Venous History Research Articles

Diagnosis of post-thrombotic syndrome: International union of phlebology (UIP) survey of medical specialists.

To review the current approaches to the diagnosis of Post-Thrombotic Syndrome (PTS) and to evaluate the potential need for a diagnostic tool. Medical specialists were invited to participate in an online survey of their current approaches to the diagnosis and management of PTS, including the use of scoring systems, diagnostic imaging techniques and the extent the practitioner reviews the patient's venous history. 502 participants completed the survey. Over 80% obtained imaging reports to confirm a history of deep vein thrombosis (DVT). 72% of participants always obtained an up-to-date duplex ultrasound for PTS diagnosis. Over 50% did not use a scoring system for either PTS diagnosis or management. 65% of the participants agreed that a new system for PTS diagnosis should be devised. Heterogeneity was observed in methods of diagnosing PTS by medical practitioners with frequent use of medical imaging studies and moderate use of scoring systems. Development of a new diagnostic tool for PTS should be considered for future studies.

International validation of a venous leg ulcer risk assessment tool

To internationally validate a tool for predicting the risk of delayed healing of venous leg ulcers (VLUs). A 10-item tool including sociodemographic factors, venous history, ulcer and lower limb characteristics, compression and mobility items to determine the risk of delayed healing of VLUs has previously been developed and validated in Australia. This study prospectively validated this tool using receiver operating characteristic (ROC) methods; using the area under the curve (AUC) to quantify the discriminatory capability of the tool to analyse the international populations of the UK, Austria and New Zealand. The validation of the tool in the UK, Austria and New Zealand has indicated that the model has moderate discrimination and goodness-of-fit with an AUC of 0.74 (95% CI: 0.66-0.82) for the total risk assessment score. The international validation of a risk assessment tool for delayed healing of VLUs will allow clinicians globally to be able to determine realistic outcomes from an early assessment and to be able to guide early tailored interventions to address the specific modifiable risk factors and thus promote timely healing.

Association between non-O blood group and spontaneous abortion in women with inherited thrombophilia

Abstract Background Spontaneous abortion is reported to be one of the most frequent pregnancy complications reaching a prevalence up to 15%. The association between congenital thrombophilia and pregnancy loss has been debated in several studies with conflicting results. We aimed to retrospectively evaluate the prevalence of inherited thrombophilia (i.e antithrombin, protein S and C deficiencies, factor V Leiden and prothrombin variant) in a group of women with a personal history of miscarriage. The prevalence non-O blood group, considered the most common thrombophilic condition, was concomitantly considered. Materials and methods A group of n. 566 women with a personal history of spontaneous abortion recruited among caregivers of patients admitted to the Medical Department of our University Hospital between December 2011 and December 2019 were enrolled. Women under 18 yrs, those with a personal history of venous and/or arterial thrombosis and with an acquired thrombophilic condition were excluded. An equally number of healthy women without a personal history of pregnancy loss acted as controls. The Odds Ratios (ORs) and 95% confidence intervals (CIs) were calculated as an estimate of pregnancy loss developing. Results Out of n. 566 enrolled women, n. 127 (22.4%) had an inherited thrombophilic condition. The prevalence of congenital thrombophilia was significantly higher in women with miscarriage than controls (OR 2.12; CI 95% 1.51–2.92). Non-O blood type was observed in n. 325 (57.4%) women. The prevalence of non-O blood group was significantly higher in women with pregnancy loss (p 0.01) and the association of thrombophilia and non-O blood type further increased the risk of pregnancy loss (OR 3.28; CI 95% 2.01–5.36). Conclusions Both inherited thrombophilia and non-O blood type should be considered risk factors for pregnancy loss. The knowledge of this information may help the clinician to better manage women with pregnancy loss. Further studies are required to confirm our findings. Funding Acknowledgement Type of funding sources: None.

A preliminary study of inherited thrombophilic risk factors in different clinical manifestations of venous thromboembolism in central Iran.

