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C0045 Protein c deficiency in a family with a history of childhood thrombosis
Abstracts / Thrombosis Research 130 (2012) S100–S202
showed significant differences with regard to C3435T and G2677A/T genotypes (p b 0.05). Comment: Ours findings suggest that C3435T and G2677A/T polymorphisms may be associated with plasma PAF and aggregation levels however similarities and differences are found when PAF levels and platelet aggregation parameters were evaluated according to MDR-1 genes 2 polimorphic regional genotypes (C3435T ve G2677A/T) in different groups. More patients are required to demonstrate the role of genotypes in this differentiation. doi:10.1016/j.thromres.2012.08.078
C0045 Protein c deficiency in a family with a history of childhood thrombosis Anicee Danaee, Jayanthi Alamelu, David Bevan Guys and St Thomas\' HospitalHaematology - Westminster Bridge Road, London SE1 7EH, UK Background: Protein C deficiency is inherited as an autosomal dominant trait. The prevalence of heterozygous protein C deficiency is 1 in 300. The frequency of symptomatic disease is 1 in 16,000. Thrombosis generally occurs in patients with additional risk factors. Methods: We report the case of a 7 year old girl, referred to our centre, with a family history of protein C deficiency. Both the girl's father and uncle, had a known c.631 C N T mutation in the protein C gene, and had both suffered from thrombosis as children. The Arg 169 (CGG–› TGG) mutation, also known as “Protein C London 1” was in fact first described in this young girl's father, who interestingly has a much more severe form of the mutation, than other heterozygotes reported, who tend to have peripheral VTEs. He suffered from an IVC thrombus at the age of 12 and his brother had a cerebral venous sinus thrombosis at the age of 11. Both have been on long term anticoagulation since the time of diagnosis. In view of family history of protein C deficiency and history of thrombosis in early childhood, this young girl was also tested and found to be heterozygous for the same mutation. Results: A family history of thrombophilia alone is not an indication for testing children. However, in this case a history of significant thrombosis in childhood would influence follow up and management. Our patient's grandmother was also tested and found to have the same mutation; she on the other hand only developed a DVT in her 50s while on HRT. Our patient is not currently on any anticoagulation, she has had imaging of her upper and lower limb venous system, with no evidence of structural venous abnormalities or malformations. The family history does raise concerns in terms of long term management of this young girl. From the pattern of thrombosis, it appears that the males in this family seem to have a much more aggressive phenotype. Neither the father nor the uncle of our patient had any additional risk factors identified on testing. Comment: This case highlights the difficulty associated with testing children for heritable thrombophilias and their subsequent management and follow up. In this case, there is clearly a very significant history of childhood thrombosis which justifies testing this young girl particularly as she is approaching puberty. She is currently being reviewed annually, with protein C levels and clinical assessments and very low threshold for intervention in the event of any thrombotic event. Testing has meant that her general practitioner and her local paediatric team can be aware of the potential for thrombosis and the signs and symptoms to look out for. The patient herself can be be adequately counselled and educated with respect high risk situations such as to long haul travel and the use of OCP when this becomes relevant. doi:10.1016/j.thromres.2012.08.079
S131
C0055 Patent foramen ovale: A pathway for myocardial infarction in pregnant patient' case report Ene Mäeots, Merle Kadarik East - Tallin Central Hospitalcardiology - Ravi 18, Tallinn, Estonia Background: Paradoxical embolism is defined as the embolic entrance of venous thrombosis into the systemic circulation through a right to left intracardiac shunt, like as presence of patent foramen ovale (PFO). Methods: 27-year-old pregnant woman without any cardiovascular risk factors, family history on cardiovascular diseases was hospitalized to coronary care unit with pain radiating to left hand and throat, nausea, syncope and weakness. An acute anterior myocardial infarction was diagnosed. The standard ECG showed severe ST segment elevation in II, III, aVF and deep horizontal ST segment depression in I, aVL, v1-v5. Results: Complete occlusion of the circumflex artery