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T L Ortel

Publications and source records attributed to T L Ortel.

At least 37 records · Page 2Linked to original sources
PubMed1999

Familial antiphospholipid antibody syndrome: criteria for disease and evidence for autosomal dominant inheritance.

OBJECTIVE: To develop diagnostic criteria for a familial form of antiphospholipid antibody syndrome (APS), identify families with >1 affected member, examine possible modes of inheritance, and determine linkage to potential candidate genes. METHODS: Family members of probands with primary APS were analyzed for clinical and laboratory abnormalities associated with APS. Families with > or =2 affected members were analyzed by segregation analysis and typed for candidate genetic markers. RESULTS: Seven families were identified. Thirty of 101 family members met diagnostic criteria for APS. Segregation studies rejected both environmental and autosomal recessive models, and the data were best fit by either a dominant or codominant model. Linkage analysis showed independent segregation of APS and several candidate genes. CONCLUSION: Clinical and laboratory criteria are essential to identify the spectrum of disease associated with APS. We believe a set of criteria was developed that can precisely define affected family members with APS. Modeling studies utilizing these criteria strongly support a genetic basis for disease in families with APS and suggest that a susceptibility gene is inherited in an autosomal dominant pattern. However, in these families, APS was not linked with HLA, Fas, or other candidate genes, including beta2-glycoprotein 1, HLA, T cell receptor beta chain, Ig heavy chain, antithrombin III, Fas ligand, factor V, complement factor H, IgK, and Fas.

Adolescent↗
PubMed1999

Clinical and laboratory manifestations of anti-factor V antibodies.

Factor V is a large, multi-domain glycoprotein that exhibits both procoagulant and anticoagulant activity. Anti-factor V antibodies may develop by several mechanisms and, depending on their epitope specificity, may produce hemorrhagic or thromboembolic complications. The clinical laboratory is an essential component in diagnosing these antibodies, and therapeutic management depends on the predominant clinical manifestations.

Animals↗
PubMed1999

Two instruments to determine activated partial thromboplastin time: implications for heparin monitoring.

STUDY OBJECTIVE: To measure the difference in therapeutic ranges of activated partial thromboplastin time (APTT) between two laboratory devices. DESIGN: Prospective, controlled laboratory study. SETTING: University-affiliated hospital. PATIENTS: Thirty inpatients receiving intravenous unfractionated heparin for treatment of myocardial infarction, unstable angina, deep venous thrombosis, or pulmonary embolism. INTERVENTIONS: Therapeutic APTT ranges were determined by a portable (whole blood assay) and a central laboratory device (plasma assay) based on heparin serum concentrations. They were compared with APTT ranges equivalent to 1.5-2.5 times the mean normal determination. MEASUREMENTS AND MAIN RESULTS: The central laboratory and portable devices produced therapeutic ranges of 61-93 and 56-73 seconds, respectively. Both differed from conventional therapeutic ratios of 1.5-2.5 times the mean normal (41-68 sec). Mean absolute APTT differences between instruments were statistically significant (12 +/- 20 sec, p<0.006), and 58% of paired APTT values differed by more than 10 seconds. CONCLUSION: A fixed APTT ratio as a goal for monitoring unfractionated heparin may result in significant underanticoagulation. Individual therapeutic APTT ranges must be reported for each instrument if more than one is used for heparin monitoring.

Adult↗
PubMed1998

Inhibitory anti-factor V antibodies bind to the factor V C2 domain and are associated with hemorrhagic manifestations.

Factor V inhibitors may develop as spontaneous autoantibodies, as alloantibodies after exposure to bovine thrombin preparations, or in factor V-deficient patients after plasma therapy. Clinical manifestations range from asymptomatic laboratory abnormalities to life-threatening hemorrhage. We have characterized the anti-factor V antibodies from 12 patients diagnosed with factor V inhibitors. In 8 patients, hemorrhagic complications (5 autoantibodies and 3 bovine thrombin-induced alloantibodies) developed, and 4 were asymptomatic (2 autoantibodies and 2 alloantibodies). The IgG fractions from all 12 patients immunoprecipitated the factor Va light chain, but only the 8 IgG fractions associated with hemorrhage inhibited factor V activity in a prothrombinase assay. Nine IgG fractions, including the 8 patients with hemorrhage, immunoprecipitated the isolated second C-type domain (C2). The 8 IgG fractions from the symptomatic patients also immunoprecipitated recombinant chimeras containing only the N-terminal third of the factor V C2 domain, and isolated recombinant C2 domain abrogated the inhibitory effect of the antibodies. Five of the inhibitory IgG fractions blocked binding of factor V to phosphatidylserine. These results suggest that inhibitory anti-factor V antibodies are associated with hemorrhagic manifestations and frequently bind to a common region within the C2 domain, whether originating spontaneously or after exposure to bovine thrombin.

Adolescent↗
PubMed1998

Recurrent thrombosis of the superior vena cava associated with activated protein C resistance: imaging findings.

