CME INDIA Case Presentation by Dr. Vijay Arora, Senior Director, Internal Medicine, Max Hospital, Delhi.

CME INDIA Case Study

A 42 year-old-male with symptoms of mild Covid

• He recovered from Mild Covid.
• He did not have any comorbidities.

He had moderately severe disease in April-May 2021 , even after 2 doses of vaccine with CTSS-13/25 , recovered after month long illness( was admitted twice)

• rt PCT was positive which became negative on 10/01/2022.
• Took only paracetamol and anti-allergic as needed.

What made him to consult further?

• He started having persistent headaches after 3 days of recovery.
• The headache was global in nature, with no associated vomiting. The evening preceding admission, the patient had also noted photophobia, speech disturbance and weakness of his right upper limb. There was no history of trauma, no relevant past medical or drug history and no family history of note. The patient did however mention partaking in unaccustomed strenuous activity earlier in the week.
• Initially self-medications were done for two days, then he consulted.
• On examination, the patient’s observations were stable with a GCS of 15/15. His pupils, fundi and speech appeared normal and there was no evidence of any focal neurological deficit or meningism.

Relevant tests were done

But Headache was so agonizing and persistent

Fundus exam was done

• It revealed B/L early papilledema.

MRV done same day

It showed Sagittal sinus Thrombosis

What was done?

• Magnetic resonance venography (MRV) confirmed the presence of a superior sagittal sinus thrombosis with a small venous infarct and the patient was subsequently anticoagulated with enoxaparin and warfarin.
• Further investigations including echocardiography, carotid artery Doppler, coagulation studies and antiphospholipid antibody titres were all normal.
• The patient is under recovery.

CME INDIA Case Discussion:

When in Covid cases anti-platelets/Anti-coagulants needed?

Dr. Sanjay Gandhi, Pune: Use of Aspirin and Rivaroxaban must be considered in almost all cases where thrombogenesis is possibly augmented by NCD + Acute viral insult and overweight/obesity background….

Dr. Satish Kumar, Bokaro: Have been using this at the time of discharge of all COVID positive ACS patients. Most of them have high D-Dimer values.

Dr. Santosh Malpani, Nanded: For Covid, literature is not that mature. Follow up studies of recovered Covid patients with different categories will throw some light on this.

Dr. Swati Srivastava, Jaipur: We used anti-coagulant and aspirin rampantly in the second wave. But in third wave probably did not even do D Dimer testing adequately. I have seen bradycardia in Covid cases in the third wave.

Dr. Basab Ghosh, Agartala: By now it’s known that Covid-19 is a thrombo-embolic disease. Might be pathophysiology of Covid-19 is the reason to go for Aspirin. Till 1st wave many recommendations suggest oral anticoagulants as prophylaxis during discharge.

Dr. Vijay Arora, Delhi: Viremia —> Inflammation—> hyperinflammation (cytokines storm) —> Thrombosis. In mild or asymptomatic patients, we don’t need anti thrombosis medications. Even with markers of thrombosis WNL, Pt has been found to have CVT.

Dr. Varun Kumar, Ranchi: Blaming everything on COVID is also not right. There are reports of AMI in COVID patients but it can be incidental also. Viral illnesses can cause vascular inflammation, plaque rupture & AMI. So, the same can be seen in COVID also. Thrombosis of coronaries due to hypercoagulable state in COVID is uncommonly seen. Diabetes itself is the biggest risk factor for CAD & any presentation of CAD in diabetic or diabetic cardiomyopathy, blame 100% goes to diabetes. It is not an incidental thing.

Dr. Pradeep Sahay, Giridih: The hypercoagulability of Covid leading to macro and micro rhrombi can cause cardiovascular and systemic derangements. Covid 19 has definitely disrupted management of those with CVS disease. Data from China showed elevated Troponin and D dimer even in the absence of CV disease. This may have been a coincidence due to the sweeping 3rd wave but in a recent Italian study, 85% of STEMI patients were found Covid positive. In a study it was seen that (2020, November) patients on aspirin had 43%less chances of ending up in the ICU,44%less chance of being put on the ventilator and 47% less chance of dying in the hospital.

