A Hematological Menace: Multiple Venous Thrombosis Complicated by Acquired Factor VIII Deficiency

Abstract

Patient: Male, 21Final Diagnosis: Acquired Factor VIII DeficiencySymptoms: Abdominal hematoma • DVT • life threatening bleedingMedication: —Clinical Procedure: Life saving medical therapySpecialty: HematologyObjective:Rare diseaseBackground:Acquired hemophilia A (AHA) classically presents with spontaneous bleeding of mucosal sites, GI tract, and sub-cutaneous tissues, often leading to large hematomas and ecchymosis. Among documented cases, 50% are idiopathic and few have been associated with trauma or surgery. We present a case of life-threatening bleeding caused by AHA, following trauma and complicated by multiple venous thrombi.Case Report:A 21-year-old man presented with multiple injuries secondary to trauma leading to extensive life-saving surgery. Two weeks post-operatively, he developed multiple deep venous thrombi and was started on anticoagulation. Twenty-four days post-operatively, he started bleeding from multiple mucosal sites and developed an abdominal hematoma. Anticoagulation was stopped, with administration of fresh frozen plasma and vitamin K. Diagnosis of AHA was made based on low factor VIII level and presence of factor VIII inhibitors after an appropriate battery of tests ruled out other possible diagnoses. He was started on steroids and recombinant factor VIIa, leading to immediate improvement. Once stable, Rituximab infusions resulted in decreasing factor VIII inhibitor levels, with gradual normalization of PTT.Conclusions:AHA remains a diagnostic challenge because of its rarity, leading to delay in diagnosis and causing significant morbidity and mortality. Elevated PTT relative to PT/INR is a strong clue which should be followed by mixing studies. Very few cases have been associated with surgery or trauma and relatively few large, controlled trials have compared different treatment modalities for AHA. Growing evidence supports anti-CD20 (Rituximab) as an effective treatment option, as in this case.

Characteristics of Acquired Inhibitors to Factor VIII and Von Willebrand Factor Secondary to Systemic Lupus Erythematosus

“…In one case report, an SLE-related AHA patient successively developed hematoma and thrombosis 28 . Several case reports have described simultaneous thrombosis and AHA 29–32 . Two underlying mechanisms have been proposed.…”

“…28 Several case reports have described simultaneous thrombosis and AHA. [29][30][31][32] Two underlying mechanisms have been proposed. First, AHA may damage the blood vessels, releasing a large amount of platelet tissue factor, which directly activates factor X, leading to thrombus development.…”

Acquired factor VIII deficiency: two case reports and a review of literature

“…Several case reports of deep venous thrombosis occurring simultaneously with both acquired hemophilia A and B exist [10, 29]. One proposed mechanism to explain the paradoxical occurrence of both is that the tissue factor–factor VIIa complex of the extrinsic coagulation pathway, which normally activates factor X via a factor XI and factor VIII-dependent route, can, in sufficient quantities, activate factor X directly, leading to the formation of a clot.…”

Simultaneous hemorrhage and venous thrombosis in a patient with systemic lupus erythematosus

“…version of table available online). [18][19][20][21][22][23][24][25] Thrombotic events in the patients in studies 3, 4, 5, 7, and 8 were associated with use of bypassing agents. [20][21][22]24,25 Hemorrhage and thrombosis represent opposite ends of the coagulation cascade, but each can be independently fatal.…”

“…[18][19][20][21][22][23][24][25] Thrombotic events in the patients in studies 3, 4, 5, 7, and 8 were associated with use of bypassing agents. [20][21][22]24,25 Hemorrhage and thrombosis represent opposite ends of the coagulation cascade, but each can be independently fatal. Deep vein thrombosis can be triggered by recent surgery, malignancy, autoimmunity, or inherited or acquired thrombophilia.…”