Search PubMed⌕ Search

Biomedical subjects

J J Michiels

Publications and source records attributed to J J Michiels.

At least 37 records · Page 2Linked to original sources
PubMed2001

Acquired von Willebrand syndrome in systemic lupus erythematodes.

Acquired von Willebrand syndrome (AvWS) in systemic lupus erythematodes (SLE) is caused by autoantibodies directed against the circulating von Willebrand factor (vWF)/factor VIII (FVIII) complex. The autoantibody-vWF/FVIII antigen complex is cleared rapidly from the circulation, leading to a moderate to severe quantitative and qualitative deficiency of both vWF and FVIIIc. Consequently, AvWS in SLE is featured by a prolonged bleeding time and normal platelet count, a prolonged activated partial thromboplastin time (APTT) and normal prothrombin time (PT), decreased or absent ristocetin-induced platelet aggregation (RIPA), and type II vWF deficiency on multimeric analysis of the vWF protein. Acquired von Willebrand syndrome type II in SLE responds poorly to 1-desamino-8-D-arginine vasopressin (DDAVP) and FVIII concentrate, but responds transiently well to high-dose gammaglobulin given intravenously. All reported cases of AvWS in SLE were cured by appropriate treatment of the underlying autoimmune disease with prednisone or immunosuppression.

Adolescent↗
PubMed2001

Acquired von Willebrand syndrome type 1 in hypothyroidism: reversal after treatment with thyroxine.

In 16 cases, acquired von Willebrand syndrome (AvWS) and hypothyroidism have been described that occur with each other: 15 women and one man, at a mean age of 32 years, range, 13 to 82 years of age. Activated partial thromboplastin time (APTT) was normal in six patients, and five patients had factor VIII concentration (factor VIIIc) levels in excess of 60%. The bleeding time was prolonged in nine of 13 evaluable patients. Activated partial thromboplastin time was prolonged in seven patients, and five of these had factor VIIIc levels between 18 and 45%, with two patients having levels in excess of 60%. A deficiency of other coagulation factors, including factor VII, V, IX, and X, caused by a generalized diminution in protein synthesis in hypothyroidism, may have contributed to the prolongation of the APTT. The AvWS was very likely type 1 in all cases because of a normal von Willebrand factor antigen/ristocetin cofactor (vWF Ag/RCF) ratio. Acquired von Willebrand syndrome was documented via cross immunoelectrophoresis in three patients and via multimeric analysis of vWF in six patients. A definite diagnosis of AvWS type I has to be confirmed by a normal response to 1-desamino-8-D-arginine vasopressin (DDAVP). Treatment of hypothyroidism with thyroxine was associated with the disappearance of the AvWS and the bleeding diathesis. Decreased factor VIIIc, vWF Ag and vWF RCF levels (50%, 33%, and 36% respectively) before thyroxine treatment increased to normal values (97%, 93%, and 107% respectively) after treatment. The absence of bleeding, or mild bleeding, symptoms, in relation to those more commonly recognized with hypothyroidism, has led to the complication of acquired vWF deficiency being underdiagnosed. Acquired von Willebrand syndrome type I should be considered whenever hypothyroidism is diagnosed and thyroid biopsy or surgery is contemplated. The complete relief of AvWS via treatment of hypothyroidism with thyroxine is the final proof of this association and causal relationship.

Adolescent↗
PubMed2000

Spontaneous proliferative megakaryocytopoiesis and platelet hyperreactivity in essential thrombocythemia: is thrombopoietin the link?

