Spontaneous antithrombin in a patient with benign paraprotein

Area of Science:

• Hematology
• Clinical Biochemistry

Background:

• Paraproteins, abnormal proteins produced by plasma cells, can interfere with hemostasis.
• Prolonged clotting times (prothrombin time, activated partial thromboplastin time, thrombin clotting time) can indicate coagulation factor deficiencies or inhibitors.

Observation:

• A 66-year-old man with peptic ulcer disease presented with spontaneously prolonged clotting tests.
• Standard coagulation assays showed abnormalities, but reptilase time was normal.
• The patient's purified fibrinogen was normal, but his serum contained an IgG inhibitor.

Findings:

• The patient's IgG paraprotein inhibited thrombin activity directly, affecting both normal plasma and purified fibrinogen.
• This inhibition mechanism differed from previously described paraproteins that interfere with fibrinogen cleavage or polymerization.
• The IgG reduced thrombin's activity on a chromogenic substrate, an effect overcome by increasing thrombin concentrations.

Implications:

• This case highlights a rare IgG paraprotein with direct antithrombin activity.
• Understanding this unique inhibitory mechanism is crucial for accurate diagnosis and management of bleeding disorders associated with paraproteins.
• Further research into the interaction between this paraprotein and thrombin may reveal novel therapeutic targets.