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Biomedical subjects

M H Horellou

Publications and source records attributed to M H Horellou.

At least 37 records · Page 2Linked to original sources
PubMed1998

[Heparin-induced thrombopenia: significance and difficulties of precise identification of the immunologic mechanism].

Heparin-induced thrombocytopenia (HIT) is a drug induced immunohematologic adverse reaction which is a rare but potentially very severe accident. Its diagnosis is important for epidemiologic and drug surveillance studies and in order to decide the most appropriate treatment. Its importance is enhanced since there is no gold standard diagnostic criteria. In clinical practice the diagnosis is based on a group of criteria related to clinical events and laboratory tests. We have established a score based on anamnestic criteria which allowed us to evaluate and compare two different laboratory tests: a platelet aggregation test (PAT) and a test for the detection of heparin dependent antibodies (Heparin Platelet Induced Antibodies or HPIA). The functional test PAT which is commonly used in expert laboratories detects antibodies inducing platelet aggregation in the presence of heparin. The HPIA test more recently developed is an ELISA test which detects antibodies directed at heparin-platelet factor 4 complexes. The relative value of theses two methods for the diagnosis of HIT is not well documented. We have analysed the results of these two tests in 273 consecutive patients with a suspicion of HIT. The results were concordant in 70% of patients. In selecting the patients with the lowest and the highest probability of HIT according to the score, PAT was found a more sensitive and HPIA a more specific test than the other. At low probability PAT is more often positive than HPIA 18% and 9% respectively. No test is 100% reliable, the specificity being limited for both tests since in about 20% of cases one or both tests are negative contrasting with a highly probable HIT. In this last group of patients, PAT was more frequently positive (86%) than HPIA (72%). Both tests are negative in 6% of patients suggesting the existence of presently unknown antigenic targets. Considering a group of 19 patients with a high probability of HIT, we have found antibodies against IL-8 or NAP-2 in only 7 patients. The discrepancy between a HPIA positive and a PAT negative encountered in 8% of patients may be explained by the existence of IgA or IgM immunoglobulins since in contrast to IgG they are unable to promote platelet aggregation via the CD32 platelet membrane receptor. This work suggests than neither test is 100% reliable and that they play a complementary role in the diagnosis of HIT. The potential advantage of using both tests should be confirmed in complementary studies

Aged↗
PubMed1997

[Multigenic thrombophilia: genetic anomaly of factor II and mutation of factor V Leiden. Study in a French family].

BACKGROUND: A genetic variation of the prothrombin (factor II) gene, a G to A transition at nucleotide position 20210, was recently found in patients with familial thrombophilia (predisposition to venous thrombosis). It seems to be frequent in patients with the factor V Leiden mutation. We report a family with the factor V Leiden and/or the genetic variation of prothrombin in 3 members. CASE REPORT: The patient had repeated episodes of deep vein thromboses starting at the age of 30 during the 4th pregnancy. She is a heterozygous carrier of both the factor V Leiden nutation and the prothrombin mutation 20210 A. She has 4 asymptomatic children, aged 28 to 32 and 3 of them have been explored: one son has the prothrombin mutation, one daughter the factor V Leiden and one has none of them. DISCUSSION: This case report illustrates the polygenic nature of thrombophilia which may explain the heterogeneity of clinical expression observed in isolated congenital abnormalities, especially in factor V Leiden mutation.

Chromosome Aberrations↗
PubMed1997

Leiden factor V mutation in four patients with small bowel infarctions.

The Leiden factor V mutation is observed in 20% of unexplained lower limb venous thromboses and involves substitution of the arginine residue at position 506 by glutamine (R506Q). It is known to decrease the anticoagulant activity of activated protein C. This case report describes 4 cases of small bowel infarction (SBI) associated with the presence of this mutation. Two cases of arterial and 2 cases of venous SBI were observed. Extensive assessment excluded the usual causes of SBI and plasma hypercoagulation syndrome (antithrombin III, protein C, and protein S deficiency and myeloproliferative syndrome). An abnormal resistance to activated protein C was observed. Molecular analysis consisting of polymerase chain reaction amplification and digestion with MnlI showed that 2 patients were heterozygous and 2 were homozygous for the R506Q mutation. Despite familial history of thrombosis in only 1 patient, first- and second-degree relatives of 2 patients also had the presence of the mutation. Examination for the presence of abnormal resistance to activated protein C should be part of the etiological assessment of SBI. Its presence may warrant consideration of long-term anticoagulant therapy, especially for patients with shortened small bowel who are treated by home parenteral nutrition with deep venous access.

Adult↗
PubMed1997

[Severe hemorrhagic complications during treatment with low molecular weight heparin. Apropos of 2 cases].