Essential thrombocythemia (ET) is one of the less rare variants of the chronic myeloproliferative disorders (MPD). The present review questions the possible link between spontaneous megakaryocytopoiesis, platelet hyperreactivity, and the occurrence of platelet-mediated vascular manifestations in acquired and hereditary ET. In acquired ET, the role of thrombopoietin (TPO) is crucial to the observed hypermegakaryocytopoiesis, which is characterized by an increased proliferation of megakaryocyte (MK) progenitors, even in conditions of culture without addition of any known megakaryocyte colony-stimulating factors. An increased reactivity of megakaryocyte progenitors to TPO remains to be precisely delineated. A defective clearance of TPO by megakaryocytes and platelets because of a reduced number of TPO receptors is possible. TPO is able to enhance platelet aggregation induced by ADP, thrombin, and collagen. A point mutation in the TPO gene as the cause of increased TPO production in hereditary ET can readily explain both spontaneous megakaryocytopoiesis and platelet-mediated microvascular manifestations simulating the phenotype of acquired ET. Nevertheless, to date, no mutation of the TPO structural gene, as shown in two families with hereditary ET, and no mutations in the TPO receptor have been found in patients with acquired ET. There is good evidence that the microvascular circulation disturbances in ET are caused by intravascular activation and aggregation of hypersensitive platelets, with sludging or occlusion of the endarterial microvasculature. In this process, the generation of platelet-derived products, endothelial cell damage, fibromuscular intimal proliferation, and platelet thrombi are essential and can be inhibited by a platelet-specific regimen of aspirin, thus providing a rationale for using low-dose aspirin as an antithrombotic agent in thrombocythemia. In contrast, the generation of thrombin appears not to be essential for the formation of platelet thrombi, thereby explaining the inefficacy of coumadin derivatives and heparin in the treatment and prevention of microvascular circulation disturbances in hereditary and acquired ET.

Blood Platelets↗
PubMed2000

Strategies for the safe and effective exclusion and diagnosis of deep vein thrombosis by the sequential use of clinical score, D-dimer testing, and compression ultrasonography.

Patients with suspected deep vein thrombosis (DVT) are subjected to leg vein compression ultrasonography (CUS) that confirms DVT in only 20 to 30% of patients. A positive CUS is consistent with DVT irrespective of clinical score. The sequential use of a simple clinical score assessment, a rapid sensitive enzyme-linked immunosorbent assay (ELISA) D-dimer test and CUS to safely exclude DVT is promising. The clinical score is a validated clinical model of complaints, signs, and symptoms, on the basis of which a pretest clinical probability for DVT can be estimated as low, moderate, and high. The safe exclusion of DVT by a rapid sensitive D-dimer test in combination with clinical score or CUS necessitates a negative predictive value of more than 99%. The negative predictive value for DVT is determined by the sensitivity of the rapid ELISA D-dimer test and the prevalence of DVT in subgroups of outpatients with suspected DVT. The prevalence of DVT in outpatients with a low, moderate, and high clinical score varies widely from 3 to 10%, 15 to 30% and more than 70%, respectively. A negative rapid ELISA D-dimer and a low clinical score (prevalence DVT 3 to 5%) will have a very high negative predictive value of more than 99.5% to exclude DVT without the need of CUS testing. A negative ELISA D-dimer test and a first-negative CUS safely exclude DVT in patients with a moderate clinical score with a negative predictive value of more than 99.5%, therefore obviating the need to repeat CUS. The use of a rapid ELISA D-dimer testing in patients with a high clinical score is not recommended. A negative CUS, a low clinical score, and a positive ELISA D-dimer, even less than 1000 ng/mL exclude DVT with a nega tive predictive value of more than 99%. Patients with a negative CUS, but a positive ELISA D-dimer, and a moderate or high clinical score have a probability of DVT of 3 to 5% and 20 to 30%, respectively, and are thus candidates for repeated CUS testing. The proposed sequential use of the clinical score assessment, a rapid ELISA D-dimer test, and CUS will be the most cost-effective diagnostic strategy for DVT because of a significant reduction of CUS examinations and gain of time for the patient and physician in charge.

Algorithms↗
PubMed2000

Exclusion and diagnosis of pulmonary embolism by a rapid ELISA D-dimer test and noninvasive imaging techniques within the context of a clinical model.

