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.

Acquired factor X deficiency in a multiple myeloma without amyloidosis: a case report.

BACKGROUND: Multiple myeloma is one of the most common hematologic malignancies. Acquired factor X deficiencies are often observed in primary (AL) amyloidosis and rarely in multiple myeloma. OBJECTIVE: We report a case of an acquired factor X deficiency in a patient with a newly diagnosed IgA lambda multiple myeloma, without any evidence of concomitant amyloidosis. METHODS: We present the patient's medical history, clinical and physical examinations, laboratory analysis, and outcome. RESULTS: A 76-year-old male presented at the emergency department with ongoing gingival bleeding. Several analytical problems with blood sample analysis arose, which eventually led to the diagnosis of a multiple myeloma. Further exploration revealed an acquired factor X deficiency, explaining the ongoing bleeding. There was no evidence of concomitant amyloidosis. The multiple myeloma was treated, leading to complete remission of the malignancy and bleeding tendency. CONCLUSION: While coagulopathy is rarely observed in patients diagnosed with multiple myeloma, considering an acquired factor X deficiency becomes relevant when such patient present with bleeding diathesis.

Postmortem diagnosis of severe factor X deficiency in a fetus with intracranial hemorrhage resulting in intrauterine death.

In patients with severe congenital factor X deficiency, spontaneous intracranial hemorrhage (ICH) is particularly frequent in early childhood. We describe a case of fetal death at 26 weeks due to massive ICH. Gene panel analysis of postmortem samples revealed homozygosity for a pathologic F10 gene variant (c.1210T>C, p.Cys404Arg), which impedes correct folding of the catalytic serine protease domain and, therefore, causes a significant reduction in FX levels. The parents, not consanguineous but of the same ethnic community, were found to be heterozygous for this variant and did not have any personal or family history of abnormal bleeding. To the best of our knowledge, this is the first reported case of severe FX deficiency resulting in ICH diagnosed through postmortem genetic analysis. It illustrates the importance of exploring the etiology of fetal or neonatal ICH, which may impact future pregnancies, and the treatment of a potential coagulopathy in the child.

Use of plasma-derived factor X concentrate in neonates and infants with congenital factor X deficiency.

BACKGROUND: Congenital factor X deficiency (FXD) is a rare bleeding disorder that often presents with severe bleeding in the neonatal period. Long-term prophylaxis with infusions of FX-containing products is recommended in patients with FXD and a personal or family history of severe bleeding. A plasma-derived FX concentrate (pdFX) is approved for on-demand and prophylactic therapy in adults and children with FXD. The safety and efficacy of pdFX has been demonstrated in patients <12 years of age, yet limited data exist regarding its use in infants. PATIENTS/METHODS: This retrospective case series details clinical experience using pdFX in four neonates with moderate and severe FXD across four institutions. RESULTS AND CONCLUSIONS: All four patients presented in the first week of life with severe bleeding. Following treatment of the acute bleed, prophylactic pdFX was initiated at an average of 29 days of life and a dose of 69 IU/kg every 48 hours. Incremental recovery (IR) in three infants averaged 1.42 IU/dL per IU/kg (min-max: 1.06-1.67 IU/dL per IU/kg). One patient experienced thrombotic complications in the setting of sepsis. After a median follow-up of 26.5 months, no patient has experienced breakthrough bleeding episodes. Our study supports the use of pdFX in neonates and infants and suggests that higher pdFX dosing of 70 to 80 IU/kg every 48 hours based on the smallest available vial size is feasible. Because of variability in IR, close monitoring of FX activity should be used to guide dosing in this age group.

Successful Treatment of Life-threatening Bleeding Caused by Acquired Factor X Deficiency Associated with Respiratory Infection.

