High Anticardiolipin Antibodies Research Articles

E030 Osteonecrosis of the spine in antiphospholipid antibody syndrome

Abstract Background/Aims Osteonecrosis (ON) is a well-known complication of several rheumatic diseases, affecting the hip, knee, shoulder, or ankle. The involvement of spine and other sites with ON has been reported with catastrophic APS, although the nature of this association is not completely clear. In antiphospholipid syndrome, thrombosis of blood vessels is considered a possible mechanism, along with other risk factors, such as active disease, thrombocytopenia, glucocorticoid use and associated autoimmune diseases, making the pathophysiology multifactorial. We report a case of a 66-year-old male with APS who developed bone infarcts/osteonecrosis after withdrawal of anticoagulation for APS, which was necessitated by a bleeding complication and introduction of steroids for immune thrombocytopenia. Methods A 66-year-old male came to us with history of unprovoked deep vein thrombosis (DVT) for which he was on antiplatelet and anticoagulation for over 20 years. He was diagnosed to have high titre anti cardiolipin antibody (ACA)(186 U/ml) without other autoimmune conditions. He had an episode of bladder hematoma in August 2022, needing his anticoagulation to be suspended temporarily. He was also found to have profound thrombocytopenia with raised inflammatory markers. Considering it to be immune mediated he was started on high dose oral corticosteroids and was later maintained with azathioprine while the oral prednisolone dose was gradually brought down to 10 mg daily in about 3 months’ time. His thrombocytopenia improved progressively however he developed an unprovoked DVT in October 2022 and was restarted on anticoagulation. He continued to have low dose steroids for about 6 months. Meanwhile, he started having a new onset of low back pain in December 2022. An MRI of the whole spine showed multilevel osteonecrosis with haemorrhagic cavities in a few vertebral bodies. Results This case highlights three interesting points. The first is the atypical presentation of the osteonecrosis involving vertebral bodies. Osteonecrotic lesions in the spine of a patient with catastrophic primary antiphospholipid syndrome has been reported. Our case signifies that although vertebral bodies are an uncommon site for avascular necrosis in patients with APS, it is not rare. Secondly, the pathogenesis of ON is complex. Whether ACA are directly responsible for this condition or whether they are the bystanders remains controversial. ACA have shown to be an independent risk factor for developing ON in many studies. Thirdly, steroids are known to be an important risk factor in patients presenting with osteonecrosis. The vascular compromise could be attributed to a steroid induced hypercoagulative state, abnormal lipid metabolism, or fat embolism. Conclusion ON in APS is unusual and its underlying pathophysiology remains multifactorial. However, when complicated by the high ACA levels, active disease, difficult anticoagulation (bleeding tendencies), thrombocytopenia or prolonged use of steroids, it can lead to hypercoagulable state causing micro thrombosis and avascularisation. Disclosure M. Shah: None. K. Putchakayala: None.

Anticardiolipin antibodies and Lupus anticoagulant; prevalence in pregnant patients with recurrent miscarriages

Objective: Evaluation of the frequency of anticardiolipin antibodies and lupus anticoagulant levels in women with histories of three or more first trimester recurrent miscarriages. Methodology: It was a descriptive case series carried out at private clinical practice in Peshawar. About 86 patients were enrolled in the study. They had three or more first trimester recurrent abortions. Pregnant patients between ages 22 and 35 years were included. Any patient diagnosed with other etiologies of recurrent miscarriages was excluded. Percentages and frequencies were used to analyze the data. Results: Mean age of pregnant patients was 28.4(±3.25) years. Mean number of miscarriages was 3.5. High anticardiolipin antibodies were detected in 23.3% of pregnant patients. There was no pronounced difference regarding high levels of IgG and IgM. No case of raised lupus anticoagulant was found. Conclusion: Pregnant patients who experience recurrent miscarriages show higher prevalence of antibodies of anticardiolipin type. It is recommended that all such cases should be subjected to APS screening.

