Diagnostic approach to the patient with a suspected inherited platelet disorder: Who and how to test

Abstract

A 4-year-old boy is referred to hematology for recurrent epistaxis (4 to 5 times per month) which have been present for 2 years and require multiple visits to the emergency department for packing/ cauterization. Ear, nose, and throat evaluation was unremarkable for structural lesions. He has dark/black stools that occur independent of the nosebleeds. Screening studies showed normal prothrombin time (PT), activated partial thromboplastin time (APTT), and a normal platelet count at 352,000/μl. Mild microcytic anemia had been noted by his pediatrician and oral iron supplements were started with almost complete normalization of hemoglobin. Laboratory studies show a von Willebrand factor (VWF) antigen of 108 IU/dl, activity by ristocetin cofactor of 105 IU/dl, and factor VIII (FVIII)

Diagnostic workup of inherited platelet disorders

“…Microthrombocytopenia (thrombocytopenia with small platelet size) includes Wiskott-Aldrich syndrome (WAS) and x-linked thrombocytopenia (XLT) [ 4 , 8 ]. Thrombocytopenia with normal platelet size is related with various IPDSs and acquired disorders, and macrothrombocytopenia (thrombocytopenia with large platelet size) can be seen in Bernard-Soulier syndrome (BSS), MYH9-related disease, 22q deletion syndrome, and Paris/Trousseau/Jacobsen syndrome (PT/J) [ 4 , 8 , 11 ]. Platelet size can be estimated using the mean platelet volume (MPV), and the presence of giant platelets is usually flagged by automated hematologic analyzers [ 15 ].…”

“…A few clinical guidelines suggest a step-by-step approach for diagnosing IPDs [ 2 , 3 , 9 , 10 ]. The first step in the diagnosis of IPDs starts with a careful clinical evaluation of the patient and family members, including history and pattern of bleeding with or without surgery and trauma, intake of food drugs that can affect platelet function, and family history of thrombocytopenia or other malignancies [ 9 , 11 ]. Since bleeding symptoms can be subjective in both patient descriptions and physician examinations, bleeding assessment tools (BAT) can standardize the severity of bleeding symptoms [ 9 , 11 , 12 ].…”

“…The first step in the diagnosis of IPDs starts with a careful clinical evaluation of the patient and family members, including history and pattern of bleeding with or without surgery and trauma, intake of food drugs that can affect platelet function, and family history of thrombocytopenia or other malignancies [ 9 , 11 ]. Since bleeding symptoms can be subjective in both patient descriptions and physician examinations, bleeding assessment tools (BAT) can standardize the severity of bleeding symptoms [ 9 , 11 , 12 ]. In the clinical setting of von Willebrand disease (vWD), an international society of thrombosis and hemostasis (ISTH) BAT score >6 showed a 99% probability of an IPD [ 11 , 13 ].…”

“…Since bleeding symptoms can be subjective in both patient descriptions and physician examinations, bleeding assessment tools (BAT) can standardize the severity of bleeding symptoms [ 9 , 11 , 12 ]. In the clinical setting of von Willebrand disease (vWD), an international society of thrombosis and hemostasis (ISTH) BAT score >6 showed a 99% probability of an IPD [ 11 , 13 ]. In addition, a complete physical examination should be performed to evaluate signs of bleeding and the features of potential syndromic IPDs [ 9 ].…”

“…Diseases that are not related to platelet function, particularly immune thrombocytopenia (ITP), should be excluded before starting diagnostic workup for IPDs. In ITP, severe and spontaneous bleeding usually occurs when the platelet count falls less than 20,000/µL [ 11 , 14 ]. If the preliminary laboratory results show no abnormalities, a diagnostic workup for IPDs should be initiated.…”