Unexplained Venous Thrombosis Research Articles

Venous thrombosis and predictors of relapse in eosinophil-related diseases

Eosinophils have widespread procoagulant effects. Eosinophilic cardiovascular toxicity mostly consists of endomyocardial damage or eosinophilic vasculitis, while reported cases of venous thrombosis (VT) are scarce. We aimed to report on the clinical features and treatment outcomes of patients with unexplained VT and eosinophilia, and to identify predictors of relapse. This retrospective, multicenter, observational study included patients aged over 15 years with VT, concomitant blood eosinophilia ≥ 1G/L and without any other moderate-to-strong contributing factors for VT. Fifty-four patients were included. VT was the initial manifestation of eosinophil-related disease in 29 (54%) patients and included pulmonary embolism (52%), deep venous thrombosis (37%), hepatic (11%) and portal vein (9%) thromboses. The median [IQR] absolute eosinophil count at VT onset was 3.3G/L [1.6–7.4]. Underlying eosinophil-related diseases included FIP1L1-PDGFRA-associated chronic myeloid neoplasm (n = 4), Eosinophilic Granulomatosis with Polyangiitis (n = 9), lymphocytic (n = 1) and idiopathic (n = 29) variants of hypereosinophilic syndrome. After a median [IQR] follow-up of 24 [10–62] months, 7 (13%) patients had a recurrence of VT. In multivariate analysis, persistent eosinophilia was the sole variable associated with a shorter time to VT relapse (HR 7.48; CI95% [1.94–29.47]; p = 0.015). Long-term normalization of eosinophil count could prevent the recurrence of VT in a subset of patients with unexplained VT and eosinophilia ≥ 1G/L.

Study of Serum Homocysteine Level in Young Patients with Myocardial Infarction and Cerebrovascular Stroke

Background: Nowadays, vascular disease is the leading cause of death and disability. India too is facing epidemic of cardiovascular and cerebrovascular disease. The established risk factors for heart disease and stroke account for one half to three fourth of cases. The remainders are the result of other factors that promote atherosclerosis. Elevated blood levels of homocysteine have been linked to increased risk of premature coronary artery disease, stroke and thromboembolism, even among people who have normal cholesterol levels. Hence screen for homocysteine is recommended in patients with premature atherosclerotic disease and unexplained venous thrombosis. Methods: The present study was performed to correlate the levels of serum homocysteine levels in young patients (</=40 yrs) with myocardial infarction and ischemic cerebrovascular stroke. Thirty cases were studied along with assessment of their risk factor. Result: It was observed that serum homocysteine levels were significantly raised in coronary artery disease and ischemic stroke patients. Conclusion: Increase levels of homocysteine is an important factor that assesses risk independently for coronary artery disease and ishchemic stroke.

Inferior vena cava anomaly: A risk for deep vein thrombosis

Context:Inferior vena cava (IVC) anomalies have a 0.5% incidence rate and could be associated with other congenital abnormalities. In later stage of the disease, trophic ulcers with or without deep vein thrombosis (DVT) is consistent finding.Case Report:A 29-year-old male patient presented with recurrent lower extremity ulcers. Further workup revealed an absent infrahepatic inferior vena cava, prominently dilated azygos and hemiazygos veins with enlarged retroperitoneal collaterals without DVT.Conclusion:IVC anomaly should be suspected in a young patient presenting with unexplained venous thrombosis and recurrent ulcers of a lower extremity. IVC anomaly would inherently lead to blood flow stasis and endothelial injury. Thus per Virchow's triad, other risk factors for hypercoagulability such as physical inactivity, smoking tobacco, oral contraceptive pills should be avoided and when hereditary thrombophilias or other irreversible risk factors are present, lifelong anticoagulation should be considered.