Case report: primary osteonecrosis associated with thrombophilia-hypofibrinolysis and worsened by testosterone therapy

BackgroundFamilial and acquired thrombophilia are often etiologic for idiopathic hip and jaw osteonecrosis (ON), and testosterone therapy (TT) can interact with thrombophilia, worsening ON.Case presentationCase 1: A 62-year-old Caucasian male (previous deep venous thrombosis), on warfarin 1 year for atrial fibrillation (AF), had non-specific right hip-abdominal pain for 2 years. CT scan revealed bilateral femoral head ON without collapse. Coagulation studies revealed Factor V Leiden (FVL) heterozygosity, 4G/4G plasminogen activator inhibitor (PAI) homozygosity, high anti-cardiolipin (ACLA) IgM antibodies, and endothelial nitric oxide (NO) synthase (eNOS) T786C homozygosity (reduced conversion of L-arginine to NO, required for bone health). Apixaban 5 mg twice daily was substituted for warfarin; and L-arginine 9 g/day was started to increase NO. On Apixaban for 8 months, he became asymptomatic. Case 2: A 32-year-old hypogonadal Caucasian male had 10 years of unexplained tooth loss, progressing to primary jaw ON with cavitation 8 months after starting TT gel 50 mg/day. Coagulation studies revealed FVL heterozygosity, PAI 4G/4G homozygosity, and the lupus anticoagulant. TT was discontinued. Jaw pain was sharply reduced within 2 months.ConclusionsIdiopathic ON, often caused by thrombophilia-hypofibrinolysis, is worsened by TT, and its progression may be slowed or stopped by discontinuation of TT and, thereafter, anticoagulation. Recognition of thrombophilia-hypofibrinolysis before joint collapse facilitates anticoagulation which may stop ON, preserving joints.

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, 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.

Thrombophilia and retinal vascular occlusion

PurposeThe purpose of this research was to assess associations of thrombophilia with central retinal vein occlusion (CRVO), central retinal artery occlusion (CRAO), and amaurosis fugax (AF); to evaluate outcomes of normalizing high homocysteine; and to study CRVO, CRAO, and AF developing in estrogens/estrogen agonists in women subsequently shown to have thrombophilia.MethodsMeasures of thrombophilia–hypofibrinolysis were obtained in 132 CRVO cases, 15 CRAO cases, and 17 AF cases. Cases were compared to 105 healthy control subjects who did not differ by race or sex and were free of any ophthalmologic disorders. All cardiovascular disease (CVD) risk factors were compared to healthy general populations.Main outcome measuresThe main outcome measure of this study was thrombophilia.ResultsCRVO cases were more likely than controls to have high homocysteine (odds ratio [OR] 8.64, 95% confidence intervals [CI]: 1.96–38), high anticardiolipin immunoglobulin M (IgM; OR 6.26, 95% CI: 1.4–28.2), and high Factor VIII (OR 2.47, 95% CI: 1.31–7.9). CRAO-AF cases were more likely than controls to have high homocysteine (OR 14, 95% CI: 2.7–71.6) or the lupus anticoagulant (OR 4.1, 95% CI: 1.3–13.2). In four of 77 women with CRVO (two found to have high homocysteine, two with inherited high Factor XI), CRVO occurred after starting estrogen–progestins, estrogen–testosterone, or estrogen agonists. In one of eight women with CRAO found to have high anticardiolipin antibody IgG, CRAO occurred after starting conjugated estrogens, and AF occurred after starting conjugated estrogens in one of eleven women with AF (inherited protein S deficiency). Therapy for medians of 21 months (CRVO) and 6 months (CRAO-AF) was 5 mg folic acid, 100 mg B6, and 2000 mcg/day B12 normalized homocysteine in 13 of 16 (81%) CRVO cases and all five CRAO-AF cases with pretreatment hyperhomocysteinemia. The CRVO cases had an excess of hypertension; CRAO-AF cases had an excess of type 2 diabetes and hypertension.ConclusionTreatable thrombophilia, hyperhomocysteinemia in particular, is more common in RVO cases than in normal controls. RVO occurs after estrogens or estrogen agonists were administered in women subsequently shown to have thrombophilia.

