Anticardiolipin Antibody Immunoglobulin Research Articles

Catastrophic antiphospholipid syndrome presented with coronary thrombosis, renal impairment, and suspected diffuse alveolar hemorrhage treated with rituximab biosimilar (CT-P10)

Catastrophic antiphospholipid syndrome (CAPS) is a lethal disease that occurs suddenly and progresses to multi-organ failure. We present a case of CAPS successfully treated with the rituximab biosimilar CT-P10. A 38-year-old man was referred with a sustained fever and unexplained elevated creatinine levels. Cardiac arrest by ventricular fibrillation occurred upon arrival at the hospital. We diagnosed probable CAPS because of coronary thrombus, renal impairment, suspected diffuse alveolar hemorrhage, and positive anticardiolipin antibody immunoglobulin G. We performed percutaneous coronary intervention for the cardiac arrest, and treated him with extracorporeal membrane oxygenation, mechanical ventilation, and continuous renal replacement therapy. When CAPS was diagnosed, we administered CT-P10 after administering high-dose glucocorticoid. Our case suggests that the use of a rituximab biosimilar is economically efficient in the treatment of CAPS, as in other rheumatic diseases. The patient was cured without recurrence at the 2-year follow-up.

The association between the levels of autoimmune related indicators and clinical condition in sudden deafness patients

This study aimed to analyze the abnormal rates of immune related factors in serum of sudden deafness (SD) patients, and to discuss the correlation between these indicators and the degree of pathological changes of SD patients. From March 2018 to January 2021, 90 patients with SD who were hospitalized in Beijing Tsinghua Changgeng Hospital were enrolled as participants, and 60 healthy examinees served as the control group. Antinuclear antibody (ANA), anticardiolipin antibody immunoglobulin G (ACA-IgG), anticardiolipin antibody immunoglobulin M (ACA-IgM), and anti-β-glucoprotein (anti-β-GP) antibody were detected by enzyme-linked immunosorbent assay (ELISA). In the SD group, 43 participants were positive for ANA, while in the control group, only 9 participants were positive for ANA. The titer of antibodies was significantly higher in the SD group than in the control group. The differences in abnormal rates of ACA-IgG, ACA-IgM, and anti-β-GP antibodies between the SD group and control group were not statistically significant (P>0.05). The pathogenesis of SD is correlated with autoimmune factors to a certain extent. In the course of clinical treatment, in addition to vasodilation, neurotrophic therapy, and thrombolytic therapy, patients can also be approached from the perspective of autoimmunity, which may achieve more ideal treatment effects.

Risk factors of pulmonary arterial hypertension in patients with systemic lupus erythematosus.

Pulmonary arterial hypertension symptoms in systemic lupus erythematosus patients are non-specific and early diagnosis and intervention are challenging. It remains essential to explore risk factors for pulmonary arterial hypertension in systemic lupus erythematosus patients to identify high risk patients and allow intensive monitoring. From January 2010 to December 2018, 84 patients with systemic lupus erythematosus and pulmonary arterial hypertension and 160 patients with systemic lupus erythematosus but without pulmonary arterial hypertension were enrolled. Clinical manifestations and laboratory test results were compared between the two groups to identify predictors of pulmonary arterial hypertension. Candidate pulmonary arterial hypertension risk factors were further compared among systemic lupus erythematosus-pulmonary arterial hypertension patients with different characteristics. Among collected patient characteristics, Raynaud's phenomenon (OR 2.32, 95% CI: 1.17-4.61), digital vasculitis (OR 4.12, 95% CI: 1.48-11.49), pericardial effusion, pulmonary interstitial lesions, positive anti-u1 ribonucleoprotein antibodies, and positive anticardiolipin antibodies immunoglobulin G were associated with significantly higher risk of pulmonary arterial hypertension in systemic lupus erythematosus patients. Among these candidate risk factors, positive anti-u1 ribonucleoprotein antibody was independently associated with severe pulmonary arterial hypertension and more active disease. Digital vasculitis was independently associated with systemic lupus erythematosus alleviation, while pericardial effusion was associated with systemic lupus erythematosus deterioration. Pericardial effusion was associated with longer pulmonary arterial hypertension duration. The significant association between studied clinical and laboratory indicators and risk of pulmonary arterial hypertension, pulmonary arterial hypertension and systemic lupus erythematosus characteristics suggested that these factors can be used to identify patients at higher risk of pulmonary arterial hypertension and adverse outcomes. Close monitoring may be indicated in patients with these risk factors, especially with more than one risk factor.

