Abstract WP239: Real Time Prospective Measurement of aPTT Predicts Paradoxical Embolism in Cryptogenic Stroke

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Bo Song ◽  
Wenjun Deng ◽  
Lindsay Fisher ◽  
I-ying Chou ◽  
Max Oyer ◽  
...  
Keyword(s):  
Real Time ◽  
Protein C ◽  
Cryptogenic Stroke ◽  
Protein S ◽  
Paradoxical Embolism ◽  
Proof Of Concept ◽  
Stroke Patients ◽  
Neurologic Diseases ◽  
Coagulation Testing ◽  
Coagulation Status

Patent foramen ovale (PFO) is an important underlying source of cryptogenic stroke (CS) associated with hematologic procoagulability. However, the association of genetically identified hyperocagulability and paradoxical embolism has been difficult to establish due to retrospective analysis and the limited numbers of of known genetically identified hypercoagulable conditions. In this study, we explored the utility of conventional coagulation status in PFO related stroke, as the patients may harbor genetically unidentified hyperocoagulable conditions. Method: Eligible pts were prospectively recruited in accordance with IRB, and underwent conventional coagulation testing (PT/PTT) testing within 12 hours of stroke. All patients underwent full cryptogenic workup such as MRI/MRA, mobile cardiac outpatient telemetry (>30 days), cardiac echo, and hypercoagulable testing. Results: We screened 4,831 pts admitted with acute neurologic diseases, and recruited 358 eligible acute ischemic stroke pts. 54 (15.1%) pts had CS and 32 pts had PFO related stroke. While there is no difference between PFO-related CS and PFO-unrelated CS on full hypercaogulable screen (protein S, protein C, FVL, PTGM, ATIII, APLAb, LA, hcy), aPTT was statistically significantly shortened in PFO-related stroke patients (PFO CS vs. non-PFO CS: aPTT 27.2±4.1s vs. 29.9±2.3s). ROC curve indicates early shortened aPTT can predict PFO related stroke (sensitivity 70%, specificity 81.5%, p=0.017) (see Figure). Conclusion: We found real time aPTT to be significantly shortened in patients eventually diagnosed with paradoxical embolism related to PFO. While studies in larger pt cohorts accounting for other potential confounders are underway, this proof-of-concept study demonstrates the importance and utility of early conventional coagulation testing in identifying paradoxical embolism. Pts with shortened aPTT may need additional workup for other underlying hypercoagulable conditions.

scholarly journals Assessment of Protein C Levels in Patients with Ischaemic Stroke in South-South Nigeria: A Study of Cases in University of Benin Teaching Hospital, Benin City

2019 ◽  
Vol 11 (14) ◽  
pp. 106
Author(s):  
Oluomachi Charity Nnachi ◽  
Robert Azu Nnachi ◽  
Chukwuemeka Okorie Eze ◽  
Ogah Emeka Onwe ◽  
Augustine Ejike Okoye ◽  
...  
Keyword(s):  
Ischaemic Stroke ◽  
Protein C ◽  
Protein S ◽  
Stroke Patients ◽  
Protein C Deficiency ◽  
Benin City ◽  
Stroke Group ◽  
Wbc Count ◽  
And Control

Background/Objective: Protein C (PC) is a vitamin K – dependent coagulation inhibitor produced in the liver. Acting together with its cofactor, protein S (PS), activated PC inhibits activated factors V and VIII thus downregulating thrombin generation which may predispose to inappropriate clot formation. This study aimed to ascertain the role of protein C deficiency in the development of ischaemic stroke in order to establish its relevance in stroke management in our environment. Materials and Methods: Sixty-five ischaemic stroke patients and controls matched for age and sex were recruited in the study, blood samples were taken for haematological indices, prothrombin and activated partial thromboplastin times (PT and APTT) and protein C. Functional and qualitative assessments of protein C were done by chromogenic and immunoassay methods respectively. Data were analyzed with SPSS version 18. Results: A total of 130 subjects comprising 65 stroke subjects and 65 controls were recruited in the study. Mean age of the stroke group was 60.4±12.3yrs and the control is 59.0±14.1yrs. The mean difference in PC Ag level, PC Ag(%) and functional activity between the groups were not statistically significant (p<0.05). Total WBC count in the stroke subjects was significantly higher than the controls (p=0.001). The platelet count was also higher and haemoglobin concentrations lower in stroke patients though not statistically significant. The prothrombin and activated partial thromboplastin times (APTT) in test and control groups are not significant. Conclusion: This study showed that protein C may not play a significant role in the development of ischaemic stroke in our population.

