, IX, and VIII). An isolated PT prolongation suggests a deficiency or inhibition of the extrinsic pathway (FVII), but mild factor X, V, and II deficiencies are also possible causes. Prolongation of both aPTT and PT suggests a deficiency or inhibition of the common pathway coagulation factors (factor X, V, and II), or a qualitative or quantitative fibrinogen defect.When evaluating an unexpected prolonged aPTT and/or PT result, the first step is to rule out preanalytical causes of inaccuracy (1 ). Anticoagulant contamination due to blood collection from a venous or arterial line flushed with heparin is a common artifact, and although most commercial PT reagents contain a substance capable of neutralizing approximately 2 U/mL of heparin, this capacity can be overwhelmed if blood is collected from heparin-containing catheters. Other preanalytical variables include the use of collection tubes containing a higher sodium citrate anticoagulant concentration (3.8% instead of 3.2%), hemolyzed samples interfering with photo-optical clot detection methods, and a prolonged time lapse between specimen collection and performance of aPTT (Ͼ4 hours) and PT (Ͼ24 hours) assays. An increase of the citrate: plasma ratio, which decreases the ionized calcium concentration [e.g., in samples from patients with high hematocrit (Ͼ55%) or samples collected in underfilled collection tubes] may produce erroneously prolonged PT and aPTT results.The second step in evaluating an unexpected prolonged aPTT and/or P...

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“…Literature on preoperative treatment protocol is scarce as FVIId comes under rare bleeding disorders. Moreover, the available data are not consistent [5,8,13]. Mariani et al [14] in her study reported of using rFVIIa successfully in seven patients of severe FVIId who underwent major surgeries.…”

Section: Discussionmentioning

confidence: 93%

“…Mean dose/procedure ranged from 13.85 to 26.29 μg/kg and the number of doses/procedure varied from 30 to 112. Other results from different groups showed that 20 -25 μg/dL of rFVII should be given at every 4 -6 h in combination with tranexamic acid which was seen to be effective in surgical settings for FVIId patients but treatment duration is not well defined [5,8,9,15]. Pharmacokinetic studies of rFVII helped in choosing the dose and time interval between the subsequent infusions, but it is still not defined about minimum requirement for FVII in plasma to attain hemostasis [15,16].…”

Section: Discussionmentioning

confidence: 99%

“…The treatment of choice for FVIId patients is rFVII as the deficient protein in plasma is substituted at a very low volume of preparations and it does not consist of any other animal or human protein in it [8]. Even though rFVII is widely used in FVIId patients, there is scarce of literature for treatment patterns in FVIId patients with surgical intervention [5,9].…”

Section: Introductionmentioning

confidence: 99%

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Management of Arthropathy in Moderately Deficient Factor VII Patients: Results From Hospital Developed Treatment Protocol

Babu¹,

Belle²,

Pathiraj³

2016

J Hematol

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Background: Factor VII deficiency (FVIId) is a rare inherited bleeding disorder whose prevalence is estimated to be 1 in 300,000 -500,000 in general population. In India, the epidemiological data on factor VII (FVII) disorder are scarce. Serious arthropathy is observed in cases which are severely affected with spontaneous bleeding and hemarthrosis. In such cases, orthopedic surgery is required. Fresh frozen plasma, prothrombin complex concentrates, factor VII concentrates -plasma derived and recombinant factor VII (rFVII) are different types of preparations which are available as therapeutic options in treatment for bleeding occurring during or after surgery in FVIId patients. The main objective of our study was to give a result of the treatment protocol for FVIId patients undergoing orthopedic surgery in our hospital and compare its results with other studies conducted around the world.

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Congenital factor VII deficiency: therapy with recombinant activated factor VII – a critical appraisal

Cited by 96 publications

References 40 publications

Hereditary Factor VII Deficiency in the Alaskan Klee Kai Dog

Hereditary Factor VII Deficiency in the Alaskan Klee Kai Dog

Evaluation of a Prolonged Prothrombin Time

Management of Arthropathy in Moderately Deficient Factor VII Patients: Results From Hospital Developed Treatment Protocol

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