Idiopathic pulmonary arterial hypertension in a patient with pyruvate kinase deficiency and paravertebral extramedullary hematopoiesis

Bachmeyer, Claude; Khalil, Anita; Kerrou, Khaldoun; Girot, Robert; Gounant, V.

doi:10.1007/s00277-008-0644-z

Cited by 7 publications

(3 citation statements)

References 9 publications

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“…These lesions are diagnosed by radiological imaging and/or a tissue biopsy. Pulmonary hypertension, diagnosed by echocardiogram and confirmed with cardiac catheterization, is a complication in 3% of patients with PKD post‐splenectomy (Bachmeyer et al , ; Grace et al , ). The aetiology in PKD is not clear but, given this well‐described complication in other haemolytic anaemias, it probably relates to ongoing haemolysis.…”

Section: Complications: Screening and Managementmentioning

confidence: 99%

How we manage patients with pyruvate kinase deficiency

2019

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Summary Novel therapies in development have brought a new focus on pyruvate kinase deficiency (PKD), the most common congenital haemolytic anaemia due to a glycolytic enzyme deficiency. With an improved recognition of its clinical presentation and understanding of the diagnostic pathway, more patients are likely to be identified with this anaemia. Complications, including gallstones and non‐transfusion‐related iron overload, require monitoring for early diagnosis and management. Current management remains supportive with red cell transfusions, chelation and splenectomy. Decisions to transfuse and/or splenectomise must be individualised. Haematopoietic stem cell transplant has been pursued in a small number of patients with mixed outcomes. Novel treatment approaches, which range from a small molecule pyruvate kinase activator to gene therapy, may transform the way in which PKD is managed in the future. In this review, we discuss the pathophysiology of PKD and present our approaches to diagnosis, monitoring and management of patients with this anaemia.

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Section: Complications: Screening and Managementmentioning

confidence: 99%

How we manage patients with pyruvate kinase deficiency

2019

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“… 1 , 20 Extramedullary hematopoiesis is very rare and may be recognized by CT scan showing paravertebral masses; 1 , 38 , 39 pulmonary hypertension has been reported, should be suspected in case of dyspnea disproportionate to anemia severity, and investigated by echocardiography and cardiologist referral. 1 , 40 Finally, leg ulcers have been seldomly reported, 20 , 41 so that physical examination for cutaneous lesions is recommended in PKD patients.…”

Section: Current Challenges In Pkdmentioning

confidence: 99%

Pyruvate Kinase Deficiency: Current Challenges and Future Prospects

Fattizzo¹,

Cavallaro²,

Marcello³

et al. 2022

JBM

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Pyruvate kinase deficiency (PKD) is a rare autosomal recessive disease marked by chronic hemolytic anemia of various severity and frequent complications including gallstones, splenomegaly, iron overload, and others. Disease phenotype is highly heterogeneous and changes over time with children, adolescents and adult patients displaying different transfusion requirement and rates of complications. The diagnosis relies on the initial clinical suspicion in a patient with chronic hemolysis and exclusion of other more common congenital forms of hemolytic anemias; it is supported by the demonstration of reduced PK enzyme activity, and further confirmed by the detection of (homozygous or compound heterozygous) mutations of PKLR gene. Therapy is mainly supportive, with vitamin supplementation and transfusions (based on symptoms and patient growth rather than on fixed Hb thresholds). Splenectomy is widely performed, although it is less effective than in membrane defects and carries thrombotic and infectious risk. In the last decade, the allosteric PK enzyme activator mitapivat showed dramatic clinical benefit in clinical trials and gene therapy is also being studied to substitute the defective enzyme. In this review, we provide an insight in the current challenges of PKD diagnosis and management and discuss the future application of novel drugs and gene therapy, including a focus on quality of life.

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“…In this patient, an evaluation for cardiopulmonary disease, such as the pulmonary hypertension that can complicate PKD, is warranted. 11 , 25 A decline in cardiopulmonary function also frequently occurs due to non-PKD-related disease or from age-related factors, which can reduce the patient’s ability to compensate for the degree of anemia. Cases such as this one emphasize that transfusion independence in PKD may come and go throughout the patient’s lifespan.…”

Section: Special Situationsmentioning

confidence: 99%

The variable manifestations of disease in pyruvate kinase deficiency and their management

et al. 2020

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Pyruvate kinase deficiency (PKD) is the most common cause of chronic hereditary non-spherocytic hemolytic anemia and results in a broad spectrum of disease. The diagnosis of PKD requires a high index of suspicion and judicious use of laboratory tests that may not always be informative, including pyruvate kinase enzyme assay and genetic analysis of the PKLR gene. A significant minority of patients with PKD have occult mutations in non-coding regions of PKLR which are missed on standard genetic tests. The biochemical consequences of PKD result in hemolytic anemia due to red cell pyruvate and ATP deficiency while simultaneously causing increased red cell 2,3-diphosphoglycerate, which facilitates oxygen unloading. This phenomenon, in addition to numerous other factors such as genetic background and differences in splenic function result in a poor correlation between symptoms and degree of anemia from patient to patient. Red cell transfusions should, therefore, be symptom-directed and not based on a hemoglobin threshold. Patients may experience specific complications, such as paravertebral extramedullary hematopoiesis and chronic debilitating icterus, which require personalized treatment. The decision to perform splenectomy or hematopoietic stem cell transplantation is nuanced and depends on disease burden and long-term outlook given that targeted therapeutics are in development. In recognition of the complicated nature of the disease and its management and the limitations of the PKD literature, an international working group of ten PKD experts convened to better define the disease burden and manifestations. This article summarizes the conclusions of this working group and is a guide for clinicians and investigators caring for patients with PKD.

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Idiopathic pulmonary arterial hypertension in a patient with pyruvate kinase deficiency and paravertebral extramedullary hematopoiesis

Abstract: . Idiopathic pulmonary arterial hypertension in a patient with pyruvate kinase deficiency and paravertebral extramedullary hematopoiesis.

Cited by 7 publications

References 9 publications

How we manage patients with pyruvate kinase deficiency

How we manage patients with pyruvate kinase deficiency

Pyruvate Kinase Deficiency: Current Challenges and Future Prospects

The variable manifestations of disease in pyruvate kinase deficiency and their management

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