was identified during primary percutaneous transluminal coronary angioplasty (PTCA). The other coronary arteries were normal. The thrombus mass 4 mm of length was aspirated. No residual stenosis and TIMI grade 3 flow. 15 minutes after reperfusion an echocardiogram was performed, showing normal measures of atria and ventricles, hypokinesis of inferior and infero-septal basal segment of left ventricular myocard. Extraction fraction was 55%. There were no abnormal findings in antithrombin III, proteins C and S, prothrombin time, partial thromboplastin time, fibrinogen and homocysteine concentrations, cardiolipin antibodies, and genotype analysis for factor II and factor V Leiden. Post-PTCA doppler ultrasound of the lower extremities revealed no pathology. New echocardiogram conducted 48 hours after perfusion, showed an atrial septal aneurysm and clear evidence of a PFO with left to right shunt directed to tricuspidal valve, that had remained undiagnosed during the initial procedure due to suboptimal posture of the patient. The patient was discharged with enoxaparin 60 mg bid in treatment schedule. Planned caesarean section was conducted during the 38 week of pregnancy. Newborn baby (2860 grams, 47 cm) with Apgar score of 8–8 was healthy. Comment: In patients with presumed paradoxical embolism, careful attention should be paid to rule out a coexistence of PFO. In the presented case, association between PFO and atrial septal aneurysm, was identified during ultrasound examination in pregnant patient. This has been shown to increase fivefold the risk of systemic embolisation [Mas et al: NEJM 2001;345: 1740–6]. doi:10.1016/j.thromres.2012.08.080
C0026 Contemporary prophylaxis of postoperative venous thromboembolism and monitoring of efficacy: Accumulated experience Arshak Vardanyan1, Robert Mumladze1, Evgeniy Roitman2, David Dolidze3, Mengkai Shieh3 1 Russian Medical Academy of Postgraduate Education, Department of Surgery - ul. Barrikadnaya, d. 2/1, Moscow, 123995, Russia; 2Federal Research and Clinical Center on Children's Hematology, Oncology and Immunology, Hemostasis Laboratory, Russia; 3Russian Medical Academy of Postgraduate Education, Department of Surgery - ul. Barrikadnaya, d. 2/1, Moscow, 123995, Russia Background: Venous thromboembolism (VTE) is a major issue in Russian healthcare and healthcare spending, with a 30% incidence of Deep Vein Thrombosis (DVT) in general surgery patients. Our main
showed significant differences with regard to C3435T and G2677A/T genotypes (p b 0.05). Comment: Ours findings suggest that C3435T and G2677A/T polymorphisms may be associated with plasma PAF and aggregation levels however similarities and differences are found when PAF levels and platelet aggregation parameters were evaluated according to MDR-1 genes 2 polimorphic regional genotypes (C3435T ve G2677A/T) in different groups. More patients are required to demonstrate the role of genotypes in this differentiation. doi:10.1016/j.thromres.2012.08.078
C0045 Protein c deficiency in a family with a history of childhood thrombosis Anicee Danaee, Jayanthi Alamelu, David Bevan Guys and St Thomas\' HospitalHaematology - Westminster Bridge Road, London SE1 7EH, UK Background: Protein C deficiency is inherited as an autosomal dominant trait. The prevalence of heterozygous protein C deficiency is 1 in 300. The frequency of symptomatic disease is 1 in 16,000. Thrombosis generally occurs in patients with additional risk factors. Methods: We report the case of a 7 year old girl, referred to our centre, with a family history of protein C deficiency. Both the girl's father and uncle, had a known c.631 C N T mutation in the protein C gene, and had both suffered from thrombosis as children. The Arg 169 (CGG–› TGG) mutation, also known as “Protein C London 1” was in fact first described in this young girl's father, who interestingly has a much more severe form of the mutation, than other heterozygotes reported, who tend to have peripheral VTEs. He suffered from an IVC thrombus at the age of 12 and his brother had a cerebral venous sinus thrombosis at the age of 11. Both have been on long term anticoagulation since the time of diagnosis. In view of family history of protein C deficiency and history of thrombosis in early childhood, this young girl was also tested and found to be heterozygous for the same mutation. Results: A family history of thrombophilia alone is not an indication for testing children. However, in this case a history of significant thrombosis in childhood would influence follow up and management. Our patient's grandmother was also tested and found to have the same mutation; she on the other hand only developed a DVT in her 