ABSTRACT As published in a recent issue of Blood Coagulation and Fibrinolysis, the hybrid peptide... more ABSTRACT As published in a recent issue of Blood Coagulation and Fibrinolysis, the hybrid peptide RGDFAP, composed of RGDF (Arg-Gly-Asp-Phe) coupled to a synthetic peptide residue of the carboxy terminal part of antiplasmin (AP26) inhibited platelet activation and augmented plasmin generation and in vitro fibrin clot lysis. This peptide contains an RGD motif which provides linkage to platelet GP IIb-IIIa. The antiplasmin part of the molecule may attach free plasminogen, which in turn increases the amount of platelet surface bound plasminogen, probably yielding enhanced lytic action at the site of thrombus formation. This hypothesis was investigated and confirmed by the results of platelet-plasminogen binding assays, using FITC-labelled antiplasmin antibodies and radioligand binding analysis. Increased platelet-linked plasminogen was detected by a chromogenic method, along with the acceleration of in vitro lysis of platelet-rich clots in the presence of RGDFAP peptide.
Thrombotic events, increased tendency toward intravascular thrombosis and decreased fibrinolysis ... more Thrombotic events, increased tendency toward intravascular thrombosis and decreased fibrinolysis seem to be possible pathologic causes for aseptic necrosis of the femoral head (ANFH) in adults. This project was to study whether either increased platelet activation or decreased fibrinolytic activity and/or any other thrombogenic factor may be implicated in the evolvement of ANFH. The speed of the in vitro lysis was significantly lower in patients (both in primary and in secondary cases) compared with healthy controls. The platelet activation (measuring with beta TG) proved to be significantly higher in the primary group as well as in the secondary group compared with healthy controls. Lp(a) levels were elevated in primary and secondary cases. This alteration was more characteristic in the primary cases. Fibrinogen levels were also elevated in the primary group, but the difference was not significant. The data shown here may further support that hypofibrinolysis and increased thrombogenesis are major causes of ANFH. Early diagnosis of ANFH increases the chances of modifying the course of this disabling disease.
The presence of a Wolf-Parkinson-White (WPW) pattern is not uncommonly discovered on a life insur... more The presence of a Wolf-Parkinson-White (WPW) pattern is not uncommonly discovered on a life insurance applicant’s ECG. How does one determine the appropriate mortality risk in this population? This article will discuss the risk of sudden cardiac death (SCD), the interpretation of electrophysiology testing results, and risk-stratification both for asymptomatic individuals and those who have had ablation treatment.
Antiphospholipid syndrome is an autoimmune disorder, defined as the association of antiphospholip... more Antiphospholipid syndrome is an autoimmune disorder, defined as the association of antiphospholipid antibodies with manifestations of venous or arterial thrombosis or pregnancy loss. Primary antiphospholipid syndrome means that the patients have the same clinical symptoms and laboratory findings but they are not suffering from systemic lupus erythematosus or a closely related autoimmune diseases. Secondary antiphospholipid syndrome occurs in association with autoimmune or other diseases. 31 pregnancies of 10 women are detailed. 22 pregnancies were without thromboembolic prophylaxis and only 2 pregnancies were successful (9.1%). Out of the 9 pregnancies with high dose low-molecular-weight heparin and low dose aspirin thromboprophylaxis throughout pregnancy 8 were successful (88.8%). All the newborns were healthy. In spite of the long-term low-molecular-weight heparin therapy side effects (osteoporosis or heparin-induced thrombocytopenia) were not observed. Considering these results h...
Results obtained by a simple in vitro clot lysis test in polycythemia vera, polyglobulia, essenti... more Results obtained by a simple in vitro clot lysis test in polycythemia vera, polyglobulia, essential thrombocythemia and chronic immun thrombocytopenic purpura are reported. Increased lysis resistance of the platelet-rich clots was demonstrated in polycythemia and essential thrombocythemia, ostensibly caused by the high plasma level of plasminogen activator inhibitor-1. Following retraction of platelet-rich clots no further increase of lysis-resistance occurred in polycythemia and essential thrombocythemia. This phenomenon is most likely due to abnormal platelet function. The well known thromboembolic complications may at least partly result from the impaired fibrinolysis in diseases with high platelet counts.
