Occurrence Of Thrombosis In Patients Research Articles

Role of Genetic Thrombophilia Markers in Thrombosis Events in Elderly Patients with COVID-19

Thrombosis is an extremely dangerous complication in elderly patients with COVID-19. Since the first months of the pandemic, anticoagulants have been mandatory in treatment protocols for patients with COVID-19, unless there are serious contraindications. We set out to discover if genetic thrombophilia factors continue to play a triggering role in the occurrence of thrombosis in patients with COVID-19 with prophylactic or therapeutic anticoagulants. We considered the following genetic markers as risk factors for thrombophilia: G1691A in the FV gene, C677T and A1298C in the MTHFR gene, G20210A and C494T in the FII gene, and (-675) 4G/5G in the PAI-I gene. In a cohort of 176 patients, we did not obtain a reliable result indicating a higher risk of thrombotic complications when taking therapeutic doses of anticoagulants in carriers of genetic markers for thrombophilia except the C494T mutation in the FII gene. However, there was still a pronounced tendency to a higher incidence of thrombosis in patients with markers of hereditary thrombophilia, such as FV G1691A and FII G20210A mutations. The presence of the C494T (Thr165Met) allele in the FII gene in this group of patients showed a statistically significant effect of the mutation on the risk of thrombotic complications despite anticoagulant therapy.

Frequency and Risk Factors for Venous Thromboembolism Among Patients with Multiple Myeloma or Aggressive Lymphoma: A 6-Year Single Center Retrospective Analysis

Background and Aims: Patients with hematologic malignancies are characterized by presence of altered hemostatic system, which translates into a high risk of venous thromboembolism (VTE) with an estimated annual incidence of VTE higher when compared with the general population (0.5% vs 0.1%). Moreover, VTE contributes to morbidity and mortality in these patients and is a frequent complication of anticancer therapy. Even VTE is clearly associated with decreased survival, the development of validated scores delineate the risk of VTE by hematological disorders subtype still lacking. In the current study, the frequency and the risk factors associated with VTE were examined among a cohort of patients with aggressive lymphoma and multiple myeloma. Methods: We retrospective analyzed clinical data of 231 patients with multiple myeloma and 227 patients diagnosed with aggressive lymphoma, followed in our institute from January 2015-December 2020. Among patients affected by myeloma, extramedullary disease was observed in 18% of patients. Among the lymphoma cohort, the most common type was diffuse large B-cell lymphoma (84%), followed by mantle cell lymphoma (8%), peripheral T cell lymphoma (4%), Burkitt lymphoma (2%), and primary mediastinal large B-cell lymphoma (2%). Results: Fourty-six (19.9%) patients with diagnosis of multiple myeloma experienced a VTE, in a median follow-up of 23.09 month (range, 1.01-135.95). Half of patients (50%) had TVP, followed by EP in 28% and TVS in 22% of patients. VTE occurred in older age (pV=0.027), bone disease (pV=0.002), and the presence of central venous catheter (pV<0.001). Instead, no clinical and laboratory features at diagnosis affect the occurrence of thrombosis in patients with myeloma. Interesting, Lenalidomide-based therapy, monoclonal antibody-based therapy, and Carfizomib-based therapy increase the risk of VTE (HR 2.55 (1.31-4.95), pV=0.005; HR 2.36 (1.07-5.19), pV=0.037; HR 6.1 (2.8-13.6), pV<0.001; respectively). Even in patients with aggressive lymphoma the frequency of VTE was 19.8% (n=45) in a median follow up of months 28.87 (range, 0.23-177.18), despite 55.5% underwent thromboprophylaxis treatment. Older patients (pV= 0.029), with concomitant HIV infection (pV=0.031), and with spleen involvement (pV=0.022) were risk factors of development of VTE. Moreover, higher level of LDH (pV=0.042), leukocytosis (pV=0.004) and higher neutrophil-to-lymphocyte ratio (NLR) (pV=0.022) were significantly associated with increased risk of thrombosis. In our analysis, VTE did not significantly affect the overall survival of patients with myeloma and aggressive lymphoma. Conclusions: VTE is a frequent complication in patients with multiple myeloma or aggressive lymphoma, and about 20% of these patients presented VTE during therapy. In our cohort of multiple myeloma, the therapeutic approach seems play a crucial role in development of thrombosis, although clinical presentation had less impact on VTE. In patients affected by aggressive lymphoma, NLR, a new inflammatory status marker, turns out to be an independent risk factor for VTE. This study showed new clinical and therapeutic risk factors for VTE, but the development of a predictive model for identifying patients with myeloma and lymphoma at high risk for developing thrombosis is an unmet need in clinical management.