Prevalence of anticardiolipin antibodies in pregnancies with history of repeated miscarriages.

Aim:This study aimed at evaluating the prevalence of high anticardiolipin antibody and lupus anticoagulant levels in women with histories of at least two miscarriages.Methods:The presence of high anticardiolipin antibody and lupus anticoagulant levels were evaluated in 52 patients with ages between 17 and 41 (mean 26.7 years old) who had histories of repeated miscarriages.Results:High anticardiolipin antibody levels were identified in 55.77% and lupus anticoagulant levels in 2% of the individuals.Conclusion:In conclusion, women who suffer from repeated miscarriages present with a high prevalence of anticardiolipin antibodies. Further studies on this issue are crucial as these antibodies are associated with hypercoagulability and thus increased the risk of thromboembolic events.

Haemorrhagic transformation of cerebral infarction in an AIDS patient – thrombophaelia screen essential!

Patients with advanced HIV disease with low CD4 count are more prone to thrombo-embolism and various predisposing factors have been identified. These include the presence of anticardiolipin antibodies and the lupus anticoagulant, deficiencies of proteins C and S, heparin co-factor II and antithrombin. Increased levels of Von Willebrand factor and d-dimers have also been linked with thrombo-embolism, as has the presence of concurrent infections and malignancies. We report a case of an AIDS patient who presented with acute hemiparesis. He was severely immunosuppressed. Computed tomography of the head confirmed cerebral infarction with haemorrhagic transformation. He had no known risk factors apart from being severely immunocompromised and had high anticardiolipin antibodies and low free protein S.

Anticardiolipin Antibodies in Patients with Type 2 Diabetes Mellitus

There is controversy about an increased prevalence of antiphospholipid antibodies in diabetic patients. The possible implications are little known. We prospectively studied all consecutive outpatients with type 2 diabetes mellitus (DM) attended to in an Internal Medicine office. IgM and IgG anticardiolipin antibodies (ACA) were determined by standardized enzyme-linked immunoassay. Fifty-six patients were included. Only one patient (1.8%) had a titer of IgM ACA higher than 15 MPL units and no patient had a titer of IgG ACA higher than 15 GPL units. Six patients (10.7%) had low IgM ACA titers (4-15 MPL units) and 18 patients (32.1%) had low IgG ACA titers (4-15 GPL units). There were no differences in the frequencies of a low IgM or IgG ACA titer or in the means of IgM and IgG ACA titers in patients with complicated and uncomplicated DM, with and without cardiovascular disease, with and without nephropathy, or with and without retinopathy. Moderate to high ACA titers must be exceptional in patients with type 2 DM. Low ACA titers may occur in patients with type 2 DM. These low titers do not seem to be associated with complicated DM, cardiovascular disease, nephropathy or retinopathy.

First Experiences with the Measurement of Thrombin Generation (TGA) on the Ceveron® Alpha in the Routine Lab

