Acquired Activated Protein C-Resistance in Patients with Lupus Anticoagulants

Ehrenforth, S.; Radtke, Klaus-Peter; Scharrer, I.

doi:10.1055/s-0038-1649818

Cited by 59 publications

(35 citation statements)

References 6 publications

(6 reference statements)

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“…However, factor V Leiden mutation has not been reported in Japan up to now. Acquired APC-R, a phenotypic APC-R that occurs in the absence of the factor V Leiden mutation, has been reported in patients with defined APS (Ehrenforth et al, 1995;Martinuzzo et al, 1996;Ruiz-Arguelles et al, 1996;Aznar et al, 1997;Picillo et al, 1998;Male et al, 2001), in patients with VTE (Zivelin et al, 1999;Haim et al, 2001), in pregnancy (Cumming et al, 1995) and in individuals using oral contraceptives (Henkens et al, 1995;Rosing et al, 1997). However, the mechanism by which acquired APC-R is generated in these conditions has not been elucidated.…”

Section: Discussionmentioning

confidence: 99%

Acquired activated protein C resistance is associated with the co‐existence of anti‐prothrombin antibodies and lupus anticoagulant activity in patients with systemic lupus erythematosus

et al. 2002

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Summary. Venous thromboembolism (VTE) is one of the common manifestations in the anti-phospholipid (aPL) syndrome. We examined the levels of IgG antibodies (Abs) to b2-glycoprotein I (b2-GP I) and prothrombin, lupus anticoagulant (LA) activity, activated protein C resistance (APC-R), and factor V Leiden in 96 patients with systemic lupus erythematosus (SLE); 19 with VTE and 77 without VTE. Acquired APC-R, which was not found in any patient with the factor V Leiden mutation, was present in 33 (34AE4%) out of the 96 patients with SLE. The presence of acquired APC-R was a strong risk factor for VTE. The SLE patients were divided into four groups according to the results of enzyme-linked immunosorbent assay (ELISA) and LA activity for each observed between APC-R and the co-existence of anti-b2-GP I Abs and LA activity or of anti-prothrombin Abs and LA activity. There was no association between APC-R and the presence of anti-b2-GP I Abs, anti-prothrombin Abs, or LA activity alone. However, when multivariate logistical regression analysis was performed, it was clear that only the co-existence of anti-prothrombin and LA activity was a significant risk factor for APC-R. These findings indicate that the co-existence of anti-prothrombin Abs and LA activity may be an important factor in the pathogenesis of acquired APC-R in patients with SLE.

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Section: Discussionmentioning

confidence: 99%

Acquired activated protein C resistance is associated with the co‐existence of anti‐prothrombin antibodies and lupus anticoagulant activity in patients with systemic lupus erythematosus

et al. 2002

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“…However, there are other reasons for an abnormal aPC-SR, such as heparin, the lupus anticoagulant [18,19], oral anticoagulant therapy [20] and vitamin K deficiency [13]. These are suspected if the patients' baseline aPTT is prolonged.…”

