Thanks to neuro-icu.com for highlighting this one: The American Heart Association and American Stroke Association have produced guidelines for the diagnosis and management of cerebral venous thrombosis. Here is a summary of their recommendations. The full text of the guidelines is available via the link at the bottom. Routine Blood Work
In patients with suspected CVT, routine blood studies consisting of a complete blood count, chemistry panel, prothrombin time, and activated partial thromboplastin time should be performed (Class I; Level of Evidence C).
Screening for potential prothrombotic conditions that may predispose a person to CVT (eg, use of contraceptives, underlying inflammatory disease, infectious process) is recommended in the initial clinical assessment (specific recommendations for testing for thrombophilia are found in the long-term management section of this document) (Class I; Level of Evidence C).
A normal D-dimer level according to a sensitive immunoassay or rapid enzyme-linked immunosorbent assay (ELISA) may be considered to help identify patients with low probability of CVT (Class IIb; Level of Evidence B). If there is a strong clinical suspicion of CVT, a normal D-dimer level should not preclude further evaluation.
Common Pitfalls in the Diagnosis of CVT
In patients with lobar ICH of otherwise unclear origin or with cerebral infarction that crosses typical arterial boundaries, imaging of the cerebral venous system should be performed (Class I; Level of Evidence C).
In patients with the clinical features of idiopathic intracranial hypertension, imaging of the cerebral venous system is recommended to exclude CVT (Class I; Level of Evidence C).
In patients with headache associated with atypical features, imaging of the cerebral venous system is reasonable to exclude CVT (Class IIa; Level of Evidence C).
Imaging in the Diagnosis of CVT
Although a plain CT or MRI is useful in the initial evaluation of patients with suspected CVT, a negative plain CT or MRI does not rule out CVT. A venographic study (either CTV or MRV) should be performed in suspected CVT if the plain CT or MRI is negative or to define the extent of CVT if the plain CT or MRI suggests CVT (Class I; Level of Evidence C).
An early follow-up CTV or MRV is recommended in CVT patients with persistent or evolving symptoms despite medical treatment or with symptoms suggestive of propagation of thrombus (Class I; Level of Evidence C).
In patients with previous CVT who present with recurrent symptoms suggestive of CVT, repeat CTV or MRV is recommended (Class I; Level of Evidence C).
Gradient echo T2 susceptibility-weighted images combined with magnetic resonance can be useful to improve the accuracy of CVT diagnosis (Class IIa; Level of Evidence B).
Catheter cerebral angiography can be useful in patients with inconclusive CTV or MRV in whom a clinical suspicion for CVT remains high (Class IIa; Level of Evidence C).
A follow-up CTV or MRV at 3 to 6 months after diagnosis is reasonable to assess for recanalization of the occluded cortical vein/sinuses in stable patients (Class IIa; Level of Evidence C).
Management and Treatment
Patients with CVT and a suspected bacterial infection should receive appropriate antibiotics and surgical drainage of purulent collections of infectious sources associated with CVT when appropriate (Class I; Level of Evidence C).
In patients with CVT and increased intracranial pressure, monitoring for progressive visual loss is recommended, and when this is observed, increased intracranial pressure should be treated urgently (Class I; Level of Evidence C).
In patients with CVT and a single seizure with parenchymal lesions, early initiation of antiepileptic drugs for a defined duration is recommended to prevent further seizures (Class I; Level of Evidence B).
In patients with CVT and a single seizure without parenchymal lesions, early initiation of antiepileptic drugs for a defined duration is probably recommended to prevent further seizures (Class IIa; Level of Evidence C).
In the absence of seizures, the routine use of antiepileptic drugs in patients with CVT is not recommended (Class III; Level of Evidence C).
For patients with CVT, initial anticoagulation with adjusted-dose UFH or weight-based LMWH in full anticoagulant doses is reasonable, followed by vitamin K antagonists, regardless of the presence of ICH (Class IIa; Level of Evidence B).
Admission to a stroke unit is reasonable for treatment and for prevention of clinical complications of patients with CVT (Class IIa; Level of Evidence C).
