INTRODUCTION — Immune thrombocytopenia (ITP) is an acquired thrombocytopenia characterized by immune-mediated destruction of platelets and/or impairment of platelet production; terminology is summarized in the table (table 1).
ITP is a diagnosis of exclusion; there are no reliable laboratory tests to confirm the diagnosis. (See "Immune thrombocytopenia (ITP) in adults: Clinical manifestations and diagnosis".)
The initial treatment and prognosis of ITP in adults is reviewed here.
Separate topic reviews discuss evaluation and additional aspects of management:
●Adults
•Evaluation – (See "Immune thrombocytopenia (ITP) in adults: Clinical manifestations and diagnosis".)
•Second-line therapy – (See "Second-line and subsequent therapies for immune thrombocytopenia (ITP) in adults".)
●Children
•Evaluation – (See "Immune thrombocytopenia (ITP) in children: Clinical features and diagnosis".)
•First-line therapy – (See "Immune thrombocytopenia (ITP) in children: Clinical features and diagnosis".)
•Chronic disease – (See "Immune thrombocytopenia (ITP) in children: Management of chronic disease".)
●Pregnancy
•Evaluation and management – (See "Thrombocytopenia in pregnancy".)
OVERVIEW OF DECISION-MAKING — Management of ITP can be challenging. The goal of treatment is to treat or prevent significant bleeding, not to normalize the platelet count. However, bleeding risk can be difficult to estimate.
The overall risk of critical or severe bleeding in ITP is relatively low (on the order of 1 percent for intracerebral hemorrhage) [1]. Risk is greatest in individuals with the following:
•Prior bleeding
•Platelet count <10,000/microL
•Older age, especially >60 years
We first consider whether treatment is indicated and then determine the urgency of treatment. Subsequent steps depend on the response to treatment, which treatments have been used, and how long thrombocytopenia has been present.
Our approach is consistent with a 2019 clinical practice guideline from the American Society of Hematology (ASH) and a 2019 international consensus report [2,3].
Definitions of bleeding severity — Definitions of bleeding severity and other terms are summarized in the table (table 1). The following definitions are used herein:
●Critical bleeding – Bleeding into a critical anatomical site or bleeding that causes hemodynamic instability or respiratory compromise [4]. Includes intracranial, intraspinal, intraocular, retroperitoneal, pericardial, or intramuscular bleeding with compartment syndrome.
●Severe bleeding – Bleeding that results in a fall in hemoglobin of 2 g/dL or more or requires transfusion of two or more units of blood but does not meet the definition of critical bleeding.
●Minor bleeding – Bleeding that does not meet criteria for severe or critical bleeding. Examples include skin bleeding or non-severe mucous membrane bleeding.
Whom to treat (indications for therapy) — In individuals with ITP, the need for therapy to raise the platelet count is based on a rapid clinical assessment that includes:
●Presence of bleeding, and if present, the site, acuity, and severity
●Platelet count
●Other bleeding risk factors
●What treatments have been given previously for bleeding or thrombocytopenia, and their effectiveness
●What treatment has been given for the current episode
All individuals with critical or severe bleeding require treatment to raise the platelet count and stop the bleeding.
●Critical bleeding requires immediate treatment that includes platelet transfusion, along with intravenous immune globulin (IVIG), glucocorticoids, and other treatments as needed (algorithm 1). (See 'Critical bleeding' below.)
●Severe bleeding requires urgent treatment with IVIG and glucocorticoids (algorithm 1). (See 'Severe bleeding' below.)
Some individuals with minor or no bleeding despite being thrombocytopenic may not require treatment. Instead, close observation and attention to other bleeding risk factors may be reasonable (algorithm 2).
Therapy to increase the platelet count in individuals who are not bleeding is generally appropriate if the platelet count is <20,000/microL and generally not used if the platelet count is ≥30,000/microL. One rare exception is the very rare patient with ITP who has antiplatelet antibodies that interfere with platelet function. These patients classically present with bleeding out of proportion to the degree of thrombocytopenia. Their management is complex and requires involvement of a hemostasis expert.
How to treat (choice of therapy) — Once a decision has been made to treat, the choice of therapy depends on the severity of bleeding and the bleeding risk. These features will dictate the rapidity with which the platelet count needs to be increased and the treatment to choose, as discussed in the sections below.
Treatments may include:
●Therapies to raise the platelet count – (See 'Therapies to raise the platelet count' below.)
●Other hemostatic products – (See 'Other hemostatic therapies' below.)
●Treatments to address other bleeding risk factors – It is always prudent to evaluate other potential factors that may be contributing to bleeding and address them. This may include medications that increase bleeding risk (aspirin, other nonsteroidal antiinflammatory drugs [NSAIDs], anticoagulants), other comorbidities (kidney or liver disease, infection), or other risk factors (lack of balance that could increase risk of falling; high-risk behaviors like climbing ladders). This applies to all severities of bleeding and to persistent thrombocytopenia without bleeding, especially if the platelet count is <50,000/microL.
●Treatment of another condition that may be responsible for secondary ITP – (See 'Evaluation for secondary ITP' below and 'H. pylori testing' below.)
Critical bleeding — Immediate treatment is required for critical bleeding (bleeding into a critical anatomical site or that causes hemodynamic instability or respiratory compromise), including the following (algorithm 1):
●Platelet transfusions – Platelet transfusion is the fastest way to increase the platelet count in critical bleeding. The typical dose is one apheresis unit or four to six units of pooled platelets. Repeated transfusions may be appropriate while waiting for other therapies to take effect, as individuals with ITP tend to have only brief, attenuated responses to platelet transfusion due to rapid immune-mediated destruction of transfused platelets. IVIG may potentiate the response to platelet transfusion [5]. (See 'Platelet transfusions' below and "Platelet transfusion: Indications, ordering, and associated risks", section on 'Ordering platelets'.)
The increase in platelet count following platelet transfusion is typically transient (eg, lasting less than one hour), and other systemic therapies are needed.
●IVIG and glucocorticoids – For critical bleeding, we use IVIG and glucocorticoids together. This is because each has a different mode of action and could be augmentative, although direct studies have not been reported.
Examples of glucocorticoids for critical bleeding include dexamethasone 40 mg intravenously once per day for four days or methylprednisolone 1 gram intravenously once per day for three days. Additional details and supporting evidence is provided below. (See 'Choice of glucocorticoid and dosing' below.)
IVIG is typically given as 1 g/kg as a single dose, repeated the next day unless the platelet count is >50,000/microL.
●Other therapies – These may include other hemostatic therapies (eg, tranexamic acid), attention to other bleeding risk factors, and therapy for underlying causes of secondary ITP. (See 'Other hemostatic therapies' below and 'Evaluation for secondary ITP' below.)
Conventional critical care measures should be instituted for life-threatening bleeding, including surgical or endoscopic procedures to treat the bleeding site, and transfusion of red blood cells if appropriate. (See "Indications and hemoglobin thresholds for red blood cell transfusion in the adult", section on 'Acute bleeding'.)