A negative rapid ELISA D-dimer test alone in out-patients with a low to moderate clinical probability (CP) on pulmonary embolism (PE) is predicted to safely exclude pulmonary embolism. The combination of a negative rapid ELISA D-dimer test and a low to moderate CP on PE followed by compression ultrasonography (CUS) for the detection of deep vein thrombosis (DVT) is safe and cost-effective as it reduces the need for noninvasive imaging techniques to about 50% to 60% of outpatients with suspected PE. A high probability ventilation-perfusion (VP) scan or a positive spiral CT consistent with PE and the detection of DVT by CUS are currently considered to be clear indications for anticoagulant treatment. Subsequent pulmonary angiography (PA) is the gold standard diagnostic strategy to exclude or diagnose PE in suspected outpatients with a negative CUS, a positive rapid ELISA D-dimer test, and a nondiagnostic VP scan or negative spiral CT to prevent overtreatment with anticoagulants. However, the willingness of clinicians and the availability of resources to perform PA is restricted, a fact that has provided an impetus for clinical investigators to search for alternative noninvasive strategies to exclude or detect venous thromboembolism (VTE). Serial CUS testing for the detection of DVT in patients with a low to moderate CP on PE and a nondiagnostic VP scan or negative spiral CT is predicted to be safe and will reduce the need for PA to less than 10% or even less than 5%. This noninvasive serial CUS strategy restricts the need for invasive PA to a minor group of patients (< 5%) with the combination of a low CP on PE and high probability VP scan or the combination of a nondiagnostic VP scan or negative spiral CT and a high CP on PE. Prospective evaluations are warranted to implement and to validate the advantages and the disadvantages of the various combinations of noninvasive strategies and to compare serial CUS testing versus PA in randomized clinical management studies of outpatients with suspected pulmonary embolism.

Antifibrinolytic Agents↗
PubMed2000

Acquired hemophilia A in women postpartum: clinical manifestations, diagnosis, and treatment.

Acquired hemophilia A in women postpartum is diagnosed by a prolonged activated partial thromboplastin time (APTT), low plasma levels of coagulant factor VIII, and the detection of an inhibitor against factor VIII in the Bethesda assay. Effective treatment of bleeding symptoms should be based upon the clinical situation and depends on the inhibitor characteristics against human and porcine factor VIII. Immunosuppression usually does not significantly affect the disappearance of the factor VIII inhibitor antibody. The natural history of acquired hemophilia postpartum is independent of immunosuppressive treatment and featured by spontaneous disappearance of the inhibitor against factor VIII in the majority of cases.

Adolescent↗
PubMed2000

Effectiveness of anagrelide in the treatment of symptomatic patients with essential thrombocythemia.

We prospectively evaluated the effect of anagrelide on platelet counts and the clinical manifestations of microvascular circulation disturbances in 17 newly diagnosed patients with essential thrombocythemia. Ten patients had symptoms related to thrombocythemia, eight at the time of starting anagrelide treatment. The platelet counts before anagrelide treatment and during maintained remission of essential thrombocythemia by anagrelide were 980 (range, 610-2030) and 378 (range, 212-546) x 10(9)/L, respectively. Spontaneous platelet aggregation was found in 6 patients (35%), which disappeared on remission of essential thrombocythemia in five cases (P = 0.02). Essential thrombocythemia-related microvascular thrombotic and hemorrhagic symptoms disappeared with the normalization of platelet count in all cases during maintained remission of essential thrombocythemia by long term continuous anagrelide treatment with a follow-up period of between 2 and 6 years. However, ET-related symptoms reappeared in three patients, coinciding with increased platelet count up to 600 x 10(9)/L caused by anagrelide dose reduction. We conclude that reduction of increased platelet to normal (< 400 x 10(9)/L) in symptomatic patients with essential thrombocythemia through use of maintained anagrelide treatment is associated with the disappearance of spontaneous platelet aggregation and the complete relief of thrombotic and hemorrhagic manifestations.

Adult↗
PubMed2000

Diagnosis and treatment of polycythemia vera and possible future study designs of the PVSG.

