Drug-induced thrombocytopenia is a poorly understood, yet common phenomenon widely encountered in clinical practice. We present a case of suspected levofloxacin-induced thrombocytopenia, a rare side effect of a ubiquitous antibiotic, in a patient without similar effect to ciprofloxacin. This report builds upon other isolated case reports of fluoroquinolone-induced thrombocytopenia and demonstrates our algorithmic approach to the issue as well as a literature review pertaining to fluoroquinolone-induced thrombocytopenia.
An 83-year-old white male with a history of type II diabetes mellitus, peripheral vascular disease, coronary artery disease, hypertension, and a diabetic foot infection with osteomyelitis of his right 5th metatarsal and proximal phalanx presented with decreased appetite and nausea. Bone biopsy one month prior to admission grew
Laboratory results revealed a platelet count on admission of 128.0 × 109/L (150–450 × 109/L), down from a count of 480.0 × 109/L one week prior to admission (and no previous episodes of thrombocytopenia) at the visit where ciprofloxacin was changed to levofloxacin. Peripheral smear showed no schistocytes, reduced peripheral platelet count without clumping, and a single anisocyte and ovalocyte per high-power field. The white blood cell count was 5.6 × 109/L (4.5–11.0 × 109/L) with 81.5% neutrophils, hemoglobin 11.0 g/dL (13.5–17.5 g/dL) with a mean corpuscular volume of 83.3 fl, and red cell distribution width of 20%. Blood chemistries showed sodium of 140 mEq/L (135–145 mEq/L), potassium of 4.0 mEq/L (3.5–5.0 mEq/L), chloride of 106 mEq/L (95–105 mEq/L), bicarbonate of 23 mEq/L (22–29 mEq/L), blood urea nitrogen of 49 mg/dL (7–18 mg/dL), creatinine of 2.2 mg/dL (0.6–1.2 mg/dL) with baseline appearing to be 1.2 mg/dL, and blood glucose of 83 mg/dL (70–115 mg/dL). Haptoglobin, lactate dehydrogenase, vitamin B12, and folate were normal. Other than the addition of the antibiotic, there was no recent changes in his medication.
The differential diagnosis for the patient’s thrombocytopenia consisted of dilutional effect secondary to fluid resuscitation, heparin-induced thrombocytopenia (HIT), myelodysplastic syndrome, splenic sequestration, and other drug-induced thrombocytopenias. During the hospital course, the hemoglobin reached a nadir of 9.5 g/d, but stabilized as the platelet count continued to trend downward ruling out dilutional effect. An absence of schistocytes on peripheral smear made intravascular consumption less likely. An ultrasound with no sign of hepatomegaly or splenomegaly decreased the likelihood of splenic sequestration. HIT was unlikely due to the fact that the patient reported no recent prior exposure to unfractionated or low molecular weight heparin, and this was confirmed by a negative HIT antibody panel. Myelodysplastic syndrome was thought to be unlikely per hematology consultants. Because of this, our concern for drug-induced thrombocytopenia increased.
Hematology consultants introduced the idea that the patient’s thrombocytopenia could be a result of a drug reaction to the fluoroquinolones. The antibiotic regimen was changed from levofloxacin to cefepime on hospital day 4 and the platelets gradually rose to 127 × 109/L at discharge (Figure
Case of patient’s platelet trend showing initial point one week prior to admission where ciprofloxacin was changed to levofloxacin, as well as trend throughout hospital stay. Levofloxacin was changed to cefepime on hospital day 4.
We diagnosed this patient with probable fluoroquinolone-induced thrombocytopenia based on decrease in platelet count after the introduction of levofloxacin and the improvement in platelet count after the removal of this agent.
Drug-induced thrombocytopenia (DIT) is a relatively common disorder marked by a moderate-to-severe thrombocytopenia and possible signs of spontaneous bleeding that range from ecchymosis and petechia to mucosal bleeding to life-threatening spontaneous intracranial hemorrhage [
A literature review on fluoroquinolone-induced thrombocytopenia shows recent case reports with patient outcomes ranging from asymptomatic reduction in platelet count to severe thrombocytopenia associated with diffuse microhemorrhage and death [
In a case reporting death, there were no bone marrow abnormalities nor microangiopathy noted on autopsy. Examination revealed diffuse petechial hemorrhages suggesting that death was caused exclusively by peripheral thrombocytopenia without associated bone marrow suppression or thrombotic thrombocytopenic purpura [
One study reports an in-depth investigation of the development of glycoprotein IIb/GIIIa directed antibodies in the serum of their patient with fluoroquinolone-induced thrombocytopenia [
The described phenomenon of a particular fluoroquinolone causing thrombocytopenia despite tolerance to another fluoroquinolone has not been described. However, anaphylaxis has been reported in a patient after levofloxacin exposure who was otherwise able to tolerate full dose oral garenoxacin after skin patch testing showed a reaction to the former but not the latter [
Certain criteria suggest possible DIT [ Therapy with the suspected drug was instituted before thrombocytopenia and platelet count recovered upon stopping medication. The suspected medication was the only new medication instituted. No other causes of low platelets were identified. Reexposure resulted in concomitant drop in platelets.
Meeting all four criteria gives a “definite” diagnosis, while meeting criteria (1), (2), and (3) gives a “probable” diagnosis and meeting criteria (1) gives a “possible” diagnosis, and the diagnosis is “unlikely” if criteria (1) is not met.
Several laboratory tests have been developed to evaluate the presence of markers of drug-induced antibodies, but these suffer from poor solubility of certain drugs, need for specific patient cells for testing, and inability to test drug metabolites for causative factor [
Recovery from DIT is variable and based on the amount of bone marrow destruction caused by the particular agent. It is recommended that a bone marrow evaluation should be undertaken in a patient that requires blood-product administration for their thrombocytopenia or myelosuppression. The presence of precursor cells in the bone marrow aspirate is a promising sign for a more rapid recovery of cell counts than absence of these cells [
Upon determining sensitivity to a particular agent, the agent should be removed from the patient’s treatment and should be listed as a drug intolerance. The immunogenic response to a particular agent is usually quite specific and similar drugs may be instituted in treatment without increased risk for DIT [
The above case demonstrates fluoroquinolones as a suspected medication causing DIT and also illustrates our algorithmic approach to this issue. Further, tolerance to one medication in a class does not confer tolerance to the entire class, as described above. It is imperative to rule out other causes of thrombocytopenia and be able to employ diagnostic criteria for DIT, especially for nonchemotherapeutic or heparin agents, to come to an accurate diagnosis.
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Neither Dr. Burkes nor Ms. Landi has any conflict of interests.