The platelet count in critical bleeding is typically <20,000/microL and often <10,000/microL. Critical bleeding can occur with a higher platelet count (eg, between 20,000 and 50,000/microL) and should be treated similarly to bleeding with a count <20,000/microL, but other reasons for bleeding should also be sought and treated, as thrombocytopenia is unlikely to be the sole reason of bleeding.
Severe bleeding — Urgent treatment with IVIG and glucocorticoids (generally given intravenously) is appropriate for severe bleeding (algorithm 1).
●IVIG or glucocorticoids – For severe bleeding, we use IVIG or glucocorticoids. IVIG will raise the platelet count within 1 to 3 days, and glucocorticoids with raise the platelet count within 2 to 14 days.
Examples of glucocorticoids for severe bleeding include dexamethasone 40 mg intravenously once per day for four days or methylprednisolone 1 gram intravenously once per day for three days. Additional details and supporting evidence are provided below. (See 'Choice of glucocorticoid and dosing' below.)
IVIG is typically given as 1 g/kg as a single dose, repeated the next day unless the platelet count is >50,000/microL. (See 'IVIG dosing and administration' below.)
●Other therapies – These may include other hemostatic therapies, attention to other bleeding risk factors, and therapy for underlying causes of secondary ITP. (See 'Other hemostatic therapies' below and 'Evaluation for secondary ITP' below.)
The platelet count in severe bleeding is typically <20,000/microL (often <10,000/microL). Severe bleeding can occur with a platelet count between 20,000 and 50,000/microL and should be treated similarly to bleeding with a count <20,000/microL, but other reasons for bleeding should also be sought and treated, as thrombocytopenia is unlikely to be the sole reason of bleeding.
Minor bleeding and severe thrombocytopenia without bleeding — The platelet count threshold for initiating ITP treatment should be individualized and may vary based on bleeding history, age, comorbidities, occupation, lifestyle, need for antithrombotic therapy, and values and preferences. Our general approach to treating minor bleeding and severe thrombocytopenia without bleeding is similar (algorithm 2).
Not all patients with thrombocytopenia require therapies to increase the platelet count; treatment is used for individuals at increased risk of bleeding, which is based on a number of factors including platelet count, comorbidities, patient values and concerns, and tolerability of therapies [3].
●We treat the majority of individuals with platelet counts <20,000/microL, and especially those with counts <10,000/microL, even if they have no bleeding symptoms. This is based on the increased risk of bleeding with counts below 20,000/microL and the greater risk below 10,000/microL.
●We treat the majority of individuals with minor bleeding. The platelet count is typically <50,000/microL, often lower.
●In some experts' experience, mucosal bleeding (also called "wet purpura"), especially blood blisters in the mouth, can be a predictor of more serious bleeding, and we typically treat these patients fairly urgently, compared with other patients with minor bleeding. Almost always these patients have a platelet count of <20,000/microL. Data to support an association between mucosal bleeding and more serious bleeding are limited. As an example, in a retrospective study involving 112 individuals with ITP who presented to the emergency department with bleeding and a platelet count <20,000/microL, the six individuals with oral mucosal bleeding subsequently developed more serious bleeding [6].
Typical initial treatment involves administration of a glucocorticoid (dexamethasone, 40 mg orally or intravenously once per day for four days, or prednisone, 1 mg/kg daily for one to two weeks, followed by a gradual taper). Rationales for choosing one or the other approach and supporting evidence are presented below. (See 'Choice of glucocorticoid and dosing' below.)
We generally do not treat individuals with platelet counts ≥30,000/microL who are not bleeding. Unnecessary treatment of asymptomatic patients with mild to moderate thrombocytopenia should be avoided, because of the risk of treatment-related toxicity with little to no reduction in bleeding risk. In many cases, the platelet count may remain stable, or, less commonly, it may increase spontaneously over time. (See 'Disease course' below.)
A 2019 British Society for Haematology (BSH) guideline emphasizes tailoring treatment to the patient and states that treatment is rarely indicated in patients with platelet counts below 20,000/microL in the absence of additional clearly identified risk factors for bleeding [3]. A 2019 American Society of Hematology (ASH) guideline suggests treating individuals with platelet counts <30,000/microL, while noting that observation may be appropriate in some cases; the guideline suggests not treating those with counts >30,000/microL [2].
Examples of exceptions include the following:
●Higher thresholds (eg, treatment at platelet counts above 20,000/microL) may be used for the following individuals:
•History of clinically significant bleeding at a higher platelet count
•Comorbidities that increase bleeding risk, such as peptic ulcer disease or liver disease
•Greater risk for injury, such as history of falling or participation in high-risk activities
•Need for concurrent anticoagulation or anti-platelet therapy (see 'Anti-platelet agents and anticoagulation' below)
●Young asymptomatic individuals with lower platelet counts may choose to be observed rather than treated.
The effect of age and prior bleeding was illustrated in a series of 117 adults with ITP that found rates of severe bleeding of 0.4 percent per patient per year for age<40 years, 1.1 percent per patient per year for age 40 to 60 years, and 10.4 percent per patient per year for age >60 years [7]. A previous bleeding event dramatically increased the risk for recurrent bleeding (relative risk [RR] 27.5).
●Individuals who cannot tolerate glucocorticoids or who are expected to have significant toxicities from glucocorticoids (uncontrolled diabetes, severe mood disorders) can be treated with IVIG or a second-line therapy such as a thrombopoietin receptor agonist (TPO-RA). (See 'Glucocorticoids and IVIG' below and "Second-line and subsequent therapies for immune thrombocytopenia (ITP) in adults".)
The ultimate decision to initiate treatment should be shared between the clinician and the patient. Patient support is available from several organizations including the ITP Support Association and the Platelet Disorder Support Association (PDSA) [8-10].
Surgery or delivery — We treat any individual who requires an invasive procedure and has a platelet count below the threshold designated by the clinician performing that procedure.
●Platelet transfusions are indicated if the patient requires an invasive procedure with significant bleeding risk on an urgent/emergency basis (eg, urgent cholecystectomy). ITP-specific therapy (glucocorticoids and/or IVIG) is also administered.
●Glucocorticoids and/or IVIG can be used alone (without platelet transfusions) if there is sufficient time to administer them before the procedure. (See 'Glucocorticoids and IVIG' below.)
●In elective procedures, a properly timed TPO-RA may also be used, especially for individuals who do not have a platelet count increase with glucocorticoids or IVIG. (See "Second-line and subsequent therapies for immune thrombocytopenia (ITP) in adults", section on 'TPO receptor agonists'.)
A 2020 trial that randomly assigned 74 adults with ITP-related thrombocytopenia who required elective surgery to receive preoperative IVIG or the TPO-RA eltrombopag found that both therapies were effective in raising the platelet count (platelet count target reached in 63 percent of the IVIG group and 78 percent of the eltrombopag group) [11].
Platelet count thresholds for selected procedures are summarized separately. (See "Platelet transfusion: Indications, ordering, and associated risks", section on 'Preparation for an invasive procedure'.)