T786C Mutation in the Endothelial Nitric Oxide Synthase Gene in Patients With Primary Osteonecrosis.

Mutations in the T786C endothelial nitric oxide synthase gene (eNOS) are associated with osteonecrosis and Prinzmetal's angina. Nitric oxide is necessary for bone health and ameliorates Prinzmetal's angina. This study compared mutations of T786C eNOS in 146 patients with primary osteonecrosis, 114 patients with Prinzmetal's angina, and 83 normal control subjects. Patients with osteonecrosis had more mutant eNOS alleles than control subjects (42% vs 22%, respectively; P<.0001) but had the same number of mutant alleles as patients with Prinzmetal's angina (42% vs 41%, respectively; P=.7), who in turn had more mutant eNOS alleles than control subjects (41% vs 22%, respectively; P=.0001). Of 146 patients with primary osteonecrosis, 65 (45%) had none of the 5 thrombophilias (Factor V Leiden heterozygosity, high levels of Factors VIII and XI, anticardiolipin antibody immunoglobulin M, and homocysteine) that otherwise distinguished patients with osteonecrosis from control subjects (P<.05). No associations were found between eNOS hetero-homozygosity and the 5 major thrombophilias in primary osteonecrosis. Of the 65 patients who had osteonecrosis but no major thrombophilias, for 41 (28% of the total sample of 146), eNOS hetero-homozygosity was the only abnormality. Normalization of nitric oxide levels with l-arginine 9 g/d or l-citrulline 800 mg/d, both of which relieve vasospastic angina in Prinzmetal's angina, which has the same eNOS genotype as primary osteonecrosis, may slow or stop the progression of osteonecrosis. Placebo-controlled trials of patients with primary osteonecrosis who are hetero-homozygous for the T786C eNOS mutation and have no major thrombophilias are needed to assess the safety and efficacy of this treatment. [Orthopedics. 2017; 40(5):e898-e903.].

STUDY THE ROLE OF HEPATITIS C VIRUS INFECTION IN PATIENTS WITH CEREBRAL INFARCTION

Background: Chronic hepatitis C virus (HCV) infection has been linked to numerous co-existing conditions including metabolic abnormalities and cardiovascular disease. Stroke is a major public health crisis world-wide. About 87% of strokes are ischemic. Between 25- 40% of ischemic stroke may be cryptogenic. HCV infection is associated with a wide spectrum of extra-hepatic manifestations, affecting different organ systems. Neurological complications occur in a large number of patients and range from peripheral neuropathy to cognitive impairment and/or cerebral infarctions (CI). Objective: Studying the role of HCV infection in patients having CI. Patients and Methods: After departmental ethics committee approval and patient consents were obtained, 60patients included in this work: 20 patients having CI and chronic hepatitis C (CHC), 20 patients having CI without CHC, and 20 patients having CHC without CI. All patients were subjected to history taking and clinical examination, complete blood count (CBC), evaluation of HCV antibodies, polymerase chain reaction (PCR) for HCV ribonucleic acid (RNA), hepatitis B surface antigen (HBs-Ag), liver function tests, renal function tests, lipid profile, antinuclear antibody (ANA), anticardiolipin antibodies immunoglobulin G (ACL-IgG), antineutrophil cytoplasmic antibodies (ANCA), cryoglobulin, fasting plasma glucose (FPG) and post-prandial plasma glucose (PPPG). In addition, ultrasound (U/S) abdomen, magnetic resonance imaging (MRI) brain, doppler study of the carotid arteries and echocardiography. Results: Group A (CI and CHC) patients were significantly younger and females were predominant in these patients than those of either group B (CI without CHC) or C (CHC without CI) .Group B patients were significantly overweighed compared to group A or C. Total cholesterol (TC), triglyceride (TG), FPG and low density lipoprotein (LDL) significantly decreased in group A and C compared with group B .Patients of group A showed significantly higher positive of HCV viremia, cryoglobulins, ANA, c-ANCA and ACL-IgG, compared with group C, while those of group B were negative for same parameters. Carotid atherosclerosis and ischemic heart disease (IHD) were significantly higher in patients of group A, compared with group (B and C), respectively. Conclusion: Chronic HCV infection is a risk factor in development of CI by multiple mechanisms including atherosclerosis, thromboembolism and vasculitis. Also, it increases stroke risk and might be considered as an important and independent risk factor.