In patients with CVT and increased intracranial pressure, it is reasonable to initiate treatment with acetazolamide. Other therapies (lumbar puncture, optic nerve decompression, or shunts) can be effective if there is progressive visual loss. (Class IIa; Level of Evidence C).
Endovascular intervention may be considered if deterioration occurs despite intensive anticoagulation treatment (Class IIb; Level of Evidence C). In patients with neurological deterioration due to severe mass effect or intracranial hemorrhage causing intractable intracranial hypertension, decompressive hemicraniectomy may be considered (Class IIb; Level of Evidence C).
For patients with CVT, steroid medications are not recommended, even in the presence of parenchymal brain lesions on CT/MRI, unless needed for another underlying disease (Class III; Level of Evidence B).
Long-Term Management and Recurrence of CVT
Testing for prothrombotic conditions, including protein C, protein S, antithrombin deficiency, antiphospholipid syndrome, prothrombin G20210A mutation, and factor V Leiden, can be beneficial for the management of patients with CVT. Testing for protein C, protein S, and antithrombin deficiency is generally indicated 2 to 4 weeks after completion of anticoagulation. There is a very limited value of testing in the acute setting or in patients taking warfarin. (Class IIa; Level of Evidence B).
In patients with provoked CVT (associated with a transient risk factor), vitamin K antagonists may be continued for 3 to 6 months, with a target INR of 2.0 to 3.0 (Table 3) (Class IIb; Level of Evidence C).
In patients with unprovoked CVT, vitamin K antagonists may be continued for 6 to 12 months, with a target INR of 2.0 to 3.0 (Class IIb; Level of Evidence C).
For patients with recurrent CVT, VTE after CVT, or first CVT with severe thrombophilia (ie, homozygous prothrombin G20210A; homozygous factor V Leiden; deficiencies of protein C, protein S, or antithrombin; combined thrombophilia defects; or antiphospholipid syndrome), indefinite anticoagulation may be considered, with a target INR of 2.0 to 3.0 (Class IIb; Level of Evidence C).
Consultation with a physician with expertise in thrombosis may be considered to assist in the pro- thrombotic testing and care of patients with CVT (Class IIb; Level of Evidence C).
Management of Late Complications (Other Than Recurrent VTE)
In patients with a history of CVT who complain of new, persisting, or severe headache, evaluation for CVT recurrence and intracranial hypertension should be considered (Class I; Level of Evidence C)
CVT in pregnancy
For women with CVT during pregnancy, LMWH in full anticoagulant doses should be continued throughout pregnancy, and LMWH or vitamin K antagonist with a target INR of 2.0 to 3.0 should be continued for at least 6 weeks postpartum (for a total minimum duration of therapy of 6 months) (Class I; Level of Evidence C).
It is reasonable to advise women with a history of CVT that future pregnancy is not contraindicated. Further investigations regarding the underlying cause and a formal consultation with a hematologist and/or maternal fetal medicine specialist are reasonable. (Class IIa; Level of Evidence B).
It is reasonable to treat acute CVT during pregnancy with full-dose LMWH rather than UFH (Class IIa; Level of Evidence C).
For women with a history of CVT, prophylaxis with LMWH during future pregnancies and the postpartum period is probably recommended (Class IIa; Level of Evidence C).
Children
Supportive measures for children with CVT should include appropriate hydration, control of epileptic seizures, and treatment of elevated intracranial pressure (Class I; Level of Evidence C).
Given the potential for visual loss owing to severe or long-standing increased intracranial pressure in children with CVT, periodic assessments of the visual fields and visual acuity should be performed, and appropriate measures to control elevated intracranial pressure and its complications should be instituted (Class I; Level of Evidence C).
In all pediatric patients, if initial anticoagulation treatment is withheld, repeat neuroimaging including venous imaging in the first week after diagnosis is recommended to monitor for propagation of the initial thrombus or new infarcts or hemorrhage (Class I; Level of Evidence C).
In children with acute CVT diagnosed beyond the first 28 days of life, it is reasonable to treat with full-dose LMWH even in the presence of intracra- nial hemorrhage (Class IIa; Level of Evidence C).
In children with acute CVT diagnosed beyond the first 28 days of life, it is reasonable to continue LMWH or oral vitamin K antagonists for 3 to 6 months (Class IIa; Level of Evidence C).
