1/8. Abnormal propeptide processing resulting in the presence of two abnormal species of protein c in plasma: characterization of the dysfunctional protein c Padua3 (protein c(R-1L/propeptide)).A heterozygous G-->T transversion at position 1388 of the protein c (PC) gene which predicted the substitution of Arg(-1) to a Leu (PC(R-1L)) was identified in a thrombophilic patient. The PC(R-1L) was purified from the patient's plasma by immunoaffinity chromatography using Ca -independent and Ca -dependent monoclonal antibodies. NH2-terminal sequencing of the light chain of PC(R-1L) revealed two amino acid sequences: one was identical to the complete propeptide sequence of PC, while the other matched the normal PC light chain sequence elongated by one amino acid (leucine at position 1). Activated PC(R-1L/propeptide) exhibited normal amidolytic and impaired anticoagulant activity. Thus, the substitution of a Leu for an Arg at position -1 of PC shifts the propeptidase cleavage site by one amino acid. In addition, in PC(R-1L/propeptide) the propeptide cleavage at Lys(-2) is less efficient since approximately 60% of PC variant molecules present in patient's plasma retained the entire propeptide. Our findings suggest that depending on the specific amino acid substitution at position-1, PC can be secreted in plasma containing the entire propeptide attached to the light chain. Impaired interaction of elongated APC molecules with a membrane-surface and/or factor va which is the physiological substrate for APC, is manifested in vivo by thrombophilia.- - - - - - - - - - ranking = 1keywords = thrombophilia (Clic here for more details about this article) |
2/8. Recurrent thromboembolism in a patient with beta-thalassemia major associated with double heterozygosity for factor V R506Q and prothrombin G20210A mutations.Double heterozygosity for factor V R506Q and prothrombin G20210A mutations was identified in a 24-year-old man with beta-thalassemia major. The patient experienced a first thrombotic event at the age of 19 years and three recurrent thromboses in a short time interval, the third occurring while the patient was receiving long-term anticoagulant treatment. This case suggests that patients with major thalassemia and congenital thrombophilic mutations need intensive and long-lasting anticoagulant treatment. Thus, even if thrombotic events could be explained by a hypercoagulable state observed in patients with major thalassemia, after a first thrombotic event has occurred these patients should be screened for acquired and congenital thrombophilia.- - - - - - - - - - ranking = 1keywords = thrombophilia (Clic here for more details about this article) |
3/8. Mural thrombus of the aorta in association with homozygous plasminogen activator inhibitor type 1 (PAI-1)-675(4G) and heterozygous GP Ia 807C/T genotypes.Thrombus formation in the thoracic and abdominal aorta without evidence of arteriosclerotic disease is very uncommon. We present a case of a 50-year-old woman with a mural thrombus of the upper abdominal aorta associated with a combination of two mutations predisposing for thrombophilia. The genetic analysis showed a homozygous mutation of plasminogen activator inhibitor type 1 (PAI-1)-675 (4G) and a heterozygous mutation of GP Ia 807C/T. To our knowledge, this is the first report of the combination of both mutations occurring in a patient with isolated thrombus formation of the aorta.- - - - - - - - - - ranking = 1keywords = thrombophilia (Clic here for more details about this article) |
4/8. Acute coronary and peripheral arterial thrombosis following percutaneous coronary intervention in a patient with previously undiagnosed inherited thrombophilia.Following pretreatment with ticlopidine 250 mg bid for three days, a 40-year-old man underwent successful angioplasty and stenting of the proximal left anterior descending coronary artery and balloon dilation of the midcircumflex coronary artery without stenting. He subsequently developed acute coronary thromboses at both arterial sites and cardiogenic shock. The patient survived after an additional percutaneous coronary intervention (PCI) and intra-aortic balloon pump assistance. This was followed by peripheral arterial thrombosis requiring repeated therapeutic interventions. Laboratory tests for thrombophilia revealed the presence of a G20210A prothrombin gene mutation. Two years later the patient remained free of angina and claudication, and underwent an unremarkable maximum exercise treadmill test. This is the first reported case of acute, multiple coronary and peripheral arterial thrombosis following PCI in a patient with previously unsuspected inherited thrombophilia. Inherited thrombophilia should be considered as a possible cause of arterial thrombosis following PCI.- - - - - - - - - - ranking = 7keywords = thrombophilia (Clic here for more details about this article) |