Retinal vascular occlusion: a window to diagnosis of familial and acquired thrombophilia and hypofibrinolysis, with important ramifications for pregnancy outcomes.

AimOur specific aim was to document the pathoetiologic importance of thrombophilia among females presenting with severe ischemic retinal vein (RVO) or retinal artery (RAO) occlusion, without typical risk factors, and to emphasize that the ophthalmologists’ diagnosis of thrombophilia has important diagnostic and therapeutic downstream ramifications for nonocular thrombosis, including reproductive outcomes.MethodsWe evaluated familial and acquired thrombophilia in 60 females with RVO (central RVO, n=52; branch RVO, n=8) and 16 with RAO (central RAO, n=11; branch RAO, n=5). They were referred by retinologists, without typical risk factors for RVO/RAO and/or severe ocular ischemic presentation. We focused on extraocular thrombotic events, particularly pregnancy complications, including unexplained spontaneous abortion, pre-eclampsia–eclampsia. Thrombophilia measurements in the 76 females were compared with 62 healthy normal females without ocular vascular occlusions (OVOs).ResultsThe 76 females with OVO were more likely than 62 normal female controls to have high homocysteine (24% vs 0%, P<0.0001), high anticardiolipin antibody (immunoglobulin M, 17% vs 3%, P=0.012), high (>150%) factor VIII (42% vs 11%, P<0.0001), and high (>150%) factor XI (22% vs 4%, P=0.004). Of the 76 females, 26 (34%) had ≥1 spontaneous abortion; 17 (22%) had ≥2 spontaneous abortions and/or pre-eclampsia–eclampsia. Compared to 62 healthy female controls, these 17 females with pregnancy complications had high homocysteine (29% vs 0%, P=0.0003), high anticardiolipin antibody immunoglobulin M (24% vs 3%, P=0.02), high factor VIII (38% vs 11%, P=0.02), and were marginally more likely to be heterozygous for the factor V Leiden mutation (19% vs 3%, P=0.058).ConclusionIn females lacking typical risk factors for retinal vascular occlusion or severely ischemic presentation, by diagnosing thrombophilia as an etiology for OVO, the ophthalmologist opens a window to family screening and preventive therapy, with particular relevance to pregnancy outcomes and venous thromboembolism.

Testosterone Therapy Can Interact With Thrombophilia, Leading to Osteonecrosis.