The present study describes clinicopathological criteria to distinguish the 5 sequential stages proposed by Wasserman et al in the natural history of newly diagnosed PV patients. The European Working Group on MPD (EWG.MPD) extended and modified the PVSG diagnostic criteria of PV by including bone marrow histopathology. From the results of prospective randomized studies in PV it became evident that new clinical trials in previously untreated PV patients should focus on comparing interferon-alpha, a non-leukemogenic approach, versus a potential leukemogenic myelosuppressive treatment modality. Hydroxyurea appears to be the least leukemogenic myelosuppressive agent in long-term prospective clinical PV-studies extending observation periods of more than 10 years. The rational for using IFN-alpha as a first-line treatment option in newly diagnosed PV-patient include its effectiveness to abate constitutional symptoms and to induce a complete remission thereby avoiding phlebotomy, iron deficiency, and macrocytosis associated with hydroxyurea. Moreover IFN-alpha may prevent or delay the development of postpolycythemic myelofibrosis if used early in the course of the disease. Clinicians will be reluctant to postpone the use of hydroxyurea in early stage PV as long as a conservative approach using phlebotomy aiming at a hematocrit below 0.45, plus low-dose aspirin for the control platelet function or anagrelide for the control platelet number is used to keep the patient healthy. Low-dose aspirin will prevent the microvascular thrombotic complications of thrombocythemia associated with PV in remission after phlebotomy, but lacks myelosuppressive activity. Control of megakaryocyte maturation and reduction of platelet production to normal (<400 x 10(9)/l) by relatively low doses of anagrelide will predict a significant reduction of vascular complications in the early stages of PV, may prevent progression to myelofibrosis during follow-up of PV and very probable will postpone the use of hydroxyurea treatment for controlling the platelet count in PV. Large scale randomized clinical trials in PV are proposed, which should aim not only for clinical and hematological response, safety, efficacy, but should also assess toxicity, the need for phlebotomy and whether the development of progressive disease such as splenomegaly, pruritus, myelofibrotic myeloid metaplasia, spent phase, myelodysplasia and acute leukemia can be delayed or prevented by IFN-alpha as compared to a conservative approach of phlebotomy plus low-dose aspirin or anagrelide followed by hydroxyurea when signs of myeloproliferative activity became evident.

Blood Platelets↗
PubMed1999

Diagnosis, pathogenesis and treatment of the myeloproliferative disorders essential thrombocythemia, polycythemia vera and essential megakaryocytic granulocytic metaplasia and myelofibrosis.

According to strict clinical, hematological and morphological criteria, the Philadelphia (Ph) chromosome negative chronic myeloproliferative disorders essential thrombocythemia (ET), polycythemia vera (PV), and agnogenic myeloid (megakaryocytic/granulocytic) metaplasia (AMM) or idiopathic myelofibrosis (IMF) are three distinct disease entities with regard to clinical manifestations, natural history and outcome in terms of life expectancy. As clonality studies have clearly demonstrated that fibroblast proliferation in AMM, as well as in many other conditions such as advanced stages of Ph(+)-essential thrombocythemia, Ph(+)-granulocytic leukemia, and Ph(-)-polycythemia vera, is polyclonal indicating that myelofibrosis is secondary to the megakaryocytic granulocytic metaplasia in these various conditions, AMM is illogically labeled as IMF. As abnormal megakaryocytic granulocytic metaplasia is the essential feature preceding the early prefibrotic stage of AMM, the term essential megakaryocytic granulocytic metaplasia (EMGM) can readily be used to characterize this condition more appropriately at the biological level. Clinical, hematological and morphological characteristics, in particular megakaryocytopoiesis and bone marrow cellularity, reveal diagnostic features, which enable a clear-cut distinction between ET, PV and EMGM or classical IMF. The characteristic increase and clustering of enlarged megakaryocytes with mature cytoplasm and multilobulated nuclei and their tendency to cluster in a normal or only slightly increased cellular bone marrow represent the hallmark of ET. The characteristic increase and clustering of enlarged mature and pleiomorphic megakaryocytes with multilobulated nuclei and proliferation of erythropoiesis in a moderate to marked hypercellular bone marrow with hyperplasia of dilated sinuses are the specific diagnostic features of untreated PV. EMGM, including the early prefibrotic stages as well as the various myelofibrotic stages of classical IMF appear to be a distinct neoplastic dual proliferation of abnormal megakaryopoiesis and granulopoiesis. The histopathology of the bone marrow in prefibrotic EMGM and in classical IMF is dominated by atypical, enlarged and immature megakaryocytes with cloud-like immature nuclei, which are not seen in ET and PV at diagnosis and during follow-up. Myelofibrosis in ET, PV and EMGM is graded into: no reticulin fibrosis (MF0), early reticulin fibrosis (MF1), advanced reticulin sclerosis with minor or moderate collagen fibrosis (MF2) and advanced collagen fibrosis with osteosclerosis (MF3). Myelofibrosis is not a feature of ET at diagnosis and during long-term follow-up. Myelofibrosis may be present in a minority of PV-patients at diagnosis and usually becomes apparent during long-term follow-up in the majority of PV-patients. Myelofibrosis secondary to the abnormal megakaryocytic and granulocytic myeloproliferation constitutes a prominent feature in the majority of EMGM/IMF at time of diagnosis and usually progresses more or less rapidly during the natural history of the disease. Life expectancy is normal in ET, normal during the 1st ten years and compromised during the 2nd ten years follow-up in PV, but significantly shortened in the prefibrotic stage of EMGM as well as in the various myelosclerotic stages of classical IMF. First line treatment options in prospective randomized clinical trials of newly diagnosed MPD-patients are control of platelet function with low-dose aspirin versus reduction of platelet count with anagrelide, interferon or hydroxyurea in ET; control of platelet and erythrocyte counts by interferon alone versus bloodletting plus hydroxyurea on indication in PV; interferon versus no treatment in the early stages of EMGM; a wait and see strategy in the fibrotic stages of EMGM or classical IMF with favorable prognostic factors, and bone marrow transplantation in classical IMF with poor prognostic factors at presentation or during short-term follow-up.

