Factor XII is a plasma protein that is involved in the initiation of the intrinsic coagulation cascade. In the majority of cases, patients remain asymptomatic, with the only pathologic finding being the prolonged activated partial thromboplastin time (aPTT) detected via laboratory testing [1] [2] [3].

Paradoxically, there is an absence of the hemorrhagic events usually associated with the deficiency of a coagulation factor. Moreover, propensity toward thrombotic events have been reported in patients with factor XII deficiency [4] [5]. Even if clear pathophysiologic association has not yet been defined, studies have delineated the potential correlation between factor XII deficiency and the development of deep venous thrombosis (DVT) and other acquired thrombotic disorders. Unexplained miscarriages have also been observed in women affected by the deficiency [6]. It should also be noted that the levels of circulating factor XII do not clearly correlate with the symptoms experienced by the patient or the severity of the disease. Furthermore, the concentration of factor XII in the serum of a patient varies, depending on each case.

• Hemophilia A

  Her brother also had hemophilia A, and her mother and grandmother seem to be hemophiliac carriers. [ncbi.nlm.nih.gov]

  hemophilia A with a deficiency in factor VIII or antihemophilic globulin, hemophilia B with a deficiency in factor IX (Christmas disease), and hemophilia C with a deficiency in factor XI. [en.wikipedia.org]

  Hemophilia B. National Hemophilia Foundation website. https://www.hemophilia.org/Bleeding-Disorders/Types-of-Bleeding-Disorders/Hemophilia-B. Accessed January 26, 2017. [bleedingdisorders.com]

  Hemophilia Program Eastern Health, Janeway Site Room 2J755 300 Prince Philip Drive St. John’s, Newfoundland A1B 3V6 Clinic directors Dr. Lynette Bowes Dr. Paul Moorehead Dr. Jacqueline Costello Dr. [hemophilia.ca]

  However, the more I thought about it, Iwondered why hemophilia A and hemophilia B are so severe since they are involved in the intrinsic pathway. [fritsmafactor.com]

• Asymptomatic

  A sister of the proposita showed the same pattern but remained asymptomatic. [ncbi.nlm.nih.gov]

  Search Search for a rare disease Congenital factor XII deficiency Disease definition A rare, autosomal recessive systemic dysfunction of the hemostatic pathway, that is due to a defect in the coagulation factor XII (FXII or Hageman factor), and is either asymptomatic [orpha.net]

  In the majority of cases, patients remain asymptomatic, with the only pathologic finding being the prolonged activated partial thromboplastin time (aPTT) detected via laboratory testing. [symptoma.com]

  FXII appears to be not essential for blood clotting, as individuals with this condition are usually asymptomatic and form blood clots in vivo. [en.wikipedia.org]

• Swelling

  (A) The boy had swelling of the whole scalp and proptosis and afferent pupillary defects in both eyes. (B) On day 7 after orbital decompression surgery, the proptosis and scalp swelling had disappeared completely. [healio.com]

  Common characteristics include bruising and soft tissue bleeding, which can lead to pseudotumors (large swellings due to accumulation of blood). There is a high incidence of head bleeding with little or no injury in severely affected individuals. [nm.org]

  Hereditary angioedema is an autosomal dominant disorder characterized by episodic local swelling involving subcutaneous or submucous tissue of the upper respiratory and gastrointestinal tracts, face, extremities, and genitalia. [uniprot.org]

• Pallor

  Author information 1 Department of Pediatrics, Gifu Prefectural General Medical Center, 4-6-1 Noishiki, Gifu 500-8717, Japan. [email protected] Abstract A 9-year-old boy with pallor and macrohematuria showed hemolytic anemia, thrombocytopenia and renal [ncbi.nlm.nih.gov]

• Diarrhea

  There was no history of diarrhea and the stool culture was negative. A diagnosis of atypical hemolytic uremic syndrome (HUS) was confirmed; however, the cause of the prolonged activated partial thromboplastin time (APTT) was unknown. [ncbi.nlm.nih.gov]

• Thrombosis

  The 10 subjects with normal FXII values (498.2 patient-years) remained thrombosis-free. One superficial vein thrombosis occurred in an unclassifiable woman. [ncbi.nlm.nih.gov]

• Hypertension

  He was not hypertensive or diabetic, of normal weight and a non-smoker, and without any cardiovascular disease. There was no family or personal history of venous or arterial thrombosis. [bjo.bmj.com]