After a concise review of the fibrinolysis modifying effect of platelets, a simple, reliable and ... more After a concise review of the fibrinolysis modifying effect of platelets, a simple, reliable and reproducible in vitro microplate clot-lysis method is described which is able to demonstrate the lytic resistance of platelet rich clots. The same method proved to be suitable to show the enhanced lysis in platelet rich lytic environment, caused probably by plasminogen attached to platelet surface. The results discussed here suggest that these effects need the presence of intact platelets.
A 52-year-old obese woman with a history of long-standing smoking, hypothyroidism, requiring thyr... more A 52-year-old obese woman with a history of long-standing smoking, hypothyroidism, requiring thyroid replacement therapy, and chronic pain, treated by methadone and hydromorphine, was found at home with a decreased level of consciousness. Nausea, vomiting, and diarrhea were present for the preceding 48 hours. Witnesses described intermittent loss of consciousness associated with clenched teeth, shaking legs, and incontinence of urine. In the ambulance, the patient became completely unresponsive and the rhythm monitor concurrently showed polymorphic ventricular tachycardia requiring DC shock of 200 J. Initial investigations revealed a serum K+ of 2.8 mmol/L with mild renal dysfunction (creatinine 129 μmol/L). Echocardiography showed a nondilated heart with diffuse hypokinesia of the left ventricle and ejection fraction calculated at 34%. A subsequent coronary angiogram showed no abnormalities. Previous medications were discontinued. Her ECG presented diffuse T-wave inversion and a long QT interval (QT 640 ms, QTc 580 ms). One week after her admission, a short asymptomatic tachycardia was observed (Fig. 1). What is the diagnosis of the tachycardia seen in Figure 1?
SummaryThe PFA-100 instrument (Platelet Function Analyzer, Dade Behring) has been reported to be ... more SummaryThe PFA-100 instrument (Platelet Function Analyzer, Dade Behring) has been reported to be superior to the bleeding time (BT) as a screening test of primary hemostasis. However evaluation of this device has been principally limited to selected populations.The study’s aim was to determine testing performance in clinical practice, by comparing the PFA-100 to the BT for the identification of von Willebrand disease (VWD) and intrinsic platelet hypofunction.From 1998-2000, PFA-100 closure time (CT) for epinephrine-collagen (EPI) and ADP-collagen (ADP) cartridges and modified Ivy BTs were performed on outpatients referred for testing for suspected or known hemorrhagic diathesis (n=346). Evaluation included assays of von Willebrand factor and platelet aggregometry in addition to platelet flow cytometry and electron microscopy when indicated. The normal distribution of PFA-100 CTs was determined using blood samples from 61 normal donors studied on 155 occasions.Results show that thirt...
A 50-year-old man with symptomatic paroxysmal atrial fibrillation and atrial flutter for 7 years ... more A 50-year-old man with symptomatic paroxysmal atrial fibrillation and atrial flutter for 7 years underwent cavotricuspid isthmus (CTI) ablation. He had a structurally normal heart and baseline right bundle branch block (RBBB). Because typical atrial flutter was the dominant rhythm, he underwent CTI ablation. Electrophysiology study and ablation was performed under general anesthesia. The patient was in atrial fibrillation on arrival and external DC cardioversion was performed. During sinus rhythm, RBBB morphology was seen with a PR interval of 180 ms and QRS width of 140 ms. A duodecapolar halo catheter, right ventricular catheter, and decapolar coronary sinus catheter were used for recording and pacing. The CTI ablation was performed in the 30◦ LAO projection during coronary sinus pacing at cycle length 600 ms with a deflectable irrigated tip, 6 French (Fr) ablation catheter (Biosense Webster, F curve). A Daig SRO, 8 Fr sheath (St. Jude Medical, Sylmar, CA, USA) was added to improve catheter stability. Ablation began near the tricuspid annulus with a large ventricular and small atrial electrogram at “6:00” on the tricuspid annulus (Fig. 1). During the first RF application, 2:1 AV block occurred during sinus rhythm. Upon discontinuation of RF current, 1:1 AV conduction was resumed. The ablation catheter was moved slightly laterally to 6:30. During the second ablation, marked and progressive PR prolongation (from 120 ms to the maximum PR of 230 ms) with subsequent 2:1 block occurred (Fig. 2). This normalized within seven beats after energy application was discontinued. Atropine 1 mg was given intravenously. Further applications were performed at the same site. Bidirectional block was achieved with further ablation with no adverse effect on AV node conduction. What are the mechanisms of AV node block during CTI ablation?
