Factor X deficiency and pregnancy.

Factor X (FX) is a vitamin K-dependent enzyme, which acts as an important coagulation factor of coagulation cascade. FX deficiency is an autosomal recessive inherited disease and is often demonstrated in families with consanguity. Pregnancy in women with congenital FX deficiency has been associated with adverse fetal outcomes. We report a case of pregnancy in women with FX deficiency. The patient needed an immediate caesarean section at 38 weeks of gestation because of severe oligohydramnios and fetal distress. FX deficiency during pregnancy was effectively managed, leading to a positive outcome through the optimal utilisation of available resources.

Acute deep vein thrombosis with concurrent new diagnosis of AL-amyloid-induced factor X deficiency.

Acquired factor X (FX) deficiency is a rare but well-documented clinical feature of AL amyloidosis. Patients with FX deficiency can present with clinically significant bleeding diathesis due to the adsorption of circulating FX to amyloid fibrils. Here, we report an unusual case of a man in his 60s who presented with 6 months of intermittent bruising, labs demonstrating new FX deficiency, elevated free lambda light chains for underlying AL amyloidosis and concurrent new peroneal vein thrombosis. This is the first report of concurrent thrombotic complications in the setting of AL-amyloid-induced FX deficiency. We discuss the diagnostic and therapeutic conundrum of diagnosing AL amyloidosis with bruising as the leading clinical symptom and the management of acute deep vein thrombosis in the setting of FX deficiency.

Fitusiran reduces bleeding in factor X-deficient mice.

ABSTRACT: Factor X (FX) deficiency is a rare bleeding disorder manifesting a bleeding tendency caused by low FX activity levels. We aim to explore the use of fitusiran (an investigational small interfering RNA that silences antithrombin expression) to increase thrombin generation and the in vivo hemostatic potential under conditions of FX deficiency. We therefore developed a novel model of inducible FX deficiency, generating mice expressing <1% FX activity and antigen (f10low mice). Compared with control f10WT mice, f10low mice had sixfold and fourfold prolonged clotting times in prothrombin time and activated partial prothrombin time assays, respectively (P < .001). Thrombin generation was severely reduced, irrespective of whether tissue factor or factor XIa was used as an initiator. In vivo analysis revealed near-absent thrombus formation in a laser-induced vessel injury model. Furthermore, in 2 distinct bleeding models, f10low mice displayed an increased bleeding tendency compared with f10WT mice. In the tail-clip assay, blood loss was increased from 12 ± 16 µL to 590 ± 335 µL (P < .0001). In the saphenous vein puncture (SVP) model, the number of clots generated was reduced from 19 ± 5 clots every 30 minutes for f10WT mice to 2 ± 2 clots every 30 minutes (P < .0001) for f10low mice. In both models, bleeding was corrected upon infusion of purified FX. Treatment of f10low mice with fitusiran (2 × 10 mg/kg at 1 week interval) resulted in 17 ± 6% residual antithrombin activity and increased thrombin generation (fourfold and twofold to threefold increase in endogenous thrombin potential and thrombin peak, respectively). In the SVP model, the number of clots was increased to 8 ± 6 clots every 30 minutes (P = .0029). Altogether, we demonstrate that reduction in antithrombin levels is associated with improved hemostatic activity under conditions of FX deficiency.

Hereditary factor X deficiency in America survey: impact on quality of life and burden of disease in patients and caregivers.

Hereditary factor X deficiency (HFXD) is a rare bleeding disorder causing delayed haemostasis and potentially life-threatening bleeds. Patient/caregiver burden and diagnosis path have not been well characterized. THE AIM OF THIS STUDY WAS TO: describe the diagnosis path, disease burden, and HFXD impact on quality of life (QoL) in patients and caregivers.This was a prospective, cross-sectional, web-based survey of patients with HFXD and caregivers addressing the patient/caregiver experience, QoL, humanistic and unmet needs.Thirty patients and 38 caregivers completed the survey with mean ages 24.7 and 44.6 years, respectively. Mean age at diagnosis was 4.1 years. The diagnostic process was somewhat/very difficult for 23% of patients and 26% of caregivers. Approximately half (53%) received single factor replacement (SFR) as prophylaxis or on-demand. Most patients (71%) reported regular prophylaxis treatment. Over one-fourth (27%) reported treatment with fresh frozen plasma. Bleeding episodes were less common in patients using SFR versus non-SFR: three bleeds or fewer were reported by 92% SFR and 75% non-SFR patients. HFXD patients reported low well being in work/school/social activities with mean HFXD-adapted Hemophilia Well being Index. Patient symptoms negatively impacted caregiver burden with a mean HFXD-adapted Hemophilia Caregiver Index (±SD) of 15.9 (4.6), but also unexpectedly had a positive impact on self-worth and inner strength.To our knowledge, this is the first study to assess patient and caregiver burden of HFXD and impact on QoL. Improvements in symptom recognition, prompt diagnosis, and adherence to expert recommendations for treatment could improve QoL and decrease burden on HFXD patients and caregivers.