scholarly journals Gerinnungsphysiologische und genetische Diagnostik bei hereditärem Protein S-Mangel/Coagulation testing and genetic diagnostics in hereditary protein S deficiency

2013 ◽  
Vol 37 (2) ◽  
Author(s):  
Sebastian Dübgen ◽  
Andrea Dick ◽  
Christoph Marschall ◽  
Michael Spannagl
Keyword(s):  
Protein C ◽  
Protein S ◽  
Genetic Diagnostics ◽  
Protein S Deficiency ◽  
Genetische Diagnostik ◽  
Systemische Inflammation ◽  
S Deficiency ◽  
Coagulation Testing

ZusammenfassungThrombophilie, die Neigung zu rezidivierenden, idiopathischen Thromboembolien, wird heute als multifaktorielle Erkrankung im Sinne einer Dysbalance des komplex regulierten Hämostasesystems verstanden. Trotz intensiver Abklärung bleibt der genaue Defekt einer erblichen Thromboseneigung oft unbekannt. Eine anerkannte Ursache, welche bei etwa 1 bis 2% der Betroffenen identifiziert werden kann, ist ein Mangel an Protein S, welches indirekt als Kofaktor von aktiviertem Protein C die Thrombinbildung limitiert. Die Einschätzung der pathogenetischen Relevanz verminderter Protein S-Spiegel ist jedoch aufgrund der sehr viel häufiger vorkommenden erworbenen Protein S-Erniedrigung unter bestimmten physiologischen und pathologischen Bedingungen (z.B. Einnahme einer hormonellen Kontrazeption oder systemische Inflammation) schwierig. Diese Arbeit eröffnet durch Hinzufügen aggregierter genetischer Daten von 136 Patienten einen neuen Blick auf die Protein S-Diagnostik im klinischen Alltag und liefert Hinweise, in welcher Konstellation mit größerer Wahrscheinlichkeit von einem echten (genetisch definierten) Mangel ausgegangen werden kann.

Abstract 3371: Inherited Thrombophilias In Cryptogenic Stroke Patients Under 55 Years Old

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Patricia Martinez-Sanchez ◽  
Marta Martinez-Martinez ◽  
Blanca Fuentes ◽  
Maria Vicenta Cuesta ◽  
Gerardo Ruiz-Ares ◽  
...  
Keyword(s):  
Brain Ischemia ◽  
Protein C ◽  
Brain Infarction ◽  
Cryptogenic Stroke ◽  
Factor V Leiden ◽  
Protein S ◽  
Prothrombin G20210a ◽  
Factor V ◽  
Factor V Leiden Mutation ◽  
G20210a Mutation