De-novo occurrence of portal vein thrombosis in patients with HCV-related cirrhosis after sustained virological response: medium to long term observations from the ongoing PITER cohort

De-novo occurrence of portal vein thrombosis in patients with HCV-related cirrhosis after sustained virological response: medium to long term observations from the ongoing PITER cohort

Catheter-Related Venous Thrombosis in Pulmonary Arterial Hypertension Patients on Intravenous Prostacyclin Therapy

Rationale: Intravenous prostacyclin (PG) therapies are used for managing severe pulmonary arterial hypertension (PAH). Most PAH patients respond to PG therapies, but some experience complications associated with presence of indwelling catheters. We observed development of venous thromboses in patients and present our experience. Methods: A retrospective chart review of PAH patients on long-term intravenous PG therapy was conducted between 2008 and 2017.Demographic, hemodynamic, six-minute walk distance (6MWD), WHO/NYHA functional class (FC) and outcome data were collected. Results: Six of 63 patients on intravenous PG therapy were identified with venous thromboses. Mean age was 44±15 years (mean ±SD, range 31 to 70 years). All patients were female. Duration of PAH diagnosis 15±7 years; duration of IV PG therapy7.4±3.8 years. One patient had antiphospholipid antibody syndrome; hypercoagulable workup was negative for other five patients. Diagnostic right heart catheterization showed mean pulmonary artery pressure of 53.6±5.4 mmHg and thermodilution cardiac output was 4.94±1.4 l/min. Echocardiogram showed RAP of 8.3±6 mmHg. Development of thrombosis occurred 4±2 years after initiation of therapy. most common site of thrombosis was subclavian vein followed by femoral vein. All patients were on anticoagulation therapy with warfarin or a novel oral anticoagulation agent prior to development of thrombosis. Because of repeated catheter infections and poor vascular access, two of three patients were successfully transitioned to oral therapies without significant change in FC. Conclusion: A small percentage of patients on intravenous PG therapy for PAH develop thrombosis in areas of venous access. There does not appear to be a difference in occurrence of thrombosis in patients who have idiopathic PAH or associated PAH. Anticoagulation did not prevent initial or subsequent thrombosis. Development of recurrent thrombosis limits vascular access available for infusion of intravenous PG, thereby necessitating transition to alternative therapy. Transitioning off intravenous PG could affect patient's symptoms and FC. Funding Statement: authors state that no funding was received for this research. Declaration of Interests: authors state: The authors have no conflicts to disclose. Ethics Approval Statement: A waiver of consent was granted by the Institutional Review Board.

Factor V Leiden mutation and high FVIII are associated with an increased risk of VTE in women with breast cancer during adjuvant tamoxifen — Results from a prospective, single center, case control study

BackgroundEstimates of the risk ratio of tamoxifen-associated venous thromboembolism (VTE) in breast cancer patients range from 2.4 to 7.1. The occurrence of thrombosis in patients with breast cancer complicates the clinical condition and causes a change of treatment. Our study was conducted in order to investigate the influence of patient-related risk factors for thrombosis development in breast cancer patients whose treatment included adjuvant tamoxifen. MethodsThe prospective, single center, case control study included 150 breast cancer women, 50 whom developed venous thrombosis during adjuvant tamoxifen and 100 whom did not have thrombosis, as a control group. Patient-related risk factors such as: age, body mass index, previous VTE, varicose veins, concomitant diseases, the presence of prothrombotic mutations (FV Leiden, FII G20210A) and FVIII activity were evaluated in both groups. ResultsIn respect of prothrombotic mutations, the FV Leiden mutation was present in a higher number of women from the VTE group (10/50 vs 7/100; P=0.020). Additionally, FVIII activity was significantly higher in the VTE group; median (IQR), of 1.79 (0.69) vs 1.45 (0.55); P<0.001 and more women in this group (24/50 vs 34/100) had increased FVIII activity; P=0.020. In those women with FVIII>1.5IU/ml, who were carriers of prothrombotic mutations, an OR of 3.76 (CI 95% 1.276–11.096; P=0.016) was obtained for VTE. ConclusionThe results of our study showed that the factor V Leiden mutation and high FVIII are associated with an increased risk of VTE in women with breast cancer during adjuvant tamoxifen.

