(With inputs from Dr Monica Vasudev)

930: Complete Fibrinolysis Shutdown in Severe COVID-19

COVID-19 not only causes hypercoagulability, but also fibrinolysis shutdown. It is associated with venous thromboembolism (VTE), stroke, and renal failure.

Complete lack of clot lysis at 30 minutes on a thromboelastogram (TEG) assay, along with a D-dimer value >2600 ng/mL, identifies high-risk individuals who will need more aggressive anticoagulation.

Patients with COVID-19 have increased risk for blood clots, both in small and large blood vessels.

These findings were published online May 7 in the Journal of the American College of Surgeons.

Wright and colleagues conducted a retrospective study of 44 COVID-19 patients (28 male; median age, 54 years). The primary outcomes included VTE events and new-onset renal failure requiring dialysis. About 93% of the patients required mechanical ventilation, 36% had acute renal failure requiring dialysis, 25% developed a VTE, and 14% had a thrombotic stroke.

Derangements in coagulation lab values included raised D-dimer level and elevated fibrinogen, with normal platelet counts in the majority of patients and mildly elevated prothrombin time (PT) and partial thromboplastin time (PTT), with median values at or slightly above the upper limits of normal.

The median International Society on Thrombosis and Haemostasis (ISTH) disseminated intravascular coagulation (DIC) score was 0. No patient had a score higher than 4. TEG variables were consistent with a hypercoagulable state with an elevated maximum amplitude and low lysis at 30 minutes.

TEG testing revealed that over half of patients (57%) had a complete lack of clot lysis at 30 minutes (LY30), and this was a significant predictor of VTE, with an area under the receiver operating characteristic curve (AUROC) of 0.742 (P = .021).

A D-dimer cutoff of 2600 ng/mL significantly predicted need for dialysis, with an AUROC of 0.779 (P = .005).

Patients with no clot lysis at 30 minutes on TEG assay and a D-dimer value >2600 ng/mL had a rate of VTE of 50%, compared with 0% for patients with neither risk factor (P = .008). The time to VTE was found to be significantly shorter in patients with fibrinolysis shutdown.

The hemodialysis rate was 80% with these two coagulation risk factors, compared with 14% without (P = .004).

Researchers stated that this cohort of critically ill COVID-19 patients was hypercoagulable, despite high normal or frankly elevated PT and PTT levels. This underscores the significance of using whole blood coagulation assays (which more closely approximate in vivo conditions including the presence of cells and platelets) such as the TEG for better risk stratification. (Medscape)

1. COVID-19 is associated with a hypercoagulable state associated with acute inflammatory changes and laboratory findings distinct from acute disseminated intravascular coagulation (DIC), save for those with very severe disease.
2. Fibrinogen and D-dimer are elevated, with modest prolongation of the prothrombin time (PT) and activated partial thromboplastin time (aPTT) and mild thrombocytosis or thrombocytopenia.
3. The presence of a lupus anticoagulant (LA) is common in those with a prolonged aPTT.
4. The risk for venous thromboembolism (VTE) is markedly increased, particularly in patients in the intensive care unit (ICU). Case series have reported prevalences of 25 to 43% in ICU patients, often despite prophylactic-dose anticoagulation.
5. The risk for other thrombotic events, such as stroke, microvascular thrombosis, is less clear.
6. All patients admitted to the hospital for COVID-19 should undergo a baseline complete blood count (CBC) assessment with platelet count, PT, aPTT, fibrinogen, and D-dimer. Repeat testing can be done based on the patients clinical status.
7. Outpatients do not require coagulation testing.
8. All inpatients should be given thromboprophylaxis unless contraindicated. Low molecular weight (LMW) heparin is the preferred agent, though unfractionated heparin can be used if LMW heparin is unavailable or if kidney function is severely impaired. Some institutional protocols include more aggressive anticoagulation with intermediate-dose or even therapeutic-dose anticoagulation for thromboprophylaxis.
9. Therapeutic-dose (full-dose) anticoagulation can be used to treat deep vein thrombosis (DVT) or pulmonary embolism (PE), unless contraindicated.
10. Though bleeding is unusual, it can occur. If it occurs, treatment is similar to non-COVID-19 patients and may include transfusions, anticoagulant reversal or discontinuation, or specific products for underlying bleeding disorders.

 (UPTODATE)

What’s new

COVID-19 hypercoagulable state (May 2020): Many reports have described a hypercoagulable state associated with COVID-19. The prevalence of venous thromboembolism (VTE) is increased, especially in critically ill individuals, often despite prophylactic anticoagulation. Arterial thrombosis has also been reported but the prevalence is not clearly known. Some individuals have considerably increased D-dimer, correlating with worse prognosis. Unlike disseminated intravascular coagulation (DIC), fibrinogen is often elevated, and clotting times and platelet counts are typically normal.

Causes of death from COVID-19 (May 2020)

Two new autopsy studies, involving 33 individuals who died of COVID-19, have revealed common causes of death as pneumonia and pulmonary embolism.

Lung histology demonstrated diffuse alveolar damage consistent with early acute respiratory distress syndrome, and inflammatory infiltrates consistent with viral or bacterial pneumonitis. In both studies, the average age was in the mid-70s, most were men, and most had preexisting conditions - heart disease, hypertension, diabetes, and obesity. Despite being small, the studies emphasize the contributions of lung inflammation and hypercoagulability to fatal illness in this disease.  [Uptodate]

RV dilatation

Respiratory distress and myocarditis common in patients hospitalized with COVID-19 affect the right ventricle (RV), but the acute effects and whether they create longer-lasting damage is not clearly understood, according to recent reports in JACC: Cardiovascular Imaging.

In a retrospective study, 31% of over 100 such patients with a clinical indication for echocardiography had RV dilation, a feature that didnt track with myocardial inflammation or injury or with pulmonary embolism (PE). It independently predicted over 4 times increase in in-hospital mortality.

The RV dilation wasnt continuous. These changes were dynamic. Patients were seen moving in either direction, going from normal ventricle to enlarged and from enlarged to normalized.

All those with RV enlargement underwent CT angiography to assess for pulmonary embolisms, and only 50% of them had PE. The echocardiography study was published May 15.

The other report presented findings on postdischarge MRI in 26 consecutive patients from one center in Wuhan, China, who had recovered from COVID-19 but experienced cardiac symptoms later on, including chest pain or palpitations; none of them had a pre-COVID-19 history of myocarditis or other heart disease.

About 58% showed MRI signatures for diffuse myocardial edema and for fibrosis by late-gadolinium enhancement (LGE), or for both along with impaired RV cardiac index and ejection fraction, despite preserved LV function.

This was compared with 20 recent historical control subjects without documented cardiovascular or inflammatory disease who underwent the same MRI examinations. There was presence of myocardial tissue abnormalities in otherwise healthy subjects, thus suggesting cardiac involvement as a lasting consequence of SARS-CoV-2 infection, reported Lu Huang, MD, PhD, Tongji Medical College and Huazhong University of Science and Technology, Wuhan, in their report published May 11. (Medscape)

Dr KK Aggarwal

President CMAAO, HCFI and Past National President IMA