In all pediatric patients with acute CVT, if initial anticoagulation is started, it is reasonable to perform a head CT or MRI scan in the initial week after treatment to monitor for additional hemor- rhage (Class IIa; Level of Evidence C).
Children with CVT may benefit from thrombophilia testing to identify underlying coagulation defects, some of which could affect the risk of subsequent rethromboses and influence therapeutic decisions (Class IIb; Level of Evidence B).
Children with CVT may benefit from investigation for underlying infections with blood cultures and sinus radiographs (Class IIb; Level of Evidence B).
In neonates with acute CVT, treatment with LMWH or UFH may be considered (Class IIb; Level of Evidence B).
Given the frequency of epileptic seizures in children with an acute CVT, continuous electroencephalography monitoring may be considered for individuals who are unconscious or mechanically ventilated (Class IIb; Level of Evidence C).
In neonates with acute CVT, continuation of LMWH for 6 weeks to 3 months may be considered (Class IIb; Level of Evidence C).
The usefulness and safety of endovascular intervention are uncertain in pediatric patients, and its use may only be considered in carefully selected patients with progressive neurological deterioration despite intensive and therapeutic levels of anticoagulant treatment (Class IIb; Level of Evidence C).
Diagnosis and Management of Cerebral Venous Thrombosis: A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association Stroke. 2011 Feb 3. [Epub ahead of print] Full Text
Made a radiologist go red with rage recently? If not, you could try showing them this paper1 in this month’s Annals of Emergency Medicine that describes accurate emergency physician ultrasound diagnosis of deep vein thrombosis after just ten minutes training!
ED patients with a suspected lower extremity deep venous thrombosis were assessed using a bedside 2-point compression technique by emergency physicians using a portable US machine and all patients subsequently underwent duplex ultrasonography performed by the Department of Radiology.
The emergency physicians had a 10-minute training session before enrolling patients
The techinque involved 2 specific points: the common femoral and popliteal vessels, with subsequent compression of the common femoral and popliteal veins. The study result was considered positive for proximal lower extremity deep venous thrombosis if either vein was incompressible or a thrombus was visualised. Free DVT ultrasound tutorial at Sonoguide.com
A total of 47 physicians performed 199 2-point compression ultrasonographic examinations in the ED.
There were 45 proximal lower extremity deep venous thromboses observed on Department of Radiology evaluation, all correctly identified by ED 2-point compression ultrasonography. The 153 patients without proximal lower extremity deep venous thrombosis all had a negative ED compression ultrasonographic result. One patient with a negative Department of Radiology ultrasonographic result was found to have decreased compression of the popliteal vein on ED compression ultrasonography, giving a single false-positive result, yet repeated ultrasonography by the Department of Radiology 1 week later showed a popliteal deep venous thrombosis. The sensitivity and specificity of ED 2-point compression ultrasonography for deep venous thrombosis were 100% (95% confidence interval 92% to 100%) and 99% (95% confidence interval 96% to 100%), respectively.
These figures may appear to fail the ‘sniff test’, ie. seem too good to be true. Not surprisingly Annals acknowledge this by providing an accompanying editorial2 by emergency ultrasound heavyweight Michael Blaivas, MD, who is healthily skeptical of such a minimal training program but is overwhelmingly supportive of the principle. Dr Blaivas also provides a fantastic summary of the existing evidence base on ED ultrasound for DVT. To me he hits the nail on the head when with a philosophical point on the practice of EM: ‘One common challenge proponents of any new application or procedure face in emergency medicine is overcoming the inertia of comfort with the status quo.’ Spot on, Dr B.
1. Compression Ultrasonography of the Lower Extremity With Portable Vascular Ultrasonography Can Accurately Detect Deep Venous Thrombosis in the Emergency Department Annals of Emergency Medicine 2010;56(6):601-10
2. Point-of-Care Ultrasonographic Deep Venous Thrombosis Evaluation After Just Ten Minutes’ Training: Is This Offer Too Good to Be True? Annals of Emergency Medicine 2010;56(6):611-3
The guys at ‘EM Live’ have a short video on how to do DVT ultrasound:
"Man, she's enormous. I can't reach the chest to auscultate!"
