LAUSR

On a Friday evening, a 54-year-old man with celiac disease presented to the emergency department following 6 days of right arm and leg pain with swelling, which limited his ambulation. He also noted an enlarging bruise extending from his right leg to his lower back, which prompted the medical evaluation. There was no personal or familial history of bleeding or clotting disorder, and he was not on an anticoagulant. Despite vital signs being within normal range, he appeared pale with two large ecchymoses: one from the right upper arm extending to his forearm and the second covering his entire right lateral torso. His initial laboratory results revealed a hemoglobin of 7.6 g/dL (reference intervals [RI]: 13.0–17), platelet count of 403 10/L (RI: 150–450), activated partial thromboplastin time (aPTT) of 102 s (RI: 22–37), prothrombin time (PT) of 13.5 s (RI: 11.9–14.4), thrombin time of 15.2 s (RI <23), and a plasma fibrinogen of 568 mg/dL (RI: 200–400) (Table 1). For a patient with an isolated prolonged aPTT without prior history of hemophilia, thrombophilia, or anticoagulation, repeat aPTT on a freshly collected specimen. aPTT could be prolonged from heparin contamination, especially in intensive care unit settings when blood is drawn from a central venous catheter. To rule out heparin contamination, perform the thrombin time or aPTT with heparinase to remove the heparin effect. Additionally, factors V and VIII are labile, and may degrade with prolonged specimen transport and processing. Evaluate history for a prior normal aPTT if possible, which typically eliminates congenital factor deficiencies such as hemophilias A or B. A thorough history should be obtained to assess the presence of liver disease or medication such as warfarin or direct oral anticoagulants (DOACs) that may affect both PT and aPTT. A mixing study to distinguish an inhibitor (factor inhibitor, inhibitor drug, or nonspecific inhibitor) from a factor deficiency would be an important diagnostic step. Patient was admitted to the medicine ward and transfused 2 units of packed red blood cells (pRBC). Given the late hour and the start of a weekend, standard coagulation studies—mixing study, factor VIII, IX, XI, and XII levels—could not be performed. However, thromboelastography (TEG 5000, Haemonetics, Boston, MA) was available to assess patient's underlying coagulopathy. A citrated whole blood sample specimen (1.0 mL) was drawn and gently mixed with kaolin. Immediately following, 340 μL of blood was transferred from the kaolin tube into a cup containing 20 μL of calcium chloride. The TEG result revealed a significantly prolonged reaction time (R value) of 86 min and an unmeasurable maximal amplitude (MA), suggestive of a complete lack of clot formation (Figure 1A (tracing A), B). With clinical presentation and TEG result suspicious for acquired hemophilia, the patient was started on a FVIII inhibitor bypassing agent (activated prothrombin complex concentrates, aPCCs; FEIBA, Baxter, Deerfield, IL) within 24 h of admission while mixing studies were pending. On day 3 of hospitalization, a mixing study showed incomplete correction of immediate mixing at room temperature (Table 1). FVIII was significantly decreased, while other aPTT dependent factors were within normal range. As the patient was acutely bleeding, the mixing study specimen was further incubated and did not correct, suggesting time and temperature-dependent inhibitor. Mixing study results should be interpreted in the context of the clinical scenario. With complete correction of immediate and incubated mixing studies, the abnormal aPTT suggests intrinsic factor deficiency (VIII, IX, XI, XII, prekallikrein or high molecular weight kininogen). If aPTT does not correct, patient's clinical scenario suggests a need for further workup. If aPTT does not correct and patient Received: 21 September 2021 Revised: 29 November 2021 Accepted: 6 December 2021