Although this effect is not widely recognized, testosterone therapy can interact with thrombophilia, causing osteonecrosis. In 12 men and 4 women who had idiopathic osteonecrosis a median of 6 months after the onset of testosterone therapy, the authors examined the interaction between testosterone therapy and previously undiagnosed thrombophilia. The authors hypothesized that patients who had osteonecrosis after starting testosterone therapy were more likely than 110 normal control subjects or 48 patients who had osteonecrosis and were not receiving testosterone therapy to have thrombophilia. Measures of thrombophilia included Factor V Leiden, prothrombin, PAI-1 gene mutations, Factor VIII, Factor XI, anticardiolipin antibody immunoglobulin G or immunoglobulin M, and homocysteine values. In 10 cases, osteonecrosis occurred 6 months or less after the onset of testosterone therapy, and in all 16 cases, it occurred after a median of 6 months of testosterone therapy. Of the 16 cases, 5 (31%) were Factor V Leiden heterozygotes vs 2 of 109 (2%) healthy control subjects (P=.0003) and 4 of 48 patients who had osteonecrosis and were not receiving testosterone therapy (P=.04). Of the 16 cases, 4 (25%) had high (>150%) Factor VIII levels vs 7 of 103 (7%) healthy control subjects (P=.04), and 3 (19%) had high (>150%) Factor XI levels vs 3 of 101 (3%) healthy control subjects (P=.03). Of the 16 patients with osteonecrosis, 14 (88%) had at least 1 abnormal procoagulant value (of the 8 measured) vs 47 of 110 (43%) healthy control subjects (P=.0009). Of the 5 men whose serum estradiol level was measured while they were receiving testosterone therapy, this level was high (≥42.6 pg/mL) in 4. When testosterone therapy is given to patients with thrombophilia, they are at increased risk for osteonecrosis.

Takayasu arteritis and antiphospholipid antibody syndrome in an elderly woman

Takayasu arteritis and antiphospholipid antibody syndrome in an elderly woman

Clinical study of giant cell arteritis in our hospital.

To investigate clinical and laboratory features of giant cell arteritis (GCA). We included 24 patients (6 men, 18 women; mean age 69.8 years) in this study. GCA was diagnosed based on the American College of Rheumatology 1990 classification criteria. Mean serum C-reactive protein was 9.03 mg/dl. GCA was classified into three types: classic temporal arteritis type (cranial GCA, nine patients); large-vessel type, affecting the aorta and its major branches without temporal arteries (12 patients); generalized type, affecting both temporal arteries and large vessels (three patients). Swelling and tenderness of temporal arteries were recognized in temporal arteritis and generalized arteritis. Ten of these patients also had histopathologic findings of arteritis, including giant cells in biopsy specimens. Examination of HLA-class 1 expression showed that one patient with cranial GCA, three with generalized GCA, and seven with large-vessel GCA were positive for HLA-A24, and four patients with large-vessel GCA were positive for HLA-B39. One patient with cranial GCA, one with generalized GCA, and six with large-vessel GCA were positive for HLA-B52. Nine patients were positive for anti-phospholipid antibodies (seven for anti-cardiolipin antibody immunoglobulin G, seven for anti-cardiolipin β2-glycoprotein-1 antibody, one for lupus anticoagulant). Our study demonstrated that HLA-class 1 expression in GCA resembles that in Takayasu arteritis, suggesting that these two arteritis types share the same genetic background. In contrast, the difference in the prevalence of anti-phospholipid antibodies in GCA and Takayasu arteritis patients shows a difference in the characteristic aspects of these two arteritis types.

The Laterality of Deep Vein Thrombosis in the Pelvic and Lower Extremity Veins.

Purpose:This study aimed to determine whether deep vein thrombosis (DVT) predominantly occurred on a particular side in the pelvic and lower extremity veins.Materials and Methods:Among 259 consecutive patients with leg swelling, 65 were confirmed to have DVT in the pelvis and lower extremities, and enrolled in this study. The serum levels of initial D-dimer, antithrombin III, tissue plasminogen activator, factor VIII, proteins C and S, anticardiolipin antibodies immunoglobulin (Ig) G and IgM and lupus anticoagulant were measured and analyzed retrospectively. Lower extremity venous system was divided into 11 anatomic segments on each side, and thrombotic involvement in each segment was recorded to determine the laterality of thrombotic involvement for each patient. The presence of thrombus in a specific vein was assigned using a Thrombus Scoring System (TSS) score of 1. Predominant direction was determined based on the TSS score for each side.Results:Left-side predominat DVT (57%) was most frequent. Patients with both-side equivalent DVT had the highest total TSS score (P=0.022). The predominant side was significantly different between men (right 44.1%) and women (left 74.2%) (P=0.022). Patients with both-side equivalent DVT had the highest mean age (69.3±9.9 years) as well as the highest mean levels of initial D-dimer (13.8±20.7 μg/mL) and anticardiolipin antibody IgM (13.4±22.8 MPL) indicating increased coagulability.Conclusion:In the current study, left-side predominant DVT is most frequent in pelvis and lower extremities, and this phenomenon is more apparent in women. And both-side equivalent DVT is associated with the most advanced age and hypercoagulability.