... One Slow Pathway or Two? UWAIS MOHAMED MBBS, FRACP,; LORNE J. GULA MD, MS, FRCPC,; ALLAN C. S... more ... One Slow Pathway or Two? UWAIS MOHAMED MBBS, FRACP,; LORNE J. GULA MD, MS, FRCPC,; ALLAN C. SKANES MD, FRCPC,; PETER LEONG-SIT MD, FRCPC,; ANDREW D. KRAHN MD, FRCPC, FACC,; RAYMOND YEE ...
A 55-year-old man with a long history of palpitations and documented wide complex tachycardia was... more A 55-year-old man with a long history of palpitations and documented wide complex tachycardia was referred to our center for further assessment. There was no history of heart disease and ejection fraction was normal. The patient underwent an electrophysiology study using four catheters and standard methods. Baseline intervals were: AH, 55 msec; HV, 55 msec; and QRS duration, 100 msec. Clinical tachycardia was induced with progressively premature atrial extrastimuli associated with sudden AH prolongation >50 msec. Twelvelead ECG during tachycardia showed alternating complete and incomplete right bundle brunch block (RBBB) with a cycle length of 397 msec, and HV interval of 55 msec. A series of progressively premature ventricular extrastimuli (PVCs) was introduced during tachycardia (Fig. 1). With regard to Figure 1, what is the differential diagnosis of the initial rhythm?
Background: The maximum voltage‐guided (MVG) approach to ablation for atrial flutter targets high... more Background: The maximum voltage‐guided (MVG) approach to ablation for atrial flutter targets high‐amplitude signals along the cavotricuspid isthmus (CTI). It is based on the observation that the isthmus is often composed of bundles of conducting tissue and the hypothesis that these bundles manifest as high‐amplitude electrograms, providing targets for selective ablation. We aim to identify patient and procedural factors that correlate with rapid isthmus ablation. Methods: All patients undergoing CTI ablation at our center from January 2005 to May 2006 were included. Patients were divided into outcome groups relative to the median value for total ablation time. The two groups were compared according to patient and procedural variables, using multivariate regression methods. Results: Seventy‐six patients were assessed with mean age 60.2 ± 10.6 years; 63 (82.9%) were male. Mean ablation time to bidirectional block across the CTI was 6.85 ± 5.87 min (range 0.68–28.7); median 4.77 min. S...
Background: AV node slow pathway conduction can persist following successful ablation for AV node... more Background: AV node slow pathway conduction can persist following successful ablation for AV node reentrant tachycardia (AVNRT). We hypothesized that careful examination of AV nodal conduction curves before and after effective AVNRT ablation in patients with persistent slow pathway conduction could shed light on this apparent paradox. Methods and Results: Thirty patients (age 40.9 ± 14.3; 8 male) were included. AV node function curves were created based on pre‐ and postablation atrial extrastimulus testing. Analysis of slow pathway function curves demonstrated significant decrease in AH for any given coupling interval after ablation (mean difference –68.1 [–94.5, –41.7] P < 0.001), graphically indicated by downward displacement of the curve. In addition, mean slow pathway effective refractory period (ERP) increased from 247.9 ± 36.1 msec to 288.6 ± 56.0 msec (P < 0.001); mean maximum AH interval decreased from 361.3 ± 114.2 msec to 306.9 ± 65.2 msec (P = 0.013); mean differenc...