The purpose of this report is to describe imaging findings in activated protein C resistance, a hereditary cause of recurrent thrombosis. The case described was unusual in that a neonate was affected, whereas the vast majority of cases occur in adulthood. This entity is important to diagnose because of the recurrent nature of thromboses and the fact that relatives are often affected.

Blood Coagulation Disorders↗
PubMed1998

Disseminated thrombosis in primary antiphospholipid syndrome: MR findings.

We report the MR imaging findings in a patient with primary antiphospholipid syndrome, adrenal infarction and widespread thrombosis involving abdominal, pelvic, and pulmonary vessels. This syndrome should be suspected in patients with thromboses and organ infarctions of otherwise undetermined etiology.

Adrenal Glands↗
PubMed1998

Cerebrovascular disease risk factors: neuroradiologic findings in patients with activated protein C resistance.

PURPOSE: To assess the patterns of abnormal neuroradiologic findings in patients with a hypercoagulable state related to activated protein C (APC) resistance. MATERIALS AND METHODS: Records in 23 patients with a hypercoagulable state related to APC resistance (18 women, five men; average age, 44.5 years) were reviewed for cerebrovascular disease risk factors and other causes of a hypercoagulable state. Computed tomographic scans, magnetic resonance (MR) images, angiograms, and transesophageal echocardiograms were also reviewed. RESULTS: Stroke risk factors or other causes of a hypercoagulable state were found in 12 patients. Arterial infarcts were seen in 18 patients. Hyperintense white matter foci were seen on MR images in six patients. Dural sinus thrombosis was found in four patients. Angiograms of intracranial circulation in six patients showed major artery occlusions in four. MR angiograms in four patients showed internal carotid artery occlusion in one. No major abnormalities were seen in extracranial cerebral vasculature in 15 patients. Transesophageal echocardiograms in 11 patients showed a patent foramen ovale in one patient but no systemic source of embolism. Seven patients had non-central nervous system thrombotic events. CONCLUSION: Patients with APC resistance and stroke appear to differ from the general stroke population in terms of age and frequency of extracranial sources of cerebrovascular disease.

Adolescent↗
PubMed1998

Systemic thrombosis in patients with antiphospholipid antibodies: lesion distribution and imaging findings.

OBJECTIVE: The purpose of this study was to determine the patterns of non-CNS thromboses in patients with a hypercoagulable state associated with antiphospholipid antibodies (APA). MATERIALS AND METHODS: A search of our institution's clinical coagulation and immunology laboratories' records of patients examined from January 1993 to January 1996 revealed 1290 patients with APA. Computerized records of radiologic studies were reviewed for evidence of thrombotic events, which were found in 93 patients (49 males and 44 females; average age, 40 years). The anatomic distribution of thrombotic events was recorded. RESULTS: Fifty-five patients (59%; 29 males and 26 females; average age, 44.2 years) had solely venous thromboses, 26 patients (28%; 15 males and 11 females; average age, 33.1 years) had solely arterial thromboses, and 12 (13%; 5 males and 7 females; average age, 35.4 years) had both types of events. Deep vein thrombosis (DVT) of the legs was the most common finding, occurring in 45 patients (48%). Six patients had recurrent DVT. Other sites of venous thrombotic events included pulmonary embolism, 30 patients (32%); thoracic veins (superior vena cava, subclavian vein, or jugular vein), 10 patients (11%); and abdominal or pelvic veins, 18 events in 11 patients (12%). Sites of arterial thromboses included arteries supplying the upper limbs (great vessels arising from the aorta or the brachial, radial, ulnar, or digital arteries), 15 events in 12 patients (13%); aorta, one patient (1%); abdominal or pelvic arteries, 11 events in eight patients (9%); and arteries supplying the lower limbs (femoral or popliteal arteries), seven patients (8%). CONCLUSION: Venous thromboses were more common than arterial thromboses in our patient group, with DVT being the most common. However, thromboses in sites that are unusual for the general population were also relatively common. APA should be suspected in patients with thromboses in unusual sites or recurrent thromboses of an otherwise unexplained cause.

Adult↗
PubMed1998

Dural sinus thrombosis associated with activated protein C resistance: MR imaging findings and proband identification.

OBJECTIVE: The purpose of this study was to report the association of dural sinus thrombosis with a hypercoagulable state associated with activated protein C resistance. CONCLUSION: In our small study population, hemorrhagic venous infarction was common (three of four patients) among patients with dural sinus thrombosis and activated protein C resistance. Four of five patients with dural sinus thrombosis had positive tests for activated protein C resistance. This finding, in conjunction with data from other studies, suggests that patients with dural sinus thrombosis may need to be studied for the presence of activated protein C resistance. A positive finding for activated protein C resistance can be important not only in helping to explain the cause of thrombosis in affected individuals but also in identifying families at risk for thrombosis.

Adult↗
PubMed1998

Antiphospholipid antibodies: findings at arteriography.