Given that thromboembolism is the leading cause of maternal death in the UK according to the latest UK CEMACE report, it would be nice to have reliable non-ionising tests in the ED to rapidly rule out this disease in pregnant women. Unfortunately, the alveolar-arterial oxygen gradient does not do the job.
A recent study compared the A-a gradient with CTPA as the gold standard. Of 102 patients who were pregnant or up to 6 weeks post-partum, there were 13 PEs (2 antepartum and 11 postpartum). The best sensitivity, specificity, and negative and positive predictive values for A-a gradients were 76.9%, 20.2%, 80.0%, and 11.5%, respectively. Assessment of the alveolar-arterial oxygen gradient as a screening test for pulmonary embolism in pregnancy Am J Obstet Gynecol. 2010 Oct;203(4):373.e1-4
In acute pulmonary embolism, a well-recognised pattern of right ventricular wall motion reported by McConnell is characterised by normal RV apex (RVa) contractility with akinesia of the RV free wall. A study using an echo techique called longitudinal velocity vector imaging (VVI) was conducted to describe RVa mechanics in relation to the rest of the RV in patients with a proven acute PE (aPE) and to compare these results to healthy volunteers and to patients with known chronic pulmonary hypertension (cPH). There were no significant differences in segmental strain patterns between the aPE and cPH groups. The authors suggest that McConnell’s sign is probably a visual illusion; preserved RVa contractility might be due to tethering of the RVa to a hyperdynamic left ventricle in the presence of an acutely dilated RV and this is the most likely explanation of the regional pattern of RV dysfunction seen in aPE patients.
Video describing McConnell’s sign from YouTube:
Academic Emergency Medicine has a free article on sonographic detection of submassive pumonary embolism, with three video clips.
One of the videos shows a nice demonstration of the McConnell sign (RV mid-segment dilation with apical sparing), which has been reported to be specific for (sub)massive PE. According to this article however, it has been reported that the McConnell sign is present in two thirds of patients with RV infarction and is only 33% specific for PE. Continuous wave Doppler helps differentiate RV infarction from submassive PE by demonstrating an increased tricuspid regurgitation RA-RV pressure gradient in submassive PE and a normal or low gradient in RV infarction.
The full article is available here
Wouldn’t it be great to have a reliable, radiation-free way to diagnose pulmonary embolism? Unfortunately, Magnetic Resonance Angiography is not it. In a study of 371 patients across 7 hospitals from the PIOPED III (Prospective Investigation of Pulmonary Embolism Diagnosis III) investigators, the test was technically inadequate because of poor-quality images in 25% of cases. In those tests that were readable, the sensitivity was only 78%. Gadolinium-Enhanced Magnetic Resonance Angiography for Pulmonary Embolism: A Multicenter Prospective Study (PIOPED III) Ann Intern Med. 2010 Apr 6;152(7):434-43
D-dimer levels below the conventional cut-off point of 500 µg/l combined with a “low/intermediate” or “unlikely” clinical probability can safely rule out the diagnosis in about 30% of patients with suspected pulmonary embolism.
However, the D-dimer concentration increases with age and its specificity for embolism decreases, which makes the test less useful to exclude pulmonary embolism in older patients; the test is able to rule out pulmonary embolism in 60% of patients aged <40 years, but in only 5% of patients aged >80.
A new, age dependent cut-off value was derived and then validated in two independent retrospective datasets from Belgium, France, the Netherlands, and Switzerland. They studied over 5000 patients aged >50 years.
The new D-dimer cut-off value was defined as (patient’s age x 10) µg/l in patients aged >50.
In 1331 patients in the derivation set with an “unlikely” score from clinical probability assessment, pulmonary embolism could be excluded in 42% with the new cut-off value versus 36% with the old cut-off value (<500 µg/l). In the two validation sets, the increase in the proportion of patients with a D-dimer below the new cut-off value compared with the old value was 5% and 6%. This absolute increase was largest among patients aged >70 years, ranging from 13% to 16% in the three datasets. The failure rates (all ages) were 0.2% (95% CI 0% to 1.0%) in the derivation set and 0.6% (0.3% to 1.3%) and 0.3% (0.1% to 1.1%) in the two validation sets. Potential of an age adjusted D-dimer cut-off value to improve the exclusion of pulmonary embolism in older patients: a retrospective analysis of three large cohorts.
