2 afibrinogenemia-case report bijan keikhaei, ahvaz jundishapur university of medical sciences...
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�ه الّر�حمن الّر�حیم بسم الّل
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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.•No positive family history.
Laboratory FindingsInvestigation 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
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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.
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
TermsDysfibrinogenemia: 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)
Aα: Red Bβ: Blue γ: Green
E-domainD-Domain D-Domain
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.
Structure
Sites of important function: Thrombin binding siteFactor XIIIa binding site, t-PA binding site, alpha-2 antiplasmin binding site platelet binding site.
Functions
ClassificationQuantitative Abnormalities
Congenital
Afibrinogenemia (uncommon, autosomal recessive)
HypofibrinogenemiaAcquired
Hypofibrinogenemia (consumptive coagulapathies, DIC)
Hyperfibrinogenemia (inflammation, neoplasia)
Qualitative abnormalities
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.
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.
Inherited afibrinogenemia
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.
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)
Treatment
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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.
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 life-threatening event, It is recommend that substitution therapy be installed promptly at presentation, before additional investigations are made .