Percutaneous Coronary Intervention (PCI) in Combined FV and FVIII Deficiency with a Novel LMAN1 Mutation.

Abstract

Abstract 4448 INTRODUCTIONPatients with congenital coagulation factor deficiencies undergoing PCI are at increased risk of both perioperative bleeding and thrombosis of coronary stents. Several cases of successful PCI have been described in patients with factor VIII (FVIII) and factor IX deficiency. We report on the first PCI in combined factor V (FV) and FVIII deficiency (F5F8D). F5F8D is an autosomal recessive disorder associated with moderate bleeding diathesis. This genetically heterogeneous disorder involves the genes LMAN1 and MCDF2, which encode for a cargo receptor complex that plays a key role in the trafficking of FV and FVIII from the endoplasmic reticulum to the golgi complex. CASE DISCUSSIONA 68 year old white male presented with dyspnea on exertion and palpitations. A myocardial perfusion stress test showed anteroseptal ischemia with a LVEF of 64%. He was referred for cardiac catheterization. He had life-long history of episodes of self-limiting mucosal bleeds, easy bruising and a large hematoma on his upper extremity provoked by a minor injury. Coagulation work up revealed a FV level of 11% and FVIII level of 7%. Before cardiac catheterization, the patient was given a loading dose of 30ml/kg of FFP. The trough levels of FV and FVIII were 37% and 31% after the procedure. The patient was given 25U/kg of recombinant FVIII (helixate FS ©) at 12 and 24 hours post PCI with a resultant FVIII level of 71% at 36 hours post PCI. Coronary angiography revealed the patient had a 95% stenosis of the left anterior descending artery. A metal stent was used to minimize the duration of antiplatelet therapy needed postoperatively. During the procedure anticoagulation was achieved using intravenous unfractionated heparin. There were no signs of local bleeding at the femoral access site through the postoperative period after using an Angioseal closure device. The patient was treated with clodipogrel 75 mg and aspirin 81 mg by mouth daily for 30 days after the procedure followed by aspirin alone long term. He had two episodes of mild self-limiting nose bleeds while on double antiplatelet therapy, no other bleeding. He remains well with no symptoms of cardiac ischemia at nine months after the procedure. Subsequent genetic analysis of both LMAN1 and MCFD2 genes showed two mutations: a novel 912delA mutation and a previously described 912-913insA mutation, both at the same location in exon 8. The mutations were confirmed first by sequencing, followed by cloning the PCR product and sequencing individual clones. Normally the LMAN1 gene has a string of 9A's at this location from 904 to 912, while our patient had 10 A's on one chromosome and 8 A's on the other chromosome. This could be explained by the patient having inherited one mutation on one chromosome and gaining a de novo mutation on the other chromosome, since this microsatellite repeat is a mutation hot spot. Unfortunately this question cannot be answered since no parent DNA was available. Informed consent was obtained prior to publication of this manuscript. CONCLUSIONSThis patient's presentation was consistent with published findings in other patients with F5F8 deficiency caused by LMAN1 mutations, with reported levels of FV 13.7% (range 1.7% to 35%) and FVIII 16% (range 2.2% to 35%). Our experience suggests that patients with F5F8D and mild bleeding diathesis can tolerate PCI for coronary artery disease followed by double antiplatelet therapy of limited duration and low-dose aspirin long term. Disclosures:No relevant conflicts of interest to declare.