Section: Discussionmentioning

confidence: 99%

Activated-Protein-C Resistance in Cancer Patients

Maliekel¹,

Sushko²,

Akhtar³

et al. 1997

Pathophysiol Haemos Thromb

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Background: Resistance to activated protein C (aPC) is usually linked to factor V Leiden, but may occur in other disorders associated with hypercoagulability. In this study, we investigated the frequency of resistance to aPC in patients with advanced cancer and examined the relationship of aPC resistance to other markers of coagulation activation. Methods: Patients (n = 39) had an established diagnosis of advanced cancer; controls (n = 20) were healthy persons. aPC resistance was measured as the ratio of activated partial thromboplastin times with and without aPC (aPC-sensitivity ratio, aPC-SR). The factor V Leiden mutation was detected by a polymerase-chain-reaction based technique. Other assays were performed by standard laboratory methods. Data were analyzed using t tests and the Pearson correlation. Results: aPC-SR was below 2 SD for 5 of the cancer patients (13%), but none of the controls; only 1 of the 5 had the factor V Leiden mutation. aPC-SR was inversely correlated (p < 0.01) with factor VIII and fibrinogen in patients and with prothrombin activation fragment 1.2 (F1.2) in controls. Patient factor VIII, von Willebrand factor, (vWF), fibrinogen, F1.2 and D dimer were all significantly increased (p < 0.01); antithrombin III, protein C and proteins were similar to controls. Factor VIII correlated with vWF (p < 0.001) and F1.2 with d-dimer (p < 0.001). Other associations (p < 0.05) were observed between factor V and protein C, fibrinogen and protein C, factor V and antithrombin III and protein C and antithrombin III. Four cancer patients had a history of thromboembolism; their aPC-SR was similar to that of patients without thrombosis. Of the several coagulation measures examined, only vWF was higher in the patients with thrombosis (p = 0.01). Interpretation: Cancer patients have evidence of intravascular coagulation and increases in procoagulants and may have aPC resistance. The aPC resistance is not due to factor V Leiden, but is rather associated with elevated levels of factor VIII and fibrinogen, and in itself does not predict thrombosis.

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“…The original test is sensitive to the presence of residual platelets in samples that have been frozen and thawed causing a reduction in the ratio [108,109]. The aPTT-based assay is affected by some acquired clinical conditions, such as inflammatory syndrome, lupus anticoagulant or antiphospholipid syndrome, pregnancy, oral contraceptives or hormonal replacement therapy [119][120][121]. It may also be affected by factor VIII levels, low levels of PS, FV, factor IX and X or by heparin or coumarin treatment [122,123].…”

Section: Measurement In Oral-anticoagulanttreated Patientsmentioning

confidence: 99%

Clinical Aspects and Laboratory Problems in Hereditary Thrombophilia

Samama

Gerotziafas²,

Conard³

et al. 1999

Pathophysiol Haemos Thromb

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Hereditary thrombophilia is a multifactorial disease which is mono- or plurigenic and its clinical expression is associated with a heterogeneous expression. Factor V (FV) Leiden and FII gene mutations are more frequent than antithrombin, and protein C and S deficiencies. All thrombophilias are not the same. Heterozygous carriers of FV Leiden or FII gene mutation have a weaker risk of venous thrombosis. The mean age at the first episode is older in the former and higher rate of recurrences is observed in the latter. The cosegregation of mutations significantly increases the risk of thrombosis. Both mutations have a geographic and ethnic distribution in relation with a gene founder effect. Clinical expression consists of deep or superficial venous thrombosis with or without pulmonary embolism, thromboses at unusual sites (e.g. cerebral, portal, mesenteric) or with an increased incidence of fetal loss and abortion. A precipitating cause is present in more than 50% of patients. The risk pf arterial thromboses seems to be restricted to some protein S and FII gene mutations. Laboratory diagnosis strategy should be oriented by careful selection of patients and preanalytical variables should be considered. It is highly probable that other unindentified gene mutations are, at least partly, other causes of the heterogeneous expression of hereditary thrombophilia.

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Acquired Activated Protein C-Resistance in Patients with Lupus Anticoagulants

Abstract: 6. Dahlbiick H, Carlsson M, Svcnsson I'J. Familial thrombophilia due to a pre viously unrecognized mechanism characterized by poor anticoagulant res ponse to activated protein (': Prediction of a cofactor to activated protein ('.

Cited by 59 publications

References 6 publications

Acquired activated protein C resistance is associated with the co‐existence of anti‐prothrombin antibodies and lupus anticoagulant activity in patients with systemic lupus erythematosus

Acquired activated protein C resistance is associated with the co‐existence of anti‐prothrombin antibodies and lupus anticoagulant activity in patients with systemic lupus erythematosus

Activated-Protein-C Resistance in Cancer Patients

Clinical Aspects and Laboratory Problems in Hereditary Thrombophilia

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