ABSTRACT As published in a recent issue of Blood Coagulation and Fibrinolysis, the hybrid peptide... more ABSTRACT As published in a recent issue of Blood Coagulation and Fibrinolysis, the hybrid peptide RGDFAP, composed of RGDF (Arg-Gly-Asp-Phe) coupled to a synthetic peptide residue of the carboxy terminal part of antiplasmin (AP26) inhibited platelet activation and augmented plasmin generation and in vitro fibrin clot lysis. This peptide contains an RGD motif which provides linkage to platelet GP IIb-IIIa. The antiplasmin part of the molecule may attach free plasminogen, which in turn increases the amount of platelet surface bound plasminogen, probably yielding enhanced lytic action at the site of thrombus formation. This hypothesis was investigated and confirmed by the results of platelet-plasminogen binding assays, using FITC-labelled antiplasmin antibodies and radioligand binding analysis. Increased platelet-linked plasminogen was detected by a chromogenic method, along with the acceleration of in vitro lysis of platelet-rich clots in the presence of RGDFAP peptide.
Thrombotic events, increased tendency toward intravascular thrombosis and decreased fibrinolysis ... more Thrombotic events, increased tendency toward intravascular thrombosis and decreased fibrinolysis seem to be possible pathologic causes for aseptic necrosis of the femoral head (ANFH) in adults. This project was to study whether either increased platelet activation or decreased fibrinolytic activity and/or any other thrombogenic factor may be implicated in the evolvement of ANFH. The speed of the in vitro lysis was significantly lower in patients (both in primary and in secondary cases) compared with healthy controls. The platelet activation (measuring with beta TG) proved to be significantly higher in the primary group as well as in the secondary group compared with healthy controls. Lp(a) levels were elevated in primary and secondary cases. This alteration was more characteristic in the primary cases. Fibrinogen levels were also elevated in the primary group, but the difference was not significant. The data shown here may further support that hypofibrinolysis and increased thrombogenesis are major causes of ANFH. Early diagnosis of ANFH increases the chances of modifying the course of this disabling disease.
The presence of a Wolf-Parkinson-White (WPW) pattern is not uncommonly discovered on a life insur... more The presence of a Wolf-Parkinson-White (WPW) pattern is not uncommonly discovered on a life insurance applicant’s ECG. How does one determine the appropriate mortality risk in this population? This article will discuss the risk of sudden cardiac death (SCD), the interpretation of electrophysiology testing results, and risk-stratification both for asymptomatic individuals and those who have had ablation treatment.
Antiphospholipid syndrome is an autoimmune disorder, defined as the association of antiphospholip... more Antiphospholipid syndrome is an autoimmune disorder, defined as the association of antiphospholipid antibodies with manifestations of venous or arterial thrombosis or pregnancy loss. Primary antiphospholipid syndrome means that the patients have the same clinical symptoms and laboratory findings but they are not suffering from systemic lupus erythematosus or a closely related autoimmune diseases. Secondary antiphospholipid syndrome occurs in association with autoimmune or other diseases. 31 pregnancies of 10 women are detailed. 22 pregnancies were without thromboembolic prophylaxis and only 2 pregnancies were successful (9.1%). Out of the 9 pregnancies with high dose low-molecular-weight heparin and low dose aspirin thromboprophylaxis throughout pregnancy 8 were successful (88.8%). All the newborns were healthy. In spite of the long-term low-molecular-weight heparin therapy side effects (osteoporosis or heparin-induced thrombocytopenia) were not observed. Considering these results h...
Results obtained by a simple in vitro clot lysis test in polycythemia vera, polyglobulia, essenti... more Results obtained by a simple in vitro clot lysis test in polycythemia vera, polyglobulia, essential thrombocythemia and chronic immun thrombocytopenic purpura are reported. Increased lysis resistance of the platelet-rich clots was demonstrated in polycythemia and essential thrombocythemia, ostensibly caused by the high plasma level of plasminogen activator inhibitor-1. Following retraction of platelet-rich clots no further increase of lysis-resistance occurred in polycythemia and essential thrombocythemia. This phenomenon is most likely due to abnormal platelet function. The well known thromboembolic complications may at least partly result from the impaired fibrinolysis in diseases with high platelet counts.
