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Hereditary Factor X Deficiency
Hereditary F10 Deficiency

Hereditary factor X deficiency is an inherited coagulation disorder with an autosomal recessive transmission, resulting from a deficiency of factor X. Factor X deficiency can also be acquired and it is more prevalent than the congenital variant.

Presentation

A general classification scheme for hereditary FX deficiency divides it into 2 categories: Type 1 and Type 2. Patients with type 1 disease lack the FX and FX functional activity (FX:C) antigens. Type 2 disease patients, on the other hand, have normal antigen levels of FX, while showing an absence of the FX:C antigen.

Hereditary FX deficiency can be further classified based on the levels of FX:C, into mild, moderate and severe groups. Adequate levels of FX:C are considered to be around 10% and patients with levels greater than 20% almost always achieve hemostasis easily [14].

Patients with the mild form of disease show FX:C levels between 5-10 %. They are usually discovered during routine blood tests done for other purposes and may have a family history of the disease. Patients with moderate disease and FX:C levels between 1-5 %, are diagnosed during times of severe hemodynamic stress, namely during surgery, trauma etc. FX:C levels less than 1% are seen in the severe form of the disease. They usually present in the neonatal or early childhood periods.

The hallmark of presentation is abnormal bleeding, varying in severity from mild to severe forms. A typical presentation of patients with FX deficiency includes frequent episodes of bleeding from the mucosal areas, gums, and nose. Recurrent hematomas, hematuria, and hemarthrosis may also be present quite commonly. Women in the childbearing age may have menorrhagia, while pregnant women suffer from an increased risk of miscarriages, antepartum and postpartum hemorrhage. Neonates may show a tendency for intracranial hemorrhage and bleeding from the umbilical stump and the gastrointestinal tract.

Hematological

  • Hemophilia A

    […] defect called hemophilia c or rosenthal's syndrome, that may resemble classical hemophilia. [icd10data.com]

    If the factor IX gene is missing on a child's X chromosome, he will have hemophilia B. For this reason, most people with hemophilia B are men. Mild cases may go unnoticed until a later age in life. [isithereditary.com]

    Convert to ICD-10-CM : 286.2 converts directly to: 2015/16 ICD-10-CM D68.1 Hereditary factor XI deficiency Approximate Synonyms Factor XI deficiency, type I Hemophilia C Hemophilia C, type 1 Hereditary factor XI deficiency disease Applies To Hemophilia [icd9data.com]

    [위키] 혈우병 Haemophilia [百] 혈우병 (血友病) hemophilia [百] 혈우병성관절증 (血友病性關節症) hemophilic arthropathy [百Br] 혈우병 [ 血友病, hemophilia ] [生] Hemophilia (혈우병) (血友病) blood clotting factor (혈액 응고 인자) 혈액 응고에 관여하는 인자들을 말하며 이 결핍에 의해 응고장애를 일으킨다. [dic.impact.pe.kr]

    View Website National Hemophilia Foundation A U.S. organization dedicated to finding better treatments and cures for inheritable bleeding disorders. [cslbehring.com]

  • Easy Bruising

    Patients may experience severe umbilical cord stump bleeding, recurrent epistaxis, soft-tissue hemorrhages, menorrhagia, easy bruising, hematuria, hemarthroses and excessive bleeding during or following surgery or delivery or trauma. [orpha.net]

    If the bleeding is left untreated after surgery, solid swellings consisting of congealed blood (hematomas) can develop in the surgical area.Other signs and symptoms of this disorder can include frequent nosebleeds, easy bruising, bleeding under the skin [icdlist.com]

    Symptoms People with mild FX deficiency experience easy bruising, nose or mouth bleeds, and bleeding after trauma or surgery. [hemophilia.org]

    See Bleeding Symptoms of Rare Clotting Factor Deficiencies Common symptoms nosebleeds (epistaxis) easy bruising bleeding in the gut (gastrointestinal hemorrhage) bleeding into joints (hemarthrosis) muscle bleeds bleeding from the umbilical cord stump [wfh.org]

