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Hypofibrinogenemia

Fibrinogenopenia

Hypofibrinogenemia is a rare disorder caused by the deficiency of fibrinogen in plasma. It can be either inherited or can be acquired following hepatic disorders, leukemias, or excessive consumption of clotting factors. It is typically diagnosed due to hemorrhage during a surgical or traumatic event.


Presentation

Hypofibrinogenemia is a quantitative deficiency of fibrinogen which can be inherited or may develop secondary to a liver or bone marrow diseases, or excessive clotting factor utilization. Congenital hypofibrinogenemia is transmitted in an autosomal recessive manner [1] with the defective locus purported to be on chromosome 4 [2]. Heterozygotes manifest this as hypofibrinogenemia while homozygotes present with afibrinogenemia [2].

As this is a rare disorder, there are very few reports of the clinical manifestations [3] [4] [5] [6]. Patients with hypofibrinogenemia may present with mild bleeding but are typically asymptomatic. Although they have a higher tendency for bleeding from mucous membranes and deep tissues they are often detected only following bleeding during a traumatic or surgical episode [7] [8]. Spontaneous bleeding, hemarthrosis, and life-threatening hemorrhage are rare [2] [9]. Spontaneous and recurrent miscarriages and thrombotic events have also been reported in these patients [10].

Acquired hypofibrinogenemia is caused by either excessive loss of blood or exhaustion of clotting factors [10]. Hypofibrinogenemia has been reported in patients with liver disease, disseminated intravascular coagulation (DIC), lymphoblastic leukemia [11], those receiving therapy with asparaginase [12] and in rare cases, following snake bites [10]. Besides clinical manifestations of the underlying disorders, patients with hypofibrinogenemia will present with bleeding diathesis.

Splenomegaly
  • The association of splenomegaly led to suspicion of Felty's syndrome. Flux cytometry was compatible with T-cell LGL leukemia. In addition, severe hypofibrinogenemia was detected.[ncbi.nlm.nih.gov]
Pseudotumor
  • Percutaneous biopsy of a pseudotumor is contraindicated due to the high prevalence of complications, including life-threatening bleeding.[ncbi.nlm.nih.gov]
Italian
  • The genetic basis of severe hypofibrinogenemia was analyzed in a 57-year-old Italian woman.[ncbi.nlm.nih.gov]
Overeating
  • The deficiency appeared to be due to severe congenital hypofibrinogenemia since the fibrinogen level remained at the same low level over a long period, without any abnormality of other coagulation proteins.[ncbi.nlm.nih.gov]
  • Regardless of hypofibrinogenemia, he was receiving anticoagulant therapy over 6 months, with no occurrence of bleeding.[ncbi.nlm.nih.gov]
  • Importantly, in the analysis of high white blood cell count (over 10 109/L) subgroup, a low fibrinogen level could efficiently discriminate APL patients from controls (AUC 0.983, sensitivity 96.4% and specificity 94.4%) with a criterion value 1.71g/L.[ncbi.nlm.nih.gov]
  • Although the patient received no treatment, her fibrinogen level increased to 307 mg/dl over the next 4 days and then remained above 260 mg/dl for the rest of her pregnancy. At 35 weeks' gestation, a healthy 2090 gm female was delivered.[ncbi.nlm.nih.gov]
  • Over 50 new and updated pieces of art highlight how results are interpreted, what equipment is used, and how various techniques are performed. Over 20 new tests prepare you for the types of tests you will encounter during your clinical experience.[books.google.com]
Shoulder Pain
  • The proposita from family B was a 37-year-old female who suffered from recurrent shoulder pain for 7 years.[ncbi.nlm.nih.gov]
Purpura
  • This is the first report of purpura and hypofibrinogenemia induced by allopurinol and the pathophysiology underlying this reaction remained unknown.[ncbi.nlm.nih.gov]
  • Purpura fulminans Type 1 Excludes disseminated intravascular coagulation (complicating): abortion or ectopic or molar pregnancy ( O00 - O07 , O08.1 ) in newborn ( P60 ) pregnancy, childbirth and the puerperium ( O45.0 , O46.0 , O67.0 , O72.3 ) congenital[icd10data.com]
  • Acquired afibrinogenemia has been observed as a complication of shock, 1 severe liver damage associated with a septic abortion and bacteremia, 2 pulmonary surgery, 3 severe tissue damage, 4 inadequate protein intake, 5 thrombotic thrombocytopenic purpura[annals.org]
  • […] coagulation [defibrination syndrome] Approximate Synonyms Abruptio placentae with disseminated intravascular coagulation (dic) Disseminated intravascular coagulation Disseminated intravascular coagulation due to placental abruption Placental abruption W DIC Purpura[icd9data.com]
  • Patients with Acute Thrombolytic Therapy Unusual Sites of Arterial Occlusion Pathogenesis and Treatment of BiomaterialAssociated Overview of Complex Thrombohemorrhagic Disorders Consumptive Thrombohemorrhagic Disorders The Thrombotic Thrombocytopenic Purpura[books.google.es]
Anger
  • […] sequence resulting in an in-frame heterozygous 5 amino acid deletion (GVYYQ 346-350; p.G372_Q376del) and that this mutation is responsible for a new splicing site at position 7688 of the genomic sequence. we suggest that the molecular defect in fibrinogen Angers[ncbi.nlm.nih.gov]
  • The structure predicted for fibrinogen Angers showed a novel helical structure in place of hole 'a' on the outer edge of γD likely to have a negative impact on fibrinogen assembly and secretion.[ncbi.nlm.nih.gov]