Sticky platelet syndrome in patients with unexplained venous thrombosis

Objective: Sticky platelet syndrome (SPS) is a common autosomal dominant inherited platelet disorder. SPS is characterized by platelet hyperreactivity and is associated with arterial and venous thrombosis. The aim of this study was to determine the role of SPS in patients with uninduced venous thrombosis.Material and Methods: The study included 28 patients (15 male and 13 female) with uninduced venous thrombosis. SPS was defined according to Mammen’s aggregation method, which is described in detail elsewhere.Results: According to the defined ranges for platelet hyperreactivity, 3 (50%) patients, 2 (33%), and 1 (17%) (n =6 [21%]) with a confirmed diagnosis were classified as type II, I, and III SPS, respectively. In 1 patient SPS was the only hereditary abnormality noted. The other 5 patients carried other inherited coagulation defects, in addition to SPS.Conclusion: The present findings indicate that the prevalence of SPS was 21% in the patients with uninduced venous thrombosis. We therefore suggest that SPS should be considered in the differential diagnosis of such cases.Conflict of interest:None declared.

Heparin-Induced Thrombocytopenia Post Reconstructive Surgery

Koichi Kitamura Department of Otorhinolaryngology, Tokyo Medical University, Tokyo, Japan E-mail: k-kita@tokyo-med.ac.jp Phone: 81-33342-6111 Heparin-induced thrombocytopenia (HIT) is a rare immune-mediated complication of heparin. The diagnosis of HIT is considered when the patients exposed to heparin present with thrombocytopenia and thrombosis. We report a case HIT after reconstruction of head and neck cancer, successfully treated with the administration of argatroban. HIT can be the cause of postoperative venous congestion. It is necessary to be aware of this disease when unexplained venous thrombosis or thrombocytopenia after reconstruction develops of head and neck cancer. Heparin-Induced Thrombocytopenia Post Reconstructive Surgery

Activated Protein C Resistance and Factor V Leiden: A Review

Factor V Leiden (FVL) is the most common heritable cause of venous thrombosis. It is caused by a single nucleotide substitution resulting in an R506Q missense mutation, resulting in factor V resistance to activated protein C (APC) inactivation. Carriers of FVL have an increased susceptibility to venous thrombosis, which is further increased in the presence of other genetic or environmental risk factors. To review the biology, clinical findings, laboratory detection methods, and screening recommendations for patients with the FVL mutation. PubMed review of published literature and online information. FVL remains an important heritable cause of hypercoagulability since its discovery more than 10 years ago. Clinical suspicion should be high in cases of unexplained venous thrombosis. APC resistance and FVL mutation can be diagnosed with high sensitivity and specificity with use of clotting time-based functional assays and genetic assays, respectively, allowing for evidence-guided clinical decision making regarding the benefit of long-term anticoagulation.

Heparin-induced thrombocytopenia syndrome as a cause of flap failure: A report of two cases

Flap failure is a major complication in reconstructive plastic surgery. One of the most frequent etiologies of flap failure is venous thrombosis. However, infrequent causes also need to be explored, especially when faced with recurrent thrombosis. Heparin is frequently used in the prevention of venous thrombosis; however, the use of the medication itself may cause a serious thromboembolic state via an immune-related pathophysiological process. This adverse reaction to heparin may be life threatening. We present two cases, one pedicled and one free flap, with venous congestion concomitant to heparin-induced thrombocytopenia syndrome, in conjunction with severe life-threatening sequelae. Heparin-induced thrombocytopenia syndrome can be the cause of postoperative venous congestion. It is necessary to be alert for this syndrome in the presence of recurrent unexplained venous thrombosis or thrombocytopenia in patients receiving anticoagulation therapy.

Hypercoagulable states in patients with leg ischaemia.

Hypercoagulable states are found in up to 10 per cent of patients with a history of unexplained venous thrombosis. To investigate the prevalence in arterial thrombosis, thrombophilia screening was performed on 124 patients who had previously undergone lower-limb revascularization, 45 claudicants and 27 controls. Of the patients who had undergone revascularization 40 per cent had a hypercoagulation abnormality (low levels of protein C, protein S and antithrombin III or presence of the lupus anticoagulant) in comparison with 27 per cent of claudicants and 11 per cent of controls (P < 0.01). Furthermore, patients who had suffered reocclusion after revascularization were significantly more likely to have a hypercoagulation abnormality than those who had not (P < 0.05), even if the occlusion had occurred more than 6 months previously. Lupus anticoagulant was the abnormality most frequently detected and, like low protein C levels, was found only in patients with peripheral vascular disease. It appears that hypercoagulable states are common in patients with arterial disease and may predispose to failure of revascularization.