Aspirin↗
PubMed1999

Thromboxane-dependent platelet activation in vivo precedes arterial thrombosis in thrombocythaemia: a rationale for the use of low-dose aspirin as an antithrombotic agent.

The clinical course of patients with polycythaemia vera (PV) and essential thrombocythaemia (ET) is frequently complicated by arterial thrombotic events. The pathogenesis is not clearly understood but attributed to abnormalities in platelet function. An increase in platelet thromboxane formation has been described in the majority of asymptomatic patients with thrombocythaemia, probably reflecting spontaneous platelet activation in vivo. In the present study we prospectively investigated whether an increase in platelet thromboxane formation actually precedes arterial microvascular thrombosis. In addition, we studied the effect of selective inhibition of platelet thromboxane formation on clinical outcome by reinstitution of low-dose aspirin (50 mg/ d). Six ET patients and one PV patient participated in this study. Within 10 d after withdrawal of aspirin, three patients developed arterial microvascular thrombosis of extremities (erythromelalgia), which was preceded by a 3-30-fold increase in urinary thromboxane excretion as compared with patients who remained asymptomatic. The increased urinary thromboxane excretion and clinical signs could be inhibited by a platelet-specific aspirin regimen of 50 mg/d without affecting vascular cyclooxygenase, indicating that platelets were the main source of the increased thromboxane generation. These data suggest that in symptomatic patients an enhanced formation of thromboxane by platelets, reflecting platelet activation in vivo, precedes the development of arterial microvascular thrombosis. These data provide a rationale for using low-dose aspirin as an antithrombotic agent in thrombocythaemia.

Adult↗
PubMed1999

Normal life expectancy and thrombosis-free survival in aspirin treated essential thrombocythemia.

Focusing on platelet-mediated erythromelalgia as a specific, presenting, and single sign of essential thrombocythemia (ET) we were able to define the characteristic peripheral blood and bone marrow findings in ET patients. From 1974 to 1986 we treated 20 symptomatic ET patients with microvascular circulation disturbances including erythromelalgia (N = 18), atypical or typical transient ischemic attacks (N = 6), or acute coronary ischemic syndrome (N = 3) with aspirin and one course of busulfan. The mean platelet counts before and after busulfan treatment were 1,009 (range 545-1,525) and 241 (range 159-315) x 10(9)/L, respectively. After induction of a complete remission, treatment with busulfan and aspirin was discontinued until symptoms returned. All 20 patients remained asymptomatic as long as ET was in maintained remission (platelet < 350 x 10(9)/L) for 4 to 61 (mean 36) months. Eight patients became symptomatic and 4 patients remained asymptomatic at relapse of ET after a follow-up period of 19 to 61 and 31 to 46 months, respectively. Platelet counts at time of symptomatic relapse in the 8 patients were 410, 450, 490, 500, 515, 545, 548, and 635 x 10(9)/L and at time of asymptomatic relapse in 4 ET patients 577, 600, 648, and 725 x 10(9)/L. Based on these observations, since 1986 we followed the strategy to treat ET patients with aspirin as long as the platelet count was between 400 and 1,000 up to 1,250 x 10(9)/L. Clear indications to reduce the platelet count were bleeding, aspirin side effects, and platelets counts above 1500 x 10(9)/L. This nonleukemogenic or least toxic approach in ET is the rationale behind the normal life expectancy and subsequent thrombosis-free survival in 68 ET patients after a mean follow-up period of 6.2 years.

