What is the management of isolated prolonged activated Partial Thromboplastin Time (APTT) coagulation?

From the Guidelines

Management of isolated prolonged activated partial thromboplastin time (aPTT) should begin with determining the underlying cause through additional testing, prioritizing the patient's morbidity, mortality, and quality of life. The first step in managing isolated prolonged aPTT is to perform a mixing study to distinguish between factor deficiencies and inhibitors, as recommended by 1. If the mixing study corrects the aPTT, specific factor assays (particularly factors VIII, IX, XI, and XII) should be ordered to identify the deficient factor.

Key Considerations

• If the mixing study fails to correct, testing for lupus anticoagulant and specific factor inhibitors is warranted, as suggested by 1.
• For factor deficiencies, treatment depends on the specific factor involved - factor VIII deficiency (hemophilia A) requires factor VIII concentrate at 20-40 IU/kg, factor IX deficiency (hemophilia B) requires factor IX concentrate at 20-40 IU/kg, while factor XI deficiency may require fresh frozen plasma at 15-20 mL/kg.
• For lupus anticoagulant without clinical thrombosis, no specific treatment is needed as this represents a laboratory abnormality rather than a bleeding risk.
• If the prolonged aPTT is due to heparin therapy, protamine sulfate can be administered at 1 mg per 100 units of heparin.

Treatment of Acquired Hemophilia A

• For acquired inhibitors like acquired hemophilia A, immunosuppression with prednisone 1 mg/kg/day and cyclophosphamide 1-2 mg/kg/day may be required, along with bypassing agents such as recombinant factor VIIa (90 μg/kg every 2-3 hours) or activated prothrombin complex concentrate for acute bleeding, as recommended by 1.
• Factor XII deficiency typically requires no treatment as it doesn't cause bleeding despite laboratory abnormalities.

Diagnostic Approach

• Patients with a prolonged aPTT and a clinical picture suggestive of AHA should have FVIII, IX, XI and XII levels measured, as suggested by 1.
• An isolated low FVIII level is suggestive of AHA, and specific tests for a lupus anticoagulant should be performed.
• Factor assays should be repeated at higher serial dilutions of the test plasma, which will attenuate the effect of the inhibitor or lupus anticoagulant on the factor measurement. In summary, the management of isolated prolonged aPTT requires a comprehensive diagnostic approach and targeted treatment to minimize morbidity, mortality, and improve quality of life, as supported by the recommendations of 1, 1, and 1.

From the Research

Causes of Isolated Prolonged APTT

• Isolated prolonged activated partial thromboplastin time (APTT) can be caused by several factors, including lupus anticoagulants, anticoagulant treatment, and deficiencies of specific coagulation factors 2, 3, 4.
• Lupus anticoagulants are a common cause of isolated prolonged APTT, and can be detected using mixing studies and modified dilute Russell viper venom time method 3, 5.
• Anticoagulant treatment, mainly heparin, can also cause isolated prolonged APTT 2, 4.
• Deficiencies of specific coagulation factors, such as factors VIII, IX, and XI, can also lead to isolated prolonged APTT 2, 4.

Diagnostic Approach

• A diagnostic algorithm can be used to differentiate between lupus anticoagulants and factor deficiencies 2.
• The identification of the cause of isolated prolonged APTT is essential for proper treatment and management of patients 3, 4.
• Paired APTTs of low and high lupus anticoagulant sensitivity can be used to detect lupus anticoagulant and distinguish it from other abnormalities 5.
• Knowledge of reagent sensitivity to lupus anticoagulant, heparin, and clotting factors is important for interpreting APTT results and troubleshooting prolonged APTTs 6.

Clinical Management

• Isolated prolonged APTT may lead to delayed surgery and emotional stress for patients and their families, and may be associated with increased costs due to re-testing and coagulation factor assessment 4.
• The correct identification of the cause of APTT prolongation is essential for proper treatment and management of patients 3, 4.
• Prolonged APTT is not considered an absolute indication for plasma infusion therapy in patients with lupus anticoagulant 3.