PURPOSE: The purpose of this study was to determine the frequency and types of abnormalities at arteriography in patients with antiphospholipid antibodies (APA) and ischemic cerebrovascular events. METHODS: Twenty-three patients with APA and ischemic cerebrovascular events who underwent arteriography were identified. Patients over the age of 65 years were excluded. No patients met diagnostic criteria for systemic lupus erythematosus. All angiograms were reviewed by two neuroradiologists. RESULTS: Seventeen patients (74%) between the ages of 28 and 64 years (average age, 40 years) had abnormal angiograms. Sixteen patients had arterial abnormalities and one had dural sinus thrombosis. Ten had solely intracranial abnormalities (nine arterial and one venous), six had solely extracranial arterial abnormalities, and one had both intracranial and extracranial arterial abnormalities. Intracranial arterial abnormalities included stem or branch occlusions of the cerebral or basilar arteries, which were generally solitary (six patients), and findings suggestive of vasculitis (four patients). Four patients had stenoses of the origins of two or more great vessels. Two patients had extracranial internal carotid artery stenoses or occlusions that were not typical of atheromatous disease, considered to be embolic in one patient. In another patient, a stenosis of the origin of the internal carotid artery was present that appeared typical of atheromatous disease. Infarctions were seen on CT or MR studies in 13 of 17 patients with abnormal angiograms. CONCLUSION: In our group of patients, typical atheromatous lesions at the common carotid artery bifurcation were rare. Some lesions that are infrequent in the general stroke population (eg, vasculitis-like findings and stenoses at the origin of great vessels) were common. Patients with APA and cerebrovascular events appear to differ from the general stroke population with regard to types of arterial abnormalities seen at arteriography.

Adult↗
PubMed1998

New treatment options for heparin-induced thrombocytopenia.

A rapidly acting anticoagulant that can either inhibit thrombin generation or inhibit thrombin itself is the optimum therapy for acute thrombosis associated with heparin-induced thrombocytopenia (HIT). In this review, the newer treatment approaches that fulfill this requirement are discussed. These newer treatments include hirudin and argatroban, direct thrombin inhibitors, and danaparoid, which inhibits thrombin generation. Preliminary outcome results from the extensive compassionate-use program for danaparoid in HIT and from a recently completed randomized clinical trial that compared danaparoid with dextran in patients with HIT are provided. Based on these data, danaparoid appears to be a useful and safe replacement for heparin in patients who develop HIT.

Anticoagulants↗
PubMed1997

Monitoring warfarin therapy in patients with lupus anticoagulants.

BACKGROUND: Recommended therapeutic international normalized ratios (INRs) for oral anticoagulation in patients with lupus anticoagulants who sustain a thromboembolic event are controversial. Patients with lupus anticoagulants often have a prolonged prothrombin time, which may complicate management of anticoagulant therapy. OBJECTIVES: To determine the validity of the INR as a monitor for warfarin therapy in patients with lupus anticoagulants and to investigate alternate approaches to monitoring warfarin therapy in these patients. DESIGN: Prospective case series. SETTING: Tertiary care hospital. PATIENTS: 34 patients with lupus anticoagulants. MEASUREMENTS: Prothrombin times were determined by using several thromboplastins, and INRs were calculated for the patients receiving warfarin. Factor II levels, chromogenic factor X levels, and prothrombin-proconvertin times were determined for patients receiving warfarin. RESULTS: For patients with lupus anticoagulants who were not receiving warfarin, prothrombin times were often elevated and varied significantly with different thromboplastins. Individual thromboplastins differed in sensitivity to the presence of a lupus anticoagulant. For patients receiving warfarin, INRs obtained by using different thromboplastins greatly varied and often overestimated the extent of anticoagulation. Chromogenic factor X levels and prothrombin-proconvertin times correlated well with each other and with established therapeutic ranges. CONCLUSIONS: Lupus anticoagulants can influence prothrombin times and lead to INRs that do not accurately reflect the true level of anticoagulation. Use of the INR to standardize prothrombin times is invalid for some patients with lupus anticoagulants. To prevent supratherapeutic or subtherapeutic anticoagulation, these patients must be individually monitored with a test that is insensitive to lupus anticoagulants.

Adolescent↗
PubMed1997

Plasma levels of factors II, VII and X and their relationship to the international normalized ratio during chronic warfarin therapy.

Monitoring of oral anticoagulant therapy is usually undertaken with the prothrombin time (PT), which is influenced by factors II, X, and VII. A number of studies have suggested that the prothrombin (factor II) level may be the most important determinant of the therapeutic efficacy of these drugs. Although some studies suggest that oral anticoagulants induce a similar residual level of plasma vitamin K-dependent proteins, others have called this into question. We therefore measured plasma levels of factors II, X, and VII in 50 patients undergoing chronic Warfarin therapy. The plasma levels of factors II, X, and VII were significantly different. Although the factor X levels of all plasmas were < 30%, levels of factors II and VII were > 30% in 14% and 50% of the samples, respectively. Multivariable analysis showed factor II levels to be the least significant of the three factors measured in determining the international normalized ratio of plasma or whole blood. Thus, plasma levels of the vitamin K-dependent coagulation factors are not equal in patients on chronic Warfarin therapy. If factor II (prothrombin) levels are indeed the major determinants of the therapeutic efficacy of Warfarin, alternative means of monitoring that more accurately reflects prothrombin levels should be evaluated.

Administration, Oral↗