5/8. Homozygous and double heterozygous Factor V Leiden and Factor II G20210A genotypes predispose infants to thromboembolism but are not associated with an increase of foetal loss.Prospective and controlled data about the individual risk profile in asymptomatic children with homozygous or double heterozygous risk genotypes for Factor V Leiden (FVL) and factor II (FII) G20210A are currently unavailable. The systematic and prospective observational study presented here was designed to determine the impact of the homozygous and double heterozygous FVL and FII G20210A genotypes on the prenatal and postnatal risk profiles of affected children. risk infants and heterozygous controls were identified by screening of 85,304 neonates. Follow-up included the comparison of prenatal and postnatal development, ultrasonography of brain and kidneys, and a panel of independent determinants of thrombophilia. The numbers of identified or expected FVL homozygotes and double heterozygotes did not differ significantly (FVL: 116 versus 91, p=0.08; FVL/FII: 94 versus 76, p=0.17), indicating the absence of a prenatal disadvantage. A prenatal advantage was suggested in FII homozygotes, whose identified number far exceeded the expected (19 versus 4, p=0.002). Clinical and/or imaging abnormalities indicated spontaneous thromboembolic events in 4 of 129 risk infants (3%) but in none of the 178 controls (p=0.02). Physical and neurological development was normal in both groups during the first 2 years of life. The risk genotypes appear to confer a significant predisposition for spontaneous thromboembolic events in infancy without impeding development within the first two years of life. Foetal risk genotypes do not cause an increased foetal loss rate. Moreover, homozygous FII G20210A appears to be associated with a prenatal advantage.- - - - - - - - - - ranking = 1keywords = thrombophilia (Clic here for more details about this article) |
6/8. A rare but life-threatening complication of ventriculo-atrial shunt.Insertion of ventriculoperitoneal and ventriculoatrial shunts is routinely performed. infarction pneumonia and atrial thrombus formation are described as very rare complications of ventriculoatrial shunts. We present the case of a female patient with ventriculoatrial shunt insertion as long term treatment for aequeductal stenosis who presented with recurrent episodes of dyspnoea, chest pain, and unilateral pleural effusion. Diagnostic evaluation revealed a positive D-dimer test, bilateral basal infiltrates and pleural effusion. Transesophageal echocardiography established the diagnosis of a thrombus in the right atrium. Laboratory testing for thrombophilia revealed a homozygous factor V Leiden mutation. In the following, a shunt revision was performed.- - - - - - - - - - ranking = 1keywords = thrombophilia (Clic here for more details about this article) |
7/8. A fatal case of enoxaparin induced skin necrosis and thrombophilia.skin necrosis caused by heparins is a rare complication. We report a case of a 71-yr-old white woman who developed painful diffuse skin lesions, most probably related to enoxaparin treatment. Other causes of skin necrosis, including heparin induced thrombocytopenia, disseminated intravascular coagulation, protein c/protein s deficiencies, anti-phospholipid antibodies, and vitamin k deficiency were less likely in this case. The concomitant combined thrombophilia possibly aggravated the patient's clinical presentation.- - - - - - - - - - ranking = 5keywords = thrombophilia (Clic here for more details about this article) |
8/8. High levels of histidine-rich glycoprotein and thrombotic diathesis. Report of two unrelated families.Two new families with history of thrombosis and high levels of histidine-rich glycoprotein (HRG) are described. The propositus of family 1 died of massive pulmonary embolism at age 34. Among his relatives, the mother and the maternal grandmother had suffered from deep and superficial vein thrombosis in their youth. A maternal aunt had several episodes of superficial vein thrombosis (SVT). High levels of HRG were found in the mother, three siblings and two nephews. In the second family, the proposita suffered from spontaneous deep vein thrombosis (DVT) at age 24. The paternal grandmother and a paternal aunt had several episodes of SVT and DVT. Also in this family, high levels of HRG cosegregated with thrombotic symptoms. These new families confirm that genetically transmitted high levels of HRG could be associated to familial and juvenile thrombophilia.- - - - - - - - - - ranking = 1keywords = thrombophilia (Clic here for more details about this article) |