|Year : 2023 | Volume
| Issue : 3 | Page : 179-183
Isolated scalp hematoma: An unusual presentation of congenital afibrinogenemia
Arnab Ghorui, Chandra Mohan Kumar, Amrita Banerjee
Department of Pediatrics, All India Institute of Medical Sciences, Patna, Bihar, India
|Date of Submission||22-Apr-2023|
|Date of Decision||18-Jun-2023|
|Date of Acceptance||05-Jul-2023|
|Date of Web Publication||14-Aug-2023|
Dr. Arnab Ghorui
Department of Pediatrics, All India Institute of Medical Sciences, Patna, Bihar
Source of Support: None, Conflict of Interest: None
Background: Congenital fibrinogen disorder is a rare autosomal recessive blood coagulation disorder, where majority of patients present with bleeding, whereas a few may paradoxically develop thrombosis. While many of the affected children have prolonged umbilical cord bleeding during the neonatal period, manifestations may go unnoticed till adolescence. We describe such a child with congenital afibrinogenemia Clinical Description: A 12-year-old boy presented with painless diffuse scalp swelling for 2 weeks without any antecedent history of trauma, hemarthrosis, muscle hematoma, or any skin bleed, except a history of prolonged bleeding post trauma since toddler age. Examination revealed diffuse, boggy, nonpulsatile swelling over the entire scalp, more prominent on the right side, without any focal neurological deficit. A noncontrast computed tomography head showed a scalp hematoma without any intracranial bleeding. Blood investigations revealed extremely elevated prothrombin time (PT) and activated partial thromboplastin time (aPTT) with normal platelet counts and normal platelet morphology on peripheral smear. A detailed coagulation work-up revealed an extremely high thrombin time and an almost undetectable Factor I (fibrinogen) level. Genetic analysis revealed a homozygous single-base pair deletion in exon 5 of the fibrinogen gene of alpha chain, thus confirming the diagnosis of congenital afibrinogenemia. Management: The child was managed with multiple fresh frozen plasma transfusions and serial PT/aPTT monitoring. Once PT and aPTT were normalized, transfusions were discontinued. The child is currently on regular follow-up maintaining a fibrinogen level of more than 0.5 g/L. Genetic counseling was done for the family. Conclusion: Congenital afibrinogenemia may be detected late in adolescence with atypical bleeding manifestations. Awareness of this entity may help the physician to suspect this disease. Early and appropriate investigations can be conducted to identify the condition, so that appropriate management can be initiated.
Keywords: Adolescent, bleeding disorder, child, genetic
|How to cite this article:|
Ghorui A, Kumar CM, Banerjee A. Isolated scalp hematoma: An unusual presentation of congenital afibrinogenemia. Indian Pediatr Case Rep 2023;3:179-83
|How to cite this URL:|
Ghorui A, Kumar CM, Banerjee A. Isolated scalp hematoma: An unusual presentation of congenital afibrinogenemia. Indian Pediatr Case Rep [serial online] 2023 [cited 2023 Sep 30];3:179-83. Available from: http://www.ipcares.org/text.asp?2023/3/3/179/383633
Congenital fibrinogen disorders (CFDs) are rare hereditary blood clotting disorders characterized by defect in quantity or quality of fibrinogen. Depending on the type of defect, the disorder is classified into two subtypes. Type I is characterized by fibrinogen deficiency (<1.5 g/L), which can manifest as either a complete absence (afibrinogenemia) or a reduced amount (hypofibrinogenemia) of fibrinogen. Type II, on the other hand, is characterized by a qualitative defect in fibrinogen, such as dysfibrinogenemia and hypodysfibrinogenemia. Congenital afibrinogenemia, a type of type I CFD, is an extremely rare condition, which usually presents with bleeding manifestations, though occasionally thrombotic events may occur. The occurrence of a nontraumatic subgaleal bleed, however, is not much reported as a complication. We present here an unusual case of a child who developed a spontaneous hematoma on his scalp and was later diagnosed with congenital afibrinogenemia.
| Clinical Description|| |
A 12-year-old apparently healthy boy presented with painless scalp swelling over the entire anterior scalp, more marked on the right side, for the past 2 weeks. There was no history of trauma or the use of any anticoagulant medications or any indigenous medications by the child. He had a history of prolonged bleeding after minor trauma since he was a toddler. Such episodes subsided with application of a compression bandage, and no medical attention was sought for the same. There was no associated history of acute-onset swelling of joints, suggestive of hemarthrosis, or blood in stool/vomitus, gingival bleeding, bleeding per rectum, nor any muscle hematoma, skin petechiae, or bruises.