• Strabismus

  J Pediatr Ophthalmol Strabismus 2004;41:367–368. The authors are from the Department of Ophthalmology, Seoul National University College of Medicine, Seoul, Korea. Dr. [healio.com]

  DRUS is observed in 0.1% of the general population, accounts for 1% to 5% of all strabismus. DRUS- 1 maps to chromosome 8q13. DRUS-2 is caused by mutation on chromosome 2q31. It has an AD inheritance pattern [ 24, 25 ]. [omicsonline.org]

• Diplopia

  By that time his diplopia had completely resolved and he had full abduction in both eyes. [bjo.bmj.com]

• Suggestibility

  The FXII activity and antigen level were both under 10%, suggesting a cross-reacting material-negative FXII deficiency. [ncbi.nlm.nih.gov]

• Headache

  Immediately after the trauma, he had a headache with whole scalp swelling. A computed tomography (CT) scan of the brain was performed, and he was diagnosed as having a subgaleal hemorrhage of the whole scalp, without orbital extension. [healio.com]

  On examination he was found to have bilateral sixth nerve palsies without any associated headache or papilloedema. Detailed magnetic resonance imaging with contrast and lumbar puncture opening pressure and investigation was normal. [bjo.bmj.com]

• Intracranial Hemorrhage

  A fourth child died with intracranial hemorrhage. In addition to the above deficiency, two of the three propositi and two siblings were mildly deficient in factor XII. [pediatrics.aappublications.org]

Individuals affected by factor XII deficiency are primarily asymptomatic. A routine blood test or one carried out due to unrelated symptoms and conditions will reveal pathologic results that lead to the diagnosis of the disorder.

Finding consistent with factor XII deficiency include a prolonged activated partial thromboplastin time which indicates coagulation impairment of the intrinsic coagulation pathway. The normal aPTT values are between 30 and 50 seconds; a prolonged time required for blood clots to form indicates various clotting pathologies, one of which is factor XII deficiency. Serum prothrombin time (PT), which is used to evaluate the extrinsic pathway of coagulation, is within normal reference values in factor XII deficiency.

Differential diagnosis includes antiphospholipid syndrome [7]. The definitive diagnosis of factor XII deficiency is established with a specific factor XII assay, that can reliably detect the activity of this coagulation factor.

Repeated transesophageal echocardiographic (TEE) studies revealed an involution of the intracardial thrombus within weeks of subsequent anticoagulatory treatment. [ncbi.nlm.nih.gov]

The material is in no way intended to replace professional medical care by a qualified specialist and should not be used as a basis for diagnosis or treatment. [orpha.net]

The outcome is expected to be good without treatment. There are usually no complications. The health care provider usually discovers this condition when running other lab tests. This is an inherited disorder. There is no known way to prevent it. [nlm.nih.gov]

Tests may include: Factor XII assay to measure the activity of factor XII Partial thromboplastin time ( PTT ) to check how long it takes for blood to clot Mixing study, a special PTT test to confirm factor XII deficiency Treatment Treatment is usually [ufhealth.org]

Treatment No treatment is required. © 2019 National Hemophilia Foundation All rights reserved. [hemophilia.org]

Outlook (Prognosis) The outcome is expected to be good without treatment. Possible Complications There are usually no complications. [ufhealth.org]

Other-Factor-Deficiencies/Factor-XII National Organization for Rare Disorders -- rarediseases.org/rare-diseases/factor-xii-deficiency NIH Genetic and Rare Diseases Information Center -- rarediseases.info.nih.gov/diseases/6558/factor-xii-deficiency Outlook (Prognosis [mountsinai.org]

Two hundred and forty-one consecutive Japanese women with a history of two or more recurrent miscarriages were prospectively assessed for their etiology by conventional screening methods. [ncbi.nlm.nih.gov]

This practical text covers disorders of thrombosis and hemostasis in a logical and sequential manner: etiology, pathophysiology, clinical and laboratory diagnosis, and management. [books.google.com]

[…] activates factor XI which eventually leads to thrombin generation via the intrinsic pathway, and also activates C1 esterase, thereby activating the complement system Images hosted on other servers: Coagulation cascade Mechanisms of factor XII activation Etiology [pathologyoutlines.com]

According to a multivariate analysis on the etiology of thrombophilia by Yamada et al., clotting factor XII deficiency has been found in 4.2% of women affected by RPL [ 20 ]. [translational-medicine.biomedcentral.com]