After a concise review of the fibrinolysis modifying effect of platelets, a simple, reliable and ... more After a concise review of the fibrinolysis modifying effect of platelets, a simple, reliable and reproducible in vitro microplate clot-lysis method is described which is able to demonstrate the lytic resistance of platelet rich clots. The same method proved to be suitable to show the enhanced lysis in platelet rich lytic environment, caused probably by plasminogen attached to platelet surface. The results discussed here suggest that these effects need the presence of intact platelets.
A 52-year-old obese woman with a history of long-standing smoking, hypothyroidism, requiring thyr... more A 52-year-old obese woman with a history of long-standing smoking, hypothyroidism, requiring thyroid replacement therapy, and chronic pain, treated by methadone and hydromorphine, was found at home with a decreased level of consciousness. Nausea, vomiting, and diarrhea were present for the preceding 48 hours. Witnesses described intermittent loss of consciousness associated with clenched teeth, shaking legs, and incontinence of urine. In the ambulance, the patient became completely unresponsive and the rhythm monitor concurrently showed polymorphic ventricular tachycardia requiring DC shock of 200 J. Initial investigations revealed a serum K+ of 2.8 mmol/L with mild renal dysfunction (creatinine 129 μmol/L). Echocardiography showed a nondilated heart with diffuse hypokinesia of the left ventricle and ejection fraction calculated at 34%. A subsequent coronary angiogram showed no abnormalities. Previous medications were discontinued. Her ECG presented diffuse T-wave inversion and a long QT interval (QT 640 ms, QTc 580 ms). One week after her admission, a short asymptomatic tachycardia was observed (Fig. 1). What is the diagnosis of the tachycardia seen in Figure 1?
SummaryThe PFA-100 instrument (Platelet Function Analyzer, Dade Behring) has been reported to be ... more SummaryThe PFA-100 instrument (Platelet Function Analyzer, Dade Behring) has been reported to be superior to the bleeding time (BT) as a screening test of primary hemostasis. However evaluation of this device has been principally limited to selected populations.The study’s aim was to determine testing performance in clinical practice, by comparing the PFA-100 to the BT for the identification of von Willebrand disease (VWD) and intrinsic platelet hypofunction.From 1998-2000, PFA-100 closure time (CT) for epinephrine-collagen (EPI) and ADP-collagen (ADP) cartridges and modified Ivy BTs were performed on outpatients referred for testing for suspected or known hemorrhagic diathesis (n=346). Evaluation included assays of von Willebrand factor and platelet aggregometry in addition to platelet flow cytometry and electron microscopy when indicated. The normal distribution of PFA-100 CTs was determined using blood samples from 61 normal donors studied on 155 occasions.Results show that thirt...
A 50-year-old man with symptomatic paroxysmal atrial fibrillation and atrial flutter for 7 years ... more A 50-year-old man with symptomatic paroxysmal atrial fibrillation and atrial flutter for 7 years underwent cavotricuspid isthmus (CTI) ablation. He had a structurally normal heart and baseline right bundle branch block (RBBB). Because typical atrial flutter was the dominant rhythm, he underwent CTI ablation. Electrophysiology study and ablation was performed under general anesthesia. The patient was in atrial fibrillation on arrival and external DC cardioversion was performed. During sinus rhythm, RBBB morphology was seen with a PR interval of 180 ms and QRS width of 140 ms. A duodecapolar halo catheter, right ventricular catheter, and decapolar coronary sinus catheter were used for recording and pacing. The CTI ablation was performed in the 30◦ LAO projection during coronary sinus pacing at cycle length 600 ms with a deflectable irrigated tip, 6 French (Fr) ablation catheter (Biosense Webster, F curve). A Daig SRO, 8 Fr sheath (St. Jude Medical, Sylmar, CA, USA) was added to improve catheter stability. Ablation began near the tricuspid annulus with a large ventricular and small atrial electrogram at “6:00” on the tricuspid annulus (Fig. 1). During the first RF application, 2:1 AV block occurred during sinus rhythm. Upon discontinuation of RF current, 1:1 AV conduction was resumed. The ablation catheter was moved slightly laterally to 6:30. During the second ablation, marked and progressive PR prolongation (from 120 ms to the maximum PR of 230 ms) with subsequent 2:1 block occurred (Fig. 2). This normalized within seven beats after energy application was discontinued. Atropine 1 mg was given intravenously. Further applications were performed at the same site. Bidirectional block was achieved with further ablation with no adverse effect on AV node conduction. What are the mechanisms of AV node block during CTI ablation?