Dr. Noni G Singha, Dibrugarh: What I feel if anyone having slightest risk factor like DM, HTN, Smokers, obese people family history of heart disease should undergo simple cardiac workup before resuming to work. It seems Covid is also a triggering factor for heart diseases. I advise to go for at least ECG and Echo to recovered people who all are having persisted tachycardia to rule out myocarditis. Three of my pts are having only high d dimer (one 27 yrs. young female with no comorbidity, mild symptomatic) with no other lab abnormalities. Anyone else has any such finding?

Dr. Prabhat Agarwal, Agra: I think Covid itself raises d dimer without any significant problem.

Points of Interest

• COVID-19 leads to higher rates of thrombotic events than previously observed in other comparable clinical situations.
• Prophylactic dosage of parenteral anticoagulants during hospitalisation is mandatory, and there is emerging consensus about optimal dose of in-hospital heparin as primary thromboprophylaxis.
• There is no consensus on extended thromboprophylaxis after hospitalisation. 
• During the COVID-19 pandemic, low-dose aspirin is used effectively in secondary prevention of ASCVD, prevention of VTE after total hip or knee replacement, prevention of pre-eclampsia and post discharge treatment for MIS-C.
• Prehospital low-dose aspirin therapy may reduce the risk of ICU admission and mechanical ventilation in hospitalised patients with COVID-19, whereas aspirin association with mortality is still debatable.
• Many consensus groups recommend the use of a low-dose aspirin regimen for primary prevention of arterial thromboembolism in patients aged 40–70 years who are at high ASCVD risk, or intermediate ASCVD risk with a risk enhancer such as the family history of premature CVD and have a low risk of bleeding.
• Aspirin protective roles in COVID-19-associated ALI/ARDS, vascular thrombosis without previous CVD and mortality needs further investigation to establish guidelines.

CME INDIA Learning Points

• Cerebral venous thrombosis can present with variable signs and symptoms.
• It include a headache, benign intracranial hypertension, subarachnoid haemorrhage, focal neurological deficit, seizures, unexplained altered sensorium, and meningoencephalitis.
• Covid and CVST:
  • There has been increasing reports associating the coronavirus disease 2019 (COVID-19) with thromboembolic phenomenon including ischemic strokes and venous thromboembolism. Cerebral venous thrombosis (CVT) is a rare neurovascular emergency that has been observed in some COVID-19 patients, yet much remains to be learnt of its underlying pathophysiology.
  • It has been proposed that COVID-19 may induce a prothrombotic state, as supported by the elevated levels of factor VIII, fibrinogen, D-dimer and circulating prothrombotic microparticles such as antiphospholipid antibodies.
  • COVID-19 should be screened in patients presenting with neurological complications CVT without prominent respiratory symptoms nor known prothrombotic risk factors.
• Cerebral venous thrombosis is common in any condition that leads to a prothrombotic state, including pregnancy, the post-partum state, or those on oral contraceptives.
• Signs and symptoms:
  • It may be acute, subacute, or chronic.
  • Most common symptom in cerebral venous thrombosis being a headache. A headache presents in up to 90% of patients.
  • Headaches may be generalized or diffuse, tend to mimic migraines, but may increase in severity slowly over days and weeks and are not relieved with sleep.
  • A headache is often worsened with Valsalva or coughing, indicative of the increase in intracranial pressure.
  • Papilledema and visual symptoms, such as diplopia caused by a sixth cranial nerve palsy when the intracranial pressure is too high, may also accompany a headache.
  • The funduscopic examination will reveal papilledema, which, depending on the severity, can cause visual impairment and even permanent blindness if it is left untreated.
• The underlying pathogenesis of CVST involves two mechanisms:
  1. Localized oedema and venous infarction due to cerebral vein occlusion.
  2. The development of raised intracranial pressure due to occlusion of one of the cerebral venous sinuses, since CSF absorbed by the arachnoid villi drains into the superior sagittal sinus.
• Cerebral venous thrombosis should be considered in any patient who presents with a headache and some combination of either focal neurologic deficit and or new onset seizures.
• Suspect:

• A negative D-dimer does not effectively rule out cerebral venous thrombosis and should not preclude neuroimaging if there is a clinical suspicion for cerebral venous thrombosis.
• D0 Neuroimaging:

1. Non-contrast computed tomography (CT)
   • A direct sign of cerebral venous thrombosis is the cord sign, which is a curvilinear hyper density within a cortical vein in the presence of thrombosis that can be seen for up 2 weeks following thrombus formation.
   • Hyper density with a triangular shape in the superior sagittal sinus, also known as the dense triangle sign. Intraparenchymal haemorrhages or infarcts may be seen on non-contrast head CT and may cross vascular boundaries.

