Iron Deficiency Anemia, a Rare and Potentially Underestimated Cause of Thrombocytopenia and a Differential Diagnosis of Immune Thrombocytopenia (ITP): Results from a Retrospective Case-Controlled Study
Authors: Huscenot Tessa , Luc Darnige , Wagner Ballon Orianne , Valentine Loustau , Gobert Delphine , Le cann Marie , Morbieu Caroline , Michel Marc 
Published: October 2019

Abstract
Introduction
Iron deficiency anemia (IDA) is the most common cause of anemia worldwide. It is classically associated with a normal or moderately elevated platelet count, but exceptionally, iron deficiency can lead to thrombocytopenia. Distinguishing IDA-related to mucosal bleeding in the setting of immune thrombocytopenia (ITP) from a true iron deficiency-related thrombocytopenia can be challenging and may lead to misdiagnosis and inappropriate treatment.
The 2 main objectives of this study were: 1) To better describe the clinical and biological baseline characteristics of clearly defined cases of iron deficiency-induced thrombocytopenia (IDIT) and 2) To identify some features that could be helpful for distinguishing IDIT and ITP.
Material and method
We performed a retrospective multicentre case-controlled study throughout the network of the French national referral center for adult' immune cytopenias. Inclusion criteria were the following: thrombocytopenia <100 x 109/L related to an IDA defined by an hemoglobin level <120 g/L and a ferritin level <30 μg/L and platelet recovery without any other treatment than iron ± transfusion of packed RBCs. Patients with pre-existing thrombocytopenia and/or other potential cause of thrombocytopenia or anemia were excluded as well as patients with a possible diagnosis of IDIT who received corticosteroids ± intravenous immunoglobulin for a putative diagnosis of ITP. Clinical and biological characteristics of the patients (i.e, the "cases") were analyzed and each case was compared to 3 newly diagnosed ITP patients (control group) matched on age (+/- 5 years) and gender.
Results
Between February 2000 and May 2018, eight (7 women, 87.5%) patients from 4 participating centers fulfilling the inclusion criteria were included. Median age at IDIT diagnosis was 43.5 years (Range: 16-72) years. Median hemoglobin level at diagnosis was 47 (range: 21 - 71) g/L, with a mean corpuscular volume (MCV) of 64 (54 - 75) fl, and a median platelet count of 30.5 (21 - 80 x 109/L). None of the patients but one had clinical bleeding manifestations such as purpura or mucosal bleeding. The platelet count got back to a normal level within a median of 6 (4 - 39) days after iron supplementation and/or transfusion in all 8 patients. When compared with these 8 cases, ITP controls had a significantly lower platelet count (median platelet count of respectively 7 [range 4 - 59] vs 30.5 [21 - 80] x 109/L , p = 0.002), and more bleeding manifestations (19/24 (79%) versus 1/8 (12.5%) respectively ,p = 0.001). On Day 7 after diagnosis, the median platelet count (after iron deficiency treatment or ITP treatment among the cases was 337 (113-1000 x 109/)L versus only 72 (13-212 x 109/L for the 24 controls (p = 0.001).
Conclusion
In case of profound IDA, and non-severe (platelet count > 20 x 109/L) and generally asymptomatic associated-thrombocytopenia may occur and must not be misdiagnosed and treated as an ITP with secondary IDA. Iron supplementation (either intravenously or orally) allows a quick and complete recovery of the platelet count with sometimes a transient thrombocytosis and may avoid the inappropriate use of steroids. Why profound iron deficiency can seldom lead to thrombocytopenia whereas mild iron deficiency often leads to thrombocytosis needs further investigation.

Disclosures
No relevant conflicts of interest to declare.