Detection of mild inherited disorders of blood coagulation: current options and personal recommendations

Abstract

Although assessment of prior personal and familial bleeding history is an important aspect of the diagnosis of bleeding disorders, patients with mild inherited bleeding disorders are sometimes clinically asymptomatic until presented with a hemostatic challenge. However, bleeding may occur after incursion of trauma or surgery, so detection of these conditions reflects an important facet of clinical and laboratory practice. Mild bleeding disorders may be detected as a result of family studies or following identification of abnormal values in first-line screening tests such as activated partial thromboplastin time, prothrombin time, fibrinogen and global platelet function screen testing, such as the platelet function analyzer. Following determination of abnormal screening tests, subsequent investigation should follow a systematic approach that targets specific diagnostic tests, and including factor assays, full platelet function assays and more extensive specialized hemostasis testing. The current report provides a personal overview on inherited disorders of blood coagulation and their detection.

Keywords:

• bleeding
• blood coagulation
• coagulation factor
• deficiency
• hemophilia
• platelet dysfunction
• von Willebrand disease

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• A proper diagnosis of mild bleeding disorders is critical to ensure that affected patients are appropriately managed (to avoid bleeding), while also avoiding inappropriate therapy for those patients not suffering these conditions (to thus prevent thrombosis and other adverse events).

• The hemostasis laboratory plays a pivotal role in identification of mild inherited disorders of blood coagulation, and also discounting the same in patients yielding non-clinically important ‘abnormal’ test results, since the testing arena takes advantage from a vast array of assays and includes different test methodologies.

• The appropriate diagnosis of any specific bleeding disorder can be facilitated by a systematic approach such as via a hierarchal algorithm, and considers the patient and family history (if present), the results of first-line screening assays and subsequent diagnostic testing to pinpoint any potential defect.

• Consideration needs to be given to preanalytical and analytical events that may give rise to false-positive and false-negative findings, as well as to repeat testing to confirm a defect before giving a specific diagnosis.

• Finally, a diagnosis should also consider and exclude the possible differential diagnoses.

Notes

^†A complete blood count including platelet count and morphology should also be included as a first-line test.

^‡May be performed as a second-line test in some laboratories.

^§May be performed as a first-line test in some laboratories.

^¶May be performed as a second-line test in some laboratories.

Performance of these tests does not necessarily infer that the patient needs to attend for separate collections at each stage. Consideration can be made for initial collection of sufficient samples for multiple assay performance, and to undertake assays from such a collection as required based on an algorithmic approach (Figure 3), or in some cases a pragmatic approach might be decided (e.g., earlier performance of platelet function testing by aggregometry to avoid multiple collections).