Portal vein thrombosis associated with psoriasis: a case report

BackgroundPsoriasis is no longer viewed as an isolated dermatological ailment and instead is considered a systemic disease. The extension of this spectrum has heightened the known risk of morbidity and mortality due to the involvement of cardiovascular system and the risk of venous thrombosis. A number of cases have reported the increased occurrence of deep vein thrombosis and pulmonary embolism in the background of psoriasis, however portal vein thrombosis has not been reported to date. We report an index case of chronic portal vein thrombosis in a diagnosed patient with psoriasis.Case presentationA 67-year-old South-Asian female previously diagnosed and treated for psoriasis presented with a four month history of abdominal pain associated with abdominal distension. Clinical examination revealed an enlarged spleen and free fluid in the abdomen. Imaging with ultrasonography and computed tomography of the abdomen revealed features compatible with chronic portal vein thrombosis with cavernous transformation.ConclusionThis case highlights the importance of having clinical awareness of occurrence of thrombosis in patients with psoriasis. Typical symptoms favoring thrombosis should prompt thorough investigation to exclude this rare yet possible complication in patients with psoriasis, including that of portal vein thrombosis. Prophylaxis with anticoagulation still lacks strength of evidence to be justified in psoriasis. The exact pathogenesis of venous thromboembolism in psoriasis is still unexplained and further studies are needed to clarify the causal association.

Coexistence of hypofibrinogenemia and factor V Leiden mutation

Congenital hypofibrinogenemia and afibrinogenemia are usually associated with an increased risk of bleeding, but occurrence of arterial or venous thrombosis has also been reported in individuals with fibrinogen deficiency. This study reports on a 25-year-old patient with hypofibrinogenemia (fibrinogen 0.6 g/l) and congenital thrombophilia due to heterozygous factor V Leiden mutation who developed spontaneous deep-vein thrombosis (DVT) in the right lower extremity. Regardless of hypofibrinogenemia, he was receiving anticoagulant therapy over 6 months, with no occurrence of bleeding. His father is also a heterozygous carrier of factor V Leiden, but with normal fibrinogen level and he remained asymptomatic despite having experienced surgery in the past. This case, as well as data from literature, suggests that risk of thrombosis in carriers of factor V Leiden mutation is not counterbalanced by moderate congenital hypofibrinogenemia, and that antithrombotic prophylaxis should not be omitted in high-risk situations for occurrence of thrombosis in patients with coinheritance of hypofibrinogenemia and factor V Leiden mutation.

Discrepant ratios of arterial versus venous thrombosis in hemophilia A as compared with hemophilia B

The occurrence of thrombosis in patients with congenital bleeding disorders represents an exceptional event. Hemophilia A and hemophilia B patients have been showed to present both arterial and venous thrombosis (85 cases of arterial thrombosis and 34 cases of venous thrombosis). The great majority of arterial thrombosis are myocardial infarction or other acute coronary syndromes, whereas the majority of venous thrombosis are deep vein thrombosis and/or pulmonary embolisms. However there are discrepancies in the proportion of arterial and venous thrombosis seen in hemophilia A versus hemophilia B. The ratio of arterial versus venous thrombosis in hemophilia A is 3.72 whereas that for hemophilia B is 1.12. This indicates that arterial thrombosis is more frequent in hemophilia A as compared to hemophilia B and the opposite is true for venous thrombosis. The potential significance of this discrepancy is discussed.

