Congenital afibrinogenemia /hypofibrino-genemia is a
rare inherited coagulation disorder and approximately 250 cases have
been reported(1). The bleeding may vary from being mild to
catastrophic(2). Hemarthrosis may develop in 20% of these patients when
they may be confused with hemophilia(3). Though, the patients with
congenital afibrinogenemia are symptomatic since early infancy but many
of the patients who have hypofibrinogenemia (fibrinogen less than 100 mg
/dL) present late and with trivial bleed.
Case Report
A 6-year-old female child, born out of
nonconsanguious marriage bond was admitted to our hospital with history
of bluish spots around the eyes and thighs of one-month duration. No
significant history of trauma, fever, jaundice or previous blood
transfusions was recorded. Patient presented to a peri-pheral health
center with similar complaints 1-year back but symptoms subsided within
seven days and during that illness no investigation was done. No family
history of similar illness was present. On examination, the child was
well-nourished, pale with ecchymotic patches on the trunk and the lower
limb and around both eyes with no evidence of haemarthrosis. Systemic
examination was essentially normal with no organomegaly. Investigations
revealed hemoglobin of 10.5g/dL, and white cell count of 5400 per cu mm,
with normal differential counts. Platelets count was 2.5 lakhs per cu
mm. Bleeding time (10 min, control 5 min), clotting time (>25 min,
control 7 min) and prothrombin time (120 sec, control 14 sec), Activated
partial thromboplastin time (480 sec, control 26 sec), thrombin time
(180 sec, control 14 sec) were all abnormally prolonged. Strikingly,
when the patient’s blood was collected in a plain vial, there was no
clot formation for 2 hours. Fibrinogen degradation product (FDP) was
negative. Liver function (LFT) and Kidney function (KFT) tests were
normal. Peripheral blood film did not reveal any evidence of
microangiopathy, hemolysis, infection or thrombocytopenia. Absolute
fibrinogen level was 35 mg / dL (normal 160-350 mg / dL). The patient
was managed conservatively without blood transfusion. She was discharged
with instructions of avoiding aspirin containing compounds and for the
measures to be taken in the future in the event of trauma, injuries or
operations.
Discussion
These patients may present with bleed of varied
severity. Our patient presented with recurrent, spontaneously occurring
ecchy-motic spots without major bleed. As CT, PT, APTT, TT were all
prolonged, this suggested the possibility of low fibrinogen level. As
absolute fibrinogen level was very low i.e. 35 mg% and acquired causes
of hypofibrino-genemia were excluded by normal LFT, absence of
malnutrition and exclusion of DIC (consumptive coagulopathy), a
diagnosis of congenital hypofibrinogenemia was con-firmed.
Congenital disorders of fibrinogen have been
attributed to chromosome 4 (q26-q28) with hypofibrinogenemia commonly
occur-ring in heterozygous and afibrinogenemia in the homozygous.
Variable phenotypic expression of the unprotected heterozygous with
levels of no more than 2.5 g/ L fibrinogen and protected heterozygous
with normal fibrinogen levels is not clear(4). Higher rates are seen
amongst the consanguineous married couples, with more incidence in
males.
Though the patients may have lifelong hemorrhagic
diathesis related to trauma or surgery, hemarthrosis is uncommon
(20%)(3). A significant percentage may experience undue bleeding
following birth trauma(2). Surprisingly, very few patients have
spontaneous bleeding. This could be attributed to the von Willebrand
factor (vWf) which binds to glycoprotein complex on platelets and
provides a back up mechanism for platelet aggregation, particularly
replacing fibrinogen. Besides, the small quantity of platelet fibrinogen
may also be a facilitator leading to reduction of symptoms. There seems
to be a peculiar susceptibility of these patients for spontaneous
splenic rupture(5).
Acute hemorrhagic episode can be treated with either
fresh frozen plasma or cryoprecipitate or fibrinogen concentrate (Cohn
fraction l). The homeostatic level of fibrinogen is above 60 mg/dL.
Therapy with 100 mg / kg of fibrinogen provides a hemo-static plasma
level. Since the plasma half-life of fibrinogen is between 3 to 5 days,
frequent infusions are not necessary(6). Treatment with either FFP [40 ×
body weight × (desired fibrinogen-patients fibrinogen)/l00] or
cryoprecipitate (225-250 mg of fibrinogen / bag) is also effective(7).
Although some authors have advocated regular prophylactic infusion of
cryoprecipitate(8) but majority of them do not recommend it on account
of potential dangers of blood product infusions and various
thromboembolic complications (1,9,10). However, a prophylactic infusion
of cryoprecipitate is mandatory in recurrent intracranial hemorrhage.
Contributors: NA and KCA managed the case and
reviewed the literature. KCA will act as the guarantor for the paper. HG
participated in data collection. SS helped with the laboratory
parameters.
Funding: None.
Competing interests: None stated.
