Thrombocytopenia

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Introduction

The average platelet lifespan is 7-10 days. Even given this short duration, because of constant bone marrow production, normal platelet counts are 150-400 x 10⁹/L. A count below 150 x 10⁹/L is termed thrombocytopenia, and is very common amongst hospitalized patients. This can be caused by decreased production, increased destruction, or increased sequestration.

The Case of Betty Awate

Betty is a 7 year-old girl who presents with a petechial rash following a viral infection. Her family physician orders bloodwork, showing a platelet count of 74 x 10⁹/L.

what are some possible diagnoses in Betty?
what investigations are required?
what treatments, if any should be pursued?

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Differential Diagnosis

The many causes of thrombocytopenia can be grouped into five major categories:

decreased production

nutritional deficiency - folate and B12 are required for platelet formation
liver dysfunction (as thrombopoietin is from the liver)
congenital (frequently autosomal dominant: Alport's, Fanconi's anemia, Montreal platelet syndrome)
bone marrow damage: malignancy, toxins, chemotherapy, radiation, tuberculosis, myelofibrosis
drugs: thiazide, alcohol, estrogens

decreased platelet survival (immune-mediated)

immune thrombocytopenic purpura (ITP)
heparin-induced thrombocytopenia (HIT)
drugs (thiazides, sulfa, quinidine)
viruses (HIV, CMV, HCV, EBV)
systemic lupus erythmatous (SLE)
lymphoproliferative disorders (ie CLL, lymphoma)
alloimmune destruction (graft-vs-host disease, pregnancy)

decreased platelet survival (non- immune-mediated)

disseminated intravascular coagulation (DIC)
thrombotic thrombocytopenic purpura (TTP)
hemolytic uremic syndrome (HUS)
antiphospholipid antibody syndrome (APLAS)
HELLP syndrome

increased sequestration

splenomegaly (CML, malignancy)
advanced liver disease

hemodilution

transfusion
cardiopulmonary bypass

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History and Physical Exam

history
physical exam

History

Spontaneous bleeding, especially highly vascularized mucous membranes, skin, and genitourinary tract, can occur in levels below 10x10⁹/L.

Physical Exam

Abdominal exam can reveal increased splenomegaly or signs of liver disease.

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Investigations

lab investigations
diagnostic imaging

Lab Investigations

Bone marrow aspiration can be helpful in distinguishing between decreased production and increased destruction. In decreased production, megakaryocytes will be decreased or absent, and offending cells (ie with malignancy) may also be seen. With increased destruction, megakaryocyte number will be increased.

Reticulated platelet count is a blood test measuring young platelets (via their enriched RNA content) and can assess platelet kinetics. Numbers will be decreased if production is down, but will be increased, as a percentage, if destruction is up.

Diagnostic Imaging

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Management

Decreased production

Platelet transfusions may be used if thrombocytopenia is due to bone marrow dysfunction, with a trigger level of 10x10⁹/L.

Sequestration

If splenomegaly is the cause for thrombocytopenia, splenectomy can be helpful. This decreases destruction and sequestration, as well as antibody production.

Imunosuppressants, such as corticosteroids, can be useful if thrombocytopenia is immune-mediated.