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PubMed This is a summary of 22 peer-reviewed journal articles Updated
Hematology

Symptoms & Warning Signs of Factor XIII Deficiency

At a Glance

Factor XIII deficiency is a rare bleeding disorder characterized by unstable blood clots. The most distinct sign is delayed bleeding that starts 24 to 48 hours after an injury, once the initial clot breaks down. In newborns, persistent bleeding from the umbilical stump is the hallmark warning sign.

Factor XIII (FXIII) deficiency is known for a very specific pattern of symptoms that sets it apart from more common bleeding disorders. Because FXIII is the “stabilizer” of the blood clot, the most common warning signs are related to clots that form but then fail to hold together [1][2].

The Hallmark: Umbilical Stump Bleeding

For many families, the first sign of Factor XIII deficiency appears shortly after birth. Umbilical cord bleeding is the most characteristic symptom of the severe form of this condition [3][4]. While most babies’ umbilical stumps heal and fall off cleanly, approximately 80% of newborns with FXIII deficiency experience persistent or recurrent bleeding from the navel area [5][6]. This bleeding can be severe and is a major “red flag” that should prompt specialized testing [7].

Understanding “Delayed Bleeding”

One of the most confusing aspects of FXIII deficiency is the timing of the bleeding. In many other disorders, a person starts bleeding immediately after an injury. In FXIII deficiency, the initial stages of clotting work normally, so the bleeding may stop right away [2].

However, because the clot is not “cross-linked” (chemically stapled together), it is weak and easily broken down by the body’s natural enzymes [8][9]. This leads to delayed bleeding, which typically occurs 24 to 48 hours after the original injury or surgery [10][11]. You might think a wound is healing perfectly, only to have it start bleeding fresh red blood a day or two later.

The Most Dangerous Sign: Intracranial Hemorrhage (ICH)

The most serious risk of FXIII deficiency is bleeding inside the brain (intracranial hemorrhage). This can happen spontaneously (without a clear injury) or after a minor bump to the head [5][12].

Warning Signs in Infants:

  • A bulging “soft spot” (fontanelle) on the head [13].
  • Rapidly increasing head size [14].
  • Extreme sleepiness (lethargy) or difficulty waking up [15].
  • Seizures or unusual vomiting [13].

Warning Signs in Children and Adults:

  • A sudden, severe headache [16].
  • Nausea or repeated vomiting.
  • Changes in vision or speech.
  • Sudden weakness in an arm or leg.

Wound Healing and “Cigarette-Paper” Scars

Factor XIII is essential not just for stopping blood, but for repairing tissue [17]. People with this deficiency often experience poor wound healing [7][18]. Wounds may take weeks to close or may heal and then pop back open. Over time, this can lead to a specific type of scarring known as “cigarette-paper” scars—scars that are very thin, pale, and look wrinkled like tissue paper [18].

Other Common Symptoms

  • Soft Tissue and Muscle Bleeds: Deep, painful bruises or lumps (hematomas) in the muscles, often appearing after minor activities [8][19].
  • Joint Bleeding: While less common than in Hemophilia, bleeding into joints can occur and cause pain and swelling [20].
  • Pregnancy Loss: For adult women, untreated FXIII deficiency is strongly linked to a very high risk of miscarriage, as the factor is needed for the placenta to stay attached to the uterus [21][22].