Acquired factor V and factor X Deficiency coexisting with acquired dysfibrinogenaemia in a patient with light chain myeloma.

An elderly woman with light chain myeloma presented with prolonged epistaxis and extensive cutaneous haematomas: her kappa/lambda ratio was high at 395, her coagulation screen, thrombin and reptilase times were abnormal, her FV and FX were in the low range in the absence of specific inhibitors, her Clauss fibrinogen was low at 0.95 g/l but antigenic FNG was 1.58 g/l. The patient denied treatment and died of progressive renal failure. We wish to describe the unusual association of FX and FV deficiency co-existing with an acquired dysfibrinogenaemia.

Anesthesia strategy for factor X deficiency coagulopathy: case report

Abstract Factor X deficiency ranks among the rarest coagulopathies and has a variable presentation spectrum. We intend to present a proposal for anesthesia protocol for individuals with the coagulopathy. The excision of an ovarian neoplasm was proposed for a 26-year-old, female, ASA II patient, with congenital Factor X deficiency. Physical examination and lab tests were normal, except for Prothrombin Time (PT) 22.1s (VR: 8-14s), International Normalized Ratio (INR) 1.99 (VR: 0.8-1.2) and Activated Partial Thromboplastin Time (aPTT) 41.4s (VR: 25-37s). We concluded that a history of bleeding should always be investigated, along with a pre-anesthetic coagulation study.

Déficit adquirido de factor X en leucemia mielomonocítica crónica: reporte de un caso / Isolated factor X deficiency in chronic myelomonocytic leukemia: Report of one case

Bleeding disorders are commonly associated with hemato-oncologic diseases. We report a 68 years old male with a chronic myelomonocytic leukemia derived from a long lasting mielodysplastic syndrome that did not respond to treatment with Azacitidine. The patient was hospitalized due to tonic clonic seizures. A CAT scan showed a hematoma in the frontal lobe. A new assessment of hemostasis revealed an isolated deficiency of Factor X. We speculate that this deficit could be secondary to consumption due to the chronic Myelomonocytic Leukemia.

Extracciones dentales atraumáticas en pacientes pediátricos con trastornos de la coagulación: descripción de la técnica y reporte de un caso / Atraumatic tooth extractions in pediatric patients with bleeding disorders: a technical description and report of a case

Se detalla y fundamenta la técnica de extracción atraumática de dientestemporales unirradiculares en pacientes pediátricos con trastornos de lacoagulación utilizando separadores elastoméricos. Se expone el caso deun paciente pediátrico con diagnóstico de defi ciencia de factor X de lacoagulación, quien requirió de la extracción atraumática de los órganosdentarios centrales superiores temporales debido a la gingivorragiapropia de la exfoliación natural.

We describe the technique of atraumatic tooth extraction for single-rooted temporary and permanent teeth in pediatric patients with bleed-ing disorders using elastomeric separators and discuss its benefi ts. We present the case of a pediatric patient diagnosed with coagulation factor X defi ciency who required the atraumatic extraction of his temporary upper central teeth due to gingival bleeding caused by natural exfoliation.

