1/101. Familial thrombophilia and the prothrombin 20210A mutation: association with increased thrombin generation and unusual thrombosis.The 20210A prothrombin mutation has recently been associated with an increased risk of venous thrombosis, but the mechanism of the increased thrombotic risk in affected persons has not been elucidated. We report on a thrombophilic family in which the proband presented with cerebral vein thrombosis and homozygosity for the 20210A prothrombin mutation as her only identifiable risk factor for venous thrombosis. Extended genotyping of family members revealed seven other affected, but asymptomatic, first-degree relatives (one A/A homozygote and six G/A heterozygotes). plasma levels of prothrombin, prothrombin fragments 1 2 and thrombin-antithrombin complexes were highest in A/A homozygotes, intermediate in G/A heterozygotes and lowest in those with the G/G homozygous normal genotype, while D-dimer levels were elevated only in A/A homozygotes. Our results suggest that the 20210A prothrombin mutation is associated with activation of coagulation and increased thrombin generation, not only in patients with a past history of thrombosis but also in otherwise healthy asymptomatic persons. In a similar fashion to the homozygous factor v Leiden mutation, patients with the homozygous 20210A prothrombin mutation could be at highest risk of thrombosis, as suggested by our patient who presented with unusual thrombosis.- - - - - - - - - - ranking = 1keywords = thrombophilia (Clic here for more details about this article) |
2/101. budd-chiari syndrome associated with factor v leiden mutation: a report of 6 patients.budd-chiari syndrome is characterized by hepatic venous outflow obstruction. Although myeloproliferative disorders are usually responsible for this severe thrombotic disorder, deficiency or dysfunction of the natural anticoagulants can be involved. Resistance to activated protein c caused by factor v Leiden mutation has been recently identified as a major cause of thrombophilia. We report 6 patients with budd-chiari syndrome associated with factor v Leiden mutation combined with another acquired thrombophilic state (myeloproliferative disorder and lupus anticoagulant in 3 cases) and without another thrombophilic disorder in the other 3 cases. We conclude that factor v Leiden mutation should be evaluated in any case of hepatic vein occlusion because the prevalence of this mutation in the general population is high.- - - - - - - - - - ranking = 0.25keywords = thrombophilia (Clic here for more details about this article) |
3/101. Resistance to activated protein c as an etiology for stroke in a young adult: a case report.Resistance to activated protein c (R-APC) is an inherited, autosomal dominant, coagulation abnormality that is increasingly recognized as an important etiology for thromboembolic disease and stroke in young adults. This report describes the case of a 27-year-old woman taking oral contraceptives who experienced an acute thrombotic right hemispheric stroke. Three days after rehabilitation admission (33 days after stroke) she developed a left femoral deep venous thrombosis (DVT) despite appropriate prophylaxis. Further diagnostic workup for the stroke and DVT identified R-APC, possibly exacerbated by oral contraceptives, as the etiology. hematology consultation recommended lifetime anticoagulation with warfarin. The patient's family history revealed that a 19-year-old cousin had died of a stroke several years earlier. Several months after discharge, an acute DVT occurred in the patient's 28-year-old brother, who tested positive for factor v Leiden, a genetic abnormality closely associated with R-APC. A thrombotic stroke occurred in her grandfather a few months later, but he was not tested. Her father demonstrated a "borderline" positive R-APC test and probably represents the genetic link. Indications for patient and family screening regarding R-APC and other forms of hereditary thrombophilia and implications for rehabilitation medicine physicians are discussed.- - - - - - - - - - ranking = 0.25keywords = thrombophilia (Clic here for more details about this article) |
4/101. Hematologic effects of thrombophilia.The hematologic effects of thrombophilia are subtle, and when recognized may provide clues for the diagnosis of hypercoagulation in patients. This article identifies aberrant, routine test results associated with the diagnosis of thrombophilia. The future expansion of laboratory testing for thrombophilia detection is presented in summation.- - - - - - - - - - ranking = 1.75keywords = thrombophilia (Clic here for more details about this article) |
