How do Hemophilia A (Factor VIII deficiency) and von Willebrand disease affect the Activated Partial Thromboplastin Time (aPTT)?

From the Guidelines

Hemophilia A (Factor VIII deficiency) and von Willebrand disease prolong the Activated Partial Thromboplastin Time (aPTT).

Mechanism of Prolongation

• The aPTT measures the time it takes for blood to clot via the intrinsic pathway, which involves factors VIII, IX, XI, and XII.
• In Hemophilia A, the deficiency of factor VIII impairs the intrinsic tenase complex, leading to a prolonged aPTT 1.
• Von Willebrand disease, which affects von Willebrand factor, a crucial component for platelet adhesion and factor VIII stabilization, also affects the intrinsic pathway and can prolong the aPTT.

Diagnostic Considerations

• The aPTT is used as a base assay for factor VIII/IX levels, with the one-stage clotting assay (OSCA) being a modified APTT mixing study 1.
• The chromogenic assay (CHR) is an alternative approach that isolates the intrinsic tenase complex, providing a more specific measurement of factor VIII and IX activity 1.

Clinical Implications

• Prolonged aPTT in Hemophilia A and von Willebrand disease increases the risk of bleeding, particularly in individuals with severe factor deficiencies 2.
• Replacement of factor VIII or IX with clotting factor concentrates can mitigate bleeding and is a crucial aspect of managing these conditions 2.

From the Research

Effect of Hemophilia A and von Willebrand Disease on aPTT

• Hemophilia A, characterized by a deficiency of factor VIII, leads to an increase in partial activated thromboplastin time (aPTT) that parallels the severity of the disease 3.
• von Willebrand disease, which affects the von Willebrand factor (a carrier for factor VIII in the circulation), can also impact aPTT levels, although the primary symptom is mucocutaneous bleeding 3.
• The aPTT test is used as a screening tool in the diagnosis of von Willebrand disease, along with other tests such as prothrombin time (PT) and platelet function analysis 4.

Relationship Between Factor VIII and von Willebrand Factor

• von Willebrand factor (VWF) is a multimeric adhesive protein that binds platelets to exposed subendothelium and carries factor VIII in the circulation 4.
• A deficiency or defect in VWF can lead to von Willebrand disease, which may result in a secondary deficiency of factor VIII procoagulant protein, affecting coagulation 5.
• The interaction between VWF and factor VIII is crucial, with VWF playing a key role in factor VIII function, production, stabilization, conformation, and immunogenicity 6.

Diagnostic Challenges

• Differentiating between hemophilia A and type 2N von Willebrand disease is essential, as therapy differs between the two conditions 7.
• Laboratory tests, including aPTT, VWF antigen, VWF activity, and factor VIII activity, are used to diagnose and classify von Willebrand disease 4.
• Genetic testing or a VWF:FVIII binding assay can help differentiate between hemophilia A and type 2N von Willebrand disease 7.