Approach considerations for primary and secondary ITP
| . | Primary ITP3,78 . | SLE79,80 . | Evans syndrome81,82 . | ALPS83,84 . | CVID85,86 . | CLL87,88 . | HIV89,90 . | Hepatitis C38 . | H pylori91,92 . | Drug induced37 . | Postvaccine93 . | Other infections94 . |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Clinical characteristics | ||||||||||||
| Age at presentation | Any age, more common at age > 65 y. | Teenagers and older | Mostly adults | Can present at any age | Young adults | >70 years, rarely younger. | Any, common at age 20-40 y. | 30-49 years, rare in younger. | Any, common at age > 60 y. | Any | Children and young adults | Any |
| Incidence | 1.6-3:100 000 | 1-10:100 000 | 1:80 000 | Rare | 1-25 000-50 000 | 4.9:100 000 | 10:100 000 | 1:100 000 | 3-14:100 | Rare | Rare | Rare |
| Distinguishing features | Isolated thrombocytopenia with petechiae/bruising in a healthy-looking patient. | Multisystem involvement, common arthralgias/arthritis and renal. | Usually not concurrent hemolysis-thrombocytopenia; hepatosplenomegaly/lymphadenopathy. | Splenomegaly/lymphadenopathy may resolve when child gets older | 10% ITP, 10% AIHA, 5% Evans syndrome; not necessarily history of infections present at diagnosis. | Suspect if increased number of small mature lymphocytes on differential and smear | Flulike illness, lymphadenopathy, opportunistic infections; thrombocytopenia secondary to high viral load. | Arthralgias, paresthesias, myalgias, pruritus, neuropathy; multifactorial thrombocytopenia. | Nausea/vomiting, abdominal pain; variable correlation with thrombocytopenia - related to geography. | History of new drug treatment; difficult to diagnose. | History of recent vaccination; most commonly <6 wk after and secondary to live vaccines. | Variable - depending on the infection. Typically constitutional symptoms. |
| Diagnostic tests | CBC, peripheral blood smear. ↓↓Plt: normal or increased in size. Normal RBC and WBC. Rule out other causes. | CBC: ↓Hb ↓Plt ±↓WBCs | ↓IgG + ↓IgM or ↓IgA | Peripheral blood smear: large atypical immature cells, ↑lymphocytes. Flow cytometry: ↑lymphocytes. | p24 by ELISA, HIV IgM/IgG by western blot, HIV DNA PCR. Flow cytometry: CD4 < 200/μL. | HCV IgM/IgG, HCV RNA, HCV genotyping, liver function tests. | Urea breath test, fecal H pylori antigen, histological confirmation - rapid urease test. | Stopping offending agent should increase plt within a few days | None | PCR, serum antibodies - depending on infection. | ||
| CRP, ESR, dsDNA+, ANA+. | ↓ANC; ↑reticulocytes, ↑bilirubin; ↓haptoglobins, Coombs+, ↓IgG; BM: normal. | Flow cytometry: α-β CD4−CD8− T cells | ||||||||||
| Molecular characteristics | None identified | None identified | None identified | Defect in FAS gene | <10% various genetic defects identified | Possible chr abnl: 11q del, 13q del, 17p del, 12 copy. | None | None | None | None | None | None identified |
| Clinical approach | Standard first- and second-line treatment | Treat underlying disease, caution for thrombosis risk. | IVIG, rituximab, sirolimus, MMF. | IVIG/steroids acutely, MMF, sirolimus long-term, rituximab. | IVIG/SCIG, rituximab (very effective but requires lifelong IVIG). | Chemotherapy, rituximab. | HAART, TPO-RA, anti-D. | Antivirals, limited TPO-RA. | Eradicate infection | Stop offending agent | Likely mild and not requiring treatment, expected to resolve. | Treat underlying cause, TPO-RA. |
| . | Primary ITP3,78 . | SLE79,80 . | Evans syndrome81,82 . | ALPS83,84 . | CVID85,86 . | CLL87,88 . | HIV89,90 . | Hepatitis C38 . | H pylori91,92 . | Drug induced37 . | Postvaccine93 . | Other infections94 . |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Clinical characteristics | ||||||||||||