Background: inherited thrombophilias cause venous thrombotic events, however, their association with brain ischemia in adult patients is controversial. Our objective was to study the association between thrombophilia and cryptogenic stroke in patients under 55 years of age. Methods: prospective observational study of consecutive patients under 55 years of age who had had a brain ischemia (transient ischemic attack of brain infarction). The patients with cryptogenic brain ischemia were compared with the controls patients with brain ischemia of known cause. We examined the presence of thrombophilia (Factor V Leiden and prothrombin G20210A gene mutations; deficiencies in protein S, protein C and antithrombin levels; resistance to activated protein C) and patent foramen ovale (PFO) in all patients. Results: Two hundred fifty-four patients were included, 108 with cryptogenic brain ischemia and 146 controls patients with brain ischemia of known cause. Patients with cryptogenic brain ischemia were younger (mean age 42.4 vs. 45.6 years old, P=0.002). The frequency of thrombophilia was significantly higher among patients with cryptogenic brain ischemia than those with brain ischemia of known cause (22.2% vs. 6.8%, P<0.001). Taking into account each thrombophilic disorder separately, prothrombin G20210A mutation and protein C or S deficiency were significantly higher in the cryptogenic brain ischemia group than in the known cause group (10.2% vs. 2.7% and 8.3% vs. 2.1%, respectively, P<0.05) while Factor V Leiden mutation was similar in both groups (4.6% vs. 2.7%, P NS). The frequency of PFO and PFO plus thrombophilia were higher among patients with cryptogenic brain ischemia (35.2% vs. 12.3% and 8.4% vs. 0%, respectively, P<0.001). The PFO (+) cryptogenic brain ischemia patients showed higher frequency of thrombophilia than the other patients (23.7% vs. 11.6%, P=0.043), in particular prothrombin G20210A mutation (15.8% vs. 4.2%, P=0.014). Multivariate analysis adjusted confounding factors showed than the presence of thrombophilia was independently associated with cryptogenic brain ischemia (OR 3.9; 95% CI, 1.69 - 8.97; P=0.001). Conclusion: there is an association between thrombophilia and cryptogenic brain ichemia in patients under 55 years old. These data suggest that systemic thrombophilic disorders are cause of thromboembolic phenomena in brain arteries

scholarly journals Levels of protein C, protein S, and anti-thrombin III in acute ischemic stroke patients at Haj Adam Malik Hospital, Medan

2019 ◽  
Vol 8 (2) ◽  
pp. 460
Author(s):  
Jenie Erawati Muchti ◽  
Yuneldi Anwar ◽  
Adi Koesoema Aman
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Protein C ◽  
Protein S ◽  
Stroke Patients ◽  
C Protein

APC Resistance and other Haemostatic Variables during Pregnancy and Puerperium

1999 ◽  
Vol 81 (04) ◽  
pp. 527-531 ◽  
Author(s):  
U. Kjellberg ◽  
N.-E. Andersson ◽  
S. Rosén ◽  
L. Tengborn ◽  
M. Hellgren
Keyword(s):  
Factor Viii ◽  
Plasminogen Activator ◽  
Protein C ◽  
Activated Protein C ◽  
Plasminogen Activator Inhibitor ◽  
Protein S ◽  
Reference Level ◽  
Soluble Fibrin ◽  
Prothrombin Fragment ◽  
D Dimer

SummaryForty-eight healthy pregnant women were studied prospectively and longitudinally. Blood sampling was performed at 10-15, 23-25, 32-34 and 38-40 weeks of gestation, within one week and at eight weeks postpartum. Classic and modified activated protein C ratio decreased as pregnancy progressed. In the third trimester 92% of the ratios measured with the classic test were above the lower reference level whereas all modified test ratios were normal. Slight activation of blood coagulation was shown with increased levels of prothrombin fragment 1+2, soluble fibrin and D-dimer. Fibrinogen, factor VIII and plasminogen activator inhibitor type 1 and type 2 increased. Protein S and tissue plasminogen activator activity decreased. Protein C remained unchanged. No correlation was found between the decrease in classic APC ratio and changes in factor VIII, fibrinogen, protein S, prothrombin fragment 1+2 or soluble fibrin, nor between the increase in soluble fibrin and changes in prothrombin fragment 1+2, fibrinogen and D-dimer.