Acquired factor X deficiency (AFXD) is a very rare coagulation disorder. A 40-year-old man with no comorbidities suffering from a fever, malaise, and severe hemorrhagic symptoms, including massive hematuria, was emergently admitted. His platelet count was normal, but his prothrombin time and activated partial thromboplastin time were markedly prolonged, which was thought to be due to autoantibody against a coagulation factor in the common pathway. Despite severe massive hematuria resulting in transient renal failure, he was successfully treated with urgent immunosuppressive therapy. Computed tomography revealed bronchopneumonia, which improved with antibiotic administration. AFXD without evidence of amyloidosis was subsequently diagnosed.

Evaluation of the anticoagulant effect of low-molecular-weight heparins based on the anti-Xa level during haemodialysis.

AIM: Evaluate the relationship between anti-Xa activity and anticoagulant effect, and ascertain whether accumulation of low-molecular-weight heparins (LMWH) occurs during haemodialysis. METHODS: There was an observational, single-centre study among participants who received the LMWH dalteparin, enoxaparin or nadroparin. A standard haemodialysis session lasted 4 hours. All included participants had anti-Xa activity measures at 0.5 and 4 hours. Extracorporeal circuit (ECC) clotting was evaluated by visual inspection of the haemodialyser and bubble trap after each haemodialysis session. The same person was tested at three consecutive haemodialysis sessions. RESULTS: Overall, 90 participants were enrolled and 259 haemodialysis sessions assessed. There was no significant difference in the mean anti-Xa activity at 0.5 and 4 hours for three consecutive sessions, so LMWH accumulation did not occur. There were 69 (26.6%) sessions in which, ECC clotting was visible. Compared with the group where circuit clotting did not occur, the LMWH dose and anti-Xa activity in the group where circuit clotting occurred were significantly lower. At 0.5 hour, anti-Xa <0.88 IU/mL had significantly higher odds of ECC clotting than that at ≥0.88 IU/mL. At 4 hours, anti-Xa <0.35 IU/mL had significantly higher odds of ECC clotting than that at ≥0.35 IU/mL. CONCLUSION: We found that over three haemodialysis sessions, no significant accumulation of LMWH was evident in subjects receiving a LMWH dose of between 2000 and 5000 IU for regular. Anti-Xa activity measurement can be used to adjust the dosage of LMWH and predict the anticoagulant effect during haemodialysis.

Severe Factor X Deficiency Presenting as Febrile Seizure in an Infant.

Factor X deficiency is a severe inherited coagulation disorder, which is characterized by severe systemic bleeding manifestations in affected individuals. It is a rare disorder with a frequency of around 1:1,000,000 in the general population. We present the case of an infant with factor X deficiency who presented with complex febrile seizure. Although febrile seizures are very common in children, a closer scrutiny leads to neuroimaging and finding of intracranial bleed. Hematologic and genetic investigations confirmed the diagnosis. A high index of suspicion should be maintained to diagnose uncommon bleeding disorders in children.

Immunoglobulin Light Chain Amyloidosis with Severe Liver Dysfunction Accompanied by Factor X Deficiency.

Severe hepatic failure is rarely a cause of death in patients with immunoglobulin light chain (AL) amyloidosis. We herein report a case of AL amyloidosis involving a bleeding tendency due to factor X deficiency and marked hepatic involvement of amyloidosis. The patient died due to severe liver dysfunction two weeks after admission. The diagnosis was confirmed histologically by AL-λ amyloidosis, with the liver and spleen as the main lesions, on an autopsy. As treatment-related toxicity is strong in advanced cases, appropriate treatments are required to improve the prognosis of AL amyloidosis with severe liver dysfunction.

Congenital Factor X deficiency in women: A systematic review of the literature.

Factor X deficiency (FXD) is a rare autosomal recessive bleeding disorder with a variable phenotypic severity. In women, heavy menstrual bleeding (HMB), recurrent ovulation bleeding with haemoperitoneum and bleeding complications in pregnancy such as retroplacental haematoma and postpartum haemorrhage have been reported. The aim of this review was to examine gynaecological problems and obstetric complications in women with congenital FXD. A total number of 49 relevant articles were identified, including 332 women, dating from 1960 to 2018. Heavy menstrual bleeding was reported in 72/284 (25%) women in total, 14/30 (47%) in case reports and 58/254 (23%) in 11 case series, 64% and 10% required blood products and blood transfusion, respectively. Haemoperitoneum from ovulation bleeding or ruptured haemorrhagic ovarian cyst requiring blood transfusion occurred in 8/322 (2.4%) women, six required surgical intervention, including oophorectomy in two. 31 pregnancies were reported in 19 women. There were four miscarriages (including a late miscarriage at 21 weeks). There was a high rate of preterm birth and neonatal death occurring in eight (30%) and three (11%) of pregnancies reaching viability stage. Postpartum haemorrhage (PPH) occurred in six (22%) of deliveries, one requiring hysterectomy. In conclusion, women with FXD are at an increased risk of heavy bleeding during menstruation and ovulation as well as adverse pregnancy outcome and postpartum haemorrhage. Collaboration in a multidisciplinary team including an obstetrician/gynaecologist, a perinatologist and a haematologist is necessary for the prevention and management of these complications.

Factor X Deficiency Caused by Nonsecretory Myeloma Successfully Corrected with Bortezomib: A Case Report and Review of the Literature.

A 62-year-old female presenting with anemia and extensive hemorrhages is reported. Coagulation tests showed significantly prolonged prothrombin time (PT) and activated partial thromboplastin time. Decreased levels of clotting factor X activity were determined (5.4%). Bone marrow biopsy revealed neoplastic plasma cells. Serum and urine protein electrophoresis were both negative for monoclonal gammopathy, and both bone marrow and abdominal fat biopsies were negative for amyloid deposition. The patient was diagnosed as suffering from nonsecretory multiple myeloma (MM) complicated by acquired factor X deficiency. A complete response (CR) of the myeloma and recovery of factor X activity (56.6%) were achieved after the administration of treatment, including chemotherapy and bortezomib. We suggest that patients with nonsecretory MM might present with factor X deficiency and should be carefully screened for light chain amyloidosis. Novel agents such as bortezomib should be highly considered as treatment in these patients.

Efficacy, safety and pharmacokinetics of a new high-purity factor X concentrate in women and girls with hereditary factor X deficiency.

Essentials Plasma-derived factor X concentrate (pdFX) is used to treat hereditary factor X deficiency. pdFX pharmacokinetics, safety and efficacy were assessed in factor X-deficient women/girls. Treatment success rate was 98%; only 6 adverse events in 2 subjects were possibly pdFX related. On-demand pdFX 25 IU kg-1 was effective and safe in women/girls with factor X deficiency. SUMMARY: Background A high-purity, plasma-derived factor X concentrate (pdFX) has been approved for the treatment of hereditary FX deficiency, an autosomal recessive disorder. Objective To perform post hoc assessments of pdFX pharmacokinetics, safety and efficacy in women and girls with hereditary FX deficiency. Patients/Methods Subjects aged ≥ 12 years with moderate/severe FX deficiency (plasma FX activity of < 5 IU dL-1 ) received on-demand or preventive pdFX (25 IU kg-1 ) for ≤ 2 years. Results Of 16 enrolled subjects, 10 women and girls (aged 14-58 years [median, 25.5 years]) received 267 pdFX infusions. Mean monthly infusions per subject were higher among women and girls (2.48) than among men and boys (1.62). In women and girls, 132 assessable bleeding episodes (61 heavy menstrual bleeds, 47 joint bleeds, 15 muscle bleeds, and nine other bleeds) were treated with pdFX, with a 98% treatment success rate versus 100% in men and boys. Mean pdFX incremental recovery was similar in the two groups (2.05 IU dL-1 versus 1.91 IU dL-1 per IU kg-1 ), as was the mean half-life (29.3 h versus 29.5 h). Of 142 adverse events in women and girls, headache was the most common (12 events in six subjects). Six events (two infusion-site erythema, two fatigue, one back pain, one infusion-site pain) in two subjects were considered to be possibly pdFX-related. Following the trial, pdFX was used to successfully maintain hemostasis in two subjects undergoing obstetric delivery. Conclusions pdFX was well tolerated and effective in women and girls with FX deficiency. Although women and girls had different bleeding symptoms and sites than men and boys, their pdFX pharmacokinetic profile was comparable.