| Age at presentation | Any age, more common at age > 65 y. | Teenagers and older | Mostly adults | Can present at any age | Young adults | >70 years, rarely younger. | Any, common at age 20-40 y. | 30-49 years, rare in younger. | Any, common at age > 60 y. | Any | Children and young adults | Any |
| Incidence | 1.6-3:100 000 | 1-10:100 000 | 1:80 000 | Rare | 1-25 000-50 000 | 4.9:100 000 | 10:100 000 | 1:100 000 | 3-14:100 | Rare | Rare | Rare |
| Distinguishing features | Isolated thrombocytopenia with petechiae/bruising in a healthy-looking patient. | Multisystem involvement, common arthralgias/arthritis and renal. | Usually not concurrent hemolysis-thrombocytopenia; hepatosplenomegaly/lymphadenopathy. | Splenomegaly/lymphadenopathy may resolve when child gets older | 10% ITP, 10% AIHA, 5% Evans syndrome; not necessarily history of infections present at diagnosis. | Suspect if increased number of small mature lymphocytes on differential and smear | Flulike illness, lymphadenopathy, opportunistic infections; thrombocytopenia secondary to high viral load. | Arthralgias, paresthesias, myalgias, pruritus, neuropathy; multifactorial thrombocytopenia. | Nausea/vomiting, abdominal pain; variable correlation with thrombocytopenia - related to geography. | History of new drug treatment; difficult to diagnose. | History of recent vaccination; most commonly <6 wk after and secondary to live vaccines. | Variable - depending on the infection. Typically constitutional symptoms. |
| Diagnostic tests | CBC, peripheral blood smear. ↓↓Plt: normal or increased in size. Normal RBC and WBC. Rule out other causes. | CBC: ↓Hb ↓Plt ±↓WBCs | ↓IgG + ↓IgM or ↓IgA | Peripheral blood smear: large atypical immature cells, ↑lymphocytes. Flow cytometry: ↑lymphocytes. | p24 by ELISA, HIV IgM/IgG by western blot, HIV DNA PCR. Flow cytometry: CD4 < 200/μL. | HCV IgM/IgG, HCV RNA, HCV genotyping, liver function tests. | Urea breath test, fecal H pylori antigen, histological confirmation - rapid urease test. | Stopping offending agent should increase plt within a few days | None | PCR, serum antibodies - depending on infection. | ||
| CRP, ESR, dsDNA+, ANA+. | ↓ANC; ↑reticulocytes, ↑bilirubin; ↓haptoglobins, Coombs+, ↓IgG; BM: normal. | Flow cytometry: α-β CD4−CD8− T cells | ||||||||||
| Molecular characteristics | None identified | None identified | None identified | Defect in FAS gene | <10% various genetic defects identified | Possible chr abnl: 11q del, 13q del, 17p del, 12 copy. | None | None | None | None | None | None identified |
| Clinical approach | Standard first- and second-line treatment | Treat underlying disease, caution for thrombosis risk. | IVIG, rituximab, sirolimus, MMF. | IVIG/steroids acutely, MMF, sirolimus long-term, rituximab. | IVIG/SCIG, rituximab (very effective but requires lifelong IVIG). | Chemotherapy, rituximab. | HAART, TPO-RA, anti-D. | Antivirals, limited TPO-RA. | Eradicate infection | Stop offending agent | Likely mild and not requiring treatment, expected to resolve. | Treat underlying cause, TPO-RA. |
↓ indicates a decrease in value; ↓↓ indicates a significant decrease in value; ↑ indicates an increase in value.
abnl, abnormalities; AIHA, autoimmune hemolytic anemia; ALPS, autoimmune lymphoproliferative syndrome; ANA, anti-nuclear antibody; ANC, absolute neutrophil count; BM, bone marrow; chr, chromosome; CRP, C-reactive protein; CVID, common variable immune deficiency; del, deletion; dsDNA, double-stranded DNA; ELISA, enzyme-linked immunosorbent assay; ESR, erythrocyte sedimentation rate; H pylori, Helicobacter pylori; HAART, highly active antiretroviral therapy; Hb, hemoglobin; HCV, hepatitis C virus; MMF, mycophenolate mofetil; PCR, polymerase chain reaction; Plt/plt, platelets; RBC, red blood cells; SLE, systemic lupus erythematosus; SCIG, subcutaneous immunoglobulin G; WBC, white blood cells.