Aims: Aim of the study was to show the suitability of the new coagulation analyzer Ceveron® alpha for determination of thrombin generation (TGA) in routine laboratories for discrimination of normal plasma samples from haemophilic and thrombophilic patient samples, from patients with a Lupus syndrome and patients with bleeding disorders.Methods: TGA was determined by a thrombin generation assay based on monitoring the formation of thrombin by means of a fluorigenic substrate upon activation of the coagulation cascade by tissue factor and phospholipids using 2 reagents with different phospholipid concentrations (RClow and RChigh) on Ceveron® alpha. Thrombin generation is measured with a specially adapted TGA fluorimetric module which is placed over the cuvette rotor. Readout parameters were lag time (tLag), peak thrombin (Peak), time to peak(tPeak), velocity index (VI) and area under the curve (AUC). In case of patients with Lupus Anticoagulants a ratio of peak thrombin values triggered with RClow and RChigh was formed. Four laboratory groups participated in the study. All patient samples used for thrombin generation measurement were characterized by routine parameters.Results: Group 1 analyzed samples with bleeding disorders. Peak thombin values showed the best discrimination between Hemophilia B patients (41.9, SD12.7nM), Hemophilia B patient after treatment (188.9nM) and normal controls (208.5nM, SD= 74.0). In Hemophilia A patients tLag was the best parameter to discriminate severe Hemophilia A (8.5min) from acquired hemophilia A and VWD (4.6 min, SD=2.1).Normal ranges for TGA established in group 1 (n=16) were tLag 2.7min (SD=0.8), tPeak 7.8min (SD=1.9), peak thrombin 208.5nM (SD= 74), AUC 1769.4 (SD=327.9).Group 2 analyzed samples of thrombophilic patients with pregnancy (n=30). Patient samples showed peak thrombin values (310.9nM, SD= 65.7) above normals (174.2nM, SD= 22.5). Even patients with heparin treatment had high peak thrombin values (340.5nM, SD=67.2). In heparin treated patients D-dimer values were pathologic as well.Group 3 determined thrombin generation in patients with Lupus Anticoagulants determined by dRVVT, APTT-LA, Lupus-Ceveron and anti-cardiolipin antibodies (ACA). Patients only with high ACA values showed normal peak thrombin ratios of RClow/RChigh 0.6 (SD= 0.07) whereas the ratio in patients with high lupus anticoagulants as measured in the coagulation tests was 0.98 (SD= 0.31) for high antibody titer and 0.83 (SD 0.01) for low antibody titer. Inter-assay CVs in the normal control determined by this laboratory were 2.67% for peak thrombin and 4.83% for AUC and in thrombophilic plasma 3.0% for peak thrombin and 1.41% for AUC.Group 4 determined TGA in orally anticoagulated patients. Normal range for peak thrombin established in this laboratory is 220nM (SD=52, n=12). Oral anticoagulant treatment lowered the AUC (from 1713.3nM, SD= 435.4 thrombin in samples with INR in the range 1 – 1.5 to 894.4nM, SD= 229.2 thrombin in samples with INR in the range 2 – 2.5) and peak thrombin formation (from 204.1nM, SD= 73.5 peak thrombin in samples with INR in the range 1 –1.5 to 79.0nM, SD= 35.2 peak thrombin in samples with INR in the range 2 – 2.5) and prolonged the tLag (from 5.5min, SD= 1.7 in samples with INR in the range 1 –1.5 to 7.6min, SD= 2.4 in samples with INR in the range 2 – 2.5.Conclusions: TGA can be measured reproducibly with low variation under routine laboratory conditions. Peak thrombin is the best parameter for discrimination of patient samples from normals in haemophiliacs, in thrombophilia, patients with a Lupus syndrome, pregnancy and bleeding disorders. With automated, standardised thrombin generation measurement on the Ceveron® alpha large prospective studies can be conducted to confirm these results.

Vaskulitis als Ursache von Kopfschmerzen

A 13-year-old girl presented to our emergency with a one week history of fever and skin rash and new onset of chorea for the last three days. There was a long standing history of right predominant headache; followed by personality change, fatigue, arthralgia and weight loss over the last few months. Previous investigations by head CT and ophthalmological examination did not explain the symptoms. Further investigations revealed peri- and pancarditis with aortic insufficiency, a renal involvement with elevated creatinin, protein- and hematuria and a hemolytic anemia. Diagnosis of lupus eythematodes was confirmed by high ANA, anti-dsDNS and Anticardiolipin antibodies. Within the first 48 hours after admission there was significant deterioration with reduced vigilance and dysarthria. MRI of the brain and dopplersonography of cerebral vessels showed a complete thrombosis of the right medial cerebral artery with a small net of collaterals, irregularities of the left cerebral artery due to vasculitis and several subacute leftsided ischemias. Immunosuppressive therapy with high-dose corticosteroids and cyclophosphamid together with antithrombotic therapy induced an improvement of neurologic, renal and cardiac function.

