How do drugs cause thrombocytopenia?

Thrombocytopenia



The worst offenders

When a patient is thrombocytopenic, one of the things on your differential should be a drug reaction. The three drugs that are most commonly responsible for thrombocytopenia are quinine, quinidine and vancomycin (and heparin, which gets its own category - see below). There are other drugs that can do it too, which you can look up if you need to, but they're much less common culprits. 

  How do drugs cause Thrombocytopenia? Drugs cause thrombocytopenia either by directly damaging platelets, or by causing the immune system to take the platelets out. Most of the time, when the immune system is involved, the problem is that the drug has bound to the platelet membrane and formed a new antigen that the immune system sees as foreign. The membrane protein that drugs seem to like to bind to the most is glycoprotein IIV/IIIa.
  Heparin-induced thrombocytopenia

Heparin can also cause Thrombocytopenia but it's separated out into its own category because it has a specific pathogenesis and potentially severe clinical consequences. Only about 5% of patients who are on heparin get thrombocytopenia. More often than not, it happens right away and doesn't mean much clinically (these cases are called type I thrombocytopenia and are due to platelet aggregation).

Less commonly, thrombocytopenia occurs a week or two after the start of heparin treatment; these cases are called type II thrombocytopenia and are much more dangerous. It turns out that heparin binds to platelet factor 4, which is a normal component of platelet granules. The immune system sees the heparin-platelet complex as foreign, and makes antibodies against it. Weirdly, as these antibodies bind to platelets, the platelets are activated, and patients can get life-threatening thromboses. You have to stop the heparin right away, and give another anticoagulant, otherwise the patient may lose a limb or worse, get a pulmonary embolus and die.