    […] susceptibility Bruise easily Easy bruisability Easy bruising [ more ] 0000978 Gastrointestinal hemorrhage Gastrointestinal bleeding 0002239 Hematuria Blood in urine 0000790 Intramuscular hematoma 0012233 Joint hemorrhage Bleeding within a joint Hemarthrosis [rarediseases.info.nih.gov]

  • Prolonged Bleeding

    Women with this disorder can have heavy or prolonged menstrual bleeding (menorrhagia) or prolonged bleeding after childbirth. [icdlist.com]

    A person with mild hemophilia may first discover the disorder with prolonged bleeding following a surgical procedure or injury. [healthofchildren.com]

    Although joint bleeding seldom occurs, some factor XI patients will experience bleeding long after an injury occurs. Some women will experience prolonged bleeding after childbirth. [medical-dictionary.thefreedictionary.com]

    Common features of factor X deficiency may include easy bruising, frequent nosebleeds, bleeding gums, blood in the urine, and prolonged bleeding after minor injuries. [rarediseases.info.nih.gov]

    […] at birth bleeding from the mouth, particularly after dental surgery or tooth extraction bleeding during or after surgery or injury Other reported symptoms heavy or prolonged menstrual bleeding (menorrhagia) bleeding after circumcision abnormal or prolonged [wfh.org]

Entire Body System

  • Surgical Procedure

    RESULTS: Five subjects (aged 14-59 years) underwent seven surgical procedures (four major and three minor). Treatment duration was 1-15 days. [ncbi.nlm.nih.gov]

    The secondary objective is to review safety data on Coagadex through the collection of any Adverse Drug Reactions (ADRs) from the first dose of Coagadex in the hospital prior to the surgical procedure until the first follow-up after discharge (i.e., follow-up [clinicaltrials.gov]

    The second study collected data on two surgical patients receiving Coagadex perioperatively. Surgical data from three patients in the first study was added and resulted in five patients undergoing seven surgical procedures. [news-medical.net]

    When the patients received Coagadex for perioperative management for 7 seven surgical procedures, Coagadex was effective in controlling blood loss during and post-surgery. No safety events were identified in both studies. [empr.com]

    The five individuals received Coagadex for perioperative management of seven surgical procedures. Coagadex was demonstrated to be effective in controlling blood loss during and after surgery in participants with mild deficiency. [europeanpharmaceuticalreview.com]

  • Amyloidosis

    Mechanism of factor X deficiency in systemic amyloidosis. N Engl J Med. 1981 Apr 2. 304(14):827-30. [Medline]. Perez Martinez J, Llamas F, Lopez Montes A, et al. [Primary amyloidosis associated to severe factor X deficiency] [Spanish]. [emedicine.medscape.com]

    Differential diagnosis Differential diagnoses include deficiencies of factors II, V, VII, VIII, IX, XI, XIII or acquired deficiencies in FX (amyloidosis) (see these terms). Genetic counseling Transmission is autosomal recessive. [orpha.net]

    Other illnesses that may result in acquired factor X deficiency include severe liver disease and amyloidosis. Amyloidosis is a disorder in which abnormal protein buildup causes poor function in your tissues and organs. [healthline.com]

    In the acquired form of FX deficiency an insufficient amount of factor X is produced by the liver due to liver disease, vitamin K deficiency, buildup of abnormal proteins in organs (amyloidosis) or certain medications (i.e. warfarin).[1] In amyloidosis [en.wikipedia.org]

  • Asymptomatic

    Heterozygote patients most often remain asymptomatic. Etiology Inherited congenital FX deficiency is caused by mutations in the F10 gene (13q34) controlling the production of plasma FX. [orpha.net]

