The Decision Process in the Laboratory Diagnosis and Management of Bleeding and Clotting Disorders
Harold R. Schumacher, William A. Rock, Sanford A. Stass in Handbook of Hematologic Pathology, 2019
2. Are the abnormalities significant in that they can predict or result in clotting or bleeding? Certainly, a platelet count of 10,000 mm3 can pose an increased risk for spontaneous bleeding, but what about 25,000 mm3, 45,000 mm3, 80,000 mm3, or 120,000 mm3? The unique circumstances of the patient must be reviewed in concert with experience, the experience of others, and recommendations from the literature. What about an aPTT of 45 sec versus 55 sec versus 70 sec? Which will more likely bleed? This depends on why the aPTT is prolonged: Heparin? Factor VIII deficiency? Factor XII deficiency? A combination of factor deficiencies? Inhibitor? Factor VIII inhibitor? Lupus anticoagulant? The point is that a prolonged aPTT has no value unless you have an idea as to why it is prolonged. Degree of prolongation will mean different effects in different patients depending on one or multiple diseases, medications, and on and on. Take the time to learn the uniqueness of each patient, and understand how the patient’s coagulation system is responding to his or her disease, and what intervention has accomplished with the disease process as well as the patient’s coagulation system. These concepts may seem somewhat lofty, but to have any real impact on what is affecting the patient, you must know the patient.
Treatment of Anti-Phospholipid Antibody Mediated Fetal Loss: The Case for Corticosteroid Therapy
E. Nigel Harris, Thomas Exner, Graham R. V. Hughes, Ronald A. Asherson in Phospholipid-Binding Antibodies, 2020
Lupus anticoagulant can be detected by any phospholipid-dependent coagulation test, but there is poor correlation among the tests with marked variation in specificity and sensitivity. Our initial experience with the kaolin clotting time (KCT) and activated partial thromboplastin time APTT(Dade) confirmed this observation (Figure 1). The assays are not equally suitable for monitoring lupus anticoagulant activity or responsiveness to corticosteroid treatment. Six coagulation assays including APTT(GD), APTT(FSL), dilute Russell’s viper venom time (DRVVT) and KCT were performed in a consecutive series of patients who presented to the Auckland Hospital Rheumatology Clinic with a known history of SLE. One or more coagulation assays was prolonged in 41% of patients. APTT(FSL) detected 73% of these abnormal patients, the KCT 44% and the anti-cardiolipin antibodies assay 29%.37Agreement on the definition of patients with lupus anticoagulant has not been reached. The KAPS Working Party on aPL antibodies hopefully will achieve this. At present it is our practice to perform the KCT, APTT (FSL), DRVVT and anti-cardiolipin assay in all women with a suggestive history of aPL antibody-mediated fetal loss.
Acquired Circulating Anticoagulants And Defective Hemostasis In Malignant Paraprotein Disorders
Genesio Murano, Rodger L. Bick in Basic Concepts of Hemostasis and Thrombosis, 2019
Acquired inhibitors to blood coagulation factors have been described in several autoimmune disorders, most commonly systemic lupus erythematosus (SLE). A specific “lupus anticoagulant” has been identified and may precede the disease by several years. The presence of lupus anticoagulant is characterized by a prolonged partial thromboplastin time (PTT), a prolonged prothrombin time, prolongation of the PTT done on a mixture of normal plasma plus patients’ plasma, and a normal thrombin time and bleeding time.22 It remains unclear as to where this anticoagulant functions in the clotting sequence. Most of the evidence suggests that the activity is directed against prothrombin or a combination of the prothrombin complex factors. The inhibitor appears in approximately 6% of patients with SLE, and in many there is an associated deficiency of prothrombin. In those cases studied, the anticoagulant does not lead to a significant bleeding diathesis unless other associated coagulation defects are also present. Inhibitory activity correlates closely with disease activity and responds to immunosuppressive therapy. Other specific inhibitors to coagulation factors may also develop in SLE or any other of the collagen vascular diseases. The factors most commonly effected are Factors VIII, IX, XI, and XIII, as previously discussed.
The significance of thrombophilia in paediatric thromboembolism
Published in Scandinavian Journal of Clinical and Laboratory Investigation, 2018
Sofie Sommer Hedegaard, Anna Christina Klein, Anne-Mette Hvas
To estimate the association between presence of thrombophilia and thromboembolic risk we used several publications including thrombophilia data in big Western populations. We compared the risk associated with factor V Leiden with the risk found by Sode et al. who included 66,000 healthy white Danish people from 1977–2010 [8]. We compared the risk of antithrombin deficiency and venous thrombosis with the prevalence in a general population in a cohort of 9669 blood donors [9] and found a substantial and significantly increased OR. The prevalence of lupus anticoagulant was compared with the prevalence of lupus anticoagulant found in 628 healthy young Dutch females in the study by Urbanus et al., [13] who measured lupus anticoagulant by a dilute Russel’s Viper Venom Time (dRVVT) assay like in the present study. As the present study population was considerably younger than the study population included by Urbanus et al, the prevalence of lupus anticoagulant was expected to be lower in our study. However, we found a significant OR at 14.8, which might be explained by the fact that two of the three children with high level of lupus anticoagulant were female at the age of 15 years, thus comparable to adults.
An update on VEXAS syndrome
Published in Expert Review of Clinical Immunology, 2023
The underlying pathogenesis of thrombosis in VEXAS remains unclear. Thrombosis in conditions of chronic inflammation is a recognised phenomenon and likely to arise from myriad dysregulated pathways, including the inappropriate formation of fibrin (attaching thrombi to the vessel walls), or reduced synthesis and increased consumption of the natural anticoagulant, protein C [58–60]. Though the number of patients analysed is small, there is limited evidence that a proportion of those with VEXAS have elevated factor VIII activity, positively associated with increased CRP [29]. In an analysis of 16 patients, Obiorah et al. showed a high incidence of isolated or persistent lupus anticoagulant (LA) positivity at 69% (11/16) and 44% (7/16), respectively. Five of those with persistent LA positivity suffered a thrombotic event, whilst two of five patients who were LA negative also developed one, indicating the presence of multiple prothrombotic mechanisms at play with the disease.
Clinical feature and anti-phospholipid antibody profiles of pregnancy failure in young women with antiphospholipid antibody syndrome treated with conventional therapy
Published in Modern Rheumatology, 2018
Kayoko Kaneko, Shuko Mishima, Mikako Goto, Mari Mitsui, Shinji Tanigaki, Kenji Oku, Nobuaki Ozawa, Eisuke Inoue, Tatsuya Atsumi, Haruhiko Sago, Atsuko Murashima
Lupus anticoagulant is known to be a risk factor for APS-associated obstetric complications in patients with SLE and in those who are positive for aPL [15]. Ruffatti et al. [9] performed a retrospective case control study with 57 patients each in successful and unsuccessful pregnancy groups; all patients received conventional treatment. They found that (a) the presence of SLE or other auto-immune diseases, (b) having a history of both thrombosis and obstetric complications, and (c) being positive for three types of antiphospholipid antibodies (LA, aCL, and anti-β2GP1 antibodies) were independent risk factors for refractory aPL-associated pregnancy failure. However, they could not demonstrate that anti-PS/PT-IgG was associated with pregnancy failure in APS patients received conventional therapy.
Related Knowledge Centers
- Antibody
- Coagulation
- In Vitro
- In Vivo
- Kidney Failure
- Partial Thromboplastin Time
- Phospholipid
- Protein
- Thrombosis
- Lupus Erythematosus