Bleeding of unknown cause and unclassified bleeding disorders; diagnosis, pathophysiology and management

Abstract

Haematologists are frequently faced by how to investigate and manage a mild bleeding tendency. If a diagnosis of an established bleeding disorder is forthcoming, then management can align with treatment guidelines. In reality, many patients do not reach a firm diagnosis for their bleeding symptoms despite clinically having a bleeding disorder. The aim of this review article is to comprehensively review the literature with regards to patients with bleeding of unknown cause (BUC) and unclassified bleeding disorders (UBD), and highlight where research is required.

Cryptogenic oozers and bruisers

“…5,12 If there is strong sus pi cion for a bleed ing dis or der of pri mary hemo sta sis, spe cific VWD test ing pan els and plate let aggregometry should be used despite the increased tech ni cal and inter pre tive com plex ity of aggregometry. 1,12 Collagen dis or ders, such as Ehlers-Danlos syn drome, should also be con sid ered and are eval u ated by joint mobil ity stud ies and genetic test ing in some cases. Because a sig nifi cant num ber of patients with Ehlers-Danlos syn drome who have an ele vated bleed ing score have been shown to also have plate let dys func tion, plate let func tion test ing is con sid ered use ful in this set ting.…”

“…Rare patients have inherited reces sive defects in the fibri no lytic inhib i tors A2AP and plas min o gen acti va tor inhib i tor 1 (PAI-1), resulting in a bleed ing dis or der with delayed bleed ing due to increased lysis of fibrin clots. 1,43 Routine clot ting times are normal. 1,44 Testing for A2AP and PAI-1 should be reserved until abnormal i ties that are more com mon have been excluded.…”

“…1,43 Routine clot ting times are normal. 1,44 Testing for A2AP and PAI-1 should be reserved until abnormal i ties that are more com mon have been excluded. Testing for fibri no lytic dis or ders can be dif fi cult to inter pret due to com plex inter ac tions between fibri no lytic acti va tors and inhib i tors and effects of preanalytical var i ables related to blood draw qual ity and tim ing.…”

“…Both inherited and acquired abnor mal i ties should be care fully con sid ered, with close atten tion to bleed ing assess ment tool results, med i cal history, fam ily his tory, med i ca tions, liver and renal func tion, and phys i cal exam i na tion fi nd ings. 1 In this review, we discuss how to best approach the lab o ra tory workup beyond the com mon tests, includ ing lim i ta tions and inter pre ta tion of lab o ra tory test ing. The arti cle is orga nized by hemo sta sis com po nent: pri mary hemo sta sis, sec ond ary hemo sta sis, and fi bri no ly sis.…”

Thrombin generation measured by two platforms in patients with a bleeding tendency: Reply

“…Bleeding of unknown course and/or unclassified bleeding disorders are a well-known unresolved phenomenon. 4 Further studies with laboratory tests beyond the conventional assays in this patient population could help to finally find a tool to assist in diagnosis and management of these patients. This was also the aim of our study.…”