50s while on HRT. Our patient is not currently on any anticoagulation, she has had imaging of her upper and lower limb venous system, with no evidence of structural venous abnormalities or malformations. The family history does raise concerns in terms of long term management of this young girl. From the pattern of thrombosis, it appears that the males in this family seem to have a much more aggressive phenotype. Neither the father nor the uncle of our patient had any additional risk factors identified on testing. Comment: This case highlights the difficulty associated with testing children for heritable thrombophilias and their subsequent management and follow up. In this case, there is clearly a very significant history of childhood thrombosis which justifies testing this young girl particularly as she is approaching puberty. She is currently being reviewed annually, with protein C levels and clinical assessments and very low threshold for intervention in the event of any thrombotic event. Testing has meant that her general practitioner and her local paediatric team can be aware of the potential for thrombosis and the signs and symptoms to look out for. The patient herself can be be adequately counselled and educated with respect high risk situations such as to long haul travel and the use of OCP when this becomes relevant. doi:10.1016/j.thromres.2012.08.079
S131
C0055 Patent foramen ovale: A pathway for myocardial infarction in pregnant patient' case report Ene Mäeots, Merle Kadarik East - Tallin Central Hospitalcardiology - Ravi 18, Tallinn, Estonia Background: Paradoxical embolism is defined as the embolic entrance of venous thrombosis into the systemic circulation through a right to left intracardiac shunt, like as presence of patent foramen ovale (PFO). Methods: 27-year-old pregnant woman without any cardiovascular risk factors, family history on cardiovascular diseases was hospitalized to coronary care unit with pain radiating to left hand and throat, nausea, syncope and weakness. An acute anterior myocardial infarction was diagnosed. The standard ECG showed severe ST segment elevation in II, III, aVF and deep horizontal ST segment depression in I, aVL, v1-v5. Results: Complete occlusion of the circumflex artery was identified during primary percutaneous transluminal coronary angioplasty (PTCA). The other coronary arteries were normal. The thrombus mass 4 mm of length was aspirated. No residual stenosis and TIMI grade 3 flow. 15 minutes after reperfusion an echocardiogram was performed, showing normal measures of atria and ventricles, hypokinesis of inferior and infero-septal basal segment of left ventricular myocard. Extraction fraction was 55%. There were no abnormal findings in antithrombin III, proteins C and S, prothrombin time, partial thromboplastin time, fibrinogen and homocysteine concentrations, cardiolipin antibodies, and genotype analysis for factor II and factor V Leiden. Post-PTCA doppler ultrasound of the lower extremities revealed no pathology. New echocardiogram conducted 48 hours after perfusion, showed an atrial septal aneurysm and clear evidence of a PFO with left to right shunt directed to tricuspidal valve, that had remained undiagnosed during the initial procedure due to suboptimal posture of the patient. The patient was discharged with enoxaparin 60 mg bid in treatment schedule. Planned caesarean section was conducted during the 38 week of pregnancy. Newborn baby (2860 grams, 47 cm) with Apgar score of 8–8 was healthy. Comment: In patients with presumed paradoxical embolism, careful attention should be paid to rule out a coexistence of PFO. In the presented case, association between PFO and atrial septal aneurysm, was identified during ultrasound examination in pregnant patient. This has been shown to increase fivefold the risk of systemic embolisation [Mas et al: NEJM 2001;345: 1740–6]. doi:10.1016/j.thromres.2012.08.080
C0026 Contemporary prophylaxis of postoperative venous thromboembolism and monitoring of efficacy: Accumulated experience Arshak Vardanyan1, Robert Mumladze1, Evgeniy Roitman2, David Dolidze3, Mengkai Shieh3 1 Russian Medical Academy of Postgraduate Education, Department of Surgery - ul. Barrikadnaya, d. 2/1, Moscow, 123995, Russia; 2Federal Research and Clinical Center on Children's Hematology, Oncology and Immunology, Hemostasis Laboratory, Russia; 3Russian Medical Academy of Postgraduate Education, Department of Surgery - ul. Barrikadnaya, d. 2/1, Moscow, 123995, Russia Background: Venous thromboembolism (VTE) is a major issue in Russian healthcare and healthcare spending, with a 30% incidence of Deep Vein Thrombosis (DVT) in general surgery patients. Our main