As noted separately, anesthesiologists may differ in the platelet count threshold for neuraxial anesthesia. Coordination in advance of the procedure will facilitate appropriate therapy and appropriate timing. Management of ITP during pregnancy and delivery, including considerations for neuraxial anesthesia, are discussed in detail separately. (See "Thrombocytopenia in pregnancy", section on 'Neuraxial anesthesia' and "Thrombocytopenia in pregnancy", section on 'ITP therapies'.)
Where to treat (home or hospital) — Decisions to treat at home or in the hospital require clinical judgment; there are no high-quality studies to evaluate thresholds for hospitalization.
●Critical or severe bleeding is treated in the hospital, often in the intensive care unit [2].
●Most individuals with established ITP who have a platelet count ≥10,000/microL without bleeding can be treated as outpatients, as long as they have good follow-up with platelet count monitoring and ready access to interventions should the need arise. This is especially true for individuals who are known to have a good response to a particular treatment in the past. For those with higher counts, decisions regarding hospitalization depend on the overall bleeding risk, which is estimated based on their age, minor bleeding symptoms, comorbidities, prior bleeding history, prior response to therapy, and social concerns (ability to rapidly recognize clinical worsening and timely access to medical care).
●Individuals with newly diagnosed ITP who have platelet counts >30,000/microL and are not having bleeding symptoms generally do not require hospitalization. Individuals with newly diagnosed ITP and platelet counts <10,000 microL are typically hospitalized. For individuals with newly diagnosed ITP and platelet counts between 10,000 and 30,000, the decision to treat at home or in the hospital is more nuanced and includes assessment of bleeding risk (eg, platelet count, age, need for concomitant antithrombotic therapy, comorbidities), certainty in the diagnosis, social support, and the patient's ability to participate in close follow-up.
When to obtain hematology consultation — Hematology consultation is appropriate for any individual with suspected or confirmed ITP.
The following are especially important settings that warrant hematology involvement:
●A new diagnosis of ITP (or suspected ITP)
●Chronic thrombocytopenia (platelet count <100,000/microL)
●Thrombocytopenia and clinically important bleeding
●Thrombocytopenia and need for an invasive procedure
●Thrombocytopenia and need for antithrombotic therapy
The urgency of consultation depends on the patient's clinical status.
THERAPIES TO RAISE THE PLATELET COUNT
Platelet transfusions — Platelet transfusions are generally reserved for critical bleeding when there is a need to raise the platelet count immediately, even if only transiently. (See 'Critical bleeding' above.)
Platelet transfusions do not appear to increase the risk of thrombosis in patients with ITP [12]. However, platelet transfusions carry other risks such as transfusion reactions and transfusion-transmitted infections, which reinforces our practice of only using platelet transfusions for critical bleeding or for an urgent/emergency procedure. These risks are discussed in more detail separately. The response to platelet transfusion (platelet count increment) is attenuated in patients with ITP; it may be enhanced by concurrent treatment with IVIG [5]. (See 'IVIG dosing and administration' below and "Platelet transfusion: Indications, ordering, and associated risks", section on 'Complications'.)
Glucocorticoids and IVIG
Comparison of therapies — Glucocorticoids and intravenous immune globulin (IVIG) both raise the platelet count; they differ in their mechanisms of action, rapidity of platelet count increase, adverse effects, and costs.
For critical bleeding, a glucocorticoid and IVIG are given together. (See 'Critical bleeding' above.)
In severe bleeding, minor bleeding, elective surgery, or severe thrombocytopenia without bleeding, we typically give glucocorticoids or IVIG. We generally prefer glucocorticoids because they are less expensive and can be easily administered in the outpatient setting without the need for an appointment in an infusion center. We generally reserve IVIG for settings in which there is a need to raise the platelet count within 12 to 24 hours, or for individuals who cannot tolerate glucocorticoids (eg, due to diabetes mellitus or significant adverse effects). (See 'Severe bleeding' above and 'Minor bleeding and severe thrombocytopenia without bleeding' above.)
Differences between glucocorticoids and IVIG include:
●IVIG works more rapidly (range, 1 to 3 days) than glucocorticoids (range, 2 to 14 days) (table 2).
●Efficacy (both short term and long term) is similar, as discussed below.
●Glucocorticoids are generally easier to administer.
●Glucocorticoids are less expensive.
●Side effect profiles differ. (See "Major side effects of systemic glucocorticoids" and "Intravenous immune globulin: Adverse effects".)
IVIG may be used for some patients who do not tolerate (or wish to avoid) glucocorticoid toxicities or added to glucocorticoid treatment for patients who require a more rapid platelet count increase (eg, for an invasive procedure), as it raises the platelet count more rapidly than glucocorticoids.
The efficacy of glucocorticoids compared with IVIG was demonstrated in a trial that randomly assigned 122 adults with previously untreated, acute primary ITP (platelet count ≤20,000/microL) to intravenous high-dose methylprednisolone (HDMP; 15 mg/kg per day on days 1 to 3) or IVIG (0.7 g/kg per day on days 1 to 3), followed by a second randomization to placebo or oral prednisone (1 mg/kg/day) for days 4 to 21 [13]. Patients were monitored for one year. Major results included the following:
●Response rates at one year were similar in patients receiving HDMP or IVIG, and responses were better in those who followed initial HDMP or IVIG with three weeks of oral prednisone rather than placebo in the second randomization.
•For those who received initial therapy followed by prednisone, responses at one year were seen in 47 percent (HDMP) and 46 percent (IVIG).
•For those who received initial therapy followed by placebo, responses at one year were seen in 32 percent (HDMP) and 29 percent (IVIG).
●The increase in platelet count was faster with IVIG than with HDMP (at day 5, platelet count >50,000/microL in 79 percent of patients receiving IVIG and in 60 percent of patients receiving HDMP).
●Both treatments were generally well tolerated. There were no deaths or life-threatening hemorrhages.
Some patients who do not have an adequate platelet count increase with one therapy may do so with the other [14]. Thus, it may be reasonable to use IVIG in patients for whom glucocorticoids are not effective and vice versa.
Intravenous anti-D immune globulin (also called Rho[D] immune globulin) is a type of immune globulin that may be effective in patients whose blood type is RhD positive and who have not had a splenectomy, but it carries a Boxed Warning regarding hemolytic anemia and is infrequently used for individuals with ITP. (See 'Anti-D as an alternative to IVIG' below.)
Choice of glucocorticoid and dosing — Glucocorticoids raise the platelet count in approximately two-thirds of patients with ITP. Most responses occur within two to five days but may take up to two weeks (table 2).
●Mechanism of action – The mechanism is uncertain but may involve increased apoptotic death of autoantibody-producing lymphocytes and downregulation of macrophage activity responsible for platelet phagocytosis [15].
