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COVID-19 Resources

COVID-19 and ITP: Frequently Asked Questions

(Version 5.0; last reviewed November 18, 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?

The many effective treatment options for ITP each 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 in the context of ITP and COVID-19 to suggest otherwise. Visits to medical facilities should be minimized to limit exposure to infection. This puts more emphasis on managing symptoms rather than relying on frequent platelet counts which may be better obtained “locally”. Severe COVID-19 infection is accompanied by a risk of thrombosis, but 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 splenectomy and thrombopoietic (TPO) agents which may be associated with some excess thrombosis in non-COVID ITP settings.

Viral infections can trigger acute ITP or result in exacerbations in those with stable disease, thus testing for SARS-CoV-2 is indicated in this setting, as supported by a recent case series documenting new onset of ITP associated with COVID-191 and anecdotal reports of patients with ITP whose platelet counts fell in association with SARS-Cov2 infection.

IVIG is not immunosuppressive, rapidly increases the platelet count, and potentially has useful immunomodulatory effects, but currently does not contain antibodies to the SARS-Cov-2 virus. Since IVIG requires prolonged and often repeated visits to an infusion center, IVIG increases attendant SARS-Cov2 exposures; home administration is a pro-active possibility. Two of the 3 available thrombopoietic agents can be taken orally, whereas the third is administered by subcutaneous injection requiring a weekly visit to a medical facility in some countries. Steroid treatment is the most widely-used first-line treatment of ITP and carries a theoretical risk of increasing viral susceptibility early in infection; however, steroid exposure has not been associated with worse outcomes in COVID-19 disease, and dexamethasone has been shown to be beneficial for mitigation of severe COVID-19 hyperinflammatory disease, although with different dosing than that recommended in ITP. No data suggests that splenectomy poses any additional risk of SARS-Cov-2 virus infection. No consensus exists as to whether anti-CD20 increases the risk of infection or severity of COVID-19 disease; however, anti-CD20 agents impair humoral responses to de novo infections and vaccines for 6 months or longer, which theoretically would delay or impair immunity following natural infection or vaccination for COVID. There is no data on platelet transfusion in COVID-19 patients. Fostamatinib can both be used to treat ITP and is under study as an anti-inflammatory therapy for severe COVID infection.

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?

Ideally, testing for active SARS-Cov2 infection would occur prior to treatment decisions. Initial therapies should be individualized based on the severity/location of bleeding and comorbidities, standard practices for managing ITP, shared decision making with patient, and minimization of exposure to SARS-Cov-2 infection. Most adults with ITP do not experience severe bleeding at platelet counts ≥ 20,000/ul in the absence of additional risk factors (including older age). Thus, if patients are generally low-risk and stable, it may be feasible to decrease frequency of measuring platelet counts and to avoid excess visits to health care facilities. Effective ITP treatments that are not immunosuppressive, such as IVIG or oral thrombopoietic (TPO) agents (eltrombopag or avatrombopag), would be reasonable initial treatment choices, although there is no evidence to date suggesting a benefit to avoidance of steroids. Romiplostim is equally effective but may requires weekly visits for injections. If an urgent platelet count increase is needed, IVIG 0.4-1 gm/kg for 1-2 days can be given with additional doses as needed, while awaiting response to other treatment, e.g. TPO agents. For patients without major bleeding or wet purpura, oral TPO agents could be used as single agents to avoid the risks of IVIG (exposure) and steroids (immunosuppression). For patients not responsive or intolerant to the various TPO-RA agents, fostamatinib could be considered.

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 result in relapse, and thus may be riskier than continuing the status quo. However, for those patients who would have to remain for months on prednisone at doses > 10mg/day or on “high” doses of immunosuppressive drugs based on this strategy, use of TPO agents or fostamatinib in those unresponsive or intolerant to TPO-RA might allow tapering of doses. The suggestion to taper immunosuppressive agents is made despite no robust evidence for poorer COVID-19 outcomes with immunosuppressive agents. We believe anti-CD20 agents should be avoided if possible, at least for now (see above).

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 decreased frequency of blood counts, and if needed and possible, 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 frequent monitoring.

How would you approach an ITP patient infected with SARS-Cov2?

Thus There does not appear to be an increased incidence of infection or severe COVID-19 disease in ITP patients. If a patient with known ITP develops SARS-Cov2 infection and the platelet count falls to very low levels, i.e., less than 10-20,000/uL, IVIG should be given with platelet transfusion reserved for major bleeding or invasive procedures. If the patient is already on a TPO agent, the dose could be increased, another TPO agent could be substituted, or fostamatinib added. Treatments for COVID-19 illness, such as dexamethasone for severe disease, should be given as appropriate. The benefit and safety of dexamethasone during the early phase of SARS-Cov2 infection is not established; although, there is no evidence currently suggesting that early administration of steroids worsens the clinical course of COVID19 infection.

ITP patients diagnosed with COVID-19 who recently received rituximab or other immunosuppressive therapies and are not expected to be able to make their own anti-SARS-Cov2 antibodies, particularly if they have additional risk factors for progression to severe COVID-19 disease, may be good candidates for administration of anti-SARS-Cov2 antibodies via convalescent plasma or engineered monoclonal antibodies, if available.

LMWH and unfractionated heparin are used widely as thromboprophylaxis in all hospitalized COVID-19 patients, and should be administered even to ITP patients unless they are bleeding or severely thrombocytopenic (<20-30,000/µL) Anticoagulation can be given at lower platelet counts in patients at high risk for pulmonary embolism or deep vein or visceral thrombosis. The potential benefits vs risk of heparin and other anticoagulants and the optimizing dosages and schedules must be weighed carefully in each ITP patient, in consultation with a hematologist.

What if my patient has had a splenectomy?

Treatment of a febrile splenectomized patient is unchanged in the setting of COVID-19 disease. 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.

Should I immunize my ITP patient to SARS-Cov2 and influenza?

Even though vaccine administration in general can occasionally result in a drop in the platelet count in otherwise stable ITP patients, the expected benefits of receiving the influenza vaccine and a SARS-CoV-2 vaccine likely outweigh this concern. The ASH vaccine FAQ discusses points to consider in the use of SARS-CoV-2 vaccines, as they become available, in immunocompromised and/or splenectomized patients, such as those with ITP, and potential impact of long-lasting B cell depletion or other types of immunosuppression or immunodeficiency common in ITP patients.

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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