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COVID-19 Resources

COVID-19 and ITP: Frequently Asked Questions

(Version 4.0; last reviewed July 23, 2020)

Input from Drs. Jim Bussel, Doug Cines, Nichola Cooper, Cindy Dunbar, Marc Michel, and Francesco Rodeghiero

Note: Please review ASH's disclaimer regarding the use of the following information.

What are the potential considerations in selecting treatment agents for ITP in the context of the pandemic, whether the ITP patient has COVID-19 disease or not?

There are many effective treatment options for ITP, each of which possess possible advantages and disadvantages in the setting of the COVID-19 pandemic. A “common sense” approach to patient management using contemporary standard ITP guidelines is advisable in the absence of extensive clinical data to date in the context of ITP and COVID-19. It is generally agreed that visits to medical facilities should be minimized to limit the risk of infection, which puts more emphasis on managing symptoms than relying on frequent platelet counts, although if need be these may be better obtained “locally” if possible. Severe COVID-19 infection is accompanied by a risk of thrombosis, but at this time there is no evidence that this risk is increased by raising platelet counts to hemostatic levels or exacerbated by any specific form of ITP management, even those such as splenectomy and thrombopoietic (TPO) agents associated with some excess thrombosis in specific non-COVID settings. The complexities involved in managing patients with the various secondary forms of ITP are not explicitly considered in this FAQ.

IVIG is not immunosuppressive and brings the platelet count up quickly. However, it currently does not contain antibody to the SARS-Cov-2 virus, so would only be used in its immunomodulatory capacity; it does not maintain the platelet count for more than 3-4 weeks, thus may require repeated visits to an infusion center with attendant exposures. Thrombopoieitic agents are quite effective, and 2 of the 3 licensed agents can be taken orally, whereas the third requires a subcutaneous injection that still requires a weekly visit to a medical facility in certain countries. Steroid treatment is the most widely-used first-line treatment of ITP, but carries a theoretical risk of increasing susceptibility to infections, however steroid exposure has not to date been associated with worse outcomes in COVID-19 disease, and in fact dexamethasone treatment has recently been shown to be beneficial for mitigation of severe COVID-19 hyperinflammatory disease. No data suggests that splenectomy poses any additional risk of infection by the SARS-Cov-2 virus. No consensus exists as to whether anti-CD20 increases the risk or severity of COVID-19 disease as no clear signal has emerged from the larger experience in patients being treated for lymphoma. However, anti-CD20 agents impair humoral responses to de novo infections and vaccines. There is no data on platelet transfusions in COVID-19 patients so their risks and benefits remain undefined in this specific setting.

For a new adult patient with ITP requiring treatment due to severe thrombocytopenia but without active infection, how would you approach initial treatment options in the setting of the COVID-19 pandemic?

An approach that involves individualization based on several factors is key: urgency of need to increase the platelet count, degree of bleeding, comorbidities, minimizing exposure to SARS-Cov-2 infection, and standard practice for ITP. Most patients with ITP do not experience severe bleeding at platelet counts ≥ 10-20,000/ul in the absence of additional risk factors. Similarly, if patients are generally stable, it is wise to decrease frequency of platelet counts and avoid visits to health care facilities. Effective ITP treatments that are not immunosuppressive, such as IVIG and oral thrombopoietic (TPO) agents (eltrombopag or avatrombopag), would be the first choices, although currently there are no clear contraindications to use of steroids; romiplostim is equally effective but requires weekly visits for injections in some countries. In patients requiring an urgent platelet count increase, IVIG at 0.4-1 gm/kg for 1-2 days can be given, with repeated doses as needed, while waiting for a response to TPO agents or steroids. However, for patients without major bleeding or wet purpura, oral TPO agents could be used as single agents, given the potential risks of exposure using prolonged IVIG infusions in a medical facility and the longer term infectious risks of high dose corticosteroids.

For chronic ITP patients without active COVID-19 disease, would you modify treatment regimens in the setting of the COVID-19 pandemic?

No modification is needed for stable patients on low doses of immunosuppressive drugs. Changing treatments requires increased monitoring and could potentially result in relapse, and thus may be riskier than continuing the status quo. For patients likely to remain for months on doses of corticosteroids (ie > 10mg/day prednisone) or high doses of other immunosuppressive drugs, use of TPO agents could allow for tapering and possibly discontinuation of these medications, despite lack of robust evidence for poorer COVID-19 outcomes with these types of immunosuppression. Currently we believe that rituximab should be avoided (see introduction) if possible.

Should blood count monitoring or thresholds to initiate treatment be modified in the setting of the higher risk currently for uninfected patients being physically present at medical care settings for blood draws and treatment?

When possible, most ITP patients should be managed by phone, text, or email according to symptoms, with a decreased frequency of blood counts, or, if they are necessary, with home blood draws. Certain patients: the elderly, those on anti-platelet agents, those with a history of major bleeding or other risk factors and those whose condition is unstable may need to continue or even increase their frequency of monitoring.

How would you approach an ITP patient who develops COVID-19 disease?

Thus far, there does not appear to be an increased incidence of infection or severe COVID-19 disease in ITP patients; but, robust data collection on this question does not yet exist. If a patient with known ITP and active COVID-19 disease shows a fall in platelet count to dangerous levels, e.g., less than 10-20,000/uL, IVIG should be given, with platelet transfusion reserved for major bleeding or for invasive procedures with a high bleeding risk. If the patient is already on a TPO agent, the dose could be increased or the TPO agent changed or another treatment added. Whether to give dexamethasone should be determined by COVID-19 severity, ie oxygen-dependent associated pneumonia and/or aggravated cytokine release syndrome, since safety during the early phase of the infection is not established, although there is no evidence currently that steroids worsen the course of COVID19. Convalescent plasma, if available, could be considered if active viral infection persists or COVID-19 disease progresses, particularly in patients on rituximab or other immunosuppressive therapies.

Viral infections can trigger acute ITP or result in exacerbations in those with stable ITP. SARS-CoV-2 testing should be considered in these settings, particularly given a recent case series documenting the new onset of ITP associated with COVID-191.

LMWH/heparin are widely used as thromboprophylaxis in all hospitalized COVID-19 patients and should be administered even to ITP patients unless they are bleeding or severely thrombocytopenic. In general, we believe the platelet count should be > 20,000/uL in patients on anticoagulation, and ideally > 30,000/uL.The potential benefits vs risk of LMWH/heparin and its best dosage and schedule must be weighed carefully in each ITP patient individually, given the paucity of data on hypercoagulability in patients with both ITP and COVID-19.

What if my patient has had a splenectomy?

Treatment of a febrile splenectomized patient is unchanged in the setting of COVID-19 disease, and urgent administration of IV antibiotics is mandatory until bacterial cultures are documented as negative, even if the fever is attributed to proven or suspected SARS-Cov-2 infection.

References

  1. Mahévas M et al, Clinical characteristics, management and outcome of Covid-19-associated immune thrombocytopenia. A French multicenter series.
    Br J Haematol. 2020 Jul 17. doi: 10.1111/bjh.17024

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