    In homozygous patients, the presentation is severe, while heterozygous patients are mostly asymptomatic, only showing symptoms in conditions of severe hemodynamic instability. [symptoma.com]

    […] trauma, dental procedures, pregnancy or circumcision, recurrent fetal loss Bleeding symptoms in severe deficiency are similar to that seen in patients with factor VIII (hemophilia A) and factor IX (hemophilia B) deficiency Heterozygotes are usually asymptomatic [pathologyoutlines.com]

    It may be asymptomatic or manifest with bleeding. [icd10data.com]

    It is amongst the rarest of the inherited coagulation disorders, with an estimated incidence of 1:500,000; its heterozygous asymptomatic form is more common with frequency of 1:500 1, 2, 5. [ispub.com]

  • Fatigue

    In both studies combined, the most common adverse events were infusion site erythema, infusion site pain, fatigue and back pain. [news-medical.net]

    SIDE EFFECTS The most common adverse drug reactions (frequency ≥ 5% of subjects) observed in clinical trials were infusion site erythema, infusion site pain, fatigue, and back pain. [rxlist.com]

    Common adverse effects of plasma-derived Factor X include back pain, infusion site erythema, fatigue and infusion site pain. [mims.co.uk]

    In clinical studies, the most common adverse reactions (frequency ≥5% of subjects) with COAGADEX were infusion site erythema, infusion site pain, fatigue and back pain. Please see Full Prescribing Information for complete prescribing details. [coagadex.com]

    Adverse Effects Two patients in the fist study reported six adverse events considered possibly related to the medication: two events of fatigue in one patient, two events of infusion site erythema in one patient, and one of infusion site pain and back [raredr.com]

  • Falling

    Diplomat opened its doors in 1975 as a neighborhood pharmacy with one essential tenet: “Take good care of patients, and the rest falls into place.” Today, that tradition continues—always focused on improving patient care and clinical adherence. [diplomat.is]

    Diplomat opened its doors in 1975 as a neighborhood pharmacy with one essential tenet: "Take good care of patients, and the rest falls into place." Today, that tradition continues—always focused on improving patient care and clinical adherence. [prnewswire.com]

    The stump usually dries up and falls off about 7 to 21 days. Women with factor X deficiency may experience heavy menstrual bleeding (menorrhagia). [rarediseases.org]

    Since VKCFD arises from a single genetic defect of either γ-glutamyl carboxylase ( GGCX ) or vitamin K 2,3-epoxide reductase complex ( VKORC ) - two proteins of the vitamin K cycle - in the revised classification it obviously falls in the second subgroup [ojrd.biomedcentral.com]

Jaw & Teeth

  • Bleeding Gums

    [4] Symptoms may include frequent nosebleeds, bruising easily, bleeding under the skin, and increased bleeding in the gums. [rarediseases.info.nih.gov]

Skin

  • Petechiae

    Ambulatory patients may have petechiae or ecchymoses in the ankle area, whereas bedridden patients may have them on the back. Petechiae may develop following blood pressure measurements in the area beneath the cuff. [emedicine.medscape.com]

    The arm distal to the blood pressure cuff was evaluated for the presence of petechiae. [clinchem.aaccjnls.org]

Face, Head & Neck

  • Epistaxis

    Patients may experience severe umbilical cord stump bleeding, recurrent epistaxis, soft-tissue hemorrhages, menorrhagia, easy bruising, hematuria, hemarthroses and excessive bleeding during or following surgery or delivery or trauma. [orpha.net]

    […] in Patients With (HHT) Conditions : Hereditary Hemorrhagic Telangiectasia (HHT); Epistaxis Interventions : Drug: Floseal; Other: Packing Sponsors : St. [haemophiliacentral.org]

    See Bleeding Symptoms of Rare Clotting Factor Deficiencies Common symptoms nosebleeds (epistaxis) easy bruising bleeding in the gut (gastrointestinal hemorrhage) bleeding into joints (hemarthrosis) muscle bleeds bleeding from the umbilical cord stump [wfh.org]

