COVID-19-associated coagulopathy

WikiDoc Resources for COVID-19-associated coagulopathy
Articles
Most recent articles on COVID-19-associated coagulopathy Most cited articles on COVID-19-associated coagulopathy Review articles on COVID-19-associated coagulopathy Articles on COVID-19-associated coagulopathy in N Eng J Med, Lancet, BMJ
Media
Powerpoint slides on COVID-19-associated coagulopathy Images of COVID-19-associated coagulopathy Photos of COVID-19-associated coagulopathy Podcasts & MP3s on COVID-19-associated coagulopathy Videos on COVID-19-associated coagulopathy
Evidence Based Medicine
Cochrane Collaboration on COVID-19-associated coagulopathy Bandolier on COVID-19-associated coagulopathy TRIP on COVID-19-associated coagulopathy
Clinical Trials
Ongoing Trials on COVID-19-associated coagulopathy at Clinical Trials.gov Trial results on COVID-19-associated coagulopathy Clinical Trials on COVID-19-associated coagulopathy at Google
Guidelines / Policies / Govt
US National Guidelines Clearinghouse on COVID-19-associated coagulopathy NICE Guidance on COVID-19-associated coagulopathy NHS PRODIGY Guidance FDA on COVID-19-associated coagulopathy CDC on COVID-19-associated coagulopathy
Books
Books on COVID-19-associated coagulopathy
News
COVID-19-associated coagulopathy in the news Be alerted to news on COVID-19-associated coagulopathy News trends on COVID-19-associated coagulopathy
Commentary
Blogs on COVID-19-associated coagulopathy
Definitions
Definitions of COVID-19-associated coagulopathy
Patient Resources / Community
Patient resources on COVID-19-associated coagulopathy Discussion groups on COVID-19-associated coagulopathy Patient Handouts on COVID-19-associated coagulopathy Directions to Hospitals Treating COVID-19-associated coagulopathy Risk calculators and risk factors for COVID-19-associated coagulopathy
Healthcare Provider Resources
Symptoms of COVID-19-associated coagulopathy Causes & Risk Factors for COVID-19-associated coagulopathy Diagnostic studies for COVID-19-associated coagulopathy Treatment of COVID-19-associated coagulopathy
Continuing Medical Education (CME)
CME Programs on COVID-19-associated coagulopathy
International
COVID-19-associated coagulopathy en Espanol COVID-19-associated coagulopathy en Francais
Business
COVID-19-associated coagulopathy in the Marketplace Patents on COVID-19-associated coagulopathy
Experimental / Informatics
List of terms related to COVID-19-associated coagulopathy

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ifrah Fatima, M.B.B.S[2]

Synonyms and keywords:

Overview

Coronavirus, named due to the "crown" like appearance of its surface projections, was first isolated from chickens in 1937.There are now approximately 15 species in this family, which infect not only humans but cattle, pigs, rodents, cats, dogs and birds (some are serious veterinary pathogens, especially chickens) .Initially, the patients were believed to have contracted the virus from seafood/animal markets which suggested animal-to-human spread.There is no established system for the classification of the hypercoagulability seen in COVID-19.Coagulopathy in COVID-19 must be differentiated from other diseases that cause DIC.

Historical Perspective

• Coronavirus, named due to the "crown" like appearance of its surface projections, was first isolated from chickens in 1937.,
• In 1965, Tyrrell and Bynoe used cultures of human ciliated embryonal trachea to propagate the first human coronavirus (HCoV) in vitro.
• There are now approximately 15 species in this family, which infect not only humans but cattle, pigs, rodents, cats, dogs and birds (some are serious veterinary pathogens, especially chickens).

• The etiological agent, a novel coronavirus, SARS-CoV-2, named for the similarity of its symptoms to those induced by the severe acute respiratory syndrome, causing coronavirus disease 2019 (COVID-19), is a virus identified as the cause of an outbreak of respiratory illness first detected in Wuhan, China.
• Initially, the patients were believed to have contracted the virus from seafood/animal markets which suggested animal-to-human spread.
• The growing number of patients however, suggest that human-to-human transmission is actively occurring.
• The outbreak was declared a Public Health Emergency of International Concern on 30 January 2020.
• On March 12, 2020 the World Health Organization declared the COVID-19 outbreak a pandemic.

Classification

There is no established system for the classification of the hypercoagulability seen in COVID-19.

