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Long Covid & Hypercoagulability

By Craig Tanio MD, FACP, IFMCP

Long Covid & Hypercoagulability

This is the second of a series of blog posts on the sequelae of long covid. We suspect that long covid will be an issue that will affect as many as 8-10 million Americans and 100+ million people globally in the next 2 years.

Hypercoagulability

Hypercoagulability is when the body’s natural clotting mechanism has its homeostasis tipped, which leads to the tendency to clot and make excessive fibrin. When this system is significantly tipped it can result in a clot in a vein or less commonly an artery. Those can manifest in a variety of clinical scenarios such as a blood clot to the leg, clot to the lung or stroke. However, there can be degrees of hypercoagulability. Often in chronic conditions, there can be a “sludge-like” situation where fibrin accumulates on the endothelial linings and there can be a significant reduction of oxygen, nutrient and hormone transport from the vessels to the cells and reduced clearing of metabolic wastes from the cells to the vessels. In addition, loss of vasodilatation and vasoconstriction can create rigid vessel walls and contribute to the worsening of autonomic responses.

Acute Covid: There is a striking amount of evidence that most patients with acute Covid-19 have a hypercoagulable state1. The incidence of documented thrombosis by ultrasound has ranged from 40 to 75% in a variety of studies on patients in the hospital setting. Clots can happen directly in the lung rather than migrating up from the leg veins. Coronary thrombosis has also been seen in Covid patients. The most common lab findings acutely are elevated D-Dimer, modest thrombocytopenia, and prolongation of the prothrombin time. Almost all treatment protocols of acute Covid-19 recommend treatment to address the underlying hypercoagulable state ranging from aspirin to low molecular weight heparin to heparin.

Long Covid: The evidence on patients with long Covid is limited to date given that the definition of long Covid requires symptoms 6 months after the onset of Covid. There are numerous case reports of patients with ongoing hypercoagulable states including antiphospholipid antibody syndrome However, hypercoagulable states have been found in a number of fatiguing illnesses similar to Long Covid including Lyme + / Post Treatment Lyme Syndrome and Chronic Inflammatory Response Syndrome from Water Damaged Buildings. For example, the fibrinogen was elevated in 67% of patients with Borreliosis2. Insights from these conditions may prove to be useful in the management of patients with long-covid symptoms.

Symptoms

Symptoms from hypercoagulability include shooting pains or deep aching pain in the limbs, limbs that fall asleep, neuropathies, sensory hypersensitivity, irritability, dysautonomia / POTS, heat intolerant, brain fog, insomnia, motor restlessness, stiffness and pain upon awakening or being sedentary, painful teeth and post exertional malaise

Patients can show a variety of signs on physical exam including mottled skin, puffy tissue, poor capillary refill, purple / red feet, dependent rubor, dermatographia, overlap with symptoms of mast cell activation, unable to measure pulse ox well because of poor circulation, encephalopathy, cognitive dysfunction

Laboratory testing for hypercoagulability can be done at LabCorp or at Quest and is usually covered by insurance. A complete panel would include the following tests

  • Anticoagulants – Antithrombin Activity III, Protein C Activity, Protein S Activity
  • Anti-fibrinolytics — Plasminogen Activase Inhibitor -1 (PAI-1), Lipoprotein(a), Alpha-2 Antiplasmin
  • Fibrinolysis – D-Dimer
  • Procoagulants – Activated Protein C Resistance, Factor II Activity, Fibrinogen, Homocysteine (cardio), Lipid panel, Prothrombin Fragment 1+2, PT / PTT , Thrombin – Antithrombin Complexes (TATs)
  • Immune – Antiphospholipid antibody

It is important to have a clinician such as our team at Rezilir who can understand the optimal levels of each of these tests and how to interpret these tests in aggregate to pick up a mild hypercoagulable state.

Treatment

When there is significant amount of clotting, such as in acute Covid, appropriate treatment can include pharmacologic options such as aspirin, low molecular weight heparin and heparin. These treatments have been studied as a part of acute treatment options in the hospital. When there is activation of the coagulation system that creates fibrin deposits on the endothelial cell but not acute clotting, a less aggressive form of treatment may be appropriate. Non pharmacologic options have not yet been studied for long Covid but have been used in other chronic conditions include Omega 3 essential fatty acids, resolvins, Red Sage / Dan Shen, Nattokinase, lumbrokinase, and Serrapeptase. These options should be guided by an experienced clinician.

References

1. Kichloo A et al. Covid-19 and Hypercoagulability: A review: Clin Appl Thromb Hemost Jan-Dec 2020;26, https://doi.org/10.1177/1076029620962853

2. https://idsa.confex.com/idsa/2003/webprogram/Paper18421.html

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