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Presentation Details
| APOLD1-Associated Vascular-Type Bleeding Disorder Presenting With Severe Postoperative Hemorrhage: A Case Report Natalie Montanez 1, 2, Rida Haider 1, 3, Joanna Larson1, 2, Harish Eswaran1, 4, Miguel Escobar1, 4. 1Gulf States Hemophilia and Thrombophilia Center, Houston, TX, USA.2University of Texas Health Science Center of Houston, McGovern Medical School, Department of Pediatrics, Division of Hematology, Houston, TX, USA.3University of Texas Health Science Center of Houston, McGovern Medical School, Department of Pediatrics, Division of Medical Genetics, Houston, TX, USA.4University of Texas Health Science Center of Houston, McGovern Medical School, Department of Pediatrics and Internal Medicine, Division of Hematology, Houston, TX, USA |
Abstract
Background:
Vascular-type bleeding disorders result from vessel wall rather than defects in coagulation factors or platelets. Emerging data suggest that heterozygous variants in APOLD1 (apolipoprotein L domain containing 1), a regulatory protein involved in endothelial barrier permeability, may cause a vascular bleeding phenotype characterized by capillary fragility, easy bruising, and spontaneous or postoperative hemorrhage. Clinical descriptions remain limited, and the phenotype is still being defined. Objectives:
To describe the clinical presentation, postoperative hemorrhagic course, laboratory evaluation, and genetic findings of a woman with vascular-type bleeding disorder associated with heterozygous APOLD1 variants of uncertain significance. Methods:
We reviewed medical records, imaging, perioperative, and laboratory data for a 29-year-old woman who developed severe hemorrhagic complications after total abdominal hysterectomy. Coagulation testing included PT, PTT, fibrinogen, fibrin split products, platelet count, thrombin time, von Willebrand studies, and platelet aggregation testing. Genetic evaluation included a next-generation sequencing panel covering >80 known or suspected bleeding-disorder genes, including APOLD1. Results:
Within days of surgery, the patient developed extensive ecchymosis and a rapidly enlarging abdominal wall hematoma. CT revealed a 5.3 × 5 cm hematoma; hemoglobin decreased from 9.2 g/dL to 7.6 g/dL. Studies showed hypofibrinogenemia (67 mg/dL), markedly elevated fibrin split products (>20 μg/mL), thrombocytopenia (108 K/μL), and a mildly prolonged INR (1.47), with normal PTT. She required urgent hemostatic resuscitation with 10 units of cryoprecipitate and 2 units of packed red blood cells, achieving hemodynamic stabilization and cessation of hematoma expansion. Her historical bleeding symptoms included seven days of oral bleeding following wisdom tooth extraction. Family history included a brother with bleeding symptoms and liver disease. ISTH-BAT score was 10, consistent with a clinically significant bleeding phenotype. She also had right lower extremity venous malformations previously treated with sclerotherapy, with prior imaging showing multiple small nodular soft-tissue densities of the right lateral hip consistent with superficial vascular malformation. Baseline, coagulation studies were unremarkable: PT 14.5 sec, PTT 32.2 sec, thrombin time 17.4 sec; VWF Ag 141%, VWF RCo 129%, FVIII 75%; fibrinogen antigen 191 mg/dL, fibrinogen activity 194 mg/dL, ratio 0.98. Platelet aggregation showed mildly to moderately decreased aggregation with all reagents, with normal aggregation at low-dose ristocetin. Initial sequencing of FGA, FGB, and FGG was negative. Expanded panel identified two heterozygous APOLD1 variants of uncertain significance: c.96+1G>A, affecting a canonical splice site, and c.70C>A (p.Leu24Met), a rare missense change. No variants were identified in other coagulation, platelet, or fibrinolytic genes. Given the clinical presentation, absence of factor deficiencies, and presence of venous malformations, these findings were considered potentially contributory to a vascular-type bleeding phenotype. Conclusions:
This case highlights severe postoperative hemorrhage in a young woman with clinical features suggestive of a vascular-type bleeding disorder and heterozygous APOLD1 variants. Her presentation supports emerging evidence that APOLD1 disruption may impair endothelial integrity, leading to capillary fragility, spontaneous hematomas, and excessive surgical bleeding. Recognition of this evolving disorder is essential for perioperative planning, prompt hemostatic support, and genetic counseling. Further studies are needed to clarify the pathogenicity and penetrance of APOLD1 variants and guide management strategies.