●Dosing – The most common treatment regimens are [2]:
•Pulse dexamethasone – Typically administered as 40 mg orally or intravenously once per day for four days with no taper. The intravenous route is generally used for critical or severe bleeding. For minor bleeding or thrombocytopenia without bleeding, dexamethasone can be given orally or intravenously.
This can be repeated for additional cycles, up to three times in total [3].
•Pulse methylprednisolone – Typically administered as 1 g intravenously once per day for three days with no taper. This may be used in critical or severe bleeding.
•Oral prednisone with a taper – Typically administered as 1 mg/kg orally, once per day (range, 0.5 to 2 mg/kg daily) for one to two weeks, followed by a gradual taper, typically completed over less than six weeks [2,3]. Administration of glucocorticoids for longer than six weeks should be avoided to minimize side effects [3]. If there is no platelet count response after two weeks, a faster taper (over one week) can be used.
The relative efficacy of a shorter or longer taper of oral prednisone has not been evaluated in randomized trials. Clinical experience suggests that a shorter taper (≤6weeks) is associated with similar efficacy and reduced toxicities compared with longer tapers. For individuals who have a drop in platelet count during the prednisone taper, we typically give an additional course, or we use an alternative therapy.
Rarely, an individual may be treated with continuous low-dose prednisone (≤5 mg per day, given daily or every other day), if this is determined to be the most effective therapy with the least toxicity for that patient.
●Choice of glucocorticoid – The choice among glucocorticoids is individualized [2,3]. Practice is variable, with some clinicians preferring dexamethasone and others preferring prednisone.
•Reasons to prefer dexamethasone include faster responses, reduced risk of dose confusion, no need for dose tapering, completion of therapy in four days, and fewer bleeding events.
•Reasons to prefer prednisone include greater ability to titrate therapy to match the patient's individual response. In our experience, the overall effectiveness of prednisone and high-dose dexamethasone are similar.
●Efficacy – Complete long-term remissions with glucocorticoids have been reported in approximately 20 percent of individuals, based on uncontrolled studies. This long-term remission rate may simply reflect the natural history of the ITP (with spontaneous resolution independent of glucocorticoid use). (See "Glucocorticoid effects on the immune system".)
Outcomes with different glucocorticoid regimens were compared in a 2016 meta-analysis of nine randomized trials that included 1138 patients with previously untreated ITP treated with high-dose dexamethasone for three cycles or oral prednisone 1 mg/kg for two to four weeks [16]. Dexamethasone was associated with a more rapid rise in the platelet count at two weeks compared with prednisone (platelet count >30,000/microL, 79 versus 59 percent). At six months, the response rates were closer together (54 percent with dexamethasone and 43 percent with prednisone). Dexamethasone was associated with fewer bleeding events during the first 10 days (12 versus 24 percent of patients) and fewer toxicities over the course of follow-up (24 versus 64 adverse events per 100 patients); however, in our experience, some patients experience more side effects with pulse dexamethasone. In the prednisone group, one-fifth of adverse events were weight gain.
The more rapid rise in platelet count with high-dose dexamethasone is likely related to the relatively higher glucocorticoid dose. It is likely that very high doses of prednisone would raise the platelet count similarly to pulse dexamethasone or methylprednisolone, but this has not been well studied. The relative antiinflammatory potencies of various glucocorticoids are shown in the table (table 3). Dexamethasone 40 mg daily is approximately equivalent to prednisone 4 mg/kg daily (equivalent to 280 mg daily for a 70 kg patient); this is based on a per-mg potency for dexamethasone that is approximately 7.5 times greater than prednisone.
Younger adults may have a greater platelet count improvement following therapy than older individuals. This was illustrated in a cohort of 117 adults with ITP who were observed during approximately three years of various therapies [7]. The number of individuals with a platelet count >30,000/microL six months after completing therapy was similar in individuals ≤60 or >60 years (91 versus 87 percent, respectively); however, the percent with a platelet count >100,000 was much higher in those ≤60 years (64 versus 17 percent).
●Lack of response – Individuals who do not have a sufficient platelet count increase with glucocorticoids should have the diagnosis re-evaluated. Individuals who do not have a sufficient platelet count increase with glucocorticoids and those who have a rapid recurrence of thrombocytopenia following glucocorticoid tapering or discontinuation should be observed or transitioned to other therapies rather than continuing glucocorticoids. According to a consensus guideline from 2019, excessive use of glucocorticoids is a common error in ITP management [3]. (See "Immune thrombocytopenia (ITP) in adults: Clinical manifestations and diagnosis", section on 'Differential diagnosis' and "Second-line and subsequent therapies for immune thrombocytopenia (ITP) in adults", section on 'Initial considerations'.)
●Adverse effects – Short-term glucocorticoid administration is generally safe and well tolerated, but glucocorticoids are associated with short-term and long-term adverse effects.
•Short term – Short-term effects include mood alterations/emotional lability, insomnia, hyperglycemia, and dyspepsia (table 4). These adverse effects may be seen with higher or more prolonged dosing, but they can also occur with standard dosing and short courses of therapy. (See "Major side effects of systemic glucocorticoids".)
Routine prophylaxis for gastrointestinal toxicity (eg, use of proton pump inhibitors or H2 receptor blockers) is not generally advised in asymptomatic individuals, but therapy is appropriate if the patient becomes symptomatic. (See "Major side effects of systemic glucocorticoids", section on 'Gastrointestinal effects' and "Approach to the adult with dyspepsia", section on 'Antisecretory therapy'.)
•Long term – Long-term effects include infections, cataracts, and osteoporosis. Attention to bone health is necessary, especially in individuals at increased risk, as outlined in a 2019 British Society for Haematology guideline [17]. Considerations about osteoporosis generally apply after approximately three months of therapy but may be relevant sooner in individuals at higher risk for low bone density. (See "Prevention and treatment of glucocorticoid-induced osteoporosis".)
Some glucocorticoid toxicities may be intolerable to patients; in such cases, it is appropriate to use IVIG or second-line therapies instead [18,19]. Although we do not advocate prolonged glucocorticoid use routinely, rare patients may be treated with long-term low-dose glucocorticoids (eg, prednisone ≤5 mg/day). For such individuals, calcium and vitamin D supplementation is appropriate to reduce the risk of osteoporosis, along with monitoring of bone mineral density. Evidence to support this practice is presented separately. (See "Glucocorticoid effects on the immune system" and "Prevention and treatment of glucocorticoid-induced osteoporosis".)
IVIG dosing and administration — Intravenous immune globulin (IVIG) is appropriate for individuals who require a more rapid increase in platelet count, those who do not have an initial platelet count increase with glucocorticoids, or those who require therapy to increase the platelet count and cannot tolerate glucocorticoids. IVIG can raise the platelet count within 12 to 24 hours in many patients with ITP; this effect is reproducible enough that a platelet count response to IVIG has been used as a diagnostic criterion for ITP [20].
IVIG may be used either as an adjunct to other therapies in an individual with critical bleeding or need for urgent surgery, or as an alternative to glucocorticoids in patients with severe bleeding.
