Acquired Hemophilia-A Mimicking Trauma-induced Coagulopathy in a Young Polytrauma Patient

Case presentation

A 20-year-old man without prior health issues was brought to the Emergency Department following a high-speed motorcycle crash.

On arrival: Glasgow Coma Scale (GCS) 13, hypotension (BP 80/40 mmHg), tachycardia, and signs of thoracoabdominal trauma. A positive Focused Assessment with Sonography for Trauma (FAST) examination prompted activation of the major trauma protocol.

Prehospital care: Within 3 hours of injury, the patient received tranexamic acid (TXA, 1 g IV) during prehospital resuscitation, along with balanced transfusion support according to major trauma guidelines.

Initial management

Whole-body computed tomography (CT) revealed multiple rib fractures, bilateral pulmonary contusions, a pelvic fracture, and a grade IV liver laceration. The patient received red blood cells, plasma, and platelets, followed by hepatic artery embolization. He was admitted to the intensive care unit (ICU) in critical condition.

Clinical progression

By day 2 (≈ 36 hours post-trauma), hemodynamic stabilization was achieved. At day 3 post-injury (≈ 60–72 hours after the crash), laboratory studies revealed a markedly prolonged activated partial thromboplastin time (aPTT > 120 s) with normal prothrombin time (PT/INR 1.1), stable platelet count (190 × 10⁹/L), and normal fibrinogen (3.2 g/L).

Clinical bleeding: Spontaneous oozing from intravenous and drain sites began approximately 48–60 hours after trauma, coinciding with aPTT prolongation. Despite prior TXA administration and conventional transfusion therapy, coagulopathy persisted.

Diagnostic ROTEM evaluation

Rotational thromboelastometry (ROTEM) was performed to characterize the coagulation disturbance.

Parameter definitions:

• CT (Clotting Time): time from assay start to initial clot formation.
• CFT (Clot Formation Time): time from the first measurable clot to defined firmness
• α-Angle: slope of clot build-up, reflecting fibrin polymerization rate.
• MCF (Maximum Clot Firmness): peak clot strength.
• ML (Maximum Lysis): percentage reduction of MCF, indicating fibrinolysis.

Interpretation

ROTEM showed a markedly prolonged INTEM CT (> 1800 s) with normal EXTEM, FIBTEM, and APTEM, confirming isolated intrinsic pathway dysfunction. Because APTEM did not correct the abnormalities and ML was normal, hyperfibrinolysis was excluded—particularly relevant given prior TXA administration. This pattern was highly suggestive of acquired hemophilia A (factor VIII inhibition) rather than trauma-induced coagulopathy (TIC), which usually presents with global derangement and reduced FIBTEM MCF.

Confirmatory testing:

• Factor VIII activity: < 1 %
• Bethesda inhibitor titer: > 5 BU
• → Diagnosis: Acquired hemophilia A.

Treatment and outcome

Immediate therapy with recombinant activated factor VII (rFVIIa) and immunosuppression (methylprednisolone + cyclophosphamide) was initiated.

Hemostasis improved within 24 hours, bleeding ceased, and coagulation parameters normalized.

The patient continued ICU management for trauma-related injuries and was discharged to hematology follow-up on day 15 with full recovery.

Comparison of ROTEM Patterns in Acquired Hemophilia A, Trauma-Induced Coagulopathy, and Hyperfibrinolysis

Interpretive summary

• Timing: Coagulopathy and bleeding onset occurred 48–60 hours post-trauma, despite early TXA administration.
• ROTEM pattern: isolated INTEM CT > 1800 s, preserved EXTEM, FIBTEM, and APTEM, excluding hyperfibrinolysis.
• Diagnosis: Acquired hemophilia A (factor VIII inhibition), confirmed by factor VIII < 1 % and inhibitor > 5 BU.

Discussion

Acquired hemophilia A (AHA) is a rare but potentially life-threatening autoimmune bleeding disorder characterized by the development of autoantibodies (inhibitors) against coagulation factor VIII (FVIII). These inhibitors neutralize FVIII activity, resulting in an isolated prolongation of the activated partial thromboplastin time (aPTT) and clinical picture of spontaneous or disproportionate bleeding. Although most cases occur idiopathically or in association with autoimmune diseases, malignancy, or the postpartum state, AHA may also arise secondary to trauma or surgical injury, as illustrated in this case.

In the present patient, coagulopathy developed 48–60 hours after a high-energy trauma, despite hemostatic stabilization and early tranexamic acid (TXA) administration. The isolated, extreme prolongation of the INTEM clotting time (CT > 1800 s) with normal EXTEM, FIBTEM, and APTEM results on ROTEM was incompatible with trauma-induced coagulopathy or hyperfibrinolysis and strongly suggested FVIII inhibition. This was subsequently confirmed by FVIII activity < 1 % and a Bethesda inhibitor titer > 5 BU, establishing the diagnosis of post-traumatic AHA.

Pathogenesis: Post-traumatic versus Idiopathic AHA

The “second-hit” hypothesis proposes that severe tissue injury can trigger autoantibody formation in genetically or immunologically susceptible individuals. Following trauma, antigen-presenting cells (APCs) and helper T cells are activated by DAMPs and inflammatory cytokines (IL-6, TNF-α, IFN-γ). This inflammatory milieu enhances presentation of FVIII-derived peptides, resulting in activation of autoreactive B cells that produce neutralizing IgG4 antibodies. The process parallels mechanisms described in drug-induced or infection-related autoimmune phenomena.

In this patient, massive tissue damage, cytokine release, and exposure of cryptic FVIII epitopes likely broke immune tolerance, initiating autoantibody production despite no prior autoimmune disease or medication exposure. The temporal association—appearance of bleeding and prolonged aPTT approximately two days after injury—supports this immunologic trigger mechanism.

Clinical relevance

Recognition of post-traumatic AHA is critical because its presentation can mimic trauma-induced coagulopathy (TIC) or disseminated intravascular coagulation (DIC), but management differs entirely. In TIC, fibrinogen replacement and plasma resuscitation are key; in contrast, AHA requires bypassing agents (e.g., recombinant activated factor VII [rFVIIa] or activated prothrombin complex concentrate [aPCC]) and immunosuppressive therapy to eradicate inhibitors. Early use of ROTEM or other viscoelastic testing enables rapid differentiation: isolated INTEM CT prolongation with preserved EXTEM and FIBTEM profiles should prompt immediate investigation for FVIII inhibitors [1-10].

Conclusion

This case illustrates post-traumatic acquired hemophilia A presenting with delayed-onset bleeding after initial hemostatic stabilization and despite early antifibrinolytic therapy. Trauma likely served as an immunological trigger, leading to FVIII autoantibody formation. Incorporating ROTEM analysis early in unexplained post-trauma coagulopathy can be life-saving by differentiating acquired inhibitors from typical trauma-related coagulopathy and guiding appropriate immunosuppressive and hemostatic therapy.