Acute Disease↗
PubMed1999

Acquired von Willebrand disease due to increasing platelet count can readily explain the paradox of thrombosis and bleeding in thrombocythemia.

The arterial microvascular thrombotic events in thrombocythemia including erythromelalgia, atypical and typical cerebral and ocular transient ischemic attacks, and acute coronary syndromes already occur at platelet counts > 400 x 10(9)/L and are sensitive to low-dose aspirin, which does not elicit bleedings at platelet counts < 1,000 x 10(9)/L. An increasing platelet count in thrombocythemia to above 1,000 x 10(9)/L is accompanied by the acquisition of a von Willebrand factor deficiency due to the loss of intermediate and large von Willebrand factor multimers. The arterial thrombotic condition in thrombocythemia changes into an overt spontaneous bleeding tendency at mean platelet counts of about 2,000 +/- 1,000 x 10(9)/L due to an acquired von Willebrand disease type II with normal values for von Willebrand factor antigen concentration but absence of intermediate and large von Willebrand factor multimers in plasma. At platelet counts between 1,000 and 2,000 x 10(9)/L, thrombosis and bleeding frequently occur in sequence or paradoxically, and low-dose aspirin does prevent thrombotic complications but aggravates or may elicit bleeding symptoms. Reduction of the platelet count < 1,000 x 10(9)/L significantly restores the von Willebrand factor deficiency with the reappearance of the intermediate and some of the large von Willebrand factor multimers and the disappearance of the bleeding tendency, but the thrombotic tendency persists as long as platelet counts are above the upper limit of normal. The acquisition of von Willebrand factor deficiency at increasing platelet counts can readily explain the paradox of thrombosis and bleeding in thrombocythemia and has important clinical implications.

Blood Platelets↗
PubMed1999

Acquired von Willebrand disease in monoclonal gammapathies: effectiveness of high-dose intravenous gamma globulin.

The reported underlying lymphoproliferative disorders associated with acquired von Willebrand disease (AvWD) include benign monoclonal gammapathy, multiple myeloma, Waldenström disease, chronic lymphocytic leukemia, non-Hodgkin lymphoma, and hairy cell leukemia. The AvWD in patients with a monoclonal gammapathy and/or a lymphoproliferative disorder is featured by a prolonged bleeding time, normal platelet count, and a decreased or absent ristocetine-induced platelet aggregation in combination with a prolonged aPTT and normal PT due to low levels of factor VIII/von Willebrand factor (vWF) parameters in the absence of a factor VIII inhibitor in the Bethesda assay. In vitro and vivo experiments consistently showed that the anti-vWF autoantibodies in monoclonal gammapathies cause a rapid clearance of the factor VIII/vWF complex from the circulation after DDAVP and factor VIII/vWF concentrate infusion. Multimeric analysis of the vWF usually show a type II-like AvWD due to the absence of large vWF multimers as the consequence of the rapid clearance of the anti-vWF-factor VIII/vWF complex from the circulation. There is a poor response to intravenous DDAVP and factor VIII/vWF concentrate infusion, but high dose intravenous gamma globulin (1 g/kg for 2 days) usually induces a transient correction of the factor VIII/vWF parameters for 1 to a few weeks.

Adult↗
PubMed1999

Exclusion and diagnosis of deep vein thrombosis by a rapid ELISA D-dimer test, compression ultrasonography, and a simple clinical model.