The effect of IVIG usually persists for two to six weeks. Thus, IVIG is most useful for patients who require a rapid, temporary increase in platelet count (for urgent management of bleeding associated with thrombocytopenia or before an urgent invasive procedure) or those who are unable to tolerate glucocorticoids and are awaiting initiation of second-line therapy. (See "Second-line and subsequent therapies for immune thrombocytopenia (ITP) in adults".)
●Mechanism of action – IVIG increases the platelet count by interfering with macrophage uptake of autoantibody-coated platelets ("overwhelming" the reticuloendothelial system). (See "Overview of intravenous immune globulin (IVIG) therapy", section on 'Suppression of inflammatory/autoimmune processes'.)
●Dosing – We typically administer IVIG at 1 g/kg daily for one or two days. A single dose of 1 g/kg for one day is often sufficient. Alternative dosing can also be used, such as 400 mg/kg daily for five days. The IVIG can be stopped when a response occurs (ie, platelet count >30,000/microL), even if the full course has not been completed.
●Efficacy – The efficacy of different IVIG doses was compared in a trial that randomly assigned 35 adults with ITP to receive IVIG at either 1 g/kg or 0.5 g/kg, given as a one-time dose [21]. Individuals receiving the 1 g/kg dose had a greater likelihood of response on day 4 than those receiving 0.5 g/kg (67 versus 24 percent). However, additional IVIG administration for a total dose of 2 g/kg made the response rates similar (78 and 88 percent for those who initially received 1 g/kg or 0.5 g/kg, respectively).
●Adverse effects – Most adverse reactions to IVIG are mild and transient, but serious reactions can occur. Headache, hypertension, chills, allergic reactions, vomiting, and hypotension may occur during or immediately following the infusion. Headache may be severe enough to cause concern for intracranial hemorrhage or meningitis. Other rare adverse reactions include anaphylaxis, hemolytic anemia, acute kidney injury, and thrombosis. However, the risk of thrombosis was not increased compared with control groups in a systematic review of randomized trials [22]. IVIG is a human plasma derivative and thus has a theoretical risk of infectious disease transmission. (See "Intravenous immune globulin: Adverse effects" and "Plasma derivatives and recombinant DNA-produced coagulation factors", section on 'Antibody products'.)
Anti-D as an alternative to IVIG — Anti-D immune globulin (anti-D, WinRho, RhoGAM, Rho[D] immune globulin) is sometimes used as an alternative to conventional intravenous immune globulin (IVIG) for patients whose blood type is RhD positive, but many clinicians are hesitant to use it because of the risk of severe hemolytic transfusion reactions, for which there is a US Food and Drug Administration (FDA) Boxed Warning. Patients receiving anti-D should be monitored for signs of an acute hemolytic reaction (fever, chills, flank pain, hemoglobinuria) for four hours following administration [23,24]. Anti-D should be avoided in patients with preexisting hemolysis or a high risk of hemolysis (eg, positive direct antiglobulin test, elevated reticulocyte count) [25].
Anti-D is an immune globulin directed against the D antigen of the Rh blood group system; it is thought to raise the platelet count by saturating macrophage Fc receptors with anti-D-coated red blood cells (RBCs). The usual dose of anti-D is 50 to 75 mcg/kg intravenously [26,27]. This can be repeated when the platelet count declines. Anti-D may be less effective in patients who have had a splenectomy. Efficacy does not correlate with the degree of hemolysis [28,29].
Common adverse effects of anti-D include infusion reactions similar to IVIG, along with predictable mild to moderate hemolytic anemia from extravascular hemolysis of anti-D-coated RBCs [30,31]. Acute hemolytic transfusion reactions are rare (eg, <1 percent), but life-threatening intravascular hemolysis with disseminated intravascular coagulation and acute renal failure has been reported [32,33]. (See "Hemolytic transfusion reactions", section on 'Acute hemolytic transfusion reactions'.)
If an RhD-positive individual who received anti-D requires a RBC or platelet transfusion, RhD-negative products should be used to avoid worsening of hemolysis [34]. Anti-D is unavailable in some European markets.
Other therapies and multiagent combinations — We reserve other approaches (multiagent combinations, second-line agents, splenectomy) for individuals for whom first-line therapy does not produce a stable, safe platelet count.
Second-line options include thrombopoietin receptor agonists (TPO-RAs), rituximab, splenectomy, other immunosuppressive agents, and combination therapy.
●Initial multiagent therapy – Some trials have evaluated intensification of therapy, such as using multiple agents (glucocorticoids plus rituximab, glucocorticoids plus a TPO-RA, glucocorticoids plus mycophenolate mofetil [MMF]). Some of these trials have demonstrated improved response rates with multiagent therapy at 6 or 12 months, often at the cost of greater toxicity, but follow-up has been insufficient to determine whether intensification of upfront therapy may lead to greater rates of cure [35]. As an example, a randomized trial comparing a glucocorticoid plus MMF versus a glucocorticoid alone showed a greater likelihood of raising the platelet count >30,000/microL in the MMF group [36]. However, there were no differences in rates of bleeding, and the patients who received MMF had decreased quality of life (more fatigue, poorer physical health). While further study is warranted, in the absence of evidence of increased cure rates, these mixed results are not compelling enough to recommend multiagent therapy in the initial treatment setting [35,37].
●Timing of splenectomy – Because some individuals may have a spontaneous remission within the first year, we generally defer splenectomy until at least one year has elapsed since diagnosis, if feasible. (See 'Disease course' below.)
Risks and benefits of these second-line options and the choice among them are discussed separately. (See "Second-line and subsequent therapies for immune thrombocytopenia (ITP) in adults".)
OTHER HEMOSTATIC THERAPIES — Other therapies may be appropriate in some cases:
●An antifibrinolytic agent – Antifibrinolytic agents are especially useful for bleeding affecting mucosal surfaces (oral, gastrointestinal, gynecologic). The two available agents have not been directly compared, and clinicians should use the one with which they are the most comfortable.
•TXA – Tranexamic acid (TXA) can be administered orally (1 to 1.5 g three to four times daily) or intravenously (10 mg/kg three times daily, or 1 g over 10 minutes, followed by 1 g over the next eight hours).
•EACA – Aminocaproic acid (also called epsilon aminocaproic acid [EACA]) has been used to manage critical bleeding in patients with ITP, typically using doses in the range of 4 to 12 g/day, administered orally or intravenously [38-40].
Additional information is presented separately. (See "Management of bleeding in patients receiving direct oral anticoagulants", section on 'Antifibrinolytics and other pro-hemostatic therapies'.)
●rFVIIa – Recombinant activated factor VII (rFVIIa) is unlikely to be appropriate in ITP, although it may be used in rare cases of severe uncontrolled bleeding when other therapies are ineffective. (See "Recombinant factor VIIa: Administration and adverse effects", section on 'Off-label uses'.)
MONITORING AND OTHER EVALUATIONS — Monitoring of patients with ITP includes clinical evaluation for bleeding and measurement of the platelet count.