Incidence of Arterial and Venous Thrombosis in Vonwillebrand Disease

AbstractAbstract 101 Objective:To date, only a few case studies have reported occurrence of thrombosis in patients with VonWillebrand disease (VWD). No studies have looked at its incidence in this patient population. The aim of this study was to test our hypothesis that decreased VonWillebrand factor (VWF) levels confer a protective effect on arterial and venous thrombosis. Methods:This is a retrospective cohort study including patients (n = 350) with the ICD-9 code of VonWillebrand disease who were identified from our hospital database over a period of 25 years (Jan 1985 – Dec 2010). An extensive review of the patients’ medical records was carried out to authenticate VonWillebrand disease, after which 198 patients were included in the analysis. A random parallel control sample without VonWillebrand disease matched for age, sex, hypertension, hyperlipidemia, atrial fibrillation and diabetes mellitus was also obtained from the hospital database. The primary outcomes were incidence of diagnosis of symptomatic arterial thrombosis [Cardiovascular events (CAD): Unstable angina, Q wave and non Q wave Myocardial infarction; Cerebrovascular events (CVD): stroke and transient ischemic attack] and venous thrombosis [deep vein (DVT), cerebral vein, portal vein, renal vein thrombosis and pulmonary embolism (PE)]. The results were computed using multivariate conditional logistic regression analysis and proportions were compared using McNemer’sChi – square test. Results:Out of 198 patients (mean age 44.2 ± 17.5, women 72%) with VWD, the incidence of arterial and venous thrombosis is reported in table 1.VWD was found to be an independent protective predictor from arterial thrombosis (OR 0.28, 95% CI 0.14 – 0.54, p <0.0001), more so in CAD (OR 0.28, 95% CI 0.12 – 0.64, p = 0.002) than in CVD (OR 0.28, 95% CI 0.10 – 0.77, p = 0.01). However this was not the case in venous thrombosis as seen in DVT (OR 0.62, 95% CI 0.20 – 1.93, p = 0.41) or PE (OR 0.50, 95% CI 0.09 – 2.75, p = 0.423).One case of portal vein thrombosis was also seen. Also the arterial thrombosis in VWD was not a predictor of mortality; 10 deaths were reported in VWD patients, while 4 in control population (OR 1.8, 95% CI 0.49 – 6.76, p = 0.37). Conclusion:In a population of relatively younger individuals with VonWillebrand disease, our study suggests a reduced incidence of arterial thrombosis but not in venous thrombosis. This brings up the possibility that there are could be other pathways or factors involved in arterial and venous thrombosis. To our knowledge, this is the first large observational study that has provided insight into the thrombotic disease in this group of patients.Table 1:Incidence rate of thrombosis.Type of ThrombosisCases (%)Controls (%)p-valueCAD8/198 (4%)26/198 (13%)0.001CVD5/198 (2.5%)17/198 (8.5%)0.009DVT5/198 (2.5%)8/198 (4%)0.41PE2/198 (1%)4/198 (2%)0.42Abbreviations; CAD, Coronary Artery Disease; CVD, Cerebrovascular Disease; DVT, Deep venous thrombosis; PE, Pulmonary Embolism Disclosures:No relevant conflicts of interest to declare.

Thrombosis in VonWillebrand disease

ObjectiveTo date, only a few case studies have reported occurrence of thrombosis in patients with VonWillebrand disease (VWD). No studies have looked at its incidence in this patient population. The aim of this study was to test our hypothesis that decreased VonWillebrand factor (VWF) levels confer a protective effect on arterial and venous thrombosis. MethodsThis is a retrospective cohort study including patients (n=350) with the ICD-9 code of VWD who were identified from our hospital database over a period of 25years, out of which 198 patients were included in the final sample. A parallel control sample without VWD matched for age, sex, hypertension, hyperlipidemia, atrial fibrillation and diabetes mellitus was also obtained from the hospital database. The primary outcomes were incidence of diagnosis of symptomatic arterial and venous thrombosis. The results were computed using multivariate conditional logistic regression analysis and proportions were compared using McNemer's Chi – square test. ResultsOut of 198 patients (mean age 44.2±17.5, women 72%) with VWD, 170 (86%) were VWD type 1, 21 (10%) were type 2 and 7 (3%) were type 3. VWD was found to be an independent protective predictor from arterial thrombosis (OR 0.28, 95% CI 0.14–0.54, p<0.0001), more so in CAD (OR 0.28, 95% CI 0.12–0.64, p=0.002) than in CVD (OR 0.28, 95% CI 0.10–0.77, p=0.01). However this was not the case in venous thrombosis (p=0.42). ConclusionIn a population of relatively younger individuals with VWD, our study suggests a reduced incidence of arterial thrombosis but not of venous thrombosis. This brings up the possibility that there could be other pathways or factors involved in arterial and venous thrombosis. To our knowledge, this is the first large observational study that has provided insight into the thrombotic disease in this group of patients.

Associated prothrombotic conditions are probably responsible for the occurrence of thrombosis in almost all patients with congenital FVII deficiency. Critical review of the literature

The occasional occurrence of thrombosis in patients with congenital bleeding disorders has received considerable attention during the past decade. Myocardial infarction, ischemic strokes and venous thromboembolism have been reported in hemophilia A or B patients, in von Willebrand disease and, also, in rare coagulation disorders, especially in factor VII (FVII) deficiency. To explain the relatively high frequency of thrombotic phenomena, mainly venous, seen in the last condition, it was speculated that a special form or variant of FVII deficiency could exist. The presence of associated prothrombotic risk factors has been occasionally reported to be present in these patients but the matter has never been duly evaluated and emphasized. The purpose of the present paper was to evaluate if the clinical setting in which thrombosis appeared in these patients could explain the occurrence of the thrombosis. All reported cases of thrombosis seen in patients with FVII deficiency have been analyzed and the presence of associated risk factors recorded. Out of a population of 33 documented cases, the presence of prothrombotic risk factors was reported in 30 instances. In two of the remaining cases, no mention is made about associated risk factors. In the last case they were explicitly excluded. The critical evaluation of the literature suggests that the occurrence of thrombosis in FVII deficiency may be due to common prothrombotic risk factors. As a consequence it may be only stated that FVII deficiency does not protect from thrombosis.