[…] trait and is not associated with a bleeding diathesis It is typically discovered in individuals with an isolated prolonged PTT Homozygous individuals have undetectable factor XII levels Heterozygous individuals have factor XII levels between 20 - 60% Epidemiology [pathologyoutlines.com]

This practical text covers disorders of thrombosis and hemostasis in a logical and sequential manner: etiology, pathophysiology, clinical and laboratory diagnosis, and management. [books.google.com]

Even if clear pathophysiologic association has not yet been defined, studies have delineated the potential correlation between factor XII deficiency and the development of deep venous thrombosis (DVT) and other acquired thrombotic disorders. [symptoma.com]

[…] reference that summarizes the association of factor XII deficiency with myocardial infarction, coronary artery disease, miscarriage, and coronary stent thrombosis, see Colman RW: Contact activation (kallikrein-kinin) pathway: Multiple physiologic and pathophysiologic [fritsmafactor.com]

Heterozygous individuals have factor XII levels between 20 - 60% Epidemiology Actual prevalence difficult to determine since individuals are asymptomatic One study of 300 healthy blood donors reported a prevalence of 2.3% ( Thromb Haemost 1994;71:68 ) Pathophysiology [pathologyoutlines.com]

Caldwell et al., Coagulation disorders and hemostasis in liver disease: pathophysiology and critical assessment of current management. Hepatology. 44, 1039 (2006) M.L. [charite.de]

Prevention This is an inherited disorder. There is no known way to prevent it. Images References Gailani D, Neff AT. Rare coagulation factor deficiencies. In: Hoffman R, Benz EJ Jr, Silberstein LE, Heslop HE, Weitz JI, Anastasi J, eds. [ufhealth.org]

Prevention This is an inherited disorder. There is no known way to prevent it. References Gailani D, Wheeler AP, Neff AT. Rare coagulation factor deficiencies. In: Hoffman R, Benz EJ, Silberstein LE, et al, eds. [mountsinai.org]

There is no known way to prevent it. F12 deficiency; Hageman factor deficiency; Hageman trait; HAF deficiency Gailani D, Wheeler AP, Neff AT. Rare coagulation factor deficiencies. In: Hoffman R, Benz EJ, Silberstein LE, et al, eds. [nlm.nih.gov]

In human plasma supplemented with silica, DNA or collagen to induce contact activation, an antibody to the FXIIa active site was more effective at preventing thrombin generation than an antibody to the α-kallikrein active site. [ncbi.nlm.nih.gov]

There is no known way to prevent it. F12 deficiency; Hageman factor deficiency; Hageman trait; HAF deficiency Gailani D, Neff AT. Rare coagulation factor deficiencies. In: Hoffman R, Benz EJ Jr, Silberstein LE, Heslop HE, Weitz JI, Anastasi J, eds. [medlineplus.gov]

1. Mariano ML, Yadira P, Ana A, Manuel L, Lopez Galvez JJ. Coagulation Factor XII Congenital Deficiency in Women with Recurrent Miscarriage. International Journal of Clinical Medicine. 2011;2:469-472.
2. Stavrou E, Schmaier AH. Factor XII: what does it contribute to our understanding of the physiology and pathophysiology of hemostasis & thrombosis. Thromb Res. 2010;125:210-215.
3. Wagenman BL, Townsend KT, Mathew P, Crookston KP. The laboratory approach to inherited and acquired coagulation factor deficiencies. Clin Lab Med. 2009;29(2):229-252.
4. Rygał P, Kuc A. Perioperative management of cardiac surgery patients with factor XII deficiency - two case reports. Anaesthesiol Intensive Ther. 2012;44(4):217-220.
5. Ganguli P, Rigvardhan and Kotwal, J. Thrombosis: Presentation of a Factor XII Deficiency in 10 Months Old Child—A Rare Case. International Journal of Advances in Case Reports. 2015;2:708-710.
6. Ozgu-Erdinc AS, Togrul C, Aktulay A, Buyukkagnici U, Yapar Eyi EG, Erkaya S. Factor XII (Hageman) levels in women with recurrent pregnancy loss. J Pregnancy. 2014;2014:459192.
7. Della Valle P, Crippa L, Garlando AM, et al. Interference of lupus anticoagulants in prothrombin time assays: implications for selection of adequate methods to optimize the management of thrombosis in the antiphospholipid-antibody syndrome. Haematologica. 1999;84(12):1065–1074.