Cerebral Infarction Followed by Myocardial Infarction in a Young Adult with Protein C and S Deficiency

Tahir, Faryal; Majid, Zainab; Arif, Taha Bin; Ahmed, Jawad

doi:10.7759/cureus.6665

Cited by 5 publications

(6 citation statements)

References 12 publications

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“…Some data have confirmed the relationship between reduced plasma concentration of protein S, a non-enzymatic element of hemostasis that regulates the activity of protein C, and the occurrence of ischemic stroke [ 36 , 37 ]. In studies conducted on mice, it was found that the injection of protein S had a neuroprotective function, reducing the size and extent of ischemic lesions [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

Platelet-Derived Drug Targets and Biomarkers of Ischemic Stroke—The First Dynamic Human LC-MS Proteomic Study

Gawryś¹,

Turek-Jakubowska²,

Gawryś

et al. 2022

JCM

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(1) Objective: The aim of this dynamic LC-MS (liquid chromatography and mass spectrometry) human platelet proteomic study was to identify the potential proteins candidates for biomarkers of acute ischemic stroke (AIS), their changes during the acute phase of stroke and to define potential novel drug targets. (2) Methods: A total of 32 patients (18–80 years old) were investigated that presented symptoms of AIS lasting less than 24 h from the onset, confirmed by neurological examination and/or new cerebral ischemia visualized in the CT (computed-tomography) scans. The analysis of platelet proteome was performed using LC-MS at baseline, and then on the third and seventh day from the onset of symptoms. The control group was demographically matched without any clinical signs of acute brain injury. (3) Results: The differences between platelets, at 24 h after first symptoms of stroke subjects and the control group included: β-amyloid A4 and amyloid-like protein 2, coactosin-like protein, thymidine phosphorylase 4 (TYMP-4), interferon regulatory factor 7 (IRF7), vitamin K-dependent protein S, histone proteins (H2A type 1 and 1-A, H2A types 2B and J, H2Av, -z, and -x), and platelet basic protein. The dynamic changes in the platelet protein concentration involved thrombospondin-1, thrombospondin-2, filamin A, B, and C. (4) Conclusions: This is the first human dynamic LC-MS proteomic study that differentiates platelet proteome in the acute phase of ischemic stroke in time series and compares the results with healthy controls. Identified proteins may be considered as future markers of ischemic stroke or therapeutic drug targets. Thymidine phosphorylase 4 (TYMP-4) holds promise as an interesting drug target in the management or prevention of ischemic stroke.

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Section: Discussionmentioning

confidence: 99%

Platelet-Derived Drug Targets and Biomarkers of Ischemic Stroke—The First Dynamic Human LC-MS Proteomic Study

Gawryś¹,

Turek-Jakubowska²,

Gawryś

et al. 2022

JCM

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“…Some individuals did not suffer from any thromboembolic event despite having low levels of PC antigen and activity [2,33]. However, death due to coronary artery disease or CVA of unknown cause has also been documented in some families [28,29,35].…”

Section: Discussion Of the Case Reportsmentioning

confidence: 99%

“…Similarly, some patients were also treated previously for thrombosis of larger veins such as portal, superior, and inferior mesenteric veins [31,33,39]. PC deficiency manifesting as recurrent episodes of CVA or MI has also been highlighted by a number of studies [3,26,28,32,34,37]. Past medical records of some patients revealed atypical symptoms such as generalized tonic-clonic seizures associated with vomiting or a brief period of truncal ataxia and gait disturbance [26,30].…”

Section: Discussion Of the Case Reportsmentioning

confidence: 99%

“…The treatment and management of PC deficiency are mostly based on previously reported cases and experiences. The mainstay of treatment in the majority of cases has been the use of anticoagulants such as heparin, warfarin, aspirin, and clopidogrel [2,[24][25][26][27][28][29][30][31][32]. There exist a paucity of data regarding the management of PC deficiency manifesting as stroke; hence, the aforementioned cases ( Table 4) have provided us some clue regarding the failure and success of various therapies.…”

Section: Managementmentioning

confidence: 99%

“…Most physicians use long-term anticoagulation therapy for the prevention of thromboembolic events [44]. Based on the cases in Table 4, cerebral ischemia and infarction secondary to PC deficiency have been successfully managed by initial administration of heparin (mostly low molecular weight heparin) after hospital admission followed by long-term use of anticoagulant (warfarin in most of the cases) [26][27][28]31,36,[39][40][41][42].…”

Section: Managementmentioning

confidence: 99%

See 2 more Smart Citations

Protein C Deficiency as a Risk Factor for Stroke in Young Adults: A Review

Majid

Tahir

Ahmed

et al. 2020

Cureus

Self Cite

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Analysis of four hereditary protein C deficiencies associated with vascular thromboembolism

Chen,

Yuan,

et al. 2024

Ann Hematol

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To analyze the clinical features and gene mutations in four families with hereditary protein C (PC) de ciency and explore their association with vascular thromboembolism. MethodsThe clinical data of four patients with PC de ciency were retrospectively analyzed. Venous blood samples were collected from the four affected patients and their family members, and relevant coagulation indexes and thrombin production and inhibition tests were performed. PCR was used to amplify and directly sequence the PROC gene of the prevalent patients. Software analysis was conducted to assess the conservativeness and pathogenicity of the mutated loci. Protein models were constructed to analyze the spatial structure before and after the mutation. ResultsThrombin generation and inhibition assays demonstrated impaired anticoagulation in all four probands. Proband 1 and 4 presented clinically with pulmonary embolism and lower extremity deep vein thrombosis (DVT), Proband 2 with cerebral infarction, and Proband 3 with DVT. Genetic analysis revealed the presence of the following mutations: c541T > G heterozygous missense mutation, c.577-579delAAG heterozygous deletion mutation, c.247-248insCT heterozygous insertion mutation, c.659G > A heterozygous missense mutation, and a new variant locus c.1146_1146delT heterozygous deletion mutation in the four probands, respectively. Conservativity and pathogenicity analyses con rmed that most of these amino acid residues were conserved, and all the mutations were found to be pathogenic. Analysis of protein modeling revealed that these mutations induced structural alterations in the protein or led to the formation of truncated proteins. ConclusionThe identi ed mutations are likely associated with decreased PC levels in each of the four families. The clinical manifestations of hereditary PC de ciency exhibit considerable diversity.

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Cerebral Infarction Followed by Myocardial Infarction in a Young Adult with Protein C and S Deficiency

Cited by 5 publications

References 12 publications

Platelet-Derived Drug Targets and Biomarkers of Ischemic Stroke—The First Dynamic Human LC-MS Proteomic Study

Platelet-Derived Drug Targets and Biomarkers of Ischemic Stroke—The First Dynamic Human LC-MS Proteomic Study

Protein C Deficiency as a Risk Factor for Stroke in Young Adults: A Review

Analysis of four hereditary protein C deficiencies associated with vascular thromboembolism

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