Factor XIII Deficiency
The affected factor is Factor XIII (C - Factor XIII deficiency). This clinical presentation—delayed umbilical cord separation with bleeding, normal PT, PTT, platelet count and function, but prolonged clot time—is pathognomonic for Factor XIII deficiency 1, 2.
Why Factor XIII Deficiency is the Answer
Factor XIII deficiency is uniquely characterized by normal routine coagulation screening tests (PT, PTT, platelet count) because these tests only measure clot formation time, not clot stability. 1, 3 Factor XIII is responsible for cross-linking fibrin polymers to create mechanically stable clots, a process that occurs after the clot has already formed 2, 4.
Classic Diagnostic Pattern
- Delayed umbilical cord separation (beyond 2-3 weeks) with bleeding from the umbilical stump is the hallmark presentation of Factor XIII deficiency in newborns 1, 2, 5
- All routine coagulation tests remain normal: PT, PTT, thrombin time, fibrinogen, and platelet count and function are unaffected 1, 3
- The only abnormality is prolonged clot time or clot instability, as the clots formed are mechanically weak and dissolve prematurely 1, 4
- Factor XIII activity is not detected by routine coagulation panels because PT and PTT only monitor the first 4% of thrombin production and clot initiation, not the subsequent stabilization phase 1, 6
Why the Other Options Are Incorrect
Factor VIII deficiency (Hemophilia A) would prolong the PTT, not leave it normal, because Factor VIII is part of the intrinsic coagulation pathway 1, 7. The explicitly normal PTT in this case rules out Factor VIII deficiency 1.
Von Willebrand disease would typically show prolonged bleeding time due to impaired platelet adhesion and abnormal platelet function testing, neither of which is present in this case 1, 7. Severe von Willebrand disease can also prolong PTT, which is normal here 1.
Diagnostic Confirmation
Specific ordering of Factor XIII activity assay is necessary for diagnosis, as routine coagulation screening will miss this deficiency entirely 1, 3. The clot solubility test (5M urea or 2% acetic acid) can be used as a screening test, showing abnormal clot dissolution at Factor XIII levels below 9-18% 4, 3.
Laboratory Approach
- Clot solubility tests become abnormal when Factor XIII activity falls below 9% (Ca-urea) or 18% (thrombin-acetic acid) 4
- Thromboelastography (TEG) shows characteristic findings: normal reaction time (R), prolonged k time, low maximum amplitude (MA), and increased clot lysis (Lys60) 4
- TEG with streptokinase addition is more sensitive than solubility tests, detecting abnormalities at Factor XIII levels below 40% 4
- Immunoturbidimetric assay for plasma Factor XIII-A subunit antigen provides definitive diagnosis 4, 3
Clinical Significance and Management
The incidence of intracranial hemorrhage in untreated Factor XIII deficiency approaches 30%, making early diagnosis and prophylaxis critical 2. Delayed diagnosis results in continued bleeding symptoms including soft tissue hematomas, intracranial bleeds, and reproductive complications 2, 5.
Treatment Protocol
- Prophylactic Factor XIII concentrate should be administered at 25-35 IU/kg every 4-6 weeks, targeting trough levels of 10-20 IU/dL 2
- Factor XIII activity of around 5 IU/dL may suffice to protect from bleeds, though trough targets should be set higher (10-20 IU/dL) due to inaccuracy of low-level measurements 2
- For acute bleeding, platelet transfusion may provide additional benefit as platelets contain Factor XIII providing cellular support 2
- Tranexamic acid serves as adjunctive therapy for mucosal bleeding 1
Critical Pitfall to Avoid
Do not assume normal PT, PTT, and platelet studies exclude a bleeding disorder in a newborn with umbilical stump bleeding. Factor XIII deficiency will be missed entirely if clinicians rely solely on routine coagulation screening 1, 8, 3. Umbilical hemorrhage in the presence of normal routine blood investigations should immediately prompt specific Factor XIII testing 8, 5.
Genetic Considerations
Factor XIII deficiency is typically inherited as an autosomal recessive disorder, and genetic counseling is recommended 1, 5. Molecular analysis can identify specific mutations such as Glu102Lys and Ser295Arg in the Factor XIII-A gene, which result in unstable Factor XIII molecules unable to fold correctly 5.