Workup

As with any bleeding disorder, clinical suspicion, detailed history and laboratory tests for coagulopathy form the mainstay of diagnosis. A family history is vital to diagnose congenital hypofibrinogenemia while a history of underlying liver or malignancy or snake bite is essential to indicate acquired causes of hypofibrinogenemia. During the physical examination, it is important to assess the severity of blood loss and identify features of hemorrhagic shock.

A complete blood count, liver function tests, and renal function tests are part of the routine workup. Standard laboratory tests for coagulation disorders such as prothrombin time (PT) and activated partial thromboplastin time (aPTT) may be normal in hypofibrinogenemia as small quantities of fibrinogen may be present to enable the formation of a clot. In some cases, PT and aPPT may be prolonged. Thrombin time is a more sensitive test for the diagnosis of hypofibrinogenemia compared to PT/ aPTT. Common tests to measure fibrinogen activity and concentration are the prothrombin time (PT)-derived fibrinogen assay and the Clauss assay [13] which is the gold standard test. These assays provide information quickly in an emergency. The ratio of fibrinogen antigen–to–clottable fibrinogen can be utilized to differentiate between dysfibrinogenemia and hypofibrinogenemia [14]. In surgical situations, viscoelastic properties of fibrin and its formation are used for diagnosis in patients suspected of congenital or acquired hypofibrinogenemia [10].

Imaging studies such as brain computed tomography (CT) or magnetic resonance imaging (MRI) are indicated only if there are clinical manifestations suggestive of intracranial bleeding.

Treatment

  • After treatment with intravenous infusion of fibrinogen and cryoprecipitate, and continued treatment with high-dose methylprednisolone, the skin rash gradually went away.[ncbi.nlm.nih.gov]
  • Suggestions for treatment guidelines and management strategies are detailed.[ncbi.nlm.nih.gov]
  • The child responded nicely to the treatment for acute osteomyelitis and congenital hypofibrinogenemia. So, in congenital hypofibrinogenemia, a joint swelling might be a resultant of an acute osteomyelitis, not mere hemarthrosis.[ncbi.nlm.nih.gov]
  • The only treatment given was a transfusion of fresh plasma prior to delivery. The importance of fibrinogen in maintaining normal placental insertion and the obstetric management of predelivery and delivery are discussed.[ncbi.nlm.nih.gov]
  • Although the patient received no treatment, her fibrinogen level increased to 307 mg/dl over the next 4 days and then remained above 260 mg/dl for the rest of her pregnancy. At 35 weeks' gestation, a healthy 2090 gm female was delivered.[ncbi.nlm.nih.gov]

