Patient Presentation
A 4-year-old female comes to clinic because of a rash for 2 days. The rash began on her feet and appeared to go up her body. It is mainly on the trunk currently. Her parents describe small, red, flat dots that haven’t changed in appearance. There is no itching.
The past medical history and family history are negative.
Her review of systems reveals no new soaps, detergents, pets, travel, medications, fever, illnesses or sick contacts, blood in stools or urine, oral lesions, or easy bruising or bleeding.
The pertinent physical exam shows pinpoint, red, non-blanching petechiae over her entire body including the palms and soles, but they are concentrated on the trunk. There are some small bruises on the shins. There are no oral lesions. She has shoddy anterior cervical and inguinal nodes. She has no hepatospleenomegaly.
Her laboratory evaluation revealed a hemoglobin of 12.1 mg/dl, hematocrit of 37%, white blood cell count of 10,500/mm² with normal differential, and a platelet count of 7,000/mm². The blood smear was normal as was a coagulation profile and liver function tests.
The diagnosis of idiopathic (immune) thrombocytopenic purpura was made. The patient was admitted for treatment with intravenous immunoglobulin because her platelet count was <10,000/mm², she had evidence of bleeding with the petechiae and she was a very active child. Her platelet count rose to 36,000/mm² at discharge and at one week follow-up had increased to 266,000/mm².

Discussion
Thrombocytopenia is usually defined as platelet counts <150,000/mm². It can be found because of easy bruising, bleeding or can be an incidental finding on a complete blood count done for other reasons.
The differential diagnosis of thrombocytopenia includes:

• Increased Platelet Destruction
  • Autoimmune hemolytic anemia – Evan’s syndrome
  • Congenital cyanotic heart disease
  • Disseminated intravascular coagulation
  • Drug – quinine, penicillin, digoxin, anti-epileptics, indomethacin, heparin
  • Idiopathic (immune) thrombocytopenic purpura
  • Neonatal illumine thrombocytopenia
  • Infection
  • Hemolytic-uremic syndrome
  • Hyperplenism
  • Kasabach-Merit syndrome
  • Thrombotic thrombocytopenia purpura

• Decreased Platelet Production
  • Bone marrow infiltration – e.g. leukemia, storage diseases, myelofibrosis, etc.
  • Bone marrow injury – infection or drugs – usually transient
  • Congenital megakaryocytic thrombocytopenia
  • Congenital bone marrow aphasia – i.e. Fanconi’s anemia
  • Chromosome abnormalities – e.g. Trisomy 13, 18, 21, Turner Syndrome
  • Congenital platelet disorders – Weskit-Aldrich syndrome, May-Hegglin anomaly, Bernard-Soulier syndrome, Alport syndrome
  • Hereditary amegakaryocytopoiesis – usually associated with TAR syndrome (thrombocytopenia-absent radius syndrome)

• Other
  • Pseudothrombocytopenia – caused by clumped platelets

Idiopathic (immune) thrombocyopenia purpura (ITP) usually occurs in children 2-10 years with a peak between ages 2-5 years. Children usually present with sudden onset of petechiae, ecchymosis, purpura, epistaxis, hematuria or gastrointestinal hemorrhage. They often are otherwise well and have a preceding minor viral illness. Physical examination usually shows only the presenting signs, but evidence of infection or malignancy must be carefully looked for.
Most children (~90%) resolve within 6 months usually without sequelae. If it lasts longer than 6 months it is called chronic ITP. Chronic ITP may resolve but this is less likely. Chronic ITP is more common in children <1 year and >10 years. Mortality from acute ITP fortunately occurs rarely and is usually due to central nervous system hemorrhage.

Laboratory testing usually shows isolated thrombocytopenia. The blood smear shows normal to increased platelet size and normal white and red cell morphology. Bone marrow examinations are often not done in typical cases but would have increased numbers of megakaryocytes.

Treatment may include careful observation, intravenous immunoglobulin, steroids and spleenectomy, and avoidance of precipitating medications. Children with atypical presentations, chronic thrombocytopenia, or children who will be treated with steroids, should have a bone marrow biopsy to rule out underlying malignancy or other causes of thrombocytopenia.

Learning Point
The approach to thrombocytopenia includes three major categories – history, physical examination and laboratory evaluation.

• History should include questions about:
  • Type of bleeding
    • Deep bleeding such as joints or bone is usually due to a clotting factor deficiency such as hemophilia A or B
    • Epistaxis, oral, or excessive menstrual bleeding is usually due to a platelet disorder or fibrinogen abnormality
  • Drug history e.g. aspirin or non-steroidal anti-inflammatory medications
  • Recent infections or immunizations
  • Family history of bleeding

• Physical examination should be carefully performed looking for:
  • Spleenomegaly with or without hepatomegaly
  • Lymphadenopathy
  • Skeletal abnormalities – these may be subtle and need radiographs to detect
  • Skin – e.g.hemangiomas, purpura

• Laboratory evaluation generally includes:
  • Complete blood count with white blood cell differential and platelet count
  • Peripheral blood smear for morphology
  • Coagulation profile
  • May also include Coombs test, liver function tests, and bone marrow examination

Questions for Further Discussion
1. When should a hematologist/oncologist be consulted?
2. What are the advantages/disadvantages and indications for using immunoglobulin or steroid treatment?

Related Cases

Disease
Idiopathic (Immune) Thrombocytopenic Purpura
Bleeding Disorders

Symptom/Presentation
Bleeding and Bruising
Rash

Specialty
Dermatology
Hematology
Pathology

Age
Preschooler

To Learn More

To view pediatric review articles on this topic from the past year check PubMed.

Information prescriptions for patients can be found at Pediatric Common Questions, Quick Answers for this topic: Bruises.

Rudolph CD, et.al. Rudolph’s Pediatrics. 21st edit. McGraw-Hill, New York, NY. 2003:1555–1559.

Woodhead JC. Pediatric Clerkship Guide. Mosby. St. Louis MO, 2003:170-179.

Author

Donna M. D’Alessandro, MD
Associate Professor of Pediatrics, Children’s Hospital of Iowa

Date
Janaury 18, 2005