Table 3.
Bone marrow failure states presenting with isolated thrombocytopenia
| Primary ITP3,78 | FA30 | CAMT109 | DC110 | SDS111 | MDS39,112 | |
|---|---|---|---|---|---|---|
| Clinical characteristics | ||||||
| Age at presentation | Any age, more common after age 65 y | Young children (6-9 y), but up to 40 y of age | Type I: newborn. Type II: 3-6 y. | Young children (<5 y) and up to 40 y of age | Infancy/early childhood and up to 30 y of age | Most common in older adults |
| Incidence | 1-6.4:100 000 | 1:1 million | Rare | <1:1 million | Rare | 1-4:1 million |
| Distinguishing features | Isolated thrombocytopenia with petechiae/bruising in a healthy-looking patient | Could present as isolated thrombocytopenia at any age; thumb/skeletal abnormalities, short stature. | Isolated severe thrombocytopenia in neonate; often progresses to complete AA within several years; 1/3 with skeletal abnormalities. | Skin/nail abnormalities | Exocrine pancreas dysfunction | Other abnormalities on CBC and dyspoiesis in BM, possibly associated with trisomy 8 or 21, FA, etc. |
| Diagnostic tests | CBC, peripheral blood smear. ↓↓plt: normal or increased in size. Normal RBCs and WBCs. Rule out other causes. | BM evaluation, DEB, MMC. Genetic panel and WES. | BM evaluation: reduced/absent megakaryocytes; genetic panel and WES. | BM evaluation. Telomere length. Genetic panel and WES. | Pancytopenia, BM, fecal studies: elastase, trypsinogen; serum trypsinogen, isoamylase; genetic panel and WES. | BM evaluation. Cytogenetics: 5q del, 7 del, trisomy 8; genetic panel and WES. |
| Rule out viral infections: PCR/IgM/IgG of CMV, hepatitis, EBV, HIV, parvovirus. Rule out drugs/toxins. Rule out renal, hepatic, thyroid dysfunction. | ||||||
| Molecular characteristics | None identified | Mutations in FANCA, FANCC, FANG genes. | Mutation in c-Mpl gene | 11 gene mutations | Mutations in SBDS gene | Monosomy 7, trisomy 8 or 21. |
| Clinical approach | Standard first- and second-line treatment | Transfusions, androgens, HSCT, TPO-RA, G-CSF. | Transfusions, HSCT. | Transfusions, androgens, HSCT, TPO-RA, G-CSF | Supportive. HSCT. Plt transfusions. | Chemotherapy. HSCT. TPO-RA (controversial). |
↓↓ indicates a significant decrease in value.
AA, aplastic anemia; BM, bone marrow; CAMT, congenital amegakaryotic thrombocytopenia; CMV, cytomegalovirus; DEB, diepoxybutane test; del, deletion; EBV, Epstein-Barr virus; G-CSF, granulocyte-colony stimulating factor; HSCT, hematopoietic stem cell transplant; MMC, mitomycin C; PCR, polymerase chain reaction; Plt/plt, platelets; RBC, red blood cells; SDS, Shwachman-Diamond syndrome; WAS, Wiskott-Aldrich syndrome; WBC, white blood cells; WES, whole-exome sequencing.