Testosterone, Thrombophilia, and Thrombosis

We describe thrombosis, deep venous thrombosis (DVT) pulmonary embolism (PE; n = 9) and hip-knee osteonecrosis (n = 5) that developed after testosterone therapy (median 11 months) in 14 previously healthy patients (13 men and 1 woman; 13 Caucasian and 1 African American), with no antecedent thrombosis and previously undiagnosed thrombophilia-hypofibrinolysis. Of the 14 patients, 3 were found to be factor V Leiden heterozygotes, 3 had high factor VIII, 3 had plasminogen activator inhibitor 1 4G4G homozygosity, 2 had high factor XI, 2 had high homocysteine, 1 had low antithrombin III, 1 had the lupus anticoagulant, 1 had high anticardiolipin antibody Immunoglobulin G, and 1 had no clotting abnormalities. In 4 men with thrombophilia, DVT-PE recurred when testosterone was continued despite therapeutic international normalized ratio on warfarin. In 60 men on testosterone, 20 (33%) had high estradiol (E2 >42.6 pg/mL). When exogenous testosterone is aromatized to E2, and E2-induced thrombophilia is superimposed on thrombophilia-hypofibrinolysis, thrombosis occurs. The DVT-PE and osteonecrosis after starting testosterone are associated with previously undiagnosed thrombophilia-hypofibrinolysis. Thrombophilia should be ruled out before administration of exogenous testosterone.

Spontaneous coronary artery dissection presenting as an ischaemic stroke in a middle-aged man with anti-cardiolipin antibodies: a case report

IntroductionCerebrovascular disease is a major cause of mortality and morbidity worldwide. Ischemic stroke is the most common manifestation, encompassing a wide variety of causative mechanisms. We present the case of a middle-aged male patient with spontaneous coronary artery dissection in the presence of anti-cardiolipin antibodies, leading to left ventricular thrombus and presenting with stroke.Case presentationA 56-year-old Caucasian man presented with dysarthria and right-sided weakness. There was a history of chest pain with autonomic symptoms four days earlier. Examination revealed right-sided hemiparesis. Electrocardiogram showed sinus rhythm with anterior Q waves. Magnetic resonance imaging of the brain showed large left parietal and smaller multiple cerebral infarcts. Echocardiogram showed anterior wall and apical akinesis with a large mural thrombus. Anti-cardiolipin antibodies immunoglobulin G and immunoglobulin M were strongly positive. Coronary angiography showed dissection of the mid left anterior descending artery with normal flow down the distal vessel. He was treated conservatively with anticoagulation and secondary prevention. He was in good health when seen in clinic four months later.ConclusionWe highlight the importance of a comprehensive approach at obtaining the correct diagnosis, input of different specialities and the fact that the presence of anti-cardiolipin antibodies is associated with coronary artery dissection in a middle-aged male patient whose presentation was stroke.

Hypothyroidism determines the clinical and immunological manifestations of Arabs with lupus