In some cases, such as with lack of the expected response, additional evaluations may be appropriate to determine if conditions other than ITP are contributing to bleeding or thrombocytopenia or if there is an underlying condition producing secondary ITP. (See "Immune thrombocytopenia (ITP) in adults: Clinical manifestations and diagnosis", section on 'Differential diagnosis' and 'Evaluation for secondary ITP' below.)
COVID-19 vaccination — ITP (new onset or exacerbation of existing ITP) has been reported following COVID-19 vaccination [41-50]. However, the risk is low, and vaccination remains the best way to reduce serious disease, hospitalization, and death from COVID-19 [51]. Individuals with ITP who have access to COVID-19 vaccination should receive it; details, and the preference for an mRNA vaccine for individuals who have a choice among vaccines (due to greater efficacy, unrelated to ITP), are discussed separately. (See "COVID-19: Vaccines", section on 'Summary and recommendations'.)
If someone is in the midst of an ITP flare, vaccination may be delayed until the flare is controlled. Rarely, patients with ITP will experience a flare after vaccination, but these flares tend to be transient and respond well to standard ITP therapy. For individuals with ITP, platelet counts should be monitored before and after vaccination (eg, one week following receipt of the vaccine), and patients should be educated about, and reminded to be vigilant for, the signs of severe thrombocytopenia. Bleeding should be reported immediately.
If an individual develops new-onset ITP or an ITP exacerbation following COVID-19 vaccination, treatment is the same as described herein. (See 'Overview of decision-making' above.)
In an observational study involving 218 individuals with ITP and 200 controls, exacerbation of ITP occurred in 30 of the 218 ITP patients (14 percent) after COVID-19 vaccination [52]. Risk factors for exacerbation included younger age, receiving ITP treatment, and platelet count <50,000/microL at the time of vaccination. Only three individuals did not complete a two-dose vaccine series. Nearly all had complete responses to ITP therapy. Vaccination was also associated with a small decrease in platelet count (by six percent) in both groups.
Prescribing information for the Janssen adenoviral vectored vaccine mentions that individuals with a history of ITP should discuss the risk of an exacerbation and the potential need for platelet monitoring following vaccination [53]. Patients with ITP should discuss the risks of any COVID-19 vaccine (or any other vaccine) with their health care team, with monitoring as described above. (See "COVID-19: Vaccines", section on 'Ad26.COV2.S (Janssen/Johnson & Johnson COVID-19 vaccine)'.)
Clinical monitoring — Regardless of therapy, all patients should be assessed for response, monitored regularly, and advised to consult their clinician for any signs of bleeding [7,54-56]. The frequency of monitoring depends on disease severity and treatment ranging from daily in critical or severe bleeding to infrequent monitoring (one to three times per year) for mild to moderate thrombocytopenia with a stable platelet count and no bleeding symptoms. It is always prudent to consider the possibility of an alternative diagnosis (drug-induced thrombocytopenia, genetic platelet disorder). (See "Immune thrombocytopenia (ITP) in adults: Clinical manifestations and diagnosis", section on 'Differential diagnosis' and 'Evaluation for secondary ITP' below.)
Individuals with ITP should be aware of the symptoms that could indicate increased concern (eg, oral blood blisters, melena, severe headache) and should be advised to consult their clinician if bleeding occurs.
Once the platelet count normalizes or rises significantly and plateaus (eg, to >50,000/microL), no additional therapy is needed. The monitoring interval is gradually extended. As an example, we monitor weekly for the first month (while tapering glucocorticoid therapy if the patient is on prednisone), and if the platelet count remains stable, we extend to every other week for a month, then monthly for six months, then every three months for a year. During this time the patient must remain vigilant for signs and symptoms of bleeding and must seek medical attention immediately if bleeding occurs. This monitoring can be performed by the hematologist or the individual's primary clinician.
If the platelet count falls during the taper of prednisone or after discontinuation of a glucocorticoid, we prefer using other therapies rather than increasing the prednisone dose and/or continuing a prolonged course of prednisone. A second course of glucocorticoids might also be reasonable if the patient had a good response to the first course, but prolonged or repeated courses of glucocorticoids should be avoided. Examples of other therapies we would use include IVIG if a rapid platelet count increase is needed, or second-line therapies, which are discussed separately. (See "Second-line and subsequent therapies for immune thrombocytopenia (ITP) in adults".)
The diagnosis should be re-evaluated in individuals who do not have a platelet count response to initial therapy. In a registry study of patients presenting with thrombocytopenia to a tertiary hematology clinic, up to 1 in 7 patients were misdiagnosed [57]. Occasionally, patients are mistakenly labeled as having ITP and are unnecessarily exposed to treatments, including long-term glucocorticoid administration and/or splenectomy, when they actually have other conditions (eg, hypersplenism, drug-induced thrombocytopenia, hereditary thrombocytopenia) [58]. (See "Immune thrombocytopenia (ITP) in adults: Clinical manifestations and diagnosis", section on 'Diagnostic evaluation' and "Diagnostic approach to the adult with unexplained thrombocytopenia".)
Evaluation for secondary ITP — Secondary ITP is important to identify because treatment of the underlying condition may result in resolution of ITP or improvement in the platelet count. Causes are summarized in the table (table 5).
●HIV and HCV– We test all individuals for HIV and hepatitis C virus (HCV), as these are treatable infections with relatively high incidence in the general population. (See "Immune thrombocytopenia (ITP) in adults: Clinical manifestations and diagnosis".)
●HBV – Although hepatitis B virus (HBV) is not considered a cause of secondary ITP, we test for HBV in any individuals who will receive rituximab for ITP treatment. Some experts routinely test all individuals with ITP, anticipating the need for immunosuppressive therapy in the future. If testing is performed, it should include hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc). However, recent treatment with intravenous immune globulin (IVIG) may confound anti-HBc results due to the passive transfer of the antibody in IVIG [59]; thus, testing for HBsAg and anti-HBc should be done before IVIG administration if the need for rituximab is likely. (See "Hepatitis B virus: Screening and diagnosis".)
The threshold for other testing varies according to clinician preference and the patient's concerns. Some clinicians test for systemic lupus erythematosus (SLE) and lymphoproliferative disorders in all adults with ITP, while others limit testing to individuals with symptoms or other findings suggestive of an underlying disorder.
●SLE – Testing for SLE with antinuclear antibodies (ANA) may be reasonable in individuals with suggestive findings, such as other cytopenias, arthralgias, or rash. Additional testing for individuals with positive ANA testing is discussed separately. (See "Clinical manifestations and diagnosis of systemic lupus erythematosus in adults".)
●Lymphoproliferative disorders – Testing is reasonable in individuals with other cytopenias, lymphadenopathy, or systemic findings (fevers, sweats, weight loss) if another cause such as an infection is not obvious. Studies may include peripheral blood flow cytometry and computed tomography scans of the chest, abdomen, and pelvis.
