A functional factor X deficiency

A functional factor X deficiency is described which caused pronounced reduction in the in vitro activation of the extrinsic system while marginally affecting the in vitro activation of the intrinsic pathway. All studies were normal with the exception of a prolonged PT, an elevated factor X antigen, and low factor X activity. Western blot analysis revealed the presence of two factor X species. The abnormal molecule was of higher molecular weight. Interestingly, there was no bleeding associated with this deficiency. The biochemical basis of this defect is currently under investigation. ©1995 Wiley-Liss, Inc.     

Spontaneous resolution of acquired factor X deficiency in amyloidosis

Abstract. We describe the case of a 51-year-old man with systemic amyloidosis in whom factor X activity was initially 6% of the normal. Amyloidosis was responsible for congestive heart failure and a nephritic syndrome but there was no bleeding diathesis. A 12-month trial of melphalan and prednisone failed to improve cardiac and renal dysfunction; factor X levels remained low. Eighteen months after this treatment was stopped, factor X spontaneously normalized although renal insufficiency persisted. We suggest that the possibility of a spontaneous factor X recovery must be considered when evaluating efficacy of therapeutic agents in amyloidosis.     

Congenital factor X deficiency: spectrum of bleeding symptoms in 32 Iranian patients

The spectrum of the clinical manifestations of congenital factor X deficiency was studied in 32 Iranian patients. The most frequent symptom was epistaxis, which occurred in 72% of patients, with all degrees of deficiency. Other mucosal haemorrhages (e.g. haematuria, gastrointestinal bleeding) were less frequent and occurred mainly in patients with unmeasurable factor X. Menorrhagia occurred in half of the women of reproductive age. Soft tissue bleeding occurred in two-thirds of the patients; spontaneous haematomas and haemarthroses led to severe arthropathy in five patients. Bleeding from the umbilical stump was an unexpected finding in nine patients. This study demonstrated that the bleeding tendency of factor X deficiency is severe and correlates with factor levels.     

Danazol therapy in factor X deficiency

Factor X (FX) deficiency is a rare coagulation disorder that usually presents with bleeding manifestations and is treated with fresh frozen plasma or prothrombin complex concentrates. We report a case of FX deficiency in which the patient presented with bleeding as well as thrombosis. The patient responded to Danazol and relapsed when the drug was stopped. The occurrence of thrombosis in FX deficiency and the role of Danazol in coagulopathies are reviewed.     

Spontaneous major bleeding in acquired factor X deficiency secondary to AL-amyloidosis

Abnormal bleeding may be seen in up to a third of patients with amyloidosis. Factor X deficiency is the commonest acquired coagulopathy in amyloidosis. While mild intracutaneous bleeding is common, spontaneous life-threatening haemorrhage is rare. We report a case of acquired FX deficiency due to amyloid light chain (AL)-amyloidosis presenting with spontaneous retroperitoneal bleeding. The diagnostic and management issues in this patient are discussed.     

Prophylactic treatment of severe factor X deficiency with prothrombin complex concentrate

Factor X (FX) deficiency is an autosomal recessive trait that occurs in fewer than 1 in 500 000 people. Not surprisingly, reports of prophylactic treatment for FX deficiency are exceedingly rare. We now report our experience of the use of prophylactic therapy in a FX-deficient patient. This 18-year-old African-American male presented at the age of 4(1/2) years with an FX level < 1%. Treatment was on demand with prothrombin complex concentrates (PCCs) given at two times the dose per kilogram of body weight for factor IX. He experienced frequent epistaxis, soft tissue bleeding and joint bleeding. The development of a target joint (right ankle) prompted the initiation of prophylactic treatment in the beginning of 1998 to the present with 30 units kg(-1) Profilnine twice per week via a home infusion programme. If breakthrough bleeding occurred, he was instructed to infuse another dose. He was instructed that Profilnine should not be infused in more than two doses in 24 h or on more than three consecutive days. A trough level drawn 48 h post-infusion showed an FX level of 30%. In the initial 12 months with prophylactic treatment, there was no breakthrough bleeding. Subsequently, with an additional 11 months of follow-up, he has reported one bleed. He rates his quality of life improved since starting prophylactic treatment. There have been no thrombotic events. Prophylaxis with PCC for FX deficiency with adequate education and follow-up can be performed capably in the home setting with a resultant decrease in the frequency of bleeding and attendant complications.     

