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There are two types of drug-induced thrombocytopenia caused by different mechanisms: the first is by direct myelosuppressive effect (e.g. chemotherapy-induced thrombocytopenia) and the second by immune-mediated destruction of platelets due to an idiosyncratic drug reaction (drug-induced immune thrombocytopenia. DITP may be caused by classic drug-dependent platelet antibodies (e.g. quinine), haptens (e.g. penicillin), glycoprotein IIb/IIIa receptor antagonists (e.g. tirofiban), stimulation of autoantibody formation (e.g. gold) and immune complex formation (e.g. heparin) . Alcohol, some herbal preparations and even certain foods and beverages can be implicated in the pathogenesis of drug-induced thrombocytopenia. Thrombocytopenia: diagnostic algorithm starting with the complete blood count (CBC)Abbreviations: CAMT, congenital amegakaryocytic thrombocytopenia; CBC, complete blood count; DITP, drug-induced immune thrombocytopenia; FTLS, familial thrombocytopenia-leukemia syndrome; HIT, heparin-induced thrombocytopenia; HIV, human immunodeficiency virus; HCV, hepatitis C virus; ITP, immune thrombocytopenia; TAR, thrombocytopenia-absent radii syndrome; VCF, velocardiofacial syndrome; WAS, Wiskott-Aldrich syndrome. Vaccinations can also be associated with thrombocytopenia, the pathogenesis of this type of thrombocytopenia being immune-complex formation. Many types of vaccinations have been implicated in the pathogenesis of thrombocytopenia. The best studied of these is measles-mumps-rubella (MMR). There is also documentation of acute thrombocytopenia developing after vaccination against pneumococcus, Haemophilus influenzae, hepatitis B virus, and varicella-zoster virus, although the incidence is very low. Special attention should be paid to recent exposure to heparin (and low-molecular weight heparin), as potential causes of severe, sometimes life-threatening thrombocytopenia [10]. Typically thrombocytopenia will occur between 5 and 14 days of the first heparin dose, but if heparin was given in the previous 100 days, the decrease in platelet count can sometimes occur within hours of exposure. Similar to ITP, heparin-induced thrombocytopenia (HIT) is an immune-mediated disorder, but characterized by consumption and thrombosis, the features that distinguish heparin-induced thrombocytopenia from ITP.
Physical examination
Important clues to diagnosis of thrombocytopenia can be obtained during systematic physical examination. First, general physical examination by inspection, palpation and auscultation can inform one on the general health of the patient e.g. the presence of comorbidities. Second, examination of the skeletal system can shed light on potential causes of thrombocytopenia as indicated below. Special attention should be paid to: Bleeding: Some patients have bleeding tendency, independently of etiology. Usually those with platelet counts less than 20 × 109/L present with petechiae, purpura and ecchymoses. Petechiae are the hallmark of platelet-related bleeding. Lymphadenopathy: Lymphoma, acute or chronic leukemia (T-cell acute lymphoblastic leukemia, chronic lymphocytic leukemia), viral infections (Epstein-Barr Virus (EBV), cytomegalovirus (CMV), HIV, tuberculosis, sarcoidosis, autoimmune lymphoproliferative (Canale-Smith) syndrome. Splenomegaly: Gaucher disease, portal hypertension, cirrhosis, certain types of lymphoma and leukemia (eg. CLL), myelofibrosis with extramedullar hematopoiesis, infections (e.g. malaria), EBV and CMV infections. Hepatomegaly: chronic hepatitis, hepatosplenic lymphoma. Skeletal abnormalities: short stature, malformations of the thumbs and forearms seen in Fanconi anemia patients, thrombocytopenia-absent radii (TAR-syndrome) characterized by bilateral shortened or absent radii, thumb abnormalities. Multiple abnormalities are common in inherited syndromes: facial dysmorphology (velocardiofacial [VCF] syndrome, Jacobsen syndrome), cleft palate (DiGeorge syndrome); eyes, kidneys and urinary tract, ears (MYH9-related disorders [May-Hegglin anomaly associated with MYH9 gene]), heart, gastrointestinal system, central nervous system abnormalities, signs of hypogonadism (Fanconi anemia). Skin abnormalities: abnormal skin pigmentation in Fanconi anemia, necrotic skin lesions in HIT patients, eczema in Wiskott-Aldrich syndrome (WAS), “lacy” skin pigmentation associated with abnormal growth and shape of nails in dyskeratosis congenita.