●Immunodeficiency states – In selected individuals, testing for immunodeficiency states such as common variable immune deficiency or selective IgA deficiency may be reasonable. (See "Clinical manifestations, epidemiology, and diagnosis of common variable immunodeficiency in adults" and "Selective IgA deficiency: Clinical manifestations, pathophysiology, and diagnosis".)
●Other autoimmune disorders – Testing may be reasonable for other autoimmune disorders including autoimmune lymphoproliferative syndrome (ALPS), Evans syndrome, large granular lymphocyte (LGL) leukemia, or antiphospholipid syndrome. (See "Autoimmune lymphoproliferative syndrome (ALPS): Clinical features and diagnosis" and "Warm autoimmune hemolytic anemia (AIHA) in adults", section on 'Evans syndrome' and "Diagnosis of antiphospholipid syndrome".)
Close consultation among clinicians should occur to ensure a coordinated plan.
H. pylori testing — Secondary ITP associated with Helicobacter pylori infection, and observational studies have suggested that therapy for H. pylori infection may improve platelet counts in some individuals with ITP [60]. However, substantial platelet count increases in patients with severe thrombocytopenia (platelet counts <30,000/microL) are uncommon with H. Pylori treatment alone. Therefore, we do not rely on H. pylori treatment as a primary means of improving platelet counts in patients who require therapy.
The role of testing for H. pylori (and treating if positive) varies among experts; in general, routine testing is becoming a more common approach. In an international survey from 2021 that included responses from 186 hematologists around the world, 55 (29 percent) always tested for H. pylori and 98 (53 percent) sometimes tested [61].
●Some experts test all individuals for H. pylori and treat if positive, based on the possibility that this therapy might be effective, and the low cost and toxicity profile of non-invasive testing and antibiotic therapy [60].
This practice is supported by a prospective study in 129 patients with ITP from Iran who were tested for H. pylori infection and treated with two weeks of triple antibiotic therapy if testing was positive [62]. Platelet counts >100,000/microL two years after treatment were seen in 30 of 62 patients successfully treated for H. pylori (48 percent), compared with no responses in the 58 H. pylori-negative patients or the nine patients in whom H. pylori eradication was unsuccessful.
●Some experts limit testing to individuals with gastrointestinal symptoms that suggest infection. The rationale is that response rates are relatively low (<50 percent) and may be delayed.
●Routine testing for H. pylori infection (using breath test or stool antigen) followed by H. pylori eradication therapy if testing is positive may be useful for patients with moderate to severe ITP who are from endemic geographic regions such as Japan and Italy.
Details of the diagnostic testing and therapy for H. pylori infection are discussed separately. (See "Indications and diagnostic tests for Helicobacter pylori infection in adults" and "Treatment regimens for Helicobacter pylori in adults".)
There is no role for the use of empiric H. pylori eradication therapy in H. pylori-negative patients or patients with unknown H. pylori status [63].
OTHER CONSIDERATIONS RELATED TO BLEEDING RISK
Myelosuppressive chemotherapy — ITP is not a contraindication to the use of myelosuppressive chemotherapy, and should not be a barrier to chemotherapy administration in patients for whom it is appropriate.
Options for management of the thrombocytopenia depend on the platelet count level, expected degree and duration of myelosuppression, and patient's bone marrow function and morphology. Thrombopoietin receptor agonists (TPO-RAs) have been used to maintain the platelet count for patients with chemotherapy-induced thrombocytopenia, and these may be considered if it would allow administration of life-saving or curative chemotherapy [64,65]. (See "Second-line and subsequent therapies for immune thrombocytopenia (ITP) in adults", section on 'TPO receptor agonists'.)
Anti-platelet agents and anticoagulation — Appropriate antithrombotic therapies (anti-platelet agents or anticoagulants) should not be withheld from a patient with mild to moderate thrombocytopenia (eg, platelet count >50,000/microL) if indicated for atrial fibrillation, venous thromboembolism treatment or prophylaxis, or other indications.
For patients with more severe thrombocytopenia, decisions are made on a case-by-case basis regarding the risks of bleeding and benefits of antithrombotic therapies. The consequences of thrombosis are generally more severe than the consequences of thrombocytopenia, and often, therapy to prevent thrombosis can be administered along with therapy to raise the platelet count if needed. A qualitative scoring system has been proposed to help clinicians determine when anticoagulation should be continued or withheld in patients with ITP [66]. This subject is discussed in more detail separately. (See "Anticoagulation in individuals with thrombocytopenia".)
High-risk physical activities — Patients who are otherwise healthy and have no manifestations of petechiae or purpura may not need to restrict their activities. Individual considerations apply to participation in certain activities. As an example, those with moderate thrombocytopenia (<50,000/microL) may need to avoid extreme sports such as boxing, rugby, and martial arts. In each case, the costs of interfering with the patient's lifestyle and triggering "bleeding anxiety" should be balanced against the actual bleeding risk to the patient.
For some patients, participation in athletic activities, military careers, or other careers with a high risk of trauma may increase the risk of bleeding due to thrombocytopenia. Patients should be counseled regarding the bleeding risks, although this may be difficult to predict for any individual patient. Depending on the value placed by patients on participation in high-risk activities, we have occasionally used interventions that are typically reserved for patients with more severe thrombocytopenia. These situations require a shared decision between the clinician and patient and ongoing communication.
Alcohol and over-the-counter products — Individuals with ITP should be aware of other medications and nonprescription remedies that may increase bleeding risk. As examples:
●We alert patients with moderate thrombocytopenia (platelet count 30,000 to 50,000/microL) that excessive alcohol consumption can increase the risk of bleeding.
●For fever or mild aches and pains, acetaminophen is preferable to aspirin or nonsteroidal antiinflammatory drugs (NSAIDs). Selective cyclooxygenase (COX)-2 inhibitors (eg, celecoxib) are not expected to affect platelet function substantially. (See "Overview of COX-2 selective NSAIDs", section on 'Lack of platelet inhibition and use during anticoagulation'.)
●Certain other over-the-counter remedies may increase bleeding risk, as discussed separately. (See "Approach to the adult with a suspected bleeding disorder", section on 'Medication use'.)
PROGNOSIS
Disease course — Most adults with ITP will eventually reach a safe, stable platelet count. However, many will require one or more therapies, and some may have bleeding complications if their thrombocytopenia is severe and/or they have other comorbidities that predispose to bleeding.
●Spontaneous remission – Spontaneous remissions (presumed to be independent of treatment) occur in up to 10 to 20 percent of adults with ITP [35,54,56,67]. These often occur within the first six months, but platelet count improvements years later have also been reported [56].
Some cases of apparent spontaneous remission may actually represent self-limited forms of thrombocytopenia due to other causes, especially drugs and infections, which may have been overlooked. As an example, a series of 343 adults with suspected ITP reassigned the diagnosis of 28 patients (8 percent) as drug-induced thrombocytopenia [56]. Quinine was the most commonly implicated agent (13 patients; half of drug-induced cases). An additional 22 patients (6 percent) had clinical or laboratory evidence of a preceding infection (eg, infectious mononucleosis). These findings emphasize the importance of making a correct initial diagnosis. (See "Immune thrombocytopenia (ITP) in adults: Clinical manifestations and diagnosis".)
