We present a comprehensive review of all acquired FXIII deficiency cases reported globally in English, with focus on clinical presentation, diagnostic assays, treatment and prognosis. [ncbi.nlm.nih.gov]

A 72-year-old woman presented with symptoms of major unprovoked bleeding but routine coagulation screening tests and platelet count were normal. [abdn.pure.elsevier.com]

• Pain

  A 48-year-old man was referred because of right hip pain due to a hematoma. Laboratory findings showed that routine coagulation tests were normal, while FXIII activity was slightly low (52.4 %). [ncbi.nlm.nih.gov]

  He had no loin pain, bowel or urinary symptoms. He had no fever, joint pain or oral ulcers. Blood pressure was 115/75 mmHg and pulse rate was 76/min. Examination of abdomen demonstrated old incisional hernia and right lower quadrant tenderness. [openaccessjournals.com]

  […] in the extremities, injection site pain, and increase in fibrin D dimer levels. [drugbank.ca]

  Factor XIII deficiency can also lead to spontaneous bleeding into joints or muscles, causing pain and disability. Affected women tend to have menorrhagia and may have spontaneous abortions. [ivami.com]

• Fever

  A 29-year-old male patient initially presented to emergency department with right mandibular mass of 2 months duration associated with intermittent fever. Laboratory workup revealed very high lactate dehydrogenase at 2,026.0 U/L. [thejh.org]

  He had no fever, joint pain or oral ulcers. Blood pressure was 115/75 mmHg and pulse rate was 76/min. Examination of abdomen demonstrated old incisional hernia and right lower quadrant tenderness. [openaccessjournals.com]

  Of the 20 cases reported, 1 involved a case of bacterial pharyngitis with symptoms of cough, fever, and throat swelling; the remaining 19 cases all involved viral infections. [karger.com]

• Fishing

  Fluorescent in situ hybridization (FISH) analysis revealed an abnormal hybridization signal pattern for CDKN2A probe, indicating biallelic (homozygous) deletion of the short arm of chromosome 9 (9p) in 94% of the cells analyzed. [thejh.org]

• Lymphadenopathy

  Although most of reported cases represent transformation of follicular lymphoma, our patient’s young age, acute onset and absent lymphadenopathies all support de novo ALL. [thejh.org]

• Intermittent Fever

  A 29-year-old male patient initially presented to emergency department with right mandibular mass of 2 months duration associated with intermittent fever. Laboratory workup revealed very high lactate dehydrogenase at 2,026.0 U/L. [thejh.org]

• Aspiration

  Bone marrow (BM) aspirate revealed infiltration with many small sized blasts of very high nucleocytoplasmic ratio, finely dispersed nuclear chromatin and prominent nucleoli. [thejh.org]

  Needle aspiration of the mass was performed, and bloody fluid was obtained. The bacterial culture was negative. A diagnosis of intra-pelvic hematoma was made. However, it was unclear why the plasma factor XIII activity level had decreased. [journals.plos.org]

• Hypertension

  Página 302 - Groszmann RJ, Atterbury CE: The pathophysiology of portal hypertension: a basis for classification. Semin Liver Dis 1982; 2:177. ‎ [books.google.es]

  22] The clotting factors themselves are also synthesized by the liver, so there is a gross deficiency of them in liver diseases. [23] [24] Even the synthesized ones are also functionally subnormal. [24] [25] Some liver pathologies like hepatic portal hypertension [explainmedicine.com]

  Her past medical history revealed mild hypertension, minor obstructive sleep apnea, and dyspnea on exertion without angina. She had a smoking history of 20 packyears. Her hypertension was treated with metoprolol and lisinopril. [anesthesiology.pubs.asahq.org]

  […] alternative causes for the TEE (table 1 ), such as concomitant treatment with other coagulation factors (in 3 cases, including plasma, cryoprecipitate, and/or whole blood) or relevant medical history and concomitant diseases (in all cases, including migraine, hypertension [karger.com]

• Liver Dysfunction

  Unrelated to inhibitors, mild acquired decreases in factor XIII can occur with a variety of conditions, such as liver dysfunction, Crohn’s disease, ulcerative colitis, disseminated intravascular coagulation (DIC), surgery, Henoch Schoenlein purpura, myeloproliferative [clinicaladvisor.com]

  dysfunction Information from the National Library of Medicine To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor. [clinicaltrials.gov]

• Ulcer

  Unrelated to inhibitors, mild acquired decreases in factor XIII can occur with a variety of conditions, such as liver dysfunction, Crohn’s disease, ulcerative colitis, disseminated intravascular coagulation (DIC), surgery, Henoch Schoenlein purpura, myeloproliferative [clinicaladvisor.com]

