Diffuse alveolar hemorrhage: a rare adverse reaction of valproic acid

SESSION TITLE: The Trouble With That Drug: Drug-Induced Lung Diseases SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/09/2023 09:40 am - 10:25 am INTRODUCTION: Valproic acid is a widely used anti-epileptic drug and is associated with several well-established side effects of cerebral edema, hepatotoxicity, and hyperammonemia. There are a few reports of valproic acid causing hematological abnormalities by disrupting the coagulation cascade, platelet abnormalities and by causing thrombocytopenia . We present a case of diffuse alveolar hemorrhage (DAH) associated with valproic acid use. In English literature, only 3 such cases have been described so far. CASE PRESENTATION: A 33-year-old male with generalized epilepsy (Dx in 2018) presented to the hospital in July 2022 with shortness of breath associated with hemoptysis for one day. His hemoptysis started in the post-ictal period after having a seizure; he also had 1 episode of post-ictal hemoptysis in the past. He had been taking valproic acid 500mg daily since 2018. On the day of the presentation, his oxygen requirements were at 10L, and he was started on inhaled tranexamic acid (TXA) for hemoptysis. Inflammatory markers were low and inconsistent with DAH from autoimmune disease. Additionally, he had no sign of systemic autoimmune disease. Chest-X-ray was done which showed non-specific bilateral opacities (Figure 1). CT Chest angiogram revealed diffuse bilateral ground-glass opacities consistent with DAH (Figure 2). Inhaled TXA helped control the hemoptysis and his oxygen requirements were weaned down to 4L and subsequently to room air. Neurology was consulted and they recommended stopping valproic acid and started patient on Lacosamide. Outpatient bronchoscopy was planned but patient was lost to follow-up. He was admitted to our facility 8 months later with another epileptic episode & on history, there was no recurrence of hemoptysis since stopping the valproic acid. DISCUSSION: DAH can be caused by both immune and non-immune causes; steroids are the mainstay of treatment for autoimmune causes of DAH . Valproic acid has been linked to DAH in the literature review and there should be a high index of suspicion if a patient on valproic acid presents with hemoptysis and dyspnea. In our case, the association between DAH and valproic acid was indirect, because patient's symptoms improved after stopping valproic acid and has remained symptom free ever since. Additionally, there exists the possibility that negative pressure pulmonary edema associated with the seizure itself was a causative or contributive factor, however the lack of recurrence after stopping valproic acid provides some evidence for the valproic acid itself as the significant factor. The mechanism of valproic associated DAH is unclear but can be explained by several hemostatic anomalies of intrinsic and extrinsic coagulation cascade, platelet abnormalities, and thrombocytopenia . Withdrawal of the valproic acid remains the mainstay of treatment with the need for steroids in some cases. CONCLUSIONS: Valproic acid associated DAH should be high on differentials if a patient on valproic acid presents with hemoptysis and has imaging findings consistent with DAH; especially if other immune related and nonimmune related causes of DAH have been excluded. Withdrawal of valproic acid remains the mainstay of treatment and close follow-up is encouraged to document resolution of hemoptysis and imaging findings of DAH. REFERENCE #1: Gerstner T, Teich M, Bell N, Longin E, Dempfle CE, Brand J, König S. Valproate-associated coagulopathies are frequent and variable in children. Epilepsia. 2006 Jul;47(7):1136-43. doi: 10.1111/j.1528-1167.2006.00587.x. PMID: 16886976. REFERENCE #2: Quadrelli S, Dubinsky D, Solis M, Yucra D, Hernández M, Karlen H, Brigante A. Immune diffuse alveolar hemorrhage: Clinical presentation and outcome. Respir Med. 2017 Aug;129:59-62. doi: 10.1016/j.rmed.2017.06.003. Epub 2017 Jun 3. PMID: 28732837. REFERENCE #3: Gerstner T, Teich M, Bell N, Longin E, Dempfle CE, Brand J, König S. Valproate-associated coagulopathies are frequent and variable in children. Epilepsia. 2006 Jul;47(7):1136-43. doi: 10.1111/j.1528-1167.2006.00587.x. PMID: 16886976. DISCLOSURES: No relevant relationships by Awais Bajwa No relevant relationships by Mohammad Jamil No relevant relationships by Bilqees Khanam No relevant relationships by Adam Przebinda No relevant relationships by Huzaifah Salat