●Stable disease without ongoing treatment – The majority of adults with ITP will eventually reach a stable, safe platelet count, as a result of spontaneous remission or therapy. The likelihood of stable disease after first-line treatment without ongoing therapy ranges from one-third to two-thirds [56].
●Need for additional treatment – Some patients may require additional second-line or other therapies. As an example, in a series of 242 patients, 30 (12 percent) required eventual splenectomy [56]. Second-line and subsequent therapy for ITP is discussed in detail separately. (See "Second-line and subsequent therapies for immune thrombocytopenia (ITP) in adults".)
●Development of an ITP-associated condition or other autoimmune disorder – The risk of developing a rheumatologic or hematologic condition associated with ITP, such as systemic lupus erythematosus (SLE) or chronic lymphocytic leukemia (CLL), is unknown. A series of 152 patients reclassified 12 individuals as having secondary ITP (8 percent) during two years of evaluation [55]. Case series have not shown a particularly high incidence of developing overt autoimmune disease (eg, autoimmune thyroiditis). As an example, in a series of 208 adults with ITP (median age, 44 years) who were monitored for up to 12 years from diagnosis, only four developed another autoimmune condition (2 percent) [54].
Mortality — The mortality rate in people with ITP is considered to be similar to or only marginally higher than an age-matched population, despite the possibility of fatal hemorrhage from thrombocytopenia or infection in the setting of therapies that cause immunosuppression [7,54-56,67-70]. Patients with ITP are more likely to die of conditions unrelated to ITP than to ITP or its treatment.
The following examples illustrate the mortality rates and causes of death:
●A series of 152 adults followed for slightly over nine years reported 21 deaths (14 percent) [55]. There were six ITP-related deaths (4 percent; two from bleeding and four from infection, which may have been a complication of immunosuppressive treatment), four cases of sudden death (3 percent), and 11 deaths unrelated to ITP (7 percent).
●A series of 245 adults followed for five years reported 27 deaths (11 percent) [56]. Three of these were attributed to hemorrhage, one to sepsis following splenectomy, and the rest to non-ITP causes.
●A series of 208 adults reexamined 14 years after their initial ITP diagnosis reported 11 deaths (5 percent) [54]. Five were from bleeding and six from causes unrelated to ITP.
●A series of 310 adults and children followed for 10 years reported a single hemorrhagic death in a 43 year old with longstanding severe thrombocytopenia [69].
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Immune thrombocytopenia (ITP) and other platelet disorders".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest).
●Basics topic (see "Patient education: Immune thrombocytopenia (ITP) (The Basics)")
SUMMARY AND RECOMMENDATIONS
●Overview – The goal of treatment is to treat or prevent significant bleeding, not to normalize the platelet count. Bleeding severity is defined in the table (table 1). The risk of critical or severe bleeding is low; risk is greatest with prior bleeding, platelet count <10,000/microL, and age >60 years. (See 'Overview of decision-making' above.)
●Management
•Critical bleeding – For critical bleeding (critical anatomical site or causing hemodynamic or respiratory compromise), we use platelet transfusion in all patients (algorithm 1). We suggest glucocorticoids (typically, pulse dexamethasone) plus intravenous immune globulin (IVIG) rather than either therapy alone (Grade 2C). (See 'Critical bleeding' above and 'Therapies to raise the platelet count' above and 'Other hemostatic therapies' above.)
•Severe bleeding – For severe bleeding (hemoglobin decrease ≥2 g/dL or requiring ≥2 units transfusion but not critical), we suggest glucocorticoids alone rather than IVIG alone or glucocorticoids plus IVIG (Grade 2C). Some people may prefer IVIG for its faster action or side effect profile. (See 'Severe bleeding' above and 'Comparison of therapies' above.)
•Minor bleeding and severe thrombocytopenia – For minor bleeding or thrombocytopenia without bleeding, the threshold for treatment is individualized (algorithm 2). (See 'Minor bleeding and severe thrombocytopenia without bleeding' above.)
-For most people with minor bleeding or platelet count <20,000/microL (especially <10,000/microL), we suggest treatment rather than observation (Grade 2C).
-Treatment at higher counts may be reasonable with greater bleeding risk or need for anticoagulation. Observation may be reasonable for young asymptomatic people with lower counts.
•Pregnancy – (See "Thrombocytopenia in pregnancy", section on 'ITP therapies'.)
•Surgery or delivery – For invasive procedures, the platelet count threshold is designated by the interventionist. Treatment may involve platelet transfusion (especially for urgent procedures with significant bleeding risk), glucocorticoids and/or IVIG, or a properly timed thrombopoietin receptor agonist (TPO-RA). (See 'Surgery or delivery' above and "Platelet transfusion: Indications, ordering, and associated risks", section on 'Preparation for an invasive procedure' and "Second-line and subsequent therapies for immune thrombocytopenia (ITP) in adults", section on 'TPO receptor agonists'.)
●Glucocorticoids – The choice of glucocorticoid is individualized. (See 'Choice of glucocorticoid and dosing' above.)
•Pulse dexamethasone produces faster responses and fewer bleeding events. Typical dosing is 40 mg orally or intravenously once daily for four days (no taper).
•Pulse methylprednisolone is typically administered as 1 g intravenously once daily for three days (no taper).
•Prednisone dosing is 1 mg/kg (range, 0.5 to 2 mg/kg) orally once daily for one to two weeks followed by a gradual taper (typically <6 weeks).
●IVIG – A typical dose is 1 g/kg daily for one or two days; one dose is often sufficient. Anti-D is an alternative. (See 'IVIG dosing and administration' above and 'Anti-D as an alternative to IVIG' above.)
●Monitoring and other testing – The table summarizes response times for therapies (table 2). All individuals should be monitored regularly and advised to consult their clinician for bleeding. (See 'Clinical monitoring' above.)
Individuals with active ITP should have platelet counts monitored before and after COVID-19 vaccination; benefits of vaccination outweigh the risk of an exacerbation in the majority of patients. (See 'COVID-19 vaccination' above.)
We test all people with ITP for HIV and hepatitis C. Testing for systemic lupus erythematosus (SLE), lymphoproliferative disorders, immune disorders, and Helicobacter pylori is individualized. (See 'Evaluation for secondary ITP' above and 'H. pylori testing' above.)
●Other contributors to bleeding risk – Additional considerations may apply with chemotherapy or antithrombotic therapy. Cautions may apply to physical activity and alcohol intake. (See 'Other considerations related to bleeding risk' above.)
●Disease course – Most adults with ITP will reach a safe platelet count, but many will require additional therapies. (See 'Prognosis' above and "Second-line and subsequent therapies for immune thrombocytopenia (ITP) in adults".)
ACKNOWLEDGMENT — The editorial staff at UpToDate would like to acknowledge James N George, MD, who contributed to many earlier versions of this topic review.
