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67. Thrombocytopenia in Children
Authors :
MOHAMMED TABISH
BUGUBAEVA MAKHABAT MITALIPOVNA
(1, Medical Student,International Medical Faculty,Osh State University,Osh ,Kyrgyzstan
2, Associate Professor ,HOD Clinical Disciplines 2,International Medical Faculty,Osh State University)
Abstract
Thrombocytopenia, a platelet count below 150 x 10⁹/L, is a common and often alarming finding in the pediatric population. It presents a wide-ranging diagnostic challenge, as its etiology can span from benign, self-limiting autoimmune processes to life-threatening emergencies like sepsis or malignancy. This review synthesizes the current understanding of platelet disorders in children, adhering to the fundamental classification of immune versus non-immune thrombocytopenias. We analyze the etiopathogenesis of these distinct pathways, with a primary focus on the most common pediatric cause: Immune Thrombocytopenic Purpura (ITP). We explore the classic clinical and diagnostic features of ITP, a diagnosis of exclusion characterized by isolated thrombocytopenia in an otherwise well child. The "discussion" is centered on the critical, real-world task of the differential diagnosis: distinguishing the benign presentation of ITP from its sinister mimics, such as leukemia, aplastic anemia, and microangiopathic hemolytic anemias (DIC, HUS). Finally, we review the modern, risk-stratified treatment and follow-up protocols for ITP, which have shifted from aggressive intervention to a "watchful waiting" approach in most cases.
Keywords: Thrombocytopenia, Immune Thrombocytopenic Purpura (ITP), Platelet Disorders, Pediatrics, Etiopathogenesis, Differential Diagnosis
1. Introduction
In pediatric practice, few laboratory findings generate as much immediate concern as a critical thrombocytopenia. Platelets, the anucleated fragments of megakaryocytes, are the frontline soldiers of primary hemostasis. A significant reduction in their number plunges the patient into a state of high bleeding risk, manifesting clinically as purpura—the spontaneous extravasation of blood into the skin (petechiae and ecchymoses). When a child presents with a sudden "crops" of bruises and petechiae, the clinician is immediately faced with a critical crossroads.
Is this Immune Thrombocytopenic Purpura (ITP), a benign, often post-viral, and self-resolving autoimmune disorder? Or is this the first, terrifying presentation of a non-immune process—a "factory" failure like leukemia or aplastic anemia, or a "consumption" catastrophe like Disseminated Intravascular Coagulation (DIC) or Hemolytic Uremic Syndrome (HUS)?
The central task for the medical student and pediatrician is not just to identify the thrombocytopenia, but to rapidly classify it. The etiopathogenesis dictates the entire clinical course, from prognosis to treatment. This review aims to synthesize the pathophysiology, classification, and clinical approach to pediatric thrombocytopenia, using ITP as the archetype for discussion.
2. Methods
This article is a comprehensive narrative review. It is not a primary research study but a synthesis of the current, evidence-based understanding of pediatric platelet disorders. Our "methodology" involved the collation and analysis of foundational information from core pediatric hematology textbooks, clinical practice guidelines from the American Society of Hematology (ASH), and key review articles from high-impact journals found in databases such as PubMed and The New England Journal of Medicine. The "results" are a synthesis of this established data, organized by pathophysiology and clinical presentation. The "discussion" focuses on the clinical application of this knowledge, including differential diagnosis, treatment, and follow-up.
3. Results (Part I): Classification and Etiopathogenesis
Thrombocytopenia is not a single disease, but a sign. It is broadly classified by its mechanism: either a failure of production or an increase in destruction/consumption/sequestration. A more clinically useful framework, however, is non-immune versus immune.
3.1. Non-Immune Thrombocytopenias
These are often the most severe and systemic conditions.
1. Decreased Platelet Production (Megakaryocyte Failure): This is a "bone marrow factory" problem.
○ Malignancy: Acute Lymphoblastic Leukemia (ALL) is the great mimic. The marrow becomes infiltrated with lymphoblasts, "crowding out" all normal hematopoietic cell lines, leading to pancytopenia (anemia, leukopenia, and thrombocytopenia).