    We report a case of 7 years old male child who presented to us as a diagnosed case of factor 7 deficiency with recurrent epistaxis. References in Article Select the SEEK icon to attempt to find the referenced article. [cogprints.org]

    Deficiency of FX may present similar to any coagulation factor abnormality i.e. epistaxis, hemarthrosis and gastrointestinal blood loss (bleeding ranges from mild to severe) 4. [ispub.com]

Neurologic

  • Intracranial Hemorrhage

    Neonates may show a tendency for intracranial hemorrhage and bleeding from the umbilical stump and the gastrointestinal tract. Till date, there are no known genetic analyses studies that can be conducted for this disease. [symptoma.com]

    Symptoms for patients with severe FX deficiency include excessive umbilical cord bleeding, joint bleeds, intramuscular bleeds, and a high risk of intracranial hemorrhage in the first weeks of life. [hemophilia.org]

    In more severe forms of Factor X deficiency, symptoms may include bleeding into joints and into the brain (intracranial hemorrhage).[1][5] Last updated: 1/22/2019 This table lists symptoms that people with this disease may have. [rarediseases.info.nih.gov]

    Singleton TC, Keane M ; Diagnostic and therapeutic challenges of intracranial hemorrhage in neonates with congenital hemophilia: a case report and review. Ochsner J. 2012 Fall12(3):249-53. Ljung RC ; Intracranial haemorrhage in haemophilia A and B. [patient.info]

    Severely affected individuals have an increased risk of bleeding inside the skull (intracranial hemorrhage), in the lungs (pulmonary hemorrhage), or in the gastrointestinal tract, which can be life-threatening. [ghr.nlm.nih.gov]

  • Excitement

    We are excited to work with BPL to deliver a highly specialized home treatment option for patients with this rare bleeding disorder.” [diplomat.is]

    We are excited to work with BPL to deliver a highly specialized home treatment option for patients with this rare bleeding disorder." [prnewswire.com]

    “We’re very excited to see this work presented, and are eager to continue developing therapies for patients with rare diseases.” About Bio Products Laboratory, Ltd. Bio Products Laboratory, Ltd. [bpl-us.com]

  • Confusion

    Confusion over the therapeutic range for monitoring oral anticoagulant therapy in North America. Thromb Haemost 1988 ; 59 : 129 -132. ↵ Hirsh J, Dalen JE, Deykin D, Poller L. [clinchem.aaccjnls.org]

Urogenital

  • Hematuria

    Patients may experience severe umbilical cord stump bleeding, recurrent epistaxis, soft-tissue hemorrhages, menorrhagia, easy bruising, hematuria, hemarthroses and excessive bleeding during or following surgery or delivery or trauma. [orpha.net]

    In contrast to some other bleeding disorders, spontaneous bleeding into the urine (hematuria), gastrointestinal tract, or skull cavity are not common in factor XI deficiency, although they can occur in severely affected individuals. [icdlist.com]

    […] during or after surgery or injury Other reported symptoms heavy or prolonged menstrual bleeding (menorrhagia) bleeding after circumcision abnormal or prolonged bleeding after childbirth first-trimester miscarriage (spontaneous abortion) blood in urine (hematuria [wfh.org]

    Factor X deficiency commonly causes nosebleeds, easy bruising, bleeding under the skin, bleeding of the gums, blood in the urine (hematuria), and prolonged or excessive bleeding following surgery or trauma. [ghr.nlm.nih.gov]

    Recurrent hematomas, hematuria, and hemarthrosis may also be present quite commonly. Women in the childbearing age may have menorrhagia, while pregnant women suffer from an increased risk of miscarriages, antepartum and postpartum hemorrhage. [symptoma.com]

Workup

Till date, there are no known genetic analyses studies that can be conducted for this disease. However, a high index of suspicion should follow an abnormal clotting profile with prolonged PT (prothrombin time) and APTT (activated partial thromboplastin time). Some hereditary forms of the disease may even have a normal clotting profile.

