Chronic Thrombocytopenia

Introduction

Chronic thrombocytopenia is a condition characterized by a low platelet count, with various underlying causes, including immune-mediated mechanisms, infections, medications, bone marrow disorders, and systemic diseases 1

Immune-mediated mechanisms, including primary immune thrombocytopenia (ITP), are the most common cause of chronic thrombocytopenia 1
Infections such as HIV, HCV, and other viral infections can cause thrombocytopenia 1
Systemic lupus erythematosus (SLE) and other autoimmune disorders can cause thrombocytopenia 1
Bone marrow disorders, including megaloblastic anemia, can cause thrombocytopenia 1
Liver diseases, such as cirrhosis, can cause thrombocytopenia 1
Malignancy, especially lymphoproliferative disorders, can cause thrombocytopenia 1
Inherited thrombocytopenias, although rare, can cause thrombocytopenia 1
Immune checkpoint inhibitor therapy can cause thrombocytopenia 2

A complete blood count with differential and peripheral blood smear examination are essential initial tests for diagnosing thrombocytopenia 1
Bone marrow examination is indicated in patients over 60 years, those with systemic symptoms, or abnormal signs 1
Rule out pseudothrombocytopenia by examining peripheral blood smear 1
The 4T score can be used to determine the clinical probability of heparin-induced thrombocytopenia (HIT), with the following criteria:

Category	Score
Thrombocytopenia	0-2
Timing of onset	0-2
Thrombosis or other sequelae	0-2
Other causes of thrombocytopenia	0-2

Patients with isolated thrombocytopenia should undergo testing for HIV and HCV, antinuclear antibodies (ANA) and antiphospholipid antibodies, and have a review of medication usage and a pregnancy test in women of childbearing potential, as recommended by the American Society of Hematology 1

Glucocorticoids are first-line therapy for immune thrombocytopenia, and intravenous immunoglobulin (IVIG) can be used for acute management of severe thrombocytopenia, as recommended by the American Society of Hematology 5, 2
Splenectomy is a second-line therapy for patients failing first-line therapy 1
Thrombopoietin receptor agonists, such as romiplostim, are used to treat refractory ITP 1
Combination chemotherapy may be used in severe cases of refractory ITP 1
Hematopoietic stem cell transplantation may be used in extremely refractory cases of ITP 1
For immune checkpoint inhibitor-related thrombocytopenia, treatment includes corticosteroids, IVIg, and possibly holding the checkpoint inhibitor 2
When HIT is suspected or confirmed, alternative anticoagulation should be initiated with one of the following: direct thrombin inhibitors (argatroban, lepirudin, bivalirudin) or factor Xa inhibitors (fondaparinux), as recommended by the American College of Chest Physicians 4, 6

Patients with chronic refractory ITP may have significant quality of life impairments and increased mortality risk 1
Platelet count thresholds should be monitored, with >50,000/μL generally being asymptomatic, 20,000-50,000/μL having a risk of mild bleeding, and <10,000/μL having a high risk of serious bleeding, as recommended by the American Society of Hematology 2, 7
Physical examination and abdominal ultrasound should be used to assess for spleen size, signs of liver disease, lymphadenopathy, and bleeding manifestations, as recommended by the American Society of Hematology 5