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Chapter 132 Thrombocytopenia Caused by Platelet Destruction, Hypersplenism, or Hemodilution 1965

Trauma (burn)-
associated
thrombo- Postoperative Resolution of Mirtazapine-induced
1800 cytopenia thrombocytosis thrombocytosis thrombocytopenia
1600
MIRTAZAPINE:
1400 tetracyclic antidepressant of the
piperazine-azapine group
1200
Platelet count × 10 9 /L 800 Abrupt unexpected
1000

platelet count fall
600
400
High-dose IVIG
200

0 Platelet count nadir
Debridement Mirtazapine (12 × 10 /L)
9
–20 –15 –10 –5 0 5 10 15 20
Days after starting mirtazapine
Fig. 132.6 DRUG-INDUCED IMMUNE THROMBOCYTOPENIA (D-ITP) SECONDARY TO MIR-
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TAZAPINE. The onset of severe thrombocytopenia (platelet count nadir, 12 × 10 /L) on day 6 of mirtazapine
therapy implicated this tetracyclic antidepressant of the piperazine-azapine group as a cause of drug-induced
immune thrombocytopenia (D-ITP) syndrome. The very rapid platelet count fall (which was already manifest
on day 5 of mirtazapine therapy) is explained by reduced platelet production (because the patient’s platelet
count was declining from postoperative thrombocytosis). Although in vitro testing for mirtazapine-dependent
antibodies was negative, the low sensitivity of these assays does not rule out mirtazapine as the cause of
D-ITP syndrome, particularly in a high pretest probability scenario such as this. IVIg, Intravenous
immunoglobulin.

Management high-dose IVIg. Some patients with persisting thrombocytopenia
benefit from splenectomy or use of gold-chelating agents (dimercap-
As many drugs as possible should be discontinued in patients with rol, N-acetylcysteine). The disorder is rarely encountered because the
suspected D-ITP. If further drug treatment is necessary, an alternate, use of gold to treat rheumatic disorders has declined.
immunologically non–cross-reactive substitute should be used.
Spontaneous improvement in the platelet count usually begins within
a few days of discontinuing the offending drug, although in some DRUG-INDUCED AUTOIMMUNE THROMBOCYTOPENIA
cases, complete recovery may take 2 weeks or longer. Platelet transfu-
sions should be given to patients with life-threatening bleeding. Certain drugs other than gold have been reported to initiate auto-
High-dose intravenous immunoglobulin (IVIg), 1 g/kg given over immune thrombocytopenia (e.g., levodopa, procainamide). Because
6–8 hours, with a second dose 1 or 2 days later if required, may be the pathogenic antibodies are by definition drug independent,
helpful in some situations. Corticosteroids appear to be relatively however, it is difficult to establish causation. The mumps–measles–
ineffective for treatment of D-ITP. rubella (MMR) vaccine can rarely (≈1 : 40,000) cause a severe but
generally self-limited thrombocytopenia that is clinically and sero-
logically indistinguishable from childhood acute ITP; MMR vaccina-
GOLD-INDUCED THROMBOCYTOPENIA tion of unimmunized children with ITP and revaccination of children
with prior ITP does not lead to recurrent thrombocytopenia.
Gold-induced ITP occurs in as many as 1% to 3% of treated
patients. A genetic predisposition is suggested by the association
with HLA-DR3, which is found in approximately 85% of affected DRUG-INDUCED IMMUNE THROMBOCYTOPENIA OF
patients. The thrombocytopenia typically occurs during the first 20 RAPID ONSET
weeks of therapy before a total of 1000 mg of gold has been given.
Rarely, the thrombocytopenia begins much later, sometimes several A rapid onset of thrombocytopenia (within hours) can occur if a
months after discontinuation of the gold. Although the onset of patient with preexisting drug-dependent antibodies is (re)exposed to
thrombocytopenia is typically abrupt, regular platelet count monitor- the drug. This situation is relatively common in HIT (≈25% of
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ing is important because an early diagnosis can be made in some patients identified) because repeated treatment with heparin is
patients. The thrombocytopenia often persists for several months common and heparin use itself can result in the complication (HIT-
after discontinuation of the gold, probably because of gold-induced associated thrombosis) that might lead to further use of heparin.
autoimmune thrombocytopenia (drug-independent gold-induced Because HIT antibodies are transient, however, rapid-onset HIT
autoantibodies against gold-induced antiglycoprotein V [GPV] have occurs in patients with recent heparin exposures, usually within the
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been implicated) (see Fig. 132.4). Although most patients will even- past 100 days. By contrast, repeated episodes of quinine-induced
tually respond to corticosteroids, immediate, albeit often transient, thrombocytopenia of abrupt onset can occur many months or
correction of severe thrombocytopenia can usually be achieved with even years apart because these antibodies persist for much longer.