FX functional activity (FX:C) can be objectively measured using serial dilutions of plasma with low levels of FX. FX levels should be matched with age especially prior to 6 months of age before a patient is labeled as FX-deficient. Neonatal levels reach adult values at about 6 months of age.

Another investigation that is particularly useful is the Russel viper venom (RVV) time. RVV directly activates FX, FV, prothrombin and thrombin and hence, detects FX deficiency easily. FX antigen levels can also be measured using ELISA (enzyme-linked immunosorbent assay) or by certain chromogenic assays. These assays are not used as screening tests because they lack sensitivity in detecting FX-deficient cases.

Treatment

Treatment is generally not required in patients who are carriers of the disease and those who have FX levels > 10% without any significant history of bleeding [15]. Hereditary FX deficiency is a rare disorder with only a handful of cases reported worldwide. As such, adequate research into its treatment protocols is lacking. However, the United Kingdom Haemophilia Centre Doctors’ Organization have released certain guidelines that may serve as a guide for the management of hereditary FX deficiency and other rare coagulation disorders.

According to this guideline, fresh frozen plasma (FFP) or prothrombin complex concentrates (PCC) can be used to replace the deficient factor X in cases of severe bleeding. Mild-moderate forms of hemorrhage are treated by topical and oral antifibrinolytics. An example is aminocaproic acid, used either as a mouthwash (15 ml every 6 hours) or orally at a dose of 50-100 mg/kg. It provides protective benefit in recurrent mouth or nosebleeds, menorrhagia and other bleeding disorders in women. An alternative is tranexamic acid, which is better tolerated. It is taken orally at a dose of 15mg/kg or 1g every 6 hours.

Antifibrinolytics should be used cautiously if treatment with PCC has already commenced in order to prevent thrombosis. In longstanding cases, it is imperative to monitor FX and FIX levels to guide further management.

Prognosis

The prognosis of hereditary factor X deficiency is good in cases that are diagnosed and treated promptly. However, it may have devastating consequences if it is improperly managed. In general, the prognosis depends on the amount of circulating FX, with extremely low levels increasing the risk of hemorrhage profoundly.

Hereditary FX deficiency persists for life and can result in severe debilitation in the quality of life due to the increased tendency for bleeding, seen especially in states of hemodynamic stress. In infants, bleeds in the central nervous system and from umbilical stumps have resulted in death in some cases. Massive hemorrhages post-surgery are also reported in the absence of proper therapy [12] [13].

Etiology

Factor X is a coagulation factor, dependent on vitamin K and its important role in the coagulation cascade cannot be overemphasized. Amongst all inherited coagulation disorders, hereditary factor X deficiency is quite rare with an incidence of 1 in 1 million. It is transmitted in an autosomal recessive fashion and clinically presents in a variety of ways, with heterozygotes being asymptomatic while the homozygotes show a multitude of bleeding manifestations.

The factor X gene is found on the long arm of chromosome 13, in close proximity to the gene for factor VII. This gene is quite similar in structure and chemical composition to the genes encoding for the other vitamin-K-dependent factors, thereby hinting at a common origin. Eight exons are found in this gene, with every exon coding for a specific functional protein domain in the gene product.

A large number of mutations have been described in the factor X gene, some of which include Gly366Ser, Arg347His, Phe31Ser, Gly133Arg, Val196Met, Gly204Arg, Glu51Lys, and Cys364Arg. Some cases have shown mutations in the GLA-domain of factor X, a component of its light chain [2] [3] [4]. A glutamine-to-glycine mutation has also been described at residue 32, affecting the gamma-carboxylation of factor X. Substitutions of serine with proline in exon VIII affect the cleavage site of factor X, thus preventing its activation.