A rare inherited coagulation disorder: combined homozygous factor VII and factor X deficiency

The combined presence in the homozygous state of more than one recessively transmitted coagulation defect may rarely occur in countries with a high rate of consanguinity. In an Iranian family consisting of two parents (second cousins) and two affected siblings, initial phenotypic analysis led to a diagnosis of mild FX deficiency (10-19% FX activity, 42-54% FX:Ag), and genotyping revealed a new homozygous missense mutation in the corresponding gene (Ser3Cys). As both of the sibs had a severe bleeding history that was not compatible with mild deficiency of FX, further phenotypic analysis revealed the additional presence of severe FVII deficiency (<1% FVII activity; 63-111% FVII:Ag) associated with the homozygous missense gene mutation Cys310Phe. In this kindred, lack of identification of the double coagulation defect might have led not only to incomplete understanding of the clinical phenotype but also to an incorrect prenatal diagnosis.     

Recombinant human factor VIIa in the management of amyloid-associated factor X deficiency

Factor X deficiency is an important complication of amyloidosis. It is associated with severe bleeding that is difficult to control with plasma or prothrombin complex concentrates. Splenectomy ameliorates the factor X deficiency, but achieving satisfactory haemostasis for this operation is problematic. We report that a new clotting concentrate, recombinant factor VIIa, readily controls bleeding and makes splenectomy feasible.     

Chronic recurrent multifocal osteomyelitis in a patient with selective immunoglobulin M deficiency

Chronic recurrent multifocal osteomyelitis is an unusual inflammatory process of unknown origin involving multiple osseous sites, often recurrently. Selective immunoglobulin M (IgM) deficiency is a rare primary immunodeficiency disease, which can be associated with autoimmune diseases such as systemic lupus erythematosus, Hashimoto’s disease, or hemolytic anemia. Here we report a case of a chronic recurrent multifocal osteomyelitis coexisting with selective IgM deficiency.     

Importance of pharmacokinetic studies in the management of acquired factor X deficiency

Up to 14% of individuals with systemic AL amyloidosis develop acquired factor X deficiency, which occurs due to adsorption of factor X onto amyloid fibrils. Although baseline factor X levels are not predictive of bleeding risk in these patients, serious hemorrhagic complications can occur, particularly during invasive procedures. Optimal management strategies to attenuate bleeding risk in these patients are unknown. We describe our experience in the management of acquired factor X deficiency, secondary to systemic AL amyloidosis, in a case series of three patients who received prothrombin complex concentrates (PCCs) for treatment and prevention of bleeding events. We performed a retrospective review extracting information on baseline demographics, laboratory data, pharmacokinetic (PK) studies, and clinically documented bleeding events. Our case series demonstrates that individuals with acquired factor X deficiency secondary to amyloidosis have variable laboratory and clinical responses to PCCs. This is likely due to distinct amyloid loads and fibril sequences, leading to different binding avidities for factor X. Our data emphasize the importance of performing PK testing prior to any invasive procedures to determine the dose and frequency interval to achieve adequate factor X levels for hemostasis, given the variable response between individuals.     

Diagnosis and treatment of inherited factor X deficiency

Summary. Factor X is a vitamin K‐dependent, liver‐produced serine protease that serves a pivotal role in coagulation as the first enzyme in the common pathway to fibrin formation. Inherited factor X deficiency is a rare autosomal recessive bleeding disorder that is estimated to occur in 1:1 000 000 individuals up to 1:500 carriers. Several international registries of FX‐deficient patients have greatly expanded the knowledge of clinical phenotype. A proposed classification of severity is based on FX:C activity measurements: an FX:C measurement <1% is severe, an FX:C measurement of 1–5% is moderate and an FX:C measurement of 6–10% is mild. Levels above 20% are infrequently associated with bleeding and heterozygotes are usually asymptomatic. Among patients with FX:C levels <10%, unlike moderate or severe haemophilia A and B, mucocutaneous bleeding symptoms such as epistaxis and menorrhagia occur in the majority. In addition, patients with moderate–severe deficiency may have symptoms similar to that of haemophilia A and B, including haemarthrosis, intracranial haemorrhage, and gastrointestinal bleeding. Genotype characterization may offer important clues about clinical prognosis. More than 80 mutations of the F10 gene have been identified, most of which are missense mutations. There is no specific FX replacement product yet readily available, but fresh frozen plasma and prothrombin complex concentrates can be used for treatment of bleeding symptoms and preparation for surgery.     