Butyrylcholinesterase activity and lymphocyte subpopulations in peripheral blood of Kuwaiti women experiencing recurrent spontaneous abortion

This study has evaluated the hypothesis that activity of the detoxifying enzyme butyrylcholinesterase (BuChE) correlates with levels of serum anti-cardiolipin antibodies (ACA) and T lymphocytes in peripheral blood of women experiencing recurrent spontaneous abortion (RSA). Peripheral venous blood from 16 non-pregnant, RSA-afflicted women and 8 healthy non-pregnant women was analyzed for frequency of T lymphocyte subpopulations by two-color flow cytometry and for serum BuChE using butyrylthiocholine iodide/spectrophotometry. RSA-afflicted women with high serum ACA, but not those with normal ACA levels, exhibited significantly increased percentages of CD4 + CD25+ cells ( p < 0.01) and CD4 + HLA-DR+ cells ( p < 0.05) relative to healthy women. CD4 + CD25+ high cells were significantly lower ( p < 0.05), while CD4 + CD25+ low cells were significantly higher ( p < 0.01), in women with elevated ACA compared to healthy women and to RSA women with normal ACA. Relative to healthy, non-pregnant subjects, serum BuChE activity in RSA patients was elevated, both for those with normal ACA ( p < 0.001) and elevated ACA levels ( p < 0.01). Among healthy controls, a significant positive correlation was observed between frequency of CD3 + NK cells and BuChE activity ( p < 0.01), but not for RSA-afflicted subjects. A positive correlation between BuChE activity and frequency of CD4 + CD25+ cells, as well as CD4 + CD25+ high cells, was observed in the RSA-afflicted subject group with elevated ACA ( p < 0.05), which may be related to induction of BuChE by toxic metabolites resulting from pathogenic T cell activity. It is concluded that, among RSA patients, high serum ACA correlates with elevated levels of activated T cells and reduced CD4 + CD25+ high/CD4 + CD25+ low cells in comparison to healthy women or those afflicted with RSA but with normal ACA. BuChE activity is observed to be elevated in RSA patients irrespective of serum ACA status.

Associations of Thrombophilia, Hypofibrinolysis, and Retinal Vein Occlusion

We prospectively assessed whether thrombophilia and hypofibrinolysis, amplified by thrombophilic hormone replacement therapy (HRT), were associated with retinal vein occlusion (RVO). We studied 44 cases (18 men, 26 women), > or = 3 months after RVO, 42 with central RVO, 2 with branch RVO, in the consecutive order of their referral by 2 community-based ophthalmologists. PCR and serologic coagulation assays were compared to 83 and 40 healthy adult normal controls, respectively. The 4G allele frequency of the plasminogen activator inhibitor-1 (PAI-1) gene, associated with hypofibrinolysis, was 56 of 88 (64%) in cases vs 79 of 166 (48%) in controls, X(2) = 5.95, p = .015. The PAI-1 gene product, plasminogen activator inhibitor activity (PAI-Fx), was higher in cases than controls (age-race-sex- adjusted mean 12.2 U/mL vs 6.3, p = .013). By stepwise logistic regression, the PAI-1 gene 4G allele was associated with RVO, odds ratio 1.94, 95% CI 1.12-3.34, p = .018. Thrombophilic resistance to activated protein C (RAPC) was present in 6 of 32 (19%) of cases vs 0 of 40 (0%) controls, Fisher's p [p(f)] = .006. Thrombophilic high factor VIII (> 150%) was present in 3 of 30 (10%) cases vs 0 of 40 (0%) controls, p = .041, p(f) = .07. Comparing 23 RVO cases < or = age 55 and controls < or = age 55 (n = 44 for PCR, n = 40 for serologic measures), RAPC was present in 17% of cases vs 0% controls (p(f) = .026), high Factor VIII in 17% vs 0% (p(f) = .026), heterozygosity for the G1691A Factor V Leiden mutation in 13% vs 2% (p(f) = 0.11), and the 4G allele frequency of the PAI-1 gene 74% vs 39% (p = .0001). PAI-Fx was higher in cases than controls (age-race-sex adjusted mean 12.7 U/mL vs 6.7, p = .016). The case-control odds ratio for the PAI-1 4G allele was 5.54, 95% CI = 1.86-16.7, p = .002. Of the 26 women, 9 (35%) took HRT; 4 of the 9 had PAI-1 gene 4G4G homozygosity, 2 had thrombophilic high anticardiolipin antibody (IgG), 1 was heterozygous for the G1691A Factor V Leiden mutation, and 2 were heterozygous for the thrombophilic PL A1/A2 mutation of the platelet glycoprotein IIb/IIIa gene. Associations between heritable coagulation disorders and RVO, most marked in cases < or = age 55, and often amplified in women by thrombophilic HRT, are, speculatively, causal.

