Drug Induced Thrombotic Microangiopathy Secondary to Quetiapine; The Second Reportable Case in Medical Literature

INTRODUCTION

Thrombotic microangiopathy (TMA) describes a group of disorders that are often related to microangiopathic hemolytic anemia (MAHA) and thrombocytopenia. A common etiology is from exposure to certain drugs. Hereby, we present the second reportable case in medical literature of TMA secondary to quetiapine exposure.

CASE PRESENTATION

A 27 years old male patient with past medical history of schizoaffective disorder and depression, was admitted for altered mental status. Patient was completely disoriented with noncoherent speech. Home medications included quetiapine 775mg and valproate 750mg. Labs on admission were significant for Hb 7.6, Platelets 16, Wbc 8.1, Na 139, K 4.7, Hco3 23, Cr 14.5. Patient received 1 PRBC unit on admission. Hb was 7.9 on day 2, and his home medication quetiapine was resumed on that evening. Within 24hrs of receiving quetiapine, Hb and platelets reached a low point of 6.6 and 11 respectively. And within 48hrs, 3 PRBCs and 1 platelet units were transfused, resulting in Hb 6.7 and platelets 45 at the end of that 48hrs period. Clinically, patient was restless and agitated. His speech became slurred. Patient also had severe AKI with oliguria requiring hemodialysis. Further workup showed undetectable haptoglobin, elevated LDH, total bilirubin 3.22 and direct bilirubin 0.72, reticulocytes 12%, schistocytes on peripheral smear, INR 1.1, normal B12 level, valproic acid level of 52.7 (within normal reference range), negative HIV and syphilis, negative Coombs test, negative ANA/ANCA panel, negative platelet antibody, AdamTS13 level 99.1% (prior to plasma exchange), negative CFH antibody. Progression of laboratory findings and treatments received are shown in the accompanying figures (Figure 1, 2). In total, patient received 7 PRBC units, 1 single donor platelets unit, methylprednisolone followed by prednisone course, 5 plasma exchange sessions, 2 Rituximab infusions. During his hospital stay, patient gradually recovered, lab values demonstrated stability, and was discharged on day 15.

DISCUSSION

Drug induced thrombotic microangiopathy (DITMA) is part of a larger entity called thrombotic microangiopathies (TMA), which is often observed with MAHA and thrombocytopenia. DITMA is subdivided into an immune mechanism with prior or ongoing exposure to a drug thereby generating antibodies, and a nonimmune mechanism usually occurring after chronic exposure to a drug resulting in accumulation or can occur with acute exposure. The clinical presentation in immune mediated DITMA usually has a severe and sudden onset, with lab findings of MAHA, thrombocytopenia, severe acute kidney injury, along with normal or mildly decreased AdamTS13 activity (above 10%). However, DITMA is a diagnosis of exclusion, therefore other differentials have to be ruled out including thrombotic thrombocytopenic purpura (TTP) that is associated with an AdamTS13 level less than 10%, complement mediated TMA that can be evaluated with CFH antibody, hemolytic uremic syndrome (HUS) that typically presents in children with diarrhea, metabolism mediated TMA that is often related to vitamin B12 deficiency. Once the diagnosis is made, management involves discontinuation of the inciting drug. However, when the diagnosis is uncertain, therapies utilized in other forms of TMA may be used. Patients with DITMA should avoid re-exposure to the implicated drug in the future.

The Oklahoma registry and the blood center of Wisconsin developed a criteria to evaluate patients with evidence of TMA and a suspected drug etiology. In our case, it meets the criteria for definite immune-mediated association with quetiapine, where other causes of TMA were excluded, quetiapine was the only drug taken during hospitalization, patient was taking this drug prior to hospitalization and subsequent exposure lead to manifestations of TMA within 24 hours. Literature review for similar reports revealed as few as 3 cases of quetiapine associated TMA, but AdamTS13 was noted to be either <10% or not documented. However, a case report published in 2021 shows quetiapine associated TMA with normal AdamTS13 level. Therefore, our case report would be the second reportable case in medical literature of quetiapine associated DITMA with normal ADAMTS13 levels.

CONCLUSION

It is of vital importance to raise awareness on how a commonly prescribed psychiatric medication such as quetiapine can cause an immune mediated TMA that is life-threatening.

No relevant conflicts of interest to declare.