A natural variant of factor X, with a deletion of Asp-185, may only show mild degrees of bleeding even in cases of severe deficiency [5].

Epidemiology

The incidence of hereditary factor X deficiency is extremely low, with only about 50 cases reported worldwide [6]. The homozygous form of this disease occurs in about 1:500,000 – 1,000,000 of the general population, while the subtler heterozygous (carrier) form is far more prevalent with a rate of 1:500 [7] [8]. In countries like Italy and the UK, it is reported to affect about 0.4-0.5% of the general population. In contrast, in countries like Iran where consanguineous relationships are prevalent, it accounts for 1.3% of all hereditary coagulation disorders, with a high prevalence of 1: 200,000 population [9].

Pathophysiology

FX plays a central role in the blood coagulation cascade. FX forms a connection between the extrinsic and intrinsic pathways of coagulation through the “common pathway” that leads to thrombus formation. FX is activated by FIXa and FVIIIa (in the intrinsic pathway) and FVIIa (in the extrinsic pathway). This activated FX then converts prothrombin to thrombin in the presence of FVa, calcium ions, and phospholipids. A deficiency of FX will thus, block the formation of thrombin (and hence, the conversion of fibrinogen to fibrin) and the patient presents with a multitude of bleeding manifestations.

FXa is inactivated by antithrombin; it forms a complex with it that is rapidly cleared from the circulation. FX is produced in the liver with concentrations in the blood reaching 10 ug/ml [11].

Prevention

Hereditary FX deficiency is a condition that lasts lifelong and the cornerstone of prevention is built on prophylactic treatment, education, and counseling. Prophylactic therapy is needed to prevent life-threatening episodes of bleeding, especially in patients with genotypes associated with an increased risk of hemorrhage. Carriers, diagnosed during routine blood tests, need to be counseled on the future risk of hemorrhage, especially in times of hemodynamic stress like surgeries, trauma etc. Pregnant women may need specialized care in hemophilia centers.

Summary

Hereditary factor X (FX) deficiency, also known as inherited factor X deficiency is a rare disease found mostly in communities where consanguinity is prevalent. It affects all age groups and both the sexes. Reported as far back as 1950 during a study conducted on patients who had some hemorrhagic disease, this disorder is also called Stuart and Prower factor deficiency owing to the fact that they were the first patients in whom the disease was first discovered.

It is inherited in an autosomal recessive fashion and manifests as a variety of bleeding disorders ranging from mild mucocutaneous bleeding to severe bleeding leading to exsanguination postoperatively, hemarthrosis and menorrhagia [1]. Newborns can present with severe umbilical stump bleeding and excessive bleeding post circumcision. Intracranial hemorrhage has also been reported, with fatal consequences.

In homozygous patients, the presentation is severe, while heterozygous patients are mostly asymptomatic, only showing symptoms in conditions of severe hemodynamic instability.

The treatment of this disorder is aimed at providing the body with activated vitamin K dependent factors through transfusion of fresh frozen plasma (FFP) or protein cell concentrate (PCC).

Patient Information

Hereditary factor X (FX) deficiency is an inherited bleeding disorder characterized by the deficiency of a coagulation factor named factor X. This deficiency predisposes the individual to an increased risk of bleeding.

It is a rare disease affecting both sexes and may present at any age. The condition is caused by a mutation in the gene responsible for controlling the production of plasma FX. The severity of bleeding is directly proportional to the FX levels in the blood.

Carriers are usually asymptomatic. Patients may present with a variety of bleeding manifestations that include severe bleeds following surgery, recurrent nosebleeds, soft tissue bleeds, excessive menstrual bleeds, blood in the urine, joints etc. It may also present with severe life-threatening bleeding in infancy.

Many are diagnosed based on a positive family history, or when they have abnormal clotting profiles that include elevated prothrombin time (PT) and activated partial thromboplastin time (APTT). Prolonged PT, APTT and Russel viper venom (RVV) times, and low levels of factor FX are the cornerstone for diagnosis.