Thrombotic Risk Factors In Primary Antiphospholipid Syndrome

Because thromboembolic events are frequently observed in primary antiphospholipid syndrome (PAPS), we assessed the risk factors for new thrombotic episodes. Fifty-six PAPS patients (mean age, 37+/-10 years) were prospectively studied for 5 years. The preliminary Sapporo classification criteria for antiphospholipid syndrome (APS; a medium-high anticardiolipin antibody [aCL] titer and/or a positive lupus anticoagulant [LA] test in the presence of vascular thrombosis and/or pregnancy morbidity) were used to confirm the diagnosis. Thrombotic episodes or pregnancy losses before a diagnosis of PAPS were considered events, and any new disease manifestation other than thrombocytopenia was considered a recurrent event. Only patients with objectively verified thrombotic events were included in the study. Twenty-one new thrombotic events were observed in 15 subjects (26.8%), including 3 (5.4%) who died during the follow-up. The patients with IgG aCL levels of >40 IgG phospholipid unit (GPL-U) showed a higher incidence of new thrombotic events (43.3%) than those with levels of < or =40 GPL-U (7.7%). Univariate analysis identified a history of recurrent clinical events (P=0.004), a highly positive aCL titer (P=0.007), and the presence of cardiac abnormalities (P=0.036) as significant risk factors for new thrombotic events. A multivariate regression model confirmed that an IgG aCL titer of >40 GPL-U was an independent risk factor for thrombosis (odds ratio, 9.17; 95% confidence interval, 1.83 to 46.05). A high IgG aCL titer is the strongest predictor of new thrombotic events in PAPS patients.

Splenic infarction in a pregnant woman with systemic lupus erythematosus

Here we describe a 20-year-old pregnant woman with systemic lupus erythematosus who had high anticardiolipin antibodies and presented with splenic infarction.

Significance of Anticardiolipin Antibodies on Short and Long Term Allograft Survival and Function following Kidney Transplantation

The significance of anticardiolipin antibodies (ACAs) prior to renal transplantation is unclear. We studied a cohort of 337 patients who underwent renal transplantation from 1996 to 2001. Follow-up continued until allograft loss, patient death or 31 December 2002. The primary outcome was a composite endpoint of death-censored allograft loss or a 25% reduction in estimated glomerular filtration rate (GFR) from 1-month post-transplant. Secondary outcomes were allograft loss, a 25% reduction in GFR, acute rejection and creatinine at 1 year. IgG and IgM ACA titers were positive (> or =15) in 18.1% of recipients. There were no significant differences at baseline between recipients, except coumadin therapy in those with positive ACA titers (20% vs. 7.4%). Post-transplant, there was no increase in the primary outcome in ACA-positive patients, even after adjustment for anticoagulation with coumadin (HR = 1.42 [0.68, 2.96]). There was no difference in secondary outcomes between those with or without positive titers. Two of five patients with very high titers (>50) who were not anticoagulated had early graft loss. A positive ACA titer prior to kidney transplantation was not associated with inferior renal outcomes after transplantation, although more research is required to address the prognostic significance of very high ACA titers.

