Transcript darman.sums.ac.ir

‫ه‬
‫بسم ّللا الره حمن الره حیم‬
Afibrinogenemia-Case Report
Bijan Keikhaei,
Ahvaz Jundishapur
University of
Medical Sciences
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Case Presentation
•A 14 Yr-old boy, was referred to the Shafa Hospital on Mehr
1392, for the Acute loss of consciousness.
•He was a known case of hereditary afibrinogenemia who
was diagnosed at age 4 th day from umbilical cord bleeding
and serum fibrinogen level <0.2 g/l.
•Until 1392, only incidental minor bleeding episodes
occurred.
•He received a few fibrinogen concentrate vials in his life for
mouth and gum bleeding.
•History of trauma was not detected.
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•No positive family history.
Laboratory Findings
Investigation findings were Hb-11gm/dl, MCV:
85Fl,MCH: 28 Pg, ESR-20mm,BUN:20 mg/dl,
Cr:1 mg/dl
Platelet count-330000/cmm , PT- 17.5 sec
(INR-1.8),
APTT- 72.8 sec,TT:Prolonged, HBSAg: Neg ,HIV
Ab: Neg, HCV Ab: Neg
No measurable fibrinogen
Physical Examination
• Findings at neurological examination
were as follows:
• global motor weakness
• GCS: 8
• Babinski reflex on the right and left
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Case report
• He was admitted in the ICU ward.
• He had two episodes of generalized tonic
colonic convulsion in the ward .
• Substitution therapy with fibrinogen were
started immediately after neurological
examination .
• The patient received 100 mg/kg
fibrinogen(Hemocomplettan P) every 48 hr.
• He also received phenytoin and
Dexamethasone.
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Brain CT Scan
Case Presentation
• While still on maintained substitution therapy, the
patient condition becomes worse everyday.
• On day 3 th admission the patients GCS was 5.
• The patient blood fibrinogen level was 3 g/l with
trough level 1.5 g/l.
• Unfortunately the patient died on the 4 th day
admission.
Discussion
Terms
Dysfibrinogenemia: fibrinogen with abnormal function.
Hypofibrinogenemia: Reduced amount of fibrinogen in the
plasma.
Hypodysfibrinogenemia: inherited fibrinogens which are both
functionally abnormal and reduced amounts in the plasma (<150
mg/dL) as measured by immunologic methods.
Afibrinogenemia: absence of circulating fibrinogen in the plasma.
Cryofibrinogenemia: Fibrinogen in the plasma (but not serum)
that precipitates on exposure to low temperatures (4 C).
Structure
340 kD glycoprotein that circulates in plasma at a
concentration of ~ 200-400 mg/dL, with a half life of 4 days
.
Hexamer, consisting of three paired polypeptide chains (Aα,
Bβ, γ).
Synthesized in hepatocytes under the control of three
different genes located on chromosome 4q.
Assembly takes place in the liver, carbohydrate side chains
are added to the beta and gamma chains before it is
secreted into plasma.
It has a trinodular structure: central E-domain
(aminoterminal portions of the three polypeptides) and two
D-domain (carboxyterminal portions)
D-Domain
E-domain
D-Domain
Aα: Red
Bβ: Blue
γ: Green
Structure
Two major forms exist, separated from each other by ion
exchange chromatography: Fibrinogen 1 and 2.
Fibrinogen 1: contains 2 γ chain (411 aa)
Fibrinogen 2: contains one γ chain and one γ’ chain (427 aa),
has a more anionic carboxyterminal sequence.
Factor XIII (protransglutaminase, fibrinoligase) binds
specifically to γ’ chain of fibrinogen 2 (factor XIII is
carried by fibrinogen 2 in the plasma). Thrombin has been
shown to bind to the anionic γ’ extension of fibrin 2.
Functions
Sites of important function:
Thrombin binding site
Factor XIIIa binding site,
t-PA binding site,
alpha-2 antiplasmin binding site
platelet binding site.
Classification
Quantitative Abnormalities
Qualitative abnormalities
Congenital
Afibrinogenemia
(uncommon, autosomal
recessive)
Hypofibrinogenemia
Acquired
Hypofibrinogenemia
(consumptive
coagulapathies, DIC)
Hyperfibrinogenemia
(inflammation,
neoplasia)
Congenital
Dysfibrinogenemia
Hypodysfibrinogenemia
Acquired
Liver disease
Malignancies,
Antifibrinogen antibodies
Inherited dysfibrinogenemia
Overall, ~ 55 % are silent.
~ 25 % manifests as bleeding .
~ 20 % experience thrombosis
with or without bleeding.
Inherited afibrinogenemia
A rare condition,
Autosomal recessive inheritance
 complete lack of circulating fibrinogen
• Bleeding manifestation range from mild to
catastrophic
• Excessive bleeding and early miscarriages in
pregnant women
• Fatal umbilical cord bleeding in the neonate
Inherited afibrinogenemia
• High fibrinogen levels are seen :
– pregnancy
–oral contraceptives.
–hypercoagulable state.
– acute-phase reactant.
Diagnosis
Initial screening tests: thrombin time (TT) and
reptilase time (RT) fibrinogen activity and
antigen.
Afibrinogenemia: Prolonged TT, RT, virtually
absent fibrinogen antigen and activity (clottable
antigen).
Dysfibrinogenemia: Prolonged TT, RT, normal
or increased fibrinogen antigen, normal or
decreased clottable fibrinogen (activity).
Treatment
• In February 1995, cryoprecipitate was
replaced by fibrinogen concentrate.
• Plasma recovery of fibrinogen has been
measured repeatedly: top levels were
approximately 1.7 g/L and trough levels
approximately 0.75 g/L.
Treatment
Patients with thrombotic complications should
receive anticoagulation.
The optimal duration of anticoagulation is
unknown (the benefit of anticoagulation
should be weighed against a potentially
higher risk of bleeding).
Patient education concerning thrombotic
risk factors (surgery, pregnancy, oral
contraceptives, immobilization)
Discussion
• Congenital afibrinogenemia is a rare disorder
associated with a high risk of spontaneous
intracerebral bleeding.
•Clinical manifestations in afibrinogenemia
range from minor to severe bleeding, often
with long asymptomatic intervals. Bleeding
may occur spontaneously as well as related to
trauma.
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Discussion
• The incidence of spontaneous intracerebral
bleeding in patients with afibrinogenemia is
unknown; a small number of case reports have
been published.
• spontaneous intracerebral bleeding must be
strongly suspected when an afibrinogenemic
patient presents with matching clinical symptoms.
Discussion
• Since intracerebral hemorrhage is a lifethreatening event, It is recommend that
substitution therapy be installed promptly at
presentation, before additional investigations
are made .