Adverse Events of Special Interest (AESI) and Related Risks: Thrombocytopenia


Definition (1): Thrombocytopenia (TP) is an abnormally low platelet count. Pathogenic mechanisms include insufficient production, abnormal distribution, or excessive destruction of platelets. A platelet count below 150×109/L-1 is the most commonly used reference value in the hematological literature. In vaccine safety studies, the threshold criteria for thrombocytopenia ranged from 100 to 150×109/L-1, and use of this value is supported by platelet count reference interval studies in different populations, representing approximately two standard deviations below average in a normal population. TP it is also known as immune thrombocytopenia (ITP), recognizing underlying immunological pathogenic causes. In primary IPT, no etiology is identified and is a reason for exclusion. Secondary IPT is recognized as an autoimmune thrombocytopenia that occurs in the course of another disease, or that follows an exogenous immune stimulus such as an infection, drug, or vaccine. 

Risk factors and diseases: Age, gender, genetics, seasonal, geographic. For secondary IPT or autoimmune disease, factors may include hematological malignancy, immunodeficiency, or vitamin B9 or B12 deficiency. For non-immune mediated thrombocytopenia or decreased  platelet production: bone marrow replacement, bone marrow failure, certain neoplasms, inheritance or transmission from parents to children (rare), alcohol consumption and alcoholism, autoimmune disease, bone marrow diseases, chemotherapy and radiotherapy, splenomegaly caused by cirrhosis of the liver or Gaucher disease,  exposure to toxic chemicals, protozoan infections, dengue, malaria, scrub typhus, rickettsial infections, meningococcus, leptospira, and certain viral infections that present with fever and thrombocytopenia.

Medications: Certain medications that occasionally induce TP include: heparin, quinine, trimethoprim/sulfamethoxazole, glycoprotein IIb/IIIa inhibitors, hydrochlorothiazide, carbamazepine, chlorpropamide, ranmpinidine, antibiotics, and drugs used to treat epilepsy, heart problems, hepatitis C, cytomegalovirus (CMV), Epstein-Barr virus (EBV), and human immunodeficiency virus (HIV).

Vaccines: Clinically apparent TP following vaccination is rare. A transient but sometimes sharp drop in platelet count has been reported after vaccination against hepatitis B, hepatitis A, influenza, diphtheria-tetanuspertussis (DTwP), diphtheria/tetanus/acellular pertussis (DTaP), haemophilus influenzae type b (Hib), measles, mumps, and rubella (MMR), and measles, mumps, rubella, varicella (MMRV). The median interval between immunization with MMR vaccine and symptom onset is 12 to 25 days (range one to 83 days), with most post-immunization TP episodes resolving within three months, although low platelet counts rarely persist for more than six months.



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