The coagulopathy may be classified according to the type of vessels and organs involved into:

• Venous thrombosis
• Arterial thrombosis
• Microvascular thrombosis

Pathophysiology

• COVID-19 induces a hypercoagulable state in the body. An increased risk of mortality has been noted in patient’s with coagulopathy in COVID-19. It is thought that the coagulopathy in COVID-19 is the result of:
  • Virchow’s triad
  • Vascular endothelial damage
  • Endothelitis- direct invasion of endothelial cells by SARS-CoV-2
  • Complement mediated damage to pericytes
  • Pro-inflammatory cytokines- IL-1, IL-6, and TNF- α, that activate the coagulation pathway and the fibrinolytic system
• Stasis- Prolonged hospital admissions causing immobilization of the patient
• Hypercoagulabe state- Evidenced by elevated fibrinogen, prothrombotic factors and hyperviscosity
• Some patients have been found to have Lupus anticoagulant (anti-cardiolipin) and anti-β2GP1 antibodies that may be contributory.

Causes

Coagulopathy in COVID-19 is caused by:

• Direct invasion of endothelial cells by SARS-CoV-2
• Pro-inflammatory cytokine storm.
• Prolonged immobilization in hospitalized patients causing stasis.

Differentiating COVID-19 associated coagulopathy from other Diseases

Coagulopathy in COVID-19 must be differentiated from other diseases that cause DIC.

The main feature of COVID-19 coagulopathy is thrombosis while the acute phase of DIC presents with bleeding:

• Similar laboratory findings are marked increase in D-dimer and normal/slightly low platelets and prolonged PT.
• Findings distinct in COVID 19 are high fibrinogen and high factor VIII activity
• The scoring system of the International Society on Thrombosis and Hemostasis should be used to detect DIC (platelet count, PT, fibrinogen, D‐dimer, antithrombin and protein C activity monitoring), but the diagnosis and subsequent treatment should be done clinically.

Epidemiology and Demographics

The incidence of venous thromboembolism in ICU patients with COVID-19 was analyzed in a study by Klok et al.

• It concluded that the cumulative incidence of acute pulmonary embolism (PE), deep vein thrombosis (DVT), ischemic stroke, MI, or systemic arterial embolism was 31%.
• The most common thrombotic complication was pulmonary embolism seen in 81% of patients. All these patients were on at least standard doses of thromboprophylaxis.
• The cumulative incidences of VTE were 16% (95% CI, 10-22) at 7 days, 33% (95% CI, 23-43) at 14 days and 42% (95% CI 30-54) at 21 days.
• Comparatively, the cumulative incidence of VTE was higher in the ICU patients - 26% (95% CI, 17-37) at 7 days, 47% (95% CI, 34-58) at 14 days and 59% (95% CI, 42-72) at 21 days) than on the floor.

Independent predictors of thrombotic complications seen were-

• Age
• Coagulopathy (defined as spontaneous prolongation of the prothrombin time > 3 s or activated partial thromboplastin time > 5 s)
• Active cancer

There is no data on gender, geographic location, and racial predilection to coagulopathy in COVID-19.

Risk Factors

Hypothesized risk factors for coagulopathy in COVID-19 pneumonia based on studies include-

• ICU admission
• Age (> 40 years)
• Hypoxia

Other general risk factors for VTE are-

• Male
• Active cancer
• Recent major surgery
• High BMI (obesity)
• Prior VTE
• Immobilization
• Trauma

Screening

Every patient with COVID-19 infection admitted to the hospital should have a baseline of basic blood investigations such as

• Complete blood count (CBC)
• Platelet count
• Prothrombin Time (PT), Activated partial thromboplastin time (aPTT)
• Fibrinogen
• D-dimer
• C- reactive protein

Routine screening with imaging is not done as there is not evidence to indicate an improvement in clinical outcomes. Depending on the clinical state of the patient and suspicion for the development of VTE or arterial thrombi, repeat testing and further imaging investigations are done.

Natural History, Complications, and Prognosis

Natural History

If left untreated, patients with coagulopathy may progress to develop VTE, arterial thrombosis, or microvascular thrombosis and ultimately succumb to death.

Complications

• Thrombotic complications :
  • Deep Vein Thrombosis
  • Pulmonary Embolism
  • Ischemic stroke
  • Myocardial infarction
  • Ischemic limbs
  • Systemic arterial events
  • Clotting of central venous catheters, dialysis catheters, and dialysis filters

Prognosis

Prognosis depends on numerous factors-

• Increased D-dimer levels- poor prognosis
• Increased fibrin degradation product (FDP) levels
• ICU admission

Diagnosis

Diagnostic Study of Choice

• The diagnosis of coagulopathy in COVID-19 is based mainly on the laboratory findings showing a pro-coagulant profile.
• The pre-test probability of DVT and PE can be calculated using the Wells' criteria
• Computed Tomography with pulmonary angiography (CTPA) is the diagnostic test of choice. Ventilation/Perfusion scan may also be done, but may not be of much yield in patients with COVID-19.

History and Symptoms

The symptoms depend on the vessels and the organ systems involved.