5/101. budd-chiari syndrome in a patient with factor v Leiden--successful treatment by TIPSS placement followed by liver transplantation.The causes of budd-chiari syndrome (BCS) comprise several diseases leading to thrombophilia. One of the most common thrombophilic disorders is resistance against activated protein c, caused by a single point mutation of the factor v gene. In December 1993, a 22-year-old patient was given a diagnosis of subacute BCS with occlusion of all major hepatic veins. Placement of a transjugular intrahepatic portosystemic stent shunt led to rapid disappearance of ascites and hepatic encephalopathy. During the following two years, recurrent partial occlusions of the shunt were treated by balloon angioplasty. The cause of the BCS still being unknown, in October 1996 we performed extensive laboratory investigations concerning states of thrombophilia and found moderately elevated IgG anticardiolipin antibodies (19.7 U/ml) and a resistance against activated protein c caused by heterozygosity for a point mutation of the factor v gene (1691G-->A; factor v Leiden). As a consequence, oral anticoagulation with coumarin was initiated. In October 1997, elective liver transplantation was performed which led to disappearance of APC resistance. Moreover, IgG anticardiolipin antibodies have been negative since then. If BCS is caused by APC resistance, liver transplantation not only treats the chronic liver disease but also cures the state of thrombophilia since factor v is mainly synthesized in the liver.- - - - - - - - - - ranking = 0.75keywords = thrombophilia (Clic here for more details about this article) |
6/101. Homozygotes for prothrombin gene 20210 A allele in a thrombophilic family without clinical manifestations of venous thromboembolism.BACKGROUND AND OBJECTIVE: A new genetic risk factor for venous thromboembolism has recently been described which involves a G to A transition at position 20210 in the 3' untranslated region of the prothrombin gene. To date, only a few homozygotes for this mutation have been reported and in most of cases, they suffered from thrombotic disease. Here, we describe a pedigree including both heterozygous and homozygous subjects for prothrombin (PT) 20210 A. DESIGN AND methods: This family was recruited in 1996 as part of our gait (Genetic Analysis of Idiopathic thrombophilia) project. To qualify for the gait study, a pedigree was required to have at least 10 living individuals in three or more generations (i.e. extended pedigree). The pedigrees were selected through probands with idiopathic thrombophilia. A complete set of plasma and dna determinations related to hemostasis was performed on this family. RESULTS: The plasma studies yielded normal results in all of the individuals. The family members who had a history of thromboembolism were heterozygous carriers of the PT 20210 A variant. In addition, 4 relatives who were heterozygous, and two who were homozygous for this A allele, failed to show clinical manifestations. These two homozygotes were 51 and 19 years old. INTERPRETATION AND CONCLUSIONS: This case exemplifies the complexity of thrombotic disease since individuals homozygous for a mutant gene do not exhibit symptoms while heterozygous individuals often do exhibit the disease. This case suggests that the new genetic risk factor for thrombosis (i.e. PT 20210 A) may not be as strong as most of the previously described genetic risk factors.- - - - - - - - - - ranking = 0.25keywords = thrombophilia (Clic here for more details about this article) |
7/101. Combined malignant hemangiopericytoma and deep venous thrombosis. A case report.Malignancies, antiproliferative drug treatment, cancer-related conditions like immobilization, perioperative status and radiotherapy are risk factors for hypercoagulability. Setting aside mass or invasion-related venous thrombosis, the differential diagnosis regarding the etiopathogenesis (paraneoplastic syndrome or antiproliferative treatment) is usually problematic. The authors report a case of combined malignant hemangiopericytoma and recurrent deep venous thrombosis in the right inferior limb. Through a literature review, the following issues are discussed: 1) the criteria for cyto-histopathologic assessment; 2) the involvement of pericytes both in coagulation and platelet aggregation; 3) the importance of discriminating true paraneoplastic syndromes from other tumor-related clinical manifestations; 4) the response to external radiotherapy of malignant hemangiopericytoma as limited disease; 5) the poor results of doxorubicin-ifosfamide polychemotherapy and dacarbazine monochemotherapy in metastatic disease. Although doxorubicin-ifosfamide treatment was in progress in the reported case, the authors conclude that the recurrent deep venous thrombosis is likely to be paraneoplastic, even if such a diagnosis has not been previously reported in the literature.- - - - - - - - - - ranking = 0.017258400335413keywords = hypercoagulability (Clic here for more details about this article) |