Two cases of fatal bleeding in patients treated with low molecular weight heparin for deep vein thrombosis are reported. Risk factors for bleeding were: severe underlying disease (cancer in one case, morbid obesity and cardiac failure in the other), age over 80 years and worsening of renal insufficiency in both cases, recent surgical procedure in one case. Anti-Xa activity was beyond the therapeutic range at the time of bleeding in both cases. The usefulness of biologically monitoring the treatment of deep vein thrombosis with low molecular weight heparin is discussed.

Aged↗
PubMed1997

[Value of plasma D-dimer assays in the diagnosis of venous thromboembolism].

The diagnostic usefulness of measuring plasma D-dimers using the ELISA method and the latex agglutination test has been prospectively evaluated in 117 patients hospitalized for suspicion of acute venous thrombo-embolism (AVTE): pulmonary embolism was suspected in 80 patients and the remaining 37 had a suspicion of deep vein thrombosis of the lower limbs. The diagnosis of AVTE was confirmed in 50% of the patients, all of whom underwent gold standard invasive investigation i.e. pulmonary angiography and/or contrast venography. The sensitivity, specificity, negative predictive value and positive predictive value of a D-dimers plasma concentration exceeding 500 ng/ml for the diagnosis of AVTE were respectively 98, 58, 97 and 70% when using the ELISA method, and 86, 71, 84 and 75% when using the latex assay. In 47 patients whose lung scans yielded abnormalities of indeterminate probability of pulmonary embolism, the sensitivity of the ELISA method was very high (94%), but that of latex assay was low (67%). Our results demonstrate that measuring the plasma D-dimers by the latex assay should not be used in the diagnosis of AVTE. On the other hand, the ELISA method might be of great interest in the diagnostic strategy of AVTE, as a normal concentration of D-dimers rules out almost definitely the diagnosis of AVTE, and hence, spares from performing invasive investigations.

Acute Disease↗
PubMed1997

[Comparison of two groups of 22 women homozygous or heterozygous for factor V Leiden mutation].

Clinical characteristics of thrombophilia associated with heterozygous mutation of factor V are well characterized. In contrast, they are not well documented in homozygous subjects who are rare. Moreover, estroprogestative intake and pregnancy are important precipitating factors of venous thromboembolism in women with factor V mutation. In order to determine difference in clinical expression between homo and heterozygous subjects, two groups of 22 age matched women were compared. A modified technique for the diagnosis of activated protein C resistance has been used, and its great specificity and sensitivity has been confirmed. In these two small series of patients, a greater severity of clinical profile was not clearly evident. However, recurrences and thrombosis during pregnancy were more frequent in homozygous than in heterozygous women. However, the differences did not reach significance. Molecular markers of hypercoagulable states were not regularly increased even in homozygous untreated patients, but they were more often increased in untreated than in treated patients. In contrast, to other varieties of thrombophilia, homozygous mutation of factor V may be associated with a minor clinical severity suggesting the role of environmental factors and/or still unknown molecular alterations.

Factor V↗
PubMed1996

[Value of an extensive biological study in venous or arterial thromboses].

OBJECTIVES: The aim of this work is to study the signification of an extensive biological evaluation in patients with "unexplained" thrombosis. We studied 78 patients with more than one arterial and/or venous thromboembolic event. METHODS: Fifty-four patients were admitted for unexplained deep venous thrombosis (group I, n = 19, 9 men and 10 women) and/or arterial thrombosis (group II, n = 35, 21 men and 14 women). A third group (group III) included 24 patients (13 men, 11 women) known to have a pathologic state which can lead to a thrombotic event. RESULTS: The patients in both groups I and II had, more often than normal subjects, a high level of homocysteinemia (26% vs 3%, p < 0.001), anti-beta 2 glycoprotein 1 (18.5% vs 3%, p < 0.001) and antiphospholipid antibodies (13% vs 3%, p < 0.02). We also found a significant association between an increase of erythrocytic aggregation and arterial thrombosis (group II). In the third group, for both arterial (n = 14) and venous (n = 10) thrombosis, we found a high level of anticardiolipin antibodies (25% vs 3%, p < 0.001), anti-beta 2 glycoprotein 1 antibodies (12.5% vs 3%, p < 0.05) and abnormal erythrocytic aggregation (16.5% vs 3%, p < 0.01). In these 3 groups the other studied parameters (Lp(a), platelet aggregation, cryoglobulin, cryofibrinogen, antinuclear antibodies, anticytoplasm antibodies, plasma and urine immunoelectrophoresis, protein C, protein S, antithrombin III, plasminogen) were not different from levels observed in normal subjects. CONCLUSION: An extensive biological analysis, including plasma homocystein level, anticardiolipin antibodies, anti-beta 2 glycoprotein 1 antibodies and a study of the erythrocytic aggregation would appear to be of value in patients presenting recurrent arterial or venous thromboembolic events. Specific therapy can be applied in case of abnormal results continued anticoagulant therapy for anticardiolipin and anti-beta 2 glycoprotein 1 antibodies, and a vitamin therapy for increased homocysteinemia.

Adolescent↗
PubMed1996

Diagnosis and clinical characteristics of inherited activated protein C resistance.

