Coagulation disorders due to circulating anticoagulants: causes, symptoms, diagnosis, treatment

Circulating anticoagulants are usually autoantibodies that neutralize specific coagulation factors in vivo (e.g., autoantibodies against factors VIII and V) or inhibit protein-bound phospholipids in vitro. Sometimes late-type autoantibodies cause bleeding in vivo by binding prothrombin.

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Forms

Isoantibodies to factor VIII develop in 15-30% of patients with severe hemophilia A as a complication of repeated exposure to normal factor VIII molecules as replacement therapy.

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Anticoagulants affecting factor VIII levels

Antibodies to factor VIII may occasionally occur in patients without hemophilia, such as postpartum women as a manifestation of a systemic autoimmune disease, in transient immune dysregulation, in elderly patients in the absence of other diseases. Life-threatening bleeding may develop in patients with factor VIII anticoagulants.

Plasma containing antibodies to factor VIII is characterized by an increase in partial thromboplastin time, which is not corrected by the addition of normal plasma or another source of factor VIII in a 1:1 ratio with the patient's plasma. Testing is performed immediately after mixing and after incubation.

Cyclophosphamide and glucocorticoid therapy may reduce autoantibody production in patients without hemophilia. In postpartum women, autoantibodies may disappear spontaneously.

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Diagnostics coagulation disorders

The presence of circulating anticoagulants should be suspected in patients with severe bleeding, an increase in both partial thromboplastin time and prothrombin time, which are not corrected when the test is repeated on a mixture of normal plasma and patient plasma in a 1:1 ratio.

Antiphospholipid antibodies usually promote thrombosis. However, in some patients, antibodies bind to the prothrombin-phospholipid complex, inducing hypoprothrombinemia, which can lead to severe bleeding.

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Treatment coagulation disorders

Cyclophosphamide and glucocorticoid therapy may reduce autoantibody production in patients without hemophilia. In postpartum women, autoantibodies may disappear spontaneously.