Successful treatment of transient acquired factor X deficiency by plasmapheresis with concomitant intravenous immunoglobulin and steroid therapy

Two patients with no history of previous bleeding diatheses presented with active bleeding from multiple body sites, declining hemoglobin levels, and markedly prolonged prothrombin times (PT) and activated partial thromboplastin times (aPTT) with incomplete correction on PT mix assays. Both patients demonstrated a severe deficiency of factor X (F.X) (<1%; reference range 60–150%). F.X levels and bleeding were refractory to multiple transfusions of fresh frozen plasma (FFP) in both patients. In contrast, daily therapeutic plasma exchange (PLEX) with concomitant administration of intravenous immunoglobulin (IV IgG) and steroids produced a rapid increase in F.X levels with cessation of bleeding, followed by stabilization and normalization of F.X levels and progressive correction of coagulation times. Neither patient has demonstrated a recurrence of the bleeding tendency following discontinuation of steroid therapy. These patients had transient acquired F.X deficiency, a rare coagulopathy, which can result in a lethal bleeding diathesis. An IgG inhibitor that selectively inhibited F.X activation in Russell's viper venom or tissue factor/F.VIIa assays was demonstrated in one patient's pretreatment plasma. Previous treatment of hemorrhage in transient acquired F.X deficiency has been prothrombin complex and/or activated clotting concentrates, which can be associated with transient hypercoagulable states. This is the first reported use of PLEX in transient acquired F.X deficiency. PLEX is safe, efficacious, and rapidly restores hemostasis in this rare acquired bleeding disorder. Am. J. Hematol. 57:245–252, 1998. © 1998 Wiley-Liss, Inc.     

An analysis of 8 cases of factor X deficiency

Background

Factor X deficiency is a rare coagulation defect. There are occasional reports of factor X deficiency from India. Difficulty in accurate diagnosis and non-availability of ideal treatment is discussed.

Methods

Eight cases of factor X deficiency, diagnosed from 1992 to 2007 are reported here

Results

Seven were male while one was female. Seven patients were symptomatic from early childhood. One patient became symptomatic from 18 years of age. Factor X assay was done in 4 patients, 3 had severe deficiency and one had mild deficiency. One patient had associated factor IX deficiency. Three patients had repeated bleeding episodes requiring multiple transfusions. Two patients had intracranial bleed and one had umbilical cord bleeding at birth. There was no mortality. No patient received prophylactic transfusion.

Conclusions

Factor X deficiency is a rare coagulation defect. Hereditary deficiency should be distinguished from acquired deficiency. CNS, joints and skin are the common sites of bleeding.

     

肝淀粉样变性合并凝血因子X缺乏1例

患者男,40岁,因反复下肢疼痛、肿胀9月余,右侧大腿疼痛明显加重约2周入院。患者于2001年6月和10月2次不慎摔伤右膝部,在当地医院诊断为“右膝关节内血肿”,经止血消     

Successful treatment of an acquired haemorrhagic diathesis due to factor X deficiency with chemotherapy

A 70-yr-old woman presented with a severe haemorrhagic diathesis due to an acquired factor X deficiency. A plasma infusion study showed that exogenous factor X was eliminated very effectively from the patient's circulation. A bone marrow biopsy was consistent with plasma cell dyscrasia. Neither an abdominal fat biopsy nor the bone marrow biopsy confirmed an amyloidosis, although clinically no other diagnosis seemed possible. Treatment with intermittent chemotherapy, consisting of vincristine, cytoxan and prednisone, yielded definite clinical and laboratory improvement.     

Acquired,non‐amyloid related factor X deficiency: review of the literature

Summary. Factor X (FX) deficiency is a rare coagulopathy due to congenital deficiency (Stuart–Prower disease) or in association with primary amyloidosis. Acquired and isolated FX deficiency occurring in the absence of a plasma cell dyscrasia has only been infrequently described. After recently diagnosing and treating a case of acquired, isolated FX deficiency, we embarked upon a review of the literature to help guide clinicians who may face this clinical situation. The literature was reviewed to identify cases of isolated, acquired FX deficiency unrelated to congenital deficiency, use of vitamin K antagonists, or amyloidosis. There were 34 cases of acquired FX deficiency identified, occurring in association with malignancy, drug exposure and infection. The majority of described cases (38%) were preceded by a non‐specific respiratory viral illness. The initial presentation was variable, ranging from no bleeding to life‐threatening haemorrhage. Twenty per cent of patients had musculoskeletal bleeding resembling patients with haemophilia. Both the prothrombin time and the activated partial thromboplastin time were markedly prolonged in nearly all patients. In 26% of patients, a specific FX inhibitor was identified. Numerous therapies have been utilized in patients with acquired FX deficiency including high‐dose glucocorticoids, plasma exchange with fresh frozen plasma and intravenous immunoglobulin. In 18% of patients, the coagulopathy resolved spontaneously. All patients achieved a complete recovery. Acquired factor X deficiency is a rare disorder, commonly associated with a preceding viral illness and a circulating FX inhibitor. Although multiple treatment modalities have been described with variable success, in many cases, it is a self‐limited condition.