2. CT Venography (CTV):  
   • While MRI does have a better sensitivity and specificity when compared to computed tomography.
   • Diagnostic and confirmatory venography is required to exclude cerebral venous thrombosis.
   • CT venography can rapidly be performed following a non-contrast head CT while the patient is still in the CT scanner makes CT venography a viable option in the emergency setting when access to MRI imaging and venography may otherwise be limited or unavailable.
   • Contrast-enhanced computed tomography illustrates the empty delta sign, which represents contrast enhancement flowing around the comparatively hypodense region of thrombosed superior sagittal sinus.
3. Magnetic resonance imaging (MRI) and magnetic resonance venography (MRV): 
   • Gold standard in diagnosing cerebral venous thrombosis as it has a higher sensitivity than computed tomography.
   • MRI is superior to CT when evaluating for parenchymal oedema as a result of cerebral venous thrombosis.
   • MRI findings are dependent on the age of the thrombus, as signal intensities change depending thrombus age.
   • An acutely formed thrombus (0 to 7 days) is harder to detect, but by week 2, abnormalities are easier to detect, with both T1 and T2-weighted images showing a hyperdense signal.
   • The combination of an abnormal signal in a venous sinus combined with the absence of flow on MRV confirms the diagnosis of cerebral venous thrombosis.
4. Cerebral angiography: 
   1. If the diagnosis is still in question after the use of MRI and MRV, then intra-arterial angiography is indicated.
   2. Angiography allows for superior visualization of the cerebral veins.
   3. It is useful in rare cases of isolated cortical vein thrombosis without sinus thrombosis and may show indirect signs such as dilated and tortuous “corkscrew” collateral veins.

• Management 
  • Identify and address life-threatening complications of cerebral venous thrombosis, including increased intracranial pressure (ICP), seizures, and coma.
  • If a patient seizes and has a lesion such as a haemorrhage or infarction on neuroimaging, then specific anticonvulsant therapy, as well as seizure prophylaxis, should be initiated.
  • The goal of anticoagulation is to prevent the thrombus propagation, to help recanalize the lumen of occluded cerebral veins, and to prevent the complications of deep venous thrombosis and pulmonary embolism in patients who already have thrombus burden. Anticoagulation forms the mainstay of treatment, even in the presence of an existing haemorrhagic venous infarct thus heparin is usually given after confirmation of the diagnosis.
  • Initial management of patients with confirmed CVST should include stabilization and the prevention of cerebral herniation. This may involve the use of Mannitol or surgery.

CME INDIA Tail Piece

References:

1. Stam J. Thrombosis of the Cerebral Veins and Sinuses. N Engl J Med. 2005;352:1791–1798. doi: 10.1056/NEJMra042354. 
2. Panigada M., Bottino N., Tagliabue P., Grasselli G., Novembrino C., Chantarangkul V., Tripodi A. Hypercoagulability of COVID‐19 patients in Intensive Care Unit. A report of thromboelastography findings and other parameters of hemostasis. J Thrombosis Haemostasis. 2020 doi: 10.1111/jth.14850. 
3. Valderrama E.V., Humbert K., Lord A., Frontera J., Yaghi S. Severe acute respiratory syndrome coronavirus 2 infection and ischemic stroke. Stroke. 2020 doi: 10.1161/strokeaha.120.030153. 
4. Zhang Y, Xiao M, Zhang S, Xia P, Cao W, Jiang W, Zhang S. (2020). Coagulopathy and antiphospholipid antibodies in patients with Covid-19. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7161262/ 
5. https://www.covid19treatmentguidelines.nih.gov/therapies/statement-on-anticoagulation-in-hospitalized-patients/
6. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)02392-8/fulltext
7. Rationales and uncertainties for aspirin use in COVID-19: a narrative review. Fam Med Community Health. 2021;9(2):e000741. doi:10.1136/fmch-2020-000741

Discover CME INDIA:

• Explore CME INDIA Repository
• Examine CME INDIA Case Study
• Read History Today in Medicine
• Register for Future CMEs

Get CME INDIA Highlights

Curated articles in your inbox.

SUBSCRIBE!

You have Successfully Subscribed!