... One Slow Pathway or Two? UWAIS MOHAMED MBBS, FRACP,; LORNE J. GULA MD, MS, FRCPC,; ALLAN C. S... more ... One Slow Pathway or Two? UWAIS MOHAMED MBBS, FRACP,; LORNE J. GULA MD, MS, FRCPC,; ALLAN C. SKANES MD, FRCPC,; PETER LEONG-SIT MD, FRCPC,; ANDREW D. KRAHN MD, FRCPC, FACC,; RAYMOND YEE ...
A 55-year-old man with a long history of palpitations and documented wide complex tachycardia was... more A 55-year-old man with a long history of palpitations and documented wide complex tachycardia was referred to our center for further assessment. There was no history of heart disease and ejection fraction was normal. The patient underwent an electrophysiology study using four catheters and standard methods. Baseline intervals were: AH, 55 msec; HV, 55 msec; and QRS duration, 100 msec. Clinical tachycardia was induced with progressively premature atrial extrastimuli associated with sudden AH prolongation >50 msec. Twelvelead ECG during tachycardia showed alternating complete and incomplete right bundle brunch block (RBBB) with a cycle length of 397 msec, and HV interval of 55 msec. A series of progressively premature ventricular extrastimuli (PVCs) was introduced during tachycardia (Fig. 1). With regard to Figure 1, what is the differential diagnosis of the initial rhythm?
Background: The maximum voltage‐guided (MVG) approach to ablation for atrial flutter targets high... more Background: The maximum voltage‐guided (MVG) approach to ablation for atrial flutter targets high‐amplitude signals along the cavotricuspid isthmus (CTI). It is based on the observation that the isthmus is often composed of bundles of conducting tissue and the hypothesis that these bundles manifest as high‐amplitude electrograms, providing targets for selective ablation. We aim to identify patient and procedural factors that correlate with rapid isthmus ablation. Methods: All patients undergoing CTI ablation at our center from January 2005 to May 2006 were included. Patients were divided into outcome groups relative to the median value for total ablation time. The two groups were compared according to patient and procedural variables, using multivariate regression methods. Results: Seventy‐six patients were assessed with mean age 60.2 ± 10.6 years; 63 (82.9%) were male. Mean ablation time to bidirectional block across the CTI was 6.85 ± 5.87 min (range 0.68–28.7); median 4.77 min. S...
Background: AV node slow pathway conduction can persist following successful ablation for AV node... more Background: AV node slow pathway conduction can persist following successful ablation for AV node reentrant tachycardia (AVNRT). We hypothesized that careful examination of AV nodal conduction curves before and after effective AVNRT ablation in patients with persistent slow pathway conduction could shed light on this apparent paradox. Methods and Results: Thirty patients (age 40.9 ± 14.3; 8 male) were included. AV node function curves were created based on pre‐ and postablation atrial extrastimulus testing. Analysis of slow pathway function curves demonstrated significant decrease in AH for any given coupling interval after ablation (mean difference –68.1 [–94.5, –41.7] P < 0.001), graphically indicated by downward displacement of the curve. In addition, mean slow pathway effective refractory period (ERP) increased from 247.9 ± 36.1 msec to 288.6 ± 56.0 msec (P < 0.001); mean maximum AH interval decreased from 361.3 ± 114.2 msec to 306.9 ± 65.2 msec (P = 0.013); mean differenc...
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