Diagnosis and monitoring

Treatment of von Willebrand disease (VWD) is dependent on a differential diagnosis, which requires classification of VWD into one of six types. Thus, in addition to initial laboratory investigation for the diagnosis of VWD, specific assays are required for the diagnosis of VWD type.

FVIII replacement therapy for patients with haemophilia A (HA) is guided by accurate laboratory-based diagnosis and post-infusion monitoring.

FIX replacement therapy for patients with haemophilia B (HB) is guided by accurate laboratory-based diagnosis and post-infusion monitoring.

The development of an inhibitor complicates the management of persons with haemophilia, limiting treatment options and resulting in poorer outcomes. Patients with haemophilia A (HA) or B (HB) who are exposed to products that contain coagulation factors should be screened for the presence of an inhibitor whenever a reduced treatment response or lower than expected factor recovery levels are observed.

Acquired haemophilia A (AHA) should be suspected in any patient with acute or recent bleeding symptoms, no previous history of a bleeding disorder, an unexplained, isolated activated partial thromboplastin time (aPTT) but a normal prothrombin time (PT).

Factor V congenital deficiency (FV CD) is characterised by prolonged activated partial thromboplastin and prothrombin times. Specific factor activity assays are required to differentiate FV CD from combined FV and FVIII deficiency.

FVII congenital deficiency (FVII CD) should be suspected in any patient presenting with an isolated prolonged prothrombin time (PT) and a normal activated partial thromboplastin time (aPTT). The diagnosis can be confirmed using a FVII activity assay and molecular genetic analysis.

As factor X (FX) plays a role in both the intrinsic and extrinsic coagulation pathways, prolonged activated partial thromboplastin time (aPTT) and prothrombin times (PT) can be an indicator of FX congenital deficiency (FX CD). Depending on the genetic variant, however, diagnostic tests can also vary. Thus, Russell’s viper venom tests and direct factor activity assays are necessary to confirm a FX CD diagnosis.

An isolated, prolonged activated partial thromboplastin time (aPTT), is suggestive of a FXI deficiency once other intrinsic pathway coagulation factors have been excluded.

Because factor XII congenital deficiency (FXII CD) does not manifest as a clinical phenotype, the finding of a prolonged activated partial thromboplastin time and diagnosis of FXII CD through a factor activity assay is often delayed.

The diagnosis of FXIII congenital deficiency (FXIII CD) must be based on results of appropriate laboratory tests. Standard coagulation screening tests, including prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen level, platelet count and bleeding time are normal, therefore a complete evaluation of the clotting system should include specific FXIII assays.

Platelet function assays serve as the basis for a differential diagnosis of Glanzmann’s thrombasthenia. Confirmation is provided by a molecular characterisation of surface glycoprotein expression and the corresponding genetic analysis.