The Long-term Outcomes after VAD plus SCT Therapy in a Patient with AL Amyloidosis and Severe Factor X Deficiency.

A 55-year-old man was admitted to our institute to undergo evaluation for proteinuria (5.4 g/day) with lambda-type Bence-Jones protein (BJP). Primary amyloid light chain (AL) amyloidosis and acquired factor X deficiency were diagnosed. High-dose melphalan combined with autologous stem cell transplantation was performed. After three years, the patient's proteinuria normalized, he was negative for urinary BJP, and his factor X activity improved to 105%. Serial renal biopsy showed no progression of amyloid deposition at a biopsy after 5 years, but showed a slight increase in the amyloid deposition after 11 years. This therapy can improve the prognosis of AL amyloidosis; however, there are limitations to the strategy.

[Acquired, non-amyloid related factor X deficiency: A first case associated with atypical chronic lymphocytic leukemia and literature review]. / Déficit non amyloïde acquis en facteur X : un premier cas satellite d'une leucémie lymphoïde chronique atypique et revue de la littérature.

INTRODUCTION: Acquired factor X deficiency is in most cases associated with AL amyloidosis. Acquired non-amyloid related factor X deficiency (DNAA-FX) has been exceptionally reported in the literature. CASE REPORT: We report the first case of acquired, non-amyloid related factor X deficiency associated with atypical chronic lymphoid leukemia in a 66-year-old patient with spontaneous hematomas. After therapeutic failure with polyclonal intravenous immunoglobulins, specific lymphoid malignancy treatment allowed symptoms and coagulation disorder resolution. CONCLUSION: DNAA-FX should be considered in case of bleeding events or coagulation disorders during low-grade hematological malignancies. Its occurrence can be considered as a treatment indication to prevent potentially fatal bleeding complications.

A family with factor X deficiency from Argentina: a compound heterozygosis because of the combination of a new mutation (Gln138Arg) with an already known one (Glu350Lys).

The objective was to investigate a family from Argentina. The proposita was a 51-year-old woman who had a moderate bleeding tendency. Some of her children showed a mild bleeding tendency. Her mother and the husband were asymptomatic. Clotting, immunological and molecular biology techniques were used. Partial thromboplastin, prothrombin, Russell Viper venom-clotting times were moderately prolonged in the proposita, whereas they were slightly prolonged in the children and in her mother. Factor X (FX) activity was about 2-3% of normal in all assay systems. FX antigen was less than 5%. Other clotting factors and platelet were normal. Genetic analysis showed a compound heterozygosis: combination of a 'new' mutation (Gln138Arg) with an already known mutation (Glu350Lys). The children had intermediate FX levels (35-63% of normal) and were carriers of one of the two mutations present in the proposita. This is the first observation of a FX deficiency in Argentina.

Intracranial Hemorrhage as the First Manifestation of Severe Congenital Factor X Deficiency in a 20-Month-Old Male: Case Report and Review of the Literature.

Factor X deficiency (FXD) is a rare bleeding disorder, which can result in severe bleeding symptoms such as intracranial hemorrhage (ICH). The most common bleeding symptoms are epistaxis and gum bleeding. ICH is reported in 9-26% of all patients with FXD, mostly during the first month of life. Here, we present a rare case of a male presenting with ICH at the age of 20 months as the first manifestation of FXD. Secondary prophylaxis with factor X substitution once weekly prevented further bleeding.