A murine model of deep vein thrombosis Characterization and validation in transgenic mice

SummaryDeep vein thrombosis (DVT) occurs with high prevalence in association with a number of risk factors, including major surgery, trauma, obesity, bed rest (>5 days), cancer, a previous history of DVT, and several predisposing prothrombotic mutations. A novel murine model of DVT was developed for applications to preclinical studies of transgenically constructed prothrombotic lines and evaluation of new antithrombotic therapies. A transient direct-current electrical injury was induced in the common femoral vein of adult C57Bl/6 mice. A non-occlusive thrombus grew, peaking in size at 30 min, and regressing by 60 min, as revealed by histomorphometric volume reconstruction of the clot. Pre-heparinization greatly reduced clot formation at 10, 30, and 60 min (p<0.01 versus non-heparinized). Homozygous FactorV Leiden mice (analogous to the clinical FactorV Leiden prothrombotic mutation) on a C57Bl/6 background had clot volumes more than twice those of wild-types at 30 min (0.121±0.018 mm3 vs. 0.052±0.008 mm3, respectively; p<0.01). Scanning electron microscopy revealed a clot surface dominated by fibrin strands, in contrast to arterial thrombi which showed a platelet-dominated structure. This new model of DVT presents a quantifiable approach for evaluating thrombosis-related murine transgenic lines and for comparatively evaluating new pharmacologic approaches for prevention of DVT.

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The Natural History of Idiopathic Erythrocythosis: A Cohort Study of 74 Patients.

Blood ◽

10.1182/blood.v104.11.1506.1506 ◽

2004 ◽

Vol 104 (11) ◽

pp. 1506-1506

Author(s):

Finazzi Guido ◽

Ruggeri Marco ◽

Marconi Monica ◽

Rodeghiero Francesco ◽

Barbui Tiziano

Keyword(s):

Cohort Study ◽

Deep Vein Thrombosis ◽

Natural History ◽

Thrombotic Event ◽

Previous History ◽

Full Blood Count ◽

Vein Thrombosis ◽

History Of ◽

Thrombotic Complications ◽

Deep Vein

Abstract Patients with absolute erythrocytosis not due to a detectable cause and not fulfilling the criteria for diagnosis of polycythemia vera (PV) are descriptively classified as Idiopathic Erythrocytosis (IE). Based on scanty and retrospective data, this disease is considered to be an heterogeneous entity, including “early” PV, unrecognized secondary erythrocytosis and other miscellaneous conditions. However, appropriate prospective studies to evaluate the natural history of patients with IE are not available. We report here the results of a cohort study of 74 patients with IE (66 males, 8 females, median age 56 years, range 14–82) followed in two Italian institutions. By definition, at baseline all IE patients had increased hematocrit (median 54%, range 48–68%) and increased red blood cell mass (> 25% above mean normal predicted value), but normal leukocyte (median values 8.1 x 109/L, range 2.3–12) and platelet counts (median values 197 x 109/L, range 117–467), as well as normal erythropoietin level, arterial O2 saturation, chest X ray and abdominal ultrasound scanning (i.e. no splenomegaly). Granulocyte PRV-1 expression was also normal in 29 patients (39%) analyzed. At diagnosis, 12 patients (16%) reported a previous history of major thrombosis (7 ischemic cardiopathies, 4 cerebral ischemic events and 1 deep vein thrombosis). All IE patients were treated with phlebotomy to maintain a target hematocrit <45% and 24 patients (32%) were given aspirin, 100 mg/die, for previous thrombosis or microvascular symptoms. No cytotoxic drugs were given. The IE cohort was followed in the outpatient clinic with physical examination and full blood count at least every three months for a median period of 3.5 years (range 1–23). Twentythree patients (31%) were followed for more than 8 years. No patient was lost to follow-up. During the observation period, no disease potentially associated with secondary eryhtrocytosis emerged and no hematological transition into overt PV, myelofibrosis or acute leukemia occurred; two patients had a major thrombotic event (1 cerebral ischemia and 1 deep vein thrombosis) with an estimated incidence of thrombotic complications of 0.8% patient-year. The incidence of thrombosis was significantly lower than observed in 205 patients with overt PV followed during the same period in one of the two institutions (Bergamo, 3.49% patient-year, p<0.05). This study indicates that: a. the natural history of patients with IE, at least in the first years, is characterized by a remarkable and unexpected homogeneity without appearance of overt PV or diseases associated with secondary erythrocythosis; b. the diagnosis of IE identifies a group of absolute erythrocythoses at lower risk of thrombotic complications not requiring cytotoxic drug therapy; c. the diagnostic work-up of patients with absolute erythrocythosis should carefully distinguish IE from PV because the natural history and management of the two diseases is different.