Mechanisms of Disease: antiphospholipid antibodies—from clinical association to pathologic mechanism

The discovery that antiphospholipid antibodies recognize plasma proteins that bind to phospholipids rather than recognizing phospholipids themselves has been a major advance in research into antiphospholipid syndrome (APS). It is now established that beta2-glycoprotein I (beta2 GPI) is the most important antigen for antiphospholipid antibodies. However, the possible pathologic mechanism is still much debated. This is mainly because not all patients with anti-beta2 GPI antibodies show clinical symptoms that are related to APS. Several reports indicate that anti-beta2 GPI antibodies with lupus anticoagulant (LA) activity are clinically of much importance. Most patients with LA caused by anti-beta2 GPI antibodies suffer from thrombosis as a result of recognition of the first domain of beta2 GPI by these antibodies. In the search for a pathologic mechanism that might explain the high occurrence of thrombosis in patients with anti-domain I antibodies (LA-causing anti-beta2 GPI antibodies), it was found that these antibodies show increased resistance to the anticoagulant activity of annexin A5. We have shown that the same population of antibodies also displays increased resistance to activated protein C. Owing to the diversity of clinical symptoms related to APS, it is likely that other pathologic mechanisms also contribute to the occurrence of APS-related symptoms.

Therapy Insight: vascular complications in patients with inflammatory bowel disease

Inflammatory bowel disease (IBD) is associated with an increased risk of vascular complications. The most important of these complications are arterial and venous thromboembolism, which represent a significant cause of morbidity and mortality in IBD patients. Recent data suggest that thromboembolism is a disease-specific extraintestinal manifestation of IBD. The most common thrombotic manifestations in IBD are deep vein thrombosis of the leg and pulmonary emboli. It has been suggested that disease activity and the extent of colonic localization are correlated with the risk of developing thromboembolism. The occurrence of thrombosis in patients with IBD is partially attributed to the existing hypercoagulable state in IBD. Both coagulation and fibrinolysis are activated in patients with IBD; this is especially true for those with active disease. The most common risk factors for thrombophilia in IBD patients with venous thromboembolism are Leiden mutation in the gene encoding factor V, hyperhomocysteinemia, and antiphospholipid antibodies. The main genetic defects that have been established as risk factors for venous thrombosis are rather uncommon in IBD, but when present increase the risk of thromboembolism. Screening for coagulation defects seems justified only in IBD patients with a history of thrombosis or a family history of venous thromboembolic events. Antithrombotic treatment of IBD patients with venous thromboembolism is similar to that of thrombotic non-IBD patients.

Possible episodes that trigger thrombotic events in patients with antiphospholipid syndrome

The presence of antiphospholipid antibodies and/or lupus anticoagulant (LA) increase the risk of thrombosis, while the onset of thrombosis is usually sudden. The objective of this study was to determine whether or not some episodes triggered thrombotic events in patients possessing antiphospholipid antibodies. Fifteen patients who presented with thrombosis (primary antiphospholipid syndrome (APS), six cases; secondary APS, nine cases) were retrospectively examined to discover whether or not any specific episodes occurred prior to a total of 21 thrombotic events. In five events occurring in five female patients, specific episodes were identified, including the wearing of tight underwear, dehydration due to fever and standing in hot and humid weather, fever following the extraction of a carious tooth, steroid pulse therapy, toxemia during pregnancy, and intrauterine fetal death. To prevent the occurrence of thrombosis in patients possessing antiphospholipid antibodies, it appears to be important to avoid such triggering episodes and also to reduce the risk factors for thrombosis.

