Keywords
afibrinogenemia - fresh frozen plasma - rare bleeding disorders - extradural hematoma
Introduction
Afibrinogenemia is an extremely rarer hereditary bleeding disorder characterized by
spectrum of bleeding manifestations. Fibrinogen constitutes an essential clotting
factor and plays important role in clot formation. Fibrinogen converts into fibrin
by the action of thrombin.[1]
[2]
[3]
[4] Further fibrinogen also plays critical role in primary hemostasis as it promotes
to aggregation of platelet by binding to glycoprotein IIb/IIIa present on the surface
of activated platelets.[5] Author reports a 2-year-old girl's case known case of afibrinogenemia, diagnosed at age of 4 days of neonatal life as she had excessive bleeding from umbilical
stump. Since then she was under regular follow-up at hematology department of our
institute and received prophylactic fresh frozen plasma transfusion every third week.
She presented with extradural hematoma, was managed with evacuation of hematoma surgically,
after receiving fresh frozen plasma on arrival in emergency department and during
perioperative period.
Case Illustration
This female baby was the first issue born to parents with nonconsanguineous marriage.
The prenatal period was uneventful. The baby was born at full term through normal
vaginal delivery. On fourth days after the birth, the mother noticed excessive bleeding
from umbilical stump. She was admitted in the neonatal unit and pediatrician consulted
hematologist. She was diagnosed as case of afibrinogenemia and further advised for
regular transfusion of fresh frozen plasma, cryoprecipitate, or recombinant fibrinogen
replacement therapy, but parent opted for fresh frozen plasma because of economic
constrain and accordingly she was regularly receiving fresh frozen plasma replacement
therapy since neonatal period. She was doing well, suddenly developed episodes of
excessive inconsolable cries associated with multiple vomiting, though there was no
definite history of trauma, or febrile illness or exanthematous rashes, and 2 hours
later she was brought to emergency services. On examination, pulse rate was 88 beats/min,
head circumference was 52 cm; pupillary asymmetry and rest of examination was essentially
within normal limits. She was subjected immediately to noncontrast computed tomographic
(NCCT) scan of the brain ([Fig. 1)] that showed a large hyperdense extra-axial mass lesion in the right temporoparietal
region from the atrium causing pressure effect on ipsilateral ventricle. Immediately
hematologist consultation sought and received two pediatric units of fresh frozen
plasma in the emergency department and planned for emergency evacuation of extradural
hematoma.
Fig. 1 NCCT of the head showing right parietal extradural hematoma causing mass effect.
The patient was given general anesthesia and positioned supine, and right-sided parietal
osteoplastic craniotomy was performed using Midas Rex drill. On bone removal, clotted
blood that was causing pressure effect was evacuated. Hemostasis was achieved and
wound closed in layer after putting extradural drain. She tolerated surgery well and
postoperative period was uneventful. NCCT scan of the head in the postoperative phase
showed complete removal of extradural hematoma ([Fig. 2)]. The baby was discharged on postoperative day 3 and she was taking oral feeds with
no further episodes of vomiting. She was doing well at the last follow-up at 6 months.
Fig. 2 Postoperative NCCT of the head showing evacuation parietal extradural hematoma with
relief in mass effect and reversal of falcine herniation.
Discussion
Afibrinogenemia is a rare hereditary bleeding disorder having autosomal recessive
genetic transmission and prevalence of 1:1,000,000 live birth.[2] The fibrinogen has three polypeptide chains, that is, Aα, Bβ, and γ, controlled
by corresponding three genes FGA, FGB, and FGG, located on chromosome 4. Mutation
of any one of three genes may affect synthesis or release of fibrinogen during formation,
assembly, stability, or secretion phases of fibrinogen.[4] The Patient with afibrinogenemia shows prolonged prothrombin time, thrombin, and
activated partial thromboplastin time, undetectable functional fibrinogen and absence
or immunoreactive fibrinogen with deranged platelet adhesion and adenosine diphosphate
(ADP)–induced platelet aggregation but normal thrombin- and collagen-stimulated platelet
aggregation.[5]
The most common symptoms are umbilical stump bleeding and hemorrhage from mucosal
surfaces, menorrhagia, epistaxis, and bleeding inside oral cavity.[3]
[5]
[6] Bleeding in the joint space and excessive bleeding during surgical procedures are
other principal manifestations, whereas spontaneous intracranial bleeding is extremely
rare,[6] although it can develop following minor trauma.[2]
[3]
[6]
[7]
Management of afibrinogenemia requires constant vigilance and anticipation; however,
during active bleeding episodes, replacement therapy remains main modalities and includes
intravenous administrations of plasma-derived fibrinogen concentrate, cryoprecipitate,
and fresh frozen plasma or recombinant synthetic fibrinogen.[5] As half-life of fibrinogen is approximately 4 days and can be administered daily
or alternate day, need is based on indication, response, and result of hematologic
laboratory investigation. For spontaneous bleeding, recommended target levels of fibrinogen
should be more than 1 g/L till securing complete hemostasis and during maintenance
phase, target till healing is greater than 0.5 g/L.[5]
[6]
[7]
Fibrinogen concentrate is replacement therapy of choice, its advantages is virally
inactivated. It needs relatively smaller infusion volume of transfusion and associated
reduced allergic reaction.[2] However, fresh frozen plasma and cryoprecipitate are another alternative replacement
agent, and it can be administered in emergencies where fibrinogen concentrate availability
is uncertain. However, our patient received fresh frozen plasma during peri- and postoperative
periods of extradural hematoma evacuation as she was regularly receiving during follow-up
under hematology physician since neonatal period. Prior to surgical intervention,
fibrinogen levels should be built up to at least 1 g/L and maintained at the same
level till completion of surgery; however, major surgical procedures in these cases,
as a precautionary measure should be performed in a well-equipped centers possessing
well-established and functioning blood bank.[8]
[9]
Indications of prophylactic infusion of fibrinogen concentrate or cryoprecipitate
are following life-threatening bleeding episodes. Prophylactic therapy includes weekly
infusions in most patients, but transfusion every 2 weeks or once a month has also
been used.[6] According to recommendation of current guidelines, regarding consideration for secondary
prophylactic treatment where risk of life-threatening bleeding and with a target fibrinogen
level should be 0.5 g/L.[9] Usually, primary prophylactic infusion is not advocated as associated risk of transmission
of infectious diseases, allergic reactions, and rare thrombotic complications are
very high.[5]
[8]
[9]
Conclusion
Constant vigilance is required for detecting early intracranial hemorrhage, and replacement
therapy should be transfused at earliest opportunity to correct fibrinogen deficiency
state and should be continued in the perioperative period. Pediatrician as well as
neurosurgeon should be aware of existence of such rare bleeding disorder while managing
such cases in the emergency services.