Prognosis

  • Expectations (prognosis) Excess bleeding is common with this condition. These episodes may be severe, or even fatal. Bleeding in the brain is a leading cause of death in patients with this disorder.[coordinatedhealth.com]
  • Outlook (Prognosis) Excess bleeding is common with this condition. These episodes may be severe, or even fatal. Bleeding in the brain is a leading cause of death in patients with this disorder.[nicklauschildrens.org]
  • Outlook (Prognosis) Excessive bleeding is common with this condition. These episodes may be severe, or even fatal. Bleeding in the brain is a leading cause of death in people with this disorder.[stlukes-stl.com]
  • Then they'll use a combination of heparin and replacement therapy (platelets, cryoprecipitate or plasma, depending on labs) Prognosis depends on the underlying disease.[micunursing.com]

Etiology

  • This practical text covers disorders of thrombosis and hemostasis in a logical and sequential manner: etiology, pathophysiology, clinical and laboratory diagnosis, and management.[books.google.com]
  • "Etiology of afibrinogenemia: fibrinogenelytic and fibrinolytic phenomena" Annals NY Acad Sci 75, 676, 1959 19. Philipps, LL , Butlor, BC , Taylor, HC .[herdin.ph]
  • Although uncommon, this usually fatal disorder has been encountered by most obstetricians of long experience. 1 2 3 For many years it has been suspected that there was a common etiologic background for this hemorrhagic disorder and toxemia of pregnancy[nejm.org]
  • The most common etiology is disease of the liver or biliary tract.[clinlabnavigator.com]

Epidemiology

  • Management of Acute Hemorrhage Platelets Plasma and Specialized Coagulation Concentrate New Approaches for the Therapy of Bleeding Disorders Overview of Venous Thromboembolism Thrombophilia Genetics Epidemiology and Risk Factors for Venous Clinical Manifestations[books.google.es]
  • Many epidemiological studies have reported an association between coronary heart disease (CHD) and various “inflammatory” factors, including plasma levels of fibrinogen, C-reactive protein, albumin, and white blood cell (WBC) count.[clinlabnavigator.com]
  • ., Epidemiology and treatment of congenital fibrinogen deficiency. Thromb Res. 2012; 130 Suppl 2: S7-11. 16. Peyvandi, F. and M. Spreafico, National and international registries of rare bleeding disorders. Blood Transfus. 2008; 6 Suppl 2: s45-8. 17.[rarediseases.org]
  • […] milder form of fibrinogen deficiency; patients have fibrinogen levels 1.5 g/L Dysfibrinogenemia is the synthesis of abnormal fibrinogen molecules Hypodysfibrinogenemia is characterized by both low levels of fibrinogen and abnormal fibrinogen molecules Epidemiology[pathologyoutlines.com]
  • Fibrinogen: biochemistry, epidemiology and determinants. QJM 2003; 96:711–729. 18. Prasad JM, Gorkun OV, Raghu H, et al Mice expressing a mutant form of fibrinogen that cannot support fibrin formation exhibit compromised antimicrobial host defense.[journals.lww.com]
Sex distribution
Age distribution

Pathophysiology

  • This is the first report of purpura and hypofibrinogenemia induced by allopurinol and the pathophysiology underlying this reaction remained unknown.[ncbi.nlm.nih.gov]
  • Nathan and Oski’s is the only comprehensive product on the market that relates pathophysiology in such depth to hematologic and oncologic diseases affecting children.[books.google.com]
  • This practical text covers disorders of thrombosis and hemostasis in a logical and sequential manner: etiology, pathophysiology, clinical and laboratory diagnosis, and management.[books.google.com]
  • Manifestations and Diagnosis of Venous Venous Thrombosis in Unusual Sites Victor J Marder Hylton V Joffe and Sam Schulman Prevention of Venous Thromboembolic Disease Treatment of Venous Thromboembolic Disease Overview of Arterial Thrombotic Disorders Pathophysiology[books.google.es]