Antiphospholipid Antibody Syndrome.

When the diagnosis of antiphospholipid antibody syndrome (aPS) is being considered in persons who have experienced an ischemic stroke or a transient ischemic attack, it is important to gauge how well the history and laboratory data fit with this diagnosis as opposed to other causes of infarct. The fewer the number of typical vascular disease risk factors and the more confirmatory the laboratory findings (ie, high anticardiolipin antibody titers or presence of lupus anticoagulant), the stronger the suspicion of aPS. There are no good prospective randomized data on stroke prevention with any form of therapy following a first stroke or transient ischemic attack associated with antiphospholipid antibody (aPL). Short-term anticoagulation with an International Normalized Ratio (INR) of 2.0 to 3.0 may be considered in these cases, as could antiplatelet agents if no clear cardiac source is found. If anticoagulation is chosen, if there is no recurrence, and if the level of aPL appears to decline, a change to a stroke prevention medication that may carry less risk, such as an antiplatelet agent, may be appropriate. In patients with more typical vascular disease risk factors and less confirmatory laboratory evidence of aPS (ie, low to moderate titer of anticardiolipin antibodies and lack of other clinical or serologic evidence of aPS), a more conservative approach may be considered and antiplatelet therapy initiated. In either situation, close follow-up for recurrent thrombosis and aPL can help determine whether more or less aggressive (risky) therapies should be considered. Results of randomized controlled trials of different treatment options for aPS are awaited.

A preliminary pilot study of treatment of thrombophilia and hypofibrinolysis and amelioration of the pain of osteonecrosis of the jaws

Objectives. In a preliminary pilot study of 30 treatments in 26 patients with osteonecrosis of the jaws and chronic disabling facial pain, our specific aim was to determine whether, to what degree, and how safely therapy of hypofibrinolysis and thrombophilia would ameliorate the chronic pain associated with osteonecrosis of the mandible and maxilla. Study Design. Thrombophilia was treated with Coumadin (DuPont) in 10 patients; hypofibrinolysis was treated with Winstrol (Sanofi-Winthrop) in 20 patients, including 4 who had mixed thrombophilia and hypofibrinolysis and had previously been treated with Coumadin. The initial treatment period was targeted to be 4 months. Each patient was asked to keep a daily written pain-relief numeric rating score and side-effects diary and to provide a summary pain-relief numeric rating score and side effects compilation for the total treatment period. Results. There were 4 men and 22 women in the study group; their mean age was 49 ± 11 years. The mean onset of their osteonecrosis pain was at age 45 ± 12 years, and the mean duration of their facial pain prior to therapy was 4.5 ± 4.2 years. Ten patients had one or more thrombophilic traits (there were two patients with protein C deficiency, five with resistance to activated protein C and/or the mutant Factor V Leiden gene, and four with high anticardiolipin antibodies). The 10 patients who were thrombophilic were treated with Coumadin (the international normalized ratio was targeted to 2.5-3.0) for 22 ± 9 weeks. By self-reported pain-relief numeric rating scores, 6 of the 10 patients with thrombophilia (60%) had ≥ 40% pain relief, 2 (20%) had no change, and 2 (20%) had increased pain (30% and 80% worse). Nine of the 10 patients with thrombophilia (90%) had no Cumadin-related side effects; 1 patient (10%) stopped Coumadin therapy (after 28 weeks) because of nosebleeds. Winstrol (6 mg per day) was used for 16 ± 9 weeks in 20 patients with hypofibrinolysis, some of whom had one or more hypofibrinolytic traits (10 had high levels of plasminogen activator/inhibitor activity, usually accompanied by low stimulated tissue plasminogen activator activity; 13 had high Lp[a] lipoprotein). Of these 20 patients with hypofibrinolysis, 9 patients (45%) had ≥40% pain relief, 3 patients (15%) had 20% to 30% relief, 5 patients (25%) had no improvement, and 3 patients (15%) had increased pain (30% worse, 60% worse, and 70% worse). Six of the 20 patients with hypofibrinolysis (30%) had no Winstrol-related side effects, while 14 (70%) had side effects that could be attributed to Winstrol, including weight gain, peripheral edema, increased facial and body hair, and acne—all of which were reversed within 6 weeks of stopping Winstrol therapy. Conclusions. We postulate that thrombophilia and hypofibrinolysis lead to impaired venous circulation and venous hypertension of the mandible/maxilla with subsequent development of osteonecrosis and chronic facial pain. In many patients, facial pain can be ameliorated by treating the pathogenetic coagulation defects with Coumadin or Winstrol. Large, double-blind, placebo-controlled crossover studies will be required in the future to validate these preliminary results and to determine whether pain relief with Coumadin or Winstrol justifies the risks and side effects associated with these medications, especially for long-term use, in osteonecrosis of the jaws.