Antibodies to Phospholipid-Binding Plasma Proteins and Occurrence of Thrombosis in Patients with Systemic Lupus Erythematosus

There is accumulating evidence that anti-phospholipid (aPL) antibodies in the sera of patients with autoimmune diseases bind to a complex of anionic phospholipids and plasma phospholipid-binding proteins, namely β2-glycoprotein I (β2-GPI) and prothrombin. It has been suggested that a conformational change in β2-GPI, induced by binding either to anionic phospholipids or to the oxygen molecules on the irradiated microtiter plate, reveals cryptic antigenic epitope(s) in the native protein. We used an enzyme-linked immunoassay for measuring antibodies against two phospholipid-binding proteins, i.e., β2-GPI and prothrombin, absorbed to an irradiated plate in an unselected series of 139 patients with systemic lupus erythematosus (SLE). Elevated levels of antibodies against β2-GPI were found in 49% of patients and antibodies against prothrombin in 34% of patients. Both antibodies were significantly associated with deep venous thrombosis in patients with SLE (P= 0.009 for both antibodies). Accordingly, testing of these antibodies seems to be clinically useful in evaluating the risk of thrombosis.

Autoantibodies directed against the epidermal growth factor-like domains of thrombomodulin inhibit protein C activation in vitro.

No consensus has been obtained about the question whether autoantibodies, in particular antiphospholipid antibodies (aPL), may cause thrombosis by inhibiting thrombomodulin (TM) mediated protein C activation. In order to clarify the mechanism by which autoantibodies inhibit TM-mediated protein C activation, we have screened 12 patients with autoimmune diseases for the presence of circulating autoantibodies inhibiting TM function. In a cross-sectional study we found that IgG fractions from two patients (who were aPL negative) inhibited TM mediated protein C activation in an assay system using purified components. A longitudinal study of six patients with a history of thrombosis of which two were aPL positive showed that all had at some time circulating antibodies inhibiting TM function, suggesting that the presence of these antibodies is transient. Three different TMs were used to identify the epitope of the antithrombomodulin antibodies (aTM): rabbit TM, which contains the entire TM molecule; Solulin, which contains the extracellular part of TM, and rEGF-TM, which contains the six epidermal growth factor (EGF) domains of TM. We showed that the aTM inhibited protein C activation mediated by all three TMs, indicating that the aTM are directed against the region containing the EGF domains. When TM was incorporated in phospholipid vesicles, no inhibition by these aTM could be demonstrated. In addition, protein C activation mediated by cultured endothelial cells (EC) could not be inhibited by aTM. The lack of inhibition of TM in phospholipid vesicles and EC-TM by a TM suggests that aTM only inhibit soluble TM. In conclusion, we demonstrated the transient presence of circulating autoantibodies directed against the region of TM containing the EGF domains in SLE patients with a history of thrombotic complications. We postulate that the presence of antibodies to soluble TM may be, in addition to aPL, a risk factor for the occurrence of thrombosis in patients with autoimmune diseases.

Venous Thrombosis Occurring in Nonspecific Ulcerative Colitis

THE OCCURRENCE of thrombosis, both venous and arterial, has been recognized for more than 30 years as a distinct complication of ulcerative colitis. The literature on this subject consists of individual case reports or incidental observations usually in clinical studies concerned with other aspects of ulcerative colitis. 1-8 As a result, the stated incidence of this complication varies widely. The incidence of thrombosis in the larger series of cases is shown in Table 1. The occurrence of thrombosis in patients with ulcerative colitis appears predictable since many of the factors characteristic of this disease are known or believed to encourage thrombosis: toxemia, anemia, emaciation, prolonged rest in bed, and frequent surgical procedures. However, as early as 1936, Bargen and Barker, 2 as a result of their observations on the extensive propagation of such thrombi, considered the possibility that an increased coagulation tendency of the blood occurs in patients with ulcerative

THROMBOSIS IN SYSTEMIC LUPUS ERYTHEMATOSUS DESPITE CIRCULATING ANTICOAGULANTS.

Abstract Systemic lupus erythematosus is often complicated by a circulating anticoagulant, yet serious hemorrhage is rare in patients with this complication. It has also been observed that thrombotic complications may occur. The authors found definite evidence of a circulating anticoagulant in 8 of 11 patients with systemic lupus erythematosus; of these, 1 had significant bleeding, and 4 others, 1 of whom died, developed thrombotic complications. The occurrence of thrombosis in patients with circulating anticoagulants has not been previously reported. The inhibition of clotting appeared to be related to suppression of platelet function and could usually be bypassed in vitro by the addition of a soybean substitute for platelets (Inosithin). The tendency toward thrombosis was manifested by an increased generation of thromboplastin as measured by the thromboplastin generation test.