Ceftriaxone induced aplastic anaemia: A deadfall trap for bone marrow

Aplastic anaemia (AA) is a life‐threatening condition which can be inherited or acquired. Around 50% of aplastic anaemia cases are acquired with common inciting agents being viral infections, drugs, radiation, and chemical exposure. Drugs are one of the rarest causes of AA with incidence being 2/million population in Europe and three times more in Asia.1

Our case, an 88‐year‐old male presented with history of itching and multiple raised skin lesions all over the body for the duration of 2 years with acute exacerbation for 1 month duration. The patient denied history of atopy or parthenium exposure. The patient also had comorbidities of hypertension, chronic obstructive pulmonary disease, cor pulmonale, and benign prostatic hyperplasia for 5 years duration. Examination revealed multiple ill to well‐defined lichenified plaques with crusting and oozing of pus discharge over the forehead, bilateral cheeks, nape of neck, trunk, and extensor aspect of extremities with sparing of eyelids and retro‐auricular folds with 90% of the body surface area involved. The patient was clinically diagnosed as having erythroderma due to chronic actinic dermatitis with secondary infection. Baseline blood counts were normal (Hb 11.2 g/dl; RBC 5.49 million/μl; total leucocyte count [TLC] 8640/μl; and platelets 3.04 lakh/μl). A wound swab showed combined growth of methicillin sensitive Staphylococcus aureus and Escherichia coli, and both were sensitive to ceftriaxone in culture studies. Following that, injection ceftriaxone 1 g intravenous 12 hourly was given for 3 days and topical steroids and emollients were prescribed for skin lesions. One day after the initiation of ceftriaxone, all the haemogram parameters showed decreasing trends (Figure 1A‐D). Peripheral blood smear showed predominantly microcytic hypochromic red blood cells with anisocytosis, markedly reduced leucocyte count with decreased platelets and few giant platelets. The reticulocyte count was 0.08%, and a bone marrow aspirate showed a hypo cellular marrow with marked suppression of granulocyte series. Blood culture, urine culture, screening for viral markers (HSV, Hepatitis B and C, HIV 1 and 2, EBV, CMV, and Parvovirus B19), and tuberculosis were negative. The patient was diagnosed as drug induced aplastic anaemia on the basis of reduced haematological parameters and hypo cellular bone marrow picture and negative viral marker profile. Ceftriaxone was identified as the inciting agent by temporal correlation, and it was stopped. He was started on injection methylprednisolone 500 mg intravenous once daily for 3 days with injection filgrastim (recombinant granulocyte colony‐stimulating factor) 300 mg subcutaneous once daily for 5 days. Haemogram parameters showed increasing trends within 3 days of initiation of therapy (Hb 7.7 g/dl; RBC 3.85 million/μl; TLC 6510/μl with 55% band forms; and platelets 76000/μl), with significant recovery in 2 weeks (Hb 8.6 g/dl; RBC 4.39 million/μl; TLC 12710/μl; platelets 9.05 lakh/μl) (Figure 1 A‐D). The skin lesions resolved around 70‐80% with topical medications and the patient got discharged.

Figure 1.

(A‐D) Decreasing trends of haematological parameters after ceftriaxone injection and normalizing trend after filgrastim injection. A, Hb levels; B, total leucocyte count levels; C, platelet count levels; D, RBC levels

Even though drugs are one of the rarest causes of aplastic anaemia, it needs to be promptly addressed since it is an important emerging problem in modern medical era. Drugs commonly associated with aplastic anaemia (AA) are anti‐rheumatic agents, anti‐thyroid drugs, sulfonamides, anti‐tuberculous drugs, analgesics, and anticonvulsants.2 Dose‐related reversible marrow suppression and dose‐independent idiosyncratic aplasia are the two possible proposed pathological mechanisms for drug induced AA.3 Cephalosporins are widely used antibiotics in the management of skin, soft tissue, respiratory, and urinary tract infections. Although cephalosporins are one of the safest drugs, AA and agranulocytosis have been reported infrequently.4 Ceftriaxone induced aplastic anaemia has not been reported in English language literature to the best of our knowledge. Experience from our case emphasizes on the early identification of ceftriaxone associated rare life‐threatening adverse effects and the need of cautious use of antibiotics.

COMPETING INTERESTS

There are no competing interests to declare.

Rajan M B, Budania A, Bohra GK. Ceftriaxone induced aplastic anaemia: A deadfall trap for bone marrow. Br J Clin Pharmacol. 2019;85:1850–1851. 10.1111/bcp.13957