A dysfibrinogenemia leading to resistance to bovine thrombin

Introduction: A 26-year-old woman presented to our institute for a routine check-up. Nothing was abnormal excepted a prolonged Thrombin Time and a low fibrinogen concentration determined by the Clauss method. Fibrinogen concentration was then measured by PT-derived method, and revealed normal levels. This was therefore suggestive for a dysfibrinogenemia. The patient had no history of haemostatic problems and was under no medication. Her family history revealed nothing relevant, but death of her father from a cerebrovascular accident. Methods and results: Complementary tests were performed: Platelet Function Assay, Factor VIII coagulant activity, von Willebrand antigen quantification, Ristocetin Cofactor activity, thromboelastogram and euglobulin lysis time were all within normal ranges. Finally, thrombin time and Clauss fibrinogen using a human thrombin instead of a bovine thrombine revealed normal results. DNA was then extracted for sequencing the genes coding for fibrinogen. This revealed the presence of a substitution Arg.Cys in position 275 of the c-chain of the fibrinogen. Discussion: This mutation has already been reported in the literature with four cases of thrombosis, three cases of haemorrhage and eight had no clinical signs. The gamma chain is implicated in several crucial interactions such as the primary polymerization 'a', the binding to calcium, the factor XIIIa-induced crosslinking, the binding to plasminogen and to tissue plasminogen activator. Results of the literature show that this mutation has several impacts on in vitro tests, and we proved that those can be corrected by the use of human thrombin

Primary Hemostasis in Chronic Liver Disease and Cirrhosis: What Did We Learn over the Past Decade?

Changes in primary hemostasis have been described in patients with chronic liver disease (CLD) and cirrhosis and are still subject to ongoing debate. Thrombocytopenia is common and multifactorial. Numerous studies also reported platelet dysfunction. In spite of these changes, primary hemostasis seems to be balanced. Patients with CLD and cirrhosis can suffer from both hemorrhagic and thrombotic complications. Variceal bleeding is the major hemorrhagic complication and is mainly determined by high portal pressure. Non portal hypertension-related bleeding due to hemostatic failure is uncommon. Thrombocytopenia can complicate management of invasive procedures in CLD patients. Recently, oral thrombopoietin agonists have been approved to raise platelets before invasive procedures. In this review we aim to bundle literature, published over the past decade, discussing primary hemostasis in CLD and cirrhosis including (1) platelet count and the role of thrombopoietin (TPO) agonists, (2) platelet function tests and markers of platelet activation, (3) von Willebrand factor and (4) global hemostasis tests

Manifestations hémorragiques et élévation isolée du temps de céphaline activée chez l’adulte : à propos d’un cas clinique

Le diagnostic différentiel de l’allongement isolé du temps de céphaline activée (TCA) est large. Une cause rare mais grave est l’hémophilie A acquise (AHA) liée à la formation spontanée d’anticorps neutralisants dirigés contre le facteur de coagulation VIII endogène. Les symptômes principaux sont secondaires à des hémorragies inattendues et sévères, parfois létales. Nous rapportons un cas d’AHA associée à une pemphigoïde bulleuse (BP), une dermatose subépidermique bulleuse chronique auto-immune. Un traitement court à base de corticoïdes et de rituximab a permis la guérison de l’AHA et un bon contrôle de la BP.[Unexpected bleeding and isolated prolongation of activated partial thromboplastin time: a case report] The differential diagnosis of isolated prolongation of the activated partial thromboplastin time (aPTT) is vast. An infrequent but severe cause is acquired hemophilia A (AHA) which is due to the spontaneous formation of neutralizing antibodies against endogenous factor VIII. About half the cases are associated with pregnancy, post-partum, autoimmune diseases, malignancies, or adverse drug reactions. Symptoms include severe and unexpected bleeding that may prove lifethreatening. We report a case of AHA associated with bullous pemphigoid (BP), a chronic, autoimmune, subepidermal, blistering skin disease. AHA was completely cured and BP wellcontrolled with a short-term treatment consisting of methylprednisolone and rituximab

Successful Management of Acquired Hemophilia A Associated with Bullous Pemphigoid: A Case Report and Review of the Literature.

BACKGROUND. Acquired hemophilia A (AHA) is a rare condition, due to the spontaneous formation of neutralizing antibodies against endogenous factor VIII. About half the cases are associated with pregnancy, postpartum, autoimmune diseases, malignancies, or adverse drug reactions. Symptoms include severe and unexpected bleeding that may prove life-threatening. CASE STUDY. We report a case of AHA associated with bullous pemphigoid (BP), a chronic, autoimmune, subepidermal, blistering skin disease. To our knowledge, this is the 25th documented case of such an association. Following treatment for less than 3 months consisting of methylprednisolone at decreasing dose levels along with four courses of rituximab (monoclonal antibody directed against the CD20 protein), AHA was completely cured and BP well-controlled. CONCLUSIONS. This report illustrates a rare association of AHA and BP, supporting the possibility of eradicating the inhibitor with a well-conducted short-term treatment