An elderly patient with multiple myeloma develops bruising and hematuria. PT is normal, but aPTT and thrombin time are prolonged and do not correct with a mixing study. Fibrinogen and reptilase times are normal. This pattern is most consistent with which cause?

An elderly patient with multiple myeloma develops bruising and hematuria. PT is normal, but aPTT and thrombin time are prolonged and do not correct with a mixing study. Fibrinogen and reptilase times are normal. This pattern is most consistent with which cause?

• A. Acquired vitamin K deficiency
• B. Heparin-like anticoagulant
• C. Factor deficiency
• D. Factor inhibitor

Answer: (B)

This pattern tests how to distinguish a simple factor deficiency or inhibitor from an inhibitor that acts like heparin. The mixing study helps you see if the prolonged coagulation tests are due to missing factors (which would correct when normal plasma is mixed in) or due to an circulating inhibitor (which would not correct). Here, the patient has a prolonged aPTT and a prolonged thrombin time, with a normal fibrinogen and a normal reptilase time. The normal reptilase time is important: it shows the fibrinogen and the clotting mechanism at the thrombin step are not intrinsically defective, and it helps separate heparin-like effects from true dysfibrinogenemia or fibrinogen deficiency (those would typically alter reptilase as well). A prolonged thrombin time points to an interference at the final step of coagulation—either heparin or a direct thrombin inhibitor, or a circulating heparin-like substance. Because the mixing study did not correct the prolonged aPTT or thrombin time, this is not a simple factor deficiency or a deficiency that would fix itself with added normal plasma. In a myeloma patient, a circulating heparin-like anticoagulant can be produced, causing prolongation of aPTT and TT that do not correct with mixing. The combination of a normal fibrinogen and normal reptilase time, plus non-correction on mixing and a prolonged TT, best fits a heparin-like anticoagulant as the cause.

This pattern tests how to distinguish a simple factor deficiency or inhibitor from an inhibitor that acts like heparin. The mixing study helps you see if the prolonged coagulation tests are due to missing factors (which would correct when normal plasma is mixed in) or due to an circulating inhibitor (which would not correct).

Here, the patient has a prolonged aPTT and a prolonged thrombin time, with a normal fibrinogen and a normal reptilase time. The normal reptilase time is important: it shows the fibrinogen and the clotting mechanism at the thrombin step are not intrinsically defective, and it helps separate heparin-like effects from true dysfibrinogenemia or fibrinogen deficiency (those would typically alter reptilase as well). A prolonged thrombin time points to an interference at the final step of coagulation—either heparin or a direct thrombin inhibitor, or a circulating heparin-like substance.

Because the mixing study did not correct the prolonged aPTT or thrombin time, this is not a simple factor deficiency or a deficiency that would fix itself with added normal plasma. In a myeloma patient, a circulating heparin-like anticoagulant can be produced, causing prolongation of aPTT and TT that do not correct with mixing. The combination of a normal fibrinogen and normal reptilase time, plus non-correction on mixing and a prolonged TT, best fits a heparin-like anticoagulant as the cause.