Pulmonary Embolism- Many symptoms of PE overlap with the respiratory symptoms seen in COVID-19.

• Maybe asymptomatic
• Dyspnea
• Chest pain
• Cough
• Some other rare presentations include- hemoptysis, shock, hypotension, death.

A positive history of the following is suggestive of and contributory-

• Immobilization or prolonged hospitalization
• Recent surgery
• Trauma
• Obesity
• History of previous venous thromboembolism (VTE)
• Malignancy
• Stroke with hemiplegia or immobility
• Age >65 years

Deep Vein Thrombosis

• Swelling
• Edema
• Pain
• Warmth

Arterial thrombosis involving various systems show the following symptoms:

• Ischemic Stroke: various focal neurological deficits depending on the large artery involved
• Myocardial infarction: Chest pain radiating to left arm and neck, sweating, dyspnea
• Acute ischemic limb: pain, pallor, poikilothermia, pulselessness, paresthesia, paralysis

Physical Examination

Pulmonary Embolism Physical examination of patients with [Pulmonary Embolism] is usually remarkable for-

• Tachycardia
• Tachypnea
• Diaphoresis

Deep Vein Thrombosis Physical examination of patients with Deep Vein Thrombosis includes-

• Unilateral swelling/edema with a difference in diameters
• Warmth
• Tenderness
• Dilated veins
• Homan's sign may also be seen but is unreliable.

Arterial thrombosis-

• Ischemic Stroke- Focal neurological deficits depending on the vessel involved
• Myocardial Infarction- uncomfortable appearing patient with diaphoresis
• Ischemic Limb- pallor, poikilothermia, pulselessness, paresthesia, paralysis

Laboratory Findings

An elevated concentration of serum/blood pro-coagulant factors is diagnostic of coagulopathy associated with COVID-19. Laboratory findings consistent with the diagnosis of COVID-19 associated coagulopathy include:

• Coagulation testing- Pro-coagulant profile
  • Platelet Counts- Normal or increased
  • Prothrombin time (PT) and activated partial thromboplastin time (aPTT)- normal or slightly prolonged
  • Fibrinogen- increased
  • D-dimer- increased
  • Factor VIII activity- increased
  • VWF antigen- increased
  • Protein C, Protein S, Antithrombin III - slightly decreased

TEG findings:

• Reaction time (R) - decreased
• Clot formation time (K)- decreased
• Maximum amplitude (MA)- increased
• Clot lysis at 30 minutes (LY30)- decreased

Electrocardiogram

An ECG may be helpful in the diagnosis of pulmonary embolism or myocardial infacrctioncaused due to hypercoagulability in COVID-19.

• Findings on an ECG suggestive of/diagnostic of pulmonary embolism include tachycardia and S1Q3T3 pattern.
• Findings on an ECG suggestive of/diagnostic of myocardial infarction include STE elevation in various leads.

X-ray

There are no specific x-ray findings associated with PE. However, an x-ray may be helpful in ruling out other causes with similar symptoms like pneumonia, cardiogenic causes of dyspnea, and pneumothorax.

Echocardiography or Ultrasound

• Echocardiography may be helpful in the diagnosis of pulmonary embolism.
• Compressive Ultrasound may be helpful in the diagnosis of deep vein thrombosis

CT scan

CTPA and Ventilation Perfusion(V/Q) Scan

• Prompt diagnosis of PE in COVID-19 patient is difficult in this regard that various symptoms of COVID-19 overlap with that of pulmonary embolism. American Society of Hematology provides the following guidelines regarding the diagnosis of pulmonary embolism:
  • Normal d-dimers level in a patient with low to moderate pretest probability is sufficient to rule out the diagnosis of PE. D-dimers level is usually elevated in COVID-19 patients. This is not applicable to a patient with a high pretest probability.
  • Inpatient with suspected PE with symptoms like hypotension, tachycardia, and sudden drop in oxygen saturation with a high pretest probability of PE, computed tomography with pulmonary angiography is used for the diagnosis. Contraindication to the use of CTPA warrants investigation with ventilation/perfusion scan.

Right-sided segmental and subsegmental pulmonary arterial filling defects (yellow arrows) in keeping with acute distal pulmonary emboli. Source: Dr Gianluca Martinellihttps://radiopaedia.org/cases/76817

MRI

There are no MRI findings associated with coagulopathy of COVID-19 unless it is used to diagnose and evaluate an ischemic stroke caused by it.

Other Imaging Findings

There are no other imaging findings associated with coagulopathy of COVID-19

Other Diagnostic Studies

There are no other diagnostic studies associated with any of the manifestations of COVID-19 coagulopathy.

Treatment

Medical Therapy

Prophylactic

References

Template:WikiDoc Sources