ECGs from a prospective study of patients in the ED with suspected pulmonary embolism were studied to identify the relative frequency of ECG features of pulmonary hypertension. For a patient to be eligible for enrollment, a physician was required to have sufficient suspicion for pulmonary embolism to order objective diagnostic testing in the ED. Such testing included D-dimer measurement, computed tomography pulmonary angiography, ventilation/perfusion scanning, or venous ultrasonography.
ECGs were done in 6049 patients, 354 (5.9%) of whom were diagnosed with pulmonary embolism. The frequency, positive likelihood ratio (LR+) and 95% confidence interval (CI) of each predictor were as follows:
S1Q3T3 8.5% with pulmonary embolism versus 3.3% without pulmonary embolism (LR+ 3.7; 95% CI 2.5 to 5.4)
nonsinus rhythm, 23.5% versus 16.6% (LR+ 1.4; 95% CI 1.2 to 1.7)
inverted T waves in V1 to V2, 14.4% versus 8.1% (LR+ 1.8; 95% CI 1.3 to 2.3)
inversion in V1 to V3, 10.5% versus 4.0% (LR+ 2.6; 95% CI 1.9 to 3.6)
inversion in V1 to V4, 7.3% versus 2.0% (LR+ 3.7; 95% CI 2.4 to 5.5)
incomplete right bundle branch block, 4.8% versus 2.8% (LR+ 1.7; 95% CI 1.0 to 2.7)
tachycardia (pulse rate>100 beats/min), 28.8% versus 15.7% (LR+ 1.8; 95% CI 1.5 to 2.2).
The authors point out that the study may be subject to reporting bias or incorporation bias because those patients with ECG abnormalities may have then been more likely to undergo further evaluation for PE.
Overall, they summarise that the main findings were that the S1Q3T3 pattern and precordial T-wave inversions had the highest LR(+) values with lower-limit 95% CIs above unity, whether or not the patient had preexisting cardiopulmonary disease, but emphasise that the sensitivities of each of these findings were low, and clinicians should not decrease their suspicion for pulmonary embolism according to their absence.
Likelihood ratios and specificities were similar when patients with previous cardiopulmonary disease were excluded from analysis. 12-Lead ECG Findings of Pulmonary Hypertension Occur More Frequently in Emergency Department Patients With Pulmonary Embolism Than in Patients Without Pulmonary Embolism Ann Emerg Med. 2010 Apr;55(4):331-5
A prospective open label randomised controlled trial from China compared two doses of r-tPA for massive or submassive PE. 50 mg / 2hr was as efficacious as 100 mg / 2hr but had fewer bleeding complications. Bleeding was much more common in patients under 65 kg, suggesting perhaps there should be dose per kg instead of a nice round number? Efficacy and safety of low dose recombinant tissue-type plasminogen activator for the treatment of acute pulmonary thromboembolism: a randomized, multicenter, controlled trial. Chest. 2010 Feb;137(2):254-62
A review article on pulmonary embolism in pregnancy reminds us that the mortality associated with untreated PE far outweighs the potential oncogenic and teratogenic risk incurred by fetal exposure to diagnostic imaging for PE. Teratogenicity
The minimum dose of radiation associated with increased risk of teratogenicity in human beings has yet to be firmly established, but on the basis of compiled mouse, rat, and human data, radiation exposure of 0·1 Gy at any time during gestation is regarded as a practical threshold beyond which induction of congenital abnormalities is possible. Oncogenicity
An exposure of the conceptus to 0·01 Gy above natural background radiation increases the probability of cancer before the age of 20 years from 0·03% to 0·04%.
Reassuringly, a chest radiograph, ventilation perfusion scan, and conventional pulmonary angiogram combined with CT pulmonary angiogram expose the fetus to a total of 0·004 Gy. Pulmonary embolism in pregnancy Lancet. 2010 Feb 6;375(9713):500-12