Prevention

  • CONCLUSIONS Routine use of Hemocoagulase For Injection for the prevention of late-onset bleeding is not recommended for patients who have undergone excision of colon polyps.[ncbi.nlm.nih.gov]
  • We discontinued tigecycline and gave the patient several blood products to prevent spontaneous bleeding. The adverse reaction disappeared after the withdrawal of tigecycline.[ncbi.nlm.nih.gov]
  • The zebrafish has orthologs to the three components of fibrinogen (fga, fgb, and fgg), but it hasn't yet been shown that zebrafish fibrinogen functions to prevent bleeding in vivo.[ncbi.nlm.nih.gov]
  • This case illustrates the course of mild FXIII and fibrinogen deficiencies during pregnancy, labor, and postpartum, and raises possible management options for prevention of antepartum and postpartum hemorrhage in women with these deficiencies.[ingentaconnect.com]
  • Warmuth Project co-operation: Philipp Mad Duration: October 2009 - January 2010 Publication : HTA Project report No. 39 - Background: Haemocomplettan P and Fibrogammin P are being increasingly used in the treatment of acquired hypofibrinogenemia to prevent[hta.lbg.ac.at]

References

Article

  1. Mannucci PM, Duga S, Peyvandi F. Recessively inherited coagulation disorders. Blood 2004; 104: 1243–52.
  2. Awasthy N, Aggarwal KC, Gupta H, Saluja S. Congenital hypofibrinogenemia. Indian Pediatrics. 2004; 41:185-187
  3. Fried K, Kaufman S. Congenital afibrinogenemia in 10 offsprings of uncle–niece marriages. Clin Genet 1980; 17: 223–7.
  4. Lak M, Keihani M, Elahi F, et al. Bleeding and thrombosis in 55 patients with inherited afibrinogenaemia. Br J Haematol 1999; 107: 204–6.
  5. Schneider D, Bukovsky I, Kaufman S, et al. Severe ovarian hemorrhage in congenital afibrinogenemia. Acta Obstet Gynecol Scand 1981; 60: 431.
  6. Peyvandi F, Duga S, Akhavan S, Mannucci PM. Rare coagulation deficiencies. Haemophilia 2002; 8: 308–21.
  7. Peyvandi F, Haertel S, Knaub S, Mannucci PM. Incidence of bleeding symptoms in 100 patients with inherited afibrinogenemia or hypofibrinogenemia. J Thromb Haemost. 2006 Jul; 4(7):1634-7.
  8. Acharya SS, Dimichele DM. Rare inherited disorders of fibrinogen. Haemophilia. 2008 Nov; 14(6):1151-8.
  9. Mammen EF. Fibrinogen abnormalities. Semin Thromb Hemost 1988; 9: 1-6.
  10. Besser MW, MacDonald SG. Acquired hypofibrogenemia: current perspectives. J Blood Med. 2016;7:217-225
  11. Hunault-Berger M, Chevallier P, Delain M, et al. Changes in antithrombin and fibrinogen levels during induction chemotherapy with L-asparaginase in adult patients with acute lymphoblastic leukemia or lymphoblastic lymphoma. Use of supportive coagulation therapy and clinical outcome: the CAPELAL study. Haematologica. 2008;93(10):1488–1494.
  12. Rodeghiero F, Castaman G, Dini E. Fibrinopeptide A changes during remission induction treatment with L-asparaginase in acute lymphoblastic leukemia: evidence for activation of blood coagulation. Thromb Res. 1990;57(1):31–38.
  13. Mackie IJ, Kitchen S, Machin SJ, Lowe GD. Haemostasis, Thrombosis Task Force of the British Committee for Standards in H. Guidelines on fibrinogen assays. Br J Haematol. 2003;121(3):396–404.
  14. Cunningham MT, Brandt JT, Laposata M, Olson JD. Laboratory diagnosis of dysfibrinogenemia. Arch Pathol Lab Med. 2002;126:499-505.

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Last updated: 2018-06-22 06:18