○ Aplastic Anemia: An immune attack on the hematopoietic stem cell itself, also leading to pancytopenia.
○ Congenital/Hereditary: Rare syndromes like Wiskott-Aldrich Syndrome (WAS) (X-linked, with eczema and immunodeficiency) or TAR Syndrome (Thrombocytopenia with Absent Radii).
2. Increased Non-Immune Consumption (Microangiopathies): The platelets are "used up" or destroyed mechanically.
○ Disseminated Intravascular Coagulation (DIC): A systemic, uncontrolled activation of the entire coagulation cascade (often by sepsis), leading to the consumption of all platelets and clotting factors.
○ Hemolytic Uremic Syndrome (HUS): Classically post-diarrheal (E. coli O157:H7), where Shiga-toxin damages endothelium, creating microthrombi that shear RBCs (creating schistocytes) and consume platelets.
○ Kasabach-Merritt Syndrome: A rare, severe thrombocytopenia caused by the "trapping" of platelets within a large vascular tumor (hemangioma).
3. Sequestration: Hypersplenism. In conditions like portal hypertension, the enlarged spleen traps a large fraction of the circulating platelet pool.
3.2. Immune-Mediated Thrombocytopenias
These are driven by antibody-mediated platelet destruction.
1. Immune Thrombocytopenic Purpura (ITP): This is the most common cause of isolated thrombocytopenia in a well child.
○ Etiopathogenesis: ITP is an acquired autoimmune disorder. In 80% of pediatric cases, it is "acute," following a viral infection (1-3 weeks prior). The leading hypothesis is molecular mimicry: the immune system creates antibodies against viral antigens, which then cross-react with glycoproteins (GPs) on the platelet surface (e.g., GP IIb/IIIa).
○ Mechanism: These IgG-coated platelets are recognized as "foreign" by macrophages in the reticuloendothelial system, primarily the spleen, and are rapidly destroyed. The bone marrow, which is perfectly healthy, responds by increasing megakaryocyte production, releasing large, young "giant platelets" into the circulation.
○ Classification:
■ Acute ITP: Self-limiting, resolving within 6-12 months.
■ Chronic ITP: Persists for > 12 months. This is more common in adults and adolescents.
2. Secondary ITP: Thrombocytopenia as a feature of another autoimmune disease (e.g., Systemic Lupus Erythematosus - SLE).
3. Neonatal Alloimmune Thrombocytopenia (NAIT): A fetal-maternal incompatibility, where the mother produces antibodies against fetal platelet antigens inherited from the father. This can cause severe thrombocytopenia and intracranial hemorrhage in the newborn.
4. Results (Part II): Focus on ITP Clinic and Diagnosis
4.1. Clinical Presentation of ITP
The hallmark of classic acute ITP is the sudden appearance of bruising and petechiae in an otherwise "well-appearing" child.
● The Patient: Typically a 2-6 year old child who is afebrile, active, and playful.
● The Rash: This is the purpura.
○ Petechiae: Pinpoint, non-blanching, non-palpable red/purple dots, often in dependent areas.
○ Ecchymoses: Superficial, "easy" bruising with minimal or no recalled trauma.
● Bleeding: Usually minor and mucocutaneous (skin and mucous membranes).
○ Epistaxis (Nosebleeds): Common.
○ Gingival Bleeding: Bleeding from the gums.
○ "Dry" vs. "Wet" Purpura: This is a key clinical distinction.
■ Dry Purpura: Skin involvement only (petechiae/bruises). Low risk.
■ Wet Purpura: Active mucosal bleeding (e.g., oral blood blisters, epistaxis, GI/GU bleeding). This, combined with a platelet count < 10,000/L, signifies a high risk of severe bleeding.
4.2. Diagnosis of ITP
ITP is a diagnosis of exclusion. There is no single "test" for it. The diagnosis is made by a combination of a characteristic history, a normal physical exam (except for purpura), and, most importantly, a Complete Blood Count (CBC) that shows isolated thrombocytopenia.
● CBC:
○ Platelets: Low (can be < 10,000/L).
○ Hemoglobin/Hematocrit: Normal.
○ WBC & Differential: Normal.