  […] certain drugs, including isoniazid, penicillin, and phenytoin. 6 Factor XIII levels can also become decreased in individuals with disseminated intravascular coagulation, severe liver disease, acute leukemia, Henoch-Schönlein purpura, Crohn's disease, or ulcerative [beta.labcorp.com]

  Multiple ulcers in the small and large intestines occurred during tocilizumab therapy for rheumatoid arthritis. Endoscopy. 2011;43(1):70–2. PubMed CrossRef Google Scholar 10. 11. Birnbaum J, Klotz E, Spies CD, Hein OV, Mallin K, Kawka R, et al. [link.springer.com]

  Treatment of patients bleeding from the small bowel in Henoch-Schölein purpura and from large bowel in ulcerative colitis with FXIII concentrate has been reported to be effective in controlling the bleeding. (34). [f13-database.de]

  Acquired decreases in factor XIII can arise in liver disease (decreased hepatic synthesis), disseminated intravascular coagulation (DIC), certain inflammatory diseases (Crohn, ulcerative colitis, Henoch-Schönlein purpura), leukemia, myelodysplasia, and [mghlabtest.partners.org]

• Short Arm

  Fluorescent in situ hybridization (FISH) analysis revealed an abnormal hybridization signal pattern for CDKN2A probe, indicating biallelic (homozygous) deletion of the short arm of chromosome 9 (9p) in 94% of the cells analyzed. [thejh.org]

  This process is due to mutations in the gene F13A1, located on the short arm of chromosome 6 (6p25.3-p24.3) and, to a lesser extent, in the F13B gene, located on the long arm of chromosome 1 (1q31- q32.1). [ivami.com]

  The F13A gene maps to the short arm of chromosome 6 (p24-25) and spans >160 kb of genomic DNA. It consists of 15 exons encoding a mature protein of 731 amino acids (9,10). [f13-database.de]

• Hip Pain

  A 48-year-old man was referred because of right hip pain due to a hematoma. Laboratory findings showed that routine coagulation tests were normal, while FXIII activity was slightly low (52.4 %). [ncbi.nlm.nih.gov]

  He was admitted again on 4 th July 2016 for two days history of right lower quadrant and right hip pain. It was increasing in severity and exacerbated by right hip flexion. There was no history of recent trauma. [openaccessjournals.com]

• Suggestibility

  The time course of recovery suggests that tocilizumab might have inhibited FXIII production. To our knowledge, this is the first report of acquired factor XIII deficiency associated with administering of tocilizumab. [ncbi.nlm.nih.gov]

  Our data suggest the presence of inhibitor-induced clearance of FXIII from plasma. [abdn.pure.elsevier.com]

  Indications for Testing Patients should be evaluated if they have abnormal bleeding history suggestive of an inherited blood coagulation factor deficiency, with or without abnormal PT or PTT, after exclusion of the most common deficiencies (eg, hemophilia [arupconsult.com]

• Epistaxis

  […] problem: defective vWF clinically moderate disease epistaxis and bruising lead to early diagnosis treat with vWF concentrate rare autosomal recessive problem: complete absence of VWF clinically severe disease epistaxis, bruising allow for early diagnosis [quizlet.com]

  See Bleeding Symptoms of Rare Clotting Factor Deficiencies Common symptoms nosebleeds (epistaxis) easy bruising heavy or prolonged menstrual bleeding (menorrhagia) bleeding in the mouth, particularly after dental surgery or tooth extraction bleeding in [wfh.org]

  Other features included haematoma formation, easy bruising, post-traumatic bleeding, delayed wound healing, gastrointestinal bleeding and epistaxis. One child presented with intracerebral bleed. [jpma.org.pk]

  […] chromosome 1 Clinical features Variable bleeding tendency, from mild to severe depending on factor levels Umbilical cord stump bleeding, intracranial hemorrhage, soft tissue hematoma, bleeding after circumcision, gastrointestinal bleeding, gingival bleeding, epistaxis [pathologyoutlines.com]

  Los signos típicos incluyen: epistaxis, menorragia, hemorragias en la cavidad bucal, sangrado de las mucosas, sangrado en los tejidos blandos, hemartrosis, fácil aparición de moratones y sangrado prolongado después de una extracción dental, trauma o cirugía [femexer.org]

• Intracranial Hemorrhage

  A 68-year-old man presented with intracranial hemorrhage in the right frontal lobe, which rapidly increased the day after admission. We performed hematoma removal with a biopsy of the cortex around the hematoma. [ncbi.nlm.nih.gov]