Background & objectives:Inherited thrombophilia is known to be an important risk factor for developing venous thromboembolism. Whether such abnormalities may impact the development of deep vein thrombosis (DVT) and pulmonary embolism (PE) differently is not well defined. This preliminary study was undertaken to compare thrombophilic polymorphism in patients with DVT and PE.Methods:A total of 35 DVT, 23 DVT/PE, and 37 PE patients admitted to the Hajar Hospital, Shahrekord, Iran, between October 2009 and February 2011 were included in the study and 306 healthy volunteers matched by age and sex from the same geographical area with no history of venous or arterial diseases were included as control group. Factor V Leiden (FV 1691G/A, rs6025), prothrombin (FII 20210G/A), methylene tetrahydrofulate reductase (MTHFR 677C/T, rs1801133), and PLA2 polymorphisms of platelet glycoprotein IIb/IIIa (GpIIIa 1565T/C, rs5918) were investigated by polymerase chain reaction-restriction fragment length polymorphism.Results:The number of patients with the investigated polymorphisms and homozygous carriers was significantly different among the groups (P<0.05). No significant difference was observed in the presence of FV 1691G/A and FII 20210G/A between any of the patients groups and the control group. GpIIIa 1565T/C and homozygous MTHFR 677C/T polymorphisms were higher in DVT patients compared with the control group (OR=6.65, 95% CI=3.09-14.30 and OR=4.08, 95% CI=1.35-12.38, respectively).Interpretation & conclusions:As none of the investigated polymorphisms were associated with PE, other thrombophilia polymorphisms may have a role in the pathogenesis of PE in these patients and should be investigated. Because of different prognostic risk factors among different types of patients, the treatment approach could be different.

Identification of Symptom Clusters in Patients With Chronic Venous Leg Ulcers

ContextPatients with venous leg ulcers experience multiple symptoms, including pain, depression, and discomfort from lower leg inflammation and wound exudate. Some of these symptoms impair wound healing and decrease quality of life (QOL). The presence of co-occurring symptoms may have a negative effect on these outcomes. The identification of symptom clusters could potentially lead to improvements in symptom management and QOL. ObjectivesTo identify the prevalence and severity of common symptoms and the occurrence of symptom clusters in patients with venous leg ulcers. MethodsFor this secondary analysis, data on sociodemographic characteristics, medical history, venous history, ulcer and lower limb clinical characteristics, symptoms, treatments, healing, and QOL were analyzed from a sample of 318 patients with venous leg ulcers who were recruited from hospital outpatient and community nursing clinics for leg ulcers. Exploratory factor analysis was used to identify symptom clusters. ResultsAlmost two-thirds (64%) of the patients experienced four or more concurrent symptoms. The most frequent symptoms were sleep disturbance (80%), pain (74%), and lower limb swelling (67%). Sixty percent of patients reported three or more symptoms at a moderate-to-severe level of intensity (e.g., 78% reported disturbed sleep frequently or always; the mean pain severity score was 49 of 100, SD 26.5). Exploratory factor analysis identified two symptom clusters: pain, depression, sleep disturbance, and fatigue; and swelling, inflammation, exudate, and fatigue. ConclusionTwo symptom clusters were identified in this sample of patients with venous leg ulcers. Further research is needed to verify these symptom clusters and to evaluate their effect on patient outcomes.

An Unusual Form of Immune Thrombocytopenic Purpura Characertized by a Platelet Activating IgG Antibody.