The child was born at term via normal vaginal delivery, at home, and cried immediately after birth. While the antenatal history was uneventful, there was a history of prolonged bleeding from the umbilical cord postnatally, which was managed conservatively at home, and no medical attention was sought. The child was relatively symptom-free throughout infancy. During early childhood, the parents had noticed prolonged bleeding following minor trauma but were never investigated. However, there was no history of events suggestive of stroke, myocardial infarction, or deep venous thrombosis.
The other members of the family had no history of similar illness, and the three-generation pedigree analysis was unremarkable. He ate an average diet and had achieved his developmental milestones within appropriate age range.
On examination, the boy was conscious, with stable vitals – a normal heart rate (86 beats/min), normal respiratory rate (24 cycles/min), normal axillary temperature (98.8°F), and normal blood pressure (116/78 mmHg, 50th–90th centile for age, gender, and height). His weight was 42 kg (50th–75th centile), his height was 150 cm (50th–75th centile), his sexual maturity rating was Tanner stage II, which was age appropriate, and his left arm. The child showed a Bacillus Calmette–Guerin scar. There was no evidence of pallor, icterus, cyanosis, clubbing, or lymphadenopathy. Head-to-toe examination revealed a diffuse boggy swelling over the entire scalp, with the right side being more prominent. The swelling was nonpulsatile and there was no audible bruit over it [Figure 1]a. There was no other evidence of bleeding in the form of joint swelling, muscle hematoma, or skin bleeding. Neurological examination showed no signs of focal neurological deficit or meningeal irritation, and ophthalmoscopic examination was also normal. Other system examinations were unremarkable.
|Figure 1: (a and b) scalp swelling in the child before and after 2 weeks of treatment (The red arrow points to the scalp hematoma)|
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| Management and Outcome|| |
Based on the history and clinical examination, the possible differential diagnoses considered for such a spontaneous scalp hematoma included a bleeding or coagulation disorder, spontaneous bleed of an underlying arteriovenous malformation of the scalp, a ruptured aneurysm of the superficial temporal artery of the scalp, or a complicated arteriovenous fistula of the scalp.
Accordingly, investigations were carried out. Laboratory investigation revealed no anemia (hemoglobin level of 12.1 g/dL), a normal leukocyte count (9750/mm3), and a normal platelet count (3.81 lakh/mm3). The hepatic and renal function tests were normal with a total bilirubin of 0.18 mg/dL, aspartate aminotransferase of 32.8 U/L, alanine aminotransferase of 16.6 U/L, total protein of 6.65 g/dL, albumin of 3.59 g/dL, urea of 34.1 mg/dL, and creatinine of 0.43 mg/dL. The serum level of sodium and potassium was within normal limits (135.22 mEq/L and 4.67 mEq/dL, respectively), and random blood sugar was normal (106 mg/dL).
A noncontrast computed tomography scan of the head revealed a scalp hematoma without any intracranial bleeding, and an ultrasonographic color Doppler scan of the scalp revealed no vascular malformations [Figure 2].
|Figure 2: Noncontrast computed tomography brain showing scalp hematoma without any intracranial bleeding|
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The coagulation study revealed extremely elevated prothrombin time (PT) >70 s (normal: <14 s) and activated partial thromboplastin time (aPTT) >180 s (normal: 30–40 s). Elevation of both the PT and aPTT can be caused by a common coagulation pathway defect such as deficiencies of Factor I (fibrinogen), Factor II (prothrombin), Factor V (labile factor), Factor X (Stuart–Prower factor), or a combined factor deficiencies such as severe hepatic impartment or severe Vitamin K deficiency, or due to consumption of clotting factors such as disseminated intravascular coagulation (DIC), or due to anticoagulant drugs such as heparin and warfarin, or due to acquired inhibitors against Factor I, II, V, or X.