There is no specific treatment available but prothrombin cell concentrates and fresh frozen plasma may be given to replace factor X directly. Such therapies help to reduce bleeding episodes and decrease the mortality of this disease. The outcome of hereditary FX deficiency is thus, dependent on prompt and early diagnosis and treatment.

References

  1. Mannucci PM, Duga S, Peyvandi F. Recessively inherited coagulation disorders. Blood. 2004;104:1243–1252.
  2. Girolami A, Allemand E, Scandellari R, Lombardi AM, Girolami B. The clinical and laboratory significance of cases of congenital FX deficiency due to defects in the Gla-domain. Hematology. 2009;14(3):177-81.
  3. Isshiki I, Favier R, Moriki T, et al. Genetic analysis of hereditary factor X deficiency in a French patient of Sri Lankan ancestry: in vitro expression study identified Gly366Ser substitution as the molecular basis of the dysfunctional factor X. Blood Coagul Fibrinolysis. 2005;16(1):9-16.
  4. Wang WB, Fu QH, Zhou RF, et al. Molecular characterization of two novel mutations causing factor X deficiency in a Chinese pedigree. Haemophilia. 2005;11(1):31-7.
  5. Lu Q, Yang L, Manithody C, Wang X, Rezaie AR. Molecular basis of the clotting defect in a bleeding patient missing the Asp-185 codon in the factor X gene. Thromb Res. 2014 Nov;134(5):1103-9. doi: 10.1016/j.thromres.2014.08.004.
  6. Roberts HR, Escobar MA. Inherited disorders of prothrombin conversion. In: Colman RW, Marder VJ, Clowes AW, Geroge JN, Goldhaber SZ, eds. Hemostasis and thrombosis — Basic principles and clinical practice. 5th ed. Lippincott Williams & Wilkins; Philadelphia,PA;2006; 923–937.
  7. Peyvandi F, Duga S, Akhavan S, Mannucci PM. Rare coagulation deficiencies. Haemophilia 2002; 8: 308–21.
  8. Graham JB, Barrow EM, Hougie C. Stuart clotting defect. II. Genetic aspects of a “new” hemorrhagic state. J Clin Invest 1956; 36: 497–503.
  9. Karimi M, Yarmohammadi H, Ardeshiri R, Yarmohammadi H. Inherited coagulation disorders in southern Iran. Haemophilia 2002; 8: 740–4.
  10. Pfeiffer RA, Ott R, Gilgenkrantz S, Alexandre P. Deficiency of coagulation factors vii and x associated with deletion of a chromosome 13 (q34). Evidence from two cases with 46,xy,t(13;y)(q11;q34) Hum Genet.1982;62:358–360.
  11. Bajaj SP, Mann KG. Simultaneous purification of bovine prothrombin and factor x. Activation of prothrombin by trypsin-activated factor x. J Biol Chem. 1973;248:7729–7741.
  12. Citak A, Ucsel R, Karabocuoglu M, Unuvar A, Uzel N. A rare cause of intracranial hemorrhage: factor X deficiency. Pediatr Emerg Care. 2001 Oct. 17;(5):349-50.
  13. Young TM, Chitnavis BP, Swallow EB, Arya R, Vadher BD. Intracerebral hemorrhage in an adult due to transient factor X deficiency. J R Soc Med. 2003 Jul. 96; (7):355-6.
  14. Kumar A, Mishra KL, Mishra D. Hereditary coagulation factor x deficiency. Indian Pediatr.2005;42:1240–1242.
  15. Acharya SS, Coughlin A, DiMichele DM, T.N.A.R.B.D.S. Group. Rare Bleeding Disorder Registry: deficiencies of factors II, V, VII, X, XIII, fibrinogen, and dysfibrinogenemias. J Thromb Haemost 2003; 2: 248–56.
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