Sticky Platelet Syndrome (SPS) as a Cause of Unexplained Thrombosis.

Background: Sticky platelet syndrome (SPS) was first described in 1983 by Holliday. The results of recent studies suggest SPS to be a common cause of arterial and venous thrombosis. With respect to otherwise unexplained venous thrombosis, the prevalence of SPS approximates that of activated protein C resistance (APC-R). It has been found that SPS accounted for about 21% of otherwise unexplained arterial events (acute myocardial infarction, cerebrovascular thrombosis, transient cerebral ischemic attacks, retinal thrombosis, and peripheral arterial thrombosis) and accounted for about 13,2% of otherwise unexplained venous events (deep vein thrombosis, with or without pulmonary embolus).SPS is an autosomal dominant platelet disorder associated with arterial and venous thromboembolic events, frequently recurrent under oral anticoagulant therapy. It is characterized by hyperaggregability of platelets in platelet-rich plasma with adenosine diphosphate (ADP) and epinephrine (type I), epinephrine alone (type II), or ADP alone (type III). Combination of SPS with other congenital thrombophilic defects have been described. Low-dose aspirin treatment (80–100 mg) ameliorates the clinical symptoms and normalizes hyperaggregability. The precise etiology of this defect is at present not known, but receptors on the platelet surface may be involved.Patients and methods: We examined fifty patients with otherwise unexplained arterial or venous thrombosis. SPS evaluations were performed according to the method of Mammen. The equipment used was PACKS-4 aggregometer.Results: SPS was detected in eight patients. Clinically SPS resulted as an arterial thrombosis in five patients (2 coronary thrombosis, 2 cerebral ischemic attacks, 1 peripheral arterial thrombosis), two individuals showed deep venous thrombosis (DVT) and one patient passed recurrent abortions. SPS was classified as type I in 2 cases, 5 patients had type II and only 1 patient was diagnosed as type III, respectively (4 of them showed a glycoprotein IIIa abnormality).Conclusion: Because treatment with heparin or warfarin will not alleviate the thrombotic tendency of SPS, but simple aspirin therapy almost always will correct the defect and protect the individual from second event, it is particularly important to define the presence of this defect.

Talking about …

Talking about …

Antiphospholipid-Thrombosis Syndromes

Antiphospholipid antibodies are strongly associated with thrombosis and appear to be the most common of the acquired blood protein defects causing thrombosis. Based upon our experience, ∼25% of patients with unexplained venous thrombosis, ∼60% of patients with cerebrovascular thrombosis, ∼37% of patients with transient ischemic attacks, ∼18% with premature coronary artery thrombosis and ∼60% of patients with recurrent fetal loss (recurrent miscarriage syndrome) harbor antiphospholipid antibodies. Although the precise mechanism(s) whereby antiphospholipid antibodies alter hemostasis to induce a hypercoagulable state remain unclear, several theories have been advanced. Since the aPTT is unreliable in patients with lupus anticoagulant and is not usually prolonged in patients with anticardiolipin antibodies, definitive tests, ELISA for IgG, IgA and IgM anticardiolipin antibodies and the dilute Russel’s viper venom time (followed by cephalin correction for confirmation) for lupus anticoagulant should be immediately ordered when suspecting the antiphospholipid syndrome in individuals with otherwise unexplained thrombotic or thromboembolic events or recurrent fetal loss. However, if one strongly suspects antiphospholipid thrombosis syndrome clinically and assays for lupus anticoagulants and anticardiolipin antibodies are negative, specific assays for all three idiotypes of phosphatidylserine, phosphatidylethanolamine, phosphatidylcholine, phosphatidylinositol and phosphatidylglycerol are available and should be considered. These may clearly be indicated for difficult diagnostic cases of fetal wastage syndrome, and cerebrovascular events, but their significance in other types of thrombosis, particularly venous, remains unclear at present. Since about 65% of patients with antiphospholipid antibodies will fail warfarin therapy (rethrombose), it is important to define this common defect and institute appropriate antithrombotic therapy for appropriate time periods.