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Swollen calf

Oxford Cases in Medicine and Surgery ◽

10.1093/oso/9780198716228.003.0034 ◽

2015 ◽

Author(s):

Hugo Farne ◽

Edward Norris-Cervetto ◽

James Warbrick-Smith

Keyword(s):

Hormone Replacement ◽

Oral Contraceptive Pill ◽

Trauma Surgery ◽

Bed Rest ◽

Major Surgery ◽

Diagnostic Challenge ◽

Vein Thrombosis ◽

Vessel Injury ◽

History Of ◽

Deep Vein

The main causes of an acutely swollen calf are shown in Figure 28.1. Note that it is possible for different pathologies to coexist: a patient may present with a deep vein thrombosis (DVT) and ruptured Baker’s cyst, for example. Also, many patients will get a swollen leg following surgery to that leg, but this shouldn’t present much of a diagnostic challenge (although you must obviously exclude DVT if the symptoms and signs warrant this) and therefore this is not included in the list in Figure 28.1. Yes, because most of the diseases listed in Figure 28.1 are local diseases and it would be highly unlikely for the patient to have two similar events in both legs at the same time. Instead, it would be more likely that the patient has either a systemic problem or a problem affecting central vessels. However, it is worth remembering that a DVT can arise in a patient with pre-existing bilateral leg oedema, so don’t rule out a DVT just because both legs are swollen. Figure 28.2 gives the main causes of bilateral swollen legs. • Are there any risk factors for venous thrombosis? Consider Virchow’s triad: ■ Hypercoagulable blood? Trauma, major surgery within the last 3 months, pregnancy and postpartum state (women are at increased risk of a venous clot for 6 weeks after birth and the risk is actually higher during the first few weeks after birth than during pregnancy itself), inflammatory bowel disease, active cancer, obesity (body mass index (BMI) >30 kg/m2), combined oral contraceptive pill or hormone replacement therapy (HRT), family history or past medical history of DVTs. ■ Stasis? Bed rest (>3 days) or long-haul travel (the actual length of flight that qualifies as ‘high risk’ is controversial). ■ Vessel injury? Trauma, surgery. • Has she felt breathless, had any chest pain, or coughed up any blood? If DVT is high on your differential list, it would be wise to enquire about symptoms of a possible pulmonary embolism (PE).

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Increased deep vein thrombosis cases during the COVID-19 quarantine

Phlebology The Journal of Venous Disease ◽

10.1177/0268355520977294 ◽

2020 ◽

pp. 026835552097729

Author(s):

Evren Karaali ◽

Osman Çiloğlu ◽

Orhan Saim Demirtürk ◽

Burak Keklikçioğlu ◽

İsmail Akçay ◽

...

Keyword(s):

Pulmonary Embolism ◽

Deep Vein Thrombosis ◽

Hospital Admissions ◽

Previous History ◽

Vein Thrombosis ◽

Symptomatic Pulmonary Embolism ◽

Number Of Patients ◽

Prophylactic Drug ◽

History Of ◽

Deep Vein

Objective The aim of this study was to compare the number of deep vein thrombosis (DVT) cases during the quarantine period for COVID-19 to that of the last year. Methods This study was conducted as a single-center and retrospective study. All hospital admissions during April 2020 and May 2020 were screened from the hospital records, and DVT cases were recorded. Likewise, all hospital admissions during April 2019 and May 2019 were screened, and DVT cases were noted. DVT cases of both years were compared. Results Among 480931 patients admitted to our hospital in April 2019 and May 2019, DVT was detected in 82 patients (0.017%) (47 males, 35 females) with a mean age of 56.99 ± 9.1 years (ranges 39 to 79 years). Besides, among 145101 patients admitted to our hospital in April 2020 and May 2020, DVT was detected in 123 patients (0.084%) (51 males, 72 females) with a mean age of 58.64 ± 8.9 years (ranges 40 to 83 years). Despite the decrease in the total number of patients admitted to the hospital, there was a significant increase in the number of DVT patients. Interestingly, there were only two symptomatic pulmonary-embolism cases in the 2019 period, whereas there were seven symptomatic pulmonary embolisms secondary to DVT in the 2020 period. Unfortunately, one patient died due to pulmonary embolism secondary to DVT in 2020. The previous history of DVT was remarkable in patients admitted during the COVID-19 confinement. Conclusion In conclusion, COVID-19 confinement seems to be associated with increased rates of DVT. Strict preventive measures such as exercise training or prophylactic drug use should be considered to prevent immobility-related DVT during the COVID-19 quarantine.

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Causative factors of deep vein thrombosis of lower limb in Indian population

International Surgery Journal ◽

10.18203/2349-2902.isj20175919 ◽

2017 ◽

Vol 5 (1) ◽

pp. 320

Author(s):

Reina Khadilkar ◽

Shubhi P. Bhatnagar ◽

Preet Dave

Keyword(s):

Deep Vein Thrombosis ◽

Previous History ◽

Vein Thrombosis ◽

Post Surgery ◽

Causative Factors ◽

Common Causes ◽

History Of ◽

And Gender ◽

A Prospective Study ◽

Deep Vein

Background: Deep vein thrombosis refers to the formation of an abnormal coagulum within the deep venous system. An accurate diagnosis of DVT is extremely important to prevent potentially fatal acute complications of pulmonary embolism (PE) and long-term complications of post phlebitis syndrome and pulmonary hypertension. There are many causative factors for DVT.Methods: This was a prospective study where 50 cases of DVT were admitted in this centre. Patients were evaluated in terms of causative factors of DVT. These were previous history of DVT, immobility, surgery, smoking, obesity and drugs. Age and gender comparisons were also done. The most common causes were recorded.Results: The most common cause was found to be immobility and post-surgery immobilization which constituted 90 % of the patients in the study. Advanced age and male gender showed a higher incidence of DVT.Conclusions: Early identification of the causes and the risk factors in the development of DVT can reduce the burden of the disease and contribute to its prevention and management.

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