No part of this publication may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the author.
Vascular-type bleeding disorders result from vessel wall rather than defects in coagulation factors or platelets. Emerging data suggest that heterozygous variants in APOLD1 (apolipoprotein L domain containing 1), a regulatory protein involved in endothelial barrier permeability, may cause a vascular bleeding phenotype characterized by capillary fragility, easy bruising, and spontaneous or postoperative hemorrhage. Clinical descriptions remain limited, and the phenotype is still being defined. Objectives:
To describe the clinical presentation, postoperative hemorrhagic course, laboratory evaluation, and genetic findings of a woman with vascular-type bleeding disorder associated with heterozygous APOLD1 variants of uncertain significance. Methods:
We reviewed medical records, imaging, perioperative, and laboratory data for a 29-year-old woman who developed severe hemorrhagic complications after total abdominal hysterectomy. Coagulation testing included PT, PTT, fibrinogen, fibrin split products, platelet count, thrombin time, von Willebrand studies, and platelet aggregation testing. Genetic evaluation included a next-generation sequencing panel covering >80 known or suspected bleeding-disorder genes, including APOLD1. Results:
Within days of surgery, the patient developed extensive ecchymosis and a rapidly enlarging abdominal wall hematoma. CT revealed a 5.3 × 5 cm hematoma; hemoglobin decreased from 9.2 g/dL to 7.6 g/dL. Studies showed hypofibrinogenemia (67 mg/dL), markedly elevated fibrin split products (>20 μg/mL), thrombocytopenia (108 K/μL), and a mildly prolonged INR (1.47), with normal PTT. She required urgent hemostatic resuscitation with 10 units of cryoprecipitate and 2 units of packed red blood cells, achieving hemodynamic stabilization and cessation of hematoma expansion. Her historical bleeding symptoms included seven days of oral bleeding following wisdom tooth extraction. Family history included a brother with bleeding symptoms and liver disease. ISTH-BAT score was 10, consistent with a clinically significant bleeding phenotype. She also had right lower extremity venous malformations previously treated with sclerotherapy, with prior imaging showing multiple small nodular soft-tissue densities of the right lateral hip consistent with superficial vascular malformation. Baseline, coagulation studies were unremarkable: PT 14.5 sec, PTT 32.2 sec, thrombin time 17.4 sec; VWF Ag 141%, VWF RCo 129%, FVIII 75%; fibrinogen antigen 191 mg/dL, fibrinogen activity 194 mg/dL, ratio 0.98. Platelet aggregation showed mildly to moderately decreased aggregation with all reagents, with normal aggregation at low-dose ristocetin. Initial sequencing of FGA, FGB, and FGG was negative. Expanded panel identified two heterozygous APOLD1 variants of uncertain significance: c.96+1G>A, affecting a canonical splice site, and c.70C>A (p.Leu24Met), a rare missense change. No variants were identified in other coagulation, platelet, or fibrinolytic genes. Given the clinical presentation, absence of factor deficiencies, and presence of venous malformations, these findings were considered potentially contributory to a vascular-type bleeding phenotype. Conclusions:
This case highlights severe postoperative hemorrhage in a young woman with clinical features suggestive of a vascular-type bleeding disorder and heterozygous APOLD1 variants. Her presentation supports emerging evidence that APOLD1 disruption may impair endothelial integrity, leading to capillary fragility, spontaneous hematomas, and excessive surgical bleeding. Recognition of this evolving disorder is essential for perioperative planning, prompt hemostatic support, and genetic counseling. Further studies are needed to clarify the pathogenicity and penetrance of APOLD1 variants and guide management strategies.
No part of this publication may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the author.