Beckenvenenthrombose im 16. Lebensjahr bei angeborener Vena-cava-inferior-Atresie und Ecstasy-Abusus

Phlebologie ◽  
2003 ◽  
Vol 32 (02) ◽  
pp. 50-53
Author(s):  
C. Pieck ◽  
P. Sander ◽  
F. G. Bechara ◽  
P. Altmeyer ◽  
M. Stücker
Keyword(s):  
Protein C ◽  
Vena Cava ◽  
Protein S ◽  
Sich Eine ◽  
Farbkodierte Duplexsonographie ◽  
Vena Cava Inferior ◽  
Vena Iliaca ◽  
Vena Femoralis

ZusammenfassungKasuistik: Eine kaukasische Patientin, die sich wegen kosmetisch störender Varizen an der Bauchdecke und den Leisten vorstellte, erlitt mit 16 Jahren während einer exzessiven Tanzveranstaltung unter dem Einfluss von Ecstasy (3,4-Methylendioxymethamphetamin) aus kompletter Gesundheit bei damals asymptomatischer Vena-cava-inferior-Atresie eine akute Beckenvenenthrombose. Diagnostik: Bidirektionale Dopplersonographie, farbkodierte Duplexsonographie, Kernspintomographie mit Magnevist-Kontrastmittel der Venen beider Beine bzw. im Bereich des kleinen Beckens, Bestimmung der Serumkonzentration von Protein C und Protein S, Ausschluss von APC-Resistenz und Faktor-V-Leiden-Mutation. Ergebnisse: In der farbkodierten Duplexsonographie thrombosierte Vena iliaca externa sowie septierte, jedoch suffiziente Vena femoralis communis beidseits, keine Insuffizienzen oder Thromben in den übrigen extraund intrafaszialen Beinvenen nachweisbar. In der Kernspintomographie der Beckenvenen stellte sich eine Hypoplasie der Vena cava inferior oberhalb der Nierenetage und eine Atresie der Vena cava inferior unterhalb der Nierenetage dar sowie ein ausgeprägter venöser Kollateralkreislauf im Bereich des Beckens über die Vv. iliacae internae beidseits und die Vv. lumbales ascendentes beidseits bei varikös entarteten Kollateralvenen im Bereich der Bauchdecke beidseits mit Anschluss an die V. femoralis communis beidseits. Die untersuchten Gerinnungsparameter blieben unauffällig. Schlussfolgerung: Ecstasy-Abusus kann in Kombination mit starker körperlicher Anstrengung zu Exsikkose und Hämokonzetration führen. Dies sehen wir als letzte Ursache der Thrombose bei bestehender Vena-cava-Aplasie.

Molekularbiologische Grundlagen und Diagnostik der hereditären Defekte von Antithrombin III, Protein C und Protein S

2002 ◽  
Vol 22 (02) ◽  
pp. 57-66
Author(s):  
I. Witt
Keyword(s):  
Protein C ◽  
Antithrombin Iii ◽  
Protein S ◽  
Klinische Relevanz ◽  
At Iii

ZusammenfassungDie enormen Fortschritte in der Molekularbiologie in den letzten Jahren ermöglichten sowohl die Aufklärung der Nukleotidsequenzen der Gene für Antithrombin III (AT III), Protein C (PROC) und Protein S (PROS) als auch die Identifizierung zahlreicher Mutationen bei hereditären Defekten dieser wichtigen Inhibitoren des plasmatischen Gerinnungssystems. Da die Gene für AT III (13,8 kb) und PROC (11,2 kb) nicht groß und relativ leicht zu analysieren sind, gibt es bereits umfangreiche »databases« der Mutationen (50, 73). Für AT III sind 79 und für PROC 160 unterschiedliche Mutationen beschrieben.Sowohl beim AT-III-Mangel als auch beim Protein-C-Mangel hat die Mutationsaufklärung neue Erkenntnisse über die Struktur-Funktions-Beziehung der Proteine gebracht. Beim Protein-C-Mangel steht die klinische Relevanz der DNA-Analyse im Vordergrund, da die Diagnostik des Protein-C-Mangels auf der Proteinebene nicht immer zuverlässig möglich ist.Das Protein-S-Gen ist für die Analytik schwer zugänglich, da es groß ist (80 kb) und außerdem ein Pseudogen existiert. Es sind schon zahlreiche Mutationen bei Patienten mit Protein-S-Mangel identifiziert worden. Eine Database ist bisher nicht publiziert. Die klinische Notwendigkeit zur Mutationsaufklärung besteht ebenso wie beim Protein-C-Mangel. Es ist zu erwarten, dass zukünftig die Identifizierung von Mutationen auch beim Protein-S-Mangel beschleunigt vorangeht.

