Thrombocytopenia

Platelets, a type of blood cell, help blood to clot. Thrombocytopenia is a group of disorders sometimes associated with abnormal bleeding in which there is an abnormally low platelet count. The disorders are not mutually exclusive, and include:

Essential thrombocythemia – a shortage of platelets not caused by other conditions
Secondary thrombocytopenia – associated with metastatic neoplasms, tuberculosis, and leukaemia involving the bone marrow, or with direct suppression of bone marrow by the use of chemical agents, or with other conditions
Thrombotic thrombocytopenic purpura (TTP) – blood clots form in blood vessels around the body, leading to purplish or reddish-brown spots on the skin, among other complications
Idiopathic thrombocytopenic purpura (ITP) – an abnormally low platelet count, leading to purplish or reddish-brown spots on the skin, among other complications
Drug-induced immune thrombocytopenia – the use of a drug leads to the formation of antibodies that attack platelets, resulting in a low platelet count
Drug-induced nonimmune thrombocytopenia – the use of a drug prevents platelets to work normally, or leads to a low platelet count, sometimes by damaging bone marrow where the platelets are made

This article looks more closely at ITP and drug-induced thrombocytopenia.

Idiopathic Thrombocytopenic Purpura (ITP)
Although ITP is idiopathic (of an unknown cause), most cases seem to be due to an attack of the platelets by antibodies. For this reason, ITP is also known as immune thrombocytopenic purpura.

There are approximately 200,000 people with ITP in the United States. There are about three times more adult women than adult men with ITP. In children, the number of girls and boys with ITP is about the same. The incidence of ITP is about 100 new cases per million per year, and there is anecdotal evidence that it is increasing. About half of the new cases are in children.

Most cases of ITP are asymptomatic, although very low platelet counts can lead to a tendency to bleed, bruise easily, and to develop hemorrhagic areas in the skin (purpura if more than 3mm in diameter, petichiae if less) that look like a purplish or reddish-brown rash.

Platelet counts are considered normal when within a range of 150,000–400,000 per mm3. In patients with a platelet count of less than 20,000 per mm3, bleeding gums and nosebleeds may occur and, in some cases, very serious complications such as subarachnoid, intracerebral hemorrhage or other internal bleeding may develop.

In November 2005, a U.S. Food and Drug Administration (FDA) alert warned that three patients in a clinical study of Campath) developed severe ITP. The alert reaffirmed that Campath, which is used to treat a form of blood cancer called B-cell chronic lymphocytic leukemia (B-CLL), is not approved for the treatment of Multiple Sclerosis (MS). It further advised that anyone concerned with taking the drug should first consult with his or her healthcare professional.

To diagnose ITP, other blood abnormalities except for low platelet count should first be excluded, and there should typically not be any physical signs other than bleeding (the spleen, for instance, is usually not enlarged in cases of ITP). Secondary causes, which make up about five to ten percent of suspected ITP cases, should then be excluded. These may include antiphospholipid syndrome, congenital causes, cirrhosis, hepatitis C, leukemia, lupus erythematosus, and medications such as quinine or heparin, and Von Willebrand factor deficiency, among others. Evans syndrome, in which autoimmune hemolytic anemia and ITP coexist, occurs in about one percent of cases.

If the diagnosis is in doubt, the patient does not respond to treatment, or the patient is over 60 years old, a bone marrow examination may be performed. A blood analysis for antiplatelet antibodies has a specificity of only 80 percent, so it depends on the particulars of each case whether it should be undertaken.

Patients with a platelet count below 20,000 usually require treatment, and those with a count above 50,000 generally do not. Treatment for patients with a platelet count in the 20,000 – 50,000 range is considered on a case-by-case basis. Any patient with significant mucocutaneous or internal bleeding, however, should be hospitalized.

Treatment usually begins with any, or a combination, of intravenous immunoglobulin (IVIg), intravenous steroids (prednisone or methylprednisolone), and/or platelet infusions. In less severe cases, or after the platelet count has been stabilized, oral prednistone is prescribed, and then the dose is gradually reduced. 60 – 90 percent of patients relapse, however, and a splenectomy (removal of the spleen) may need to be considered (the spleen is where a large number of the platelets are ultimately destroyed). Splenectomy tends to be less successful in older patients.

Newer treatments being used or considered include:

Anti-D – can only be used if the patient is Rh+
Immunosuppressants (mycophenolate mofetil, azathioprine) – these are becoming more popular for their effectiveness
Rituximab (Rituxan, MabThera) – has shown positive results in some patients
AMG 531 – clinical trials have shown it to be effective in treating chronic ITP
PROMACTA (eltrombopag olamine or SB 497115) – clinical trials have shown an increase in platelet counts and reduced bleeding in patients with chronic ITP
Antibiotics used in treating Helicobacter Pylori – there are indications that these bacteria are linked to ITP. The eradication of H. Pylori infections have resulted in dramatic increases in platelet counts

Drug-Induced Thrombocytopenia
The most important factor in the treatment of drug-induced thrombocytopenia is the identification and removal of the causative agent. This is especially urgent when the causative agent is one of the numerous drugs an acutely ill patient has been exposed to since such patients are likelier to have preexisting hemostatic defects that place them at further risk of complications resulting from drug-induced thrombocytopenia. Time-critical complications include clinically significant bleeding or thrombosis if the causative agent is heparin (traces of which may be present in an IV catheter).

The three principal mechanisms by which drug-induced thrombocytopenia occurs are immune-mediated destruction, platelet aggregation, and bone marrow suppression. The drug history specific to these mechanisms can help clinicians in rapidly isolating the causative drug. So can preliminary laboratory findings and clinical characteristics.

In any case, the patient’s history of all over-the-counter and prescription medications should be reviewed. The history should include the ingestion of tonic water in cocktails and bitter lemon beverages by those sensitized by a previous treatment with quinidine or quinine. In addition to heparin, the following drugs have been associated with drug purpura: