Alloantibody developed in a factor XIII A subunit deficient patient during substitution therapy; characterization of the antibody

Pénzes, Krisztina; Vézina, Catherine; Bereczky, Z.; Katona, Éva; Meng, Kun; Muszbek, László; Rivard, Georges E.

doi:10.1111/hae.12786

Cited by 18 publications

(26 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, data on rFXIII cover mostly prophylaxis and the management of bleeds and surgery should be subject of future clinical studies. Also, the very rare but often severe 15,34 acquired forms of FXIII deficiency are unique, and the management strategies of comprehensive care centers are important to be shared in case reports. Platelets contain FXIII and provide cellular support; thus, FXIII deficient patients may benefit from platelet transfusion during problematic bleeds.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Clinical Use of Factor XIII Concentrates

Lassila

2016

Semin Thromb Hemost

View full text Add to dashboard Cite

Factor (F) XIII deficiency is a congenital rare bleeding disorder (RBD), with an estimated prevalence of 1 in 1 to 2 million individuals, and more than 1,200 patients have been diagnosed to date. In newborns, umbilical cord bleeding is typical, and later in life during trauma, surgery and even spontaneously prolonged bleeds, reproduction, and delivery complications occur frequently without appropriate replacement therapy. Also, an acquired form of FXIII deficiency may occur via massive bleeds or neutralizing antibodies. In the inherited form of FXIII deficiency, prophylaxis with FXIII concentrate is administered to prevent the very high risk of intracranial bleeds, the incidence being close to 30%. Laboratory diagnosis of FXIII deficiency is based on measuring plasma FXIII antigen and activity, and it is claimed that FXIII activity of around 5 IU/dL would suffice to protect from bleeds. However, at the low levels of detection, most FXIII methods are inaccurate, and quality controls and collaboration with reference laboratories are important to improve the accuracy of low-level FXIII measurements. The trough target for prophylaxis should be set to 10 to 20 IU/dL, which is achievable by administration of 25 to 35 IU/kg every 4 to 6 weeks. However, general risk factors influencing hemostasis should be carefully evaluated, including anemia and hypertension. Fibrin cross-linking by FXIII is of major importance and red cells bind to fibrin partially via platelets and FXIII to promote clot strength. Physiologically, platelets and macrophages contain FXIII providing cellular support; thus, the patients may benefit from platelet transfusion during problematic bleeds. Plasma-derived and recently a recombinant FXIII concentrate are available; however, the latter has mainly anecdotal data regarding management of bleeds and surgery, and its access is limited due to the high cost. The international registry RBD database, (RBDD) continues to gain cumulative knowledge, and registration of all FXIII deficient patients, both inherited and acquired, is highly recommended.

show abstract

Section: Resultsmentioning

confidence: 99%

“…33 Recently, a fatal case associated with unmanageable alloantibody in a factor XIII deficient patient was reported. 34 Fibrin is structurally altered and susceptible to early fibrinolysis when plasma is deficient in FXIII. α 2 -Antiplasmin is also bound to fibrin via FXIII aiming at local plasmin inhibition.…”

Section: Emergencies Surgery Pregnancy and Deliverymentioning

confidence: 99%

Clinical Use of Factor XIII Concentrates

Lassila

2016

Semin Thromb Hemost

View full text Add to dashboard Cite

show abstract

“…In hemophilia A, the incidence is approximately 30%, whereas in FXIII deficiency it is extremely rare. In a PubMed search we were able to recover only five publications on anti-FXIII-A alloantibodies involving four cases, [67][68][69][70][71] and only a single case of an anti-FXIII-B alloantibody has been reported. 72 All patients with an anti-FXIII-A alloantibody demonstrated a severe hemorrhagic diathesis, which was extremely difficult to manage.…”

Section: Allo-and Autoantibodies Against Fxiii Subunits Alloantibodiementioning

confidence: 99%

“…In one of the cases fatal outcome was reported. 71 In the patient with an anti-FXIII-B alloantibody, FXIII activity was in the range of 7 to 10% and the bleeding diathesis was of moderate severity. 72…”