Autoimmune thrombocytopenia (ITP) is classically a disorder of accelerated platelet clearance and ineffective platelet production due to antibodies directed against common platelet membrane glycoproteins. The most common clinical manifestation of severe thrombocytopenia is bleeding. We report an unusual case of ITP in a 49 y.o. female with a 4 year history of thrombocytopenia, venous and arterial thrombosis secondary to a platelet activating IgG antibody.The patient was referred to one of the authors (HAL) for a second opinion with a diagnosis of ITP and a history of venous and arterial thrombosis. On presentation the patient was noted to have a platelet count of 34 × 109/L, a decreased fibrinogen of 128 mg/dL and D-dimers of greater than 4000 ng/ml. A diagnosis of chronic DIC was made and the patient was treated with therapeutic doses of LMW heparin resulting in an increase in her fibrinogen to 260 mg/dL, reduction in her D-dimers to <500 ng/ml and an increase in her platelet count to 118 × 109/L. An extensive clinical and laboratory evaluation, included screening for occult malignancy, cavernous hemangioma, antiphospholipid antibodies, dysfibrinogenemia, inhibitory antibodies against protein C and S, failed to disclose an etiology for her chronic consumptive coagulopathy. After 2 months of LMWH therapy the patient had a progressive drop in her platelet count to <30 × 109/L without evidence of recurrent coagulopathy. The patient's thrombocytopenia was refractory to corticosteroids, Rituxan, azathioprine, cyclosporine, but responsive to IVIG. When the patients LMW heparin was stopped, the patient had evidence of a recurrence of her DIC as defined by an increase in her D-dimer and decreased fibrinogen. The patient underwent an open splenectomy which was complicated by portal vein and superior mesenteric vein thrombosis requiring catheter directed fibrinolysis and reinstitution of LMW heparin therapy. Repeated ELISA and functional assays for heparin induced thrombocytopenia were negative. However, the patient's heat inactivated plasma and serum were shown to induce spontaneous aggregation. Patient IgG was subsequently isolated by staph A chromatography and found to be a potent inducer of platelet aggregation. Platelet specific IgG was further isolated from the patient's IgG by affinity chromatography on a column of solubilized platelet membrane proteins. The affinity isolated antibody was then analyzed by the Western blotting using solubilized platelet membranes. Patient antibody was found to react with a 50 kD platelet membrane protein which has yet to be fully characterized.At the present time the patient remains on LMW heparin, but requires frequent infusions of IVIG to maintain platelet counts above 30 × 109/L. We are aware of only one other reported case of a spontaneous platelet activating antibody and no other case characterized by chronic DIC.

The G1691 --> A mutation of factor V, but not the G20210 --> A mutation of factor II or the C677 --> T mutation of methylenetetrahydrofolate reductase genes, is associated with venous thrombosis in patients with lupus anticoagulants.

Arterial and venous thrombosis are the most common manifestations of antiphospholipid syndrome. To investigate whether genetic determinants contribute to their thrombotic risk, we studied the prevalence of the G1691 --> A mutation in the gene coding for factor V, the G20210 --> A mutation in the prothrombin gene and the C677 --> T mutation in the methylenetetrahydrofolate reductase gene in 152 patients with lupus anticoagulants. One hundred and twenty-eight cases (84%) also had increased titres of anticardiolipin antibodies. History of thrombosis was present in 96 patients (63%); 67 suffered from venous thrombosis only, 23 cases had arterial thrombosis only, six patients had both venous and arterial thrombosis. Five patients were heterozygous for the G1691 --> A mutation in the factor V gene (3%). All of them (100%) suffered from venous thrombosis compared with 68 out of the 147 cases without the mutation (46%) (P = 0.0474). The prevalence of the G20210 --> A mutation in the prothrombin gene was evaluated in 145 patients; eight of these patients were heterozygous (5%). Four of these patients (50%) experienced venous thrombosis compared with 65 out of the 137 patients without the mutation (47%) (P = ns). Neither mutation was associated with arterial thrombotic events. No patient carried both mutations. The C677 --> T mutation in the methylenetetrahydrofolate reductase gene was assessed in 83 patients; 15 of them (18%) were homozygous and 37 (44%) were heterozygous. There was no significant association between the status of the mutation and history of venous and arterial thrombosis. No significant correlation was found among the three groups. In conclusion, only the G1691 --> A mutation in the factor V gene was associated with the thrombotic risk of patients with lupus anticoagulants.