Common questions in this guide

Why does bleeding start again days after an injury?
In Factor XIII deficiency, the initial blood clot forms normally but isn't chemically stabilized. This means the clot is weak and breaks down prematurely, causing bleeding to restart 24 to 48 hours after the original injury or surgery.
What is the first warning sign of Factor XIII deficiency in babies?
The most characteristic sign in newborns is persistent bleeding from the umbilical cord stump. While most stumps heal and fall off cleanly, about 80% of babies with this deficiency experience ongoing bleeding from the navel area.
How can I tell if my infant has bleeding in the brain?
Warning signs of brain bleeding in infants include a bulging soft spot (fontanelle), rapidly increasing head size, extreme sleepiness, seizures, or unusual vomiting. Immediate medical attention is required if these occur.
Does Factor XIII deficiency affect pregnancy?
Yes, untreated Factor XIII deficiency is strongly linked to a high risk of miscarriage. The factor is essential for the placenta to remain properly attached to the uterus during pregnancy.
What do scars look like with Factor XIII deficiency?
Because the factor is needed for tissue repair, wounds may take a long time to close or reopen easily. Healed wounds often leave behind "cigarette-paper" scars, which are very thin, pale, and wrinkled.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.What should I do if my child bumps their head, even if they seem fine at first?
  2. 2.Can you explain how to recognize the early signs of an intracranial hemorrhage in a toddler?
  3. 3.Why did my child's belly button bleed for so long after birth, and could that have been the first sign?
  4. 4.What is the process for managing surgeries or dental work to prevent delayed bleeding?
  5. 5.How can we monitor for internal muscle or joint bleeds that might not be visible from the outside?

Questions For You

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

Related questions

Why Do I Get Cigarette-Paper Scars with FXIII Deficiency?Does Factor XIII Deficiency Cause Permanent Joint Damage?

References

References (22)
  1. 1

    State of the art in factor XIII laboratory assessment.

    Durda MA, Wolberg AS, Kerlin BA

    Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis 2018; (57(6)):700-704 doi:10.1016/j.transci.2018.07.006.

    PMID: 30087086
  2. 2

    Subgaleal Hematoma in a Female With Normal Coagulation Tests.

    Ataei-Azimi S, Bos MHA, Rahimi H, Mansouritorghabeh H

    Case reports in hematology 2025; (2025()):5481806 doi:10.1155/crh/5481806.

    PMID: 40919234
  3. 3

    Delayed and prolonged umbilical stump bleeding in a Caucasian newborn as a presenting feature of factor XIII deficiency.

    Lim DBN, Mangles S, Goturu A

    BMJ case reports 2022; (15(10)) doi:10.1136/bcr-2022-248743.

    PMID: 36207057
  4. 4

    The Role of Different Matrixin Gene Expressions on Cerebral Bleeding among Patients with Deficiency of Coagulation Factor XIII.

    Mao L, Huang Y, Jia W, et al.

    Cellular and molecular biology (Noisy-le-Grand, France) 2022; (68(8)):129-132 doi:10.14715/cmb/2022.68.8.23.

    PMID: 36800823
  5. 5

    Congenital factor XIII deficiency caused by F13A1 gene mutations presenting with intracranial hemorrhage: a case report.

    Wang H, Yang R, Li J

    Frontiers in pediatrics 2025; (13()):1732065 doi:10.3389/fped.2025.1732065.

    PMID: 41488895
  6. 6

    Factor XIII deficiency in south of Tunisia.

    Maaloul I, Medhaffer M, Louhichi N, et al.

    Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis 2017; (28(6)):485-489 doi:10.1097/MBC.0000000000000649.

    PMID: 28704210
  7. 7

    Factor XIII deficiency in the Saudi population, an underestimated bleeding risk. Review article and an illustrative case report with dental complications.

    Aljabry M

    The Saudi dental journal 2023; (35(4)):305-309 doi:10.1016/j.sdentj.2023.03.015.

    PMID: 37251713
  8. 8

    Hyperfibrinolysis secondary to acquired factor XIII deficiency A case report.

    Gao L, Li D, Ding M

    Medicine 2022; (101(29)):e29446 doi:10.1097/MD.0000000000029446.

    PMID: 35866832
  9. 9

    Medical and Surgical Management of Postpartum Hemorrhage in a Woman with Factor XIII Deficiency.

    Cheng M, Nassim J, Angha A, et al.

    Case reports in obstetrics and gynecology 2016; (2016()):7963874 doi:10.1155/2016/7963874.

    PMID: 27635271
  10. 10

    Recurrent Intramuscular Hematoma Revealing Moderate Congenital Factor XIII Deficiency.

    Ben Halima N, Riahi S, Mazlout I, et al.

