Point-of-Care Testing in Patients with Hereditary Disorders of Primary Hemostasis: A Narrative Review

Abstract

Inherited disorders of primary hemostasis, such as von Willebrand disease and congenital platelet disorders, can cause extensive, typically mucocutaneous bleeding. Assays to diagnose and monitor these disorders, such as von Willebrand factor activity assays and light transmission aggregometry, are performed in specialized hemostasis laboratories but are commonly not available in local hospitals. Due to the complexity and relative scarcity of these conventional assays, point-of-care tests (POCT) might be an attractive alternative in patients with hereditary bleeding disorders. POCTs, such as thromboelastography, are increasingly used to assess hemostasis in patients with acquired hemostatic defects, aiding clinical decision-making in critical situations, such as during surgery or childbirth. In comparison, the use of these assays in patients with hereditary hemostasis defects remains relatively unexplored. This review aims to give an overview of point-of-care hemostasis tests in patients with hereditary disorders of primary hemostasis. A summary of the literature reporting on the performance of currently available and experimental POCTs in these disorders is given, and the potential utility of the assays in various use scenarios is discussed. Altogether, the studies included in this review reveal that several POCTs are capable of identifying and monitoring severe defects in the primary hemostasis, while a POCT that can reliably detect milder defects of primary hemostasis is currently lacking. A better understanding of the strengths and limitations of POCTs in assessing hereditary defects of primary hemostasis is needed, after which these tests may become available for clinical practice, potentially targeting a large group of patients with milder defects of primary hemostasis.

Fig. 1

Overview of search and included articles. “Language” indicates non-English articles. “Subject” indicates not related to topic. CR, case report; CSA, clot signature analyzer; PFA, platelet function analyzer; POCT, point-of-care test; ROTEM, rotational thromboelastometry; RV, review; TEG, thromboelastography; T-TAS, total Thrombus formation analysis system. ^a indicates two reviews with meta-analysis aspects were included. ^b indicates one article was included despite the full text being unavailable, as the main outcomes were clear from the abstract. ^c indicates one and two additional articles were identified through targeted searches on PubMed for “Platelet mapping” and “whole blood lumi,*” respectively. ^d indicates a questionnaire study on what assays are used in practice for patients with (suspected) inherited platelet disorders.

Fig. 2

( A and B ) Overview of studies directly comparing platelet function analyzer (PFA) and bleeding time (BT) in patients with von Willebrand disease ( A ) and platelet function disorders (PFDs) ( B ). Bars represent number of patients tested with the assay. Patients with an abnormal result (true-positive) are depicted in blue, patients with a normal result (false-negative) are depicted in red.

Fig. 3

Schematic overview of the described POC assays. CIFT, collagen-induced thrombus formation time; CPA, cone and plate(let)/impact-R analyzer; CSA, clot signature analyzer; CT, clotting time; PHT, platelet hemostasis time; PFA, platelet function analyzer; POC, point-of-care; ROTEM, rotational thromboelastometry; TEG, thromboelastography.

Fig. 4

Example of a thromboelastography (TEG) and rotational thromboelastometry (ROTEM) tracing. All parameters reflect on distinct aspects of coagulation. Initiation phase: reaction-time (R-time) and clotting time (CT), the time from start of the assay until an amplitude of 2 mm is reached. Propagation phase: kinetic-time (K-time) and clot formation time (CFT), time from 2-mm amplitude until 20-mm amplitude; a-angle, slope between R-time/CT and K-time/CFT; clot strength, maximal amplitude (MA) and maximal clot firmness (MCF), highest amplitude reached; fibrinolysis, clot lysis 30 (CL30) and lysis 30 (LY30), decrease of amplitude after 30 minutes compared with MA/MCF.

Fig. 5

Reported sensitivity of platelet function analyzer in von Willebrand disease patients. Only studies that performed both the epinephrine and adenosine diphosphate cartridge were included unless sensitivity was 100%, despite only one of these cartridges being used, as in these cases using both cartridges would not have altered the sensitivity. Studies written by authors who published multiple publications on this subject are depicted in colors identifying the particular author. Size of the points signifies the number of patients included in the study. Author and year of publication are depicted for studies reporting a sensitivity < 70%.

Fig. 6

Reported sensitivity of the platelet function analyzer in patients with platelet function disorders. Either an abnormal test result with the epinephrine or adenosine diphosphate cartridge is considered a positive test. Size of the points represents number of patients included in the study. Colors represent the disease studied. NOS, not otherwise specified.