Data on thyroid disease in Arabs with lupus is scarce. We conducted a cross-sectional and retrospective case-control study to report the prevalence of thyroid diseases in 110 Arabs with lupus who attended our Rheumatology Clinic between January 2002 and January 2007, and to delineate the clinical and immunological features of Arabs lupus patients with thyroid diseases. We found hypothyroidism in 15 (13.7%) patients. Overall, 25.6% had elevated thyroid peroxidase antibodies, 14.6% had elevated anti-thyroglobulin antibodies, and 13.7% were positive for both antibodies. Lupus patients with hypothyroidism had a significantly higher frequency of polyarthritis (OR = 9.3, CI: 2.0-41.7, P < 0.001), cutaneous manifestations (OR = 5.6, CI: 2.4-14.3, P < 0.0001), positive anti-thyroglobulin antibodies (OR = 19.9, CI: 8.38-47.4, P < 0.0001), and thyroid peroxidase antibodies (OR = 12.3, CI: 6.27-24.1, P < 0.0001) than lupus patients with normal thyroid function. Furthermore, neuropsychiatric (OR = 0.36, CI: 0.14-0.93, P < 0.05) and hematological (OR = 0.52, CI: 0.29-0.91, P < 0.05) manifestations were significantly lower in patients with hypothyroidism than in euthyroid patients. Surprisingly, the prevalence of anticardiolipin antibody immunoglobulin G (aCL IgG) (OR = 0.34, CI: 0.13-0.86, P < 0.05), lupus anticoagulant (OR = 0.02, CI: 0.001-0.35, P < 0.0001), and anticardiolipin syndrome (OR = 0.02, CI: 0.001-0.43, P < 0.0001) were significantly lower in lupus patients with hypothyroidism than in lupus patients with normal thyroid function. In conclusion, the prevalence of hypothyroidism in Arabs with lupus is comparable to that reported in the literature. Arab lupus patients with hypothyroidism have distinctive clinical and immunological features that differentiate them from euthyroid patients.

Antiphospholipid Syndrome Associated With Human Herpesvirus-6 Infection

The case of a patient with basal ganglia infarction associated with primary human herpesvirus-6 infection is reported. Anticardiolipin antibody immunoglobulin G was elevated after human herpesvirus-6 infection and then decreased gradually. The transient elevation in the antiphospholipid antibody level suggests that the human herpesvirus-6 infection can induce antiphospholipid syndrome, thus resulting in a cerebral infarction.

LEGG-CALVÉ-PERTHES DISEASE AND THROMBOPHILIA

Thrombophilia has previously been identified as a potential etiologic factor in Legg-Calve-Perthes disease. We prospectively studied the association between Legg-Calve-Perthes disease and coagulation abnormalities by comparing seventy-two children who had the disease with 197 healthy controls. A nonselected, consecutive series of seventy-two patients with Legg-Calve-Perthes disease (mean age [and standard deviation], 6.6 +/- 2.6 years) was studied in their order of referral and compared with 197 healthy controls (mean age, 7.6 +/- 5.1 years). Assays were done for factor-V Leiden, prothrombin G20210A, methylenetetrahydrofolate reductase C677T, and plasminogen activator inhibitor-1 4G/5G gene mutations. Levels of anticardiolipin antibodies immunoglobulin G and M (IgG and IgM), homocysteine, protein C, protein S, antithrombin III, and plasminogen activator inhibitor-1 were also measured. The factor-V Leiden mutation was more common in the patients (eight of seventy-two) than in the controls (seven of 197) (chi-square = 5.7, p = 0.017). After we controlled for the false-discovery rate, the case-control difference remained significant (p = 0.017). The odds ratio for the development of Legg-Calve-Perthes disease in the presence of the factor-V Leiden mutation was 3.39 with a 95% confidence interval of 1.18 to 9.73. A high level of anticardiolipin antibodies (IgG and/or IgM) was found in nineteen of the seventy-two patients compared with twenty-two of the 197 controls (chi-square = 9.5, p = 0.002). After we controlled for the false-discovery rate, the case-control difference remained significant (p = 0.002). The odds ratio of patients with Legg-Calve-Perthes disease having one or more abnormalities in factor V, anticardiolipin antibody IgG, or anticardiolipin antibody IgM as opposed to normal values for all three variables was 3.29 (95% confidence interval, 1.73 to 6.24; p = 0.0003). Two thrombophilic risk factors, the factor-V Leiden mutation and anticardiolipin antibodies, are associated with Legg-Calve-Perthes disease, an association that may reflect causality. Prognostic study, Level II-1 (retrospective study). See Instructions to Authors for a complete description of levels of evidence.

Increased anticardiolipin antibody IgG titers do not predict recurrent stroke or TIA in children.