As the liver function tests were normal, it ruled out the possibility of combined factor deficiencies, and the lack of a history of anticoagulant drug intake ruled out the anticoagulant drug-related cause.
Further detailed coagulation study revealed normal D-dimer <0.5 mg/L fibrin equivalent unit (FEU) (normal: <0.5 mg/L FEU) and normal fibrin degraded product <5 μg/ml (normal: <5 μg/ml), which ruled out the possibility of DIC. In the mixing study, there was improvement after mixing with normal plasma, which ruled out the possibility of inhibitors. Thereafter, the test for evaluating the common coagulation pathway revealed an extremely high thrombin time (TT) >100 s (normal: 15–19 s), and to rule out the possibility of heparin contamination, we also tested for the reptilase time (RT), which was also extremely high >100 s (normal: 14–20 s). The fibrinogen level was undetectable (normal: 1.5–4 g/L), suggesting that type I CFD hypofibrinogenemia was likely the cause. The fibrinogen level was estimated, which was found to be undetectable <0.1 g/L (normal: 1.5–4 g/L), indicating hypofibrinogenemia (type I CFD) as the likely cause.
We also tested for the other common clotting factor deficiencies that cause clotting disorders, such as Factors VIII and IX. Factor VIII activity was 129% (normal: 50%–150%), and Factor XI activity was 198% (normal: 50%–150%), both of which were within the normal range.
Finally, for further confirmation, a genetic study for congenital fibrin disorder was done, which revealed the presence of a homozygous single-base pair deletion in exon 5 of the fibrinogen gene of alpha chain (FGA) gene, confirming the diagnosis of congenital afibrinogenemia. Therefore, the constellation of a thorough history, clinical examination, and laboratory results led to the diagnosis of congenital afibrinogenemia (type I CFD).
We tested the coagulation profile (PT/aPTT), TT, and fibrinogen level of both parents and the elder sibling, which turned out to be normal. The parents were also advised to have genetic testing done for themselves and the elder sibling to determine the carrier state, but they were unable to do so due to financial constraints.
Due to a lack of availability of fibrinogen concentrates, the child was transfused with fresh frozen plasma (FFP) at a total dose of 60 ml/kg, which contains approximately 2.5 g of fibrinogen, thereby providing the child fibrinogen at a dose of 100 mg/kg. The PT/aPTT was normalized. Thereafter, FFP was been transfused at a dose of 30 ml/kg every 4th day to maintain a trough level of fibrinogen above 0.5 g/L, as recommended by the United Kingdom Haemophilia Centre Doctors' Organisation.
Gradually, scalp swelling decreased in size with the treatment and completely resolved over a period of 2 weeks [Figure 1]b. The child is now receiving intermittent prophylaxis with FFP at a dose of 30 ml/kg once or twice per week to keep the target trough level of fibrinogen above 0.5 g/L. Genetic counseling was provided to the parents before family planning in view of the autosomal recessive nature of the disease. To date, the child has had 2 months of follow-up, and no further bleeding episodes have occurred.
| Discussion|| |
The above description of the child depicts an interesting case of congenital afibrinogenemia, with a rare presentation as an isolated scalp hematoma.
Congenital afibrinogenemia is rarely encountered in pediatric practice, with an estimated incidence of 1 in every 1,000,000 people. It is an autosomal recessive disorder that equally affects males and females. Quantitative fibrinogen disorders (type I CFDs) have been divided into various categories based on the severity of hypofibrinogenemia by the European Network of Rare Bleeding Disorders and the International Society on Thrombosis and Haemostasis. These are mild hypofibrinogenemia (fibrinogen level: 1.5–1.0 g/L), moderate hypofibrinogenemia (fibrinogen level: 0.9–0.5 g/L), severe hypofibrinogenemia (fibrinogen level: 0.5–0.1 g/L), and afibrinogenemia (undetectable fibrinogen level, i.e., <0.1 g/L). A crucial part of the common coagulation pathway is played by fibrinogen, a 340 kDa plasma glycoprotein. It is synthesized by the hepatocytes and stored in the platelet alpha granules, enabling a local increase in fibrinogen concentration at the sites of platelet activation.