SYNDROMES OF THROMBOSIS AND HYPERCOAGULABILITY: Congenital and Acquired Causes of Thrombosis

Blood coagulation protein and platelet defects are now known to account for up to ninety percent of unexplained venous thrombosis and up to seventy percent of unexplained arterial thrombotic or ischemic events. This article summarizes the common and uncommon blood protein and platelet defects which should be suspected, and searched for, in patients with such events. Defining such defects will have major impact on secondary prevention and duration of antithrombotic therapy in the afflicted patient and impact on primary prevention for identified family members in those harboring hereditary defects.

Sticky Platelet Syndrome: A Common Cause of Unexplained Arterial and Venous Thrombosis

Sticky platelet syndrome (SPS) was first described in 1983. However, not until 1995 did the prevalence of SPS receive significant recognition in the medical literature. In 1995 we began to routinely add an SPS evaluation to patients re ferred for assessment for causation of arterial and venous thromboses to a large thrombosis hemostasis referral center. The results of our first 2-year experience suggest SPS to be a common cause of arterial and venous thromboses. With respect to otherwise unexplained venous thrombosis, the prevalence of SPS approximates that of activated protein C resistance (APC- R). During the past 24 months, we have evaluated 153 patients referred for evaluation of unexplained arterial or venous events. An evaluation for common and uncommon blood coagulation protein defects and SPS has been applied to these patients. It has been found that SPS accounted for about 21 % of otherwise unexplained arterial events (acute myocardial infarction, cere brovascular thrombosis, transient cerebral ischemic attacks, retinal thrombosis, and peripheral arterial thrombosis) and ac counted for about 13.2% of otherwise unexplained venous events (deep vein thrombosis, with or without pulmonary em bolus). These findings strongly suggest SPS to be a common cause of arterial and venous thromboses and a workup for SPS should be considered a routine assay in the workup of indi viduals with otherwise unexplained arterial or venous throm botic events. Because treatment with heparin or warfarin will not alleviate the thrombotic tendency of SPS, but simple aspirin therapy almost always will correct the defect and protect the individual from second events, it is particularly important to define the presence of this defect. Key Words: Thrombosis— Platelet defects—DVT—Coronary thrombosis—Cerebral thrombosis—Recurrent miscarriage.

Acquired risk factors for unexplained venous thrombosis

Acquired risk factors for unexplained venous thrombosis

Hereditary Heparin Cofactor II Deficiency and the Risk of Development of Thrombosis

Heparin cofactor II (HC II) levels were measured by electro-immunoassay in healthy volunteers, and patients with liver disease, DIC, proteinuria or a history of venous thrombosis. Analysis of the data in 107 healthy volunteers revealed that plasma HC II increases with age (at least between 20 and 50 years). HC II was found to be decreased in most patients with liver disease (mean value: 43%) and only in some patients with DIC. Elevated levels were found in patients with proteinuria (mean value 145%). In 277 patients with a history of unexplained venous thrombosis three patients were identified with a HC II below the lower limit of the normal range (60%). Family studies demonstrated hereditary HC II deficiency in two cases. Among the 9 heterozygotes for HC II deficiency only one patient had a well documented history of unexplained thrombosis. Therefore the question was raised whether heterozygotes for HC II deficiency can also be found among healthy volunteers. When defining a group of individuals suspected of HC II deficiency as those who have a 90% probability that their plasma HC II is below the 95% tolerance limits of the normal distribution in the relevant age group, 2 suspected HC II deficiencies were identified among the healthy volunteers. In one case the hereditary nature of the defect could be established. It is concluded that hereditary HC II deficiency is as prevalent among healthy volunteers as in patients with thrombotic disease. Further it is unlikely that heterozygosity for HC II deficiency in itself is a risk factor for the development of venous thrombosis.