Increased anticardiolipin antibody (ACLA) immunoglobulin (Ig) G titers are commonly found in children with arterial ischemic stroke (AIS) or TIA (AIS/TIA). The associated risk of recurrent thromboembolism is unknown. To determine the risk of recurrent thromboembolism associated with persistently increased ACLA titers of the IgG isotype in children with AIS/TIA. The authors studied a cohort of children surviving first AIS/TIA tested by standardized ELISA for beta2-glycoprotein I-dependent ACLA of the IgG isotype. Children with ACLA titers >15 IgG phospholipid (GPL) units (per manufacturer's cutoff point) on more than two occasions > or =6 weeks apart were classified as ACLA-positive (ACLA+) and compared with ACLA-negative (ACLA-) children with respect to recurrent thromboembolic events (AIS/TIA, sinovenous thrombosis, and extracerebral thromboembolism). The authors recruited 34 ACLA+ children and 151 ACLA- children. Most ACLA+ children (30/34; 88%) had ACLA titers < or =40 GPL units. During the follow-up period (median duration, 2.8 years for ACLA+ children and 3.0 years for ACLA- children), AIS/TIA recurred in 26% of ACLA+ children and in 38% of ACLA- children; none developed sinovenous thrombosis or extracerebral thromboembolism. Based on survival analysis, this difference was nonsignificant (p = 0.54). Using binary partition evaluation, no titer criteria for ACLA positivity (range, 0 to 60 GPL units) predicted recurrent AIS/TIA. In children surviving arterial ischemic stroke/TIA, increased anticardiolipin antibody immunoglobulin G titers do not predict recurrent thromboembolism.

Role of thrombotic and fibrinolytic disorders in osteonecrosis of the femoral head.

Some studies have suggested that thrombotic and fibrinolytic disorders may be etiologic causes of osteonecrosis of the femoral head. A case-control study was done to determine whether these disorders are associated with osteonecrosis of the femoral head in East Asian patients with nontraumatic osteonecrosis of the femoral head. Twenty-four consecutive patients who had been diagnosed as having nontraumatic osteonecrosis of the femoral head were matched with 24 control subjects for gender, age (1-year range), and the time of presentation (1-year range). Thrombotic factors including protein C activity, protein S activity, antithrombin III, anticardiolipin antibody immunoglobulins G and M, and lupus antibody were investigated. Fibrinolytic factors including tissue-plasminogen activator, plasminogen activator inhibitor-1, tissue-plasminogen activator and plasminogen activator inhibitor-1 ratio, lipoprotein (a), and plasminogen also were investigated. There were no significant differences in the levels of thrombotic and fibrinolytic factors. In eight patients with idiopathic osteonecrosis, anticardiolipin antibody immunoglobulin G, an antiphospholipid antibody which is associated with thrombotic phenomena, was lower than that in respective control subjects. These data do not confirm an etiologic role for thrombotic and fibrinolytic disorders in East Asian patients with nontraumatic osteonecrosis of the femoral head.

Hypercoagulability, a serious problem in patients with ESRD on maintenance hemodialysis, and its correction after kidney transplantation

Background:Recurrent vascular access thrombosis (VAT) resulting in failure to continue maintenance hemodialysis (HD) therapy is not an uncommon event. The cause of VAT in these circumstances remains uncertain. We describe results of our studies to identify changes in hemostatic balance in patients on maintenance HD therapy that probably contributed to a hypercoagulable state. Methods:We studied 82 patients with end-stage renal disease on maintenance HD therapy who underwent HD for 11 to 52 months (39.3 ± 27.4 months). Forty-nine episodes of VAT occurred in 22 patients; a single episode occurred in 12 patients; and 2 or more episodes, in 10 patients. Blood coagulation studies, including assays of inhibitors and activated protein C (PC) resistance (APCR), were performed using standard techniques. Results:Investigations showed the presence of lupus anticoagulant (LA) in 5.6%, anticardiolipin antibody immunoglobulin G (IgG) in 3.9% and IgM in 5.3%, APCR in 20.5%, and deficiencies in protein S (PS), PC, and antithrombin III (ATIII) in 32.1%, 24.4%, and 19.2%, respectively. When parameters were compared between patients with and without VAT episodes, LA, PC, PS, and APCR levels were significantly abnormal in those who experienced VAT. Sixteen subjects with hypercoagulable states on HD therapy underwent renal transplantation and were evaluated 9.3 ± 4.2 months posttransplantation. Deficiencies in PC (P = 0.014), PS (P = 0.001), ATIII (P = 0.017), and APCR (P = 0.0001) were completely corrected in all subjects. Conclusion:Hypercoagulability is a risk factor for recurrent VAT in HD patients, and renal transplantation successfully corrects these abnormalities.