  Prophylactic therapy with FXIII concentrate should be indicated to prevent recurrent bleedings such as intracranial hemorrhage. Prognosis Intracranial hemorrhage can be life threatening, but prognosis is favorable if adequate treatment is provided. [orpha.net]

  Serious bleeding events such as intracranial hemorrhage may be heralded by less serious bleeding symptoms. [pediatrics.aappublications.org]

  A factor XIII polymorphism (Val34Leu), present in nearly half of the population, is suspected to protect against deep venous thrombosis and is somewhat more frequent in patients with intracranial hemorrhage. 3,4 Factor XIII has a long half-life of 10- [mghlabtest.partners.org]

  hemorrhage, soft tissue hematoma, bleeding after circumcision, gastrointestinal bleeding, gingival bleeding, epistaxis, hematuria, surgical site bleeding, menorrhagia, joint bleeding, delayed healing, spontaneous abortion, recurrent miscarriage Plasma [pathologyoutlines.com]

• Stroke

  Página 222 - CAIRNS JA, CONNOLLY SJ: Nonrheumatic atrial fibrillation: risk of stroke and role of antithrombotic therapy. Circulation 1991; 84: 469-481. ‎ [books.google.es]

  Catto AJ, Kohler HP, Bannan S, et al, "Factor XIII Val 34 Leu: A Novel Association With Primary Intracerebral Hemorrhage," Stroke, 1998, 29(4):813-6. 5. Standen G, Birchall J, Morse C, et al, "A Large Bruise," Lancet, 1999, 353(9168):1934. 6. [mghlabtest.partners.org]

  A statement for healthcare professionals from the American Heart Association, the European Resuscitation Council, the Heart and Stroke Foundation of Canada, the Australian Resuscitation Council, and the Resuscitation Councils of Southern Africa. [genecelltissue.com]

Laboratory workup revealed very high lactate dehydrogenase at 2,026.0 U/L. Peripheral blood revealed pancytopenia with many circulating blasts (about 77%). [thejh.org]

Available online at http://emedicine.medscape.com/article/209742-workup. Accessed August 2016. Mir, M.A. (Updated 2016 May 12). Nonplatelet hemostatic disorders. Medscape. Available online at http://emedicine.medscape.com/article/210467-overview. [labtestsonline.org]

On POD 4, an extensive coagulation workup demonstrated a severe Factor VIII deficiency (4%) as the most significant pathologic value ( table 1 ). [anesthesiology.pubs.asahq.org]

• Colitis

  Unrelated to inhibitors, mild acquired decreases in factor XIII can occur with a variety of conditions, such as liver dysfunction, Crohn’s disease, ulcerative colitis, disseminated intravascular coagulation (DIC), surgery, Henoch Schoenlein purpura, myeloproliferative [clinicaladvisor.com]

  […] including isoniazid, penicillin, and phenytoin. 6 Factor XIII levels can also become decreased in individuals with disseminated intravascular coagulation, severe liver disease, acute leukemia, Henoch-Schönlein purpura, Crohn's disease, or ulcerative colitis [beta.labcorp.com]

  Treatment of patients bleeding from the small bowel in Henoch-Schölein purpura and from large bowel in ulcerative colitis with FXIII concentrate has been reported to be effective in controlling the bleeding. (34). [f13-database.de]

  Acquired decreases in factor XIII can arise in liver disease (decreased hepatic synthesis), disseminated intravascular coagulation (DIC), certain inflammatory diseases (Crohn, ulcerative colitis, Henoch-Schönlein purpura), leukemia, myelodysplasia, and [mghlabtest.partners.org]

  Lorenz R, Born P, Olbert P, Classen M: Factor XIII substitution in ulcerative colitis. Lancet 1995;345:449-450. [karger.com]

• Multiple Ulcerations

  Multiple ulcers in the small and large intestines occurred during tocilizumab therapy for rheumatoid arthritis. Endoscopy. 2011;43(1):70–2. PubMed CrossRef Google Scholar 10. 11. Birnbaum J, Klotz E, Spies CD, Hein OV, Mallin K, Kawka R, et al. [link.springer.com]

[…] and during treatment with tocilizumab. [journals.plos.org]

It is also used for the treatment of established CMV infection (eg, CMV pneumonia, renal parenchymal infection) in association with virucidal treatment. [blood.gov.au]

Bleeding There are different types of treatments that can be used to control bleeding, depending on the seriousness of the bleeding episode. Factor VIII replacement is not the recommended treatment for acquired hemophilia. [rarebleedingdisorders.com]

Recently, we experienced a case of hemorrhagic-acquired factor XIII deficiency that occurred during treatment with the IL-6 inhibitor tocilizumab for rheumatoid arthritis. A 48-year-old man was referred because of right hip pain due to a hematoma. [ncbi.nlm.nih.gov]