DISCORDANT EFFECTS ON EICOSANOIDS AND FIBRIN DEGRADATION PRODUCTS IN TWO MURINE MODELS OF ANTIPHOSPHOLIPID ANTIBODY

Two murine models of lupus were employed to challenge an hypothesized mechanism by which antiphospholipid antibodies (APLA) might promote thrombosis: altering prostacyclin (PGI 2) and thromboxane (TX) production. PGI 2 levels in mouse blood and the ex vivo release of PGI 2 and TX from mouse kidney were measured. Since APLA have been reported to alter synthesis or activation of several molecules mediating fibrinolysis, murine plasma levels of the fibrin degradation product, D-dimer were also determined. Two murine strains, one prone to spontaneous “lupus-like” illness (MRL-lpr) and related strain (MRL-++), were compared. The assays confirm that MRL-lpr mice have increased anticardiolipin antibody (ACA) and two-fold increased release of TX from renal tissues compared to MRL-++ mice. However, these mice have low levels of plasma D-dimer. NIH Swiss mice injected with IgG (containing APLA) from thrombosis-prone lupus patients had high blood ACA titers and D-dimer levels, but both ACA and D-dimer were low or non-detectable in Swiss mice injected with saline or normal IgG. Unlike mice with spontaneous lupus-like illness, healthy mice injected with APLA did not differ from controls with respect to plasma or tissue PGI 2 or TX levels. The two murine models of lupus differ, because an altered PGI 2-TX ratio is a finding in the chronic murine lupus strain MRL-lpr, but is not seen when APLA are injected into normal mice. It is unlikely that APLA alone has a direct effect on cellular production of eicosanoids in vivo. Copyright © 1997 Elsevier Science Ltd

Pseudotumor cerebri in systemic lupus erythematosus

Objective: To assess the association between pseudotumor cerebri (PC) andsystemic lupus erythematosus (SLE), and to seek a pathogenic mechanism that may elucidate the appearance of PC in patients with SLE. Data Source: Original English articles having the terms SLE, PC, or benign intracranial hypertension in their titles were identified by Medline search. In addition we report three new patients with this association. Study Synthesis: Thirteen articles were found and 21 patients were analyzed. Data Extraction: Of the reported 21 patients, 18 were previously reported and 3new patients with coexisting PC and SLE are described. The clinical characteristics of the patients is presented. Patients with PC and SLE generally had a more severe course of SLE; renal involvement occurred in 79%, massive proteinuria in 47%, and hematologic abnormalities were detected in a third. A hypercoagulable state manifest by either recurrent thromboembolic events or a high anti-cardiolipin antibody titer was detected in 58% of the patients described. Conclusions: The association of PC and SLE is probably not coincidental. The high prevalence of serologic or clinical evidence of a hypercoagulable state suggests that microscopical thromboembolic events play a role in the genesis of PC.