The BEST study--a prospective study to compare business class versus economy class air travel as a cause of thrombosis.

As many as 10% of airline passengers travelling without prophylaxis for long distances may develop a venous thrombosis. There is, however, no evidence that economy class travellers are at increased risk of thrombosis. A suitably powered prospective study, based on the incidence of deep-vein thrombosis (DVT) reported in previous studies on long-haul flights, was designed to determine the incidence of positive venous duplex scans and D-dimer elevations in low and intermediate-risk passengers, comparing passengers travelling in business and economy class. Eight hundred and ninety-nine passengers were recruited (180 travelling business class and 719 travelling economy). D-dimers were measured before and after the flight. A value greater than 500 ng/ml was accepted as abnormal. A thrombophilia screen was conducted which included the factor V Leiden mutation, the prothombin 20210A mutation, protein C and S levels, antithrombin levels, and anticardiolipin antibodies immunoglobulin G (IgG) and immunoglobulin M (IgM). On arrival, lower limb compression ultrasonography of the deep veins was performed. Logistical regression analysis was used to determine the risk factors related to abnormally high D-dimer levels. Only 434 subjects had a full venous duplex scan performed. None had ultrasonic evidence of venous thrombosis. Nine passengers tested at departure had elevated D-dimer levels and these volunteers were excluded from further study. Seventy-four of the 899 passengers had raised D-dimers on arrival. Twenty-two of 180 business class passengers (12%) developed elevated D-dimers compared with 52 of 719 economy class passengers (7%). There was no significant association between elevation of D-dimers and the class flown (odds ratio (OR) 0.61, p = 0.109). The factor V Leiden mutation, factor VIII levels and the use of aspirin were, however, associated with raised D-dimers (OR 3.36, p = 0.024; OR 1.01, p = 0.014; and OR 2.04, p = 0.038, respectively). Five hundred and five passengers were contacted within 6 months and none reported any symptoms of a clinical thrombosis or pulmonary embolus. The incidence of ultrasonically proven DVT is much lower than previously reported. However, more than 10% of all passengers developed raised D-dimers, which were unrelated to the class flown. A rise in D-dimers is associated with an inherent risk of thrombosis and/or thrombophilia, demonstrates activation of both the coagulation and fibrinolytic systems during long-haul flights, and may indicate the development of small thrombi.

Anticardiolipin antibody in vascular parkinsonism.

Vascular parkinsonism (VP) is characterized by predominantly lower body involvement with gait impairment and postural instability, often without tremor, and by relative levodopa unresponsiveness. Neuroimaging studies demonstrate multiple infarcts or ischemic changes in periventricular white matter. Anticardiolipin antibodies (ACLA) are associated with hypercoagulable states and increased stroke risk. Review of our Movement Disorders Clinic records identified 44 individuals with a diagnosis of VP. ACLA have been obtained in 22 of these patients (mean age, 78.3 years; mean Mini-Mental Status Exam score, 25.8). Gait disturbance was the initial clinical feature in 82% of the patients, and levodopa responsiveness was present in 18% of those treated. In 9 of the 22 (40.9%), ACLA immunoglobulin G was positive. No significant differences in clinical features or risk factors (hypertension, diabetes, coronary artery disease, and clinical stroke) were evident between ACLA+ and ACLA- groups. Since the presence of ACLA in individuals with stroke is usually treated by full-scale anticoagulation with warfarin, our findings raise the question whether such treatment should also be used in persons with VP who are ACLA positive.