○ If the Hb or WBC are also low, it is NOT ITP. This is a "red flag" for a bone marrow failure syndrome.
● Peripheral Smear: This is a mandatory test. It must be reviewed to:
1. Confirm the thrombocytopenia (ruling out "pseudothrombocytopenia" from platelet clumping).
2. Check RBC/WBC morphology. The smear should be normal except for giant platelets.
3. Rule out schistocytes (which suggest HUS/DIC).
4. Rule out blast cells (which suggest leukemia).
● Coagulation (PT/PTT): Normal (rules out DIC).
● Bone Marrow Aspiration: This is no longer routinely performed. It is reserved only for atypical cases (e.g., if other cell lines are low, if there is hepatosplenomegaly or bone pain, or if the patient is refractory to treatment) to definitively rule out leukemia or aplastic anemia.
5. Discussion: Differentials, Treatment, and Follow-up
The "results" show ITP is a benign diagnosis of exclusion. The "discussion" is how to safely arrive at that exclusion.
5.1. The Critical Differential Diagnosis
When a child presents with petechiae, the clinician's job is to run this mental checklist:
1. Is this thrombocytopenia?
○ No: Henoch-Schönlein Purpura (IgA Vasculitis). This is the other common cause of purpura. The key difference: HSP has a palpable (raised) rash and a NORMAL platelet count.
2. Is the child WELL or SICK?
○ SICK (Febrile, Lethargic, Ill): Think DIC (sepsis) or HUS (post-diarrheal, renal failure). Look for schistocytes and coagulopathy.
3. Is it isolated thrombocytopenia?
○ No (Pancytopenia): This is a RED FLAG. The child must be evaluated for Leukemia (ALL) or Aplastic Anemia. Look for hepatosplenomegaly, lymphadenopathy, or bone pain.
4. If it IS isolated thrombocytopenia in a WELL child:
○ Yes: This is Classic ITP.
5.2. Treatment and Medical Follow-up
The management of pediatric ITP has shifted dramatically. We no longer "treat the number"; we "treat the patient."
● Observation ("Watchful Waiting"): This is the preferred strategy for >80% of children.
○ Who: Children with "dry purpura" and a platelet count > 10,000 - 20,000/L.
○ What: Activity restrictions (no contact sports, no aspirin/NSAIDs), and close outpatient follow-up. Most cases resolve spontaneously in 3-6 months.
● Active Treatment:
○ Who: Children with "wet purpura" (active mucosal bleeding) or a platelet count < 10,000/L (high risk for severe bleed).
○ Goal: To rapidly raise the platelet count to a "safe" level (e.g., > 20,000/L), not to normalize it.
○ First-Line Therapies:
■ Corticosteroids (Prednisone/Prednisolone): Suppresses the immune system's autoantibody production.
■ Intravenous Immunoglobulin (IVIg): "Fools" the spleen. The high dose of infused IgG saturates the Fc-receptors on the splenic macrophages, so they "ignore" the antibody-coated platelets. This works very quickly (within 24-48 hours).
● Management of Chronic ITP (> 12 months):
○ Second-Line Therapies: Rituximab (anti-B-cell) or TPO-mimetics (Romiplostim, Eltrombopag) which stimulate the bone marrow to "out-produce" the destruction.
○ Splenectomy: A last resort in refractory, severe cases. It is highly effective (removes the primary site of platelet destruction) but carries a lifelong risk of overwhelming post-splenectomy sepsis.
6. Conclusion
Pediatric thrombocytopenic purpura is a classic and common diagnostic challenge. It forces the clinician to be a careful detective. While the majority of cases represent benign, self-limiting ITP, the physician's primary responsibility is to maintain a high index of suspicion for the life-threatening mimics. The key to navigating this differential is a thorough history, a careful physical exam (is the child well or sick?), and a critical review of the entire CBC and peripheral smear, not just the platelet count. By differentiating isolated thrombocytopenia (ITP) from pancytopenia (leukemia, aplastic anemia) or microangiopathic processes (DIC, HUS), the clinician can safely reassure the vast majority of families and reserve aggressive treatment for the small subset of children truly at risk.
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