We present a comprehensive review of all acquired FXIII deficiency cases reported globally in English, with focus on clinical presentation, diagnostic assays, treatment and prognosis. [ncbi.nlm.nih.gov]

The impact of such therapy on patient prognosis is incompletely known. No Reference information available - sign in for access. No Citation information available - sign in for access. No Supplementary Data. No Article Media No Metrics [ingentaconnect.com]

Prognosis Intracranial hemorrhage can be life threatening, but prognosis is favorable if adequate treatment is provided. The documents contained in this web site are presented for information purposes only. [orpha.net]

[…] mixing test using patient plasma and normal pooled plasma is usually performed to rule out the presence of an inhibitor Confirmatory testing uses a quantitative factor XIII activity assay Prognostic factors Although there is a life-long risk of bleeding, prognosis [pathologyoutlines.com]

Página 330 - Intestinal infections in patients with the acquired immunodeficiency syndrome (AIDS): etiology and response to therapy. ‎ [books.google.es]

Etiology Congenital FXIII deficiency is usually caused by mutations in the F13A1 gene (6p24.2-p23) encoding the catalytic A subunit, but mutations have also been found in the F13B gene (1q31-q32.1) encoding the B subunit. [orpha.net]

[…] final step in the coagulation cascade by cross-linking fibrin (in the presence of calcium) Deficiency is due to a defect in either the A gene (type 2) or B gene (type 1) Diagrams / tables Images hosted on other servers: Diagram of factor XIII activation Etiology [pathologyoutlines.com]

Numerous factors can contribute to its etiology. Among these, both inherited and acquired disorders of coagulation and/or thrombocyte function need to be taken into account. 1,2 Acquired hemophilia can be caused by antibodies to coagulation factors. [anesthesiology.pubs.asahq.org]

Summary Epidemiology Prevalence of homozygous forms is estimated at around 1/2,000,000. Both sexes are equally affected. Clinical description Congenital FXIII deficiency can manifest at any age, but diagnosis is often made during infancy. [orpha.net]

[…] bowel disease, leukemia, disseminated intravascular coagulation, Henoch-Schonlein purpura, systemic lupus erythematosus and exposure to certain drugs (phenytoin, isoniazid, valproate) Terminology Factor XIII is also known as fibrin stabilizing factor Epidemiology [pathologyoutlines.com]

Val34Leu polymorphism of plasma factor XIII: biochemistry and epidemiology in familial thrombophilia. Blood 2000 ; 96 : 2479 -2486. ↵. National Committee for Clinical Laboratory Standards. [clinchem.aaccjnls.org]

Página 302 - Groszmann RJ, Atterbury CE: The pathophysiology of portal hypertension: a basis for classification. Semin Liver Dis 1982; 2:177. ‎ [books.google.es]

Although the inhibitor against FXIII has recently been focused as the cause of haemorrhagic acquired FXIII deficiency, the pathophysiology of inhibitor-negative cases could also be involved. [journals.lww.com]

[…] factor Epidemiology Estimated at 1 in 2 to 5 million births More frequent in regions where consanguineous marriages are more common Sites Skin and mucosa, joints, soft tissue, gastrointestinal tract, genitourinary tract, CNS (see clinical features below) Pathophysiology [pathologyoutlines.com]

The beneficial effect of the absence of cross-linked fibrin on pathophysiologic processes was proven in an animal model of widespread thrombosis. [emedicine.medscape.com]

[…] g002 The plasma factor XIII activity level is relative to the plasma factor XIII quantitative concentration in RA patients treated with biologics Subsequently, we measured the plasma factor XIII quantitative concentrations in order to investigate the pathophysiological [journals.plos.org]

In addition, Hepatitis B immunoglobulin helps prevent hepatitis B infection in infants born to mothers with hepatitis B. [blood.gov.au]

Página 302 - Lee GC-Y, et al: Prevention of perinatally transmitted hepatitis B virus infection with hepatitis B immune globulin and/or HB vaccine, in Vyas GN, Dienstag JL, Hoofnagle JH (eds): Viral Hepatitis and Liver Disease. ‎ [books.google.es]

[…] miscarriage, maintain factor XIII levels > 10% in early gestation and > 30% at time of delivery to prevent significant bleeds Differential diagnosis Acquired factor XIII deficiency Back to top [pathologyoutlines.com]

A loss of activity of this protein weakens blood clots, preventing clots stop blood loss effectively. [ivami.com]

Supplementation of analgesia by regional anesthesia was avoided to prevent spinal hematoma. After standard anesthesia induction, size three Proseal laryngeal mask airway was inserted smoothly. [joacp.org]