    Cureus 2025; (17(10)):e95841 doi:10.7759/cureus.95841.

    PMID: 41328102
  11. 11

    Abnormally Prolonged Bleeding After an Arthroscopic Knee Reconstruction Because of an Inherited Factor XIII Deficiency: A Case Report.

    Wattakavanich N, Boonrod A, Wanitpongpun C, Tharakulphan S

    JBJS case connector 2021; (11(4)) doi:10.2106/JBJS.CC.21.00419.

    PMID: 35102034
  12. 12

    Hemorrhagic Shock after Neonatal Circumcision: Severe Congenital Factor XIII Deficiency.

    Cohen EL, Millikan SE, Morocco PC, de Jong JLO

    Case reports in pediatrics 2021; (2021()):5550199 doi:10.1155/2021/5550199.

    PMID: 34007504
  13. 13

    Factor XIII Deficiency: A Rare Cause of Hydrocephalus in Infancy.

    Alali A, Meshal T, Alali Z, et al.

    Clinical case reports 2025; (13(10)):e70962 doi:10.1002/ccr3.70962.

    PMID: 41069757
  14. 14

    Factor XIII deficiency with intracranial haemorrhage.

    Ejaz M, Saleem A, Ali N, Tariq F

    BMJ case reports 2019; (12(8)) doi:10.1136/bcr-2018-228682.

    PMID: 31451452
  15. 15

    Factor XIII deficiency in a neonate presenting as subpial haemorrhage.

    Karthikeyan MG, Ronda P, Sugumaran PC

    SA journal of radiology 2022; (26(1)):2344 doi:10.4102/sajr.v26i1.2344.

    PMID: 35747783
  16. 16

    Acute Occlusion of the Ventriculoperitoneal Shunt Due to Factor XIII Deficiency-related Postoperative Hemorrhage: A Case Report.

    Yamanishi S, Kimura H, Hayashi H, et al.

    NMC case report journal 2021; (8(1)):573-577 doi:10.2176/nmccrj.cr.2020-0330.

    PMID: 35079519
  17. 17

    Congenital Factor XIII Deficiency With the Presence of Inhibitor: A Case Study.

    Karaman S, Akkaya E, Genc S, et al.

    Journal of pediatric hematology/oncology 2021; (43(1)):e99-e102 doi:10.1097/MPH.0000000000001671.

    PMID: 31764516
  18. 18

    The impact of acquired coagulation factor XIII deficiency in traumatic bleeding and wound healing.

    Kleber C, Sablotzki A, Casu S, et al.

    Critical care (London, England) 2022; (26(1)):69 doi:10.1186/s13054-022-03940-2.

    PMID: 35331308
  19. 19

    Bilateral Compartment Syndrome Affecting the Upper Limbs in a Patient With Chronic Myeloid Leukemia.

    Varadhan A, Bagavandoss A, Edmunds CT, Oyibo SO

    Cureus 2024; (16(11)):e74104 doi:10.7759/cureus.74104.

    PMID: 39568494
  20. 20

    Acquired factor XIII deficiency presenting with multiple intracranial hemorrhages and right hip hematoma: A case report.

    Wang L, Zhang N, Liang DC, et al.

    World journal of radiology 2024; (16(9)):439-445 doi:10.4329/wjr.v16.i9.439.

    PMID: 39355391
  21. 21

    Gynecological and obstetric outcome in the French cohort of women with factor XIII deficiency.

    Rugeri L, Martinaud C, Beurrier P, et al.

    Thrombosis research 2020; (191()):22-25 doi:10.1016/j.thromres.2020.04.010.

    PMID: 32360976
  22. 22

    Treatment with Recombinant Factor XIII (Tretten) in a Pregnant Woman with Factor XIII Deficiency.

    Abdel-Samad N

    The American journal of case reports 2017; (18()):436-439 doi:10.12659/ajcr.901502.

    PMID: 28432284

This page describes symptoms of Factor XIII deficiency for educational purposes. If you suspect you or your child has a bleeding disorder, consult a hematologist for proper diagnosis and testing.

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