A 31-year-old male with prolonged bleeding after an oral sur

You are asked to consult on a 31-year-old male with prolonged bleeding after an oral surgery procedure. He has no prior history of bleeding diathesis or family history of bleeding disorders. The patient's past medical history is remarkable for infection with the human immunodeficiency virus, with a CD4 count of 51/mL3. The examination is remarkable only for spotty lymphadenopathy. The platelet count is 230,000 cells/mL. His international normalized ratio (INR) is 1.5. Activated partial thromboplastin time is 40 s. Peripheral blood smear shows no schistocytes and is otherwise unremarkable. A 1:1 mixing study corrects both conditions immediately and after a 2-h incubation. Fibrinogen level is normal. Thrombin time is prolonged. What is the diagnosis?

A. Disseminated intravascular coagulation (DIC)
B. Dysfibrinogenemia
C. Factor V deficiency
D. Liver disease
E. Factor XIII deficiency

B. Dysfibrinogenemia

Explanation:

Fibrinogen is a 340-kDa dimeric molecule made up of two sets of three covalently linked polypeptide chains. Thrombin cleaves multiple peptides to produce fibrin monomer that factor XIII stabilizes by cross-linking. Although fibrinogen is needed for platelet aggregation and fibrin formation, even severe fibrinogen deficiency such as afibrinogenemia produces mild, rare bleeding episodes, most often after surgery. Dysfibrinogenemia refers to a constellation of disorders that involve mutations that alter the release of fibrinopeptides, affect the rate of polymerization of fibrin monomers, or alter the sites of fibrin cross-linking. Dysfibrinogenemia is either inherited in an autosomal dominant fashion or acquired. Patients with liver disease, hepatomas, AIDS, and lymphoproliferative disorders may develop an acquired form of dysfibrinogenemia. The presence of altered partial thromboplastin time (PTT) and prothrombin time (PT)/INR reflects an abnormality in coagulation from the prothrombinase complex downstream to fibrin. Correction with a mixing study eliminates factor inhibition as a cause of the coagulation disorder. Other causes of prolongation of the PT and PTT include factor deficiencies in factor V or X, afibrinogenemia or dysfibrinogenemia, and consumption of coagulation factors from DIC. The absence of schistocytes from the blood smear makes DIC unlikely. The thrombin time tests the interaction with thrombin directly on fibrinogen. Its prolongation indicates an abnormality with that interaction and suggests a diagnosis of dysfibrinogenemia. Factor XIII deficiency is a bleeding disorder that manifests in childhood and is not consistent with this presentation.