8/101. Hypercoagulability in a patient with hypodysfibrinogenemia: implications for clinical management.Dysfibrinogenemia accounts for approximately 0.7% of thrombophilia in patients with venous thromboembolic disease. In 20% of these patients, plasma thrombophilic dysfibrinogen is below 1.0 mg/ml, defining hypodysfibrinogenemia. We describe a young female patient, in whom hypodysfibrinogenemia was the cause of several severe thromboembolic events which occurred even under oral anticoagulation monitored by a standard prothrombin time (PT) test. In this patient, the standard PT test according to Quick underestimated the plasma coagulability in vivo, presumably due to the low levels of dysfunctional fibrinogen as the substrate of the thromboplastin reagent. A PT test supplemented with bovine plasma fibrinogen (Thrombotest) revealed lower fibrinogen-independent international normalized ratio (INR) values in the proposita on oral anticoagulation compared to a control group with eufibrinogenemia. Monitoring therapy with the fibrinogen-independent Thrombotest secured safe anticoagulation in this patient. We suggest to consider PT tests with exogenous fibrinogen (e.g. Thrombotest) to monitor oral anticoagulation in the rare thrombophilic patients with hypodysfibrinogenemia.- - - - - - - - - - ranking = 0.25keywords = thrombophilia (Clic here for more details about this article) |
9/101. Heterozygous prothrombin gene mutation: a new risk factor for early renal allograft thrombosis.BACKGROUND: Underlying thrombophilic disorders increase the risk of early allograft loss after renal transplantation. We report three cases of early graft thrombosis in two carriers of a recently discovered prothrombotic variation of the prothrombin gene. case reports: The first patient, an adolescent girl, developed multiple thrombotic shunt occlusions after the initiation of hemodialysis until continuous cumarin anticoagulation was instituted. During living-related kidney transplantation, peracute thrombosis of the renal arteries and veins occurred during surgery despite excellent intraoperative conditions and continuous low-dose heparinization. A few hours after reperfusion of the organ by immediate thrombectomy and intrarenal fibrinolysis, an irreversible rethrombosis occurred. A detailed evaluation of the coagulation system showed highly elevated prothrombin protein activity and concentrations. A heterozygous G-->A transition at position 20210 of the prothrombin gene was identified. Hemodialysis was resumed using recombinant hirudin, a direct and selective thrombin inhibitor, as an anticoagulant. The second patient, a girl with end-stage renal failure due to atypical hemolytic uremic syndrome, lost two cadaver kidney allografts, each time by massive thrombosis a few days after transplantation. In this patient also, elevated prothrombin activity and concentrations were present and a heterozygous G-->A transition at position 2210 of the prothrombin gene was detected. CONCLUSIONS: The prothrombin gene mutation is a new risk factor for thrombotic complications both on hemodialysis and after renal transplantation. It may be useful to screen for this disorder in the pretransplant thrombophilia work-up.- - - - - - - - - - ranking = 0.25keywords = thrombophilia (Clic here for more details about this article) |
10/101. Recurrent optic nerve head infarctions associated with combined factor v Leiden- and factor II:G20210A-mutation.PURPOSE: To demonstrate the association of bilateral recurrent optic nerve head infarctions with thrombophilia due to combined factor v:R506Q- and factor II:G20210A-mutation. methods: Case report. We examined a 55-year-old man with a two-year history of three segmental optic nerve head infarctions. visual acuity was 20/80 on the left and 20/25 on the right eye. RESULTS: Ophthalmologic, cardiologic, radiologic, neurologic and hematologic-immunologic examinations were unremarkable except for increased APC-resistance (APC ratio: 1.4; normal value >2) due to heterozygous factor v:R506Q-mutation and high factor II-levels due to factor II:G20210A-mutation. Therapy with coumarin was instituted at INR 2.0-3.0 and no relapse has occurred over the past 1-year period. CONCLUSION: Combined occurrence of thrombogenic factor II:G20210A-mutation and factor v:R506Q-mutation may be causally linked to recurrent optic nerve head infarctions.- - - - - - - - - - ranking = 0.25keywords = thrombophilia (Clic here for more details about this article) |
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