Deficiencia congénita en factor X de la coagulación sanguínea: resultado exitoso del empleo de concentrados de complejo protrombínico en el control de la tendencia hemorrágica en operación cesárea en 2 embarazos / Congenital deficiency of blood coagulation factor X: successful result of prothrombin complex concentrates use in hemorrhagic diathesis in cesarean section in 2 pregnancies

There is little experience in the prevention of the severe hemorrhagic diathesis of factor X coagulation factor deficiency, before surgical procedures. A female with congenital deficiency of factor X that received prothrombin complex concentrates that contained 1000 IU of factor X (16.7 U/I Kg BW) inmediately prior to a cesarean section in two occasions, is reported. Factor X concentration rose from 1 to 25 percent in the first ocassion and from 10 to 63 percent in the second. In both episodes, factor X decreased in the first 24 h of the postoperative period and required new infusions of prothrombin complex concentrates. No episodes of abnormal bleeding were observed. It is concluded that the infusion of prothrombin complex concentrates prevents the hemorrhagic diathesis of factor X deficiency, despite its modest increase in plasma. A initial infusion of 1.000 UI of factor X (16-20 IU/Kg BW), followed by 500 IU (8-10 IU/Kg) every 24 hours is suggested for an adequate management of this condition

Defecto congénito de los factores II, VII, y X / Congenital defect of factors II, VII, and X

Se analizan las principales características clínicas y de laboratorio de las deficiencias aisladas y combinadas de los factores II, VII y X. Se señala la importancia del uso de diferentes reactivos y metodologías para poderlos clasificar, sobre todo las variantes, debido a que en estos casos se presentan niveles inmunológicos normales con niveles disminuidos de actividad funcional o coagulante. Se discute brevemente el diagnóstico diferencial de estos trastornos, asi como se esbozan algunas pautas para el manejo del paciente con estas complicaciones hemorragicas hereditarias

Un caso de amiloidosis sistémica y deficiencia de factor X asociada con mieloma múltiple / A case of systemic amyloidosis and factor X deficiency associated with multiple myeloma

Se describe el caso de un paciente masculino de 50 años con síndrome de amiloidosis primaria y deficiencia adquirida de factor X asociada con mieloma múltiple. Las manifestaciones clínicas más importantes consistieron en infiltracion amiloide sistémica y hemorragia por mucosa gingival. El estudio integral del paciente se llevó a cabo a partir del hallazgo inicial de prolongación del tiempo de protrombina y del tiempo de tromboplastina activado. La reacción al tratamiento fue insatisfactoria, y el paciente falleció poco después de haberse logrado aparentemente la estabilización de sus complicaciones cardiovasculares y renales

Deficiencia herediatria del factor X de la coagulacion.Estudio en diez casos de una familia en Mexico. / Hereditary deficiency of coagulation factor X. Study of 10 cases in a family in Mexico

La enfermedad herediatria do tipo hemorragico, condicionada por deficiencia del factor X es poco frecuente. Se han informado cerca de 50 familias en el mundo y en Mexico dos casos en dos familias. En este estudio la deficiencia del factor X de la coagulacion fue encontrada en diez casos de una familia originaria del Estado de Puebla, sin antecedentes de endogamia. Se manifesto en miembros de ambos sexos por su caracter autosomico recesivo: dos casos fueron homocigotos y ocho heterocigotos.En la forma homocigota, existio prolongacion del tiempo de tromboplastina parcial (TTP) y del tiempo de protrombina (TP) desde el estudio basal y una actividad del factor X coagulante (Xc) del 25% o menor. Los casos heterocigotos mostraron tres patrones diferentes en los estudios basales del TTP y del TP. La actividad del factor Xc se encontro en cerca de la mitad de lo normal y los estudios del TTp y TP en dilucion salina detectaron a los heterocigotos, a pesar de que el estudio basal fuera normal No obstante la baja incidencia de la deficiencia del factor X en el mundo, en Mexico se pudo recabar informacion acerca de dieciocho casos afectados y la existencia de cinco familias; lo que da importancia a los estudios orientados hacia su diagnostico

Deficiencia probablemente heredada de factor X (Prower-Stuart). Presentacion de un caso y breve revision de la bibliografia. / Probably inherited factor X deficiency (Power-Stuart). Report of a case and brief review of the literature

Se reporta el caso de una mujer de 8 anos de edad, con el antecedente de un primo materno diagnosticado como "hemofilico".Muestra alargamiento en el tiempo de tromboplastina parcial, el de protrombina y la generacion de tromboplastina, con un nivel de factor X de 15%, deficiencia aparentemente de tipo familiar. Se hace una breve revision monografica del factor X y bibliografica de su deficiencia, senalando sus caracteristicas clinicas y de laboratorio