The classical clinical signs of deep vein thrombosis (DVT) are unspecific and may be found in several other conditions besides DVT. Therefore, patients suspicious of DVT are subjected to elaborate invasive or noninvasive evidence-based procedures that actually confirm DVT in only 20% to 30% of patients in this setting. However, simple laboratory tests and noninvasive strategies to exclude and diagnose DVT are becoming available in the clinical emergency setting of outpatients. In the presented literature, a sound basis is provided for quantifying clinical judgment for the diagnosis of acute proximal DVT. The number of positive clinical findings at time of first suspicion of DVT appears to correlate directly with the probability of acute proximal DVT. The modified clinical model of Landefeld and Wells for DVT allows reasonable accurate classification of patients into low, moderate, and high probability for suffering DVT. The rapid automated enzyme-linked immunoabsorbant assay (ELISA) VIDAS D-dimer presently available can be rapidly performed in daily practice and emergency situations and is accurate to a high degree, especially in ruling out ongoing venous thromboembolic processes. The sequential use of the rapid ELISA VIDAS D-dimer test and compression ultrasonography in a well-designed clinical setting using a simple clinical model predicts a significant improvement due to a high sensitivity near 100% for the exclusion and diagnosis of DVT in the majority of outpatients with suspect DVT. A prospective decision analysis management study is proposed to exclude and diagnose DVT based on the rapid ELISA VIDAS D-dimer test and compression ultrasonography within the context of a ready-to-use simple clinical model. The proposed simple model of a rational diagnosis of deep vein thrombosis (RADIA DVT) has to be tested in a large multicenter study of more than 1,000 outpatients with suspected DVT. This model would be less expensive, easy to perform, and likely yield a significant simplification and improvement of highly accurate evidence-based exclusion or diagnosis of DVT on the basis of which clear-cut indications of anticoagulation could be appropriately initiated or safely withheld.

Enzyme-Linked Immunosorbent Assay↗
PubMed1999

Aspirin and platelet-lowering agents for the prevention of vascular complications in essential thrombocythemia.

Low-risk essential thrombocythemia patients include patients aged 18 to < 80 years with no vascular risk factor or previous thrombosis, no associated disease, a normal life expectancy, and a platelet count between 400 and 1,000 x 10(9)/L up to 1,500 x 10(9)/L. Asymptomatic essential thrombocythemia patients may be at risk for microvascular circulation disturbances. The indication for low-dose aspirin in asymptomatic essential thrombocythemia patients is uncertain, therefore randomization for aspirin 50 mg versus placebo is recommended. Symptomatic essential thrombocythemia patients with erythromelalgia and its ischemic complications, atypical transient ischemic attacks, minor stroke, visual disturbances and "superficial thrombophlebitis" in the absence of bleeding, vascular risk factors, or vascular disease have a clear indication for aspirin in a regular dose. To determine whether 50 mg/day is as effective as 100 mg/day for the prophylaxis of microvascular circulation disturbances in essential thrombocythemia, a randomized trial comparing low-dose aspirin 50 mg versus 100 mg at platelet counts between 400 and 1,000 up to 1,500 x 10(9)/L is recommended. To address the question whether reduction of the platelet count to normal (< 350 x 10(9)/L) is as effective as low-dose aspirin for the long-term relief of microvascular circulation disturbances, a randomized study comparing low-dose aspirin with the correction of platelet count to normal by anagrelide is recommended. High-risk essential thrombocythemia patients have a clear indication for platelet reductive therapy, including: (a) platelets > 1,500 x 10(9)/L, history of major thrombosis (myocardial infarction, stroke, peripheral occlusive vascular disease), or presence of vascular disease (e.g., arteriosclerosis); (b) history or presence of spontaneous or major bleedings, bleedings elicited by low-dose aspirin for the secondary prevention of vascular complications in essential thrombocythemia at platelet counts < 1500 x 10(9)/L, and side effects of long-term aspirin treatment such as gastritis; and progression from low- to high-risk essential thrombocythemia patients during follow-up or progressive myeloproliferative disease such as significant splenomegaly, myelofibrosis, leukocytosis, etc. To address the question of optimal treatment of high-risk essential thrombocythemia patients, randomization for anagrelide versus interferon at < 65 years of age and anagrelide versus hydroxyurea at an age > 65 years is recommended.

Adolescent↗