The Frequency of Type I Heterozygous Protein S and Protein C Deficiency in 141 Unrelated Young Patients with Venous Thrombosis

1988 ◽  
Vol 59 (01) ◽  
pp. 018-022 ◽  
Author(s):  
C L Gladson ◽  
I Scharrer ◽  
V Hach ◽  
K H Beck ◽  
J H Griffin
Keyword(s):  
Venous Thrombosis ◽  
Protein C ◽  
Antithrombin Iii ◽  
Young Patients ◽  
Protein S ◽  
Type I ◽  
Protein S Deficiency ◽  
Protein C Deficiency ◽  
Low Protein ◽  
S Deficiency

SummaryThe frequency of heterozygous protein C and protein S deficiency, detected by measuring total plasma antigen, in a group (n = 141) of young unrelated patients (<45 years old) with venous thrombotic disease was studied and compared to that of antithrombin III, fibrinogen, and plasminogen deficiencies. Among 91 patients not receiving oral anticoagulants, six had low protein S antigen levels and one had a low protein C antigen level. Among 50 patients receiving oral anticoagulant therapy, abnormally low ratios of protein S or C to other vitamin K-dependent factors were presented by one patient for protein S and five for protein C. Thus, heterozygous Type I protein S deficiency appeared in seven of 141 patients (5%) and heterozygous Type I protein C deficiency in six of 141 patients (4%). Eleven of thirteen deficient patients had recurrent venous thrombosis. In this group of 141 patients, 1% had an identifiable fibrinogen abnormality, 2% a plasminogen abnormality, and 3% an antithrombin III deficiency. Thus, among the known plasma protein deficiencies associated with venous thrombosis, protein S and protein C. deficiencies (9%) emerge as the leading identifiable associated abnormalities.

Activated Protein C Increases Fibrin Clot Lysis by Neutralization of Plasminogen Activator Inhibitor No Evidence for a Cofactor Role of Protein S

1988 ◽  
Vol 60 (02) ◽  
pp. 328-333 ◽  
Author(s):  
N J de Fouw ◽  
Y F de Jong ◽  
F Haverkate ◽  
R M Bertina
Keyword(s):  
Plasminogen Activator ◽  
Protein C ◽  
Blood Platelets ◽  
Plasminogen Activator Inhibitor ◽  
Protein S ◽  
Tissue Type ◽  
Clot Lysis ◽  
Activator Inhibitor ◽  
Pai 1

summaryThe effect of purified human activated protein G (APC) on fibrinolysis was studied using a clot iysis system consisting of purified glu-plasminogen, tissue-type plasminogen activator, plasminogen activator inhibitor (released from endothelial cells or blood platelets), fibrinogen, 125T-fibrinogen and thrombin. All proteins were of human origin.In this system APC could increase fibrinolysis in a dose dependent way, without affecting fibrin formation or fibrin crosslinking. However, this profibrinolytic effect of APC could only be observed when plasminogen activator inhibitor (PAI-l) was present. The effect of APC was completely quenched by pretreatment of APC with anti-protein C IgG or di-isopropylfluorophosphate. Addition of the cofactors of APC:protein S, Ca2+-ions and phospholipid-alone or in combination did not enhance the profibrinolytic effect of APC. These observations indicate that human APC can accelerate in vitro clot lysis by the inactivation of PAI-1 activity. However, the neutralization of PAI-1 by APC is independent of the presence or absence of protein S, phospholipid and Ca2+-ions.

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