The diagnostic strategies and clinical characteristics of thrombophilia associated with heterozygous or homozygous factor V Leiden mutation have been determined according to the literature and to a personal study in 51 families. Factor V mutation was present in the 51 propositi and in 84 out of 125 family members (81 heterozygous, 3 homozygous). Venous thrombosis was observed in all the propositi, in 17 of the 84 family members with the mutation and in 6 of the 41 with a normal APC resistance test and no mutation. An associated protein C or protein S deficiency was present in 5 families (10%). The most frequent clinical manifestations were superficial or deep vein thrombosis and/or pulmonary embolism, but also thrombosis at an unusual site (cerebral, mesenteric or central retinal vein). A causal relationship is frequently difficult to demonstrate. A precipitating factor was observed in 84% of cases and a recurrent thrombotic episode occurred in 50% of propositi. The risk of thrombosis associated with pregnancy was high in the post-partum period, especially in homozygous women. In the 28 homozygous subjects, markers of coagulation activation were frequently elevated in untreated patients. Finally, the efficacy of anticoagulant treatment is suggested but the long period often observed between treatment interruption and a recurrence does not militate in favour of long term treatment.

Anticoagulants↗
PubMed1996

Coagulation studies, factor V Leiden, and anticardiolipin antibodies in 40 cases of cerebral venous thrombosis.

BACKGROUND AND PURPOSE: Cerebral venous thrombosis (CVT) is an infrequent condition with a large variety of causes. However, in 20% to 35% of cases, no cause is found. We studied coagulation parameters, including activated protein C resistance associated with factor V gene mutation (factor V Leiden) and anticardiolipin antibodies, in a large series of patients with CVT with or without identified cause or risk factor. METHODS: Forty patients (30 women and 10 men) aged 19 to 71 years (mean age, 36.2 years) with CVT diagnosed by angiography and/or MRI were studied 1 to 18 years after thrombosis. No known cause was found in 10 idiopathic cases. Coagulation studies included the following tests: fibrinogen, antithrombin, protein C, protein S, plasminogen, anticardiolipin antibodies, activated protein C resistance, and factor V Leiden. RESULTS: Six cases of thrombophilia (15%) were found: 1 protein C deficiency, 1 protein S deficiency, and 4 activated protein C resistance with heterozygous factor V Leiden mutation (10%). Only 1 case (protein S deficiency) was found in the group of 10 patients with idiopathic CVT. In the other 5, there was another cause or risk factor. Three patients (8%) had increased anticardiolipin antibodies: 1 with systemic lupus and 2 with primary antiphospholipid syndrome; 2 of these 3 patients also had factor V Leiden mutation. CONCLUSIONS: Although present in a number of CVT cases, acquired (anticardiolipin) or congenital varieties of thrombophilia (factor V Leiden being the most frequent) are almost invariably associated with other predisposing factors. This suggests that (1) these abnormalities should be looked for in patients with CVT, whether a cause is found or not, and (2) their presence should not deter the search for other potential causes. The detection of such abnormalities has major practical consequences on the long-term management of patients to prevent further thrombotic episodes.

Adult↗
PubMed1995

[Resistance to activated protein C in venous thromboembolic complications. Incidence and clinical manifestations].

OBJECTIVES: The frequency of activated protein C resistance is not well established for patients with venous thromboembolic disease. We studied resistance to activated protein C in patients with a past history of deep vein or superficial vein thrombosis. METHODS: Activated protein C resistance was measured in 175 patients (37 males, 138 females; mean age 40.9 +/- 13.8 years; range 15-77) who had suffered a venous thromboembolic event more than one month earlier. Exclusion criteria were malignancy, known autoimmune disease or known coagulopathy. A control population of 50 healthy subjects were also tested to establish a normal lower limit (mean ratio minus 2 SD). RESULTS: The lower limit was established at 2.14. According to this definition, there were 29 thromboembolic patients who were resistant to activated C protein (17%). Two of the subjects considered healthy in the control group were also resistant (4%). There was no difference for age or sex between resistant and non-resistant subjects. Comparing our findings with those reported in the literature confirmed that 3 to 5% of healthy subjects and 15 to 25% of patients with history of venous thromboembolism are resistant to activated C protein. CONCLUSION: Resistance to activated C protein thus appears as a risk factor for thrombotic events which is comparatively more frequent than other causes of thrombotic disease.

Adolescent↗
PubMed1995

Central retinal vein thrombosis associated with resistance to activated protein C.

PURPOSE/METHODS: Activated protein C resistance was recently described as a major cause of venous thrombosis. We observed a central retinal vein thrombosis in a woman with activated protein C resistance. RESULTS/CONCLUSION: DNA analysis showed the patient to be heterozygous for the factor V gene mutation, which is related to activated protein C resistance. Patients with retinal vein thrombosis should be examined for activated protein C resistance.

DNA Mutational Analysis↗