Section: Allo-and Autoantibodies Against Fxiii Subunits Alloantibodiementioning

confidence: 99%

“…For such binding assay one needs purified FXIII-A, FXIII-B, and FXIII-A 2 B 2 , bound to a solid surface, such as nitrocellulose membrane, 72 microtiter plate, 80 or sensor chip used for surface plasmon resonance (SPR) assay. 71 In the latter technique, if the patient's IgG is immobilized to the surface of the sensor chip and FXIII or its subunits are used as analyte, the equilibrium dissociation constant can be determined; that is, direct information on the affinity of the antibody is obtained.…”

Section: Detection and Classification Of Anti-fxiii Antibodiesmentioning

confidence: 99%

See 1 more Smart Citation

Diagnosis and Management of Congenital and Acquired FXIII Deficiencies

Muszbek

Katona

2016

Semin Thromb Hemost

View full text Add to dashboard Cite

Inherited deficiency of FXIII A subunit (FXIII-A) is a rare (1:2,000,000) but very severe bleeding diathesis. The incidence is much higher in communities where the practice of consanguineous marriage is combined with founder effect mutation. Because of the high risk of intracranial bleeding, life-long prophylaxis, preferably using FXIII concentrate, is mandatory. In FXIII-B subunit deficiency the bleeding diathesis is mild to moderate. FXIII deficiency is frequently associated with impaired wound healing. Women suffering from FXIII deficiency cannot carry pregnancies to term; in severe cases spontaneous abortion occurs in the first trimester. Plasma-derived heat-inactivated FXIII concentrate and recombinant FXIII-A are available for prophylaxis; a 4 weekly dose of 35 to 40 U/kg is recommended and a trough level of greater than 5% FXIII activity should be aimed for. During pregnancy, 2 weekly prophylaxis with a target trough level of greater than 10% is recommended, and during labor FXIII activity should exceed 30%. During surgical procedures, the target should be higher than 50% FXIII activity. Alloantibodies make FXIII deficiency difficult to manage, but fortunately they are extremely rare. Acquired FXIII deficiency may involve both subunits. Autoantibodies against FXIII subunits also manifest in severe bleeding complication with a relatively high mortality rate. The first-line test in the diagnosis of FXIII deficiency should be a quantitative functional assay based on the measurement of ammonia release or amine incorporation. The sensitivity of the traditional clot solubility assay is not sufficiently robust to enable proper screening. Antigen assays are needed for the classification of FXIII deficiencies. In the case of anti-FXIII antibodies, the diagnostic armory should be supplemented by a mixing test/Bethesda-type inhibitor assay and by assays that detect/measure the binding of antibodies to FXIII and to its subunits.

show abstract

Assessment of Factor XIII

Muszbek

Katona

Kerényi

2017

Methods in Molecular Biology

View full text Add to dashboard Cite

Blood coagulation factor XIII (FXIII) is essential for maintaining hemostasis. The absence of FXIII results in severe bleeding diathesis, which without prophylaxis frequently leads to fatal bleeding. As the usual hemostasis screening tests remain normal, the diagnosis of FXIII deficiency needs specific tests. Here, we describe FXIII activity determination by the ammonia release assay, which is the first-line test in the diagnostic algorithm for FXIII deficiency. The method for another activity test, the undeservedly rarely used fibrin cross-linking assay, is also presented. Further tests used for the classification of FXIII deficiencies, measurement of FXIII activity in platelets, ELISAs for the measurement of complex plasma FXIII (FXIII-AB) antigen and for FXIII-A in plasma and platelets are also included. Detailed description of the methods for the detection and measurement of neutralizing auto- and alloantibodies is also provided.

show abstract

Alloantibody developed in a factor XIII A subunit deficient patient during substitution therapy; characterization of the antibody

Abstract: The anti-FXIII-A alloantibody caused an unmanageable bleeding complication. The antibody was of combined subtype which accelerated the elimination of FXIII and exerted a multiple inhibitory effect on FXIII activation/activity.

Cited by 18 publications

References 40 publications

Clinical Use of Factor XIII Concentrates

Clinical Use of Factor XIII Concentrates

Diagnosis and Management of Congenital and Acquired FXIII Deficiencies

Assessment of Factor XIII

Contact Info

Product

Resources

About