Fibrinogen B??14 Arg???Cys

A single base substitution (C-->T) in exon II of the Bbeta fibrinogen gene resulting in an Arg14-->Cys replacement was identified in a young woman with a history of recurrent thrombotic stroke. The patient's plasma showed prolongation of the thrombin and Reptilase times, and plasma fibrinogen, which was low when determined by chronometric assay (Clauss technique) was normal by clot weight. Dysfibrinogenaemia associated with the same mutation was identified in eight family members including two siblings with a history of venous and arterial thrombosis. Fibrin monomer polymerization with thrombin, Reptilase and Agkistrodon contortrix contortrix venom was defective. Polymerization studies revealed a reduced rate of polymerization compared with normal plasma, which improved on cooling from 37 degrees C to 20 degrees C. Plasma viscosity in the affected individuals was normal. Flow cytometric analysis of platelets from the proband and another affected member showed no increase in surface bound fibrinogen. Euglobulin clot lysis time was normal. The same point mutation has been described previously in individuals with thrombosis. This family adds further to the genotype-phenotype correlation of the dysfibrinogenaemias and provides strong evidence for a genuine association of fibrinogen BbetaArg14Cys with thrombosis. The mechanism underlying a causal relationship with the increased incidence of thrombosis remains obscure but a review of related dysfibrinogens suggests that the addition of a free thiol group rather than the loss of the thrombin cleavage site may be important.

Rapid detection of a protein C gene mutation present in the asymptomatic and not in the thrombosis-prone lineage.

The presence of mutations in the serine protease domain of protein C was investigated by temperature gradient gel electrophoresis of PCR products in five patients with protein C deficiency and thrombosis. Molecules with an altered melting behaviour were detected in one subject with a history of venous and arterial thrombosis. Direct sequencing showed that a G deletion, present in the heterozygous state, caused a reading frame shift at Trp 300 and subsequently a premature termination at the codon 335. The resulting suppression of the protein C catalytic function explains the reduction of protease activity to half. In addition the mutation caused a reduction of the antigen level in plasma. Temperature gradient gel electrophoresis enabled the rapid detection of the gene alteration in the family of the propositus. Several members of the paternal lineage had had severe thrombotic episodes. Unexpectedly the mutation was found to be inherited from the clinically asymptomatic maternal lineage, thus suggesting that an additional unknown defect from the paternal lineage is present in the thrombosis-prone propositus.

Methods for detecting lupus anticoagulants and their relation to thrombosis and miscarriage in patients with systemic lupus erythematosus.

To examine the sensitivity and specificity to past thrombotic events of four different coagulation tests, which screen for lupus anticoagulant (LA), and of anticardiolipin antibodies in patients with systemic lupus erythematosus. Fifty three consecutive patients with systemic lupus erythematosus were studied of whom three males and 21 females, aged 21-60 years, had a history of venous and arterial thrombosis, or miscarriage, or both. Activated partial thromboplastin time (aPTT), dilute Russell's viper venom time (dRVVT), kaolin clotting time (KCT), dilute aPTT and the circulating titre of anticardiolipin antibodies were investigated in the two groups of patients and in 20 healthy control subjects. The prolonged dilute aPTT was more sensitive to thromboses or miscarriages, or both than dRVVT (p less than 0.05), KCT (p less than 0.01), and aPTT (p less than 0.001). No significant differences in specificity were found among aPTT (100%), dRVVT (93%), KCT (93%) and dilute aPTT (86.2%); but aPTT and dRVVT were significantly more specific (p less than 0.01, p less than 0.05, respectively) than anticardiolipin antibodies. The study shows a strong association between lupus anticoagulant and thrombosis when a very sensitive test such as the dilute aPTT is used. The combination of this assay with a very specific test such as dRVVT might enable patients with SLE at high risk of thrombosis to be identified.