Fibrinogen is made up of two sets of three similar polypeptide chains (Aα, Bβ, and γ). Three distinct genes (FGA, fibrinogen gene of beta chain, and fibrinogen gene of gamma chain, respectively) encode these fibrinogen polypeptides (Aα, Bβ, and γ). CFD is an autosomal recessive disorder caused by homozygous or compound heterozygous missense mutations in any of the three genes responsible for fibrinogen production. Congenital afibrinogenemia is diagnosed by the presence of undetectable levels of immunoreactive fibrinogen, extremely prolonged thrombin and RTs, and significantly prolonged PT and aPTT. On the basis of coagulation profiles, it can be difficult to distinguish between severe hypofibrinogenemia and afibrinogenemia because both conditions show noticeably prolonged PT and aPTT. A thorough history, physical examination, and laboratory tests aid in the diagnosis [Table 1]. It is necessary to take fibrinogen of differentials levels into consideration for accurate differentiation between these conditions due to the limited sensitivity of coagulation tests at fibrinogen levels below 0.5 g/L.
|Table 1: Approach to various differentials of prolonged prothrombin time and activated partial thromboplastin time|
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Congenital afibrinogenemia patients typically have bleeding symptoms, though thrombotic events can also be present in a small percentage of cases. The most frequent clinical symptoms include mucosal surface bruising and bleeding, gastrointestinal and genitourinary bleeding, as well as bleeding after trauma or surgery. Bleeding from the umbilical cord (nearly 85% of cases) and after circumcision is common during the neonatal period. Infants frequently experience intracranial hemorrhage, whereas children and adolescents frequently experience hemarthrosis and painful bone cysts in the diaphysis of long bones, possibly as a result of recurrent hemorrhages during bone remodeling. The child described by us, though an adolescent boy, showed no evidence of hemarthrosis or bleeding from any other site, except the scalp. Females with afibrinogenemia are prone to menometrorrhagia (abnormal uterine bleeding) and spontaneous abortions. Afibrinogenemia is also associated with spontaneous splenic rupture in some patients. Patients with afibrinogenemia have occasionally been reported to experience severe and recurrent thromboembolic complications. The possible mechanism is that, in the absence of fibrinogen, thrombin usually persists in circulation for a longer time as it cannot be used to convert fibrinogen to fibrin, resulting in hypercoagulability.
Since afibrinogenemia is inherited as an autosomal recessive trait, pregnant women with a family history should be properly counseled about the risk of having a child with the disorder., The antenatal diagnosis should be planned as early as possible in pregnancy by taking chorionic villous sample, and the treatment should be started soon after the birth, before the first bleeding. Neerman-Arbez et al. performed the first prenatal detection of afibrinogenemia in a Palestinian family with two affected daughters in 2003.
The standard treatment (treatment on demand) is episodic, in which fibrinogen is administered as fibrinogen concentrates after the onset of bleeding; alternatives include cryoprecipitate and FFP. In other circumstances, prophylaxis can be started after a bleeding episode has been treated to stop recurrences, i.e., secondary prophylaxis. According to the United Kingdom Haemophilia Centre Doctors' Organisation's recommendations for an unprovoked hemorrhage, the target fibrinogen level is suggested to be above 1 g/L until hemostasis is achieved and above 0.5 g/L until the bleeding surface is fully restored. However, there is no consensus regarding the dosage and intervals of administration of fibrinogen concentrates. The trough levels of fibrinogen should be kept above 0.5 g/L in cases of prophylaxis against spontaneous hemorrhage and above 1 g/L in cases of surgery and pregnancy.
To conclude, congenital afibrinogenemia is an extremely rare condition, rarely encountered in general pediatric practice. By reading this article, physicians will become aware of such a disorder and may consider the same etiology in some children presenting with bleeding disorders.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the legal guardian has given consent for images and other clinical information to be reported in the journal. The guardian understands that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]